Cartilage was obtained from eight matched knee (tibiofemoral and femoropatellar) and ankle (taloc... more Cartilage was obtained from eight matched knee (tibiofemoral and femoropatellar) and ankle (talocrural) joints of five different donors (both left and right from donors 14, 22, and 38 years of age, and left only from donors 31 and 45 years of age) within 24 hours of death. All cartilage was graded as normal by the macroscopic visual Collins' scale and the histological Mankin scale. Cylindrical disks of cartilage were harvested from 10 sites within the tibiofemoral and femoropatellar joint surfaces and four sites within the talocrural joint. and uniaxial confincd compression measurements were performed to quantify a spectrum of
Un appareil microfluide de matrice MxN pour realiser une matrice de reactions, l'appareil aya... more Un appareil microfluide de matrice MxN pour realiser une matrice de reactions, l'appareil ayant une pluralite de cellules de reaction en communication avec soit une entree d'echantillon ou une entree de reactif par une voie formee dans un bloc elastomere de l'appareil. Les methodes fournies comprennent une methode pour former des voies en parallele dans une couche elastomere d'un bloc elastomere d'un dispositif microfluide, la methode comprenant l'utilisation de masques photoresistants imprimes et de reactifs d'attaque pour detacher des zones ou des portions d'une couche elastomere du bloc elastomere.
L'invention concerne un substrat biologique, par exemple une puce microfluidique. Le substrat... more L'invention concerne un substrat biologique, par exemple une puce microfluidique. Le substrat contient un materiau de substrat rigide lequel presente une region de surface pouvant faire office de substrat de manipulation. Le substrat comprend egalement une couche de fluide deformable couplee a la region de surface. Une ou plusieurs regions de puits sont formees dans une premiere portion de la couche de fluide deformable et sont capables de contenir un fluide. Une ou plusieurs regions de canaux sont formees dans une seconde partie de la couche de fluide deformable et elles sont couplees a une ou a plusieurs des regions de puits. Une region active est formee dans la couche de fluide deformable. Au moins trois marquages d'alignement sont formes a l'interieur de la region non active et ils sont disposes d'une maniere spatiale associee a au moins l'une des regions de puits. Une couche de commande est couplee a la couche de fluide.
Background: Measurement of cardiac Troponin-I (cTnI) has been designated the gold standard for di... more Background: Measurement of cardiac Troponin-I (cTnI) has been designated the gold standard for diagnosis of acute myocardial infarction and as indicative of cardiac disease. Measurement of cTnI can be used for diagnosis of acute myocardial infarction and in the risk stratification of patients with non-ST segment elevation acute coronary syndromes, with respect to relative risk of mortality, myocardial infarction, or increased probability of ischemic events requiring urgent revascularization procedures. Recently a new ultra-sensitive assay for in vitro diagnostic measurement of cTnI has become available in the Singulex Clinical Laboratory (CLIA#:05D1092709, CLF#:338067). This assay utilizes the Erenna Immunoassay System, which is based on single-molecule detection. Objective: Evaluate the analytical performance of the Erenna cTnI assay for the Singulex Clinical Laboratory. Methods: Analytical accuracy and spike recovery were determined by preparing and testing spiked samples of EDTA plasma from a single donor. This plasma was spiked with cTnI standard from NIST (SRM 2921, Gaithersburg, MD) to generate a series of samples ranging from 5.2-52 pg/mL. Assay precision and lot-to-lot variability of assay reagents were assessed using two controls prepared by spiking two EDTA plasma samples to levels of 6 and 55 pg/mL, respectively, with a cTnI reference standard from HyTest (Turku, Finland). A reference range for the Erenna cTnI diagnostic assay was established using specimens from 153 apparently healthy blood donors (122 male, 31 female, average age 34.5 yrs, age range 19-63 yrs), and the 99th%, 10%CV and inter-quartile reference ranges were determined. Results: Analytical sensitivity of the Erenna cTnI assay was 0.2 pg/mL (0.0002 ng/L) with a LLoQ of 1.0 pg/mL with good linearity (1-70 pg/mL, slope = 1.01, R 2 = 0.999) and spike recovery (98-103%) of the HyTest cTnI material. Analytical accuracy, determined using NIST-spiked plasma, was >85% over a range of 6 pg/mL to 50 pg/mL (y = 0.9x-0.3261, R 2 = 0.9993) with average spike recovery of 89.1% (range 85.4-91.5%). Within-and between-run precision varied between 6-8%, with acceptable lot-to-lot variability (<15%) in testing of HyTest-spiked control plasma. Using donor plasma (n=153), the distribution of cTnI concentration was Gaussian, with a mean (±SD) of 1.97 (±1.85) pg/mL, and a calculated 99th percentile value of 6.28 pg/mL (≤10%CV). Conclusions: The Erenna cTnI assay shows excellent analytical performance in the Singulex Clinical Laboratory, with a 99th% cutoff value far below that of other clinically available in vitro diagnostic immunoassay systems. CLIA-regulated availability of this new, ultra-sensitive assay is an important step towards enabling early disease detection and clinical investigations into cardiac disease.
