Abstract
Ingestible electronics can potentially be used to track and treat gastrointestinal diseases in real time. In the past decade, substantial improvements have been made to ingestible electronic pills at the sensor, circuit and system levels, which has improved the clinical applicability of the technology by increasing device sensitivity, lifetime and location awareness. Here we explore the development of ingestible electronics and provide a step-by-step guide for the design of ingestible capsules at the system level. We consider the anatomical and physiological characteristics of gastrointestinal organs, which set requirements and constraints on ingestible electronics in terms of size, shape, topology and the materials used for packaging. We then examine the key design components: sensors and actuators, integrated circuits, communication, power, packaging, localization and locomotion. We also consider the challenges that must be addressed to realize the full application potential of ingestible electronics.
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References
Jacobson, B. & Mackay, R. S. A pH-endoradiosonde. Lancet 269, 1224 (1957).
Farrar, J. T., Zworykin, V. K. & Baum, J. Pressure-sensitive telemetering capsule for study of gastrointestinal motility. Science 126, 975â976 (1957).
Iddan, G., Meron, G., Glukhovsky, A. & Swain, P. Wireless capsule endoscopy. Nature 405, 417â417 (2000).
Steiger, C. et al. Ingestible electronics for diagnostics and therapy. Nat. Rev. Mater. 4, 83â98 (2019).
Litvinova, O. et al. Digital pills with ingestible sensors: patent landscape analysis. Pharmaceuticals 15, 1025 (2022).
Miley, D. et al. Video capsule endoscopy and ingestible electronics: emerging trends in sensors, circuits, materials, telemetry, optics, and rapid reading software. Adv. Devices Instrum. 2021, 9854040 (2021).
Smart Pills Market by Application (Capsule Endoscopy, Drug Delivery, Patient Monitoring), Target Area (Esophagus, Small Intestine, Large Intestine, Stomach), End User (Hospitals, Diagnostic Centers) & RegionâGlobal Forecast to 2028 (Markets and Markets, 2023); https://www.marketsandmarkets.com/Market-Reports/smart-pill-technology-market-840.html
Kalantar-Zadeh, K., Ha, N., Ou, J. Z. & Berean, K. J. Ingestible sensors. ACS Sensors 2, 468â483 (2017).
Beardslee, L. A. et al. Ingestible sensors and sensing systems for minimally invasive diagnosis and monitoring: the next frontier in minimally invasive screening. ACS Sensors 5, 891â910 (2020).
Cummins, G. Smart pills for gastrointestinal diagnostics and therapy. Adv. Drug Deliv. Rev. 177, 113931 (2021).
Browning, K. N. & Travagli, R. A. Central nervous system control of gastrointestinal motility and secretion and modulation of gastrointestinal functions. Compr. Physiol. 4, 1339 (2014).
Dieterich, W., Schink, M. & Zopf, Y. Microbiota in the gastrointestinal tract. Med. Sci. 6, 116 (2018).
Sensoy, I. A review on the food digestion in the digestive tract and the used in vitro models. Curr. Res. Food Sci. 4, 308â319 (2021).
Tsang, K. W. & Lam, S.-K. Helicobacter pylori and extra-digestive diseases. J. Gastroenterol. Hepatol. 14, 844â850 (1999).
Montoro-Huguet, M. A., Belloc, B. & DomÃnguez-Cajal, M. Small and large intestine (I): malabsorption of nutrients. Nutrients 13, 1254 (2021).
Tong, J. W. V., Lingam, P. & Shelat, V. G. Adhesive small bowel obstructionâan update. Acute Med. Surg. 7, e587 (2020).
Qin, J. et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464, 59â65 (2010).
David, L. A. et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505, 559â563 (2014).
Luna, R. A. et al. Distinct microbiomeâneuroimmune signatures correlate with functional abdominal pain in children with autism spectrum disorder. Cell. Mol. Gastroenterol. Hepatol. 3, 218â230 (2017).
Chandra, S. et al. Healthy gut, healthy brain: the gut microbiome in neurodegenerative disorders. Curr. Top. Med. Chem. 20, 1142â1153 (2020).
Fan, Y. & Pedersen, O. Gut microbiota in human metabolic health and disease. Nat. Rev. Microbiol. 19, 55â71 (2021).
Stearns, J. et al. Bacterial biogeography of the human digestive tract. Sci. Rep. 1, 170 (2011).
Lavelle, A. & Sokol, H. Gut microbiota-derived metabolites as key actors in inflammatory bowel disease. Nat. Rev. Gastroenterol. Hepatol. 17, 223â237 (2020).
Kalantar-Zadeh, K., Berean, K. J., Burgell, R. E., Muir, J. G. & Gibson, P. R. Intestinal gases: influence on gut disorders and the role of dietary manipulations. Nat. Rev. Gastroenterol. Hepatol. 16, 733â747 (2019).
Dave, L. A., Montoya, C. A., Rutherfurd, S. M. & Moughan, P. J. Gastrointestinal endogenous proteins as a source of bioactive peptides-an in silico study. PLoS ONE 9, e98922 (2014).
