Design of micro/nanocantilevers with adsorbed biomacromolecules using molecular modelling

随着世界范围内生物战的威胁越来越大，各种高传染性疾病的爆发，制定战略和设备以检测和控制这些生物因素和疾病的传播至关重要。为此，能够识别生物元素和病毒携带者的存在变得非常可取。最近，几个研究小组已经表明，使用表面修饰的微悬臂，可以检测到一些与疾病相关的DNA(例如前列腺癌)。这是因为一旦目标DNA结合到微悬臂梁表面，微悬臂梁就会弯曲。最可取的是进一步发展检测由高传染性/危险病毒或其他生物物质所拥有的各种蛋白质分子的技术。由于DNA和蛋白质分子具有不同的特性，因此将该技术扩展到检测目标病毒蛋白质分子具有挑战性。涉及的关键技术问题是作为探针分子的蛋白质分子的选择和固定、在微小浓度下测量目标分子的能力和检测时间。除非上述技术问题得到解决，否则构建这样的商业化生物传感器是不可行的。为了做到这一点，需要对探测原理所涉及的物理学有一个基本的了解。这也是本研究的主旨。拟议的研究计划将专注于开发基于分子动力学模拟和/或密度泛函理论计算的分子模拟策略，以研究DNA/蛋白质分子在微/纳米机械悬臂表面的杂交。如果我们成功，我们可以预见，结果可以用来指导杂交过程中探针分子的选择，以及用于地面士兵和国土安全应用的手持生物传感器原型的设计。

With the increasing threat of biological warfare worldwide and the outbreak of various highly contagious diseases, the development of strategies and equipment to detect and control the spread of these biological elements and diseases is of vital importance. To this end, being able to identify the existence of biological elements and virus carriers becomes highly desirable. Recently, several research groups have shown that, using surface modified micro-cantilevers, a few disease-related DNAs (e.g., prostate cancer) can be detected. This is because upon binding of the target DNA onto the micro-cantilever surface, the micro-cantilever would bend. It would be most desirable to further the technique to detect various protein molecules possessed by highly contagious/dangerous viruses or other biological substances. The extension of the technique to detect target viral protein molecules is challenging since DNA and protein molecules possess different characteristics. Key technical issues involved are the selection and immobilization of protein molecules that would function as probe molecules, the ability to measure the target molecules at minute concentrations and the detection time. Unless the above technical issues are resolved, construction of such a commercial biosensor is not feasible. In order to do so, a fundamental understanding of the physics involved in the detection principle is required. And this is the major thrust of the proposed research. The proposed research program will focus on developing molecular modelling strategies, based on molecular dynamics simulation and/or density functional theory calculation, to investigate hybridization of the DNA/protein molecules on micro/nano-mechanical cantilever surfaces. If we succeed, we envision that the results could be used to guide the selection of probe molecules for the hybridization process and the design of a prototype of hand-held biosensor for ground solider and homeland security applications.