CAREER: 2D Nanoelectronic Devices Integrated with Nanofluidic Structures for Biosensing Applications

职业：与纳米流体结构集成的二维纳米电子器件用于生物传感应用

• 批准号: 1452916
• 负责人: Xiaogan Liang
• 金额: $ 50万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-03-01 至 2021-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1452916&HistoricalAwards=false
• 关键词: CAREER; 2D; Nanoelectronic; Devices; Integrated

The ability to detect and quantify low-abundance biomolecules is critical for clinical diagnostics and drug development. For example, such ability can be used for early-stage cancer diagnosis. Surface plasmon resonance is the standard method for such analysis, but it still suffers from drawbacks such as low sensitivity, poor detection limit, and slow analysis process. These limitations motivate the efforts to create new nanoscale electronic biosensors for realizing efficient, label-free, multiplexing biomolecule quantification at low detection limits. The work described in this proposal aims at constructing a new biosensor by integrating emerging two-dimensional (2D) nanoelectronic materials into nano/microfluidic structures. Such a 2D-material-integrated nanofluidic biosensor, if successfully realized, will greatly advance the capability for illness-related biomarker detection and quantification. The work proposed here holds significant potential for realizing new cost/time-effective immunoassay chips that can address global needs for new capabilities for diagnosis and stratification of diseases and US industrial competitiveness. Beyond advancing fundamental academic research capabilities, the proposed education/research-integrated program will provide relevant knowledge and technical skills to a broad range of people, including K-12 students/educators, undergraduates, graduates, as well as students from underrepresented and minority groups. Specifically, the proposed education/outreach program will include a new after-school program for instructing K-12 students to learn basic knowledge related to microfluidic/electronic-integrated biosensors; extending the collaboration with academic programs at the University of Michigan to provide research opportunities for undergraduates; introducing new topics related to nanofluidics and nanoelectronics into graduate/undergraduate courses.The proposed device-oriented research seeks to leverage superior electronic/structural properties of 2D materials and unique electrokinetics in nanofluidic devices for enabling low-abundance biomolecule detection at single-molecule levels. To realize this goal, the PI will overcome a series of challenges related to nanoelectronics, nanofluidics, and biosensing. Specifically, (i) create a nanofabrication method capable of integrating nano/microfluidic structures with nanoscale 2D transistors and producing large device arrays, therefore enabling the device miniaturization and multiplexing capability required for the envisaged bio-assays. (ii) Create a biofunctionalization route for realizing the selective functionalization of nanoelectronic sensors and an electrokinetic approach for efficiently transporting/concentrating target molecules toward the sensing areas, which are critical for preventing non-specific adsorption and obtaining a low limit-of-detection required for low-abundance molecule quantification. Non-specific adsorption will be further suppressed through using specific blocking buffers and optimizing nanofluidic architectures. (iii) Obtain a comprehensive understanding of the complex interactions between nanoelectronic and nanofluidic characteristics of the proposed device, which include electrokinetic transport rates of biomolecules toward sensors, effects of nanofluidic environments on biomolecule concentration distributions, dynamic behaviors of transistor parameters in response to bioconjugation processes, and relationship between the dissociation constant of an analyte-receptor pair and the sensor's detection limit/specificity. (iv) Develop multiplexed device arrays capable of rapidly determining multiple biomolecule concentrations. The proposed biosensor, if successfully created, can firstly serve as a generic device platform for analyzing a broad range of molecular interactions. Especially, it can be used for measuring the affinities and kinetics of various analyte-receptor pair interactions with sensitivities down to femtomolar concentrations (or single-molecule-level detection limits). Such knowledge will greatly advance the understanding of complex cellular events, such as the development of cancers and immune-responses. The large arrays of the proposed biosensors would eventually allow for rapid (minute-scale sample-to-result elapsed times), highly precise (single-molecule-level detection limits) immunoassay for clinical diagnostics. The detection principle of the proposed biosensor is completely electrical and does not need any off-chip optics required for conventional fluorescence-based assays. This will enable stand-alone device capability required for point-of-care applications.

检测和量化低丰度生物分子的能力对于临床诊断和药物开发至关重要。例如，这种能力可用于早期癌症诊断。表面等离子体共振是进行此类分析的标准方法，但它仍然存在诸如低灵敏度，检测极限和缓慢分析过程之类的缺点。这些局限性促使努力创建新的纳米级电子生物传感器，以实现在低检测限制下有效，无标签，多重多重分子定量。该提案中描述的工作旨在通过将出现的二维（2D）纳米电源材料整合到纳米/微流体结构中来构建新的生物传感器。如果成功实现的话，这种2D材料综合的纳米流体生物传感器将大大提高与疾病相关的生物标志物检测和定量的能力。此处提出的工作具有实现新的成本/时间效率的免疫测定芯片的巨大潜力，这些芯片可以解决全球对疾病诊断和分层新功能和美国工业竞争力的新能力需求。除了提高基本学术研究能力外，拟议的教育/研究综合计划还将为包括K-12学生/教育工作者，本科生，毕业生以及来自代表性不足和少数群体的学生提供相关的知识和技术技能。具体而言，拟议的教育/外展计划将包括一项新的课后计划，用于指导K-12学生学习与微流体/电子集成生物传感器有关的基本知识；扩展与密歇根大学学术课程的合作，为大学生提供研究机会；将与纳米流体和纳米电子学有关的新主题引入研究生/本科课程中。拟议的面向设备的研究旨在利用2D材料的卓越电子/结构性能和纳米富集设备中独特的电动电机的卓越电子/结构特性，以使低金额生物蛋白质的单核酸杆菌降低。为了实现这一目标，PI将克服与纳米电子，纳米流体和生物传感有关的一系列挑战。具体而言，（i）创建一种能够将纳米/微流体结构与纳米级2D晶体管整合并产生大型设备阵列的纳米化方法，因此可以使设备的小型化和所设想的生物测定所需的多发性能力进行多发性多样化。 （ii）创建一种生物官能化途径，以实现纳米电信传感器的选择性功能化和一种电动方法，用于有效地将/浓缩靶分子传输到传感区域，这对于预防非特异性吸附和获得低位量的低限量的潜在至关重要。通过使用特定的阻止缓冲液和优化纳米流体体系结构，将进一步抑制非特异性的吸附。 （iii）获得对拟议装置的纳米电信和纳米荧光特征之间复杂相互作用的全面理解，其中包括生物分子对传感器的电动传输速率，纳米流通环境的影响，生物分子浓度分布的影响，对生物分布的动力学对生物分布的动态行为，以及跨性别的参数范围的动态行为。分析物受体对和传感器的检测极限/特异性。 （iv）开发能够快速确定多个生物分子浓度的多路复用装置阵列。提出的生物传感器（如果成功创建）可以首先用作分析各种分子相互作用的通用设备平台。尤其是，它可用于测量各种分析物受体对相互作用的亲和力和动力学，其灵敏度一直降低到feytoloral浓度（或单分子级检测极限）。这种知识将大大提高人们对复杂细胞事件的理解，例如癌症和免疫反应的发展。所提出的生物传感器的大型阵列最终将允许快速（经过的微小尺度样品到量度），高度精确（单分子级检测限）用于临床诊断。所提出的生物传感器的检测原理是完全电气的，并且不需要基于常规荧光的测定所需的任何外芯片光学元件。这将实现“ Pare Point Point”应用所需的独立设备功能。