Nanoelectromechanical resonator arrays for the analysis of biomolecular mixtures

在分子生物学的许多基础问题中，生物分子的鉴定和分析是至关重要的。微机械装置已被提出作为高灵敏度的传感器，用于快速检测和分析分子系统。更具体地说，共振机械传感器通过监测与结合相关的共振频率的变化来工作。机械谐振器单位面积的吸附灵敏度随着其尺寸的减小而减小，为开发具有精致质量灵敏度的大型分子传感器阵列提供了令人信服的途径。这些阵列将实现多重结合分析，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，可以实现窄至20纳米的纳米机械谐振器，收率接近100%。我们还演示了使用单个谐振器对生物分子（如蛋白质）的特定检测。因此，该设备平台已准备好应用于涉及每平方厘米数百万个谐振器的多路分析。为此，该项目将重点关注以下四个目标：i)通过使用中等大小的阵列分析DNA结合亲和力来初步证明概念，ii)通过使用中等大小的阵列分析肽代谢物亲和力来进行第二次概念证明，iii)使用纳米压印光刻实现超大阵列，iv)开发全光自动读出系统。该跨学科项目将培养一批器件研究关键领域的研究生，如硅表面加工和MEMS/NEMS技术基础。它还将使他们接触其他重要领域，如化学和生物科学。该项目还将包括与省际合作活动有关的大量协同作用。最后，它将带来与过去五年在发现计划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.