Tribute To Dr. Takuo Aoyagi, Inventor of Pulse Oximetry: Special Article

Journal of Anesthesia (2021) 35:671–709
https://doi.org/10.1007/s00540-021-02967-z
SPECIAL ARTICLE
Tribute to Dr. Takuo Aoyagi, inventor of pulse oximetry

Katsuyuki Miyasaka1 · Kirk Shelley2 · Shosuke Takahashi3 · Hironami Kubota4 · Kazumasa Ito5 · Ikuto Yoshiya6 ·
Akio Yamanishi7 · Jeffrey B. Cooper8 · David J. Steward9 · Hiroshi Nishida10 · Joe Kiani11 · Hirokazu Ogino12 ·
Yasuhiko Sata13 · Robert J. Kopotic14 · Kitty Jenkin15 · Alex Hannenberg15 · Atul Gawande15
Received: 7 June 2021 / Accepted: 30 June 2021 / Published online: 2 August 2021
© The Author(s) 2021
Abstract
Introduction Dr. Takuo Aoyagi invented pulse oximetry in 1974. Pulse oximeters are widely used worldwide, most recently
making headlines during the COVID-19 pandemic. Dr. Aoyagi passed away on April 18, 2020, aware of the significance of
his invention, but still actively searching for the theory that would take his invention to new heights.
Method Many people who knew Dr. Aoyagi, or knew of him and his invention, agreed to participate in this tribute to his
work. The authors, from Japan and around the world, represent all aspects of the development of medical devices, including
scientists and engineers, clinicians, academics, business people, and clinical practitioners.
Results While the idea of pulse oximetry originated in Japan, device development lagged in Japan due to a lack of busi-
ness, clinical, and academic interest. Awareness of the importance of anesthesia safety in the US, due to academic foresight
and media attention, in combination with excellence in technological innovation, led to widespread use of pulse oximetry
around the world.
Conclusion Dr. Aoyagi’s final wish was to find a theory of pulse oximetry. We hope this tribute to him and his invention will
inspire a new generation of scientists, clinicians, and related organizations to secure the foundation of the theory.
Keywords Pulse oximetry · Patient monitoring · Anesthesia safety · History
8
* Katsuyuki Miyasaka Department of Anesthesia, Critical Care and Pain Medicine
katsmiyasaka@mac.com Center for Medical Simulation, Harvard Medical School,
Massachusetts General Hospital, Boston, MA, USA
1
St. Luke’s International University, 3‑4‑2‑3602 Toyosu, 9
Department of Anaesthesia and Pharmacology, University
Koto‑ku, Tokyo 135‑0061, Japan
of British Columbia, Vancouver, Canada
2
Department of Anesthesiology, Yale University, New Haven, 10
Tokyo Women’s Medical University, Tokyo, Japan
CT, USA
11
3 Masimo & Patient Safety Movement Foundation, Irvine, CA,
Kyushu University, Medical Corporation Soseikai,
USA
Fukuoka City, Fukuoka, Japan
12
4 Nihon Kohden Corporation, Tokyo, Japan
K and K Japan Co. Ltd, Tokyo, Japan
13
5 Tokibo, Inc, Tokyo, Japan
Vital Sign Sensor Technology Development Division,
14
Technology Development Operations, Nihon Kohden Critical Care Manager of Clinical and Medical Affairs,
Corporation, Tokyo, Japan Edwards Lifesciences, Irvine, CA, USA
6 15
Department of Anesthesiology, Osaka University Medical Lifebox Foundation, Brooklyn, NY, USA
School, Osaka, Japan
7
Medical Equipment Division, Minolta Camera Co.,
Ltd. (Konica Minolta Co., Ltd., at present), Tokyo, Japan
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Vol.:(0123456789)
672 Journal of Anesthesia (2021) 35:671–709
Introduction I am from a generation that experienced anesthesiol-

ogy before the development of pulse oximeters. I was
Katsuyuki Miyasaka, MD studying abroad in North America from 1973, when Dr.
Aoyagi thought of the principle of pulse oximetry, until the
Preface end of 1977. This was just about the time when Minolta
began selling a finger type device, and I knew nothing
I feel greatly honored to have been asked by the previous of Dr. Aoyagi’s existence or the idea of pulse oxime-
Editor-in-Chief of Journal of Anesthesia (JA), Dr. Yama ters. Japan was just starting to shed the image of Made
kage, to organize a special memorial issue on Dr. Takuo in Japan = cheap and poorly made. The HP 8-wavelength
Aoyagi in English. I would like to thank him for his wise ear oximeter was already in use at a research laboratory.
decision to take this timely opportunity to tell the world Although it appeared accurate, it seemed to be cumber-
about the great contribution Dr. Aoyagi made to humanity. some for clinical use.
Many contributors are from countries other than Japan, all It was not until 6 years after returning to Japan that I met
of whom showed great interest in this project. They kindly Dr. Aoyagi at a Japanese Subcommittee of the International
agreed to search their files and memories from 40 years Organization for Standardization. We attempted, unsuccess-
ago and to send their memorial contributions on a tight fully, to establish a standardized calibration method. In the
schedule, so that we would have time to translate their 36 years since I have had the privilege of learning from him
articles into English. Furthermore, Dr. Yamakage has also and having lived through the same generation as a clinician
contributed by editing them into an organized special arti- and a developer, I feel a responsibility to record his achieve-
cle, which is fitting for an international journal, JA. ments. I am most grateful for being entrusted with recording
As you read through this collection of articles, many how his great invention was born and how it grew.
of you will find new information and developments previ- I hope that by translating the Japanese articles for this
ously unknown to the public. I hope that this memorial memorial into English, a wide range of medical profession-
will give all of us the opportunity to reconfirm what we als in the whole world will learn more about the birth and
know of the great legacy left to us by the late Dr. Aoyagi. development of pulse oximetry. This memorial issue is being
published to honor Dr. Aoyagi on the first anniversary of
his death. Due to time constraints, the authors did not have
Oximetry: principle, but no theory much time to write, and I appreciate their cooperation. The
authors, including me, are not historians and most never
First, I would like to share with you one of Dr. Aoya- thought that they would be called upon to write a memorial
gi’s final wishes. He always used to say “It is the role of article on short notice. There was not enough time to check
researchers like me to establish a theory, but without a for objectivity and consistency. There is no doubt that some
theory, there are limits to what devices can do. It concerns uncertain statements, based on memories from long ago, are
me that clinicians and society at large do not understand included. I hope you will understand the reasons for this and
how this affects them.” see that there is great meaning in publishing this compila-
The pulse oximeter is a very special type of patient tion in terms of further development of pulse oximeters, just
monitor that still, as of this date, has no standard method as Dr. Aoyagi wished. A short introduction to each of the
of calibration. It is generally thought that pulse oxime- authors can be found at the end of the compilation.
try simply measures photometric color changes of arte- I am truly grateful to Dr. Yamakage for making the pub-
rial blood. It is actually more complicated, as it meas- lication of this memorial issue possible in a timely fashion,
ures changes in arterial blood color through dynamically the first year after Dr. Aoyagi’s death.
changing filters, such as surrounding blood vessels, blood- May Dr. Takuo Aoyagi rest in peace.
filled tissue, bone and skin. Interference from these cur-
rently unpredictable, ever-changing factors, complicates
the calculation of pulse oximetry measurement and it is The ratio of ratios and the Nobel Prize
difficult to separate the effects of these various factors on
arterial blood oxygenation. Kirk Shelley M.D., Ph.D.
As an engineer and a developer, Dr. Aoyagi depended Professor Emeritus of Anesthesiology.
on clinicians like me to play an educational role and I Yale University, New Haven, CT, USA.
believe that this memorial edition is important for letting I was truly heartbroken to hear of Dr. Aoyagi’s passing.
people know about Dr. Aoyagi’s vision. His remarkable genius created the device that I have spent
most of my life devoted to studying. He was a warm and gen-
tle man who was profoundly humble. Shortly after the Yale
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Journal of Anesthesia (2021) 35:671–709 673
symposium of the Innovations and Applications of Moni- the 900 nm wavelength was selected to avoid interference
toring Perfusion Oxygenation and Ventilation conference by the ICG dye. From the transmitted light intensity data,
(IAMPOV) in 2012, the Nobel Prize Committee approached the pulsation amplitude AC and the total intensity DC were
me for a nomination for the 2013 Nobel Prize in Physiology obtained, and the ratio, AC/DC, was calculated. This AC/
or Medicine. This was done under an air of great secrecy. DC ratio was obtained at both wavelengths, and their ratio,
I wrote up Dr. Aoyagi’s nomination with care and thought- phi (Φ), was calculated. This is the so-called ratio of ratios.
fulness. I am disappointed to say that he was not given the This phi (Φ) was supposed to correspond to SaO2.”
award. To this day, I see this as my failure and not his. Dr. Aoyagi was correct; the ratio of ratios did correspond
When we met again face to face in 2015 in Tokyo at their to the arterial saturation. The pulse oximeter has gone on to
IAMPOV. I took Dr. Aoyagi aside and broke the strict confi- become a critical piece of medical equipment that is used
dentiality rule. I explained to him that he had been formally all around the world on a daily basis. Its use is now consid-
nominated and considered for the Nobel Prize in Medicine in ered to be a standard of care during surgical procedures and
2013. I apologized for the ineptness of my writing in being is part of a routine set of vital signs [3]. Its importance is
unable to convey the importance of the lifesaving nature of further emphasized by the initiative, by the World Health
his work. He smiled warmly, thanking me most graciously. Organization (WHO), called the “Global Pulse Oximetry
Now that he has passed away, I am content that I violated Project”. This project was committed to the introduction of
my confidentiality agreement. He deserved to know how he pulse oximetry technology throughout the world with an
came to be considered for the award and in what high regard emphasis on developing countries [4].
people held him in. Below contains the essence and update The Nobel Prize committee has a tradition of awarding
of what I wrote in 2012. I have been subsequently invited significant technical innovation in medicine. Willem Ein-
to submit additional nominations over the years for other thoven, in 1924 for his discovery of the electrocardiogram
potential candidates. I find that I am unable to because of (ECG), Allan Cormack with Sir Godfrey Hounsfield, in
the sadness I feel at the passing of Dr. Aoyagi. 1979 for the development of computed tomography (CT)
and Sir Peter Mansfield, in 2003 for his discoveries concern-
ing magnetic resonance imaging (MRI) are such examples.
A letter of recommendation I believe Dr. Aoyagi discoveries concerning pulse oximetry
had achieved that degree of significance (Table 1).
It was my pleasure and honor to nominate Dr. Takuo Aoyagi
for the Nobel Prize in Medicine for 2013. My nomination
was based upon his discovery of the “Ratio of Ratios”.
Adoption of pulse oximetry into the JSA
That discovery is the core technology behind the modern-
anesthesia safety guidelines—the brilliance
day pulse oximeter. In 1972, Dr. Aoyagi was interested in
of Aoyagi’s intellectual legacy
measuring cardiac output noninvasively by the dye dilution
method using a commercially available ear densitometer. He
Shosuke Takahashi, M.D., Ph.D.
concluded that it would require calibration, because arterial
Professor Emeritus, Kyushu University.
pulsatile “noise” prevented accurate recording of the dye
Medical Corporation Soseikai, Fukuoka, Japan.
clearance, and he invented a method to eliminate this noise,
which led to his great contribution [1].
To quote Dr. Aoyagi [2], “These [pulsations] prevented Preface
accurate extrapolation of the down-slope of the dye curve
after recirculation begins. I investigated this problem math- When the concept of anesthesia for surgery was first intro-
ematically using the Lambert–Beer law. Then, I conceived duced half a century ago, only one cardiograph was available
the idea of eliminating the pulsation by computing the ratio at the operating theater, and we were checking for signs of
of optical densities of the two wavelengths. This supposition crisis using this device in combination with visual inspec-
was proved workable by experiments.” tion, palpation, percussion, auscultation, intermittent manual
Dr. Aoyagi goes on to say, “For this prototype, compo- measurement of the blood pressure, and also clinical intui-
nents of the dye densitometer were used. The light source tion. After pulse oximetry was introduced, it became possi-
was a small tungsten lamp. The transmitted light was divided ble to evaluate the status of oxygenation, ventilation, circula-
into two beams, and each beam was received by a combination, body temperature and muscle relaxation using scientific
tion of an interference filter and a phototransistor. I used indicators, on the basis of the principle of vigilance. For
wavelengths of 630 nm and 900 nm. The wavelength of example, it became possible to detect imminent cardiac
630 nm was selected to maximize the hemoglobin extinc- arrest about 1 min before its occurrence if arterial blood
tion change caused by the oxygen saturation change, and oxygen saturation ( SpO2) monitoring was performed, and
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Table 1 Short curriculum vitae

