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NASA NTRS2004

New optical scheme for a polarimetric-based glucose sensor

A new optical scheme to detect glucose concentration in the aqueous humor of the eye is presented. The ultimate aim is to apply this technique in designing a new instrument for, routinely and frequently, noninvasively monitoring blood glucose levels in diabetic patients without contact (no index matching) between the eye and the instrument. The optical scheme exploits the Brewster reflection of circularly polarized light off of the lens of the eye. Theoretically, this reflected linearly polarized light on its way to the detector is expected to rotate its state of polarization, owing to the presence of glucose molecules in the aqueous humor of a patient's eye. An experimental laboratory setup based on this scheme was designed and tested by measuring a range of known concentrations of glucose solutions dissolved in water. (c) 2004 Society of Photo-Optical Instrumentation Engineers.

Evaluation Studies↗

NASA NTRS2002

A New Optical Scheme for a Polarimetric-Based Glucose Sensor

We describe a new optical scheme to perform polarimetric measurements to detect glucose concentration in the aqueous humor of a model eye. The ultimate aim is to apply this technique in designing a new instrument for measuring glucose levels in diabetic patients routinely, frequently, and non-invasively. The scheme exploits the Brewsterreflection of circularly polarized light off of the lens of the eye. Theoretically, this backreflected linearly polarized light on its way to the detector is expected to rotate its state of polarization due to the presence of glucose molecules in the aqueous humor of patients. An experimental laboratory setup based on this scheme was designed and tested by measuring a range of known concentration of glucose solutions dissolved in water.

Ansari, Rafat R.↗

NASA NTRS2007

Method for Texturing Surfaces of Optical Fiber Sensors Used for Blood Glucose Monitoring

Disclosed is a method and the resulting product thereof comprising a solid light-conducting fiber with a point of attachment and having a textured surface site consisting a textured distal end prepared by being placed in a vacuum and then subjected to directed hyperthermal beams comprising oxygen ions or atoms. The textured distal end comprises cones or pillars that are spaced upon from each other by less than 1 micron and are extremely suitable to prevent cellular components of blood from entering the valleys between the cones or pillars so as to effectively separate the cellular components in the blood from interfering with optical sensing of the glucose concentration for diabetic patients.

Banks, Bruce A.↗

NASA NTRS2006

Improved Oxygen-Beam Texturing of Glucose-Monitoring Optics

An improved method has been devised for using directed, hyperthermal beams of oxygen atoms and ions to impart desired textures to the tips of polymethylmethacrylate [PMMA] optical fibers to be used in monitoring the glucose content of blood. The improved method incorporates, but goes beyond, the method described in Texturing Blood-Glucose- Monitoring Optics Using Oxygen Beams (LEW-17642-1), NASA Tech Briefs, Vol. 29, No. 4 (April 2005), page 11a. The basic principle of operation of such a glucose-monitoring sensor is as follows: The textured surface of the optical fiber is coated with chemicals that interact with glucose in such a manner as to change the reflectance of the surface. Light is sent down the optical fiber and is reflected from, the textured surface. The resulting change in reflectance of the light is measured as an indication of the concentration of glucose. The required texture on the ends of the optical fibers is a landscape of microscopic cones or pillars having high aspect ratios (microscopic structures being taller than they are wide). The average distance between hills must be no more than about 5 mso that blood cells (which are wider) cannot enter the valleys between the hills, where they would interfere with optical sensing of glucose in the blood plasma. On the other hand, the plasma is required to enter the valleys, and high aspect ratio structures are needed to maximize the surface area in contact with the plasma, thereby making it possible to obtain a given level of optical glucose-measurement sensitivity with a relatively small volume of blood. There is an additional requirement that the hills be wide enough that a sufficient amount of light can propagate into them and, after reflection, can propagate out of them. The method described in the cited prior article produces a texture comprising cones and pillars that conform to the average-distance and aspect-ratio requirements. However, a significant fraction of the cones and pillars are so narrow that not enough light can propagate along them. The improved method makes it possible to form wider cones and pillars while still satisfying the average-distance and aspect-ratio requirements. In the improved method, as in the previously reported method, multiple optical fibers are first bundled together for simultaneous texturing of their distal tips. However, prior to texturing by exposure to an oxygen beam, the tips are first coated by vapor deposition of a thin, sparse layer of aluminum: The exposure to the aluminum vapor must be short enough (typically of the order of seconds) so that the aluminum nucleates into islands separated by uncoated areas. The coated tips are textured by exposure to a directed beam of hyperthermal (kinetic energy >1 eV) oxygen atoms and/or ions in a vacuum chamber, as in the previously reported method. The aluminum islands partially shield the underlying PMMA from oxidation and erosion by the beam, so that the cones or pillars remaining after texturing are wider than they would otherwise be. To some extent, the dimensions of the hills and the distances between them can be tailored through choice of the thickness of the aluminum coat and/or the oxygen-beam fluence. The figure illustrates an example of texturing of the tip of a PMMA optical fiber without and with prior aluminum coating.

