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NASA NTRS2003

Microencapsulated Bioactive Agents and Method of Making

The invention is directed to microcapsules encapsulating an aqueous solution of a protein, drug or other bioactive substance inside a semi-permeable membrane. The microcapsules are formed by interfacial coacervation where shear forces are limited to 0-100 dynes per square centimeter. The resulting uniform microcapsules can then be subjected to dewatering in order to cause the internal solution to become supersaturated with the dissolved substance. This dewatering allows controlled nucleation and crystallization of the dissolved substance. The crystal-filled microcapsules can be stored, keeping the encapsulated crystals in good condition for further direct use in x-ray crystallography or as injectable formulations of the dissolved drug, protein or other bioactive substance.

Dennis R Morrison↗

NASA NTRS2003

Experimental Study of Arcing on High-Voltage Solar Arrays

The main obstacle to the implementation of a high-voltage solar array in space is arcing on the conductor-dielectric junctions exposed to the surrounding plasma. One obvious solution to this problem would be the installation of fully encapsulated solar arrays which were not having exposed conductors at all. However, there are many technological difficulties that must be overcome before the employment of fully encapsulated arrays will turn into reality. An alternative solution to raise arc threshold by modifications of conventionally designed solar arrays looks more appealing, at least in the nearest future. A comprehensive study of arc inception mechanism suggests that such modifications can be done in the following directions: 1) To insulate conductor-dielectric junction from a plasma environment (wrapthrough interconnects); 2) To change a coverglass geometry (overhang); 3) To increase a coverglass thickness; 4) To outgas areas of conductor-dielectric junctions. The operation of high-voltage array in LEO produces also the parasitic current power drain on the electrical system. Moreover, the current collected from space plasma by solar arrays determines the spacecraft floating potential that is very important for the design of spacecraft and its scientific apparatus. In order to verify the validity of suggested modifications and to measure current collection five different solar array samples have been tested in a large vacuum chamber. Each sample (36 silicon based cells) consists of three strings containing 12 cells connected in series. Thus, arc rate and current collection can be measured on every string independently, or on a whole sample when strings are connected in parallel. The heater installed in the chamber provides the possibility to test samples under temperature as high as 80 C that stimulates the LEO operational temperature. The experimental setup is described below.

Vayner, Boris↗

NASA NTRS2001

TGF-beta1 release from biodegradable polymer microparticles: its effects on marrow stromal osteoblast function

BACKGROUND: Controlled release of transforming growth factor-beta1 (TGF-beta1) to a bone defect may be beneficial for the induction of a bone regeneration cascade. The objectives of this work were to assess the feasibility of using biodegradable polymer microparticles as carriers for controlled TGF-beta1 delivery and the effects of released TGF-beta1 on the proliferation and differentiation of marrow stromal cells in vitro. METHODS: Recombinant human TGF-beta1 was incorporated into microparticles of blends of poly(DL-lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG). Fluorescein isothiocynate-labeled bovine serum albumin (FITC-BSA) was co-encapsulated as a porogen. The effects of PEG content (0, 1, or 5% by weight [wt%]) and buffer pH (3, 5, or 7.4) on the protein release kinetics and the degradation of PLGA were determined in vitro for as long as 28 days. Rat marrow stromal cells were seeded on a biodegradable poly(propylene fumarate) (PPF) substrate. The dose response and biological activity of released TGF-beta1 was determined after 3 days in culture. The effects of TGF-beta1 released from PLGA/PEG microparticles on marrow stromal cell proliferation and osteoblastic differentiation were assessed during a 21-day period. RESULTS: TGF-beta1 was encapsulated along with FITC-BSA into PLGA/PEG blend microparticles and released in a multiphasic fashion including an initial burst for as long as 28 days in vitro. Increasing the initial PEG content resulted in a decreased cumulative mass of released proteins. Aggregation of FITC-BSA occurred at lower buffer pH, which led to decreased release rates of both proteins. The degradation of PLGA was increased at higher PEG content and significantly accelerated at acidic pH conditions. Rat marrow stromal cells cultured on PPF substrates showed a dose response to TGF-beta1 released from the microparticles similar to that of added TGF-beta1, indicating that the activity of TGF-beta1 was retained during microparticle fabrication and after growth factor release. At an optimal TGF-beta1 dosage of 1.0 ng/ml after 3 days, the released TGF-beta1 enhanced the proliferation and osteoblastic differentiation of marrow stromal cells over 21 days of culture, with increased total cell number, alkaline phosphatase activity, and osteocalcin production. CONCLUSIONS: PLGA/PEG blend microparticles can serve as delivery vehicles for controlled release of TGF-beta1, and the released growth factor enhances marrow stromal cell proliferation and osteoblastic differentiation in vitro. CLINICAL RELEVANCE: Controlled release of TGF-beta1 from PLGA/PEG microparticles is representative of emerging tissue engineering technologies that may modulate cellular responses to encourage bone regeneration at a skeletal defect site.

