Nanoelectromechanical resonator arrays for the analysis of biomolecular mixtures

生物分子的鉴定和分析在分子生物学的许多基础问题中是至关重要的。微机械器件已被提出作为用于快速检测和分析分子系统的高灵敏度传感器。更具体地，共振机械传感器通过监测与结合相关联的共振频率的偏移来操作。机械谐振器的每单位面积的吸附灵敏度随着其尺寸的减小而有利地缩放，为开发具有精致质量灵敏度的大阵列分子传感器提供了一条引人注目的路径。这些阵列将能够实现多重结合测定，其可以量化分子系统的复杂混合物。我们最近开发了一种制造工艺，允许实现窄至20 nm的纳米机械谐振器，产量接近100%。我们还展示了使用单个谐振器对生物分子（如蛋白质）的特异性检测。因此，该设备平台准备应用于涉及每平方厘米数百万个谐振器的多路复用测定。为此，该项目将重点关注以下四个目标：i）通过使用中等规模阵列分析DNA结合亲和力进行初步概念验证，ii）通过分析中等规模阵列上的肽-代谢物亲和力进行第二次概念验证，iii）使用纳米压印光刻实现超大阵列，iv）开发全光学自动读出系统。这个跨学科的计划将培养一批研究生在器件研究的关键领域，如硅表面加工和MEMS/NEMS技术的基础。它还将使他们接触其他重要领域，如化学和生物科学。该项目还将包括在省际合作活动方面的大量协同作用。最后，它将实现与过去五年在探索计划的支持下开发的新型纳米加工技术相关的知识产权。

Identification and analysis of biological molecules are vital in many fundamental problems in molecular biology. Micromechanical devices have been proposed as highly-sensitive transducers for the rapid detection and assaying of molecular systems. More specifically, resonant mechanical sensors operate by monitoring shifts of resonance frequencies associated to the binding. The adsorption sensitivity per unit area of mechanical resonators scales favorably as their dimensions are reduced, offering a compelling path for the development large arrays of molecular sensors with exquisite mass-sensitivities. These arrays would enable the realization of multiplexed binding assays that could quantify complex mixtures of molecular systems. We have recently developed a fabrication process allowing the realization of nanomechanical resonators as narrow as 20 nm and with a yield approaching 100%. We have also demonstrated the specific detection of biomolecules such as proteins using individual resonators. This device platform is therefore ready to be applied to multiplexed assays involving millions of resonators per square centimetre. To that end, this project will focus on the four following goals: i) Initial proof of concept through analysis of DNA binding affinity using moderately large arrays, ii) A second proof of concept through analysis of peptide-metabolite affinity on moderately large arrays, iii) Realization of ultra-large arrays using nano-imprint lithography, and iv) Development of all-optical automated read-out system. This cross-disciplinary program will train a group of graduate students in key areas of device research such as silicon surface machining and the fundamentals of MEMS/NEMS technology. It will also expose them to other important areas such as the chemical and the biological sciences. The project will also include a significant amount of synergy with respect to the inter-provincial collaborative activities. Finally, it will bring to fruition intellectual property related to the novel nanomachining technique that was developed during the last five years under support of the Discovery Program.