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Biomedical subjects

G L Coté

Publications and source records attributed to G L Coté.

14 recordsLinked to original sources
PubMed2005

A new paradigm for graduate research and training in the biomedical sciences and engineering.

98Emphasis on the individual investigator has fostered discovery for centuries, yet it is now recognized that the complexity of problems in the biomedical sciences and engineering requires collaborative efforts from individuals having diverse training and expertise. Various approaches can facilitate interdisciplinary interactions, but we submit that there is a critical need for a new educational paradigm for the way that we train biomedical engineers, life scientists, and mathematicians. We cannot continue to train graduate students in isolation within single disciplines, nor can we ask any one individual to learn all the essentials of biology, engineering, and mathematics. We must transform how students are trained and incorporate how real-world research and development are done-in diverse, interdisciplinary teams. Our fundamental vision is to create an innovative paradigm for graduate research and training that yields a new generation of biomedical engineers, life scientists, and mathematicians that is more diverse and that embraces and actively pursues a truly interdisciplinary, team-based approach to research based on a known benefit and mutual respect. In this paper, we describe our attempt to accomplish this via focused training in biomechanics, biomedical optics, mathematics, mechanobiology, and physiology. The overall approach is applicable, however, to most areas of biomedical research.

Biological Science Disciplines↗
PubMed2001

Measurement of the glucose transport time delay between the blood and aqueous humor of the eye for the eventual development of a noninvasive glucose sensor.

In the recent past, several noninvasive optically based methods have been proposed for physiologic glucose sensing. One proposed optical sensing site has been the eye, which, due to its unique optical properties, can be considered as a transparent optical window into the body. In particular, the aqueous humor within the anterior chamber of the eye has been shown to contain glucose levels correlated to those of blood. Concern, however, has been expressed that using the aqueous humor solution as a measure of blood glucose may be problematic due to the potential transport time delay between the blood and the aqueous humor glucose concentrations. This investigation was performed to measure the transport time delay in a rabbit model. The time delay between the blood and aqueous humor glucose concentrations was measured invasively in five New Zealand White rabbits over a series of weeks. An anesthesia protocol containing the drug Xylazine was used to elevate the blood glucose levels to a level commonly seen in diabetic patients. The difference between the glucose peak location times occurring in the blood and aqueous humor glucose response was measured and defined as the transport time delay. The average transport time lag was measured to be under 5 min. This measured time delay indicates that, indeed, the eye could potentially be used as a sensing site for indirect blood glucose measurements and may eventually aid the development of a noninvasive glucose sensor due to its unique optical properties compared to other biological tissues.

Anesthetics, Local↗
PubMed2001

Noninvasive and minimally-invasive optical monitoring technologies.

With recent advancements in micro-fabrication and nano-fabrication techniques as well as advancements in the photonics industry, there is now the potential to develop less invasive portable sensors for monitoring micronutrients and other substances used to assess overall health. There have been many technology innovations in the central laboratory for these substances for overall health status but the primary motivation for the research and development of a portable field instrument has come from a diabetic patient and market-driven desire to minimally invasively or noninvasively monitor glucose concentrations in vivo. Such a sensor system has the potential to significantly improve the quality of life for the estimated 16 million diabetics in this country by making routine glucose measurements less painful and more convenient. In addition, there is a critical need for the development of less invasive portable technologies to assess micronutrient status (iron, vitamin A, iodine and folate), environmental hazards (lead) and for other disease-related substances, such as billirubin for infant jaundice. Currently, over 100 small companies and universities are working to develop improved monitoring devices, primarily for glucose, and optical methods are a big part of these efforts. In this article many of these potentially less invasive and portable optical sensing technologies, which are currently under investigation, will be reviewed including optical absorption spectroscopy, polarimetry, Raman spectroscopy and fluorescence.

Child↗
PubMed2000

X-ray structure determination and modeling of the cyclic tetrasaccharide cyclo.

The cyclic tetrasaccharide cyclo-[-->6)-alpha-D-Glcp-(1-->3)-alpha-D-Glcp-(1-->6)-alpha-D-Glcp-(1-->3)-alpha-D-Glcp-(1-->] is the major compound obtained by the action of endo-alternases on the alternan polysaccharide. Crystals of this cyclo-tetra-glucose belong to the orthorhombic space group P2(1)2(1)2(1) with a = 7.620(5), b = 12.450(5) and c = 34.800(5) A. The asymmetric unit contains one tetrasaccharide together with five water molecules. The tetrasaccharide adopts a plate-like overall shape with a very shallow depression on one side. The shape is not fully symmetrical and this is clearly apparent on comparing the (phi, psi) torsion angles of the two alpha-(1-->6) linkages. There is almost 10 degrees differences in phi and more than 20 degrees differences in psi. The hydrogen bond network is asymmetric, with a single intramolecular hydrogen bond: O-2 of glucose ring 1 being the donor to O-2 of glucose ring 3. These two hydroxyl groups are located below the ring and their orientation, dictated by this hydrogen bond, makes the floor of the plate. Among the five water molecules, one located above the center of the plate occupies perfectly the shallow depression in the plate shape formed by the tetrasaccharide. Molecular dynamics simulation of the tetrasaccharide in explicit water allows rationalization of the discrepancies observed between the X-ray structures and data obtained previously by NMR.

