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.
