Microfluidic Cell Sorting and Manipulation Based on Bulk Acoustic Waves

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An award is made to University of Southern California (USC) to advance the transducer technology based on focused bulk acoustic waves for cell sorting and manipulation in microfluidic systems. Specifically targeted biological applications will be on cell sorting based on cell’s size or mechanical stiffness, microinjection of genes into living cells, and selective collection of cell-containing droplets in a microfluidic channel. As the transducers are based on bulk acoustic waves, the technology offers tweezing live cells without force limitation, heat, or requirement of transparent media. Moreover, since the transducer focuses acoustic energy only on a very small spot and is capable of delivering acoustic energy through an intermediate solid, it can be applied to various microfluidic platforms for management of cells, liquids, particles and proteins. The transducer’s electrical controllability on the location/direction of the trapping force, combined with amenability of the transducers being formed into an array, allows the creation of complex biochemical assays and/or biomedical treatments at high throughput. Thus, the transducer’s unprecedented capability of capture and on-demand manipulation of living cells and/or particles (tens - hundreds of microns in diameter) in three dimensional (3D) space will open up many new possibilities in cell study, gene transfection, juxtaposition and manipulation. Sets of the transducers and power amplifiers will be delivered to four selected biological labs during the years 2 and 3 of the research period so that the labs may use them for sorting, gene delivery or any other biological experiments in their labs. The results of the research will be incorporated into the second edition of the principal investigator’s textbook on microelectromechanical systems (MEMS), entitled “Fundamentals of MEMS,” as well as in the MEMS curriculum at USC. Outreach activities will include research experience for undergraduate and high school students who will be excited with the experiments involving cells and microparticles. Also, students from underrepresented groups will be actively recruited for the proposed research.The transducers will be based on Multi-foci Fresnel Transducer (MFT) capable of capturing and moving microparticles in 3D space on demand. Specifically targeted biological applications of the capture and move will include gene microinjection (through sonoporation) and lipid-mediated gene delivery. Also developed will be MFT-based cell sorting in microfluidic channels as well as formation and collection of cell-containing droplets in a microfluidic channel. An advanced version of MFT having two overlapping circular electrodes has been shown to make the ultrasonic waves arrive at a narrow region along the vertical axis with constructive wave interference to create a narrow Bessel-beam-like focal zone with long depth-of-focus. This process also produces bottle beams and quasi-Airy beams where radiation force toward the inner region exists and thus, multiple particles can be trapped. This advanced version along with various other versions of MFT will be developed, optimized and tested for the specific biological instrumentations. Electrical controllability of the tweezing location in 3D space will be developed so that the captured cells may be: (1) moved from one location to another, (2) stretched or compressed, (3) brought into contact with other cells or gene-containing liposomes, all upon electrical command signal without having to move the transducers.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.