Carbohydrate Conformation↗
PubMed2000

A transparent tool for seemingly difficult calibrations: the parallel calibration method.

A new easy-to-understand calibration method for the analysis of spectral data is developed. The "parallel calibration" method is logically simple and intuitive yet often provides an improvement over more complex standard calibration methods. A description of the algorithm with a technical justification for the parallel algorithm is presented, underscoring the simplicity of the approach. In addition, performance as compared to that of the standard methods of classical least-squares (CLS) and partial least-squares (PLS) regression is studied. Calibrations are carried out on a computer-generated simulation data set as well as two scientific data sets. The results show that the parallel method gives results comparable to or better than those of CLS and PLS methods in terms of mean squared error.

Algorithms↗
PubMed2000

Monte Carlo modeling for implantable fluorescent analyte sensors.

A Monte Carlo simulation of photon propagation through human skin and interaction with a subcutaneous fluorescent sensing layer is presented. The algorithm will facilitate design of an optical probe for an implantable fluorescent sensor, which holds potential for monitoring many parameters of biomedical interest. Results are analyzed with respect to output light intensity as a function of radial distance from source, angle of exit for escaping photons, and sensor fluorescence (SF) relative to tissue autofluorescence (AF). A sensitivity study was performed to elucidate the effects on the output due to changes in optical properties, thickness of tissue layers, thickness of the sensor layer, and both tissue and sensor quantum yields. The optical properties as well as the thickness of the stratum corneum, epidermis, (tissue layers through which photons must pass to reach the sensor) and the papillary dermis (tissue distal to sensor) are highly influential. The spatial emission profile of the SF is broad compared that of the tissue fluorescence and the ratio of sensor to tissue fluorescence increases with distance from the source. The angular distribution of escaping photons is more concentrated around the normal for SF than for tissue AF. The information gained from these simulations will be helpful in designing appropriate optics for collection of the signal of interest.

Algorithms↗
PubMed2000

Simultaneous optical and nuclear magnetic resonance spectroscopy for monitoring cardiac energetics in vivo.

There are a number of applications in which it is useful to simultaneously collect data from what are traditionally separate instrumentation modalities. In particular, in vivo physiological investigations in which data from parallel experiments must be correlated would benefit from simultaneous data collection through 1) elimination of subject variability, 2) elimination of treatment variability, and 3) a reduction in the number of animal preparations required. Here we describe the simultaneous collection of fluo-3 optical fluorescence and 31P nuclear magnetic resonance (NMR) spectra to measure intracellular calcium levels and high-energy phosphate metabolism, respectively, in vivo. This work is part of ongoing research into the profound anoxia tolerance exhibited by the hearts of certain turtle species. An NMR compatible optical fluorescence spectrometer was constructed and tested. In the 31-cm bore of a 2 T superconducting magnet, NMR and optical spectra were collected every 10-15 min from the in situ, in vivo hearts of anesthetized turtle subjects prior to and during one to three hours of anoxia. It was found that while PCr stores became significantly depleted during anoxia, beta-adenosine triphosphate (ATP) levels remained within 20% of control values, and intracellular diastolic calcium levels did not vary by more than 10%. The ability to make simultaneous phosphorus and calcium measurements on a single subject is important to understanding the exact relationship between phosphorus energy state and maintenance of calcium homeostasis.

Adenosine Triphosphate↗
PubMed2000

Optical glucose sensing in biological fluids: an overview.

Recent technological advancements in the photonics industry have led to a resurgence of interest in optical glucose sensing and to realistic progress toward the development of an optical glucose sensor. Such a sensor has the potential to significantly improve the quality of life for the estimated 16 million diabetics in this country by making routine glucose measurements more convenient. Currently over 100 small companies and universities are working to develop noninvasive or minimally invasive glucose sensing technologies, and optical methods play a large role in these efforts. This article reviews many of the recent advances in optical glucose sensing including optical absorption spectroscopy, polarimetry, Raman spectroscopy, and fluorescent glucose sensing. In addition a review of calibration and data processing methods useful for optical techniques is presented.

Body Fluids↗
PubMed1999

A fluorescence-based glucose biosensor using concanavalin A and dextran encapsulated in a poly(ethylene glycol) hydrogel.