Banks, Bruce A.↗

NASA NTRS1993

Non-invasive optical detection of glucose in cell culture nutrient medium

The objective of the proposed research was to begin the development of a non-invasive optical sensor for measuring glucose concentration in the output medium of cell cultures grown in a unique NASA bioreactor referred to as an integrated rotating-wall vessel (IRWV). The input, a bovine serum based nutrient media, has a known glucose concentration. The cells within the bioreactor digest a portion of the glucose. Thus, the non-invasive optical sensor is needed to monitor the decrease in glucose due to cellular consumption since the critical parameters for sustained cellular productivity are glucose and pH. Previous glucose sensing techniques have used chemical reactions to quantify the glucose concentration. Chemical reactions, however, cannot provide for continuous, real time, non-invasive measurement as is required in this application. Our effort while in the fellowship program was focused on the design, optical setup, and testing of one bench top prototype non-invasive optical sensor using a mid-infrared absorption spectroscopy technique. Glucose has a fundamental vibrational absorption peak in the mid-infrared wavelength range at 9.6 micron. Preliminary absorption data using a CO2 laser were collected at this wavelength for water based glucose solutions at different concentrations and one bovine serum based nutrient medium (GTSF) with added glucose. The results showed near linear absorption responses for the glucose-in-water data with resolutions as high at 108 mg/dl and as low as 10 mg/dl. The nutrient medium had a resolution of 291 mg/dl. The variability of the results was due mainly to thermal and polarization drifts of the laser while the decrease in sensitivity to glucose in the nutrient medium was expected due to the increase in the number of confounders present in the nutrient medium. A multispectral approach needs to be used to compensate for these confounders. The CO2 laser used for these studies was wavelength tunable (9.2 to 10.8 micrometers), however, it was to unstable across wavelengths to test the multispectral approach. From this research, further NASA support was obtained to continue the work throughout the year in which a more stable light source will be used at smaller, near-infrared, wavelengths. It is anticipated that a more compact, non-invasive, optical glucose sensor will be realized which can be used with a bioreactor on future space shuttle missions. It is also anticipated that a multispectral optical sensor may be used to determine the concentration of other molecules needed within the NASA bioreactor, such as fructose and galactose.

Cote, Gerald L.↗

NASA NTRS2001

ISS Biotechnology Facility - Overview of Analytical Tools for Cellular Biotechnology Investigations

The ISS Biotechnology Facility (BTF) platform provides scientists with a unique opportunity to carry out diverse experiments in a microgravity environment for an extended period of time. Although considerable progress has been made in preserving cells on the ISS for long periods of time for later return to Earth, future biotechnology experiments would desirably monitor, process, and analyze cells in a timely way on-orbit. One aspect of our work has been directed towards developing biochemical sensors for pH, glucose, oxygen, and carbon dioxide for perfused bioreactor system developed at Johnson Space Center. Another aspect is the examination and identification of new and advanced commercial biotechnologies that may have applications to on-orbit experiments.

