This proposal integrates the very mature CMOS processing technology for sensing electronics, with a versatile single-molecule detector, the nanopore. By employing a unique combination of digital and analog circuit techniques, feedback and close physical coupling afforded by nanofabrication, this platform will enable a new class of sensors. This unique sensor architecture, that exhibits low-noise and high-sensitivity, will enable the discovery of new physics at the nanoscale. Furthermore, by functionlization of these nanoscale detectors with molecular recognition units, such as aptamers, a new class of biosensors can be designed. This proposal also address the challenges of building ultrathin nanopore detectors, that are crucial to building an electronic DNA sequencer, by fabricating nanopores in graphene sheets.
Intellectual Merit: Traditionally biosensors concentrate mainly on the detection platform and not on signal processing. This decoupling can lead to inferior sensors and is exacerbated in nanoscale devices, where device noise is large and large dynamic range is required. This proposal outlines a novel platform that integrates the nano, micro and macroscales in a closely coupled manner that mitigates many of these problems. Specifically, this proposal integrates the superior molecular recognition properties of aptamers with the versatility of the nanopore detector to design a new class of biosenors in a CMOS compatible platform. The functionalized nanopore detector is designed to allow for unambiguous interpretation of scientific data, rather than ease of experimentation, thanks in large part to the versatility of the unique CMOS platform proposed. Since nanopore detectors measure changes in pore resistance due to the presence or absence of the target, sensitivity is function of nanopore thickness. This proposal also explores the sensitivity of the ultimate nanopore detection platform i.e atomically thin nanopore detectors based on graphene. The unique integration of electrodes and electronics afforded by the CMOS platform allows for the pore resistance to be dominant rather than the access resistance as in conventional approaches. Superior sensing and bandwidth is achieved in this proposal by using a novel bit-stream based computational approach rather than traditional sensor electronics. These techniques have the potential to greatly enhance the measured data because the digital feedback can augment and control front-end electronics without sacrificing bandwidth. This offers the potential to discover new phenomena, which are beyond the reach of conventional measurement schemes. Additionally, unique integration of the multiple physical scales involved enable the design of cheap, disposable and robust biosensors. We will evaluate our sensors on a broad range of criteria such as sensitivity, selectivity, response time and dynamic range with appropriate controls to verify each criterion.
Broader Impact: An inexpensive single-molecule DNA sequencer has tremendous impact in areas as diverse as medicine and health, both domestically and abroad. Furthermore, aptamer-encoded nanopore biosensors can be used for the early detection of disease and in mitigating biothreats and easy deployment to the third-world where it is needed most. This platform also serves as an unique opportunity for dissemination of bioengineering research to under-served populations. A Summer Course and Research Internship in BioEngineering (SCRIBE) is outlined to effectively serve the target population of community college students. Community colleges disproportionately serve under-represented minorities and represent a wealth of talent for recruitment of students into the STEM disciplines. SCRIBE will also serve as a teaching tool for the professional development of graduate students by enabling them to mentor students and develop courses and lab exercises. UCSB has the largest minority student complement of all UC campuses, largely through very active diversity programs. The senior capstone project in the ECE department is an additional area of attracting the interest of minority freshman. The concepts outlined in this proposal will serve as the source of multiple capstone projects. Attracting the interest of minority freshman in engineering programs will help with the retention issues currently faced by all engineering programs.
