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

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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.