Development of a Miniaturized Electromechanical Biosensing Platform

该项目的目标是开发一种小型化、低成本、高通量的生物传感技术，可以在医学诊断和生物医学研究中广泛应用。美国的医疗保健支出非常高，而且还在不断增长，这使得不断膨胀的医疗保健成本成为美国面临的一个重大挑战。可负担得起的和无处不在的筛查技术使频繁检测早期诊断疾病成为减少保健费用的有效预防方法。这项提议的努力可以为低成本传感器铺平道路，这些传感器具有简单而快速的传感程序，可用于家庭监测常规身体功能/参数，以及更复杂疾病的即时诊断。此外，在学术环境中进行这样的研究还有一个额外的优势，那就是可以培养出一些高技能的工程师，这些工程师可以在他们的职业生涯中对行业做出重大贡献。在目前高科技的美国经济中，微、纳米和生物医学科学与工程方面的专业知识需求量很大。两名全日制博士生和最多三名本科生研究人员将接受教育，并参与拟议的研究和发展活动。为了促进多样性，将努力从代表性不足的群体和少数群体中招收高素质的学生参加活动。该项目还将通过为课程、实验室参观和演示提供有价值的新知识和有趣的材料，使研究人员能够丰富和活跃他们正在进行的微/纳米技术教育和推广计划。所提出的生物传感平台利用微纳米级机电谐振器作为高灵敏度的质量传感器，能够检测和测量单分子层在其表面上的吸附。在过去的二十年中，微/纳米级机电谐振器技术取得了重大进展，主要是由频率参考和滤波元件等器件在电子领域的应用所驱动的。由于尺寸在低到亚微米范围内，这种器件的质量灵敏度可以在微尺度的皮克到飞克范围内，而在纳米尺度的谐振器中，质量灵敏度可以低到阿托克或更低。这比传统的石英晶体微天平（QCM）好几个数量级。高分辨率的生物分子传感器可以通过在这些器件的表面覆盖一层选择性分子识别元件（MRE）的自组装单层来实现。然而，尽管具有巨大的潜力，微/纳米机械谐振器在生物传感应用中的应用仍然几乎不存在。这主要是由于在与液体介质接触时操作此类设备的主要瓶颈，几乎所有生物传感活动都发生在液体介质中。由于谐振腔的尺寸小，因此其表面积体积比大，当浸入液体中时，其质量因子Q显著下降，直至谐振响应完全消失。在该项目下，将开展全面的多方面努力，进一步提高MEMS谐振器与生物解决方案接触的性能，并解决开发通用生物传感器阵列技术的一些相关挑战，该技术可应用于各种传感应用。提出了一种新型的微机械结构，该结构是由压电谐振器制作在薄膜上，其背面有一个反应腔，在反应腔中分子与薄膜发生键合。该膜将谐振器及其操作所需的电信号与生物样品隔离开来，以便在与液体接触时实现器件的最佳性能。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The objective of this project is to develop a miniaturized, low cost, and high throughput biosensing technology that can be applied to a wide range of applications in medical diagnosis and biomedical research. U.S. health care spending is dramatically high and growing, making the ballooning cost of healthcare a major challenge for the nation. Affordable and ubiquitous screening technologies allowing frequent testing for early diagnosis of diseases are effective preventive methods to reduce health care cost. The proposed effort can pave the way towards low-cost sensors with simple and rapid sensing procedures for home based monitoring of regular bodily functions/parameters, and point-of-care diagnosis of more complex disorders. Furthermore, performing such research in an academic environment has the added advantage of training a few highly skilled engineers that can have significant contributions to the industry over the course of their career. Expertise in micro, nano and biomedical science and engineering is in high demand in the current high-tech US economy. Two full-time PhD students and up to three undergraduate researchers will be educated and involved in the proposed research and development activities. To promote diversity, efforts will be devoted to recruitment of highly qualified students from under-represented and minority groups to be involved in the activities. This project will also allow the investigators to enrich and invigorate their ongoing micro/nanotechnology educational and outreach programs by producing valuable new knowledge and interesting material for courses, lab tours, and demos.The proposed biosensing platform utilizes micro to nanoscale electromechanical resonators as highly sensitive mass sensors capable of detecting and measuring adsorption of fractions of single molecular layers onto their surfaces. There have been significant advances in micro/nanoscale electromechanical resonator technologies over the past two decades, mainly driven by applications of such devices as frequency references and filtering elements in electronics. With dimensions in the lower to submicron range, such devices can have mass sensitivities in the pico-gram to femto-gram range for microscale, and down to atto-grams and below for nanoscale resonators. This is several orders of magnitude better than that of conventional quartz crystal microbalances (QCM). High-resolution biomolecular sensors can be realized by covering the surface of such devices with a self-assembled monolayer of a selective molecular recognition element (MRE). However, despite their tremendous potential, utilization of Micro/Nano-mechanical resonators in biosensing applications remains almost non-existent. This is mainly due to the major bottleneck of operating such devices in contact with liquid media, where almost all biosensing activity takes place. Due to their small dimensions and consequently large surface area to volume ratio, the quality factor (Q) of such resonators drops significantly when immersed in liquid to the point that their resonance response completely disappears. Under this project, a comprehensive multi-faceted effort will be launched to further enhance MEMS resonator performances in contact with biological solutions and address some of the associated challenges for development of a general purpose biosensor array technology that can be applied to a wide variety of sensing applications. A new micromechanical structure is proposed, comprising of a piezoelectric resonator fabricated on a thin membrane with a backside reaction cavity where the molecular bonding to the membrane occurs. The membrane isolates the resonator and electrical signals required for its operation from the biological sample in order to achieve optimal performance for the device in contact with liquid.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.