Development of an acoustofluidic device for high-throughput 3D imaging and sorting of C. elegans

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Abstract C. elegans are millimeter-long, transparent worms that are widely used in biomedical research and drug discovery. Due to their fully sequenced genome, genetic homology with humans, extremely well characterized anatomy, and ease of lab cultivation, C. elegans are an ideal model organism for studying fundamental biological processes and have provided key insights into the pathologies of various human diseases. Many research efforts involving C. elegans require image-based analysis and subsequent sorting based on factors such as the age of the worms or phenotypic differences. Although several platforms for imaging-based analysis exist, they either lack high-resolution 3D imaging capabilities, are prohibitively expensive, have low biocompatibility, and/or are far too time and labor intensive to be suitable for high-throughput studies. These drawbacks detract from the overall quality of C. elegans research, particularly in drug discovery, where tens of thousands of worms must be rapidly sorted based on minute differences that can only be detected with high-resolution imaging. The objective of this SBIR project is to overcome the limitations of existing C. elegans imaging and sorting technologies and address unmet needs in the market by developing and commercializing a biocompatible worm analysis platform capable of high-resolution, rapid C. elegans 3D imaging and sorting using acoustofluidic (i.e., the fusion of acoustics and microfluidics) technologies. During our work on the Phase I project, we successfully demonstrated the utility and feasibility of the proposed technology by developing acoustofluidic chips capable of high- throughput (155 worms/min), high-viability (~99.2%), and high-resolution C. elegans 3D imaging and sorting. In Phase II, our commercialization activities will focus on significantly improving the performance of the acoustofluidic-based 3D imaging and sorting chips, developing self-contained, beta-testing-ready prototypes, and validating and optimizing the beta prototypes with end users. By optimizing the design of our acoustofluidic chips, we will improve the throughput (>1,000 worms/min), rotational resolution (<1°), and sorting accuracy (>99%), while retaining the high biocompatibility (>99%) of our acoustofluidic technology. The proposed acoustofluidic technology will be the only automated worm analysis platform capable of rapid 3D imaging and sorting on a single device. By enabling precise, rapid 3D imaging and sorting of C. elegans in an automated manner, our acoustofluidic technology can address critical needs in many fields including pharmaceutical development, where technological limitations have thus far prevented the widespread use of C. elegans in high- throughput drug screening. Due to its superior speed, precision, accuracy, and functionalities, we believe that our acoustofluidic technology will become the platform of choice for the imaging, analysis, and sorting of C. elegans and will help to streamline workflows, expand capabilities, and accelerate progress in many areas of biomedical research.