Le changement d'impedance d'un tissu du un changement de la matrice extracellulaire resul... more Le changement d'impedance d'un tissu du un changement de la matrice extracellulaire resultant d'une degradation du cartilage est utilise pour detecter la degradation du cartilage articulaire. Une sonde comportant des electrodes delivre un courant au cartilage articulaire, ce qui entraine une repartition de charges electriques et donc un champ electrique au sein du cartilage, ainsi qu'une chute de tension associee entre les electrodes. L'amplitude de cette chute de tension est alors mesuree et divisee par le courant applique pour determiner l'impedance du tissu. La mesure de l'impedance du tissu d'un patient et la comparaison de l'impedance detectee chez le patient avec une valeur normale pour le tissu obtenue a partir d'un tissu cliniquement normal permettent de determiner si le tissu du patient est degrade ainsi que l'importance de la degradation. De preference, l'impedance est mesuree a l'aide d'une sonde dotee d'electrod...
Currently, detection of the onset of osteoarthritis is very difficult without using destructive t... more Currently, detection of the onset of osteoarthritis is very difficult without using destructive techniques. Without early detection, pharmaceutical intervention to reverse or prevent osteoarthritis cannot be achieved. A technique developed by Frank and Grodzinsky takes advantage of an electromechanical property inherent in cartilage. Upon the introduction of an electrical field to the cartilage surface, a mechanical stress at the surface is produced via an electrokinetic effect. This electrokinetic effect in cartilage is a function of the molecular composition and integrity of the tissue. Past designs to measure this phenomenon have now resulted in a handheld in-vivo probe that utilizes the technology of piezo-electric films. These piezo-electric films can sensitively measure the mechanical stresses developed within the cartilage and convert them into a quantitative electrical signal. Potential applications of this probe include use in arthroscopic surgery to provide surgeons with more quantitative information for diagnostics and therapeutic intervention. By testing the probe on human tissue and validating such measurements, the goal of this thesis is to show that the size of the handheld in-vivo probe can be reduced for arthroscopic surgery and that the measurements made by the probe can be correlated to the physical properties of cartilage.
Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Aeronautics and Astronautics, 1998... more Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Aeronautics and Astronautics, 1998.Includes bibliographical references (leaves 83-88).by Emerson Cheung Quan.M.S
Detection of cardiac injury by measurement of cardiac troponin (cTn) is essential for diagnosis o... more Detection of cardiac injury by measurement of cardiac troponin (cTn) is essential for diagnosis of acute myocardial infarction (AMI) and provides information for risk stratification. Recent guidelines recommend use of the 99th percentile cutoff value with assay imprecision <10%1,2, ...
Detection of cardiac injury by measurement of cardiac troponin (cTn) is essential for diagnosis o... more Detection of cardiac injury by measurement of cardiac troponin (cTn) is essential for diagnosis of acute myocardial infarction (AMI) and provides information for risk stratification. Recent guidelines recommend use of the 99th percentile cutoff value with assay imprecision <10%1,2, ...
Detection of cardiac injury by measurement of cardiac troponin (cTn) is essential for diagnosis o... more Detection of cardiac injury by measurement of cardiac troponin (cTn) is essential for diagnosis of acute myocardial infarction (AMI) and provides information for risk stratification. Recent guidelines recommend use of the 99th percentile cutoff value with assay imprecision <10%1,2, ...
Detection of cardiac injury by measurement of cardiac troponin (cTn) is essential for diagnosis o... more Detection of cardiac injury by measurement of cardiac troponin (cTn) is essential for diagnosis of acute myocardial infarction (AMI) and provides information for risk stratification. Recent guidelines recommend use of the 99th percentile cutoff value with assay imprecision <10%1,2, ...
