Abstract

Cellular Biologic Application Specific Integrated Circuits (BASICs) [1-8] are developed for quantitative systems biology, molecular medicine, and drug discovery. Soft-state BASI Cs are created by connecting existing and novel nano- or microfluidic circuits for biological analysis in new ways. We are creating a library of these “building blocks” to develop multifunctional biological microprocessor on-a-chip. In order to build a solid foundation of future quantitative and systematic drug discovery, we have established critical modules of BASIC such as Integrated Multiple Patch-clamp Array Chip Technology (IMPACT) [1, 2], integrated dynamic cell culture and multiplexed bioreactors [3], integrated cell lysing [4], cell separation [5], single cell electroporation [6], dynamic single cell analysis [7, 8], cell-cell communication biochips [9], and artificial liver on-a-chip.

Particle biophysics will be the foundation of the systematic studies of living cells. Gold quantum nanoplasmonic particles are ideal probes for nanoscale spectroscopic molecular imaging, photothermal therapeutic, and gene regulation applications [10-13]. Nanophotonic crescents have structures with a sub-10 nm sharp edge, which can enhance local electromagnetic field at the edge area. The formation of unconventional nanophotonic crescent structure is accomplished by the interfacing both bottom-up and top-down methods, which allows an effective batch nanofabrication and precise controls of surface enhanced Raman scattering (SERS) hot spot coupling nanogap. The nanocrescent probes can be used for label-free molecular detection and understanding electron transfers of biomolecules. In this talk I will also describe our recent work on the design, synthesis and characterizations of molecular optical switches and PRET (Plasmonic Resonance Energy Transfer) nanospectroscopic imaging which might impact on the areas of nanobiology, control of gene regulation & protein expression, bioimaging, systems biology, and drug discovery.

[1] Cristian Ionescu-Zanetti, et al., “Mammalian Electrophysiology on a Microfluidic Platform,” PNAS 102 (26), 9112-9117 (2005). [2] Adrian Y. Lau, et al., “Open-access microfluidic patch-clamp array with raised lateral cell trapping sites,” Lab Chip, 6, 1510 (2006) [3] Paul Hung, et al. “A Continuous Perfusion Microfluidic Cell Culture Array for High Throughput Cell-based Assays,” Biotechnology & Bioengineering, 89, 1-8 (2005). [4] Dino Di Carlo, et al., “On-Chip Cell Lysis by Local Hydroxide Generation,” Lab on a Chip 5 (1) (2005). [5] Wesley C. Chang, et al. “Biomimetic Technique for Adhesion-based Collection and Separation of Cells in a Microfluidic Channel,” Lab on a Chip, 5 (1), 64-73 (2005). [6] Michelle Khine, et al., “A Single Cell Electroporation Chip,” Lab on a Chip, 5 (1), 38-43 (2005). [7] Dino Di Carlo et al. “Dynamic Single-Cell Analysis for Quantitative Biology,” Anal Chem, 78, 7918-7925 (2006). [8] Dino Di Carlo, Liz Y. Wu, Luke P. Lee, “Dynamic single cell culture array,” Lab Chip, 6, 1445-1449 (2006). [9] Philip J. Lee, et al. “Microfluidic Application Integrated Device for Monitoring Direct Cell-Cell Communication via Gap Junctions Between Individual Cell Pairs,” Appl. Phys. Lett. 86, 223902 (2005). [10] Yu Lu, et al. “Nanophotonic Crescent Moon Structures with Sharp Edge for Ultrasensitive Biomolecular Detections by Local Electromagnetic Field Enhancement Effect,” Nano Letters, 5(1), 119-124 (2005). [11] Gang L. Liu, et al. “Magnetic Nanocrescents as Controllable Surface Enhanced Raman Scattering Nanoprobes for Biomolecular Imaging,” Advanced Materials, 17, 2683-2688 (2005). [12] Gang Liu et al. “Optofluidic Control via Photothermal Nanoparticles,” Nature Materials 5(1), 27-32 (2006). [13] Gang Liu et al. “A nanoplasmonic molecular ruler for measuring nuclease activity and DNA footprinting,” Nature Nanotechnology, 1, 47-52 (2006).