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At least 91 records · Page 5

Space Biosensor Systems: Implications for Technology Transfer

To meet the need for continuous, automated monitoring of animal subjects, including; humans, during space flight, NASA is developing advanced physiologic sensor and biotelemetry system technologies. The ability to continuously track basic physiological parameters, such as heart rate, blood pH, and body temperature, in untethered subjects in space is a challenging task. At NASA's Ames Research Center, where a key focus is gravitational biology research, engineers have teamed with life scientists to develop wireless sensor systems for automated physiologic monitoring of animal models as small as the rat. This technology is also being adapted, in collaboration with medical professionals, to meet human clinical monitoring needs both in space and on the ground. Thus, these advanced monitoring technologies have important dual-use functions; they meet space flight data collection requirements and constraints, while concurrently addressing a number of monitoring and data acquisition challenges on the ground in areas of clinical monitoring and biomedical research. Additional applications for these and related technologies are being sought and additional partnerships established that enhance development efforts, reduce costs and facilitate technology infusion between the public and private sectors. This paper describes technology transfer and co-development projects that have evolved out of NASA's miniaturized, implantable chemical sensor development efforts.

Hines, J. W.

Plasma Enhanced Growth of Carbon Nanotubes For Ultrasensitive Biosensors

The multitude of considerations facing nanostructure growth and integration lends itself to combinatorial optimization approaches. Rapid optimization becomes even more important with wafer-scale growth and integration processes. Here we discuss methodology for developing plasma enhanced CVD growth techniques for achieving individual, vertically aligned carbon nanostructures that show excellent properties as ultrasensitive electrodes for nucleic acid detection. We utilize high throughput strategies for optimizing the upstream and downstream processing and integration of carbon nanotube electrodes as functional elements in various device types. An overview of ultrasensitive carbon nanotube based sensor arrays for electrochemical bio-sensing applications and the high throughput methodology utilized to combine novel electrode technology with conventional MEMS processing will be presented.

Cassell, Alan M.

Plasma Enhanced Growth of Carbon Nanotubes For Ultrasensitive Biosensors

The multitude of considerations facing nanostructure growth and integration lends itself to combinatorial optimization approaches. Rapid optimization becomes even more important with wafer-scale growth and integration processes. Here we discuss methodology for developing plasma enhanced CVD growth techniques for achieving individual, vertically aligned carbon nanostructures that show excellent properties as ultrasensitive electrodes for nucleic acid detection. We utilize high throughput strategies for optimizing the upstream and downstream processing and integration of carbon nanotube electrodes as functional elements in various device types. An overview of ultrasensitive carbon nanotube based sensor arrays for electrochemical biosensing applications and the high throughput methodology utilized to combine novel electrode technology with conventional MEMS processing will be presented.

Cassell, Alan M.

Nine-analyte detection using an array-based biosensor

A fluorescence-based multianalyte immunosensor has been developed for simultaneous analysis of multiple samples. While the standard 6 x 6 format of the array sensor has been used to analyze six samples for six different analytes, this same format has the potential to allow a single sample to be tested for 36 different agents. The method described herein demonstrates proof of principle that the number of analytes detectable using a single array can be increased simply by using complementary mixtures of capture and tracer antibodies. Mixtures were optimized to allow detection of closely related analytes without significant cross-reactivity. Following this facile modification of patterning and assay procedures, the following nine targets could be detected in a single 3 x 3 array: Staphylococcal enterotoxin B, ricin, cholera toxin, Bacillus anthracis Sterne, Bacillus globigii, Francisella tularensis LVS, Yersiniapestis F1 antigen, MS2 coliphage, and Salmonella typhimurium. This work maximizes the efficiency and utility of the described array technology, increasing only reagent usage and cost; production and fabrication costs are not affected.

NASA Discipline Life Sciences Technologies

Modeling of the Near Field Coupling Between an External Loop and an Implantable Spiral Chip Antennas in Biosensor Systems

In this paper, the near field coupling between an external hand-held loop antenna and an implantable miniature (1x1 mm) printed square spiral chip antenna used in bio-MEMS sensors for contact-less powering and RF telemetry is investigated. The loop and the spiral are inductively coupled and effectively form a transformer. The numerical results include the quasi-stationary magnetic field pattern of the implanted antenna, near zone wave impedance as a function of the radial distance and the values of the lumped elements in the equivalent circuit model for the transformer.

Simons, Rainee N.