Cartilage was obtained from eight matched knee (tibiofemoral and femoropatellar) and ankle (taloc... more Cartilage was obtained from eight matched knee (tibiofemoral and femoropatellar) and ankle (talocrural) joints of five different donors (both left and right from donors 14, 22, and 38 years of age, and left only from donors 31 and 45 years of age) within 24 hours of death. All cartilage was graded as normal by the macroscopic visual Collins' scale and the histological Mankin scale. Cylindrical disks of cartilage were harvested from 10 sites within the tibiofemoral and femoropatellar joint surfaces and four sites within the talocrural joint. and uniaxial confincd compression measurements were performed to quantify a spectrum of physical properties including the equilibrium modulus, hydraulic permeability, dynamic stiffness, streaming potential, electrokinetic coupling coefficient, and electrical conductivity. Matched specimens from the same 14 sites were used for complementary measurements of biochemical composition and molecular interaction, including water content, hypotonic swelling behavior, and sulfated glycosaminoglycan and collagen contents. In comparison of the top 1-mm slices of talar cartilage with the top 1-mm of tibiofemoral cartilage. the talar cartilage appeared denser with a higher sulfated glycosaminoglycan content, lower water content. higher equilibrium modulus and dynamic stiffness, and lower hydraulic pcrmcability. The equilibrium modulus increased with increasing sulfated glycosaininoglycans per wct wcight and decreased with increasing water content for all joint surfaces. Multiple linear regression showcd that greater than 80% of the variation in the equilibrium modulus could be accounted for by variations in the biochemical parameters (water content, sulfated glycosaminoglycansiwet weight, and hydroxyproline contentiwcl wcight) for each joint surface. Nonhomogeneous depth-dependent changes in the physical properties and biochemical composition of fullthickness distal femoral cartilage were consistent with previous reports. Since the comprcssive deformation of cartilage during cyclic loading is confined to the more superficial rcgions, the differences in properties of the upper regions of the talar compared with tibiofemoral or femoropatellar cartilage may be important in the eliology of osteoarthritis.
Cartilage was obtained from eight matched knee (tibiofemoral and femoropatellar) and ankle (taloc... more Cartilage was obtained from eight matched knee (tibiofemoral and femoropatellar) and ankle (talocrural) joints of five different donors (both left and right from donors 14, 22, and 38 years of age, and left only from donors 31 and 45 years of age) within 24 hours of death. All cartilage was graded as normal by the macroscopic visual Collins' scale and the histological Mankin scale. Cylindrical disks of cartilage were harvested from 10 sites within the tibiofemoral and femoropatellar joint surfaces and four sites within the talocrural joint. and uniaxial confincd compression measurements were performed to quantify a spectrum of
Un appareil microfluide de matrice MxN pour realiser une matrice de reactions, l'appareil aya... more Un appareil microfluide de matrice MxN pour realiser une matrice de reactions, l'appareil ayant une pluralite de cellules de reaction en communication avec soit une entree d'echantillon ou une entree de reactif par une voie formee dans un bloc elastomere de l'appareil. Les methodes fournies comprennent une methode pour former des voies en parallele dans une couche elastomere d'un bloc elastomere d'un dispositif microfluide, la methode comprenant l'utilisation de masques photoresistants imprimes et de reactifs d'attaque pour detacher des zones ou des portions d'une couche elastomere du bloc elastomere.
L'invention concerne un substrat biologique, par exemple une puce microfluidique. Le substrat... more L'invention concerne un substrat biologique, par exemple une puce microfluidique. Le substrat contient un materiau de substrat rigide lequel presente une region de surface pouvant faire office de substrat de manipulation. Le substrat comprend egalement une couche de fluide deformable couplee a la region de surface. Une ou plusieurs regions de puits sont formees dans une premiere portion de la couche de fluide deformable et sont capables de contenir un fluide. Une ou plusieurs regions de canaux sont formees dans une seconde partie de la couche de fluide deformable et elles sont couplees a une ou a plusieurs des regions de puits. Une region active est formee dans la couche de fluide deformable. Au moins trois marquages d'alignement sont formes a l'interieur de la region non active et ils sont disposes d'une maniere spatiale associee a au moins l'une des regions de puits. Une couche de commande est couplee a la couche de fluide.
