Microfluidics Pressure-Based Switching and Valving Array

This invention provides a method and system for fabricating a biomarker sensor array by dispensing one or more entities using a precisely positioned, electrically biased nanoprobe immersed in a buffered fluid over a transparent substrate. Fine patterning of the substrate can be achieved by positioning and selectively biasing the probe in a particular region, changing the pH in a sharp, localized volume of fluid less than 100 nm in diameter, resulting in a selective processing of that region. One example of the implementation of this technique is related to Dip-Pen Nanolithography (DPN), where an Atomic Force Microscope probe can be used as a pen to write protein and DNA Aptamer inks on a transparent substrate functionalized with silane-based self-assembled monolayers. But it would be recognized that the invention has a much broader range of applicability. For example, the invention can be applied to formation of patterns using biological materials, chemical materials, metals, polymers, semiconductors, small molecules, organic and inorganic thins films, or any combination of these.

The NASA developed Micro-Organ Device (MOD) platform technology is a small, lightweight, and reproducible in vitro drug screening model that can inexpensively biomimic different mammalian tissues for a multitude of applications. The technology is automated and imposes minimal demands for resources (power, analytes, and fluids). The MOD technology uses titanium tetra(isopropoxide) to bond a microscale support to a substrate and uses biopattering and 3D tissue bioprinting on a microfluidic microchip to eliminate variations in local seeding density while minimizing selection pressure. With the MOD, pharmaceutical companies can test more candidates and concentrate on those with more promise therefore, reducing R&D overall cost. This innovation overcomes major disadvantages of conventional in vitro and in vivo experimentation for purposes of investigating effects of medicines, toxins, and possibly other foreign substances. For example, the MOD platform technology could host life-like miniature assemblies of human cells and the effects observed in tests performed could potentially be extrapolated more readily to humans than could effects observed in conventional in vitro cell cultures, making it possible to reduce or eliminate experimentation on animals. The automated NASA developed technology with minimal footprint and power requirements, micro-volumes of fluids and waste, high throughput and parallel analyses on the same chip, will advance the research and development for new drugs and materials.

JSC's technology provides hazard-free, microgravity-compatible hardware for DNA/RNA isolation. It also allows PCR analysis to be used outside the lab in environments where pipetting is difficult and/or where hazardous chemicals must be confined to an enclosed container, such as military settings and remote clinical operations. This self-contained device for isolating DNA/RNA, proteins, and cells is a component system that includes syringes and pistons, membranes of different capacities, reagents, four-way valves, and small pumps. The pre-filled reagents are the same as those used in conventional PCR laboratory isolation analysis. The DNA and RNA isolation kits are novel and process small sample amounts using a self-enclosed and pipette-free technique. Multiple kits can be stacked to allow several samples to be processed simultaneously. The system can be used in conjunction with existing analysis modules, such as commercially available DNA instruments. The process can be fully automated and programmed and can potentially be applied to other biological processes. The JSC innovation will permit the extension of laboratory isolation protocols to many applications. This NASA Technology is available for your company to license and develop into a commercial product. NASA does not manufacture products for commercial sale.

Many diseases are accompanied by characteristic odors. Their recognition can provide diagnostic clues, guide the laboratory evaluation, and affect the choice of immediate therapy. The study of the chemical composition of human breath using gas chromatography mass spectrometry (GC/MS) has shown a correlation between the volatile compounds and the occurrence of certain illnesses. The presence of those specific compounds can provide an indication of physiological malfunction and support the diagnosis of diseases. This condition requires an analytical tool with very high sensitivity for its measurement. A number of volatile compounds, so called biomarkers, are found in breath samples, normally at low parts per billion (ppb) levels. For example, the acetone in the exhaled breath from human with other biomarkers can indicate Type I diabetes. Usually, the concentration of the volatile compounds in human breath is very low and the background relative humidity is high, almost 100%. NASAs invention utilizes an array of chemical sensors combined with humidity, temperature, and pressure for real-time breath measurement to correlate the chemical information in the breath with the state and functioning of different human organs. This tool provides a non-invasive method for fast and accurate diagnosis at the medical point of care or at home. The sensor chip includes multisensors for a comprehensive measurement of chemical composition, temperature, humidity, and pressure/flow rate. The sensor data collected from this chip can be wired or wirelessly transmitted to a computer terminal at the doctors desk or hospital monitoring center. The sensor chip can be connected directly or via Universal serial bus (USB) to a cell phone for data transmission over a long distance and receive an instruction from a doctors office for an immediate therapy.

The technology provides miniaturized techniques for extracting trace amounts of organic molecules (lipids) from natural samples. It operates as an autonomous, miniaturized fluidic system, integrating lab techniques for lipid analysis while minimizing reagent volumes and concentrating organics for analysis, thereby increasing signal-to-noise ratios by orders of magnitude. The non-aqueous fluidic system described herein for astrobiological and life-detection missions (either in situ or returned sample) is configured to extract lipid organics from regolith using (1) a fluidic sample processor made of materials compatible with organic solvents and (2) a machine-learning system to select processing steps and parameters to maximize lipid yield. A critical gap is bridged by integrating technologies into a system that replicates analytical lab procedures autonomously on a spaceflight instrument scale with fidelity to original lab techniques. Automated fluidic devices combine controlled handling of liquids with sequential operations and parallelization of replicate processes. By designing such systems to closely interface with both sample-delivery and analytical measurement systems, laboratory analyses are automated. The technology adapts best practice laboratory methods for lipid analysis, overcoming analytical challenges like low organic abundance, interference of minerals/salts, and degradation of origin-diagnostic molecular structures. The extraction and concentration techniques from rock/soil samples can be applied to any biomarkers by changing the solvent, temperature, and agitation.