of Takuo Aoyagi: 1958 Graduated electric engineering course of Faculty of Engineering, Niigata University
Entered Shimadzu Corporation, Kyoto City as a researcher in the Central Research Laboratory
1966 Joined the Electronic Division, Faculty of Engineering, Tokyo University, where he studied
cardiac output measurement using the dye dilution method
1971 Entered in Nihon Kohden Corporation, Tokyo City, where he engaged in the study of:
< 1 > cardiac output measurement using dye dilution method
< 2 > pulse oximetry: invention, making pilot model, and first announcement
< 3 > pulse oximetry: constructing theory for improvement of pulse oximetry
< 4 > pulse dye densitometry: for measurement of circulating blood volume
< 5 > biomedical impedance method for lung monitoring
1993 Received a Ph.D. of Engineering at the Tokyo University, with a thesis topic of: "Study of
noninvasive measurement of light absorbing materials in the blood using the arterial pulse."
1995 Achievement Prize by the Medical Instrument Society of Japan
2007 The Medal with Purple Ribbon (given by Japanese Emperor)
Social Prize by the Japanese Society of Anesthesiologists
2012 The Harvey W. Wiley Lifetime Achievement Award
2013 J.S. Gravenstein Award Lifetime Achievement by Society for Technology in Anesthesia
2015 IEEE Medal for Innovations in Healthcare Technology
several min before its occurrence if end-tidal carbon dioxide lantern, including my seeing Dr. Aoyagi, while he was
(ETCO2) monitoring was performed, whereas the time from alive, and events related to him during the days when I was
the detection of signs of cardiac arrest to the occurrence involved in spreading the clinical application of pulse oxime-
of cardiac arrest was only 10 s when ECG monitoring was ters. On this occasion, I would like to present some of those
performed. scenes in memory of Dr. Aoyagi while dedicating my deep
respect and gratitude to him.
Background
Operating room safety management committee
For us anesthesiologists whose mission is to protect the
life of patients under conditions of body invasion, in which It was in 1976 that the Operating Room Safety Management
there may be only s/min left until the onset of a critical Committee was constituted within the Japanese Society of
condition, introduction of the pulse oximeter enabling non- Anesthesiologists (JSA). Prof. Hideo Yamamura (University
invasive measurement of S pO2 was a great relief, as if we of Tokyo) served as the first chairman of this committee.
had met Buddha in hell. This was a brilliant achievement Later, the role of the chairman was passed on to Profes-
which later triggered advances in the monitoring of vital sors Toyohisa Arai, Keizo Takahashi, Ken’ichi Kobayashi
signs as well. Discovery by Dr. Takuo Aoyagi, in 1974, and Masahiro Suzuki in that order, and the baton was also
of the principle of measurement of the arterial oxygen handed at one time to the author. In those days, anesthesia
saturation using cardiac pulsations by pulse oximetry has was viewed unfavorably by people, and there prevailed a
contributed greatly to mankind. At first, an ear oximeter negative attitude about anesthesia itself being a risk factor
was manufactured on a trial basis for clinical application for operation. For example, when the patient died as a result
of this principle, but the device was not commercialized, of a poor operative outcome, explanation like the following
and research for its commercialization suffered a setback was often offered without hesitation: “The operative proce-
and delay. dure itself was successful, but the patient failed to wake up
Nearly, 10 years later, pulse oximeters with fingertip sen- from anesthesia,” etc.
sors were developed in the US, followed by the rapid spread On the 31st Conference of the JSA in 1984, a symposium
of these devices. Japan hastily introduced the devices made titled “Towards Safer Anesthesia” was organized. This was
in the US without laying claim to the fact that the pulse oxi- the first meeting focusing on the safety of anesthesia in the
meter principle was first invented in Japan (by Dr. Aoyagi), setting of an academic conference. Around that time, I began
until Prof. Severinghaus (University of California, San Fran- to place great importance to the activities within the frame-
cisco) publicized the fact in 1986. work of the Operating Room Safety Management Commit-
I was shocked when I was informed by Prof. Michiaki tee, which eventually led to the publication of “Guidance
Yamakage (Chief Secretary, Japan Association for Clinical on Monitoring for Safe Anesthesia” on April 21, 1993.
Monitoring) of the death of Dr. Takuo Aoyagi on April 18, The process until preparation of this guidance is described
2020. At that time, my memory of him ran like a revolving in the published monograph “Guidebook—Guidance on
13
Monitoring for Safe Anesthesia by the JSA” (edited by acts under environments that lack preparation for risk man-
Masahiro Suzuki and Toyohisa Arai, published by Koku- agement are unacceptable. MAC is “a preparatory step for
seido Co., Ltd., 1995). This guidance has been revised four wiping out the demon” hidden behind medical acts. In Japan,
times and provides easily understandable guidance while however, reimbursement for MAC is not provided by the
avoiding ambiguous expressions. national health insurance system to the physicians in charge
A survey of accident cases related to anesthesia was con- of vigilance, putting a considerably heavy burden on the
ducted in parallel with the creation of this guidance. At some healthcare providers.
point of time, some of the survey staff proposed that the
survey be discontinued, because data collection and entry Japan association for clinical monitoring
were labor-intensive. However, our definitive determina-
tion to continue with the survey was understood by suc- When talking about Dr. Aoyagi, I cannot omit to referring to
cessive members of the committee and the staff in charge the Japan Association for Clinical Monitoring founded under
of the survey at each leader hospital, so that the survey has the initiative of Prof. Akira Okuaki (Fukushima Prefectural
been continued to date, without interruption. Analysis of Medical University). At the meetings of this association, Dr.
the data collected during this survey has yielded significant Aoyagi often presented research data aimed at improving the
outcomes, such as the creation of the guidance for counter- precision of pulse oximeters and optimizing the cost of this
measures against massive bleeding and guidance for preven- device. He also made a presentation at the 7th conference
tion of pulmonary embolism. of this association held in Fukuoka and was awarded the
Okuaki Memorial Prize in the following year. In those days,
Why was the guidance created so rapidly? Prof. Katsuyuki Miyasaka (National Children’s Hospital)
was also actively involved as a co-researcher in the research
Development of a concrete guidance was started at a time conducted by Dr. Aoyagi. Prof. Okuaki invited researchers
when standards on intraoperative monitoring were being from varied specialties to this association to allow multidis-
published one after another in European countries, mod- ciplinary wisdoms to debate an issue, and Dr. Aoyagi was a
eled after the standard published in 1986 by the American very valuable asset for this association. It was also impres-
Society of Anesthesiologists (ASA). Needless to say, the sive that Prof. Kunio Suwa (University of Tokyo), who was
introduction of pulse oximetry served as a driving force for the best speaker on oxygen-related topics among Japanese
these actions. researchers, enthusiastically suggested that the performance
Another factor which prompted rapid creation of the of Dr. Aoyagi was worthy of a Nobel Prize.
guidance was the death of two patients caused by accidental
erroneous inhalation of pure nitrous oxide at an influential Talk of Nobel Prize
national hospital in Kyushu in 1987. The episode was attrib-
uted to an error in the arrangement of the supply pipes for Awarded to the research on hypoxia‑inducible factor (HIF)
oxygen and nitrous oxide made during the construction of
the hospital. Although the anesthesiologists involved in the The year 2001 was the 100th anniversary of awards of the
care of the victims were exempted from legal responsibility, Nobel Prize. In those days, Prof. Lindahl (Department of
a tense atmosphere prevailed in those days at the mention Anesthesiology, Karolinska Institute) was the chairman of
of anesthesia, and we resolved to never have such accidents the Nobel Committee for Physiology or Medicine. I became
recur. acquainted with him in those days, and we became reason-
ably good friends as we were around the same age (born in
Preparation for wiping out the demon: Monitored 1943). Prof. Lindahl always talked passionately about the
Anesthesia Care (MAC) beauty and novelty of science.
We asked him to deliver a special speech at the 49th Con-
In recent years, it has become mandatory for the guidance ference of the Japanese Society of Anesthesiologists in 2002.
on monitoring to be followed if a test or treatment requiring We asked him to refer to the (1) criteria for selection of a
anesthesia is undertaken even outside the operating room. Nobel Prize winner and (2) introduction of the research in
Introduction of such a regulation is also being debated now our field that would be the worthiest of this prize, when
in Japan, under the so-called MAC. If anesthesia provided delivering the special speech. He immediately responded
without the MAC results in an adverse event, the healthcare to this request, saying that the answer to (1) was “good for
provider concerned will be judged as “having been negli- mankind”, i.e., great contribution to mankind, and to (2)
gent, i.e., there is a default obligation on experts to predict was the research on biological reactions to hypoxia from
the possible risks associated with a given medical act and to the standpoint of molecular genetics. On that day at the
take steps to avoid the risks.” Simply said, invasive medical
13
Conference, his audience was fascinated by his smart and (linked to US patent registration), publication of papers in
appealing special speech. journals, such as Anesthesiology and Anesth Analg, and
The Nobel Prize in Physiology or Medicine 2019 was awards of many professional society prizes, such as the Pat-
awarded to 3 researchers, including Prof. Semenza (Johns ent Agency Director’s Encouraging Prize, the Science and
Hopkins University), for their contribution to elucidation Technology Director Award, the Medal with Purple Ribbon,
of the mechanism of cellular sensing and responses related Gravenstein Lifetime Achievement Award of the Society for
to oxygen utilization. We were excited much by the Nobel Technology in Anesthesia (USA), the Institute of Electrical
Prize having been awarded for a field of research that was and Electronic Engineers (IEEE) Medal For Innovations In
of interest to us. According to the special article by Prof. Healthcare Technology, and so on. Thus, global recogni-
Kiichi Hirota (Kansai Medical University), published in the tion of the performance of Dr. Aoyagi has been deepening.
November issue of LiSA, 2019 in Japanese, these 3 research- Although not satisfying the criteria for the Nobel Prize, the
ers were awarded the prize for their detection and isolation intellectual relics left by Dr. Aoyagi will remain brilliant
of HIF as a factor, a component of the molecular mechanism forever.
involved in the induction and maintenance of erythropoietin
expression, as well as elucidation of the molecular mecha-
nism for oxygen tension-dependent HIF activity modulation. Different roles of Japanese and US industry
I hear that Prof. Hirota was involved in isolating the gene in the clinical introduction of pulse
encoding the HIF molecule as a member of the laboratory oximeters
led by Prof. Semenza.
Very broadly speaking perhaps, the connection between Hironami Kubota.
SpO2 and HIF can be viewed as a dialogue between oxy- Medical devices market research consultant.
gen and the living body during the course of external and K and K Japan Co. Ltd., Tokyo, Japan.
internal respiration closely involved in homeostasis and
evolution. Long way from development to commercialization
Criteria for award of the Nobel Prize The invention of the pulse oximeter by Dr. Takuo Aoyagi in
1974 has been viewed as a typical case of medical device
During the 75 years after World War II, slightly more than development achieved under a plan based on definite goal
25 Japanese have been awarded the Nobel Prize. Why setting. The favorable outcome of such an approach to
was Dr. Aoyagi not awarded the Nobel Prize? Prof. Kunio development is shown by the fact that the medical device
Suwa had pointed out on several occasions that Dr. Aoyagi developed thus has been commercialized and adopted widely
deserved this prize, and Prof. Katsuyuki Miyasaka had also across the globe. In the medical device industry, charac-
provided strong support for the awarding of this prize to terized by small-lot large-variety production, scarcely any
Dr. Aoyagi. I also tried to use the best of my limited abili- medical device has contributed as significantly to healthcare
ties for this purpose, advising Prof. Lindahl (Chairman of as the pulse oximeter. Thus, it may be called “a good model
the Nobel Committee) that the performance of Dr. Aoyagi of medical device development.”
satisfied the criterion “good for mankind” for award of the I have just given the conclusion at the beginning of this
Nobel Prize. At that time, I thought the chairman subtly told paper. When the project led by Dr. Aoyagi was under way,
me that while his work was great, it was still some distance I was also a member of the Development Department of
from deserving the Nobel Prize. However, because of my Nihon Kohden Corporation. In those days, I could hardly
poor language abilities, I am not confident that I understood have imagined that the device development under way at
his response completely. He did seem, though, to suggest the the neighboring section would advance to such a remark-
weak points of Dr. Aoyagi, i.e., the fact that his first paper able extent, because the missions of different sections of
was written in Japanese and that the intellectual proprietor- the department differed completely from each other. Neigh-
ship of the outcome of his research had not been established boring sections were expected to make efforts together for
by a globally valid method. It has been pointed out for many improvement through friendly rivalry. The job that I was
years that the basis for the protection of intellectual propri- in charge of in those days pertained to improving patient
etorship is weak in Japan and that Japanese enterprises show monitors (e.g., adoption of wireless monitor systems), which
poor capability for translating advanced technologies. I think had already advanced to a certain degree, and this mission
that these shortcomings remain open issues even until date. was different in nature from that of in which Dr. Aoyagi was
Despite such limitations, the greatness of Dr. Aoyagi’s engaged. In other words, the topic of development assigned
performance has been steadily enriched. His research has led to my section, which pertained to improving the practical
to submission of many applications for patent registration aspects of existing products, differed in dimension from
13
the innovative development topic assigned to the Aoyagi for establishment of the path towards development and com-
Project. mercialization of pulse oximeters for routine use.
“Optical Oxygen Measuring Device,” application for However, the clinical usefulness, in the true sense of the
patent registration was filed in 1974 in Japan. This device term, of pulse oximeters became apparent only after the
later served as the prototype of the pulse oximeter. To this products were marketed by two American companies. The
document, the memo “Registration NO. 947,714” was later term “pulse oximeter” became popular only at in those days.
added manually. This memo is a valuable relic written by This is because this kind of device was shown to play a sig-
Dr. Aoyagi himself. A noteworthy phrase used in this bul- nificant role in the fields of anesthesiology/critical care and
letin is the “earpiece-type oximeter” as an example of patent neonatal management.
embodiment. This was commercialized as the initial prod- Table 2 summarizes the course of pulse oximeter develop-
uct of an “ear oximeter.” Here, the term “oximeter” means ment, focusing on the actions/events in Japan and the USA.
“measuring oxygen” and the phrase “earpiece-type” indi- It can be seen from this table at a glance that the efforts made
cates “measurement attaching to the earlobe.” in Japan primarily pertained to the principle and develop-
From the standpoint of engineering, the ear oximeter was ment, while those in the USA contributed to implementation
characterized by the use of an analog device, with utiliza- of pulse oximeters. On the basis of the efforts made in these
tion of primitive electric parts like light bulbs as the source two countries under such role assignment, pulse oximeters
of light. It is an undeniable fact that these characteristics of have so far grown into a group of devices that are used exten-
the ear oximeter led to unstable of the measurements, result- sively in routine clinical practice around the world.
ing in the development of the domestic impression that the
product was “useless.” Biased towards the two extremes (high‑functioning
Efforts to overcome such a challenge were made by products vs. extensively applicable products)
Minolta Camera, Inc. (currently named “KonicaMinolta,
Inc.”). OXIMET, which was the first oximeter marketed by Pulse oximeters that were successfully commercialized by
Minolta Camera, was characterized by the utilization of a the two American companies Nellcor and Biox (Ohmeda)
“finger sensor”. It is noteworthy that this product for routine as products for routine use were both standalone-type (Type
use was marketed only several years after the ear oximeter A) products and were intended primarily for use in criti-
was launched in the market. Considering that most pulse cal care (intraoperative care in severely sick patients, pre-
oximeters currently on the market adopt this type of sensor, mature infant/neonate management, and so on). Develop-
we may say that the OXIMET served as the driving force ment of these products was led by Prof. Severinghaus of the
Table 2 Course of pulse oximeter development—comparison between Japan and the US

Year Role of Japan Role of the US
1974 Patent application for the pulse oximetry principle filed by Takuo
Aoyagi (Nihon Kohden)
1977 Pulse oximeter marketed by Akio Yamanishi et al. (Minolta Cam-
era)
1981 Pulse oximeter (the first full-scale product) marketed by Nellcor
and Ohmeda
1992 International Standard on Pulse Oximeter ISO 9919 enforced
1994 Wrist watch-type pulse oximeter marketed by Techna Electronic
Industry (currently named “T & RK”)
1996 Fingertip-type pulse oximeter marketed by Nonin
1998 Software (Signal Extraction Technology) for improving the
precision of measurement with pulse oximeters developed by
Masimo
2000 ~ Portable/wearable products developed by many manufacturers,
including Nihon Seimitsu-sokki, Inc
2005 Pulse oximeter allowing measurement under the environment for
MRI marketed by Nonin
2011 International Standard on Pulse Oximeter ISO 800,601–2-61 (revision of ISO 9919) enforced
2014 Domestic standard on pulse oximeter JIS T80601-2–61 enforced
2020 “Blood Oxygen Wellness” introduced into common products by
Apple Inc
13
University of California, San Francisco, who emphasized Essential nature of pulse oximeters and its
the significance of continuous monitoring of arterial blood relationship to international standards
oxygen saturation enabled by pulse oximeters. The contribu-
tion of Prof. Severinghaus is particularly consequential, in Now, the term “pulse oximeter” is known well; people hear-
that he positioned a pulse oximeter as an optimal device for ing this word are likely to imagine a compact-sized Type B
use in intraoperative respiratory management and thus, as device. However, during the stage of development and early
an indispensable device for anesthesia management. At that phase of commercialization, i.e., until the 1980s, only the
time, he announced to the world that this principle related full-scale type (Type A) of pulse oximeters were available in
to a pulse oximeter was actually discovered by Dr. Takuo the market. After the turn of the century, however, this mar-
Aoyagi of Japan [5]. It was Dr. Kunio Suwa (Department ket changed dramatically, and Type B products have become
of Anesthesiology, University of Tokyo, in those days) who predominant. Now, I shall refer to open issues related to
actively disseminated this information in Japan. This infor- Type B pulse oximeters, the currently predominantly used
mation, announced ten-odd years after registration of the type of oximeter.
related patent in Japan, was perceived as “information that My greatest concern pertains to the large discrepancy
had never been heard before” or “information that should between the international standards and the current status
prompt re-recognition,” even in Japan, the country where of Type B pulse oximeters available in the market. The cur-
the researcher originated from. rent international standard ISO80601-2–61: 2011 was set
Thereafter, new types of pulse oximeters were marketed forth, covering Type A full-scale pulse oximeters as the main
one after another, not only by American manufacturers, but target. For example, the section about precision of measure-
also by Japanese and European manufacturers. In the 1990s, ment in this standard requires implementation of a study
pulse oximeters became general-purpose devices, applicable involving strict comparison between the arterial oxygen
also to the care of moderately severe patients and in gen- saturation (SaO2) measured by the oximeter and the S aO2
eral wards. In the 2000s, technological advances in pulse in the patient’s arterial blood (in arterial blood samples) in
oximeters became accelerated, resulting in the development healthy volunteers under induced hypoxemia. This means
of compact-sized/portable products and wearable products that even though a pulse oximeter is “essentially a non-inva-
(Type B), thereby enabling more extensive use of pulse sive device,” the standard requires that it provides clinical
oximeters. Among others, spread of the fingertip sensor- evaluation results equivalent in precision to those of “highly
combined type of pulse oximeter generated a new role for invasive devices” of a different nature.
the pulse oximeter (a spot checker of oxygen saturation in When viewed from the angle of underlying principle or
ordinary patients and in health management in general; Type the design concept during development, the primary prin-
B), in addition to its previous role of patient monitoring; ciple of a pulse oximeter is “(non-invasive) extracorporeal
Type A. measurement of oxygen saturation with the use of light.” It
The standalone-type pulse oximeters (Type A) mainly is no exaggeration to say that this principle or concept served
consist of high-functioning products often made overseas as the basis for the global spread of this type of device. Con-
(e.g., USA). An example is a pulse oximeter that offers sidering that the predominantly used type of pulse oximeters
improved precision of measurement and is “capable of deal- changed from Type A monitors to the current compact-sized
ing also with bodily movements” [6] or “enabling measure- type monitors, it is understandable that a large discrepancy
ment even during hypoperfusion.” There are also products arose between the international standard and the actual sta-
which have been categorized as “pulse photometry” products tus of type B pulse oximeters. However, a fundamental issue
that are capable of measuring abnormal hemoglobin (car- is that no ideal standard criterion device for “non-invasive”
bon monoxide-bound hemoglobin, methemoglobin, etc.), in calibration of a pulse oximeter is available until date.
addition to measuring the oxygen saturation level. There is another factor that needs to be borne in mind.
Among the Type B products, Japanese products are pre- In Japan, the ISO standard mentioned above was translated
dominant. While typically, it is difficult for big businesses directly, to yield JIST80601-2–61:2014. Then, this part of
to enter this market, the entry by venture companies, such the JIS was cited directly in the pulse oximeter accreditation
as small- and medium-sized enterprises, is rather remark- criteria set forth pursuant to the Pharmaceutical and Medical
able; as many as more than 30 such companies have entered Devices Act. This poses a problem. Originally, each provi-
this market in Japan, with Japan Precision Instruments, Inc., sion of the international or domestic standards serves as “a
serving as the market leader. This device is fitted with a standard” and cannot be interpreted as indicating “must”
wireless communication function and is linkable to smart- (mandatory). However, if such a provision of the interna-
phones and clouds, reflecting the latest trends in the field of tional or domestic standards is incorporated directly into the
information technology. accreditation criteria based on the Pharmaceutical and Medi-
cal Devices Act, the provision suddenly changes to assume
13
the meaning “must” (mandatory). We see a possibility that now under way over measurement of the respiratory rate
those involved in legislation of the law were not aware of from changes in the pulse wave, and so on. In addition, fur-
this hidden mechanism. ther efforts will be made to explore the possibility of improv-
Thus, the issue has two aspects: (1) the standard avail- ing the precision of oxygen saturation measurement using
able at present does not match up to the current status and a multiple wavelength system (a topic to which Dr. Aoyagi
(2) the law has carelessly converted the “standard” into a dedicated his passion), adding the capability for measuring
“mandatory rule.” I fear that although the pulse oximeter has other parameters, and so on. Contactless sensors for use in
grown in stature to one of the most frequently used medi- pulse oximeters are also under development and their com-
cal devices in the world, a lack of sufficient understanding mercialization in the near future is highly probable.
of this device by the regulatory authorities/administrative In the end, I would like to add that the heritage left by
organs can hamper or markedly delay new development and/ Dr. Aoyagi (given the shining title of “Father of Pulse Oxi-
or clinical introduction of pulse oximeters for medical use. meter”) and his guidance on new research and development
give us a strong impression that pulse oximeters will con-
tinue to evolve in the future.
Relationship to IT and perspectives for future
The spread and expansion of the use of pulse oximeters Using a fundamental approach to improve
across the world are showing no signs of stopping or slow- the accuracy of pulse oximetry—the
ing down. This can be viewed as an outcome of the efforts research to which Dr. Aoyagi devoted his life
made to date by manufacturers around the world towards
“commercialization” of their products while adopting new Kazumasa Ito.
ideas/designs and competing with each other. In other words, Vital Sign Sensor Technology Development Division,
“rivalry/free competition” serves as the basis for device Technology Development Operations.
improvement, and this should be viewed as a very favorable Nihon Kohden Corporation, Tokyo, Japan.
direction of development. Furthermore, interlinking with the
latest IT-related devices in terms of technology and mer- Introduction
chandise has also been achieved, resulting in elevation of
the value of pulse oximeters as a merchandise. Around 2007, Dr. Aoyagi once attended an in-company lab
For example, the new concept of “Blood Oxygen Well- meeting with a newspaper clipping. The article reported a
ness” was introduced into Japan, in September 2020 to the medical accident due to a missed alarm. At the very begin-
Apple Watch 6. The function and performance of this watch ning, he insisted, “The performance of the device is the root
are estimated to be approximately comparable to those of cause. Performance improvement is essential in medical
existing pulse oximeters in terms of the technique and prin- settings. We have to improve measurement technologies to
ciple of measurement. A difference lies in that existing terms reduce medical accidents.” He showed a strong sense of mis-
such as “pulse oximetry” and “SaO2” are not used in this sion, saying, “fundamental improvement in the performance
watch, and this product has been viewed as a product reflect- of pulse oximeters by constructing a theory not only allows
ing the manufacturer’s intention of creating the new concept a reduction in the burden on patients of blood collection, but
of healthcare or wellness devices derived from the exist- also leads to the prevention of alarm-related accidents due
ing concept of medical devices. I have already stated that to health care workers’ alarm fatigue [7]. Furthermore, it
from a historical point of view, pulse oximeter use is shifting widens the possibility of application contributing to health
from Type A to Type B devices. Apple Watch 6 should be care, as a method of noninvasive and continuous measure-
classified as another new type of device. From an industrial ment of light-absorbing materials in blood.”
standpoint, this product may be viewed as creating a new Today, devices with closed-loop control function have
field and can serve as a starting point for arguments over the begun to be actively used, and the level of accuracy required
form and nature of devices used for health promotion and for pulse oximeters is changing. From the beginning, Dr.
management from now on. However, from the legal point of Aoyagi had a clear vision that “the ultimate ideal of health
view, no statement has been issued by the regulatory authori- care is automatic control of treatment,” and he worked
ties like the Pharmaceutical and Medical Devices Agency actively to improve the performance. In this article, I intro-
(PMDA) in Japan or the approval/accreditation system of duce Dr. Aoyagi’s research on theory construction by multi-
Food and Drug Administration (FDA, USA) about approval/ wavelength pulse oximetry.
accreditation of this type of product.
We may expect further sophistication in the software used
for pulse oximeters in the future. For example, research is
13
Accuracy of pulse oximetry as the S pO2 value by performing all calculations in the oxy-
gen saturation range of 1–100%. Other companies have also
First, I would like to explain the accuracy of pulse oximetry, adopted technologies to separate components corresponding
which Dr. Aoyagi pursued throughout life. Although prod- to arterial oxygen saturation by extracting the characteristics
ucts currently on the market have an accuracy of approxi- of the pulse wave, but either technology involve assump-
mately ± 2% SpO2 according to specifications, it should be tions. In contrast, Dr. Aoyagi tried to express all phenomena
noted that while two-thirds of the SpO2 values are within affecting the accuracy of pulse oximetry through mathemati-
the range of accuracy specified, one-third are outside the cal formulae (i.e., to fix the theory). He tried to fundamen-
range, and that the range does not correspond to the 95% tally improve the accuracy of pulse oximetry, with the belief
confidence interval. In addition, hypoxia exposure testing that if all the ongoing phenomena can be explained, an accu-
to verify the accuracy is performed under almost ideal con- rate SpO2 value can be obtained.
ditions in healthy subjects, and various factors may further In the course of research, Dr. Aoyagi paid attention to the
decrease accuracy in the actual clinical environment. Lambert–Beer law, which is the basis for two-wavelength
Dr. Aoyagi cited oxygen management in neonates as an pulse oximetry. According to the law, the attenuation of
example and set the goal of realizing true second-generation light entering a medium (degree of optical attenuation) is
pulse oximetry with increased absolute accuracy, to reduce proportional to the extinction coefficient, which indicates
the patient burden by preventing retinopathy of prematurity how much light a medium absorbs, and the thickness of the
and reducing the number of blood collections. medium if the medium is homogeneous. Oxygen saturation
is supposed to be easily measured according to this law on
A challenge to fundamentally improving the assumption that the pulsatile component of light trans-
the accuracy mission through living tissues is caused by light absorption
of arterial blood (Fig. 1a two-wavelength model). However,
Dr. Aoyagi recognized that there was room for improvement practically, the degree of optical attenuation is not simply
in the accuracy of pulse oximetry soon after the dissemina- proportional to the extinction coefficient and the change in
tion of two-wavelength pulse oximeters in Japan. A theory thickness, because it is affected by complex factors including
considering the effects of changes other than those in the not only light absorption, but also light scattering. Since the
arterial blood is required to improve the accuracy of pulse theory has not been established, numerical values are dis-
oximetry. Changes other than those in the arterial blood played according to a look-up table based not on theoretical
itself are caused by body motion and other factors, and he calculations, but on measured values obtained from subjects
started a study based on the fundamental idea that the con- under severe hypoxic conditions. This method is invasive
struction of this theory would lead to the elimination of body and reflects the reality in which there are no standardized
motion artifacts and provide a basis for significant future calibration methods. Establishment of a theoretical formula
development. will lead not only to improved accuracy and elimination of
In products of Masimo Corporation, which is a pioneer the effects of body motion, but also to the establishment of
of algorithms with improved body motion-resistance per- a standardized calibration method, which is not currently
formance, the most provable oxygen saturation is displayed available.
Fig. 1 Models of principles