Jeevarajan, A. S.↗

NASA NTRS2001

Electron tunneling infrared sensor module with integrated control circuitry

In an integrated electron tunneling sensor, an automatic tunneling control circuit varies a high voltage bias applied to the sensor deflection electrode in response to changes in sensor output to maintain the proper gap between the sensor tip and membrane. The control circuit ensures stable tunneling activity in the presence of large signals and other disturbances to the sensor. Output signals from the module may be derived from the amplified sensor output. The integrated sensor module is particularly well adapted for use in blood glucose measurement and monitoring system.

Boyadzhyan-Sevak, Vardkes V.↗

NASA NTRS2015

Nanopore Device for Reversible Ion and Molecule Sensing or Migration

Disclosed are methods and devices for detection of ion migration and binding, utilizing a nanopipette adapted for use in an electrochemical sensing circuit. The nanopipette may be functionalized on its interior bore with metal chelators for binding and sensing metal ions or other specific binding molecules such as boronic acid for binding and sensing glucose. Such a functionalized nanopipette is comprised in an electrical sensor that detects when the nanopipette selectively and reversibly binds ions or small molecules. Also disclosed is a nanoreactor, comprising a nanopipette, for controlling precipitation in aqueous solutions by voltage-directed ion migration, wherein ions may be directed out of the interior bore by a repulsing charge in the bore.

Pourmand, Nader↗

NASA NTRS2006

Replaceable Sensor System for Bioreactor Monitoring

A sensor system was proposed that would monitor spaceflight bioreactor parameters. Not only will this technology be invaluable in the space program for which it was developed, it will find applications in medical science and industrial laboratories as well. Using frequency-domain-based fluorescence lifetime technology, the sensor system will be able to detect changes in fluorescence lifetime quenching that results from displacement of fluorophorelabeled receptors bound to target ligands. This device will be used to monitor and regulate bioreactor parameters including glucose, pH, oxygen pressure (pO2), and carbon dioxide pressure (pCO2). Moreover, these biosensor fluorophore receptor-quenching complexes can be designed to further detect and monitor for potential biohazards, bioproducts, or bioimpurities. Biosensors used to detect biological fluid constituents have already been developed that employ a number of strategies, including invasive microelectrodes (e.g., dark electrodes), optical techniques including fluorescence, and membrane permeable systems based on osmotic pressure. Yet the longevity of any of these sensors does not meet the demands of extended use in spacecraft habitat or bioreactor monitoring. It was therefore necessary to develop a sensor platform that could determine not only fluid variables such as glucose concentration, pO2, pCO2, and pH but can also regulate these fluid variables with controlled feedback loop.

Mayo, Mike↗

NASA NTRS2004

Microminiature Monitor for Vital Electrolyte and Metabolite Levels of Astronauts

Ions, such as proton (pH) and potassium, play a crucial role in body fluids to maintain proper basic functioning of cells and tissues. Metabolites, such as glucose, control the energy available to the entire human body in normal as well as stress situations, and before, during, and after meals. These molecules diffuse easily between blood in the capillaries and the interstitial fluid residing between cells and tissues. We have developed and approach to monitoring of critical ions (called electrolytes) and glucose in the interstitial fluid under the human skin. Proton and potassium levels sensed using optode technology that translates the respective ionic concentrations into variable colors of corresponding ionophore/dye/polymeric liquid membranes. Glucose is monitored indirectly, by coupling through immobilized glucose oxidase with local pH that is then detected using a similar color scheme. The monitor consists of a tiny plastic bar, 100-200 microns wide and 1-2 mm long, placed just under the skin, with color changing spots for each analyte as well as blanks. The colors are read and translated into concentration values by a CCD camera. Direct optical coupling between the in vivo sensing bar and the ex vivo detector device requires no power, and thus eliminates the need for wires or optical fibers crossing the skin. The microminiature bar penetrates the skin easily and painlessly, so that astronauts could insert it themselves. The approach is fully compatible with telemetry in space, and thus, in vivo clinical data will be available real time in the Earth based command center once the device is fully developed. The information provided can be used for collecting hitherto unavailable vital data on clinical effects of space travel. Managing clinical emergencies in space with the sensor already in place should also become much more efficient than without a continuous monitor, as is currently the case. Civilian applications may include better glucose control of patients with moderate to severe diabetes: a growing health problem in the US and World-wide.

