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ROCKVILLE, MD, United States

Stefansson S.,Fuzbien Technology Institute Inc. | Knight M.,Cc Biotech, Llc | Ahn S.N.,Fuzbien Technology Institute Inc.
Nanomaterials and Nanotechnology

Amyloids constitute a class of protein and protein fragments believed to be involved in the pathologies associated with Alzheimer's, Parkinson's and Creutzfeldt- Jakob diseases. These proteins can self-assemble into unique fibrillar structures that are resistant to normal protein degradation. Interesting recent developments in the study of amyloid fibrils demonstrate that they bind carbon allotropes. In this study, using single-walled carbon nanotube fieldeffect transistors (SWCNT-FETs), we show that the fibrillar form of Alzheimer's amyloid β (1-40) and (1-42) peptides specifically bind non-functionalized SWCNT in a saturable manner. Both peptides exhibited near identical binding curves with half-maximal binding concentrations of approximately 12 μg/ml. Binding of the peptides to SWCNTs was diminished by including dimethyl sulphoxide (DMSO) at concentrations that inhibits fibril formation. Lastly, a monoclonal antibody (BAM-10), which binds to the N-terminal region of Alzheimer's amyloid fibrils, recognizes the amyloid peptides adhering to SWCNTs in the absence of DMSO, but not in the presence of 75% DMSO. Taken together, these results suggest that the fibrillar form of the Alzheimer's amyloid peptides are specifically binding to SWCNTs. © 2012 Stefansson et al. Source

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 100.00K | Year: 2008

DESCRIPTION (provided by applicant): Despite great progress in cell culture technology to produce proteins and biologics in high yields from large volume fermentations, there is a bottleneck in the industry because of the lack of high throughput in the pur ification process. Centrifugal precipitation chromatography, a new method invented at the National Institutes of Health and licensed by CC Biotech LLC, offers unique capabilities for the purification of large molecules. In gradients of salt or solvents, di screte fractionation of large molecules is possible, aided by centrifugal forces. This method is well adapted to proteins, DNA and many bio-polymers. In a flow-through centrifuge, proteins are held by a filtration membrane as they are precipitated by the e luting agents. The process of precipitation and re-dissolving is repeated many times, causing the components to separate from each other at their different rates in the process. Special eluting conditions can be created for many types of molecules. This pr oject is aimed at manufacturing the instrument for the research laboratory market such that its use will develop novel purification methods to simplify the process for biotechnology products and additionally, develop parameters for scaling up in the indust ry. PUBLIC HEALTH RELEVANCE: A new technique of purification is centrifugal precipitation chromatography which is especially suitable for the large bio-molecules. As a result of this research, purification processes for new therapeutic biologics wil l be simplified, and the costs lowered, to provide very pure drugs and vaccines for healthcare. New manufacturing techniques will be applied to make an improved instrument for introduction on the market.

Agency: National Science Foundation | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 100.00K | Year: 2007

This Small Business Innovation Research (SBIR) Phase I project focuses on a new design of a spiral flow-through separation coil for planetary centrifuge chromatographs that are already commercialized for natural products and synthetic small molecule purification. This scientific and engineering project will extend the advantageous high resolution, solid support-free, highly scaleable process to the biotechnology field. Success in purification of high molecular weight compounds by countercurrent chromatography will lower the manufacturing costs of biotechnology products, including therapeutics. Improvement in the separation process for the purification of more complex therapeutic products is needed in the industry. An all-liquid process that can purify in high yield, compounds in any solvent system designed for their solubility is extended to the larger MW compounds, including biological molecules. The proposed design retains the more viscous and heavy two-phase solvent systems that are suitable for proteins, peptides and particles, and prevent denaturation - thereby enabling the recovery of high activity.

Agency: National Science Foundation | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 150.00K | Year: 2016

The broader impact/commercial potential of this project lies in the availability of single-wall carbon nanotubes in their most highly purified form in laboratory scale quantities. This would be enabled by the use of a spiral countercurrent chromatograph, invented and made in the USA. Single-wall carbon nanotube is one of the most promising semi-conductor materials and is being actively considered for making state-of-the-art high performance electronic circuits. The associated know-how will be of great value to the high volume semi-conductor manufacturing industry. The availability of discrete chiral types of the single-wall carbon nanotubes separated by the proposed system will have additional impact on the research market. Research labs in the semi-conductor industry and academic labs may be able to develop the carbon nanotube based nanomaterials, components and final products for point of care diagnostics, genomics devices and sensors for environmental and security identification. The societal benefits of these potential applications are significant. The benefits extend more broadly to the life science research industry also where the technology works for protein and particle separations in the development of novel vaccines and drug delivery. This Small Business Innovation Research (SBIR) Phase I project focuses on developing a novel laboratory scale system for carbon nanotube purification. Carbon nanotubes are challenging to manufacture and isolate in their pure form for use as robust logic and sensor elements in advanced electronics. They are hard crystal carbon polymers that are heterogeneous tubes of various lengths and diameters and occur as single-walled or multi-walled with other structures. The existing processes to solubilize and purify the various single-walled semi-conductor species are quite difficult and have low mass yields. The methods mostly used to date are column chromatography and density gradient ultracentrifugation. To meet the need of higher mass loading and increased selectivity, this proposal focuses on developing spiral countercurrent chromatography. A new spiral design rotor used with a polymer solvent mix has shown improved nanotube fractionation over static extraction in preliminary experiments. Recent innovative research on dextran polymer liquid stationary phase makes it possible to improve the fractionation of carbon nanotubes even further. It also opens up many exciting options for large molecule separation. This development has a very significant intellectual merit for both chromatography and semi-conductor research.

Cc Biotech, Llc | Date: 2012-11-18

Chromatography apparatus for laboratory use.

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