The lack of a single-cell manipulation technique that can simultaneously achieve high throughput, high precision, and high cell integrity is a major roadblock for studies of intercellular communication. Recently, our interdisciplinary team has developed a surface acoustic wave (SAW)-based microfluidic platform called "acoustic tweezers" that possesses significant advantages over existing cell-manipulation techniques for single-cell analysis. Our acoustic tweezers platform is able to modulate the distances between individual cells with sub-micron precision. In addition, it is highly scalable and capable of creating a large array of celluar arrangements for high-throughput studies. Cells do not need to be labelled and can be cultured in their native media. Furthermore, the acoustic power and frequency used to manipulate cells are in the same range as those used in ultrasonic imaging, which has proven to be highly biocompatible. Finally, the components required for SAW generation are small and inexpensive, and the device itself is easy to operate. With these advantages, the acoustic tweezers are groundbreaking in their ability to provide precise spatiotemporal control of intracellular communication at the single-cell level in a high-throughput manner while preserving cell integrity. The transformative potential of acoustic tweezers has already been demonstrated in studies on gap junction-mediated functional intercellular communication in several homotypic and heterotypic cell populations by visualizing the transfer of fluorescent dyes between cells. Our objective in this project is to conduct advanced development of acoustic tweezers and validate them in studies on the effects of intercellular communication on metabolic pathways within the cell. We will, therefore, pursue the following specific aims: (1) advanced development of acoustic tweezers for high-yield, high-throughput characterization of intercellular communication and purinosome assembly at the single-cell level;(2) multi-parametric investigation of purinosome assembly in a primary cell model using acoustic tweezers;and (3) single-cell analyses of purinosome assembly and purine metabolism in a neuronal model using acoustic tweezers. At the completion of the proposed project, we hope to uncover the mechanism for how a genotype affects complex phenotype using Lesch-Nyhan disease (LND) as the disease model and purinosome as an indicator of metabolic state. Due to its unique ability to create multicellular assemblies with prescribed architectures in high throughput, we expect that the acoustic tweezers will become an invaluable tool for single-cell analysis and will fulfill many unmet needs in the bioengineering, biomedical, and pharmaceutical research communities.

Public Health Relevance

The proposed project is to develop a device called acoustic tweezers that can precisely control cell-cell interactions at the single-cell level and can study many individual cells and cell pairs at once without damaging them. The project will also validate the acoustic tweezers by studying the effects of intercellular communication on metabolic pathways within certain cells. The acoustic tweezers proposed in this project will address many unmet research needs and can have wide application across multiple disciplines, including immunology, infectious diseases, cancer biology, neuroscience, and developmental biology.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Exploratory/Developmental Grants Phase II (R33)
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Special Emphasis Panel (ZRG1-BST-A (50))
Program Officer
Conroy, Richard
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Pennsylvania State University
Engineering (All Types)
Schools of Engineering
University Park
United States
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Mao, Zhangming; Xie, Yuliang; Guo, Feng et al. (2016) Experimental and numerical studies on standing surface acoustic wave microfluidics. Lab Chip 16:515-24
Chen, Kejie; Wu, Mengxi; Guo, Feng et al. (2016) Rapid formation of size-controllable multicellular spheroids via 3D acoustic tweezers. Lab Chip 16:2636-43
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Guo, Feng; Mao, Zhangming; Chen, Yuchao et al. (2016) Three-dimensional manipulation of single cells using surface acoustic waves. Proc Natl Acad Sci U S A 113:1522-7
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Ren, Liqiang; Chen, Yuchao; Li, Peng et al. (2015) A high-throughput acoustic cell sorter. Lab Chip 15:3870-9
Li, Peng; Mao, Zhangming; Peng, Zhangli et al. (2015) Acoustic separation of circulating tumor cells. Proc Natl Acad Sci U S A 112:4970-5

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