Non-NASA Center↗

NASA NTRS1997

The first living systems: a bioenergetic perspective

The first systems of molecules having the properties of the living state presumably self-assembled from a mixture of organic compounds available on the prebiotic Earth. To carry out the polymer synthesis characteristic of all forms of life, such systems would require one or more sources of energy to activate monomers to be incorporated into polymers. Possible sources of energy for this process include heat, light energy, chemical energy, and ionic potentials across membranes. These energy sources are explored here, with a particular focus on mechanisms by which self-assembled molecular aggregates could capture the energy and use it to form chemical bonds in polymers. Based on available evidence, a reasonable conjecture is that membranous vesicles were present on the prebiotic Earth and that systems of replicating and catalytic macromolecules could become encapsulated in the vesicles. In the laboratory, this can be modeled by encapsulated polymerases prepared as liposomes. By an appropriate choice of lipids, the permeability properties of the liposomes can be adjusted so that ionic substrates permeate at a sufficient rate to provide a source of monomers for the enzymes, with the result that nucleic acids accumulate in the vesicles. Despite this progress, there is still no clear mechanism by which the free energy of light, ion gradients, or redox potential can be coupled to polymer bond formation in a protocellular structure.

Review↗

NASA NTRS2005

Atmospheric Electron-induced X-Ray Spectrometer (AEXS) Instrument Development

Instrument Development: The membrane properties were investigated in detail due to its critical role. A series of experiments determined that our designed membranes have high electron transmission, yet are capable of isolating high vacuum, are able to withstand differential pressure in excess of one atmosphere, survive vibrational shocks of a magnitude to be expected during a planetary mission. Our initial work has been with a 10 keV source and a 200 nm thick Silicon Nitride (SiN) encapsulation membrane micro-fabricated within a Si support frame (1.5 mm x 1.5 mm window openings. Fig 2 compares the spectra taken with the 10 keV source with spectra taken within SEM. Introduction: This paper describes the progress in the development of the AEXS instrument in our laboratory at JPL. The AEXS is a novel miniature instrument[1-3] based on the excitation of characteristic X-Ray Fluorescence (XRF) and luminescence spectra using a focused electron beam, for non-destructive evaluation of surfaces of samples in planetary ambient atmosphere. In situ operation is obtained through the use of a thin electron transmissive membrane to isolate the vacuum within the AEXS electron source from the outside ambient atmosphere. The impinging electrons excite XRF spectra from the irradiated spots on samples in external atmosphere with high-to-medium (sub-mm to cm-scale) spatial resolution at Mars atmospheric pressure. The XRF spectra are analyzed using an energy-dispersive detector to determine surface elemental composition, or in the case of electron-induced luminescence to identify unusual formations on surface that cathodo-luminescence (CL). The AEXS system (Fig 1) consists of a high-energy (>10keV) electron gun encapsulated by the isolation membrane, an EDX detection and analyzer system to determine the elemental abundance, an optional CL detection system, and a high voltage power supply. The approach to demonstrating a proof of concept of the AEXS has been through 1) demonstrating the viability of micro-fabricated membranes, 2) assembling AEXS setups with increasingly integrated functional components, and 3) simulating the AEXS observational capabilities. This paper will focus on description of the development of the instrument.