Yang, X. et al. Pathophysiologic role of neurotransmitters in digestive diseases. Front. Physiol. 12, 567650 (2021).
Atsawarungruangkit, A., Elfanagely, Y., Asombang, A. W., Rupawala, A. & Rich, H. G. Understanding deep learning in capsule endoscopy: can artificial intelligence enhance clinical practice? Artif. Intell. Gastrointest. Endosc. 1, 33â43 (2020).
Nadimi, E. S. et al. Application of deep learning for autonomous detection and localization of colorectal polyps in wireless colon capsule endoscopy. Comput. Electr. Eng. 81, 106531 (2020).
Moen, S., Vuik, F. E., Kuipers, E. J. & Spaander, M. C. Artificial intelligence in colon capsule endoscopyâa systematic review. Diagnostics 12, 1994 (2022).
Sahafi, A. et al. Edge artificial intelligence wireless video capsule endoscopy. Sci. Rep. 12, 13723 (2022).
Raza, W. Gastroscopic image processingâOpenMV Cam H7. Edge Impulse https://docs.edgeimpulse.com/experts/prototype-and-concept-projects/tinyml-gastroscopic-image-processing (2023).
Qiu, Y. et al. Ultrasound capsule endoscopy with a mechanically scanning micro-ultrasound: a porcine study. Ultrasound Med. Biol. 46, 796â804 (2020).
Kimchy, Y. et al. Radiographic capsule-based system for non-cathartic colorectal cancer screening. Abdom. Radiol. 42, 1291â1297 (2016).
Gluck, N. et al. Novel prep-less X-ray imaging capsule for colon cancer screening: a feasibility study. Gut 68, 774â775 (2019).
Tabatabaei, N. et al. Tethered confocal endomicroscopy capsule for diagnosis and monitoring of eosinophilic esophagitis. Biomed. Opt. Express 5, 197â207 (2014).
Gora, M. J. et al. Tethered capsule endomicroscopy enables less invasive imaging of gastrointestinal tract microstructure. Nat. Med. 19, 238â240 (2013).
Qiao, P., Liu, H., Yan, X., Jia, Z. & Pi, X. A smart capsule system for automated detection of intestinal bleeding using HSL color recognition. PLoS ONE 11, e0166488 (2016).
Schostek, S. et al. Volunteer case series of a new telemetric sensor for blood detection in the upper gastrointestinal tract: the hemopill. Dig. Dis. Sci. 61, 2956â2962 (2016).
Demosthenous, P., Pitris, C. & Georgiou, J. Infrared fluorescence-based cancer screening capsule for the small intestine. IEEE Trans. Biomed. Circuits Syst. 10, 467â476 (2016).
Zhu, C., Wen, Y., Liu, T., Yang, H. & Sengupta, K. A packaged ingestible bio-pill with 15-pixel multiplexed fluorescence nucleic-acid sensor and bi-directional wireless interface for in-vivo bio-molecular sensing. In 2020 IEEE Symposium on VLSI Circuits 1â2 (IEEE, 2020).
Singh, S. et al. Sa1717âdevelopment of a swallowable diagnostic capsule to monitor gastrointestinal health. Gastroenterology 156, S-376 (2019).
Manickam, A. et al. A fully integrated CMOS fluorescence biochip for DNA and RNA testing. IEEE J. Solid State Circuits 52, 2857â2870 (2017).
Machida, T. A study of intragastric pH in patients with peptic ulcerâwith special reference to the clinical significance of basal pH value. Gastroenterol. Jpn. 16, 447â458 (1981).
Press, A. et al. Gastrointestinal pH profiles in patients with inflammatory bowel disease. Aliment. Pharmacol. Ther. 12, 673â678 (1998).
Maurer, J. M. et al. Gastrointestinal ph and transit time profiling in healthy volunteers using the intellicap system confirms ileo-colonic release of colopulse tablets. PLoS ONE 10, e0129076 (2015).
Arefin, M. S., Redouté, J.-M. & Yuce, M. R. Integration of low-power ASIC and mems sensors for monitoring gastrointestinal tract using a wireless capsule system. IEEE J. Biomed. Health Inform. 22, 87â97 (2017).
Cheng, C. et al. A wireless, ingestible pH sensing capsule system based on iridium oxide for monitoring gastrointestinal health. Sens. Actuators B 349, 130781 (2021).
Hasler, W. L. The use of smartpill for gastric monitoring. Expert Rev. Gastroenterol. Hepatol. 8, 587â600 (2014).
Caffrey, C. M., Twomey, K. & Ogurtsov, V. Development of a wireless swallowable capsule with potentiostatic electrochemical sensor for gastrointestinal track investigation. Sens. Actuators B 218, 8â15 (2015).
Salama, R., Arshavsky-Graham, S., Sella-Tavor, O., Massad-Ivanir, N. & Segal, E. Design considerations of aptasensors for continuous monitoring of biomarkers in digestive tract fluids. Talanta 239, 123124 (2022).
