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Space Biotech: Hindsight, Insight, Foresight

Over the past forty years, microgravity has inspired and enabled applications in a wide range of sectors including medicine, materials, computers, communications, and national defense. Trends show that demand for high-tech solutions is increasing in these sectors, solutions that require higher resolution, greater precision, novel materials, innovative processes, and more sophisticated tools. These are areas where microgravity can offer unique capabilities for innovation. The Emerging Space Office (ESO) has engaged in multiple studies over the past year that have found that microgravity RD is one of the most promising technology areas for contributing to economic growth and to NASAs mission. The focus of these studies was on terrestrial markets rather than NASA applications, applied research rather than basic research, and commercial rather than academic investigators. There have been more success stories than are generally appreciated and there are significant areas of promising future potential. Many of the problems that have limited commercial microgravity development in the past are being solved. Microgravity research and development (RD) requires iteration and learning, as rapidly as possible. New technologies enable high throughput and rapid data collection in increasingly small payloads. The International Space Station is in orbit and provides a laboratory that is available 247 at least until 2024. Frequent flights by commercial space providers to and from the ISS now enable the fast learning cycles needed by high-tech industries. Launch costs are decreasing and the ability to return payloads to Earth is increasing. New commercial space laboratories, such as those being developed by SpaceX and Bigelow Aerospace, are in the final stages of development and testing. This ecosystem for microgravity RD has never been available before. These are game-changer conditions for attracting high-tech industries to space for terrestrial, as well as NASA, applications. However, few know that these capabilities are available or how to use them. In aggregate, the potential value for new applications from microgravity RD over the next ten years could add billions of dollars per year in terrestrial applications to the future economy, create new jobs, and generate a wide range of public benefits in medical advances, while broadening the customer base for the emerging space industry.

biotech↗

New Programs Utilizing Light Scattering and Flow Imaging Techniques for Macromolecular Crystal Growth and Fluid Dynamics Studies

Dr. Phil Segre, a physicist by training, is a recent addition to the Biotech group, SD46, having joined NASA in August of 2000. Over the past two years he has been developing a laboratory for the study of macromolecular and protein crystal growth. The main apparatus for this work is a Dynamic Light Scattering apparatus, DLS, which is capable of making highly precise measurements of size distributions of both protein solutions and protein crystals. With Drs. Chernov and Thomas (USRA), he has begun a collaboration studying the affects of protein impurities on protein crystal growth and subsequent crystal quality. One of the hypotheses behind the differences between Earth and space grown protein crystals is that the absorption of harmful impurities is reduced in space due to the absence of convective flows. Using DLS measurements we are examining crystal growth with varying amounts of impurities and testing whether there is a strong physical basis behind this hypothesis. With Dr. Joe Ng of UAH he has been collaborating on a project to examine the folding/unfolding dynamics of large RNA complexes. A detailed understanding of this process is necessary for the handling of RNA in biotech applications, and the DLS instrument gives details and results beyond that of other instruments. With Prof. Jim McClymer of the University of Maine (summer faculty visitor to NASA in 2001, 2002), we have been studying the crystallization process in model colloidal suspensions whose behavior in some cases can mimic that of much smaller protein solutions. An understanding of the self-assembly of colloids is the first step in the process of engineering novel materials for photonic and light switching applications. Finally, he has begun an investigation into the physics of particle sedimentation. In addition to the DLS instrument he also has an instrument (called PIV) that can measure flow fields of fluids. The applications are to the dynamics of protein crystal motions both on earth and in low-gravity.

Source record↗

Industrial Processes Influenced by Gravity

In considering new directions for low gravity research with particular regard to broadening the number and types of industrial involvements, it is noted that transport phenomena play a vital role in diverse processes in the chemical, pharmaceutical, food, and biotech industries. Relatively little attention has been given to the role of gravity in such processes. Accordingly, numerous industrial processes and phenomena are identified which involve gravity and/or surface tension forces. Phase separations and mixing are examples that will be significantly different in low gravity conditions. A basis is presented for expanding the scope of the low gravity research program and the potential benefits of such research is indicated.

Ostrach, Simon↗

Decrease in T Cell Activation and Calcium Flux during Clinorotation

We investigated the effect of altered gravitational environments on T cell activation. We isolated human, naive T cells (CD3+CD14-CD19-CD16-CD56-CD25-CD69-CD45RA-) following IRB approved protocols. These purified T cells were then incubated with 6 mm polystyrene beads coated with OKT3 (Ortho Biotech, Raritan, NJ) and antiCD28 (Becton Dickinson (BD), San Jose, CA) at 37 C for 24 hours. Antibodies were at a 1:1 ratio and the bead-to-cell ratio was 2:1. Four incubation conditions existed: 1) static or "1g"; 2) centrifugation at 10 relative centrifugal force (RCF) or "10g"; 3) clinorotation at 25 RPM (functional weightlessness or "0g"); and 4) clinorotation at 80 RPM ("1g" plus net shear force approx.30 dynes/sq cm). Following incubation, T cells were stained for CD25 expression (BD) and intracellular calcium (ratio of Fluo4 to Fura Red, Molecular Probes, Eugene, OR) and analyzed by flow cytometry (Coulter EPICS XL, Miami, FL). Results: Static or "1g" T cells had the highest level of CD25 expression and intracellular calcium. T cells centrifuged at 10 RCF ("10g") had lower CD25 expression and calcium levels compared to the static control. However, cells centrifuged at 10 RCF had higher CD25 expression and calcium levels than those exposed to 24 RPM clinorotation ("0g"). T cells exposed to 24 RPM clinorotation had lower CD25 expression, but the approximately the same calcium levels than T cells exposed to 80 RPM clinorotation. These data suggest that stress-activated calcium channel exist in T cells and may play a role during T cell activation.

Sams, Clarence↗

Thioaptamer Diagnostic System (TDS)

AM Biotechnologies, LLC, in partnership with Sandia National Laboratories, has developed a diagnostic device that quickly detects sampled biomarkers. The TDS quickly quantifies clinically relevant biomarkers using only microliters of a single sample. The system combines ambient-stable, long shelf-life affinity assays with handheld, microfluidic gel electrophoresis affinity assay quantification technology. The TDS is easy to use, operates in microgravity, and permits simultaneous quantification of 32 biomarkers. In Phase I of the project, the partners demonstrated that a thioaptamer assay used in the microfluidic instrument could quantify a specific biomarker in serum in the low nanomolar range. The team also identified novel affinity agents to bone-specific alkaline phosphatase (BAP) and demonstrated their ability to detect BAP with the microfluidic instrument. In Phase II, AM Biotech expanded the number of ambient affinity agents and demonstrated a TDS prototype. In the long term, the clinical version of the TDS will provide a robust, flight-tested diagnostic capability for space exploration missions.

Yang, Xianbin↗