of pulse oximetry. a Two-
wavelength model. Only arterial
blood pulsates, while the
tissue does not move. b Three-
wavelength model. The tissue Arterial blood Arterial blood
is pushed by the pulsation of
arterial blood
Tissue Tissue
(a) Two-wavelength model (b) Three-wavelength model

Only arterial blood pulsates, while The tissue is pushed by the pulsation
the tissue does not move. of arterial blood.
13
Although light scattering was an unfamiliar field for Dr. Consideration of the effects of tissues
Aoyagi, he worked energetically and tried to make improve-
ments in the following order: Dr. Aoyagi first paid attention to non-blood living tissues
as a significant factor other than arterial blood. When the
1) To establish a theoretical formula for light absorp- effects of tissues are taken into account, arterial oxygen
tion/scattering, including error factors (Schuster theory saturation and the effects of tissues are variable factors. Dr.
adopted for scattering [8]). Aoyagi obtained two attenuation ratios by measurements
2) To increase the number of light wavelengths and to at three wavelengths to allow separation of the effects of
equalize the number of equations for the attenuation changes in the arterial blood and changes in the tissues
ratio between two wavelengths (Φ) to the number of (Fig. 1b three-wavelength model). Attenuation changes by
unknowns. ΔAi at each wavelength λi (i = 1, 2, 3) depend on the changes
3) To set up simultaneous equations for Φ. in the arterial oxygen saturation and tissue thickness, and
4) To obtain accurate SpO2 values from the simultaneous Fig. 2 shows the results of the simulations on the assumption
equations. of one of the two changing. The vertical axis represents the
attenuation ratio of the two wavelengths used in conven-
tional pulse oximeters ΔA2/ΔA3 (corresponding 1:1 to the
SpO2 value), and the horizontal axis represents the attenua-
The attenuation ratio in the two-wavelength system:
tion ratio ΔA1/ΔA2 obtained using an additional wavelength

ΔA2/ΔA3 (corresponding to the SpO2 value)
Due to changes
in oxygen saturation (λi). The line passing through points A and B represents the
B b change in the attenuation ratio when the tissue thickness
90% does not change and only the oxygen saturation changes,
O while the line passing through points a and b represents the
95% change in the attenuation ratio when the oxygen saturation
remains constant, and the tissue thickness changes. Although
the oxygen saturation is different between points A and a, the
100%
a A two-wavelength system cannot distinguish the difference and
displays the same oxygen saturation. It also cannot distin-
guish the difference between points B and b. Measurements
The attenuation ratio obtained by adding a wavelength:
ΔA1/ΔA2
at three wavelengths allow accurate determination of the
oxygen saturation corrected for the effects of changes in the
tissue thickness.
Fig. 2 Simulations considering the effects of tissues. Changes in the
At first, after his proposal of the theory in relation to
attenuation ratio when tissue pulsation is absent and only oxygen sat-
uration changes. Changes in the attenuation ratio when oxygen satura- tissues, this theory was not easily understood by people
tion is constant and the tissue thickness changes around him, due to the complicated behavior of light in vivo.
Blood
Transparent Blood Transparent
(changes periodically)
elastic plate (changes periodically) elastic plate
Photo
Photo LED
LED Diode
Diode
Layer of cow’s milk
Light-scattering Light-scattering
simulating tissues
plate plate
Open
(a) (b)
Fig. 3 In vitro experimental models. a Single-layer model (only arter- of cow’s milk (tissues). The thickness of the blood layer is changed
ies change). Changes in the blood layer reduces the thickness of the periodically by changing the pressure of blood using a transparent
open air layer. b Two-layer model (the effects of tissues were simu- elastic plate on one side of the blood layer.
lated). Changes in the blood layer reduces the thickness of the layer
13
Consideration of the effects of veins
To further improve the accuracy, Dr. Aoyagi paid attention

Blood oxygen saturation
to the effects of venous blood in addition to those of tissues.

Although it was difficult to construct a theory considering
venous blood, he believed that the accuracy can be funda-
mentally improved by constructing a five-wavelength model
considering the following four factors with optical effects.
1) Effects of arterial oxygen saturation.

2) Effects of venous oxygen saturation.
3) Effects of tissues.
4) Effects of changes in the venous blood volume.
Attenuation ratio He thought that since there are 4 unknowns, if measure-

ments are made at 5 wavelengths and simultaneous equa-
Fig. 4 Comparison of measured values between the in vitro models tions with 4 unknowns for the attenuation ratio Φ are set up,
and humans [13]. The measurement results in the two-layer model accurate SpO2 values could be obtained.
tended to be more closely similar to those in humans than those in the
single-layer model. Figure 5 shows an example of a comparison between
the two- and five-wavelength systems. Figure 5 (1) shows a
comparison with the oxygen saturation measured in blood
However, Dr. Aoyagi confirmed his theory and explained it samples collected at rest, which confirms that the five-wave-
with conviction by the following procedure. He investigated length system improves the accuracy. Figure 5 (2) shows
the effects of tissues by in vitro experiments using cuvettes a comparison of the SpO2 values obtained with the two-
(thin cells). Using a single-layer model in which only the wavelength system (b) and five-wavelength system (c) in
arteries change (Fig. 3a) and a two-layer model in which experiments in which the oxygen saturation was changed
tissues are simulated by a layer of cow’s milk (Fig. 3b), the by asking the subject to hold the breath and administration
attenuation ratio was measured when blood oxygen satura- of 100% O 2 by inhalation, while body motion was added (I
tion in the cuvette was changed to compare the relation- served as the subject of this study). Probes were attached
ship between the oxygen saturation and the attenuation ratio to both hands, and body motion was added by asking the
with that in human subjects (Fig. 4). The results showed subject to rub a desk with one hand at random time intervals
that the relationship between the oxygen saturation and the ranging from 0.5 to 2 s. SpO2 values obtained with the five-
attenuation ratio in the single-layer model was different from wavelength system were closer to those on the resting side as
human data that in the two-layer model was consistent with compared to the two-wavelength system. As expected at the
human data. He confirmed that the effects of tissues are a start of the study, the five-wavelength system was confirmed
major error factor and concluded that the accuracy can be not only to improve the accuracy, but also the body motion-
improved by wavelength multiplexing. resistance performance.
Fig. 5 Comparison between

the two- and five-wavelength Five- Two-
systems 100 wavelength 100 wavelength
system system
[%]
[%]
90 90
SpO22 [%]
SpO22 [%]
SpO
SpO
80 80
70 70
60 60
60 70 80 90 100 60 70 80 90 100
SaO2[%]
SaO2 [%] SaO2[%]
SaO2 [%]
13
Future issues/prospects We dedicate the following brief history of the develop-

ment of pulse oximetry and its clinical application to our
Construction of the theory of pulse oximetry considering the good old rival, the late Dr. Takuo Aoyagi.
effects of tissues and veins has only been half accomplished.
The projects introduced here are still in the research stage, Background
and many problems remain to be resolved before the prod-
ucts are launched in the market. As a researcher working In 1969, members of the research and development group
on improving the performance together with Dr. Aoyagi, I of Minolta Camera watched the astronauts, Neil Arm-
would like to follow in his footsteps and try to realize true strong and Buzz Aldrin, become the first humans on the
second-generation pulse oximeters. moon. They carried a high-resolution exposure meter,
Dr. Aoyagi paid attention to pulse wave signals causing Space Meter 1° aboard their spacecraft, Apollo 11. Ear-
noise during measurement of the cardiac output by the dye lier, in 1962, a Minolta Himatic Camera with a selenium
dilution method and conceived the idea of pulse oximetry. photocell photosensor was on board the spacecraft, Friend-
If the theory of pulse oximetry is completed, signals causing ship 7, as Mr. John H. Glenn Jr. orbited the earth. Over the
noise could also be used as new information in the measure- next decade, the photosensor evolved from a selenium pho-
ment of arterial oxygen saturation. At present, in periopera- tocell, to a cadmium sulfide (CdS) photocell, and then a
tive systemic management, cardiac output and great vessel silicone photodiode (SPD). In 1972, Masaichirou Konishi,
pressures are managed as representative values, and I think who acted as a negotiator with NASA, returned to Japan
that the development of a device that can noninvasively from the US. On his return, a new research institution
and continuously measure oxygen metabolism at the level was established in Sakai, Osaka, to develop industrial and
of each organ/tissue, which is the ultimate indicator, will medical measuring devices. The first medical device devel-
contribute to improve the outcome of patients or treatment. oped in the new institution was a photoelectric pulse wave
meter (photoplethysmograph). It utilized a light emission
diode (LED) and a silicone photodiode (SPD) to generate
The development of pulse oximeters and analyze transmitted red light through the fingertip.
in Japan: good competitors, Nihon Kohden Although the response time of SPD was far shorter than
and Minolta Camera CdS, the device did not become popular in the medical
field. This photoelectric pulse wave meter, however, turned
Ikuto Yoshiya, M.D., Ph.D. out to be the precursor of the fingertip pulse oximeter,
Honorary Professor, Department of Anesthesiology, OXIMET-Met-1417.
Osaka University Medical School. Osaka, Japan. In 1973, Morimasa Takeda et al. reported that the pulsa-
Akio Yamanishi. tile wave obtained by the photoelectric measurement of light
Former Chief, Medical Equipment Division, Minolta transmitted through the fingertip represented the fluctuation
Camera Co., Ltd. of the thickness of blood in accordance with pulsation in
(Konica Minolta Co., Ltd., at present), Tokyo, Japan. Japanese journal. This was the moment that the Minolta
The pulse oximeter is currently one of the most indis- team became aware of the possibility of developing a non-
pensable devices in the medical world, like the ECG or the invasive device to measure arterial oxygen saturation.
sphygmomanometer. Even in early spring, 2021, as SARS- The principle of Wood-type ear oximetry (Wood EH and
CoV-2 is still killing thousands of people per day around Geraci JE, 1949 [9]) utilized the difference of absorption of
the world, some local governments in Japan are reportedly transmitted light between when the earlobe was arterialized
providing pulse oximeters to COVID-19 patients who are by warming and when it was made ischemic by pressing it
not hospitalized and have to quarantine themselves at home. with a translucent balloon. It occurred to Yamanishi and his
It was indeed a great achievement to invent pulse oxime- colleagues that pressing and depressing the earlobe made a
try, improve its accuracy, and miniaturize the pulse oximeter. kind of pulsation. Having just developed a fingertip pulse-
All three aspects were essential for the pulse oximeter to wave meter, they soon created an algorithm to obtain oxygen
become popular worldwide. In April 2020, Takuo Aoyagi, saturation of arterial blood. In short, the incidental light that
Ph.D., who was the first inventor of the pulse-type oximeter travels across the fingertip is absorbed by arterial and venous
in the world, passed away to the great regret of his colleagues blood as well as by the tissues of the fingertip (skin, muscle,
as well as everyone in the medical community who knew of bone, connective tissue). Assuming that pulsatile fluctuation
his great achievements. The authors, Akio Yamanishi and of the transmitted light is caused solely by the inflow of
Ikuto Yoshiya, and their colleagues, were competitors of Dr. arterial blood, hemoglobin oxygen saturation can be calcu-
Aoyagi and his team as they worked on the development and lated by the mathematical subtraction of light absorption by
clinical application of pulse oximeters. fingertip tissues from whole light absorption when arterial
13
blood is full. The Minolta team was more than excited in incorporated into the chassis of the instrument and incident/
anticipating an entirely new type of in vivo oximetry, the emission light traveled through a pair of fiberoptic paths.
first since Wood and Geraci [9]. However, a few weeks later, In 1977, this device was marketed as OXIMET-Met-1471
the team members were astonished and disappointed to find (Fig. 6).
a Japanese paper by Aoyagi et al. entitled “The improvement
of ear-piece oximeter” in the Proceedings of the 1974 Spring Clinical application of OXIMET
Meeting of the Japanese Society of Medical Electronics and
Biological Engineering. Minolta made a patent application In 1977, one of the authors, I. Yoshiya, was consulted by the
as soon as possible, but it turned out the original idea of other author, A. Yamanishi, about the clinical applicabil-
pulse oximetry by Aoyagi was 1 year ahead of Minolta as ity of OXIMET. Yoshiya was then working in the Intensive
was recorded in Aoyagi’s research notes (in Japanese). Care Unit (ICU) of Osaka University Hospital and jumped
Aoyagi’s invention of the principle of pulse oxime- at the suggestion, because ICU patients needed invasive arte-
try started when he was working on the development of a rial gas measurements too frequently. OXIMET seemed to
cardiac output measurement device using the dye dilution have potential as a bed-side monitoring device in critically
method. Aoyagi had noticed that the spectrophotometric dye ill patients.
dilution curve fluctuated with heartbeats. It was a kind of First, we (I. Yoshiya and Y. Shimada, et al.) calibrated
reversed thinking to utilize the pulse wave to estimate arte- the instrument against the oxygen saturation measurements
rial oxygen saturation in a non-invasive manner. The authors obtained from blood samples of ICU patients [11]. It seemed
feel proud of Aoyagi’s great invention originally conceived that the pulse oximeter tended to overestimate arterial oxy-
in Japan. We are also happy to have run a good race with gen saturation below 90%, compared with the oxygen satura-
Aoyagi and his colleagues at the same time. tion measured on blood samples with Radiometer OSM-2.
The Minolta and Osaka University team tested the hypoth-
Development of the fingertip pulse oximeter esis that the overestimation of oxygen saturation with the
(OXIMET‑Met‑1471, Minolta Camera, Co., Ltd.). pulse oximeter was due to the multiple scattering of inci-
dent light by the blood corpuscles. K. Hamaguri (Minolta)
After the first patent application made by Minolta for the devised a model cell to which blood or hemoglobin solution
basic principle of pulse oximetry, Minolta made a more was pumped in and out by a rotary pump (Fig. 7). Using
detailed patent application for an apparatus, including cir- the device, the effect of multiple scattering was successfully
cuits, designed by T. Kisanuki and Y. Majima. Calculation compensated for, as was previously reported by Shimada
of oxygen saturation was made by a simple linear equation et al. [10]. The accuracy of measurements by OXIMET has
from light absorption at the wavelengths 805 nm (isosbestic been reported by Yoshiya et al. [11] and Sarnquist et al. [12].
point) and 650 nm [10]. The 1980 report by Yoshiya et al. [11] has the honor of being
Although a light emission diode (LED) was used as the the first publication in English to introduce pulse oximetry
light source for the pulse wave meter, a halogen lamp was as reported by E. C. Jr. Pierce at the 3 4th E.A. Rovenstine
employed with the pulse oximeter because of a shortage of Memorial Lecture. A. Fukunaga (Professor of Anesthesiol-
LED lights. Because of this, the light emission lamp was ogy, UCLA, Harbor, at that time) informed Yoshiya about
this lecture, but regretfully the latter failed to attend the ple-
nary lecture.
The authors utilized OXIMET as a safety monitor in the
intensive care ward and in the operating theater. It was also
used as a monitor for patients with sleep apnea, but it could
not be used routinely due to the size and weight of the finger-
probe with fiberoptics.
Downsizing and weight reduction of pulse

oximeters for clinical use
As stated above, the probe and fiberoptic cables of OXIMET