Li, J. et al. A tissue-like neurotransmitter sensor for the brain and gut. Nature 606, 94â101 (2022).
Kim, J. et al. Edible electrochemistry: food materials based electrochemical sensors. Adv. Healthc. Mater. 6, 1700770 (2017).
Montiel, V. et al. Direct electrochemical biosensing in gastrointestinal fluids. Anal. Bioanal. Chem. 411, 4597â4604 (2019).
De la Paz, E. et al. A self-powered ingestible wireless biosensing system for real-time in situ monitoring of gastrointestinal tract metabolites. Nat. Commun. 13, 7405 (2022).
Hafezi, H. et al. An ingestible sensor for measuring medication adherence. IEEE Trans. Biomed. Eng. 62, 99â109 (2015).
Flores, G. P. et al. Performance, reliability, usability, and safety of the ID-Cap system for ingestion event monitoring in healthy volunteers: a pilot study. Innov. Clin. Neurosci. 13, 12â19 (2016).
Chai, P. R. et al. Ingestible electronic sensors to measure instantaneous medication adherence: a narrative review. Digit. Health 8, 20552076221083119 (2022).
Ghoreishizadeh, S. S., Taurino, I., De Micheli, G., Carrara, S. & Georgiou, P. A differential electrochemical readout asic with heterogeneous integration of bio-nano sensors for amperometric sensing. IEEE Trans. Biomed. Circuits Syst. 11, 1148â1159 (2017).
Herstein, J. J. et al. A pilot study of core body temperatures in healthcare workers wearing personal protective equipment in a high-level isolation unit. J. Occup. Environ. Hyg. 18, 430â435 (2021).
OâBrien, C., Hoyt, R. W., Buller, M. J., Castellani, J. W. & Young, A. J. Telemetry pill measurement of core temperature in humans during active heating and cooling. Med. Sci. Sports Exerc. 30, 468â472 (1998).
West, M. R., Costello, S., Sol, J. A. & Domitrovich, J. W. Risk for heat-related illness among wildland firefighters: job tasks and core body temperature change. Occup. Environ. Med. 77, 433â438 (2020).
Monnard, C. R. et al. Issues in continuous 24-h core body temperature monitoring in humans using an ingestible capsule telemetric sensor. Front. Endocrinol. 8, 130 (2017).
Kalantar-Zadeh, K. et al. A human pilot trial of ingestible electronic capsules capable of sensing different gases in the gut. Nat. Electron. 1, 79â87 (2018).
Mimee, M. et al. An ingestible bacterial-electronic system to monitor gastrointestinal health. Science 360, 915â918 (2018).
Inda-Webb, M. et al. Sub-1.4 cm3 capsule for detecting labile inflammatory biomarkers in situ. Nature 620, 386â392 (2023).
Inami, A., Kan, T. & Onoe, H. Ingestible wireless capsule sensor made from edible materials for gut bacteria monitoring. In 2022 IEEE 35th International Conference on Micro Electro Mechanical Systems Conference (MEMS) 110â113 (IEEE, 2022).
Guozheng, Y., Biao, H. & Peng, Z. Design of battery-less and real-time telemetry system for gastrointestinal applications. In 2007 IEEE International Conference on Control and Automation 245â249 (IEEE, 2007).
Liao, C.-H. et al. An ingestible electronics for continuous and real-time intraabdominal pressure monitoring. J. Pers. Med. 11, 12 (2020).
Beardslee, L. A. et al. Blast capsule: an embedded pressure sensing system for internal blast pressure measurement. IEEE Sens. Lett. 5, 1â4 (2021).
Yunus, N. A. M., Halin, I. A., Sulaiman, N., Ismail, N. F. & Sheng, O. K. Valuation on MEMS pressure sensors and device applications. Int. J. Electron. Commun. Eng. 9, 834â842 (2015).
Dagdeviren, C. et al. Flexible piezoelectric devices for gastrointestinal motility sensing. Nat. Biomed. Eng. 1, 807â817 (2017).
Dileena, L., Sreeja, S. B. & Sreekala, C. A comparative study on piezoelectric and piezoresistive pressure sensor using comsol simulation. Mater. Today Proc. 46, 3121â3126 (2021).
Hoang, M. C. et al. A robotic biopsy endoscope with magnetic 5-DOF locomotion and a retractable biopsy punch. Micromachines 11, 98 (2020).
Son, D., Gilbert, H. & Sitti, M. Magnetically actuated soft capsule endoscope for fine-needle biopsy. Soft Robot. 7, 10â21 (2020).
Yim, S., Gultepe, E., Gracias, D. H. & Sitti, M. Biopsy using a magnetic capsule endoscope carrying, releasing, and retrieving untethered microgrippers. IEEE Trans. Biomed. Eng. 61, 513â521 (2014).
Hoang, M. C. et al. Untethered robotic motion and rotating blade mechanism for actively locomotive biopsy capsule endoscope. IEEE Access 7, 93364â93374 (2019).
Finocchiaro, M. et al. Design of a magnetic actuation system for a microbiota-collection ingestible capsule. In 2021 IEEE International Conference on Robotics and Automation (ICRA) 6905â6911 (IEEE, 2021).
