(Verbatim from the application) The overall aim of this proposal is to design, build, and test an integrated optical and microfluidics system that will enable the performance of novel biochemical assays in single living cells. The device will be tested in biomedical systems relating primarily to cancer, and cell growth, and development, though it will have wide application in the areas of molecular medicine and drug development. This project is submitted in response to the PAS-99-010 to support Bioengineering Research Partnerships (BRP's). It involves a close collaboration amongst three academic research labs, each with a very different focus and expertise: (1) photonics/microscopy (Berns & Venugopalan); (2) BioMEMS/microfluidics (Li & Bachman); (3) analytical chemistry/cell biology (Albritton & Sims). The project's specific aims are: (1) the development of a laser microscope platform for single cell manipulation and analysis; (2) development of a multipurpose, modular microfluidics chip for single cell assays; (3) development of a broad range of analytes which can be assayed in single cells. Development of the microscope platform will involve, (a) basic studies to characterize and optimize the physical mechanisms of laser interaction with the cells and BioMEMS materials, and (b) development of a fluorescence module for detection of substrates and analytes in the integrated microfluidic system. Development of the microfluidic system will involve (a) basic engineering of the MEMS microfabrication process, (b) design engineering of different chip configurations, and (c) biomaterials compatibility studies. In addition, the BioMEMS microfluidic systems will be integrated with both the microscope platform and the chemical analysis systems described below. The third specific aim involves further perfection of a unique new bioassay system through the development of new enzyme assays for activation of kinases and proteases, and the transfer of these assays to the integrated device. A multidisciplinary approach is required to accomplish the tasks involved in the development and integration of this system. The achievement of the technological objectives interfaced into one platform will provide an enabling technology with a wide variety of applications in molecular medicine and biomedical research.
| Xu, Jingsong; Van Keymeulen, Alexandra; Wakida, Nicole M et al. (2007) Polarity reveals intrinsic cell chirality. Proc Natl Acad Sci U S A 104:9296-300 |
| Wakida, Nicole M; Lee, Christopher S; Botvinick, Elliot T et al. (2007) Laser nanosurgery of single microtubules reveals location-dependent depolymerization rates. J Biomed Opt 12:024022 |
| Quinto-Su, Pedro A; Venugopalan, Vasan (2007) Mechanisms of laser cellular microsurgery. Methods Cell Biol 82:113-51 |
| Rau, Kaustubh R; Quinto-Su, Pedro A; Hellman, Amy N et al. (2006) Pulsed laser microbeam-induced cell lysis: time-resolved imaging and analysis of hydrodynamic effects. Biophys J 91:317-29 |
| Venugopalan, Vasan; Guerra 3rd, Arnold; Nahen, Kester et al. (2002) Role of laser-induced plasma formation in pulsed cellular microsurgery and micromanipulation. Phys Rev Lett 88:078103 |
