SBIR Phase I: A Microprocessor for Complex, Multidimensional Cell Reprogramming: Acoustic-Electric Micro-Vortices Technology for Precise, Sequential Delivery of Genetic Molecules

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is to make cell engineering more accessible, enabling a wider range of users, from students to experienced researchers, to perform complex cellular modifications with ease. Similar to how 3D printing revolutionized manufacturing, this project aims to develop a microchip-based, miniaturized liquid and cell handling technology that makes advanced cell engineering feasible in diverse laboratory settings. By streamlining these processes, the technology has the potential to accelerate discoveries in cell and gene therapy, fields that are rapidly expanding to address conditions such as cancer, autoimmune disorders, and infectious diseases. The ability to perform complex cell engineering with precision is critical for the future of personalized medicine, where custom-engineered cell-based treatments could improve patient outcomes and expand therapeutic options. Beyond healthcare, this innovation will also impact biotechnology, drug development, and regenerative medicine, fostering advancements that benefit both scientific research and clinical applications. This Small Business Innovation Research (SBIR) Phase I project addresses critical challenges faced by existing technologies in multiplex and complex cell engineering. These challenges include low efficiency in genetically modifying cells, the generation of heterogeneous populations of engineered cells, limited processing throughput, and restricted compatibility with different cell types. The proposed microchip technology leverages sound waves and electric fields to manipulate cells and sequentially deliver customizable combinations of genetic coding molecules. In Phase I, the instrument’s components will be designed and optimized to generate homogeneous populations of engineered cells with high efficiency and throughput. To validate the platform’s versatility, the technology will be tested across a variety of cell types, including cancer cells and primary human T cells, using a broad range of genetic materials such as DNA, messenger RNA (mRNA), and proteins. To further enhance commercial and societal impact, the platform will be used to demonstrate multiplex genome editing of T cells for chimeric antigen receptor (CAR) T cell manufacturing, a critical area in cancer immunotherapy research and therapeutic development. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.