Waimin, J. F. et al. Smart capsule for non-invasive sampling and studying of the gastrointestinal microbiome. RSC Adv. 10, 16313â16322 (2020).
Rezaei Nejad, H. et al. Ingestible osmotic pill for in vivo sampling of gut microbiomes. Adv. Intell. Syst. 1, 1900053 (2019).
Chen, L., Gruzinskyte, L., Jørgensen, S. L., Boisen, A. & Srivastava, S. K. An ingestible self-polymerizing system for targeted sampling of gut microbiota and biomarkers. ACS Nano 14, 12072â12081 (2020).
Shalon, D. et al. Profiling the human intestinal environment under physiological conditions. Nature 617, 581â591 (2023).
Kong, K., Yim, S., Choi, S. & Jeon, D. A robotic biopsy device for capsule endoscopy. J. Med. Devices 6, 031004 (2012).
Durán-Lobato, M., Niu, Z. & Alonso, M. J. Oral delivery of biologics for precision medicine. Adv. Mater. 32, 1901935 (2020).
Castro, R., Libânio, D., Pita, I. & Dinis-Ribeiro, M. Solutions for submucosal injection: what to choose and how to do it. World J. Gastroenterol. 25, 777 (2019).
Yamaguchi, D. et al. Colorectal endoscopic mucosal resection with submucosal injection of epinephrine versus hypertonic saline in patients taking antithrombotic agents: propensity-score-matching analysis. BMC Gastroenterol. 19, 1 (2019).
Traverso, G. et al. Microneedles for drug delivery via the gastrointestinal tract. J. Pharm. Sci. 104, 362â367 (2015).
Abramson, A. et al. An ingestible self-orienting system for oral delivery of macromolecules. Science 363, 611â615 (2019).
Abramson, A. et al. Oral delivery of systemic monoclonal antibodies, peptides and small molecules using gastric auto-injectors. Nat. Biotechnol. 40, 103â109 (2022).
Abramson, A. et al. A luminal unfolding microneedle injector for oral delivery of macromolecules. Nat. Med. 25, 1512â1518 (2019).
Our technology. Biograil https://biograil.com/the-technology/(2023).
Aran, K. et al. An oral microjet vaccination system elicits antibody production in rabbits. Sci. Transl. Med. 9, eaaf6413 (2017).
Beccani, M. et al. A magnetic drug delivery capsule based on a coil actuation mechanism. Procedia Eng. 120, 53â56 (2015).
Sarker, S. et al. A novel capsule-delivered enteric drug-injection device for delivery of systemic biologics: a pilot study in a porcine model. IEEE Trans. Biomed. Eng. 69, 1870â1879 (2021).
Srinivasan, S. S. et al. Robocap: robotic mucus-clearing capsule for enhanced drug delivery in the gastrointestinal tract. Sci. Robot. 7, eabp9066 (2022).
Söderlind, E. et al. Validation of the IntelliCap® system as a tool to evaluate extended release profiles in human GI tract using metoprolol as model drug. J. Control. Release 217, 300â307 (2015).
Koo, J. et al. Wirelessly controlled, bioresorbable drug delivery device with active valves that exploit electrochemically triggered crevice corrosion. Sci. Adv. 6, eabb1093 (2020).
Bal, S. M., Caussin, J., Pavel, S. & Bouwstra, J. A. In vivo assessment of safety of microneedle arrays in human skin. Eur. J. Pharm. Sci. 35, 193â202 (2008).
Miller, D. & Niichel, R. Advancing high tech drug delivery systems for the treatment of Crohnâs disease. Gastroenterology 160, S2âS3 (2021).
Dhalla, A. K. et al. A robotic pill for oral delivery of biotherapeutics: safety, tolerability, and performance in healthy subjects. Drug Deliv. Transl. Res. 12, 294â305 (2022).
Schoellhammer, C. M. et al. Ultrasound-mediated gastrointestinal drug delivery. Sci. Transl. Med. 7, 310ra168 (2015).
Schoellhammer, C. M., Langer, R. & Traverso, G. Of microneedles and ultrasound: physical modes of gastrointestinal macromolecule delivery. Tissue Barriers 4, e1150235 (2016).
Arnold, M. et al. Global burden of 5 major types of gastrointestinal cancer. Gastroenterology 159, 335â349 (2020).
A study of high intensity focused ultrasound for cancer of the rectum. Cancer Research UK https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-of-high-intensity-focused-ultrasound-for-cancer-of-the-rectum#undefined (2019).
Li, M., Wan, G., Yu, H. & Xiong, W. High-intensity focused ultrasound inhibits invasion and metastasis of colon cancer cells by enhancing microrna-124-mediated suppression of stat3. FEBS Open Bio 9, 1128â1136 (2019).
Stewart, F. et al. Ultrasound mediated delivery of quantum dots from a proof of concept capsule endoscope to the gastrointestinal wall. Sci. Rep. 11, 2584 (2021).