Biosensors for EVA: Muscle Oxygen and pH During Walking, Running and Simulated Reduced Gravity

During lunar excursions in the EVA suit, real-time measurement of metabolic rate is required to manage consumables and guide activities to ensure safe return to the base. Metabolic rate, or oxygen consumption (VO2), is normally measured from pulmonary parameters but cannot be determined with standard techniques in the oxygen-rich environment of a spacesuit. Our group developed novel near infrared spectroscopic (NIRS) methods to calculate muscle oxygen saturation (SmO2), hematocrit, and pH, and we recently demonstrated that we can use our NIRS sensor to measure VO2 on the leg during cycling. Our NSBRI-funded project is looking to extend this methodology to examine activities which more appropriately represent EVA activities, such as walking and running and to better understand factors that determine the metabolic cost of exercise in both normal and lunar gravity. Our 4 year project specifically addresses risk: ExMC 4.18: Lack of adequate biomedical monitoring capability for Constellation EVA Suits and EPSP risk: Risk of compromised EVA performance and crew health due to inadequate EVA suit systems.

Lee, S. M. C.

Fluorogenic Cell-Based Biosensors for Monitoring Microbes

Fluorogenic cell-based sensor systems for detecting microbes (especially pathogenic ones) and some toxins and allergens are undergoing development. These systems harness the natural signaltransduction and amplification cascades that occur in mast cells upon activation with antigens. These systems include (1) fluidic biochips for automated containment of samples, reagents, and wastes and (2) sensitive, compact fluorometers for monitoring the fluorescent responses of mast cells engineered to contain fluorescent dyes. It should be possible to observe responses within minutes of adding immune complexes. The systems have been shown to work when utilizing either immunoglobulin E (IgE) antibodies or traditionally generated rat antibodies - a promising result in that it indicates that the systems could be developed to detect many target microbes. Chimeric IgE antibodies and rat immunoglobulin G (IgG) antibodies could be genetically engineered for recognizing biological and chemical warfare agents and airborne and food-borne allergens. Genetic engineering efforts thus far have yielded (1) CD14 chimeric antibodies that recognize both Grampositive and Gram-negative bacteria and bind to the surfaces of mast cells, eliciting a degranulation response and (2) rat IgG2a antibodies that act similarly in response to low levels of canine parvovirus.

Curtis, Theresa

Biosensors for EVA: Improved Instrumentation for Ground-based Studies

During lunar excursions in the EVA suit, real-time measurement of metabolic rate is required to manage consumables and guide activities to ensure safe return to the base. Metabolic rate, or oxygen consumption (VO2), is normally measured from pulmonary parameters but cannot be determined with standard techniques in the oxygen-rich environment of a spacesuit. Our group has developed novel near infrared spectroscopic (NIRS) methods to calculate muscle oxygen saturation (SmO 2), hematocrit, and pH, and we recently demonstrated that we can use our NIRS sensor to measure VO 2 on the leg during cycling. Our NSBRI project has 4 objectives: (1) increase the accuracy of the metabolic rate calculation through improved prediction of stroke volume; (2) investigate the relative contributions of calf and thigh oxygen consumption to metabolic rate calculation for walking and running; (3) demonstrate that the NIRS-based noninvasive metabolic rate methodology is sensitive enough to detect decrement in VO 2 in a space analog; and (4) improve instrumentation to allow testing within a spacesuit. Over the past year we have made progress on all four objectives, but the most significant progress was made in improving the instrumentation. The NIRS system currently in use at JSC is based on fiber optics technology. Optical fiber bundles are used to deliver light from a light source in the monitor to the patient, and light reflected back from the patient s muscle to the monitor for spectroscopic analysis. The fiber optic cables are large and fragile, and there is no way to get them in and out of the test spacesuit used for ground-based studies. With complimentary funding from the US Army, we undertook a complete redesign of the sensor and control electronics to build a novel system small enough to be used within the spacesuit and portable enough to be used by a combat medic. In the new system the filament lamp used in the fiber optic system was replaced with a novel broadband near infrared LED light source. The compact grating spectrometer was replaced with a chip-scale spectrometer. With this new design, the sensor is 4 in 2 in 0.5 in, weighs 60 g, and no fiber optic cables are needed. The sensor, which contains the light source and the spectrometer, is adhered directly to the skin with medical grade adhesive. The sensor can be powered via the USB port of the laptop computer that controls the sensor operation. Alternatively, for studies in the spacesuit, the sensor can be powered by a small battery pack and operated by an ultra-portable hand-held computer. Both the handheld computer and battery pack will easily fit within the PLSS of the test spacesuit. System automation was significantly improved, to add features suggested by our colleagues in the Cardiovascular Laboratory and the NASA JSC Exercise Physiology and Countermeasures Project. The functionality and portability of this system were demonstrated in our UMass laboratory.

Soller, B.