were too large and heavy to be used as a bed-side moni-
Fig. 6 OXIMET Met 1471. The light emitted by a light emission tor or a monitor for critically ill patients during emergency
diode travels to the finger probe and the transmitted light is analyzed
transportation. It was essential for both the finger probe and
by a silicon photodiode mounted in the chassis. The incident and
transmitted light travels to and from the chassis through the fiberop- the amplifier to be downsized and made lighter to allow
tics, respectively the pulse oximeter to be widely used in the clinical field.
13
saving, vibration resistance, ease of handling, and cost

reduction.
Aoyagi’s continuing effort to develop pulse oximetry
was indeed admirable. He led the development team of
Nihon Kohden to release OLV-1100/1200 into the market
in 1987 and never stopped developing more accurate and
motion-resistant pulse oximeters by adopting newer scat-
tering theories and multiple-wavelengths to compensate for
the scattering of light by blood corpuscles and body move-
ment of the patient [13]. He gave a speech at the 34th Annual
Meeting of the Japan Society of Technology in Anesthesia
in commemoration of receiving the 2015 IEEE Medal for
Innovations in Healthcare Technology. He said they had suc-
cessfully settled the problem of body movement. Yamanishi
remembers Aoyagi remarked in a chat with him “You’ll go
and find pulse oximeters at supermarkets or electronic shops
in the not-too distant future”. His prophecy has come to pass
as of 2019–2021, in the pandemic of COVID-19.
Pulse oximetry was first invented by Aoyagi (Nihon Koh-
den), but there was competition from Minolta in Japan. The
Fig. 7 A pulse-generating apparatus for the in vitro pulse oximetry idea soon propagated to the US, where a device was pro-
devised by Hamaguri. A rotary pump generates pulse waves in an duced using a smaller probe applicable for use in clinical
artificial cell with a pair of translucent glass windows on both sides of settings. The improved pulse oximeter was imported back to
the cell. Light emitted by a halogen lamp travels across the windows.
The transmitted light is spectrophotometrically analyzed for oxygen
Japan and was further improved and miniaturized. Currently,
saturation by using the pulse oximetry principle. By changing the Konica-Minolta has a pulse oximeter weighing less than
hematocrit of the sample blood pumped in the cell one can estimate 40 g, and pulse oximeters are routinely used on COVID-
the effect of scattering of light by blood corpuscles. Namely, the oxy- 19 patients worldwide. The authors feel Aoyagi would have
gen saturation by the in vitro pulse oximetry and that measured by a
Radiometer (OSM-2) are compared with different hematocrit of the
been happy about the internationalization of the develop-
sample blood ment of the pulse oximeter.
Finally, we would like to express our sincere condolences
to Dr. Aoyagi’s family.
In 1981, Nellcor and Ohmeda, respectively, released pulse
oximeters into the market with small finger probes utilizing
LED and SPD. The pulse oximeter soon became popular in
the US, particularly in the operation theater. Several years Aoyagi’s legacy in the US: what influenced
later, the pulse oximeter was imported from the US to its its acceptance?
birthplace, Japan.
Minolta also developed PULSOX-7 in 1987 that consisted Jeffrey B. Cooper, Ph.D.
of a finger probe using LED/SPD and a small, lightweight Professor of Anesthesia, Harvard Medical School,
analyzer with a memory chip. This portable pulse oximeter Department of Anesthesia, Critical Care & Pain Medicine,
was widely used for monitoring home oxygen therapy, sleep Massachusetts General Hospital, Boston, MA, USA
apnea, and transportation of critically ill patients. In 1990, Executive Director Emeritus & Senior Fellow, Center for
PULSOX-7 climbed the summit of Mount Xixabangma Medical Simulation
(height: 8,027 m) carried by Akira Demizu, M.D. who was While Takuo Aoyagi’s name was not widely known in
then a staff anesthesiologist at Osaka University Hospital. the US, his invention of a practical way to monitor oxygen
Demizu used to be a member of Kyoto University Alpine saturation has had a huge impact on healthcare, on anesthe-
Club and joined the Kyoto University Medical Research siology in particular. He is highly deserving of the honors
Expedition to Xixabangma in 1990, to investigate the rela- that have been bestowed on him for this contribution. Now,
tionship between insomnia and arterial oxygen saturation at on his passing, it is fitting that we pay tribute and recognize
high altitude. The successful Himalayan expedition of the him for the countless lives his invention has saved and for his
pulse oximeter was attained by the ceaseless efforts of the creativity and persistence that brought this gift to the world.
Minolta team to attain size and weight reduction, energy I am not an historian. I do not have all the facts or even
empirical evidence to claim exactly what influenced the
13
relatively rapid acceptance of this new technology by a pro- Perhaps, the most appealing feature was the changing sound
fession that typically is skeptical of the latest technology of the pulse tone with decreasing saturation. My guess is
fad and demands evidence before action. In addition, in my that the combination of these attributes was the most impor-
experience, anesthesiologists pride themselves on individual tant reasons for quick adoption in anesthesia. This is a good
responsibility, competence and vigilance to maintain the example of remarkable human factors being heavily respon-
safety of the care of their patients. Attention to vital signs sible for a lifesaving technology, not just the measurement
that could be easily observed, including heart rate, blood itself.
pressure, ECG and skin color were thought by many to be I suspect many believe that the standards for minimal
sufficient for the attentive anesthesiologist. This is especially monitoring during anesthesia established by the Ameri-
so for those who had grown up in a time, where there was can Society of Anesthesiologists (ASA) in October 1986
little technology and before the term “patient safety” was played a role in dissemination of this innovation. While
coined. they may have had some influence on raising awareness of
How did so many come to accept pulse oximetry in the the need for some monitoring technologies, the standards
absence of definitive trials of its effectiveness in preventing did not at first require pulse oximetry or even strongly
harm? Yes, there were some studies to point to its useful- encourage its use. The ASA standard was a direct evo-
ness, but little to justify the expense on a cost/benefit basis. lution from the standard promulgated by the Anesthesia
What influences led to almost ubiquitous use of pulse oxime- Departments of Harvard Medical School in 1985; that
try in just a few years after the introduction of the first prac- standard did not mandate pulse oximetry. The rationale
tical commercial monitors in the US? I will explore what I in developing a standard (I was there and promoted that
think were a few key factors, but without the data I cannot rationale) was to first establish the precedent for a basic
draw definitive conclusions. standard. To achieve acceptance that meant including only
I think the most critical factor for accepting pulse oxi- items that had stood the test of time and that no reason-
metry is that it tapped into a visceral desire for all anesthe- able anesthesiologist could argue against. We thus could
siologists to eliminate the guesswork to ascertain the state not immediately require pulse oximetry, because there was
of a patient’s oxygenation. I do not know who first realized still even little widespread personal experience among
the huge potential, but Bill New, an anesthesiologist and anesthesiologists. While including a requirement for it
engineer certainly played a key role as did his colleague and would have been prescient, in the absence of data or wide
partner in the business, Mark Yelderman, also an anesthesi- experience, the idea of a standard may have been success-
ologist. From their own clinical experience, they recognized fully opposed by vocal skeptics who might have a strong
that having such information, updating continuously within voice in opposition to any standards.
a few heart beats, would make any anesthesiologist feel a bit The rationale for the original ASA “Standards for Basic
less anxious, especially during critical moments. Intra-Operative Monitoring” was similar, as described in an
Much credit has to be given to the design of the N-100 article in the Spring, 1987 APSF Newsletter [14]:
Pulse Oximeter (Nellcor), especially its simplicity and bril- “The ASA committee debated whether to include cap-
liant human factors design features (Fig. 8). Getting such nography and pulse oximetry as the “standard of care”. At
critical information from a single number, clearly displayed that time, it was felt impractical to mandate very specific
via LED’s (a relatively new technology at the time), was a (and very expensive) high tech equipment when the greatest
game-changer. The ease of application of the sensor also focus of the effort was the general extension of the vigi-
contributed to easy use and acceptance. The look and func- lance of the anesthesiologist. The committee also considered
tion of the large adjusting knob were elegant and practical. the questions of the consistency of performance of these
two instruments and the availability at that time relative
to the potential demand. However, E. C. (“Jeep’) Pierce,
M.D., committee member and past president of the ASA,
now states, “Capnography and oximetry are becoming so
widespread that they will be functional standards. Projecting
current trends, it is likely that by the end of 1988, enough
oximeters will have been sold for there to be one available
for every operating room in the country”.
It was not until 1989 that the ASA standard was amended
to require pulse oximetry for all anesthetics. It was likely
that almost all anesthesiologists were by then using pulse
oximetry for every anesthetic.
Fig. 8 N-100 Pulse Oximeter (1983, Nellcor)
13
Over the years, I have heard it said that The Anesthesia during anaesthesia was virtually never routinely monitored.
Patient Safety Foundation strongly influenced adoption of Trans-cutaneous oxygen tension t cpO2 monitors were devel-
pulse oximetry. Being one of the founders of APSF, I know oped and marketed in 1976 and soon were in use in NICU.
that we were careful not to promote specific technologies However, these were generally unsatisfactory for use during
over others because of concerns of any appearance of con- anaesthesia. Their accuracy was compromised by anaesthe-
flict of interest, since some of those companies donated to sia induced changes in cutaneous blood flow and also by the
the organization. I do suspect that APSF’s strong advocacy direct effect of volatile agents on the sensor [19].
for patient safety and focus of attention on errors in prac- The Hewlett-Packard Company marketed an ear oxi-
tice raised awareness of all anesthesia providers about the meter in 1976. This was cumbersome to apply and was
need to take stronger measures than just relying on their never widely adopted. Its performance during anaesthesia
own vigilance. in healthy volunteers was reasonably accurate, but the reli-
I think that there was another strong force that was ability during anaesthesia induced circulatory disturbances
responsible for relatively rapid spread of pulse oximetry in was uncertain [20]. There was obviously interest amongst
anesthesia. Fineberg et al., in 1978, reported on a survey anaesthesiologists in the possibility of monitoring arterial
of how new ideas were adopted into practice in anesthesi- oxygenation, but there was as yet no simple easy way to
ology using three different examples [15]. While publica- reliably accomplish this.
tions are generally the most influential means to persuade In early 1982, when I was serving as the Head of the
anesthesiologists to adopt new ideas into practice, learning Department of Anaesthesia at the Hospital for Sick Chil-
from colleagues is a close second influence. Those findings dren (HSC) in Toronto, then the largest academic pediatric
likely applied to the spread of pulse oximetry, which was service in North America, I had a visit from Dr. William
introduced only a few years after that study. I suspect that New. He brought with him a prototype of a pulse oximeter
it often happened that anesthesiologists heard excited anec- (Fig. 9). This machine needed no calibration and was very
dotes from their colleagues about how valuable this addition easy to apply to the patient using a flexible adhesive dispos-
to their practice was. Perhaps, they heard of a great save able sensor, or a reusable clip-on sensor. He asked if we
resulting from early discovery of an error or of the confi- would be prepared to evaluate this machine on some of our
dence during intubation on hearing that so recognizable tone patients.
indicating the state of saturation. Such word of mouth may At that time (1982), I understood that Dr. New had been
have contributed greatly to pulse oximetry “spreading like an anaesthesiologist at Stanford University and that previ-
wildfire” even in the absence of much empirical evidence ously he had been a graduate electrical engineer at Hewl-
of its effectiveness. ett Packard. He had now become an entrepreneur and was
Regardless of exactly how the idea spread so quickly, forming a company to produce and market this oximeter. He
all anesthesiologists and, more so, all patients having an had a PhD in physiology from UCLA (1963) and an MS in
anesthetic, are indebted to Takuo Aoyagi for his marvelous business from Stanford Univ. (1981).
ingenuity that has so greatly contributed to the dramatic We agreed to conduct a study and I assigned a post-
improvements in anesthesia patient safety. graduate fellow, Dr. Rainer Deckhard to this project. We
studied the performance of the prototype in a series of
Nellcor: Continuous perioperative oximetry

comes to North America
David J. Steward MB BS, FRCPC.