Rao, S. S., Lembo, A., Chey, W. D., Friedenberg, K. & Quigley, E. M. Effects of the vibrating capsule on colonic circadian rhythm and bowel symptoms in chronic idiopathic constipation. Neurogastroenterol. Motil. 32, e13890 (2020).
Ron, Y. et al. Safety and efficacy of the vibrating capsule, an innovative non-pharmacological treatment modality for chronic constipation. Neurogastroenterol. Motil. 27, 99â104 (2015).
Nelson, A. D. et al. A single-center, prospective, double-blind, sham-controlled, randomized study of the effect of a vibrating capsule on colonic transit in patients with chronic constipation. Neurogastroenterol. Motil. 29, e13034 (2017).
Yu, J. et al. Safety and efficacy of a new smartphone-controlled vibrating capsule on defecation in beagles. Sci. Rep. 7, 2841 (2017).
Miyashita, S. et al. Ingestible, controllable, and degradable origami robot for patching stomach wounds. In 2016 IEEE International Conference on Robotics and Automation (ICRA) 909â916 (IEEE, 2016).
Ponce, J., Quebbemann, B. B. & Patterson, E. J. Prospective, randomized, multicenter study evaluating safety and efficacy of intragastric dual-balloon in obesity. Surg. Obes. Relat. Dis. 9, 290â295 (2013).
Kaan, H. L. et al. First-in-man feasibility study of a novel ingestible magnetically inflated balloon capsule for treatment of obesity. Endosc. Int. Open 8, E607âE610 (2020).
Freitas, R., Rodrigues, J., Puga, H. & Correia, J. Design, simulation, and fabrication of an ingestible capsule with gastric balloon for obesity treatment. Biomed. Phys. Eng. Express 7, 055024 (2021).
Do, T. N., Seah, T. E. T., Yu, H. K. & Phee, S. J. Development and testing of a magnetically actuated capsule endoscopy for obesity treatment. PLoS ONE 11, e0148035 (2016).
Do, T. N., Ho, K. Y. & Phee, S. J. A magnetic soft endoscopic capsule-inflated intragastric balloon for weight management. Sci. Rep. 6, 1â10 (2016).
Phan, P. T. et al. EndoPil: a magnetically actuated swallowable capsule for weight management: development and trials. Ann. Biomed. Eng. 49, 1391â1401 (2021).
Cutts, T., Luo, J., Starkebaum, W., Rashed, H. & Abell, T. Is gastric electrical stimulation superior to standard pharmacologic therapy in improving GI symptoms, healthcare resources, and long-term health care benefits? Neurogastroenterol. Motil. 17, 35â43 (2005).
Abell, T. L. et al. Effectiveness of gastric electrical stimulation in gastroparesis: results from a large prospectively collected database of national gastroparesis registries. Neurogastroenterol. Motil. 31, e13714 (2019).
Abramson, A. et al. Ingestible transiently anchoring electronics for microstimulation and conductive signaling. Sci. Adv. 6, eaaz0127 (2020).
Maisiyiti, A. & Chen, J. D. Systematic review on gastric electrical stimulation in obesity treatment. Expert Rev. Med. Devices 16, 855â861 (2019).
Yao, G. et al. Effective weight control via an implanted self-powered vagus nerve stimulation device. Nat. Commun. 9, 5349 (2018).
TSMC MPW full block tapeouts. MUSE SEMICONDUCTOR https://www.musesemi.com/full-block-tapeout-pricing (2022).
Liao, Y.-T., Yao, H., Lingley, A., Parviz, B. & Otis, B. P. A 3-μW CMOS glucose sensor for wireless contact-lens tear glucose monitoring. IEEE J. Solid State Circuits 47, 335â344 (2012).
FCC Online Table of Frequency Allocations Title 47, Ch. 2, Part 106 (Federal Communications Commission, 2021).
Khaleghi, A. & Balasingham, I. On selecting the frequency for wireless implant communications. In IEEE Loughborough Antennas & Propagation Conference (LAPC) 1â4 (IEEE, 2015).
Liu, Y. & Gitlin, R. D. A phenomenological path loss model of the in vivo wireless channel. In 2015 IEEE 16th Annual Wireless and Microwave Technology Conference (WAMICON) 1â3 (IEEE, 2015).
Faerber, J. et al. In vivo characterization of a wireless telemetry module for a capsule endoscopy system utilizing a conformal antenna. IEEE Trans. Biomed. Circuits Systems 12, 95â105 (2018).
Basir, A., Zada, M., Cho, Y. & Yoo, H. A dual-circular-polarized endoscopic antenna with wideband characteristics and wireless biotelemetric link characterization. IEEE Trans. Antennas Propag. 68, 6953â6963 (2020).
Christoe, M. J. et al. Meandering pattern 433 MHz antennas for ingestible capsules. IEEE Access 9, 91874â91882 (2021).
Suzan Miah, M., Khan, A. N., Icheln, C., Haneda, K. & Takizawa, K.-I. Antenna system design for improved wireless capsule endoscope links at 433 MHz. IEEE Trans. Antennas Propag. 67, 2687â2699 (2019).
