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Single Molecule Detection and Manipulation
Our understanding of chemistry and biology comes almost exclusively from experiments on ensembles of molecules, by which a vast number of duplicate behaviors are investigated and averaged responses are recorded. However, a lot of important information for fundamental genomic and proteomic exploration such as intermediates and time-dependent pathways of molecular interactions, are difficult to be identified by the ensemble methods. The ability to make measurements at the single molecule level provides information on time trajectories of individual objects and their conformational fluctuations that help lead to a detailed understanding of heterogeneities in a system that would otherwise be hidden.
Professor Tza-Huei Wang’s lab is interested in developing new technology platforms for analysis of single biomolecules (DNA, RNA and protein). A high-throughput single molecule tracing platform for quantification of low-concentration DNA has been developed based on confocal spectroscopy and microfluidic manipulations. Fluorescence of molecular beacon probes, emitting upon hybridization with complementary target sequences, is resolved at the single-molecule level using a confocal fluorescence spectroscope. Transport of individual molecules is precisely directed through a minute confocal detection region via electrokinetic forces on a microfluidic chip, achieving accurate and high-throughput analysis of biomolecular targets. This technique enables accurate quantification of biomolecules at low-abundant and is capable of detecting subtle changes in molecular quantities such as gene expression changes in a singe cell. Thus, this technology provides an effective platform for exploring the heterogeneities in a biological system unattainable by conventional methods.
Publications
T. H. Wang, Y. H. Peng, C. Y. Zhang, P. K. Wong, C. M. Ho, " Single-molecule tracing on a fluidic microchip for quantitative detection of low-abundance nucleic acids," Journal of the American Chemical Society 127 (15): 5354-5359 2005
H. C. Yeh, S. Y. Chao, Y. P. Ho, T. H. Wang," Single-Molecule Detection and Probe Strategies for Rapid and Ultrasensitive Genomic Detection," Current Pharmaceutical Biotechnology 6(6):453-461, 2005
C. Y. Zhang, S. Y. Chao., T. H. Wang, " Comparative quantification of nucleic acids using single-molecule detection and molecular beacons," Analyst 130 (4): 483-488 2005