Honorary Professor, Department of Anaesthesia and
Pharmacology.
University of British Columbia, Canada.
Instruments intended to non-invasively measure the oxy-
gen saturation of arterial blood were introduced as early as
1942 [16]. Very rarely, their potential value as a monitor
in anaesthetized patients was evaluated, as, for example,
during pediatric tonsillectomy in Montreal in 1951 [17].
A similar instrument was also used in Toronto to monitor
anaesthetized infants during the 1950s in the earliest days
Fig. 9 Nellcor Pulse Oximeter Prototype as delivered to us in 1982.
of cardiac surgery [18]. However, as late as 1982, in North Note the absence of the "N-100" designation, this was added at a later
America, the hemoglobin oxygen saturation of patients date as N-100A. The first commercial model was called N-100B.
13
cardiac surgical patients between 6 months and 9 years The accompanying catalogue description includes the
of age and found good correlation with co-oximeter read- following:
ings on withdrawn blood samples. We also studied its "Like most modern medical devices pulse oximeters
performance in a series of preterm infants in the NICU represent advancements in technology and a culmina-
who were also being monitored by a tcPO2 monitor. Thus, tion of years of knowledge in basic and clinical sciences
we compared the two methods of monitoring directly. We gained by the trial and error of numerous researchers.
reported our findings in 1984 in Critical Care Medicine Japanese researcher, Takuo Aoyagi is often recognized
[21]. It is of some interest that the publication of our for putting the "pulse" in pulse oximetry by using the
paper was considerably delayed in the review process. It waveform produced by the arterial pulse to measure and
was finally published unchanged. Much later, I discov- calculate SpO2. He first reported on the work of his team
ered that this delay had been due to the action of a single in 1974."
reviewer, who, it appeared had an interest in a company
that marketed tcPO2 monitors!
In mid-1984, I left HSC Toronto to assume the posi- Pulse oximeter: dissemination in neonates
tion as Chief of Anaesthesia at the newly opened British and its history
Columbia’s Children’s Hospital in Vancouver. When I
arrived there, I found that on the proposed budget for the Hiroshi Nishida, M.D., Ph.D.
department was a t cPO 2 monitor! I cancelled this order Professor Emeritus, Tokyo Women’s Medical University,
and replaced it with an order for Nellcor 100 pulse oxi- Tokyo, Japan.
meters. By the middle of 1985, we had one Nellcor pulse
oximeter in every operating room.
Introduction
The model N-100 was marketed by Nellcor in 1983
with an extensive advertising campaign. They mass pro-
Experts have already discussed the basic principles and his-
duced a machine which was extremely easy to apply to the
tory of development of pulse oximeters in other sections.
patient, required no calibration, and appeared to reliably
Therefore, in this chapter, I provide an overview of the his-
follow arterial oxygen saturation levels. Although Nell-
tory of introduction of pulse oximeters in neonatal care in
cor’s promotions through ASA and IARS meetings and in
Japan. I also explain the significance of development of
the journals were outstanding, it was a product that sold
blood oxygen level monitors dedicated to neonates, particu-
itself and it was a product whose time had come!
larly premature infants, in the context of their clinical sig-
Sales of the machines rapidly accelerated, and though
nificance in reducing the risk of retinopathy of prematurity
there were some other models available, "Nellcor" and
and hypoxic brain damage.
"Pulse Oximeter" became almost synonymous. By the end
of 1986, a pulse oximeter was in nearly every operating
room, recovery room, and intensive care unit in North Characteristics of medical care of neonates,
America. The Anesthesia Patient Safety Foundation bul- particularly premature infants
letin of Spring 1987 predicted:
"Projecting current trends, it is likely that by the end of Human babies, even full-term (40 wks) infants, are born
1988, enough oximeters will have been sold for there to with physiological immaturity, in compensation for the
be one available for every operating room in the country”. large brain supporting the high level of human intelligence.
In October of 1986, the American Society of Anesthe- This can be easily imagined from the fact that while other
siologists recommended that every anesthetized patient large mammals begin to walk independently almost imme-
should have arterial oxygen level constantly monitored. diately after birth, human neonates can just begin to hold
“During all anesthetics, a quantitative method of their heads up by 3 months after birth and begin to walk
assessing oxygenation such as pulse oximetry shall be alone by around the age of 1 year. In particular, in regard to
employed. When the pulse oximeter is utilized, the vari- respiration, gas exchange between the fetus and the mater-
able pitch pulse tone and the low threshold alarm shall nal placenta occurs through the umbilical cord and fetuses
be audible to the anesthesiologist or the anesthesia care make breathing-like movements in the womb, but pulmonary
team personnel [22].” function only begins to be established at birth. Infants easily
In 5 years, something that had almost never been done become apneic due to pulmonary immaturity, and sudden
before became a recommended standard of practice. infant death syndrome (SIDS), which occurs due to delayed
An original Nellcor N-100 monitor is on display in the recovery from sleep apnea, is a well-known entity.
Wood Library-Museum of Anesthesiology in Chicago. For this reason, in the history of medical care of pre-
mature infants, apnea monitors are counted as the medical
13
devices that have contributed the most to preventing SIDS transcutaneous bilirubin measurement method, which has
and brain damage due to hypoxia. In 1972, when I became a also spread from Japan to the world, together with Akio
neonatologist, I remember that young residents, equivalent Yamanishi of Minolta Co., Ltd (who also invented the fin-
to human monitors, used to be stationed near the incubators gertip pulse oximeter, the currently commonly used type of
for premature infants all day long; at present, however, the pulse oximeter around the world).
world of medical care has changed dramatically, and prema- In transcutaneous partial pressure of oxygen measure-
ture infants are monitored by pulse oximetry in every NICU. ment, the skin is warmed to arterialize the capillaries and
the blood partial pressure of oxygen is measured using the
principle of polarography. At first, a German obstetrician,
Retinopathy of prematurity and blood oxygen levels
Prof. Huch, developed this device to measure fetal scalp par-
tial pressure of oxygen, and it was Dr. Itsuro Yamanouchi
Retinopathy of prematurity (ROP) is thought to be caused by
who demonstrated that the device is also clinically useful
the toxicity exerted by high concentrations of oxygen. At one
for neonates, which led to its commercialization by German
time in the US, instituting the limitation of the oxygen con-
and Swiss companies. Thus, in contrast to pulse oximeters,
centration that could be administered to premature infants to
transcutaneous partial pressure of oxygen monitors were
40% decreased the incidence of ROP, but increased the fre-
developed in Europe, while their usefulness in neonates was
quency of brain damage occurrence, which triggered a dis-
demonstrated by Dr. Yamanouchi in Japan. However, the
cussion on whether it was more important to protect the eyes
sensors of transcutaneous partial pressure of oxygen moni-
or the brain. Since, it has been revealed that ROP is caused
tors must be replaced every 2–3 h, because they could get
not by high oxygen concentrations per se, but by retinal tis-
hot (heated up to 43.5 °C), and when the skin of the pre-
sue ischemia induced by constriction of the retinal arteries
mature infants begins to thicken with age, the accuracy of
caused by oxygen supplementation at high concentrations,
the measurement would decrease; therefore, transcutaneous
which has led to a focus on the necessity of adequate meas-
partial pressure of oxygen monitors began to be replaced by
urement of the arterial blood oxygen levels. However, the
pulse oximeters of oxygen saturation monitoring. At that
partial pressure of oxygen in arterial blood, specimens of
time, Dr. Yamanouchi was concerned that the use of pulse
which are difficult to obtain, was not found to be correlated
oximeters in neonates might be associated with a gradual
with the incidence of ROP. This suggests that an accurate
increase in the incidence of ROP, because in the measure-
assessment cannot be made by a single measured value of
ment of high blood oxygen levels, a slight difference in the
the partial pressure of oxygen, which changes continuously,
arterial oxygen saturation corresponds to a large difference
but by continuous monitoring of the arterial oxygen tension.
in the arterial partial pressure of oxygen [23]. Fortunately,
Namely, it became clear that devices that allow continuous,
however, the incidence of ROP did not increase with the
not intermittent, monitoring and recording of the arterial
introduction of pulse oximeters, due to the improvement in
blood oxygen levels are required to prevent ROP, which has
the accuracy of pulse oximetry measurements and the care-
led to the development of transcutaneous partial pressure of
ful management by nurses and other staff working in NICUs
oxygen monitors and pulse oximeters.
across Japan.
Widespread use of these medical devices has greatly
decreased the incidence of acquired blindness in prema-
History of appropriate dissemination of pulse
ture infants. However, at present, while many very preterm
oximeters in Japanese neonatal care
infants with a birth weight of 500 g or less (approximately
23 weeks of gestation) grow normally, ROP is encountered
As mentioned in other chapters, the principle of pulse oxi-
even in infants managed with adequate blood oxygen levels.
metry was discovered in Japan, but Japan lagged far behind
Therefore, immaturity is at the root of the pathogenesis, and
the US in allowing its clinical application to spread as a
I would like to add that further studies are ongoing.
monitor. In neonates, in particular, this is partly because
transcutaneous partial pressure of oxygen monitors had
From transcutaneous partial pressure of oxygen
already been widely introduced, and furthermore, because
monitors to pulse oximeters
not only medical device manufacturers, but also medical
professionals did not yet fully understand the usefulness of
Transcutaneous partial pressure of oxygen monitors were
pulse oximeters in neonatal care.
initially developed to continuously monitor the blood oxy-
In those days, pulse oximeters were very unpopular; phy-
gen levels in neonatal care, and there is the late Dr. Itsuro
sicians and nurses working in Japanese NICUs felt that pulse
Yamanouchi’s interesting episode of their introduction
oximeters were useless, because they were too sensitive to
in Japan. He believed that noninvasive care is important
body motions and generated too many false alarms, and that
in the medical care of premature infants and developed a
they were unreliable as compared to transcutaneous oxygen
13
monitors. In addition, the manufacturers themselves also of pulse oximeters. As a result, pulse oximeters are currently
had insufficient knowledge, and I remember once when I used routinely to monitor the blood oxygen levels even in
complained that I was having trouble with the breakage of neonates.
the wires of the sensors attached to the hands and legs of the
neonates, the electrical engineers who visited the NICU in Concluding remarks
response to my complaint, who had previously exclusively
observed only anesthetized, immobilized adult patients, In the chapter entitled “Japan’s contribution to the world
were astonished to observe the continuous body motions of in the development of blood oxygen monitors that protect
the neonates in incubators. Furthermore, low temperature the brain and eyes” in my book entitled “Trajectory of the
burns due to pulse oximeters, which they had bluntly said Development of Japanese Neonatal Care (in Japanese),
were unbelievable, were considered to result from local heat Medicus Shuppan Publishers, Co., Ltd., 2015,” I stated that
retention caused by slight wire breakage in the light-emitting “the historic achievements of Dr. Itsuro Yamanouchi in dem-
part and inhibition of perfusion due to compression. Subse- onstrating the efficacy of transcutaneous partial pressure
quently, various technical improvements have been made, of oxygen monitors in neonates and of Dr. Takuo Aoyagi in
and pulse oximeters have evolved to sufficiently withstand discovering the principles of pulse oximetry, are the pride of
daily use in NICUs; however, the experiences with early Japan, worthy of special mention, as they have contributed
models left a strong impression on the users, which could to saving the lives of many neonates and preventing blind-
explain why the use of pulse oximeters has spread rather ness due to ROP worldwide.”
slowly in Japanese neonatal care. In particular, pulse oximeters are used for medical pur-
Dr. Katsuyuki Miyasaka took up the mission to remove poses in wide areas not limited to neonatal care, and Lindahl
this unfavorable impression and disseminate the clinical from Sweden, who was a member of the Nobel Commit-
importance of pulse oximeters in NICUs throughout Japan. tee and gave a keynote speech at the 1997 Annual Meeting
Dr. Miyasaka organized the “Hakone workshop on neo- of the Japanese Society of Pediatric Anesthesiology stated
natal pulse oximeters” at the Fujiya Hotel, Miyanoshita, that Dr. Aoyagi’s contribution to humanity deserves a Nobel
Hakone, which is famous as one of the three major classic Prize. Dr. Aoyagi stated, in his letter to me (September
Japanese hotels, on July 11, 1987, to which he invited the 2017), that he was trying to obtain theoretical pulse oxime-
chiefs of major NICUs across Japan. The original purpose try values based on the theory of scattered light to leave his
of the workshop was to determine whether the algorithms footprints as a researcher deserving it. He accomplished this
of foreign pulse oximeter manufacturers for calculating the task before his demise, and his achievements went down in
arterial oxygen saturation were also applicable to Japanese history, although he missed the Nobel Prize.
neonates, by comparing pulse oximeter (Omeda Biox 3700)
measurements with measurements of the arterial oxygen
levels made in samples collected via an arterial line, as How pulse oximetry influenced medicine
part of the research projects of the Psychosomatic Disorder and how its evolution will influence
Research Neonatal Management Group of the Ministry of medicine
Health and Welfare (leader: Kazuo Okuyama, co-investi-
gator: Hiroshi Nishida). Another purpose was to have Dr. Joe Kiani, BSEE, MSEE.
Joyce Peabody, a neonatologist from Loma Linda Univer- Founder, Masimo & Patient Safety Movement Founda-
sity, provide a thorough explanation about the principles of tion, Irvine, CA, USA.
blood oxygen monitors and discuss the actual status of use In 1974, Japanese bioengineer Dr. Takuo Aoyagi made
of pulse oximeters in NICUs in the US, so that Japanese neo- one of the most impactful inventions in patient monitoring
natologists could clearly understand the principles and show and with it improved patient safety [24]. Dr. Aoyagi was in
greater interest in the use of pulse oximeters. At that time, pursuit of noninvasive cardiac output monitoring, but instead
Dr. Miyasaka mentioned differences between functional oxy- invented pulse oximetry. Prior to Dr. Aoyagi’s invention,
gen saturation (So2) and fractional So2, from the point of oxygen saturation monitoring was relegated to the laboratory
view of neonatal care: methemoglobin levels increase when due to the bulkiness of the devices that measured it, such as
nitric oxide (NO) inhalation therapy is provided for persis- the 8-wavelength ear oximeter developed by Hewlett Pack-
tent pulmonary hypertension of the neonate (PPHN) and the ard. Dr. Aoyagi filtered the arterial pulse signal and normal-
carbon monoxide (CO)–hemoglobin concentration increases ized it against all of the variables that the 8-wavelength ear
with bilirubin production. oximeter had to account for (such as tissue thickness, skin
This, along with advances in the functioning of pulse oxi- pigmentation and other factors) by dividing the filtered arte-
meters, such as improvements of the measurement accuracy rial pulse information by all the information the photo detec-
and simplicity of use, led to improvements in the reliability tor measured [25]. This was Dr. Aoyagi’s so-called “AC/
13
DC” invention. Then, dividing the ratio at one wavelength just S pO 2, but pulse rate, respiratory rate, fluid levels,
(sensitive to oxygenated hemoglobin) by the ratio at another respiration effort, total hemoglobin, carboxyhemoglobin,
wavelength (sensitive to both oxygenated and deoxygenated methemoglobin, perfusion index (PI), and oxygen reserve
hemoglobin) gave us the “ratio of ratios,” which is corre- index (ORi).
lated with arterial oxygen saturation (empirically derived Takuo Aoyagi’s curious fascination and ardent research
from laboratory studies). Through his pioneering work and gave the world the gift of pulse oximetry. He had an idea
meticulous research, Dr. Aoyagi invented conventional pulse and he made it his life’s work to realize it. In the years
oximetry. Today, many consider pulse oximetry to be the before he passed away, he even brought out his nonin-
“fifth vital sign.” vasive cardiac output monitor. Clinicians, patients and
Dr. Aoyagi’s invention of pulse oximetry was a signifi- engineers owe Dr. Aoyagi a debt of gratitude. We will
cant advancement in patient monitoring and safety. Before remember Dr. Aoyagi for his boundless work, signifi-
the advent of pulse oximetry, the rates of anesthesia- cant contributions to clinical care, and his kindness and
related deaths and brain injury were very high, because humility.
the only methods available to the anesthesiologist to
check arterial oxygen saturation were intermittent blood
lab tests or observing the color of the lips, purple indi- Pulse oximetry and innovation—ability
cating low oxygen saturation. Although a 20,000-patient to translate invention to innovation
study showed no difference in mortality of patients with
or without pulse oximetry [26], anesthesia-related fatali- Hirokazu Ogino, MBA, MS,
ties dropped from 1-in-10,000 to 1-in-1 million after the President and Chief Executive Officer of Nihon Kohden
advent of pulse oximetry [27]. Clinicians immediately Corporation, Tokyo, Japan.
recognized the immense value of pulse oximetry and it On June 20, 2015, I witnessed a historical moment in
quickly became a standard of care in operating rooms and the ballroom of the Waldorf Astoria hotel in New York.
intensive care units. Dr. Takuo Aoyagi, who invented pulse oximetry, was being
Dr. Aoyagi’s pulse oximeter paved the way for Masi- awarded a Medal for Innovations in Healthcare Technology,
mo’s invention of Measure-through-Motion and Low the first for a Japanese, by the Institute of Electrical and
Perfusion technology [28]. Continued innovation is para- Electronics Engineers (IEEE), the world’s largest association
mount to improving patient outcomes. While Dr. Aoyagi’s for electrical and electronic engineers, the founders of which
invention assumed all blood that pulsates is arterial blood, included greats like Thomas Alva Edison. Even though he
Masimo’s invention accounted for venous blood during was 79 years at that time, Dr. Aoyagi walked resolutely on to
motion by separating venous blood pulsation from arte- the stage in a tuxedo, gave an acceptance speech which, even
rial blood, hence providing increased accuracy for spe- if not fluent, was clear and powerful, and received a great
cific patients, such as the poorly perfused in the OR, ICU ovation [33]. This was a moment of recognition of the great
patients, such as neonates, and awake patients in post- invention by Dr. Aoyagi and of the contribution of Japan to
surgical wards and at home. medical safety worldwide (Fig. 10).
Multiple clinical studies using the Measure-through- Nihon Kohden Corporation also takes great pride in the
Motion technology have demonstrated a host of success- invention of pulse oximetry by Dr. Aoyagi, although it has
ful patient outcomes, including a dramatic reduction
in Retinopathy of Prematurity (ROP) in NICUs [29],
the ability to detect Critical Congenital Heart Disease
(CCHD) [30], and to detect patient deterioration from
Opioid Induced Respiratory Depression (OIRD) [31, 32].
Pulse oximetry is no longer limited to the hospital. Clini-
cians can now monitor their post-surgical patients that
have been prescribed opioids or COVID-19 patients who
may not need ICU care in the comfort of their homes.
In the future, pulse oximetry may indeed become the
most important of the five vital signs. Not only because
oxygen is necessary for life, but its measurement and
principles of measurement have resulted in a greater
understanding of the heart, lungs, and systemic issues.
Today, the modern pulse oximeter, which we call the
Pulse CO-Oximeter, has the capability to measure not Fig. 10 A souvenir photo from the 2015 IEEE Honors Ceremony
13
“Nellcor, Inc. (snip) widely advertised the clinical impor-

