2010-08-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/678427摘要：以感測懸臂梁力學行為為主的生物微感測器因擁有高靈敏性、不需任何標定物、成本低廉、容易透過標準微機電製程批量生產等特性，近年來越來越受到重視。相對於微懸臂梁生物感測器在製程或應用的快速進展，我們對其基礎連結生物感測的解析與預測模擬能力卻相當匱乏。透過此前瞻與創新性研究計畫，我們希望能探索與擴展此新興領域，發展多尺度動力理論與生物分子在溶液及pH環境的原子尺度模擬，適當耦合微觀的生物分子吸附機制與巨觀力學行為，探討微懸臂梁生物感測器在化學-生物-力學交互作用下之熱力學與動力行為。 本研究在分子尺度吸附分析將探索peptide 於水溶液的吸附特性。我們將擴展本研究團隊發展高效能分子動力軟體，並採用implicit solvent model理論(AGBNP) 模擬溶液環境。其能量計算包含靜電(Generalized Born)及非極性(non-polar)的貢獻，並延伸implicit solvent model理論模擬const-pH溶液環境。本研究也將透過 constrained kinematics and dynamics的基本架構，發展創新的多尺度理論，耦合微觀的生物分子吸附機制與巨觀力學行為。最後將在本研究團隊新成立之分子力學與物理實驗室進行關鍵實驗，驗證及比較本研究所發展出的多尺度理論與模擬特定peptide吸附於懸臂梁微感測器之力學行為。 <br> Abstract: Microcantilever-based biosensors are rapidly becoming an enabling sensing technology for a variety of label-free biological applications due to their extreme applicability, versatility and low cost. It is thus imperative for us to reveal the physical origin of adsorption-induced deformation, and to further analyze its implication of microscopic mechanisms on macroscopic deformation. The objective of this project is therefore to investigate theory and multiscale modeling to revealing physical origin of surface stresses induced by interaction or adsorption of biomolecules. Peptides with their high potential impact on drug design will be the focus of this study. For the theory and simulation to be relevant to biosensing, two major challenges need to be overcome: one is to bridge atomic and continuum scales and the other is to model solvent environment atomistically. Concerning the first challenge, novel multiscale theory will be derived based on constrained kinematics and dynamics framework. It will help to shed insight on how biomolecular interactions and environments contribute to mechanical behavior of microcantilever. To address the second challenge, non-polar and constant-pH molecular dynamics simulations will be developed to understand microscopic chemo-bio-mechanical interaction of peptides in solvent. Implicit solvent methodologies which play an increasingly important role in molecular modeling of biomolecular structure will be used and implemented into our in-house high-performance molecular dynamics program. Finally, limited but critical experiments will be performed in our M-Lab (molecule enabling mechanics and physics laboratory, established in 2009) to validate the theory and models developed herein.化學-生物-力學交互作用生物微懸臂梁感測器表面吸附溶液多尺度模擬Chemo-bio-mechanical interactionMicrocantilever biosensorMultiscale analysisSolventAdsorption