Nanoelectromechanical resonator arrays for the analysis of biomolecular mixtures

在分子生物学的许多基本问题中，生物分子的鉴定和分析是至关重要的。微机械器件已被认为是用于分子体系快速检测和分析的高灵敏度传感器。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移位来工作。随着尺寸的减小，机械谐振器的单位面积吸附灵敏度具有良好的伸缩性，这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一条引人注目的途径。这些阵列将使多重结合分析得以实现，从而可以对复杂的分子体系混合物进行定量。我们最近开发了一种制造工艺，可以实现窄至20 nm的纳米机械谐振器，成品率接近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用于每平方厘米数百万个谐振器的多路分析。为此，该项目将侧重于以下四个目标：i)通过分析中等大阵列的DNA结合亲和力来初步验证概念，ii)通过分析中等大阵列上的多肽-代谢物亲和力来再次证明概念，iii)利用纳米压印光刻实现超大阵列，以及iv)开发全光学自动读出系统。这个跨学科的项目将培养一批设备研究的关键领域的研究生，如硅表面加工和MEMS/NEMS技术的基础。它还将使他们接触到其他重要领域，如化学和生物科学。该项目还将包括省际协作活动方面的大量协同作用。最后，它将实现与过去五年在发现计划支持下开发的新型纳米机械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.