tance of pulse oximeters.”
Using this past failure as a lesson, Nihon Kohden has
since attempted to disseminate new inventions derived from
pulse oximeters worldwide. Estimated continuous cardiac
output (esCCO), first invented by Dr. Yoshihiro Sugo of our
company, is a non-invasive measure of the pulse wave transit
time from the electrocardiographic waveform and the pulse
wave from a fingertip pulse oximeter, and provides a con-
tinuous estimate of the cardiac output [35–37]. Considering
that Dr. Aoyagi conceived of the principles of pulse oxime-
try during the study of cardiac output measurement using the
dye-dilution method, I am deeply moved by the fact that the
cardiac output can also be estimated by a different method
using pulse oximetry.
Similarly, “cap-ONE,” which is the world’s smallest
Fig. 11 The world’s first pulse oximeter (ear oximeter OLV-5100) and lightest mainstream C O 2 sensor developed by Dr.
Shinji Yamamori of our company, is more like a break-
through toward implementation than invention. The
since become a story of success and failure. Innovation is achievement of microminiaturization (approximately 4 g,
said to represent invention translated into implementation.
Our company successfully invented pulse oximetry, but has
fallen behind other companies in its implementation.
Looking back into history, pulse oximetry may have
been invented a bit too early, like many other inventions.
In 1974, when Dr. Aoyagi invented the principles of pulse
oximetry, semiconductor devices, such as light-emitting
diodes (LEDs) [34], had not yet become well established,
and small probes suitable for clinical use could not be
developed (Fig. 11). Therefore, it took nearly another
10 years before LED-mounted small probes were intro-
duced. In addition, the market for continuous monitor-
ing of blood oxygen saturation was still not recognized.
A change occurred in the first half of the 1980s, when
intraoperative medical accidents became an issue in the
US. Nellcor, Inc., which was founded by Dr. New, caught
the wave of technological innovation and market changes Fig. 12 Mainstream CO2 sensor cap-ONE (TG-980P)
at this time, and paved the way for the implementation of
continuous oxygen saturation monitoring. In the 1990s,
Masimo Corporation, founded by Kiani, distinguished
itself by creating the current market for pulse oximeters.
Why did Nihon Kohden Corporation fail to seize the
market opportunity, even though it invented the principles
of pulse oximetry? A look into this problem revealed the
deep gap between invention and implementation. What is
required to overcome this gap is an ability different from
inventive ability alone; that is, the ability to disseminate
innovative technology to the market, in other words, mar-
keting capability. Regarding the contribution of these com-
panies to the development of pulse oximeters, Dr. Aoyagi
stated the following in the Japanese journal, in his contri-
bution in 1990:
Fig. 13 MRI-compatible CO2 sensor module (TG-MR9T)
13
one-fifth compared with the previous model) using an lack of interest in Japan. The negotiations started out well,
original technology enabled its application into various but as they entered the final stages towards signing a con-
clinical settings (Fig. 12). Recently, our company success- tract, Nellcor told me to meet with the vice-president of
fully implemented magnetic resonance imaging (MRI)- a large automobile parts manufacturer (SE, Inc.). I was
compatible mainstream C O2 monitoring for the first time told that I would understand why the meeting was impor-
in the world (Fig. 13) [38–40]. tant when I went. The moment I walked in the door, the
To develop the ability to translate invention to innova- vice-president said “Don’t you know that our company
tion, this is the challenge that Dr. Aoyagi and the history manufactures the diodes for Nellcor’s pulse oximeter, one
of pulse oximetry left us. of its most crucial parts. Our SE Company has the rights
to sell this product in Japan.” I was hit with this one-sided
announcement without warning. I thought, “What were all
The role played by an import company those negotiations about anyway? This is ridiculous!” I
in introducing pulse oximetry to Japan—Me, felt like a fool and had great regret.
my company and pulse oximeters The work of a retail company selling medical devices
is not just to simply sell machines. It is important to have
Yasuhiko Sata. background knowledge of, experience with, and techni-
President and Chair, Tokibo, Inc., Tokyo Japan. cal knowledge of the product to provide the best service
and advice. This will result in the development of a good
relationship with the customer. I was disappointed by Nell-
Introduction cor’s decision to allow SE Company to sell their products,
even though they were not familiar with the way things
The pulse oximeter was invented by Dr. Takuo Aoyagi worked in the medical industry in Japan. I did not think
of the company Nihon Kohden. The device originated that it was in Nellcor’s best interest.
in Japan, but at that time (late 1970s to mid-1980s), the
device was hardly sold in Japan at all. Our company works
closely with both Japanese and foreign anesthesiologists Introducing Ohmeda’s pulse oximeter and our sales
in selling ventilators and anesthetic devices, so we were activity
keeping a close eye on the developments in the market
for pulse oximeters in the US. Perhaps, because Japanese About a year later, the US journal “Anesthesiology” pub-
clinicians were not involved in the development of pulse lished a review of the pulse oximeter developed by Ohm-
oximetry, the devices from Japan lacked in both function eda BOC Healthcare. Ohmeda’s product (Ohmeda Biox
and design. Understanding of and interest in pulse oxi- 3700) was found not to be inferior in accuracy compared
meters by Japanese anesthesiologists was not very high. to Nellcor’s device [41].
I still had bad feelings toward Nellcor and SE Com-
pany, so I contacted the president of Ohmeda Japan
How I came upon my first pulse oximeter right away and started to negotiate the right to sell their
product. Things did not go well at first, but eventually,
While pulse oximeters that use sensors attached to the fin- we convinced them that ours was the only company with
gertips or ears to measure oxygen saturation in the blood in the experience needed to sell a new product like this. We
a non-invasive manner are as essential as echocardiograms finally signed a contract as their sales representative. We
and respiratory monitors in modern medicine, this was not started a drive to sell this product. It was not well known
the case in Japan around 1983. Very few physicians paid in Japan and in order for the Biox pulse oximeter to make
attention to this new technology. The US is a free country inroads in Japan, it was important to deal with the issue
that gives all people a chance to start their own venture that it was not covered by Japanese health insurance. We
companies and many clinicians have started such compa- also had to negotiate with Ohmeda to reduce their price so
nies. Nellcor is a venture company started by a clinical that Japanese hospitals could afford to buy them. We cut
anesthesiologist (with a background in electrical engineer- the price in half, from 3,600,000 yen to about 1,800,000
ing), Dr. New, to manufacture and sell pulse oximeters. yen. We were encouraged by Japanese anesthesiologists
He designed and sold a small, but sophisticated device who predicted that one day every patient would have their
and gathered attention from many anesthesia departments own pulse oximeter.
in the US. We also felt that it was important to improve the prod-
Our company approached Nellcor around 1983 after uct to make it more appealing to anesthesiologists. Pulse
realizing the importance of pulse oximetry, despite the oximeters produce stable readings of 97 to 98% in healthy
13
people, and unless the person is very sick, it will not Importance of sale activity characterized
show lower readings. Using this to our advantage, at the to Japanese medical situation
suggestion of an anesthesiologist, we talked to Ohmeda
about adding a brand-new function, the first in the world, Due to these efforts, Ohmeda’s pulse oximeter was selling
of showing the waveform so you could see the validity of well. Nellcor’s device did not sell well, and while it was
the measurement at one glance. Ohmeda implemented this rumored that SE Company had given up, after a while CM
immediately. The device started selling very well due to Company, the medical device subsidiary that imported medi-
its low price and the visual functionality of its continu- cal devices for a large trading company (IC Company) took
ous waveform display (showing the normal status of the over sales. At the time, Ohmeda had the largest share of the
patient and the device) which increased the confidence pulse oximeter market in Japan. While Nellcor held the larg-
medical staff had in the device. est share in other countries, the reverse trend in Japan was
unusual from the point of view of both sides.
Broad clinical studies to be covered by national Our company has had one mission from the start, and that
health insurance is not just to sell devices, but to help deepen the understand-
ing physicians and nurses who use these devices have. This
It was important to study the clinical efficacy of pulse oxi- applies to selling products from Bird or Newport ventilators.
meters as that is what was used to determine whether it This is invaluable in Japan, where continuing education for
would be covered by national health insurance, so following post-graduates is not well developed. I think that this mis-
the enthusiasm of physicians at the National Children’s Hos- sion for our company helps explain why were able to suc-
pital, the ‘Pulse Oximeter Research Group’ was established cessfully introduce pulse oximetry to Japan and contribute
and physicians in major hospitals from Sapporo in the north to a healthy spread of its use.
and Okinawa in the south participated in this research. The
group came up with a protocol and began clinical studies. Termination of the contract and the end of our
Most people with influence in academics in Japan at the time dealing with pulse oximeters
were from public universities and staff physicians who were
required to comply with a high standard of conflict of inter- We thus expanded sales of Ohmeda’s pulse oximeter and
est guidelines. Thus, the research group formed voluntarily were planning on strengthening the market even more.
by qualified anesthesiologists was very welcome. However, suddenly 1 day, Ohmeda told us that they were
The Research Group, consisting of physicians from par- cancelling our sales contract with them. A new company
ticipating hospitals, met about once every 3 months for (OS Company) was formed with Ohmeda and a subsidiary
2 years on a voluntary basis and discussed the clinical use of a large electronic manufacturing company (N Company)
of the device and other issues, presenting a wide range of called S Company that manufactured and sold medical
studies in academic conferences related to pulse oximetry devices. They planned on selling all over Japan. At the time,
use. In 1987, Ohmeda held a workshop in Hakone, Japan, the Ohmeda Company itself was caught in the currents of
the first of its kind in the world outside the field of anes- change of the medical setting, which continues even today,
thesia, on how to conduct research on pulse oximeters in where mergers are based simply on monetary relations and
newborn infants. We co-sponsored the meeting. The first not the convenience of customers. Once more it was our
book in Japanese on pulse oximetry grew out of this meet- fate to accept the loss of our retail stores and the products in
ing. This meeting was the neonatal equivalent of the Interna- which we invested so heavily. Looking back, OS Company’s
tional Chartridge Meeting held in 1985, outside of London. plans failed completely, and I have heard that it took years
It was organized by Drs. Payne and Severinghaus, and the to resolve all the issues.
naming of SpO2 was agreed upon there. The next step we took was to get the rights to sell the
Thanks to the great effort and time spent on research and pulse oximeter from the American company, CS (a company
participation in the research group, even though it took a that sells products for the ICU). Compared to the previous
while, pulse oximetry achieved formal recognition in the negotiations, the contract was concluded relatively smoothly.
national health care system. At last pulse oximetry found a However, at the time change was coming to the market for
place in the Japanese medical system. The Pulse Oximeter pulse oximeters. This was the rise of disposable sensors.
Research Group decided to expand its role after achieving CM Company, a subsidiary of a large trading company, the
its first purpose. It developed into the Japanese Association new representative of Nellcor in Japan, aggressively tried
of Clinical Monitoring. to attain the number one share of the market. Our company
had been left out by the Ohmeda Company, giving Nellcor
a better chance. They lent their devices out for free and tried
13
to increase their sales by making money out of selling dis- with DM by email and telephone, but we were unable to get
posable sensors. a clear response from them regarding the patent. We went
However, CS Company, that dealt with the American straight to DM in the US through our American subsidiary,
market, was too late in putting out their line of disposable TKB-I. We argued with the president, but were discour-
sensors. The functionality of the device was not that good, aged by his lack of sincerity. In the end, we terminated our
and sales lagged. We considered ending our involvement contract with DM. Our company has not dealt with pulse
with the products of CS Company, but we could not find a oximeters since then.
replacement sales company. To keep our responsibility to the
hospitals who had already bought these products, we con- Pride of our agency
tinued to sell their products in a non-exclusive relationship.
Our company trades mainly in sales of imported medical
Topics associated with disposable sensors devices. We place great importance on the promotion and
proliferation of imported clinical devices that are at the cut-
It was under these circumstances that we signed a sales con- ting edge of the field that might otherwise not be introduced
tract with DM Company, a subsidiary of a large American into the Japanese medical field. This is true of the pulse
airport surveillance device company. This company had oximeter, as well as the first hemodialysis machines, mass
disposable sensors that were compatible with the Nellcor spectrometers, Holter ECGs, etc. We have a policy not to
device, and they sold pulse oximeters as well all over the deal with medical devices that are easily accessible in the
world. They also handled devices for veterinary devices. The Japanese market or in a price war. The essence of our busi-
owner was from India and had close contact with a company ness model is to contribute to the health of people through
that primarily sold X-ray machines to inspect airport lug- medical professionals, but it is not necessarily an easy way
gage. The company was quite successful. We were not sure to be profitable. The road is rough, with many barriers, but
whether to get involved, as we had never dealt incompatible we are proud of our company.
or generic products, only original products. We were reas-
sured by the size of the company and by their claim that the Afterword
patent for disposable sensors by Nellcor had expired and
they were free to make and sell copies. I am grateful for being given the chance to talk about our
Before signing a contract, we too looked into the pat- experience with spreading knowledge of imported medical
ent issue and signed a contract based on DM Company’s devices in Japan and our efforts to increase anesthesia safety
promise to guarantee the product. We began to sell pulse through this special memorial to the great achievements of
oximeters and sensors. I felt that our company was better Dr. Takuo Aoyagi, inventor of pulse oximetry. I hope this
equipped to handle sales in Japan than Nellcor (partnering will be of some use to anesthesiologists in Japan and to peo-
with the CM Company to sell in Japan). We proceeded to ple who work in the medical field. It would please me greatly
promote these products to the network of people we knew in if this report is useful in the field.
the ICU, NICU, and Emergency Medicine, who were using
our company’s original Newport ventilator. There were some
problems with the device and with the sensors, but we solved Commemoration of Dr. Takuo Aoyagi’s
them through our sales force and technical skills. We were Impact—a tree that was heard to fall
making inroads all over Japan, especially around Nagoya,
where we received a very large order. Robert J. Kopotic, MSN, RRT, PhDh (Eng).
Nellcor (CM Company) was beginning to show results, Critical Care Manager of Clinical and Medical Affairs,
and with the purpose of holding onto their customers, started Edwards Lifesciences, Irvine, CA, USA.
changing the connectors between the device and the disposa- Takuo’s sojourn into mortality came on February 14,
ble sensors so as to make generic products incompatible with 1936 when he arrived to his parents Monshichi and Tatsu
it. However, we felt that there were enough older machines Aoyagi. In 1958, he graduated from Niigata University with
around, and enough hospitals that would continue to use the a degree in electrical engineering and started work in the
original product, that our business would be all right. Just as medical device industry with the Shimadzu Corporation. In
we thought the products from DM Company were doing well 1971, he joined the Nihon Kohden Corporation, where he
in the market, we got a registered letter from Nellcor saying completed his life’s work over the next almost 50 years. He
that DM was infringing on its patent for disposable sensors. received a PhD in engineering from the University of Tokyo
We gathered a team of company executives and company with his thesis: “Non-invasive measurement of light absorp-
workers involved in this project and along with a legal team tion in blood based on pulsatile variation of light transmitted
from Japan came up with a strategy. We were in contact through body tissue.”
13
device in 1977, stimulating other firms to further improve