Wilcox, J. Z.↗

NASA NTRS2005

Experimental Study of Arcing on High-voltage Solar Arrays

The main obstacle to the implementation of a high-voltage solar array in space is arcing on the conductor-dielectric junctions exposed to the surrounding plasma. One obvious solution to this problem would be the installation of fully encapsulated solar arrays which were not having exposed conductors at all. However, there are many technological difficulties that must be overcome before the employment of fully encapsulated arrays will turn into reality. An alternative solution to raise arc threshold by modifications of conventionally designed solar arrays looks more appealing, at least in the nearest future. A comprehensive study of arc inception mechanism [1-4] suggests that such modifications can be done in the following directions: i) to insulate conductor-dielectric junction from a plasma environment (wrapthrough interconnects); ii) to change a coverglass geometry (overhang); iii) to increase a coverglass thickness; iiii) to outgas areas of conductor-dielectric junctions. The operation of high-voltage array in LEO produces also the parasitic current power drain on the electrical system. Moreover, the current collected from space plasma by solar arrays determines the spacecraft floating potential that is very important for the design of spacecraft and its scientific apparatus. In order to verify the validity of suggested modifications and to measure current collection five different solar array samples have been tested in large vacuum chamber. Each sample (36 silicon based cells) consists of three strings containing 12 cells connected in series. Thus, arc rate and current collection can be measured on every string independently, or on a whole sample when strings are connected in parallel. The heater installed in the chamber provides the possibility to test samples under temperature as high as 80 C that simulates the LEO operational temperature. The experimental setup is described below.

Vayner, Boris↗

NASA NTRS2006

Effect of Environments on Degradation of Molding Compound and Wire Bonds in PEMs

Degradation of wire bonds (WBs) is one of the major factors limiting reliability of plastic encapsulated microcircuits (PEMs) at high temperatures. Use of PEMs in military and aerospace applications requires extended and thorough evaluation of encapsulating materials and reliability of packages in harsh environments. However, the effect of environmental conditions on characteristics of molding compounds (MCs) and reliability of wire bonds has not been studied sufficiently to date. In this work, two types of PEMs in QFP-style packages have been stored in different environments at temperatures from 130 C to 225 C for up to 4,500 hours in some cases. To assess the effect of oxygen, the parts were aged at 198 C in air and vacuum chambers. The effect of humidity was evaluated during long-term highly accelerated temperature and humidity stress testing (HAST) at temperatures of 130 C and 150 C. Thermo-mechanical and thermo-gravimetrical analyses were used to evaluate the effect of environment on characteristics of molding compound used. Measurements of contact resistances of wire bonds and their mechanical strength were employed to monitor degradation of wire bonds throughout the testing. Correlation between degradation of MC and WB failures has been analyzed. The effect of environmental conditions on accelerating factors of WB failures has been assessed, and the mechanism of wire bond degradation due to the presence of moisture and oxygen is discussed.

Teverosky, Alexander↗

NASA NTRS1998

Contamination sampling device

A contamination sample collection device has a wooden dowel with a cotton swab at one end, the cotton being covered by a nylon cloth and the wooden dowel being encapsulated by plastic tubing which is heat shrunk onto the dowel and onto a portion of the cotton swab to secure the cotton in place. Another plastic tube is heat shrunk onto the plastic that encapsulates the dowel and a portion of the nylon cloth to secure the nylon cloth in place. The device may thereafter be covered with aluminum foil protector. The device may be used for obtaining samples of contamination in clean room environments.

Delgado, Felix A.↗

NASA NTRS2004

Method for determining the three-dimensional structure of a protein

Microcapsules prepared by encapsulating an aqueous solution of a protein, drug or other bioactive substance inside a semi-permeable membrane by are disclosed. The microcapsules are formed by interfacial coacervation under conditions where the shear forces are limited to 0-100 dynes/cm.sup.2 at the interface. By placing the microcapsules in a high osmotic dewatering solution, the protein solution is gradually made saturated and then supersaturated, and the controlled nucleation and crystallization of the protein is achieved. The crystal-filled microcapsules prepared by this method can be conveniently harvested and stored while keeping the encapsulated crystals in essentially pristine condition due to the rugged, protective membrane. Because the membrane components themselves are x-ray transparent, large crystal-containing microcapsules can be individually selected, mounted in x-ray capillary tubes and subjected to high energy x-ray diffraction studies to determine the 3-D structure of the protein molecules. Certain embodiments of the microcapsules of the invention have composite polymeric outer membranes which are somewhat elastic, water insoluble, permeable only to water, salts, and low molecular weight molecules and are structurally stable in fluid shear forces typically encountered in the human vascular system.