Enzyme-Cascade Analysis of the Rio Tinto Subsurface Environment: A Biosensor Experiment

The Portable Test System (PTS), designed & developed by Charles Rivers Laboratories, Inc. (Charleston, SC) is a portable instrument that was designed to perform analysis of enzymatic assays related to rapid assessment of microbial contamination (Wainwright, 2003). The enzymatic cascade of Limulus Amebocyte Lysate (LAL) is known to be one of the most sensitive techniques available for microbial detection, enabling the PTS to be evaluated as a potential life detection instrument for in situ Astrobiology missions. In the summer of 2003 the system was tested as a part of the Mars Astrobiology Research and Technology Experiment (MARTE) ground truth science campaign in the Rio Tinto Analogue environment near Nerva, Spain. The preliminary results show that the PTS analysis correlates well with the contamination control tests and the more traditional lab-based biological assays performed during the MARTE field mission. Further work will be conducted on this research during a second field campaign in 2004 and a technology demonstration of a prototype instrument that includes autonomous sample preparation will occur in 2005.

McKay, David S.

The Lunar Explorer Instrument for Space Biology Applications (LEIA) Pre-Flight Tests: Mechanical Considerations​

The BioSensor payload on the upcoming LEIA platform aboard the CLPS (CP-22) lander will carry yeast to the Moon's south pole to study the effects of lunar radiation and gravity. From Earth, BioSensor will transport desiccated yeast within 16 fluidic cards, each containing 16 fluidic wells of 100 microliters volume. At the start of the experiment, these microbes will be autonomously rehydrated on the Moon, and optical absorbance measurements at three wavelengths will be performed across all 256 wells. Absorbance measurements in fluidic wells are susceptible to noise and artifacts due to bubble formation during well rehydration and microbial growth. BioSensor, as a biofluidics system, faces significant data anomalies caused by payload vibrations, particularly from the operation of the co-located PROSPECT’s ProSEED drill, to assess lunar resources by penetrating the subsurface. To evaluate the impact of drill vibrations, fully assembled and filled fluidic cards were subjected to sine sweep signals in the x, y, z planes, ranging from 5 - 2560 Hz at g-loads of 0.25 and 0.5, with on-board accelerometer for localized vibration measurement. Wells with various fill conditions, including partial fills with different bubble sizes and completely filled wells, were tested. Results indicated that small bubbles adhered to well walls at high frequencies but were dislodged at low frequencies, causing data anomalies. Medium and large bubbles exhibited higher interference with optical data due to lower surface tension and variable bubble surface flexion. Overall, it was found that irrespective of the fill type, low-frequency vibrations were most detrimental to optical readings. Understanding the drill schedule and correlating it with BioSensor timestamps will help identify periods when BioSensor data is unreliable, a crucial step for accurately interpreting the microbial response data and ensuring the validity of the BioSensor's scientific measurements on the lunar surface.

Chinmayee Govinda Raj

Microbial spies and bloggers: programming cells to convert environmental information into discernible signals

Microbes regulate their dynamic behaviors using the chemical and physical characteristics of their environment. The ability of microbes to continuously convert this physicochemical information into biochemical information and to use organic matter in the environment as a power source makes these organisms attractive as chassis for building sensors. However, most biosensors have severe limitations when considering applications in hard-to-image settings like soils, sediments, and wastewater. Emerging technologies at the interface of biomolecular design, microbiome engineering, and synthetic biology offer new tools to program cells and communities as biosensors for these settings. Here, in this review, we describe innovations in biosensor outputs that are enabling new applications in complex environments, including reporters that are read out using electrochemical, gas chromatography, hyperspectral imaging, and next-generation sequencing methods. We also discuss computational advances that are accelerating the diversification of sensing components by mining metagenomics data for new transcriptional regulators and by designing allosteric protein switches that directly regulate reporter outputs using analytes. We highlight emerging opportunities for programming undomesticated microbes in communities to function as distributed sensors in the environment. Finally, we discuss the need for responsible biosensor development and to modernize regulatory frameworks to support evidence-based assessment of environmental biosensors.

analyte

Highly multiplexed design of an allosteric transcription factor to sense new ligands

Allosteric transcription factors (aTF) regulate gene expression through conformational changes induced by small molecule binding. Although widely used as biosensors, aTFs have proven challenging to design for detecting new molecules because mutation of ligand-binding residues often disrupts allostery. Here, we develop Sensor-seq, a high-throughput platform to design and identify aTF biosensors that bind to non-native ligands. We screen a library of 17,737 variants of the aTF TtgR, a regulator of a multidrug exporter, against six non-native ligands of diverse chemical structures – four derivatives of the cancer therapeutic tamoxifen, the antimalarial drug quinine, and the opiate analog naltrexone – as well as two native flavonoid ligands, naringenin and phloretin. Sensor-seq identifies biosensors for each of these ligands with high dynamic range and diverse specificity profiles. The structure of a naltrexone-bound design shows shape-complementary methionine-aromatic interactions driving ligand specificity. To demonstrate practical utility, we develop cell-free detection systems for naltrexone and quinine. Sensor-seq enables rapid and scalable design of new biosensors, overcoming constraints of natural biosensors.

59 BASIC BIOLOGICAL SCIENCES