Health, Medicine, and Biotechnology

PATENT PORTFOLIO
Health, Medicine, and Biotechnology
Health, Medicine, and Biotechnology
The development and manufacture of a technique or product to provide for the maintenance of a healthy level of physical, mental, and psychological fitness, the use of organic substances that are only existing in or derived from plants, animals or other living tissue, organisms or microorganisms to biologically engineer a compound or substance to improve lives, and the use of inorganic substances to perform chemical processing or to produce other materials that improve lives, industrial processes, and the environment.
Multiwalled CNT
Biochemical Sensors Using Carbon Nanotube Arrays
Vertically aligned carbon nanofibers (CNFs) are fabricated by wafer-scale plasma enhanced chemical vapor deposition (PECVD) on prefabricated microelectrode pads and encapsulated in SiO2 or polymer dielectrics with only the very end exposed at the surface to form an inlaid nanodisk electrode array. As the size of an electrode is reduced, one can obtain: (1) higher sensitivity, i.e., the signal-to-noise ratio, which is inversely proportional to the radius (r) of the electrode, (2) lower detection limit, (3) higher temporal resolution (proportional to 1/r), and (4) miniaturization. Therefore, nanoelectrodes have great properties for electroanalysis. Carbon nanofibers can be fabricated at wafer scale, as high-aspect-ratio metallic wires, down to a few nanometers in diameter on metal microcontact pads to form well-defined nanoelectrode arrays. In addition, CNFs have a wide potential window, well-defined surface functional groups, and good biocompatibility,which are all highly demanded properties for biosensors. CNF arrays have been successfully fabricated on micropatterns. The electrical and electrochemical properties of the embedded CNF nanoelectrode arrays have been thoroughly characterized to show well-defined nanoelectrode behavior. In some schemes, selective covalent functionalization of probe oligonucleotides, antibodies or aptamers have been achieved through the formation of amide bonds at the exposed end of CNFs. Direct electrochemical detection of a target molecules oxidation signal, which is the signal from an electrochemical label, or change in charge transfer resistance, has been demonstrated for DNA, rRNA, proteins, catecholamines, and ions.
Space Station graphic
In-Situ Resource Utilization (ISRU): Methylotrophic Microorganisms Expressing Soluble Methane Monooxygenase Proteins
Microorganisms are unique from the standpoint that they can be employed as self-replicating bio-factories to produce both native and engineered mission relevant bio-products. Methane (CH<sub>4</sub>) usage in In-Space Manufacturing (ISM) platforms has been discussed previously for human exploration and has been proposed to be used in physicochemical systems as a propulsion fuel, supply gas, and in fuel cells. Carbon Dioxide (CO<sub>2</sub>) is abundant on Mars and manned spacecraft. On the International Space Station (ISS), NASA reacts excess CO<sub>2</sub> with Hydrogen (H<sub>2</sub>) to generate CH<sub>4</sub> and Water (H<sub>2</sub>O) using the Sabatier System (Figure 1). The resulting water is recovered in the ISS, but the methane is vented to space. Recapturing this methane and using it for microbial manufacturing could provide a unique approach in development of in-space bio-manufacturing. Thus, there is a capability need for systems that convert methane into valuable materials. Methane (CH<sub>4</sub>) is a potential carbon substrate for methanotrophic microorganisms which are able to metabolize CH<sub>4</sub> into biomass. The innovative technology from NASA Ames Research Center ports Soluble Methane Monooxygenase (sMMO) to <i>Pichia</i>, that is, it moves the methane metabolism into a robust microbial factory (<i>Pichia pastoris</i>) (Figure 2). The yeast <i>Pichia pastoris</i> is a refined microbial factory that is used widely by industry because it efficiently secretes products. <i>Pichia</i> could produce a variety of useful products in space. <i>Pichia</i> does not consume methane but robustly consumes methanol, which is one enzymatic step removed from methane. This novel innovation engineers <i>Pichia</i> to consume methane thereby creating a powerful methane-consuming microbial factory and utilizing methane in a robust and flexible synthetic biology platform.
High Quality Tissue Formation Method
High Quality Tissue Formation Method
This technology is a simple, reproducible, and cost-effective process that creates 2D and 3D human tissue formations by high-density spot seeding (HDSS) of cells. The method entails the spot seeding of cells at a specific concentration onto a Petri dish, but without the need of extracellular matrix components. Cells are then incubated to allow attachment. The culture is rinsed with a medium to remove unattached cells and a growth medium is added to enable the cells at the periphery of the spot to proliferate and differentiate, outward from the center cells. This pattern of growth results in a 2D model of dense, organized, mature cells. It is proposed that the 2D formations can be stacked upon another via lamination process to create 3D tissues. By forming tissue using this method, the technology enables the creation of unique models for R&D, pharmaceutical development and perhaps even regenerative medicine. For instance, for basic R&D, the study of mechanistic pathways involved in normal and/or diseased tissue becomes possible. This technology can also be used as an in-vitro tissue model for drug screening and toxicology testing in the pharmaceutical development field. The HDSS method may also be advantageous for high-throughput screening assays, where large volume of screenings are done simultaneously.