Morrison, Dennis R.↗

NASA NTRS2008

Controlled-Release Microcapsules for Smart Coatings for Corrosion Applications

Corrosion is a serious problem that has enormous costs and serious safety implications. Localized corrosion, such as pitting, is very dangerous and can cause catastrophic failures. The NASA Corrosion Technology Laboratory at Kennedy Space Center is developing a smart coating based on pH-sensitive microcapsules for corrosion applications. These versatile microcapsules are designed to be incorporated into a smart coating and deliver their core content when corrosion starts. Corrosion indication was the first function incorporated into the microcapsules. Current efforts are focused on incorporating the corrosion inhibition function through the encapsulation of corrosion inhibitors into water core and oil core microcapsules. Scanning electron microscopy (SEM) images of encapsulated corrosion inhibitors are shown.

Source record↗

NASA NTRS2009

Improved Aerogel Vacuum Thermal Insulation

An improved design concept for aerogel vacuum thermal-insulation panels calls for multiple layers of aerogel sandwiched between layers of aluminized Mylar (or equivalent) poly(ethylene terephthalate), as depicted in the figure. This concept is applicable to both the rigid (brick) form and the flexible (blanket) form of aerogel vacuum thermal-insulation panels. Heretofore, the fabrication of a typical aerogel vacuum insulating panel has involved encapsulation of a single layer of aerogel in poly(ethylene terephthalate) and pumping of gases out of the aerogel-filled volume. A multilayer panel according to the improved design concept is fabricated in basically the same way: Multiple alternating layers of aerogel and aluminized poly(ethylene terephthalate) are assembled, then encapsulated in an outer layer of poly(ethylene terephthalate), and then the volume containing the multilayer structure is evacuated as in the single-layer case. The multilayer concept makes it possible to reduce effective thermal conductivity of a panel below that of a comparable single-layer panel, without adding weight or incurring other performance penalties. Implementation of the multilayer concept is simple and relatively inexpensive, involving only a few additional fabrication steps to assemble the multiple layers prior to evacuation. For a panel of the blanket type, the multilayer concept, affords the additional advantage of reduced stiffness.

Ruemmele, Warren P.↗

NASA NTRS2010

Analysis of Shroud Options in Support of the Human Exploration of Mars

In support of the Mars Design Reference Architecture (DRA) 5.0, the NASA study team analyzed several shroud options for use on the Ares V launch vehicle.1,2 These shroud options included conventional "large encapsulation" shrouds with outer diameters ranging from 8.4 to 12.9 meters (m) and overall lengths of 22.0 to 54.3 meters, along with a "nosecone-only" shroud option used for Mars transfer vehicle component delivery. Also examined was a "multi-use" aerodynamic encapsulation shroud used for launch, Mars aerocapture, and entry, descent, and landing of the cargo and habitat landers. All conventional shroud options assessed for use on the Mars launch vehicles were the standard biconic design derived from the reference shroud utilized in the Constellation Program s lunar campaign. It is the purpose of this paper to discuss the technical details of each of these shroud options including material properties, structural mass, etc., while also discussing both the volume and mass of the various space transportation and surface system payload elements required to support a "minimum launch" Mars mission strategy, as well as the synergy, potential differences and upgrade paths that may be required between the Lunar and Mars mission shrouds.

