Cells are fundamental building blocks of life. The ability to manipulate single cells individually in a liquid environment with high precision will enable many fundamental biological studies on cell-to-cell and cell-to-environment interactions that could not be achieved before. Such discoveries will provide key insights into the effect of the environment on cellular structure, function, and signaling, and would have wide applications across multiple disciplines in life sciences, agriculture and medicine. Due to their small size and also soft nature, it is extremely difficult to handle single cells with a physical device, such as mechanical tweezers, without causing damage to the delicate subcellular structures. Alternatively, focused electrical fields, laser beams, and ultrasound waves can be utilized to generate microscale forces at the focal point, serving as virtual tweezers for single cell manipulation. Among them, the 'acoustic tweezers' are the most compatible with the cells due to cell's higher tolerance of sound pressure over electrical field and laser illumination. However, unlike the laser beams that can be easily focused and steered with a glass lens and a rotating mirror, agile focusing and steering of ultrasound waves requires complex and expensive transducer arrays and control electronics. This situation has prevented the wide use of 'acoustic tweezers' in single cell manipulation. The proposed work is to develop an acoustic phased array to enable acoustic steering and focusing of ultrasound beams for their applications in high-resolution acoustic manipulation of single cells.

Among all existing single cell manipulation techniques, the ultrasound phased array has the greatest potential due to its unique ability to achieve electronic beam forming (without physically scanning the transducer(s)). Using this unique beam forming technique to focus ultrasonic radiation at precise locations presents unprecedented manipulation capabilities compared with other methods. However, in current ultrasound phased array systems, multiple channels of ultrasound signals are first converted into electronic ones with an array of transducer elements. The phase shift is then accomplished in the electronic domain. As the operation frequency and the number of the channels increases, the phased array system becomes increasingly complex, bulky, power-consuming and costly. Therefore, current acoustic phased arrays are not suitable for on-chip microfluidic platforms for single cell manipulation. To address this issue, this research aims to develop a new micromachined ultrasound phased array. It will consist of an array of micromachined silicon acoustic delay lines with tunable delay lengths to create the desired phase shift for multiple ultrasound signals without the need for electronic conversion. This enables ultrasound beam forming with a single-element transducer and a single-channel ultrasound transceiver. With advanced micromachining processes, it can be readily fabricated and even integrated together with microfluidic components onto the same substrate for single-chip operation. To achieve the research objective, the following three research tasks will be accomplished: 1) Conduct acoustic and electromechanical design and optimization of the acoustic phase shifter; 2) Develop an on-chip microfabrication process to achieve multi-channel integration; and 3) Demonstrate dexterous acoustic manipulation and positioning of single cells using the ultrasound phased array. This multidisciplinary research is expected to provide unique learning and training opportunities for both graduate/undergraduate students. Students in grades 7-12 will be involved through Engineering Summer Camps and Open House activities. Research results will be incorporated into the PI's course development at all levels. They will also be disseminated through publications, outreach activities, invited talks, and a project website.

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.

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Duke University
United States
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