Biomolecular Motor Smart Microarrays: Self-Contained, High-Throughput, Ultrasensitive Multiplexed Biomolecular Sensing

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AbstractBiomolecular Motor Smart Microarrays: Self-Contained, High-Throughput, Ultrasensitive Multiplexed Biomolecular SensingPI: Katsuo KurabayashiCo-PIs: Pei-Cheng Ku, Edgar MeyhoferIn recent years, biomolecular motors (BMMs) ? highly efficient molecular machines that nature has evolved for over millions of years ? have been employed in miniaturized analysis systems and play important roles in bionanotechnology applications, such as biosensing, molecular sorting, fluidic pumping, micromechanical powering, and molecular assembly. They are compact with a nanometer size, yield robust movement in a fluidic environment, and are readily fueled by adenosine triphosphate (ATP) containing solution. This eliminates the need for an external energy source for micro/nanofluidic actuation. In addition, BMMs efficiently manipulate individual biological molecules and proteins, making possible the development of a motor protein-based biosensing system with a nanoscale mass transport/concentration function. This NSF award by Biosensing/CBET program supports research by Professors Kurabayashi, Ku, and Meyhofer at the University of Michigan on the development of a new biosensing chip technology, namely the biomolecular motor (BMM) smart microarrays, which allows high-throughput, ultrasensitive (at attomolar concentrations) biosensing for multiplexed on-chip protein binding assays. Incorporating a BMM-based mass transport/sensing mechanism in a microfluidic system, the BMM smart microarrays enable autonomous sample handling that involves specific binding, sorting, transporting, and concentrating of multiple target analytes via kinesin motor protein-driven microtubules. The proposed method combines biomolecular motors, photonics and nanofluidics in a single biosensor to simultaneously transport and concentrate large numbers (10) of molecular analytes to specific detectors for ultra-sensitive quantification.The proposed effort will have broader impact on clinical applications such as stratified medicine and personalized medicine through developing a high-throughput ultra-sensitive multiplexed biomolecular sensing method. The aimed multiplexed biosensing technology will allow for monitoring of the early-stage subtle onset of diseases and early warning of biological threats. The proposed fundamental studies towards combining bionanotechnology and LED-based solid state lighting technology for ultrasensitive multiplexed protein sensing can ultimately be extended to enable the early detection of diseases with a very simple and robust battery-operated handheld module setting. This may open the door for the development of a new commercial product for point-of-care applications under an environment of limited resources. The fundamental knowledge gained from this research will be assimilated the PIs? graduate courses on nanobiomechanics, MEMS, and photoelectronic device technology. In this project, the involved graduate and undergraduate students will be trained to obtain integrated knowledge and skills in MEMS technology, micro/nano manufacturing, biophysics, biochemistry, and photonics, in collaboration with researchers across several fields. The students? communication and networking skills will grow through their presentations at national/international MEMS and Nanotechnology conferences, and research will be incorporated in the PIs? interdisciplinary graduate courses in MEMS and Nanomanufacturing. Summer interns from underrepresented groups will be actively recruited to this project through the National Nanotechnology Infrastructure Network (NNIN) Research Experience for Undergraduates Program (REU) supported by the NSF. This research represents transformative potential because it (1) presents the first technique that demonstrates the use of BMM-based nanoscale mass transport and biosensing for multiplexed biosensing; and (2) provides a new approach to realizing robust, cost-effective, simple point-of-care clinical diagnostics with advanced scientific knowledge on controlling BMMs within a man-made engineering structure and on obtaining weak biofluorescent signals at a high signal-to-noise ratio for low-concentration samples.