and market pulse oximeters worldwide in the mid-1980s.”
Severinghaus summarized, “Greatness in science often, as
here, comes from the well-prepared mind turning a chance
observation into a major discovery.” [1]
I received the news of Dr. Aoyagi’s passing from Dr Kat-
suyuki Miyasaka (“Kats”), who as a physician researcher,
worked closely with Takuo for over 30 years. During that
same period, I became associated with Kats as we were co-
investigators in the NIH-NHLBI, Collaborative Clinical
Trial on High Frequency Ventilation in Premature Infants."
Contract #NO1-HR-46005 (RFP-NHLBI-84–4; HIFI-Trial).
In that study, pulse oximetry data were part of the collected
parameters. Kats and I grieved about the loss of a brilliant
mind, kind friend, and noble man that had blessed our
lives. I then reminisced with Kats about Takuo and his wife
(Yoshiko) telling me about meeting someone else of my faith
(i.e., the Church of Jesus Christ of Latter-Day Saints). Takuo
had a valued relationship with the renowned Dr. Homer
Richards Warner from the University of Utah. A cardiolo-
Fig. 14 A photo at the Lifetime Achievement recognition during the gist by training, Homer was the first to develop an electronic
Innovations and Applications of Monitoring Perfusion, Oxygenation medical record system in the US, but he had some experi-
and Ventilation (IAMPOV, 2012) symposium on the campus of Yale ence with the dye dilution method. The two couples stayed
University at each other’s homes on multiple occasions. I remember
Takuo speaking highly of Warner’s contributions to medi-
Dr. Aoyagi has received many accolades and honors but, cine and Warner reciprocating. Takuo reminded me and my
in my opinion, the finest came from Professor John Sever- son, that he knew another Christian missionary, i.e., "Elder
inghaus, who in 1987 met Takuo and then recognized him Homer Warner that came to Japan as a young man." Takuo
in the worldwide medical literature for invention of the pulse and Yoshiko mentioned their cherished visits to Homer and
oximeter. In the attached photo (Fig. 14), Takuo is standing Kay Warner in Salt Lake City.
next to me and Dr. Severinghaus is to his side, while they John Severinghaus credited the development of the CO2
both received Lifetime Achievement recognition during the electrode to Richard Stow (John refined Stow’s design to
2012 Innovations and Applications of Monitoring Perfusion, include a more stable electrolyte, which then became the
Oxygenation and Ventilation (IAMPOV) symposium on the Stow–Severinghaus electrode used for measuring CO2 in
campus of Yale University. The following IAMPOV was blood gas analyzers). Similarly, Takuo gave credit to others
held at St. Luke’s International University in Tokyo in 2015. for refining pulse oximetry, “I appreciate Minolta. Without
The next meeting will be held in London in 2021. their recognition of idea of pulse oximeter, the idea might
In the proceedings of the 2007 IAMPOV symposium, be buried.”
John Severinghaus walked the attendees through several While his intimate family of survivors include his wife
decades of advancements in optical spectroscopy of the ear, (Yoshiko), and three children (Kaori, Midori and Yasutoshi),
a method that allowed the calculation of blood’s saturation so many others have been and continue to be blessed by
with oxygen but required complex calibration. This work Takuo’s creation of pulse oximetry and his never-ending
was mainly focused on assessing pilots in flight. Then came curiosity of the interrelationship of engineering concepts
Takuo that “was interested in measuring cardiac output non- related to human physiology, particularly with interactions
invasively by the dye dilution method using a commercially between heart, lung and vascular function. Sense Takuo’s
available ear oximeter. He found through computation that vision, when with Kats 20 years ago he wrote, “Opening of
dividing the absorptions of the red (805) and infrared (930) the first door of pulse photometry gave us pulse oximetry.
signals by each other cancelled the pulse noise which pre- The next door of pulse photometry opens to multi-wave-
vented measuring the dye washout accurately. He then real- length pulse photometry. Dyshemoglobins (e.g., COHb and
ized that these pulsatile changes could be used to compute MetHb) can be measured with a multi-wavelength system.
saturation from the ratio of ratios of pulse changes in the red The elimination of artifacts caused by body movement is
and infrared. His ideas and equations were shared, adapted, possible without sacrificing response time. It may also
and improved by Minolta into the first practical finger type
13
become possible to measure hemoglobin concentration.” In surgery, the critical innovation of the pulse oxime-
[42]. ter was not just that it can display the level of oxygen in
“Dr. Aoyagi hoped to use the oximeter to develop a non- the blood, but that it can also do it instantly and continu-
invasive way of measuring cardiac output (the amount of ously, producing a variable pitch auditory signal with each
blood pumped by the heart) through a method known as dye heartbeat. For surgical teams, these features allowed them
dilution, in which dye is injected into a patient. Rather than to “see” whether a patient was getting enough oxygen to
aid fighter pilots in dogfights, he hoped that his invention survive when under anesthesia. Anesthesia providers often
would signal a hospital patient’s need for artificial ventila- refer to their pulse oximeter as their “eyes and ears”.
tion.” [43] In high-income countries, such as Japan and the US,
I wish to take minor liberty with a quote from Sir Isaac pulse oximeters have been the bedrock of anesthetic care
Newton, "If WE have seen further, it is by standing upon the for decades. Unfortunately, due to price and adaptability
shoulders of giants." For me that is certainly the case for my constraints, pulse oximeters are still lacking from many
apprentice association with Takuo Aoyagi. His engineer- operating rooms in low- and middle-income countries.
ing efforts raised awareness that ischemia is a precursor of In 2011, Lifebox estimated that 77,000 operating rooms
major organ failure and that patients are benefitted through around the world still lacked this essential piece of medi-
its early detection by monitoring oxygen carrying capacity cal equipment. Seeking to address this problem, four of
and perfusion. Dr. Aoyagi was small in height but mighty the world’s leading medical organizations joined together
tall in deed and in humility. I treasure his impact upon my to globalize Dr. Aoyagi’s invention. The Association of
life, many kind words, and thoughtful critiques of ways I Anaesthetists of Great Britain and Ireland, Brigham and
could be better personally and professionally. Women’s Hospital, Harvard T.H. Chan School of Public
Health, and the World Federation of Societies of Anaes-
thesiologists led the way with the creation of Lifebox—a
Pulse oximetry: The heart of Lifebox’s non-profit organization that works to make surgery and
work—honoring Dr. Takuo Aoyagi anesthesia safer. Lifebox’s founding aim was to close the
“oximetry gap” by equipping operating rooms with pulse
Kitty Jenkin, Head of Communications. oximeters.
Alex Hannenberg, M.D., Trustee. Today, nearly, a decade later, Lifebox focuses on three
Atul Gawande, M.D., M.PH., Co-Founder and Chair. core pillars of safer surgery—improving anesthesia safety,
Lifebox Foundation, Brooklyn, NY, USA. reducing surgical infection rates, and strengthening surgical
Dr. Takuo Aoyagi’s invention of the pulse oximeter has teamwork. By working alongside local partners, it provides
saved the lives of millions of people across the globe. After the training and tools needed to save lives through safer sur-
the sadness of his death this year, Lifebox, a non-profit gery. All of this work is rooted in the World Health Organi-
founded by Dr. Atul Gawande with four leading medical zation’s Surgical Safety Checklist.
organizations to improve surgical outcomes globally, is com- The Checklist is a simple communication tool that has
memorating his legacy and the evolution that Dr. Aoyagi’s been proven to reduce complications and deaths from unsafe
work led to across the healthcare setting. surgery by up to 40%. When the WHO Surgical Safety
“It is hard to express the scale of transformation in patient Checklist was introduced in 2008, the only piece of equip-
care that resulted from Dr. Takuo Aoyagi’s invention of the ment included on the Checklist was a pulse oximeter—a
pulse oximeter. Effective safety monitoring is an essential testament to the international recognition of the undisputed
part of patient care. Pulse oximeters gave us a way to moni- critical role Dr. Aoyagi’s invention has played in improving
tor, with a simple finger probe, the oxygenation of people’s surgical safety.
blood. That rapidly made them indispensable and lifesaving When Lifebox launched, it developed a pulse oximeter
across health care - from the operating room and intensive specifically designed for use in low-resource settings—with
care, to the identification of childhood pneumonia, to the tri- robust construction and rechargeable batteries that stay on
age of COVID-19 patients. They have become so universal, even when the power fails. To date, more than 26,000 Life-
we can all too easily forget that this transformation in patient box pulse oximeters have been distributed throughout 116
care happened in our lifetime. We hope that Dr. Aoyagi’s countries for vital patient monitoring. The distribution is
family and loved-ones will find solace in the millions of lives accompanied by oximetry and anesthesia safety training,
that have been - and will continue to be - saved throughout recognizing that for many of the recipients, this is their first
the world because of his genius. Our gratitude to Dr. Aoyagi patient monitoring technology.
is boundless. On behalf of Lifebox, thank you,” “Following a routine cesarean section, I put a pulse oxi-
Dr. Atul Gawande, Lifebox Co-Founder and Chair. meter onto the newborn baby as she was wheeled into recov-
ery with the mother. As I prepared for the next patient, I
13
heard the beep of the Lifebox suddenly change pitch; I ran Background of the contributors (bold)
over and saw the alarm going off, as the baby’s saturation and how things developed in Japan: From
started to drop,” explained a nurse anesthesia provider in the inception to the present
Sierra Leone who received a Lifebox pulse oximeter. “There
was a time in this hospital when this baby would have died Pulse oximeters can be used on all people no matter their
because we did not have appropriate oximetry available, but color, race, age, body shape, place of measurement, or type
the oximeter is a second set of eyes and ears. Instead, I was of device. By merely turning on a switch, a clear number
able to immediately attend to the infant, and support her from 0 to 100% is displayed stably and in healthy people a
breathing. A minute more and it would have been a differ- number that “seems right” shows up. However, according
ent story - nine months of labor and an operation ending in to Dr. Aoyagi, the numbers displayed just “happen to look
tragedy.” right,” and to correctly interpret the results, clinicians must
Dr. Aoyagi lived to see his invention become one of the also consider the background in which the number gets dis-
most crucial tools in fighting the COVID-19 pandemic. played. In other words, besides the safety, stability and ease
“Silent hypoxia” is a defining feature of COVID-19, with of use of the device, it is important not to overlook the preci-
patients slowly starving of oxygen without the usual short- sion and reliability of the measurement parameters, and also
ness of breath that would see them seek care. By the time to understand the physiological and medical issues involved
many COVID-19 patients are having trouble breathing, they to correctly interpret the number displayed.
are already critically ill. The best tool to detect these patients Pulse oximeters measure oxygenation, not respiration, but
is a pulse oximeter. ordinary people and even some medical people tend to over-
With the start of the COVID-19 pandemic in early 2020, look this [44]. In patients receiving oxygen during sedation
Lifebox pivoted its activities to support healthcare work- for procedures, a display of 100% is not cause for relief. It is
ers to provide safe surgical and COVID-19 care and pro- a percutaneous measurement subject to various factors, but
tect themselves. The mainstay of this response has been the is highly reliable when there is no body movement with a
distribution of 6,500 Lifebox pulse oximeters to frontline good pulse. In cases of extremely low measurements, some-
healthcare providers across 43 countries along with guidance times, it is better to believe the numbers than the patient’s
on how to use them in COVID-19 care. Lifebox’s COVID- clinical presentation. It is known by Japanese media that
19 response will last as long as the pandemic continues to such lack of knowledge can have unhappy results.
devastate health systems and lives, but the core mission—to As has been seen in the COVID-19 pandemic, there are
improve the safety of surgery and anesthesia—remains the indications that it is possible for such things to occur, as
same. Pulse oximetry remains at the heart of this work. overlooking silent hypoxia in patients with no symptoms
There is still much work to be done in the global access [45, 46]. Dr. Aoyagi was strongly concerned about the lack
to pulse oximetry. Lifebox will expand beyond operating of understanding of pulse oximeter measurements, even
room use to ensure monitoring is available for the full perio- before the devices became popular with the general public.
perative process—from pre- to post-op—in intensive and This concern guided his research on establishing a theory of
neonatal intensive care units, and in the transfer of patients pulse oximetry in his later years. Even if you do not consider
to a higher level of care. the pandemic, it has been reported that it is possible that
Lifebox celebrates the life of Dr. Aoyagi with every pulse moderate hypoxia in black people is overlooked almost three
oximeter distributed to a healthcare provider. We cannot times as much as it is in white people [47]. While skin color
think of a more lasting legacy to Dr. Aoyagi than the mil- may not be a problem in Japan, where there is little diversity,
lions of pulse oximeters in use across the world keeping it is possible that other such reports will come out from other
patients safe. areas of the world. The best memorial to Dr. Aoyagi, who
died before he could finish his work, would be for those of us
in clinical research to spread correct understanding of pulse
Pulse oximeters: The invention oximetry to medical professionals and society in general.
that changed the paradigm of patient
safety around the world—in summary Dr. Aoyagi’s contributions and recognition
and in closing this special feature both inside and outside Japan
Katsuyuki Miyasaka, M.D., Ph.D. The inventor of pulse oximetry, Dr. Takuo Aoyagi
Professor Emeritus, St. Luke’s International University, (1936–2020), died on April 18, 2020. He was 84 years. The
Tokyo, Japan. first case of the new corona virus (COVID-19) in Japan was
found in mid-Jan., 2020 and seemed to show signs of being
rampant in mid-February. In hindsight, the peak of the first
13
wave (500 cases nationwide) just happened to coincide with 3 days, to see a group of people from all over the world,
Dr. Aoyagi’s demise. Vaccinations in some countries finally interested in the same issues, gather and discuss our research
started at the end of 2020, but at that point about 83 million freely, with no restraint, regardless of specialty or affiliation
people around the world had been infected and 1,850,000 (Fig. 15).
people had died [48]. It is thought that pulse oximeters were Contributors from IAMPOV to this memorial issue are
used in almost all these patients, many outside medical facil- Dr. Bob Kopotic, from the secretariat, and Dr. Kirk Shel-
ities. Dr. Aoyagi did not live to see that day. It is regrettable ley, professor at Yale and the organizer of the 3 rd IAMPOV
that he left us before he could complete his work on multi- in 2012. Dr. Kirk Shelley, told us how he nominated Dr.
wave theory and its precision and reliability. Aoyagi for the 2013 Nobel Prize in Physiology or Medi-
Dr. Aoyagi’s passing was reported immediately and cine. Unfortunately, with his death, Dr. Aoyagi will not get
widely by foreign media, such as the New York Times (US) the Nobel Prize, but I would like to express my gratitude
[49], Washington Post (US) [43], Globe and Mail (Canada) and respect for Dr. Shelley’s courage in telling us what hap-
[50], and CNN (worldwide) [50]. I was struck by the sharp pened, so that it will not disappear from history. Dr. Aoyagi
contrast between the high interest shown by those overseas has received many honors. In 2015, he was awarded the pres-
with reporting in Japan [51, 52]. I have attended quite a few tigious IEEE (Institute of Electrical and Electronics Engi-
conferences overseas with Dr. Aoyagi and have been moved neers) Medal for Innovations in Healthcare Technology (as
by how researchers around the world would come up to him prestigious as the Nobel Prize in his field). The American
each and every time to thank him for his invention. I also Society of Anesthesiology (ASA) voted to give him honor-
feel how inadequate was the recognition he was given in ary membership, one of their rare honors, in 2020. ASA will
Japan. Against this background, the 4 th IAMPOV (Innova- present the award in his memory at their annual meeting
tions and Applications of Monitoring Perfusion, Oxygena- in October 2021. On Dec 25, 2020, he was posthumously
tion and Ventilation) international symposium was held in awarded the 4 th Grand Prize for Medical Research and
Dr. Aoyagi’s home ground, Japan. With the support of the Development by the Prime Minister of Japan. Mr. Hirokazu
Japan Association for Clinical Monitoring and other groups, Ogino, the CEO of Nihon Kohden received the award on
a group of approximately 180 enthusiastic people (60 from behalf of Dr. Aoyagi. This is the most prestigious award in
abroad) gathered in Tokyo. It was a moving experience for Japan in this field [53]. It can now be said that the reputation
Fig. 15 Memorial photo in 2015 Tokyo IAMPOV Symposium (at auditorium in St. Luke’s International University)
13
of Dr. Aoyagi in Japan has finally caught up to what it is a theory of measurement through the years, and after a break
overseas. of about 10 years, Nihon Kohden renewed its development.
They allowed Dr. Aoyagi to pursue his research until the end
Contributions of pulse oximetry to patient safety and Dr. Aoyagi fulfilled their expectations.
On another front, Mr. Akio Yamanishi’s group was taking
In addition to the great recognition Dr. Aoyagi had previ- advantage of the new LED technology to develop fingertip
ously (IEEE Award and nomination for the Nobel Prize), plethysmography, etc. and the development of a pulse oxi-
many others from abroad joined in to add their voices to meter was one of their primary projects. They succeeded in
his memory: Ms. Kitty Jenkin of LifeBox, and five other developing the world’s first fingertip pulse oximeter. Two
individual contributors. One of the founders of the LifeBox contributors to this issue, Dr. Ikuto Yoshiya (Anesthesia
Foundation was Dr. Atul Gawande, who was a pioneer in the Professor at Osaka University at the time) and Dr. Yasuhiro
development of the now indispensable Surgical Check List. Shimada (Assistant Professor at the same University) were
The foundation works to make pulse oximeters available to involved, but their contributions were limited to improv-
operating rooms around the world. Ms. Kitty Jenkin, in ing precision through analysis. Minolta started selling their
charge of communications at the foundation, has contrib- device (OXIMET 1471) through Mochida Pharmaceuticals
uted to this memorial issue signed by Dr. Gawande and all in June 1977, but rather than using LED as a light source,
the members of the board, representing a wide spectrum of they used a combination of tungsten and fiberoptic cable, so
countries and backgrounds. although the device was usable, it was difficult to operate.
Eight Japanese people who have worked with Dr. Aoy- It is possible that the red spectrum in LEDs at the time was
agi directly have added their articles, so that we cover Dr. not sufficient, but it was an unfortunate choice.
Aoyagi’s career from his initial ideas to what we know of I would like to note that there was absolutely no sense of
him today. I believe that we have covered all the steps of competition between Nihon Kohden and Minolta at the time.
the development of pulse oximeters and the important roles Minolta had been pursuing this project since the late 1960s
other people played. Fortunately, most people have clear at the time of the Apollo Project, so as part of the company’s
memories and impressions, and I’m sure Dr. Aoyagi would protocols, they began to apply for a patent for Yamanishi’s
have been very proud of what they wrote. group at the end of 1973. Dr. Aoyagi’s application, sent in
before his presentation at a conference, just happened to
Pulse oximetry: Two beginnings arrive at the patent office a few weeks earlier. I can only
imagine how shocked the Minolta group must have been. Dr.
The invention of pulse oximetry started in Japan and is now Aoyagi’s patent was restricted to within Japan, but Minolta
used in both medicine and by ordinary people around the obtained an international patent. I do not have detailed pat-
world. Surprisingly enough, two patents were filed at almost ent information and I have no idea how latecomers managed
the same time in 1974. Dr. Aoyagi, on behalf of Nihon Koh- to overcome patent issues, but it was good for mankind that
den (patent filed March 29, 1974) and Mr. Akio Yamanishi, Dr. Aoyagi’s patent did not restrict the sound competition of
on behalf of Minolta (patent filed April 24, 1974) came upon pulse oximeter development.
this idea completely independently. Dr. Aoyagi’s device, Most of the information on Dr. Aoyagi is only in Japa-
that came first, used a dye densitometer on the earlobe to nese, and his company, Nihon Kohden, did not try to develop
measure cardiac output. He came upon his idea during an the product. In 1987, Dr. John Severinghaus (Fig. 16) dis-
experiment to eliminate superimposed pulsation noise. His covered Aoyagi’s achievements and made him known to the
light source was an incandescent lightbulb, and his point of world, including Japan which was unaware of his invention.
measurement was the earlobe, both of which made it difficult The first serious published paper on pulse oximeters in Eng-
to develop a practical device and the project ended. Chances lish was written by Dr. Yoshiya in 1980 [11] and influenced
are that it was not pursued because the invention was a side researchers and inventors all over the world (Pierce EC: ASA
product and did not align with the company’s main project. The 34th Rovenstine Lecture, 1995). This history is already
Dr. Aoyagi reported on his invention to his supervisor, well known, and on behalf of Dr. Severinghaus, who is
and it just happened that a physician the supervisor was visit- advanced in years, Dr. Robert Kopotic, a central figure in
ing heard about it and work on a prototype was started. They IAMPOV, has written some of this history for us.
were less interested in the significance of oxygen saturation
and were mainly looking at new methods of measurement. Clinical significance unrecognized in Japan
Dr. Aoyagi told me that once the paper was published, there
was no more mention of turning it into a clinical device. I do The OXIMET 1471 pulse oximeter that went on the market
not know what really happened, but the result is as we know in 1977 seems to have been reviewed by several university
it. However, Aoyagi continued his research into establishing academic anesthesiologists in Japan. However, while the
13
Fig. 16 Memorial photo at

the 3rd IAMPOV Symposium
Award Ceremony, 2012
device was judged to be useful at some level as a research

measurement device, it seems that either there were no sug-
gestions to help it spread as a clinical device or that if there
were, they were not heeded. Only 200 devices in total were
sold. Dr. Kunio Suwa (Associate Professor of Anesthesiol-
ogy at Tokyo University) tried it out in 1992 on his own
volition, but unfortunately even then, as now, a structural
problem existed in Japan’s medical device industry.
The very first time Dr. Aoyagi presented his invention, the
pulse oximeter, to Japanese anesthesiologists was in 1989 at
The Japan Society for Clinical Anesthesia Academic Meet-
ing in Tokyo. At that time, most anesthesiologists in Japan
had heard of Nihon Kohden, where Dr. Aoyagi worked, but
it was not until 2002 when the Japanese Society of Anes-
thesiologists gave Dr. Aoyagi an award for his contribution
to society, that his name and Nihon Kohden’s pulse oxime-
ter became familiar to anesthesiologists in Japan. The first
person to tell the world about Aoyagi’s achievements was,
as mentioned above, Dr. Severinghaus of UCSF [1, 5]. Dr.
Severinghaus himself has made great contributions to the
Fig. 17 HP Company ad for an ear oximeter (1973). Eight wave-
field of blood gas analysis and is known for his development lengths (650-1,050 nm), heated ear probe to obtain arterialization.It
of an electrode for partial pressure measurement of CO2. was accurate, but large and hard to operate. It was not a monitor.
Minolta’s OXIMET‑1471 pulse oximeter goes