Lei, W. & Guo, Y.-X. Design of a dual-polarized wideband conformal loop antenna for capsule endoscopy systems. IEEE Trans. Antennas Propag. 66, 5706â5715 (2018).
Song, M. et al. A millimeter-scale crystal-less MICS transceiver for insertable smart pills. IEEE Trans. Biomed. Circuits Syst. 14, 1218â1229 (2020).
Abdigazy, A. & Monge, M. A bimodal low-power transceiver featuring a ring oscillator-based transmitter and magnetic field-based receiver for insertable smart pills. IEEE Solid State Circuits Lett. 5, 154â157 (2022).
Mondal, S. & Hall, D. A. A 67-μW ultra-low power PVT-robust MedRadio transmitter. In 2020 IEEE Radio Frequency Integrated Circuits Symposium (RFIC) 327â330 (IEEE, 2020).
Shi, Y., Chen, X., Kim, H.-S., Blaauw, D. & Wentzloff, D. 28.3 a 606μW mm-scale bluetooth low-energy transmitter using co-designed 3.5âÃâ3.5 mm 2 loop antenna and transformer-boost power oscillator. In 2019 IEEE International Solid-State Circuits Conference (ISSCC) 442â444 (IEEE, 2019).
Shibata, K. et al. A 22nm 0.84 mm 2 BLE transceiver with self IQ-phase correction achieving 39dB image rejection and on-chip antenna impedance tuning. In 2022 IEEE International Solid-State Circuits Conference (ISSCC) Vol. 65, 398â400 (IEEE, 2022).
Ba, A. et al. A 0.33 nJ/bit IEEE802. 15.6/proprietary MICS/ISM wireless transceiver with scalable data rate for medical implantable applications. IEEE J. Biomed. Health Inform. 19, 920â929 (2015).
Jang, J., Bae, J. & Yoo, H.-J. Understanding body channel communication: a review: from history to the future applications. In 2019 IEEE Custom Integrated Circuits Conference (CICC) 1â8 (IEEE, 2019).
Jang, J. et al. A four-camera VGA-resolution capsule endoscope system with 80-mB/s body channel communication transceiver and sub-centimeter range capsule localization. IEEE J. Solid State Circuits 54, 538â549 (2018).
Chang, T. C., Wang, M. L., Charthad, J., Weber, M. J. & Arbabian, A. 27.7 A 30.5mm3 fully packaged implantable device with duplex ultrasonic data and power links achieving 95kb/s with <10â4 BER at 8.5cm depth. In 2017 IEEE International Solid-State Circuits Conference (ISSCC) 460â461 (IEEE, 2017).
Zhang, Y. & Shepard, K. L. A 0.6-mm2 powering and data telemetry system compatible with ultrasound B-mode imaging for freely moving biomedical sensor systems. In 2019 IEEE Custom Integrated Circuits Conference (CICC) 1â4 (IEEE, 2019).
Sonmezoglu, S. & Maharbiz, M. M. 34.4 A 4.5mm3 deep-tissue ultrasonic implantable luminescence oxygen sensor. In 2020 IEEE International Solid-State Circuits Conference (ISSCC) 454â456 (IEEE, 2020).
Chuo, L.-X. et al. 7.4 A 915MHz asymmetric radio using Q-enhanced amplifier for a fully integrated 3âÃâ3âÃâ3mm3 wireless sensor node with 20m non-line-of-sight communication. In 2017 IEEE International Solid-State Circuits Conference (ISSCC) 132â133 (IEEE, 2017).
Chen, Y. et al. A review of lithium-ion battery safety concerns: the issues, strategies, and testing standards. J. Energy Chem. 59, 83â99 (2021).
Le, S. et al. Status of zincâsilver battery. J. Electrochem. Soc. 166, A2980 (2019).
Ciuti, G., Menciassi, A. & Dario, P. Capsule endoscopy: from current achievements to open challenges. IEEE Rev. Biomed. Eng. 4, 59â72 (2011).
Li, C. et al. An advance review of solid-state battery: challenges, progress and prospects. Sustain. Mater. Technol. 29, e00297 (2021).
Kumar, P. et al. Melanin-based flexible supercapacitors. J. Mater. Chem. C 4, 9516â9525 (2016).
Mittal, N., Ojanguren, A., Niederberger, M. & Lizundia, E. Degradation behavior, biocompatibility, electrochemical performance, and circularity potential of transient batteries. Adv. Sci. 8, 2004814 (2021).
Chen, Y. et al. Physicalâchemical hybrid transiency: a fully transient Li-ion battery based on insoluble active materials. J. Polym. Sci. B 54, 2021â2027 (2016).
Kutbee, A. T. et al. Flexible and biocompatible high-performance solid-state micro-battery for implantable orthodontic system. npj Flex. Electron. 1, 7 (2017).
Li, N., Chen, Z., Ren, W., Li, F. & Cheng, H.-M. Flexible graphene-based lithium ion batteries with ultrafast charge and discharge rates. Proc. Natl Acad. Sci. USA 109, 17360â17365 (2012).