Ambulance
Ultrasonic System To Assess Compartment Syndrome
The technology uses ultrasonic waves to categorize pressure build-up in a body compartment. The method includes assessing the body compartment configuration and identifying the effect of pulsatile components on at least one compartment dimension. An apparatus is used for measuring excess pressure in the body compartment having components for imparting ultrasonic waves such as a transducer, placing the transducer to impart the ultrasonic waves, capturing the reflected imparted ultrasonic waves, and converting them to electrical signals, a pulsed phase-locked loop device for assessing a body compartment configuration and producing an output signal, and means for mathematically manipulating the output signal to thereby categorize pressure build-up in the body compartment to the point of interference with blood flow in the compartment from the mathematical manipulations.
First Responders
Subcutaneous Structure Imager
Current subcutaneous vessel imagers use large, multiple, and often separate assemblies with complicated optics to image subcutaneous structures as two-dimensional maps on a wide monitor, or as maps extracted by a computer and focused onto the skin by a video projection. The scattering of infrared light that takes place during this process produces images that are shadowy and distorted. By contrast, Glenn's innovative approach offers a relatively compact and inexpensive alternative to the conventional setup, while also producing clearer images that can be rendered in either two or three dimensions. Glenn's device uses off-the-shelf near-infrared technology that is not affected by melanin content and can also operate in dark environments. In Glenn's novel subcutaneous imager, a camera is configured to generate a video frame. Connected to the camera is a processor that receives the signal for the video frame and adjusts the thresholds for darkness and whiteness. The result is that the vein (or other subcutaneous structure) will show very dark, while other surrounding features (which would register as gray) become closer to white due to the heightened contrast between thresholds. With no interval of complex algorithms required, the image is presented in real-time on a display, yielding immediate results. Glenn's advanced technology also allows the operator to achieve increased depth perception through the synchronization of a pair of imaging devices. Additionally, the novel use of a virtual-reality headset affords a three-dimensional view of the field, thereby improving the visualization of veins. In short, Glenn's researchers have produced an inexpensive, lightweight, high-utility device for locating and identifying subcutaneous structures in patients.
Bioprint
3D Construction of Biologically Derived Materials
Once genes for a desired material type, delivery mode, control method and affinity have been chosen, assembling the genetic components and creating the cell lines can be done with well-established synthetic biology techniques. A 3D microdeposition system is used to make a 3D array of these cells in a precise, microstructure pattern and shape. The engineered cells are suspended in a printable 'ink'. The 3D microdeposition system deposits minute droplets of the cells onto a substrates surface in a designed print pattern. Additional printer passes thicken the material. The cell array is fed nutrients and reagents to activate the engineered genes within the cells to create and deposit the desired molecules. These molecules form the designed new material. If desired, the cells may be removed by flushing. The end product is thus a 3D composite microstructure comprising the novel material. This innovation provides a fast, controlled production of natural, synthetic, and novel biomaterials with minimum resource overhead and reduced pre- and post-processing requirements.
Diagram showing the mounting of the transducer.
Non-invasive Intracranial Pressure Measurement
This technology and a product based on it offer new analytical capabilities for assessment of intracranial dynamics. It offers the possibility for the monitoring of transcranial expansion and related physiological phenomena in humans resulting from variations in intracranial pressure (ICP) caused by injuries to the head and/or brain pathologies. The technology uses constant frequency pulse phase-locked loop (CFPPLL) technology to measure skull expansion caused by pressure and its variations in time. This approach yields a more accurate, more robust measurement capability with improved bandwidth that allows new analytical approaches for assessing the physiology of skull expansion under pulsatile cerebral blood flow. The dynamical quantities assessable with the CFPPLL include skull volume expansion and total fluid. Such an instrument can serve to measure intracranial dynamics with equation based algorithms, and offers a path to measure or determine quasistatic intracranial pressure, along with the pulsatile related intracranial pressure increments. Supportive measurements, such as time dependence of arterial pressure waveforms together with time dependent phase change of transcranial expansions can serve as the basis of noninvasive techniques to measure intracranial pressure.
Comprehensive Oculomotor Behavioral Response Assessment (COBRA)
Microorganism
Surface Attached BioReactor (SABR) for Microbial Cell Cultivation
The Surface-Adhering BioReactor (SABR) is a novel microbial cell cultivation platform that mimics the way vascular plants use transpiration to deliver nutrients to their cells. In this biomimetic platform, microbial cells are cultivated as immobilized cells on a porous substrate where transpiration is used to passively deliver water and nutrients as well as harvest and concentrate secreted biomolecules by the microbial cells. The SABR transports nutrients to microorganisms without using a pump. Instead, evaporation and the cohesive property of water are exploited to pull the nutrient medium through the device, with a high degree of control, on an as needed basis. It eliminates the hydrodynamic shear stress on the cells and decreases the working volume of water needed for cultivation by a factor of 25 compared to planktonic bioreactors. Furthermore, the transpiration mechanism allows for the concentration of secreted products in areas of relatively fast evaporation, thus providing a passive means of secreted product harvesting. By matching the time scales of nutrient medium delivery and product harvesting with the time scales of growth and product formation, minimal energy is wasted in bioreactor operation. Transpiration enables a passive cooling system for the cells where either externally imposed or internally generated heat due to cellular activity is mitigated, thus preventing overheating that can lead to decreased productivity or even cell death. This technology enables significant reductions in energy input for cultivating microorganisms.
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