Development of the AcoustoDrop platform: an acoustofluidic-based, automated, liquid-handling system for manipulating and dispensing dropletsin a rewritable, biocompatible, and high-throughput manner

Abstract Automated liquid handling technologies play a pivotal role across the diverse realms of biomedical research by streamlining experimental processes and enhancing precision. In the context of genomics, these technologies enable high-throughput sample preparation for DNA sequencing, advancing our understanding of genetics and its role in disease. In drug discovery, liquid handling technologies expedite the screening of compounds against various targets, accelerating the identification and development of potential therapeutics. Nonetheless, a fundamental limitation plagues most automated liquid handling technologies: they require liquids to engage in physical contact with solid structures during manipulation. Consequently, remnants of reagents tend to adhere to the contact surface, potentially dissolving into and contaminating subsequent liquid samples. In this SBIR project, we will develop and commercialize the AcoustoDrop technology, which overcomes many of the key obstacles associated with existing liquid-handling systems, such as surface adsorption, surface degradation, and intra-droplet polarization. AcoustoDrop is an acoustic-based, programmable, contactless liquid-handling technology that allows one to transport, merge, mix, split, and eject reagents within aqueous droplets in a rewritable, programmable biocompatible, and high-throughput manner. In our Phase-I-type R&D efforts, Ascent has successfully demonstrated the utility and feasibility of the proposed AcoustoDrop devices by meeting or exceeding the target values of each of the five key parameters identified in the Measures of Success. In Phase II, our commercialization activities will improve the performance of the AcoustoDrop chips, develop self- contained, beta-testing-ready prototypes, and validate their performance across two well-established applications in stem cell therapeutics and high-throughput drug screening. Our proposed AcoustoDrop technology has the following features: (1) High throughput (> 2,500 reactions/sec) in comparison to benchmark technologies (~384 reactions/sec); (2) High programmability (> 20 cascade layers) in comparison to benchmark technologies (1-2 cascade layers); (3) Low levels of cross-contamination (< 10-10 % diffusion); (4) High biocompatibility: Instead of being directly subjected to strong acoustic pressure or high electric fields, the droplets are manipulated in a contactless, gentle manner. Our preliminary results show that the AcoustoDrop platform does not have a significant effect on the viability of cells. (5) High versatility: The AcoustoDrop platform suitable for handling a wide range of liquids, even for challenging samples such as low-polarity fluids (e.g., organic solvents), sticky or viscous samples (e.g., blood and sputum), and solids (e.g., fecal samples and model organisms). With the aforementioned features, the proposed AcoustoDrop technology has the potential to exceed current industry standards, address unmet needs in the field, and provide a compelling platform for the development of a robust, rewritable, high-throughput, and digitally-programmable fluidic processor.