The goal of this project is to develop the technology for biochemo-opto-mechanical (BioCOM) chips for high-throughput and highly sensitive proteomic and genomic analyses that are critical in early diagnosis, monitoring and prognostic evaluation of cancer. The chip will contain an array of pixels, with each pixel providing quantitative analysis for a certain analyte by producing a color-based optical signal. In contrast to existing microarray biochip technologies, the BioCOM chip would not require any external power, external or on-board electronics, or fluorescent dyes and associated optics for its operation, which will keep its costs low while keeping is simple to use in clinical research and laboratories. Each pixel of the BioCOM chip will contain an array of microcantilever springs, one surface of which will be derivatized with either an antibody coating for detecting cancer-associated antigens or a coating of single-stranded nucleic acid capture sequences complementary to cancer-associated mRNAs or mutant sequences. Recent experiments have confirmed that molecular binding on such derivatized cantilevers can generate sufficient chemomechanical force due to molecular conformational energy changes to produce an observable deflection of the cantilever springs. The underlying innovation in the BioCOM chip is to exploit this phenomenon using fabricated microstructures embedded in the springs that utilize interference and diffraction of background white light to produce iridescent colors in each pixel. Once optimized, the proposed technology will be able to screen literally hundreds of molecules, and these can be transcribed mRNAs or proteins. For protein expression, in particular, this technology would represent a new paradigm in the evaluation of multiple proteins from serum or from a single tissue, and could represent a cost-effective way to assess multiple cancer antigens in screening and monitoring programs. The approach is to first quantitatively demonstrate (R21 phase) the existence of chemomechanical signatures for two representative molecules - prostate specific antigen (PSA) and PSA coding DNA sequence. Subsequently, the R33 phase will involve the development of a comprehensive chemomechanical database for a large number of cancer-associated proteins and nucleic acid sequences. This, in combination with engineering mechanics of cantilever beams and wave optics of interference and diffraction, will be used to design the BioCOM chip. The chips will be microfabricated using processing techniques widely employed in microelectronics and microelectromechanical systems (MEMS). Optimization of the chips will occur through clinical tests by controlling the biochemistry of protein/DNA immobilization on cantilever surfaces and the mechanics and optics of cantilever beams.