A fluorescence biosensor is described that is based on a photopolymerized poly(ethylene glycol) (PEG) hydrogel incorporating fluorescein isothiocyanate dextran (FITC-dextran) and tetramethylrhodamine isothiocyanate concanavalin A (TRITC-Con A) chemically conjugated into the hydrogel network using an alpha-acryloyl, omega-N-hydroxysuccinimidyl ester of PEG-propionic acid. In the absence of glucose, TRITC-Con A binds with FITC-dextran, and the FITC fluorescence is quenched through fluorescence resonance energy transfer. Competitive glucose binding to TRITC-Con A liberates FITC-dextran, resulting in increased FITC fluorescence proportional to the glucose concentration. In vitro experiments of hydrogel spheres in a solution of 0.1 M phosphate-buffered saline (pH 7.2) and glucose were conducted for multiple TRITC-Con A/FITC-dextran ratios. Hydrogels were characterized on the basis of the percent change in fluorescence intensity when FITC-dextran was liberated by increasing glucose concentrations. The optimum fluorescent change between 0 and 800 mg/dL was obtained with a TRITC-Con A/FITC-dextran mass ratio of 500:5 micrograms/mL PEG. Fluorescent response was linear up to 600 mg/dL. At higher concentrations, the response saturated due to the displacement of the majority of the FITC-dextran and to concentration quenching by free FITC-dextran. Dynamic fluorescent change upon glucose addition was approximately 10 min for a glucose concentration step change from 0 to 200 mg/dL.

Biosensing Techniques↗
PubMed1999

The use of polarized laser light through the eye for noninvasive glucose monitoring.

BACKGROUND: In order to optimally manage diabetes mellitus, it is recommended blood glucose levels be monitored several times daily so an appropriate action can be taken to maintain tight control of these levels within a normal physiological range. All commercially available devices to measure blood glucose concentrations require the extraction of a drop of blood, normally obtained via the lancing of a finger. The main drawback to this method is the pain, often leading to low patient compliance. Therefore, a noninvasive glucose sensing method would greatly facilitate the management of diabetes. METHODS: In this article, we describe in vitro and in vivo results from a laser-based optical polarimetry system using the anterior chamber of the eye as a potential method to noninvasively monitor glucose levels in the body. RESULTS: It is shown, in vitro, that glucose can be predicted in the presence of albumin at physiological levels and, through the use of a novel light coupling mechanism, it is demonstrated that a polarimetric signal can be detected, in vivo, through a rabbit eye. CONCLUSIONS: Although the commercial production of a feasible noninvasive glucose monitoring method is still years away, laser-based polarimetry remains a viable alternative due to its potential to extract concentration information using the eye as a unique optical window into the body.

Animals↗
PubMed1995

Application of a multivariate technique to Raman spectra for quantification of body chemicals.

Raman spectroscopy is a highly specific technique for the identification of molecules by way of the associated characteristic spectra. The aim of this feasibility study is to assess the combination of the multivariate calibration technique of Partial Least-Squares with Raman spectroscopy for the estimation of glucose, lactic acid, and urea concentrations in the presence of each other in a water substrate. The instrument is a CCD-based Raman spectrometer utilizing the 514.5 nm argon laser line. The estimates for the analyte concentrations yielded a standard deviation of concentration residuals of 20.71 mg/dL for glucose, 12.92 mg/dL for lactic acid, and 19.07 mg/dL for urea.

Calibration↗
PubMed1992

Noninvasive optical polarimetric glucose sensing using a true phase measurement technique.

The focus of this paper was to describe the development and testing of a noninvasive true phase optical polarimetry sensing system to monitor in vivo glucose concentrations. To demonstrate the applicability of this optical sensor for glucose measurement, we first calibrated the system and then tested it in vitro using both a glass test cell filled with glucose solution in the physiologic range, with a path length of 0.9 cm to approximate one centimeter path length present in the anterior chamber of the eye, and then on an excised human eye. Our technique used helium neon laser light which was coupled through a rotating linear polarizer along with two stationary linear polarizers and two detectors to produce reference and signal outputs whose amplitudes varied sinusoidally with a frequency of twice the angular velocity of the rotating polarizer, and whose phase was proportional to the rotation of the linear polarization vector passing through the glucose solution.

Blood Glucose↗
PubMedDate not supplied

Nonlinear closed-loop control system for intracranial pressure regulation.

A nonlinear closed-loop control system with flat pressure-versus-flow characteristics that is aimed at regulating intracranial pressure (ICP) by adjusting the volume of cerebral spinal fluid (CSF) was designed, built, and tested. The control system design allows both the pressure setpoint and hysteresis to be adjusted to overcome the difficulties inherent in differential pressure-activated, fixed resistance, open-loop shunts. A dynamic six-compartment bench-top fluid system, which mimics the cerebral spinal fluid system, was designed, built, and tested. A computer simulation was developed which included the nonlinear on-off controller with hysteresis and a sixth-order, linear, multicompartmental model of the CSF system. The computer model and in vitro system results showed the ability of the system to track and compensate for pressure variations above and below normal as well as for spurious outputs that mimic such in vivo problems as blood pressure changes, sneezing, or coughing. There was one discrepancy between the simulated and in vitro results. The in vitro system had a higher rate of increase in pressure due to the more rigid compliance of the materials used, whereas the computer model compliance, based on the basal in vivo compliance of the CSF system, was less rigid. Based on these findings, the controller was modified to account for short-duration, extremely elevated pressures.

Body Fluid Compartments↗