Feldman, Stuart↗

NASA NTRS2006

Mercury Shopping Cart Interface

Mercury Shopping Cart Interface (MSCI) is a reusable component of the Power User Interface 5.0 (PUI) program described in another article. MSCI is a means of encapsulating the logic and information needed to describe an orderable item consistent with Mercury Shopping Cart service protocol. Designed to be used with Web-browser software, MSCI generates Hypertext Markup Language (HTML) pages on which ordering information can be entered. MSCI comprises two types of Practical Extraction and Report Language (PERL) modules: template modules and shopping-cart logic modules. Template modules generate HTML pages for entering the required ordering details and enable submission of the order via a Hypertext Transfer Protocol (HTTP) post. Shopping cart modules encapsulate the logic and data needed to describe an individual orderable item to the Mercury Shopping Cart service. These modules evaluate information entered by the user to determine whether it is sufficient for the Shopping Cart service to process the order. Once an order has been passed from MSCI to a deployed Mercury Shopping Cart server, there is no further interaction with the user.

Pfister, Robin↗

NASA NTRS2005

Low-Shear Microencapsulation and Electrostatic Coating

A report presents additional information on the topic of a microencapsulation electrostatic processing system. Information in the report includes micrographs of some microcapsules, a set of diagrams that schematically depict the steps of an encapsulation process, and brief descriptions of (1) alternative versions of the present encapsulation processes, (2) advantages of the present microencapsulation processes over prior microencapsulation processes, and (3) unique and advantageous features of microcapsules produced by the present processes.

Morrison, Dennis R.↗

NASA NTRS2003

High-Fidelity Piezoelectric Audio Device

ModalMax is a very innovative means of harnessing the vibration of a piezoelectric actuator to produce an energy efficient low-profile device with high-bandwidth high-fidelity audio response. The piezoelectric audio device outperforms many commercially available speakers made using speaker cones. The piezoelectric device weighs substantially less (4 g) than the speaker cones which use magnets (10 g). ModalMax devices have extreme fabrication simplicity. The entire audio device is fabricated by lamination. The simplicity of the design lends itself to lower cost. The piezoelectric audio device can be used without its acoustic chambers and thereby resulting in a very low thickness of 0.023 in. (0.58 mm). The piezoelectric audio device can be completely encapsulated, which makes it very attractive for use in wet environments. Encapsulation does not significantly alter the audio response. Its small size (see Figure 1) is applicable to many consumer electronic products, such as pagers, portable radios, headphones, laptop computers, computer monitors, toys, and electronic games. The audio device can also be used in automobile or aircraft sound systems.

Woodward, Stanley E.↗

NASA NTRS2011

Principles, Techniques, and Applications of Tissue Microfluidics

The principle of tissue microfluidics and its resultant techniques has been applied to cell analysis. Building microfluidics to suit a particular tissue sample would allow the rapid, reliable, inexpensive, highly parallelized, selective extraction of chosen regions of tissue for purposes of further biochemical analysis. Furthermore, the applicability of the techniques ranges beyond the described pathology application. For example, they would also allow the posing and successful answering of new sets of questions in many areas of fundamental research. The proposed integration of microfluidic techniques and tissue slice samples is called tissue microfluidics because it molds the microfluidic architectures in accordance with each particular structure of each specific tissue sample. Thus, microfluidics can be built around the tissues, following the tissue structure, or alternatively, the microfluidics can be adapted to the specific geometry of particular tissues. By contrast, the traditional approach is that microfluidic devices are structured in accordance with engineering considerations, while the biological components in applied devices are forced to comply with these engineering presets. The proposed principles represent a paradigm shift in microfluidic technology in three important ways: Microfluidic devices are to be directly integrated with, onto, or around tissue samples, in contrast to the conventional method of off-chip sample extraction followed by sample insertion in microfluidic devices. Architectural and operational principles of microfluidic devices are to be subordinated to suit specific tissue structure and needs, in contrast to the conventional method of building devices according to fluidic function alone and without regard to tissue structure. Sample acquisition from tissue is to be performed on-chip and is to be integrated with the diagnostic measurement within the same device, in contrast to the conventional method of off-chip sample prep and subsequent insertion into a diagnostic device. A more advanced form of tissue integration with microfluidics is tissue encapsulation, wherein the sample is completely encapsulated within a microfluidic device, to allow for full surface access. The immediate applications of these approaches lie with diagnostics of tissue slices and biopsy samples e.g. for cancer but the approaches would also be very useful in comparative genomics and other areas of fundamental research involving heterogeneous tissue samples.

