Design of micro/nanocantilevers with adsorbed biomacromolecules using molecular modelling

随着世界范围内生物战威胁的增加和各种高度传染性疾病的爆发，发展战略和设备来检测和控制这些生物因素和疾病的传播至关重要。 为此，能够识别生物元件和病毒载体的存在变得非常期望。 最近，几个研究小组已经表明，使用表面修饰的微杠杆，一些疾病相关的DNA（例如，前列腺癌）可以被检测到。 这是因为当靶DNA结合到微悬臂表面上时，微悬臂将弯曲。 最期望的是进一步发展检测高传染性/危险性病毒或其他生物物质所具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征，因此将该技术扩展到检测靶病毒蛋白质分子是具有挑战性的。 所涉及的关键技术问题是选择和固定的蛋白质分子，将作为探针分子，测量的能力，在微小的浓度和检测时间的目标分子。 除非解决上述技术问题，否则构建这种商业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基本的了解。 这是本研究的主要目的。 拟议的研究计划将侧重于开发分子建模策略，基于分子动力学模拟和/或密度泛函理论计算，以研究微/纳米机械悬臂梁表面上的DNA/蛋白质分子的杂交。 如果我们成功了，我们设想，结果可以用来指导选择探针分子的杂交过程和设计的原型手持生物传感器的地面士兵和国土安全应用。

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.