Development of an acoustic-based smart Petri dish for contact-free, precise, versatile bioparticle manipulation

Abstract Acoustic tweezers are a promising technological development for the biocompatible, precise manipulation of delicate bioparticles such as cells and extracellular vesicles. However, their widespread usage is hindered by their low compatibility with many existing workflows in biological laboratories. In this SBIR project, we will address this unmet need by developing and commercializing fully integrated, multifunctional, acoustic tweezers on a Petri dish, termed the smart Petri dish, that can (1) manipulate cells and other bioparticles in Petri dishes in a precise (resolution: <0.5 µm), contact-free, biocompatible, programmable, high-throughput, high-speed, and easy-to-use manner, and (2) perform multiple functions (e.g., cell patterning, 3D tissue construction, nano/micro particle concentration, and cell lysis) within a single Petri dish. In our Phase-I-type R&D efforts, Ascent has successfully demonstrated the utility and feasibility of the proposed devices by meeting or exceeding the target in all eight key parameters identified in the Measures of Success. In Phase II, our commercialization activities will improve the performance of the acoustic-based smart Petri dish chips, develop self-contained, beta-testing-ready prototypes, and validate their performance across two well-established applications in stem cells and tissue engineering. Compared to the existing Petri-dish-compatible technologies, our acoustic-based smart Petri dish technology has the following advantages: (1) High precision: While most current Petri dish-based technologies can only reach resolutions (for cell/particle positions) of >100 µm, the proposed acoustic-based smart Petri dish can achieve a resolution (for cell/particle positions) of <0.5 µm, allowing for far more precise and reliable manipulation. (2) High versatility and programmability: Our proposed acoustic-based smart Petri dish can be configured to generate various acoustic wavefields and manipulate objects across length scales of nm to mm regardless of their shape, optical, electric, or magnetic properties. Our device also allows for both translational and rotational manipulation in all three dimensions and realizes precise manipulation with six degrees of freedom. It is capable of manipulating both collective groups of cells and individual cells, as confirmed in our preliminary results. (3) Contact-free nature and high biocompatibility: Our proposed acoustic-based smart Petri dish manipulates bioparticles in a contactless, label-free, and gentle manner. Our preliminary results already demonstrated the ability of our acoustic-based Petri dish to maintain the viability of highly sensitive, fragile cells, such as human-derived mesenchymal stem cells, even after 7 days of acoustic treatment. With these advantages, we expect our smart Petri dish to vastly expand the utility of the classic Petri dish as a biological tool, providing unprecedented access to a large array of functions, both essential and new, that biomedical scientists can adopt to simplify their workflows, increase the speed and accuracy of their experiments, and enable them to make discoveries that otherwise would not be possible.