Background: Measurement of cardiac Troponin-I (cTnI) has been designated the gold standard for di... more Background: Measurement of cardiac Troponin-I (cTnI) has been designated the gold standard for diagnosis of acute myocardial infarction and as indicative of cardiac disease. Measurement of cTnI can be used for diagnosis of acute myocardial infarction and in the risk stratification of patients with non-ST segment elevation acute coronary syndromes, with respect to relative risk of mortality, myocardial infarction, or increased probability of ischemic events requiring urgent revascularization procedures. Recently a new ultra-sensitive assay for in vitro diagnostic measurement of cTnI has become available in the Singulex Clinical Laboratory (CLIA#:05D1092709, CLF#:338067). This assay utilizes the Erenna Immunoassay System, which is based on single-molecule detection. Objective: Evaluate the analytical performance of the Erenna cTnI assay for the Singulex Clinical Laboratory. Methods: Analytical accuracy and spike recovery were determined by preparing and testing spiked samples of EDTA plasma from a single donor. This plasma was spiked with cTnI standard from NIST (SRM 2921, Gaithersburg, MD) to generate a series of samples ranging from 5.2-52 pg/mL. Assay precision and lot-to-lot variability of assay reagents were assessed using two controls prepared by spiking two EDTA plasma samples to levels of 6 and 55 pg/mL, respectively, with a cTnI reference standard from HyTest (Turku, Finland). A reference range for the Erenna cTnI diagnostic assay was established using specimens from 153 apparently healthy blood donors (122 male, 31 female, average age 34.5 yrs, age range 19-63 yrs), and the 99th%, 10%CV and inter-quartile reference ranges were determined. Results: Analytical sensitivity of the Erenna cTnI assay was 0.2 pg/mL (0.0002 ng/L) with a LLoQ of 1.0 pg/mL with good linearity (1-70 pg/mL, slope = 1.01, R 2 = 0.999) and spike recovery (98-103%) of the HyTest cTnI material. Analytical accuracy, determined using NIST-spiked plasma, was >85% over a range of 6 pg/mL to 50 pg/mL (y = 0.9x-0.3261, R 2 = 0.9993) with average spike recovery of 89.1% (range 85.4-91.5%). Within-and between-run precision varied between 6-8%, with acceptable lot-to-lot variability (<15%) in testing of HyTest-spiked control plasma. Using donor plasma (n=153), the distribution of cTnI concentration was Gaussian, with a mean (±SD) of 1.97 (±1.85) pg/mL, and a calculated 99th percentile value of 6.28 pg/mL (≤10%CV). Conclusions: The Erenna cTnI assay shows excellent analytical performance in the Singulex Clinical Laboratory, with a 99th% cutoff value far below that of other clinically available in vitro diagnostic immunoassay systems. CLIA-regulated availability of this new, ultra-sensitive assay is an important step towards enabling early disease detection and clinical investigations into cardiac disease.
Le changement d'impedance d'un tissu du un changement de la matrice extracellulaire resul... more Le changement d'impedance d'un tissu du un changement de la matrice extracellulaire resultant d'une degradation du cartilage est utilise pour detecter la degradation du cartilage articulaire. Une sonde comportant des electrodes delivre un courant au cartilage articulaire, ce qui entraine une repartition de charges electriques et donc un champ electrique au sein du cartilage, ainsi qu'une chute de tension associee entre les electrodes. L'amplitude de cette chute de tension est alors mesuree et divisee par le courant applique pour determiner l'impedance du tissu. La mesure de l'impedance du tissu d'un patient et la comparaison de l'impedance detectee chez le patient avec une valeur normale pour le tissu obtenue a partir d'un tissu cliniquement normal permettent de determiner si le tissu du patient est degrade ainsi que l'importance de la degradation. De preference, l'impedance est mesuree a l'aide d'une sonde dotee d'electrod...