Aeby, X., Poulin, A., Siqueira, G., Hausmann, M. K. & Nyström, G. Fully 3D printed and disposable paper supercapacitors. Adv. Mater. 33, 2101328 (2021).
Crespilho, F. N. et al. Non-corrosive, low-toxicity gel-based microbattery from organic and organometallic molecules. J. Mater. Chem. A 7, 24784â24787 (2019).
Liu, L., Towfighian, S. & Jin, Z. A cylindrical triboelectric energy harvester for capsule endoscopes. In 2015 IEEE Biomedical Circuits and Systems Conference (BioCAS) 1â4 (IEEE, 2015).
Yoshida, S., Miyaguchi, H. & Nakamura, T. Development of ingestible thermometer with built-in coil antenna charged by gastric acid battery and demonstration of long-time in vivo telemetry. IEEE Access 9, 102368â102377 (2021).
Dong, K. et al. Microbial fuel cell as power supply for implantable medical devices: a novel configuration design for simulating colonic environment. Biosens. Bioelectron. 41, 916â919 (2013).
Han, Y., Yu, C. & Liu, H. A microbial fuel cell as power supply for implantable medical devices. Biosens. Bioelectron. 25, 2156â2160 (2010).
Zhao, L., Annayev, M., Oralkan, Ã. & Jia, Y. An ultrasonic energy harvesting IC providing adjustable bias voltage for pre-charged CMUT. IEEE Trans. Biomed. Circuits Systems 16, 842â851 (2022).
Abid, A. et al. Wireless power transfer to millimeter-sized gastrointestinal electronics validated in a swine model. Sci. Rep. 7, 46745 (2017).
Iqbal, A., Sura, P. R., Al-Hasan, M., Mabrouk, I. B. & Denidni, T. A. Wireless power transfer system for deep-implanted biomedical devices. Sci. Rep. 12, 13689 (2022).
Ingestible Telemetric Gastrointestinal Capsule Imaging SystemâFinal Class II Special Controls Guidance Document for Industry and FDA (US FDA, 2001); https://www.fda.gov/medical-devices/guidance-documents-medical-devices-and-radiation-emitting-products/ingestible-telemetric-gastrointestinal-capsule-imaging-system-final-class-ii-special-controls
General Considerations for Animal Studies Intended to Evaluate Medical Devices (US FDA, 2023); https://www.fda.gov/regulatory-information/search-fda-guidance-documents/general-considerations-animal-studies-intended-evaluate-medical-devices
Wang, Y.-C. et al. Adverse events of video capsule endoscopy over the past two decades: a systematic review and proportion meta-analysis. BMC Gastroenterol. 20, 364 (2020).
Lee, S. Y., Lee, J. Y., Lee, Y. J. & Park, K. S. Natural elimination of a video capsule after retention for 1 year in a patient with small bowel crohn disease: a case report. Medicine 98, e17580 (2019).
Saad, M. K., Fiani, E., El Hajj, I. & Saikaly, E. A rare complication of capsule endoscopy, retained in diverticula: a report of two cases. Int. J. Gastrointest. Interv. 10, 36â39 (2021).
Inui, T., Koga, H., Nogi, M., Komoda, N. & Suganuma, K. A miniaturized flexible antenna printed on a high dielectric constant nanopaper composite. Adv. Mater. 27, 1112â1116 (2015).
Rai, T., Dantes, P., Bahreyni, B. & Kim, W. S. A stretchable RF antenna with silver nanowires. IEEE Electron Device Lett. 34, 544â546 (2013).
Tsang, M. et al. A MEMS-enabled biodegradable battery for powering transient implantable devices. In 2014 IEEE 27th International Conference on Micro Electro Mechanical Systems (MEMS) 358â361 (IEEE, 2014).
Hu, L., Wu, H., La Mantia, F., Yang, Y. & Cui, Y. Thin, flexible secondary Li-ion paper batteries. ACS Nano 4, 5843â5848 (2010).
Bonacchini, G. E. et al. Tattoo-paper transfer as a versatile platform for all-printed organic edible electronics. Adv. Mater. 30, 1706091 (2018).
Kang, S.-K., Koo, J., Lee, Y. K. & Rogers, J. A. Advanced materials and devices for bioresorbable electronics. Acc. Chem. Res. 51, 988â998 (2018).
Umay, I., Fidan, B. & Barshan, B. Localization and tracking of implantable biomedical sensors. Sensors 17, 583 (2017).
Wang, M. L., Chang, T. C. & Arbabian, A. Ultrasonic implant localization for wireless power transfer: active uplink and harmonic backscatter. In 2019 IEEE International Ultrasonics Symposium (IUS) 818â821 (IEEE, 2019).
Chen, H., Rogalski, M. M. & Anker, J. N. Advances in functional X-ray imaging techniques and contrast agents. Phys. Chem. Chem. Phys. 14, 13469â13486 (2012).
Koziolek, M. et al. Investigation of pH and temperature profiles in the GI tract of fasted human subjects using the IntelliCap® system. J. Pharm. Sci. 104, 2855â2863 (2015).
