SBIR-STTR Award

There is a need to expand the use of cell-based assays in high throughput screening systems for diabetes research as well as research into other digestive systems diseases. Genome Data Systems, Inc. (GDS) proposes to design, fabricate and commercialize a high throughput drug discovery system based on its proprietary fluidic chip technology. In this approach, the cell growth and assay are separated into two modules and growth of cells for prolonged periods in small volumes is not required. Moreover, the disposable components are simple-to-fabricate and are inexpensive, while the more expensive chips can be reused. The technology lends itself to development of compact high throughput screening instruments. GDS is assembling a team of experts in microfluidics, micro-fabrication, detection optics and genomics to ensure success of this project. This SBIR project is focused on the design and fabrication of a high throughput screening instrument for apoptosis assays with an integrated generic fluidic chip and other necessary components. The proposed commercial applications of such technology include drug discovery for the NIDDK focus areas; however, the technology will have broad applications in drug discovery in other therapeutic areas as well. At the successful development of GeneCard and GeneCube, GDS will manufacture them for commercialization and wide distribution to genomic research community. PROPOSED COMMERCIAL APPLICATION: Current commercial applications of the proposed instruments and microfluidics chips include drug discovery, chemical detection, diagnostic testing, genomics, proteomics, and pharmaceutical research.

Thesaurus Terms:
apoptosis, cytology, drug discovery /isolation, fluid flow, high throughput technology, technology /technique development biomedical automation, consumable /disposable biomedical equipment, genome, pharmacogenetics biotechnology, fluorescence microscopy, tissue /cell culture

This Phase II SBIR project is focused at the development of a high-throughput screening method and instrument for drug discovery using miniaturized, cell-based assays. For developing new drugs against complex diseases such as diabetes, cancer and neurological and cardiovascular disorders, high throughput screening using cell-based assays will be essential. Miniaturization of cell-based assays for automation and reduced costs is required. GeneCard-HTS enables drug discovery using adherent cell-based assays. During the Phase I project, the feasibility of the GeneCard approach was demonstrated using apoptosis assays. A prototype instrument to automate GeneCard assay process was developed and assembled. During Phase II, the versatility and flexibility of the GeneCard platform will be investigated by performing other cell-based assays used in drug discovery. The proposed plan investigates the following three specific aims: 1. Build a high-throughput screening prototype system based on GeneCard technology (GeneCard-HTS). 2. Miniaturize multiple cell-based assays for GeneCard-HTS platform. We will miniaturize four commonly used drug discovery assays in the GeneCard-HTS platform, i) Apoptosis assays using the Mitosensor reagents, ii) cell-based kinase assays, iii) fluorescent cytotoxicity assays, and iv) gene expression profiling assays. We will measure the performance of these assays in GeneCard-HTS platform and compare with performance obtained at present. 3. Validate GeneCard-HTS by cell-based screening of compound libraries. In order to validate the Genecard-HTS system, we will perform screening of a 5,000 compound focused library using cell-based kinase and apoptosis assays. We will measure validation parameters such as system lifetime, operating temperature and humidity range, inter- and intra- assay variability, and day-to-day variability. Commercial applications of the proposed system include pharmaceutical and biotechnoiogy drug discovery. Further integration of the instrument based on design specifications prepared in Phase I will be performed. Screening of drug compound libraries to identify potential lead compounds will be performed.

Thesaurus Terms:
biomedical automation, biomedical equipment development, drug discovery /isolation, drug screening /evaluation, high throughput technology, method development, microarray technology, miniature biomedical equipment apoptosis, cell mediated lymphocytolysis test, chemical registry /resource, gene expression profiling, pharmacokinetics bioengineering /biomedical engineering, biotechnology, computer program /software