Wade, Lawrence A.↗

NASA NTRS2012

Fabrication of a Cryogenic Bias Filter for Ultrasensitive Focal Plane

A fabrication process has been developed for cryogenic in-line filtering for the bias and readout of ultrasensitive cryogenic bolometers for millimeter and submillimeter wavelengths. The design is a microstripline filter that cuts out, or strongly attenuates, frequencies (10 50 GHz) that can be carried by wiring staged at cryogenic temperatures. The filter must have 100-percent transmission at DC and low frequencies where the bias and readout lines will carry signal. The fabrication requires the encapsulation of superconducting wiring in a dielectric-metal envelope with precise electrical characteristics. Sufficiently thick insulation layers with high-conductivity metal layers fully surrounding a patterned superconducting wire in arrayable formats have been demonstrated. A degenerately doped silicon wafer has been chosen to provide a metallic ground plane. A metallic seed layer is patterned to enable attachment to the ground plane. Thick silicon dioxide films are deposited at low temperatures to provide tunable dielectric isolation without degrading the metallic seed layer. Superconducting wiring is deposited and patterned using microstripline filtering techniques to cut out the relevant frequencies. A low Tc superconductor is used so that it will attenuate power strongly above the gap frequency. Thick dielectric is deposited on top of the circuit, and then vias are patterned through both dielectric layers. A thick conductive film is deposited conformally over the entire circuit, except for the contact pads for the signal and bias attachments to complete the encapsulating ground plane. Filters are high-aspect- ratio rectangles, allowing close packing in one direction, while enabling the chip to feed through the wall of a copper enclosure. The chip is secured in the copper wall using a soft metal seal to make good thermal and electrical contact to the outer shield.

Chervenak, James↗

NASA NTRS2012

Processes that Drove the Transition from Chemistry to Biology: Concepts and Evidence

Two properties are particularly germane to the transition from chemistry to biology. One is the emergence of complex molecules (polymers) capable of performing non-trivial functions, such as catalysis, energy transduction or transport across cell walls. The other is the ability of several functions to work in concert to provide reproductive advantage to systems hosting these functions. Biological systems exhibit these properties at remarkable levels of efficiency and accuracy in a way that appears effortless. However, dissection of these properties reveals great complexities that are involved. This opens a question: how a simple, ancestral system could have acquired the required properties? Other questions follow. What are the chances that a functional polymer emerges at random? What is the minimum structural complexity of a polymer to carry out a function at a reasonable level of efficiency? Can we identify concrete, protobiologically plausible mechanisms that yield advantageous coupling between different functions? These and similar questions are at the core of the main topic of this session: how soulless chemistry became life? Clearly, we do not have complete answers to any of these questions. However, in recent years a number of new and sometimes unexpected clues have been brought to light. Of particular interest are proteins because they are the main functional polymers in contemporary cells. The emergence of protein functions is a puzzle. It is widely accepted that a well ]defined, compact structure (fold) is a prerequisite for function. It is equally widely accepted that compact folds are rare among random amino acid polymers. Then, how did protein functionality start? According to one hypothesis well folded were preceded by their poorly folded, yet still functional ancestors. Only recently, however, experimental evidence supporting this hypothesis has been presented. In particular, a small enzyme capable of ligating two RNA fragments with the rate of 106 above background was evolved in vitro. This enzyme does not look like any contemporary protein. It is very flexible and its structure is kept together just by a single salt bridge between a charged residue and a coordinating zinc. A similar picture emerges from studies of simple transmembrane channels that mimic those in ancestral cells. Again, they are extremely flexible and do not form a conventional pore. Yet, they efficiently mediate ion transport. Studies on simple proteins that are on-going in several laboratories hold promise of revealing crucial links between chemical and biological catalysis and other ubiquitous cell functions. Interaction between composition, growth and division of protobiologically relevant vesicles and metabolic reactions that they encapsulate is an example of coupling between simple functions that promotes reproduction and evolution. Recent studies have demonstrated possible mechanisms by which vesicles might have evolved their composition from fatty acids to phospholipids, thus facilitating a number of new cellular functions. Conversely, it has been also demonstrated that an encapsulated metabolism might drive vesicle division. These are, again, examples of processes that might have driven the transition from chemistry to biology.

Pohorille, Andrew↗