Currently, detection of the onset of osteoarthritis is very difficult without using destructive t... more Currently, detection of the onset of osteoarthritis is very difficult without using destructive techniques. Without early detection, pharmaceutical intervention to reverse or prevent osteoarthritis cannot be achieved. A technique developed by Frank and Grodzinsky takes advantage of an electromechanical property inherent in cartilage. Upon the introduction of an electrical field to the cartilage surface, a mechanical stress at the surface is produced via an electrokinetic effect. This electrokinetic effect in cartilage is a function of the molecular composition and integrity of the tissue. Past designs to measure this phenomenon have now resulted in a handheld in-vivo probe that utilizes the technology of piezo-electric films. These piezo-electric films can sensitively measure the mechanical stresses developed within the cartilage and convert them into a quantitative electrical signal. Potential applications of this probe include use in arthroscopic surgery to provide surgeons with more quantitative information for diagnostics and therapeutic intervention. By testing the probe on human tissue and validating such measurements, the goal of this thesis is to show that the size of the handheld in-vivo probe can be reduced for arthroscopic surgery and that the measurements made by the probe can be correlated to the physical properties of cartilage.
Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Aeronautics and Astronautics, 1998... more Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Aeronautics and Astronautics, 1998.Includes bibliographical references (leaves 83-88).by Emerson Cheung Quan.M.S
Detection of cardiac injury by measurement of cardiac troponin (cTn) is essential for diagnosis o... more Detection of cardiac injury by measurement of cardiac troponin (cTn) is essential for diagnosis of acute myocardial infarction (AMI) and provides information for risk stratification. Recent guidelines recommend use of the 99th percentile cutoff value with assay imprecision <10%1,2, ...
Detection of cardiac injury by measurement of cardiac troponin (cTn) is essential for diagnosis o... more Detection of cardiac injury by measurement of cardiac troponin (cTn) is essential for diagnosis of acute myocardial infarction (AMI) and provides information for risk stratification. Recent guidelines recommend use of the 99th percentile cutoff value with assay imprecision <10%1,2, ...
Detection of cardiac injury by measurement of cardiac troponin (cTn) is essential for diagnosis o... more Detection of cardiac injury by measurement of cardiac troponin (cTn) is essential for diagnosis of acute myocardial infarction (AMI) and provides information for risk stratification. Recent guidelines recommend use of the 99th percentile cutoff value with assay imprecision <10%1,2, ...
Detection of cardiac injury by measurement of cardiac troponin (cTn) is essential for diagnosis o... more Detection of cardiac injury by measurement of cardiac troponin (cTn) is essential for diagnosis of acute myocardial infarction (AMI) and provides information for risk stratification. Recent guidelines recommend use of the 99th percentile cutoff value with assay imprecision <10%1,2, ...
Cartilage was obtained from eight matched knee (tibiofemoral and femoropatellar) and ankle (taloc... more Cartilage was obtained from eight matched knee (tibiofemoral and femoropatellar) and ankle (talocrural) joints of five different donors (both left and right from donors 14, 22, and 38 years of age, and left only from donors 31 and 45 years of age) within 24 hours of death. All cartilage was graded as normal by the macroscopic visual Collins' scale and the histological Mankin scale. Cylindrical disks of cartilage were harvested from 10 sites within the tibiofemoral and femoropatellar joint surfaces and four sites within the talocrural joint. and uniaxial confincd compression measurements were performed to quantify a spectrum of physical properties including the equilibrium modulus, hydraulic permeability, dynamic stiffness, streaming potential, electrokinetic coupling coefficient, and electrical conductivity. Matched specimens from the same 14 sites were used for complementary measurements of biochemical composition and molecular interaction, including water content, hypotonic swelling behavior, and sulfated glycosaminoglycan and collagen contents. In comparison of the top 1-mm slices of talar cartilage with the top 1-mm of tibiofemoral cartilage. the talar cartilage appeared denser with a higher sulfated glycosaminoglycan content, lower water content. higher equilibrium modulus and dynamic stiffness, and lower hydraulic pcrmcability. The equilibrium modulus increased with increasing sulfated glycosaininoglycans per wct wcight and decreased with increasing water content for all joint surfaces. Multiple linear regression showcd that greater than 80% of the variation in the equilibrium modulus could be accounted for by variations in the biochemical parameters (water content, sulfated glycosaminoglycansiwet weight, and hydroxyproline contentiwcl wcight) for each joint surface. Nonhomogeneous depth-dependent changes in the physical properties and biochemical composition of fullthickness distal femoral cartilage were consistent with previous reports. Since the comprcssive deformation of cartilage during cyclic loading is confined to the more superficial rcgions, the differences in properties of the upper regions of the talar compared with tibiofemoral or femoropatellar cartilage may be important in the eliology of osteoarthritis.
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