Tohda, Koji↗

NASA NTRS1988

Dynamic cell culture system: a new cell cultivation instrument for biological experiments in space

The prototype of a miniaturized cell cultivation instrument for animal cell culture experiments aboard Spacelab is presented (Dynamic cell culture system: DCCS). The cell chamber is completely filled and has a working volume of 200 microliters. Medium exchange is achieved with a self-powered osmotic pump (flowrate 1 microliter h-1). The reservoir volume of culture medium is 230 microliters. The system is neither mechanically stirred nor equipped with sensors. Hamster kidney (Hak) cells growing on Cytodex 3 microcarriers were used to test the biological performance of the DCCS. Growth characteristics in the DCCS, as judged by maximal cell density, glucose consumption, lactic acid secretion and pH, were similar to those in cell culture tubes.

NASA Program Flight↗

NASA NTRS2000

Monitoring Astronaut Health at the Nanoscale Cellular Level Through the Eye

A user friendly goggles-like head-mounted device equipped with a suite of instruments for several non-invasive and quantitative medical evaluation of the eye, skin, and brain is desired for monitoring the health of astronauts during space travel and exploration of neighboring and distant planets. Real-time non-invasive evaluation of the different structures within the above organs can provide indices of the health of not just these organs, but the entire body. The techniques such as dynamic light scattering (for the early detection of uveitis, cholesterol levels, cataract, changes in the vitreous and possibly Alzheimer's disease), corneal autofluorescence (to assess extracellular matrix biology e.g., in diabetes), optical activity measurements (of anterior ocular fluid to evaluate blood-glucose levels), laser Doppler velocimetry (to assess retinal, optic nerve, and choroidal blood flow), reflectometry/oximetry (for assessing ocular and central nervous system oxygen metabolism), optical coherence tomography (to determine retinal tissue microstructure) and possibly scanning laser technology (for intraocular tissue imaging and scanning) will he integrated into this compact device. Skin sensors will also be mounted on the portion of the device in contact with the periocular region. This will enable monitoring of body temperature, EEG, and electrolyte status. This device will monitor astronaut health during long-duration space travel by detecting aberrations from pre-established "nonns", enabling prompt diagnosis and possibly the initiation of early preventative/curative therapy. The non-invasive nature of the device technologies permits frequent repetition of tests, enabling real-time complete crew health monitoring. This device may ultimately be useful in tele-medicine to bring modern healthcare to under-served areas on Earth as well as in so-called "advanced" care settings (e.g. diabetes in the USA).

Ansari, Rafat R.↗

NASA NTRS2004

Multisensor Instrument for Real-Time Biological Monitoring

The figure schematically depicts an instrumentation system, called a fiber optic-based integration system (FOBIS), that is undergoing development to enable real-time monitoring of fluid cell cultures, bioprocess flows, and the like. The FOBIS design combines a micro flow cytometer (MFC), a microphotometer (MP), and a fluorescence-spectrum- or binding-force-measuring micro-sensor (MS) in a single instrument that is capable of measuring multiple biological parameters simultaneously or sequentially. The fiber-optic-based integration system is so named because the MFC, the MP, and the MS are integrated into a single optical system that is coupled to light sources and photometric equipment via optical fibers. The optical coupling components also include a wavelength-division multiplexer and diffractive optical elements. The FOBIS includes a laserdiode- and fiber-optic-based optical trapping subsystem (optical tweezers ) with microphotometric and micro-sensing capabilities for noninvasive confinement and optical measurement of relevant parameters of a single cell or other particle. Some of the measurement techniques implemented together by the FOBIS have long been used separately to obtain basic understanding of the optical properties of individual cells and other organisms, the optical properties of populations of organisms, and the interrelationships among these properties, physiology of the organisms, and physical processes that govern the media that surround the organisms. For example, flow cytometry yields information on numerical concentrations, cross-sectional areas, and types of cells or other particles. Micro-sensing can be used to measure pH and concentrations of oxygen, carbon dioxide, glucose, metabolites, calcium, and antigens in a cell-culture fluid, thereby providing feedback that can be helpful in improving control over a bioprocess. Microphotometry (including measurements of scattering and fluorescence) can yield further information about optically trapped individual particles. In addition to the multifunctionality not previously available in a single biological monitoring system, the FOBIS offers advantages of low mass, sensitivity, accuracy, portability, low cost, compactness (the overall dimensions of the fully developed FOBIS sensor head are expected to be less than 1 by 1 by 2 cm), and immunity to electromagnetic interference at suboptical frequencies. FOBIS could be useful in a variety of laboratory and field settings in such diverse endeavors as medical, veterinary, and general biological research; medical and veterinary diagnosis monitoring of industrial bioprocesses; and analysis of biological contaminants in air, water, and food.