to the US to make the machine easier to use on patients in a clinical
setting.
A large Japanese trading company tried to sell Minolta’s However, this offering turned into an opportunity as it
OXIMET-1471 pulse oximeter in the US, and in connection can be thought that Dr. William New saw the device. Dr.
with this, they offered use of the machine for evaluation to New, who later founded Nellcor and who used to work for
an anesthesiologist (Dr. Charles Whitcher) at Stanford Uni- HP as an engineer, played an extremely important role in the
versity in 1977 and it was used clinically [12]. The develop- development of the currently used clinical pulse oximeter.
ment team at Minolta focused on scientific analysis of the Dr. New is an anesthesiologist who has a background in
tendency to overestimate at low oxygenation levels, but they electrical engineering and biology. He was working in the
were not particularly interested in making improvements same hospital as Dr. Whitcher at the time. Dr. New was very
familiar with the HP ear oximeter (Fig. 17).
13
In 1980, Professor Whitcher’s group reported on the the missing link! The secret to the success of the Nellcor
Minolta Oximeter Model 101 (OXIMET-1471) at the N-100 lay in the input from top level clinical pediatric
Annual Meeting of the American Society of Anesthesi- anesthesiologists. There is no doubt that the spread of
ologists (ASA). They clinically evaluated the device on 5 pulse oximeter use in a clinical setting was due to the pro-
healthy male subjects and indicated the possibility of its ficient efforts of Nellcor in making early and skillful use of
being a clinically effective way to pinpoint the tendency to recently matured LED technology from Japan and putting
overestimate at low oxygenation levels. Their abstract quotes everything together to make a practical clinical monitor.
from an article by Suzukawa in 1978 (translated into Eng- There is also another factor, the raised social awareness
lish), but the presentation at ASA was not published. of the number of malpractice cases charged against anes-
Corning Medical was also involved in this research as thesiologists in the US and the high cost of malpractice
they had just started to sell an invasive blood gas analyzer insurance for anesthesiologists in the US in the 1980s.
in Japan. I had a chance to visit Corning in October 1982 for Above all, in 1986 the ASA Guidelines for anesthesia
a different reason and I was asked about it directly, but it is monitoring included the use of pulse oximeters as one
unclear how the relationship between Corning and Minolta possible choice. These Guidelines spread, not just in the
developed afterward. This story is from the year before Nell- US, but all over the world and were a big turning point for
cor started selling the N-100. anesthesia safety.
Minolta contributed to the initial spread of pulse oxime-
ters and OXIMET-1471 was good enough. Minolta played Increased momentum for awareness of anesthesia
an important role in the initial spread of pulse oximeters safety in the US
and OXIMET-1471 was equipped with very high stand-
ard technology. The precision was at research level and There were many factors in the movement to improve
impressive, but without the system needed for Japanese patient safety during anesthesia, boosted by Cooper’s
anesthesiologists to give appropriate feedback on its use- study in the late 1970s [55]. The high cost of malpractice
fulness as a clinical device, there was no way to improve it insurance for anesthesiologists led to the discussion of for-
enough to take advantage of being the front runner. mulating the “Harvard Guidelines,” drawn up by a group
of people from the hospitals associated with Harvard
University (1983). Other factors were ABC’s television
Nellcor appears on the scene documentary, “The Deep Sleep: 6,000 Will Die or Suffer
Brain Damage”(1982), the establishment of APSF, and
Nellcor was founded in 1981. A close copy of the fingertip incorporation of the ASA Guidelines. Dr. Jeffrey Cooper,
device by Minolta was made into the prototype N-100A known as the Father of Patient Safety, was involved in the
in 1982 and was being sold in 1983 [54]. It was signifi- formulation of the “Harvard Guidelines” and has written
cantly and overwhelmingly an excellent device in terms an article for this memorial.
of performance, design, operability and clinical sensibil- He discusses the role played by numerous factors, such
ity. A rise in the call for safety awareness in anesthesia as the possibilities of non-invasive measurement (inven-
also helped the device spread rapidly. The founder of the tions), the development of excellent devices based on
company himself was an anesthesiologist, but advice from human engineering (Nellcor N-100), and education about
pediatric anesthesiologists was taken into account during the clinical significance of monitoring (ASA Monitor
development. The latest and most important pulse oxime- Standards).
ter for anesthesia to hit the market, and the one that played Japanese companies were left behind as they were unable
a major role, was Nellcor’s. Dr. William New, its founder, to fathom the wave of the times. They could not see the
passed away in 2017 and unfortunately, none of the people importance of the background of devices, in other words, it
close to him that I contacted were available to write an was not just technology that was important, but the role of
article for this memorial. the people for whom the device is being created. There was
With great luck, I learned that Dr. David J. Steward a lack of understanding of the importance of such factors as
(at that time at the Hospital for Sick Children in Toronto) cooperation between the developers of medical devices and
had been asked directly by Dr. New to evaluate the pro- the clinical setting, including social aspects. There was also
totype Nellcor N-100A. He agreed to write about what a lack of understanding of the entire production process,
he knew and submitted an invaluable photo of the proto- including education and how products reach clinicians and
type N-100A. I knew Dr. R. Raphaely (staff at the pedi- are applied (concept of BioDesign).
atric anesthesia department of the Children’s Hospital of When the Harvard Guidelines started to be discussed in
Philadelphia), the person who introduced Dr. New to Dr. the early 1980s, one of the most important missions was to
Steward. I knew most of what happened after, but this was establish rules that anesthesiologists would have to adhere
13
to, even in the country of the free. Discussion was focused Widening interest in research
on fundamentally important issues that no conscientious
anesthesiologist could argue, such as having anesthesiolo- Approximately 50 world leaders in physiology and anesthe-
gists be physically present, rather than introducing still argu- siology, including Dr. Jim Payne and Dr. John Nunn from
able monitoring devices. England and Dr. John Severinghaus and Dr. Kevin Trem-
Thus, although incorporating the use of capnometers or per from the US, gathered in Chartridge, a suburb outside
pulse oximeters in the guidelines was discussed, they were London in May 1985. From Japan, Dr. Kunio Suwa (Tokyo
eventually left out, because they were still in the early stages University, Anesthesia Department) talked about the oxy-
of development [56]. The ASA Anesthesia Standards from gen dissociation curve [58], and Dr. Katsuyuki Miyasaka
1986 recommend the use of oxygenation monitors, but the (National Children’s Hospital, Anesthesia Department), the
requirement to use pulse oximeters did not come until 1989 sole pediatric anesthesiologist there, talked about his clinical
when the standards were amended. Up until this point, the experience with tragus probes adapted from adult earlobe
issue of anesthesia safety was centered mainly on activity probes for Biox III in pediatric patients [57]. The conference
in the US, just as Nellcor’s N-100 was playing a central role provided an opportunity to discuss a wide range of issues
in the market. from the definition of S
pO2 and the categorization of oxygen
However, in 1984, the British giant BOC/Ohmeda pro- saturation, to the clinical usefulness of pulse oximetry and
cured an American firm Biox and new activity began in Eng- the significance of biological research.
land. Biox products were widely used in Japan and played In response to this, in 1986, Dr. Kunio Suwa (Tokyo
a central role. University, Associate Professor), Shosuke Takahashi
(Kyushu University, Professor of Anesthesia) and Dr.
Influence of Biox/Ohmeda Hiroshi Sankawa (National Children’s Hospital, head of
the Anesthesia Department) were the primary movers to
The American market for oximeters started in 1979 with start the Japan Research Group on Pulse Oximetry. In 1987,
Biox’s (Denver) device, Biox II. According to Dr. Jonas Dr. Katsuyuki Miyasaka (National Children’s Hospital,
Pologe (personal communication) who was involved in Department of Anesthesia) organized an international con-
development at Biox, the device, an ear oximeter, was made ference (Hakone Conference) to discuss the use of pulse
after considerable study of both Aoyagi’s and Minolta’s pub- oximeters primarily in neonatal medicine. Sales of the Biox
lished reports. I did clinical research on Biox III in the latter 3700 in Japan suddenly started to grow in the fields of anes-
half of 1984 in Japan and found it to work in a clinical setting thesia and NICU. Dr. Hiroshi Nishida (Tokyo Women’s
with good performance. I reported on this research in 1986 Medical College, Professor Emeritus) recalls the impor-
[57]. It was a stable and convenient patient monitor during tant role that pulse oximetry played in increasing a healthy
anesthesia, and while it was better than Minolta’s or Nell- interest in such hot topics as prevention of retinopathy of
cor’s devices, it was primarily a research device designed for prematurity, lung surfactant replacement therapy, and high
respiratory internists. With little input from clinical anes- frequency oscillation (HFO).
thesiologists at Biox, Nellcor’s device, that came after, was
clearly and overwhelmingly better for clinical use. From anesthesia to critical care
In 1984, Biox was bought by the British Company BOC,
a world leader at the time in anesthesia related products. The The Japanese Society of Anesthesiologists created their
fingertip model, Biox 3700, was introduced [41]. In antici- first safety guidelines (Monitoring Guidelines for Anesthe-
pation of selling in Japan, they sought input from Japanese sia Safety) and recommended use of pulse oximeters during
sales offices and anesthesiologists. Improvements, such as anesthesia. This was 7 years after ASA released their first
waveform display and the shape of re-usable probes, were Monitoring Guidelines for Anesthesia in 1986 in the US.
made. The efforts by Mr. Yasuhiko Sata (Tokibo) to use Professor Shosuke Takahashi played an important role, but
sales techniques unique to Japan were successful, and in more than half of physicians who engaged in anesthesia did
Japan, Biox sold much more than Nellcor that had already not have access to even one pulse oximeter in their institu-
captured the anesthesia market in North America and tions. Domestic competition was practically non-existent.
Europe. At this point, neither Nihon Kohden nor Minolta Interest in pulse oximeters grew rapidly in the field of anes-
had products that were better than foreign ones. The domi- thesia, but when their use expanded from during anesthesia
nation of the Japanese market by foreign brands continued. when patients did not move to the recovery room, ICU and
13
general wards, a big problem arose in how to deal with false Nihon Kohden starts development of pulse
alarms from body movement. When venous waves are super- oximeters again; problems with multi‑wavelengths
imposed on pulse waves, the convenient assumption of pulse and precision
oximeters that all pulsation is arterial pulsation no longer
holds. In efforts to decrease false alarms, many strategies In 1984, Dr. Aoyagi was put back in charge of the devel-
were tried, such as temporarily freezing alarm information, opment of pulse oximeters at Nihon Kohen. Dr. Aoyagi
prolonging the moving average time of the data, and extrac- formed a team including Mr. Masayoshi Fuse and Dr. Naoki
tion of the arterial waveform during synchronization with Kobayashi. As opposed to the clinical, practical approach
electrocardiograms, but none of these served as a funda- that helped Masimo succeed, Nihon Kohden followed a con-
mental solution. servative, theoretical approach to achieve great precision.
A group from the Masimo Corporation, founded in 1989 The theory of multi-wavelengths (5 wavelengths) was
by Mr. Joe Kiani, focused on the problem of false alarms proposed in 2008 [60] and was established by Dr. Aoyagi in
from body movement (in other words how to deal with body 2015, but they are still verifying the theory and no product
movement and low perfusion) in pediatric patients with heart has been made. However, this cautious approach is not nec-
disease who tend to be agitated and move a lot, and unavoid- essarily a failure to act. A long-term issue for the prevention
able body activity in the PICU (Pediatric Intensive Care), as and survival prognosis of neonatal retinopathy was about the
compared to adult ICUs or NICUs. need to adjust the threshold for low perfusion or adjust the
fine calibration curve [61]. In 2020, the topic of the clinical
Emergence of Masimo Corporation significance of measurement differences due to racial dif-
ferences (skin color) [47] came up, but there was little basis
From the early 1990s, the Masimo Corporation, looking for discussion, because there was no theory and no way to
into cooperation with the major electronic company NEC, compare numbers using a standardized calibration. The only
found little interest in the problem of body movement in conclusion is that we’ve reached a limit. In other words, con-
the field of anesthesia in adults, so they developed deeper veniently neglecting differences in skin color, race, adults,
relationships with Dr. Katsuyuki Miyasaka and Dr. Yas- infants, body shape, place of measurement, device, etc. is
uyuki Suzuki from the Intensive Care Department of the not questioned for the sake of convenience. It is impossi-
National Children’s Hospital (now the National Center for ble to standardize calibration using actual measurements on
Child Health and Development, Tokyo). They were study- human beings who cannot be standardized (no more than
ing the reliability of and problem of false alarms in respira- calibration can be standardized), between manufacturers
tory monitors in pediatric ICUs and respiratory therapy in and devices, different probes, etc. The road laid down for us
home care pediatric patients. They had also introduced a by Dr. Aoyagi is of great importance to break the deadlock
project called the “Sound of Silence” to address the prob- of the acceptance of differences of 1–2% especially in the
lem of alarm fatigue in pediatric anesthesia and pediatric low SpO2 range and to establish a theory, as emphasized by
ICUs such that all alarms were silenced within 3 times of Nihon Kohden.
beeping. Thus, they were able to obtain many hours of raw
data and video recordings from pulse oximeters and patients. The challenge of in vitro calibration
It was not a comparative study, and it was not published,
but this data on Japanese patients in pediatric ICUs helped Dr. Aoyagi and I have known each other since 1980. In our
strengthen strategies to deal with body movement, and thus work for ISO TC-121 SC3 (mainly patient monitor devices),
low perfusion in adults. It helped in improving of Masimo we came to be concerned about the precision of pulse oxi-
SET (ver. 2.2) that functions well even in patients who move meters that were being produced without regard for the lack
(2000) [28, 59]. of a method for standard calibration. As ISO searched for a
Even without a theory of pulse oximetry, they developed solution for a standard, I suggested incorporating the device
a method of measuring S pO2 using arithmetic chips and into an international standard, without fully understanding
powerful statistical methods. They further added multiple the reason for why there was no calibration standard. I ended
wavelengths and are introducing new monitor indices, such up being put in charge. Fortunately, Mr. Yamanishi and Dr.
as carboxyhemoglobin and other abnormal hemoglobins, Aoyagi were able to participate in the project. At the time,
total hemoglobin, oxygen reserve index (ORi), and various I was using a small roller pump for development of the
circulating blood volume indices. They are pioneering a road world’s smallest ECMO for pediatrics [62], and I figured out
of their own. This is a little different from big data analy- that if I clipped a probe onto the circuit, I could get decent
sis, but by proceeding from special extractions and relative pulsation. Without sacrificing any people, I thought I could
relationships, they found causal relationships and I hope this calibrate under extreme hypoxic conditions.
will result in the establishment of a theory.
13
“We might have a principle of pulse oximetry, but no is committed to solving this difficult problem, and has sub-
theory.” mitted an article to this memorial issue that shows his dedi-
When I told Dr. Aoyagi my idea, he said in no uncertain cation to this cause.
terms “That’s pointless, pulse oximetry has a principle, but
it does not have a theory.” Struck by this Zen-like opinion, I The spread of pulse oximeters in society
was deeply shocked. In the 40 years, since I have known Dr. and the issues involved
Aoyagi, he never used strong words like that again. After a
short discussion, I said, “Well, it’s your job to establish a While Dr. Aoyagi was pleased with the widespread use of
theory or whatever. If you do not, you will not get a Nobel pulse oximeters, he feared that without a theory, the number
Prize.” In response to my young arrogance, his manner fell displayed might take on a life of its own. It is not possible to
apart and he said, “Aah. You won that one.” Then he gave a rule out the influence this strong reluctance Dr. Aoyagi had
carefree smile, and with a gesture of friendship, stopped the about believing the reliability of the number displayed had
argument, and continued his considerate explanation with on how he did not come up with a product. But under the
a pencil. shadow of the great usefulness of the device for COVID-19,
it is a concern that pulse oximeters are being used not just in
Research on multi‑wavelengths the operating room, but everywhere, by medical profession-
als and ordinary people alike, without a proper understand-
In the end, I never succeeded in establishing an in vitro cali- ing of what it means.
bration method for ISO [63], but this was the same as saying Mr. Hironami Kubota, who once worked at Nihon
the theory had not been established. The most recent ISO Kohden at the same time as Dr. Aoyagi and engaged in
standard ended up mandating empirical calibration using the development of central patient monitoring systems,
blood sampling in healthy adults who are exposed to a non- has added a discussion to his article in this memorial issue
physiological level of hypoxia. Thus, the accuracy of cur- about how the use of pulse oximeters, developed for use
rently available pulse oximeters ignores such factors as race, on seriously ill patients in a special environment, does
age (adult or child), or individual devices. Mr. Hironami not match its current use elsewhere, from general patient
Kubota questions whether regular household devices really wards to the non-medical general population. While pulse
need to go through such a complicated calibration process. oximeters are classified as medical devices requiring regu-
It is a very complicated issue. lar maintenance in Japan, they are being used widely by
Dr. Aoyagi started working on a complete theory and the general population without being aware of what they
after verification with experiments with multi-wavelength are, or even escaping safety rules by being embedded in a
simulation models that took into account light scattering large number of products. Their performance is improv-
and pulsation, and also the effect of surrounding tissue, he ing as a common device and the difference between pulse
presented his work at IAMPOV 2015 (Tokyo) [13]. The oximeters for medical use is hard to understand. Noninva-
main reason for his studies using multi-wavelengths was to sive patient monitors, such as pulse oximeters in wearable
improve precision. However, since he was not looking at form, will continue to flood the market and influence our
such factors as abnormal hemoglobin, I think it is possible daily lives. They cause little harm as electronic devices,
his research was not considered important enough to result but if you misinterpret the numbers displayed, critical
in product development and never became a major project. harm can result. The current regulatory system to protect
users from suffering this kind of harm is inadequate.
Research that was a stretch We, as clinicians, have to inform people of possible
dangers from these devices. It is becoming more and more
Against this background, Dr. Aoyagi continued his experi- important to let people know how to interpret the number
ments, where a small number of subjects held their breath displayed. Although the device is not recommended for
to create a state of hypoxia, sometimes for a long time. He running or for measurements other than on the fingertip,
came to my research lab at the hospital when he felt there they are used without a second thought if the number dis-
was a chance that it would help to have a doctor around. played looks right. There is no problem legally speaking if
The subjects usually were himself and Mr. Masayoshi Fuse, the number displayed is not on a device labeled for medi-
a long-time member of his team. Over 70 years of age, he cal use. In the current state of affairs, where the appropri-
felt the overstretched research was ghastly. As a result, the ate use of pulse oximeters is not guaranteed, people will
issues for Dr. Aoyagi’s multi-wavelength theory have not not even be able to tell if a device is poorly made as long
yet been fully verified or followed up. As someone who rep- as the number looks right. When something that can be
resents the researchers continuing Dr. Aoyagi’s work, Mr. used by anybody by just clipping on a probe and reading a
Kazumasa Ito, who worked on Dr. Aoyagi’s later research, number, combined with the situation, where pulsations of
13
healthy people are strong, any product will show “normal” I must make special note of the fact that I never once
values. Even if there was a dangerous condition, no one stepped into Dr. Aoyagi’s research lab. He always came
would notice a problem as long as the number is within alone to the room where I worked in the hospital, waiting
the “normal” range. to talk to me in between patients. Sometimes, he would
Even if you do not call it a diagnosis, interpreting the let me know ahead of time and send documents for me to
number shown, or particularly judging the line between nor- read, and sometimes I had the chance to hear him discuss
mal and not normal, requires medical understanding. While things for hours. That time was so special, but I could not
it is necessary to educate users about correctly understand- share it with my staff, because it was not possible to fit it
ing the number, the regulations demanding proper educa- in around our work schedules. Truthfully, I did not know
tion of the general public in Japan are vague. The manuals what Dr. Aoyagi’s position was in his company or what his
included in the devices say “seek a doctor’s opinion if there research and development goals were. I do not think he had
is a problem,” but this warning is of no use to the lay public, the opportunity to let his supervisors in his company know
because as things are now, there is no way for them to know what was really on his mind. The fact that it was not pos-
if there is a problem or not. However, people use the device sible to create a structure to join the forces of a top-class
to “find a problem.” Thus, the user is left believing in the research developer from a privately-owned company with a
device without adequate understanding and no one including physician like me, working in a national hospital, is typical
the company or government has responsibility for misuse of of the limitations faced by scientists trying to develop new
the device. medical devices in Japan.
While the authorities in charge may be interested in the There is a distinct difference between evaluating “fin-
safety of electronic products, they are not interested in how ished” pharmaceuticals and “unfinished” developing medi-
the numbers displayed are interpreted or in the safety of the cal devices. How to apply medical devices to patients is of
medical device embedded in the device. There are very few paramount importance in medical device development. It
cases, where clinicians are involved in product inspection. is essential for the user and developer to work together in
Our mission is to educate the public whenever we have a developing new medical devices. Unfortunately, even now
chance and provide them with the knowledge they need to there is no such system of cooperation in public hospitals in
evaluate products, where medical quality and non-medical Japan, rather it is restricted.
quality products are combined. Dr. Aoyagi’s explanations and his presentations at con-
ferences had a very unique style using Excel for projection
Epilogue and hand-written explanations. His unique structural style
was convincing. You can see this in his invention notes from
After participating in this memorial issue and reading all 1973. Somehow, he reminds me of Maestro Herbert Blomst-
the manuscripts, I feel great gratitude for the immense con- edt, the 93-year-old conductor (Honorary Conductor Laure-
tribution Dr. Aoyagi made to human health. When I think ate of the NHK Symphony Orchestra) in manner and looks.
how the lives of so many people have been saved and how The Dr. Aoyagi I know outside of work is a person with
many more will be saved in the future, I feel incredibly for-
tunate to have lived and worked with Dr. Aoyagi. In 2000,
I co-authored a paper, “Theory and applications of pulse
spectrophotometry,” which raised my expectations as a clini-
cal researcher for the future of pulse oximetry in the next
generation of patient monitors. I realized how privileged I
was to have helped develop pulse oximetry for 30 years, but
I felt how much regret Dr. Aoyagi had for leaving his task
unfinished, while the rest of us continued to treat cavalierly
the lack of the true basis of measurement, the theory. Plan-
ning for this memorial issue has helped me realize that on
the other side of his great contribution to clinical medicine,
was the limited number of clinicians directly involved.
It is not that Dr. Aoyagi was untalkative or anti-social, but
he definitely did not talk much about things other than his
research. I knew him for the better part of 35 years, but even
if we talked a bit about art, I do not remember ever talking to
him about his family or him personally. I guess I too belong Fig. 18 Dr. Aoyagi showing his work to Dr. Byron Aoki of the Uni-
to an era of Japan where that was not unusual. versity of Hawaii (at the author’s office at NCCHD, 2002)
13
deep knowledge of music and art. Sometimes he surprised Open Access This article is licensed under a Creative Commons Attri-
me with his extraordinary knowledge of art history and the bution 4.0 International License, which permits use, sharing, adapta-
tion, distribution and reproduction in any medium or format, as long
arts. He was like a pure young man who threw himself fully as you give appropriate credit to the original author(s) and the source,
into whatever interested him (Fig. 18). provide a link to the Creative Commons licence, and indicate if changes
I have a special memory from being with him at a meeting were made. The images or other third party material in this article are
of ISO in September 1987 in Moscow, part of the previous included in the article’s Creative Commons licence, unless indicated
otherwise in a credit line to the material. If material is not included in
Soviet Union. At the time, the Soviet Union was subject to the article’s Creative Commons licence and your intended use is not
the ups and downs of perestroika, a bit like what things are permitted by statutory regulation or exceeds the permitted use, you will
like in North Korea now. Dr. Aoyagi arrived at the Mos- need to obtain permission directly from the copyright holder. To view a
cow airport on a different plane from me and was supposed copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
to give me my visa. But he forgot and had passed through
immigration, leaving me in the hands of Soviet immigration
for an entire day at the airport. He never realized the serious- References
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Tribute To Dr. Takuo Aoyagi, Inventor of Pulse Oximetry: Special Article

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Journal of Anesthesia (2021) 35:671–709

Tribute to Dr. Takuo Aoyagi, inventor of pulse oximetry

Keywords Pulse oximetry · Patient monitoring · Anesthesia safety · History

Introduction I am from a generation that experienced anesthesiol-

Table 1 Short curriculum vitae

Table 2 Course of pulse oximeter development—comparison between Japan and the US

Fig. 1 Models of principles

(a) Two-wavelength model (b) Three-wavelength model

tion ratio ΔA1/ΔA2 obtained using an additional wavelength

Consideration of the effects of veins

To further improve the accuracy, Dr. Aoyagi paid attention

to the effects of venous blood in addition to those of tissues.

1) Effects of arterial oxygen saturation.

Attenuation ratio He thought that since there are 4 unknowns, if measure-

Fig. 5 Comparison between

Future issues/prospects We dedicate the following brief history of the develop-

Downsizing and weight reduction of pulse

As stated above, the probe and fiberoptic cables of OXIMET

saving, vibration resistance, ease of handling, and cost

Nellcor: Continuous perioperative oximetry

David J. Steward MB BS, FRCPC.

“Nellcor, Inc. (snip) widely advertised the clinical impor-

device in 1977, stimulating other firms to further improve

Fig. 16 Memorial photo at

device was judged to be useful at some level as a research

Minolta’s OXIMET‑1471 pulse oximeter goes

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