Development of a Miniaturized Electromechanical Biosensing Platform

本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，可广泛应用于医疗诊断和生物医学研究。 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。 负担得起的和无处不在的筛查技术，允许频繁的测试，早期诊断疾病是有效的预防方法，以减少医疗保健成本。 所提出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和快速的感测程序，用于基于家庭的常规身体功能/参数的监测，以及更复杂疾病的即时诊断。 此外，在学术环境中进行此类研究具有额外的优势，可以培养一些高技能的工程师，这些工程师可以在其职业生涯中为行业做出重大贡献。 微，纳米和生物医学科学和工程方面的专业知识在当前的高科技美国经济中需求量很大。 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开发活动。 为了促进多样性，将努力从代表性不足和少数群体中招募高素质的学生参加活动。 该项目还将使研究人员丰富和振兴他们正在进行的微/纳米技术教育和推广计划，通过生产有价值的新知识和有趣的材料的课程，实验室图尔斯，和demose.The拟议的生物传感平台利用微纳米机电谐振器作为高灵敏度的质量传感器，能够检测和测量吸附到其表面上的单分子层的分数。 在过去的二十年中，微/纳米机电谐振器技术已经取得了显著的进步，主要是由诸如频率参考和滤波元件等器件在电子学中的应用所驱动的。 由于尺寸在较低至亚微米范围内，这种装置对于微米尺度可以具有在皮克至毫微微克范围内的质量灵敏度，并且对于纳米级谐振器可以具有低至阿托克和更低的质量灵敏度。 这是几个数量级优于传统的石英晶体微量天平（QCM）。 高分辨率的生物分子传感器可以通过用选择性分子识别元件（MRE）的自组装单层覆盖这种装置的表面来实现。 然而，尽管其巨大的潜力，利用微/纳米机械谐振器在生物传感应用仍然几乎不存在。 这主要是由于操作与液体介质接触的这种装置的主要瓶颈，几乎所有的生物传感活动都发生在液体介质中。 由于它们的小尺寸和因此大的表面积与体积比，当浸入液体中时，这种谐振器的品质因数（Q）显著下降到它们的谐振响应完全消失的点。 在该项目下，将开展一项全面的多方面工作，以进一步提高MEMS谐振器与生物溶液接触的性能，并解决开发可应用于各种传感应用的通用生物传感器阵列技术的一些相关挑战。 提出了一种新的微机械结构，包括一个压电谐振器上制作的薄膜与背面的反应腔的分子键合发生的膜。 该膜将谐振器和其操作所需的电信号与生物样品隔离，以使设备在与液体接触时实现最佳性能。该奖项反映了NSF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.