Zhang, Sean (Zhanxiang)↗

NASA NTRS2010

Electrochemical Detection of Multiple Bioprocess Analytes

An apparatus that includes highly miniaturized thin-film electrochemical sensor array has been demonstrated as a prototype of instruments for simultaneous detection of multiple substances of interest (analytes) and measurement of acidity or alkalinity in bioprocess streams. Measurements of pH and of concentrations of nutrients and wastes in cell-culture media, made by use of these instruments, are to be used as feedback for optimizing the growth of cells or the production of desired substances by the cultured cells. The apparatus is designed to utilize samples of minimal volume so as to minimize any perturbation of monitored processes. The apparatus can function in a potentiometric mode (for measuring pH), an amperometric mode (detecting analytes via oxidation/reduction reactions), or both. The sensor array is planar and includes multiple thin-film microelectrodes covered with hydrous iridium oxide. The oxide layer on each electrode serves as both a protective and electrochemical transducing layer. In its transducing role, the oxide provides electrical conductivity for amperometric measurement or pH response for potentiometric measurement. The oxide on an electrode can also serve as a matrix for one or more enzymes that render the electrode sensitive to a specific analyte. In addition to transducing electrodes, the array includes electrodes for potential control. The array can be fabricated by techniques familiar to the microelectronics industry. The sensor array is housed in a thin-film liquid-flow cell that has a total volume of about 100 mL. The flow cell is connected to a computer-controlled subsystem that periodically draws samples from the bioprocess stream to be monitored. Before entering the cell, each 100-mL sample is subjected to tangential-flow filtration to remove particles. In the present version of the apparatus, the electrodes are operated under control by a potentiostat and are used to simultaneously measure the pH and the concentration of glucose. It is anticipated that development of procedures for trapping more enzymes into hydrous iridium oxide (and possibly into other electroactive metal oxides) and of means for imparting long-term stability to the transducer layers should make it possible to monitor concentrations of products of many enzyme reactions for example, such key bioprocess analytes as amino acids, vitamins, lactose, and acetate.

