In order to reduce the costs of drug development and improve methods of detecting environmental effects of xeniobiotics, there is a need for in vitro methods of xeniobiotics identifying toxicity of materials to specific organs that do not require a whole-animal model. In particular, methods capable of identifying hepatotoxicity either require extensive animal studies or do not take into account differences in metabolic pathways that cannot be predicted by genomic approaches. American Research Corporation of Virginia (ARCOVA) proposes the development of a novel sensitive aptamer array that is capable of differentiating multiple metabolic products on a real-time basis through metabonomics. This proposal is innovative in developing an aptamer array having improved selectivity and sensitivity to changes of low molecular weight metabolic products resulting from hepatotoxicity in the cell culture. Phase I specific aims include preparation of liver metabolite-specific capture aptamers and capture aptamer-analyte probe aptamers for fabrication of surface-sensitive diode laser (SSDL) array elements, modification of SSDL aptamer array to improve sensitivity and reproducibility, design and fabrication of experimental workstation for the characterization of an engineering model SSDL array sensor head and acquisition of families of test data from an SSDL array and optimization of an engineering model for the metabolic monitor. In Phase II of the program, a prototype strip panel will be constructed and field-tested in preparation for commercialization during Phase III of the program. Successful completion of the Phase I program will result in an SSDL-based aptamer array for detection of hepatotoxicity-related metabolic products. The aptamer array will find commercial use in biomedical point-of-care monitoring, evaluation of treatment protocols and veterinary medicine.