Ye, Y., Khan, U. & Pahlavan, K. Accuracy bounds for RSS and TOA based RF localization in capsule endoscopy. In Proc. 33rd IEEE Annual International Conference of Engineering in Medicine and Biology Society (EMBC) 5602â5607 (IEEE, 2011).
Vasisht, D. et al. In-body backscatter communication and localization. In Proc. 2018 Conference of the ACM Special Interest Group on Data Communication 132â146 (ACM, 2018).
Chen, F., Liu, J. & Liao, H. 3D catheter shape determination for endovascular navigation using a two-step particle filter and ultrasound scanning. IEEE Trans. Med. Imaging 36, 685â695 (2017).
Parent, F. et al. Intra-arterial image guidance with optical frequency domain reflectometry shape sensing. IEEE Trans. Med. Imaging 38, 482â492 (2019).
Hu, C., Meng, M.-H. & Mandal, M. Efficient linear algorithm for magnetic localization and orientation in capsule endoscopy. In 2005 IEEE Engineering in Medicine and Biology 27th Annual Conference 7143â7146 (IEEE, 2005).
Hu, C. et al. A cubic 3-axis magnetic sensor array for wirelessly tracking magnet position and orientation. IEEE Sens. J. 10, 903â913 (2010).
Gao, H., Lin, Y. & Monge, M. Towards magnetic field gradient-based imaging and control of in-body devices. In 2021 IEEE Biomedical Circuits and Systems Conference (BioCAS) 1â4 (IEEE, 2021).
Rustom, M. & Sideris, C. Wireless frequency-division multiplexed 3D magnetic localization for low power sub-mm precision capsule endoscopy. In 2022 IEEE Custom Integrated Circuits Conference (CICC) 01â02 (IEEE, 2022).
Rustom, M. & Sideris, C. Design and implementation of a low power wireless frequency-division multiplexed magnetic 3D localization scheme with sub-mm precision for capsule endoscopy applications. IEEE Solid State Circuits Lett. 6, 37â40 (2023).
Sharma, S. et al. Location-aware ingestible microdevices for wireless monitoring of gastrointestinal dynamics. Nat. Electron. 6, 242â256 (2023).
Carta, R. et al. Wireless powering for a self-propelled and steerable endoscopic capsule for stomach inspection. Biosens. Bioelectron. 25, 845â851 (2009).
Liang, H., Guan, Y., Xiao, Z., Hu, C. & Liu, Z. A screw propelling capsule robot. In 2011 IEEE International Conference on Information and Automation 786â791 (IEEE, 2011).
Wang, K., Yan, G., Ma, G. & Ye, D. An earthworm-like robotic endoscope system for human intestine: design, analysis, and experiment. Ann. Biomed. Eng. 37, 210â221 (2009).
Chen, Z., Liu, J., Wang, S. & Zuo, S. A bio-inspired self-propelling endoscopic device for inspecting the large intestine. Bioinspir. Biomim. 14, 066013 (2019).
Kim, H. M. et al. Active locomotion of a paddling-based capsule endoscope in an in vitro and in vivo experiment (with videos). Gastrointest. Endosc. 72, 381â387 (2010).
Valdastri, P. et al. A new mechanism for mesoscale legged locomotion in compliant tubular environments. IEEE Trans. Robot. 25, 1047â1057 (2009).
Mosse, C., Mills, T. N., Appleyard, M. N., Kadirkamanathan, S. S. & Swain, C. Electrical stimulation for propelling endoscopes. Gastrointest. Endosc. 54, 79â83 (2001).
Woo, S. H., Kim, T. W., Mohy-Ud-Din, Z., Park, I. Y. & Cho, J.-H. Small intestinal model for electrically propelled capsule endoscopy. Biomed. Eng. Online 10, 108 (2011).
Keller, J. et al. Inspection of the human stomach using remote-controlled capsule endoscopy: a feasibility study in healthy volunteers (with videos). Gastrointest. Endosc. 73, 22â28 (2011).
Rey, J.-F. et al. Blinded nonrandomized comparative study of gastric examination with a magnetically guided capsule endoscope and standard videoendoscope. Gastrointest. Endosc. 75, 373â381 (2012).
Schostek, S. et al. Telemetric real-time sensor for the detection of acute upper gastrointestinal bleeding. Biosens. Bioelectron. 78, 524â529 (2016).
Zhuang, Z. et al. Alterations of the gut microbiota and plasma biomarkers in Parkinsonâs disease. Parkinsonism Relat. Disord. 81, 179â184 (2020).
Kang, D.-W. et al. Microbiota transfer therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study. Microbiome 7, 10 (2019).
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Y.K. acknowledges support from USC Viterbi School of Engineering.
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Abdigazy, A., Arfan, M., Lazzi, G. et al. End-to-end design of ingestible electronics. Nat Electron 7, 102â118 (2024). https://doi.org/10.1038/s41928-024-01122-2
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DOI: https://doi.org/10.1038/s41928-024-01122-2
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