Rauh, R. David↗

NASA NTRS2006

NASA Tech Briefs, October 2006

Topics covered include: Protein Sensors Based on Optical Ring Resonators; Phase Sensor for Aligning a Segmented Telescope Mirror; Control Software for Advanced Video Guidance Sensor; Generating Control Commands From Gestures Sensed by EMG; Multiple-Flat-Panel System Displays Multidimensional Data; 3D X-Ray Luggage-Screening System; Probe Station and Near-Field Scanner for Testing Antennas; Photodetector Arrays for Multicolor Visible/Infrared Imaging; Semiconductor Bolometers Give Background-Limited Performance; Multichannel X-Band Dielectric-Resonator Oscillator; Automatic Alignment of Displacement-Measuring Interferometer; Earth Observing System Data Gateway; Power User Interface; Mercury Shopping Cart Interface; Cassini Archive Tracking System; Architecture Adaptive Computing Environment; Computing Fault Displacements from Surface Deformations; Oxygen-Permeable, Hydrophobic Membranes of Silanized alpha-Al2O3; SiC Composite Turbine Vanes; Retaining Device for the Interior Structure of a Spacecraft Payload; Tool for Torquing Circular Electrical-Connector Collars; System for Continuous Deaeration of Hydraulic Oil; Solar-Powered Cooler and Heater for an Automobile Interior; Improved Oxygen-Beam Texturing of Glucose-Monitoring Optics; Tool for Two Types of Friction Stir Welding; Stationary Apparatus Would Apply Forces of Walking to Feet; Instrument Would Detect and Collect Biological Aerosols; Boundary Condition for Modeling Semiconductor Nanostructures; Miniature Distillation Column for Producing LOX From Air; Even Illumination from Fiber-Optic-Coupled Laser Diodes; Optically Driven Deformable Mirrors; Algorithm for Automated Detection of Edges of Clouds; Exploiting Quantum Resonance to Solve Combinatorial Problems; Hybrid Terrain Database; On Release of Microbe-Laden Particles from Mars Landers; A Concept for Run-Time Support of the Chapel Language; Thermoelectric Inhomogeneities in (Ag(sub 1-y)SbTe2)(sub x)(PbTe)(sub 1-x); and Spacecraft Escape Capsule.

Source record↗

NASA NTRS2003

Advanced sensor systems for biotelemetry

The present invention relates to telemetry-based sensing systems that continuously measures physical, chemical and biological parameters. More specifically, these sensing systems comprise a small, modular, low-power implantable biotelemetry system capable of continuously sensing physiological characteristics using implantable transmitters, a receiver, and a data acquisition system to analyze and record the transmitted signal over several months. The preferred embodiment is a preterm labor and fetal monitoring system. Key features of the invention include Pulse Interval Modulation (PIM) that is used to send temperature and pressure information out of the biological environment. The RF carrier frequency is 174-216 MHz and a pair of RF bursts (pulses) is transmitted at a frequency of about 1-2 Hz. The transmission range is 3 to 10 feet, depending on the position of the transmitter in the body and its biological environment. The entire transmitter is encapsulated in biocompatible silicone rubber. Power is supplied by on-board silver-oxide batteries. The average power consumption of the current design is less than 30 .mu.W., which yields a lifetime of approximately 6-9 months. Chip-on-Board technology (COB) drastically reduces the size of the printed circuit board from 38.times.28 mm to 22.times.8 mm. Unpackaged dies are flip-chip bonded directly onto the printed circuit board, along with surface mount resistors and capacitors. The invention can monitor additional physiological parameters including, but not limited to, ECG, blood gases, glucose, and ions such as calcium, potassium, and sodium.

Hines, John W.↗

NASA NTRS2003

Advanced Sensor Systems for Biotelemetry

The present invention relates to telemetry-based sensing systems that continuously measures physical, chemical and biological parameters. More specifically, these sensing systems comprise a small, modular, low-power implantable biotelemetry system capable of continuously sensing physiological characteristics using implantable transmitters, a receiver, and a data acquisition system to analyze and record the transmitted signal over several months. The preferred embodiment is a preterm labor and fetal monitoring system. Key features of the invention include Pulse Interval Modulation (PIM) that is used to send temperature and pressure information out of the biological environment. The RF carrier frequency is 174-216 MHz and a pair of RF bursts (pulses) is transmitted at a frequency of about 1-2 Hz. The transmission range is 3 to 10 feet, depending on the position of the transmitter in the body and its biological environment. The entire transmitter is encapsulated in biocompatible silicone rubber. Power is supplied by on-board silver-oxide batteries. The average power consumption of the current design is less than 30 microW, which yields a lifetime of approximately 6 - 9 months. Chip-on-Board technology (COB) drastically reduces the size of the printed circuit board from 38 x 28 mm to 22 x 8 mm. Unpackaged dies are flip-chip bonded directly onto the printed circuit board, along with surface mount resistors and capacitors. The invention can monitor additional physiological parameters including, but not limited to, ECG, blood gases, glucose, and ions such as calcium, potassium, and sodium.

Hines, John W.↗