SBIR Phase I: An Automated Microfluidic Platform for Delivery of Biomolecules Into Cells

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is to address a major barrier in fundamental biological research and next-generation clinical treatments: Delivering materials into cells. Cells are the basic functional unit of the body yet understanding their role in disease and harnessing their inherent potential to combat ailments has been limited by our inability to deliver material to their cytoplasm. By facilitating access to a cell's interior one could enable rapid progress in the ability to probe intracellular processes and engineer cell function for therapeutic purposes. This project aims to further develop a promising new concept of intracellular delivery capable of overcoming many conventional barriers associated with the current state-of-the-art. The platform will potentially facilitate the development of novel therapeutics based on a deeper understanding of cell function and a more robust ability to engineer cell fate. Indeed, addressing such a fundamental challenge in the biomedical field would provide substantial benefits to society and could impact numerous commercial opportunities. Potential applications include basic research, high-throughput drug discovery screening, and cell-based therapies to treat cancer immunotherapies. This SBIR Phase I project proposes to develop a vector-free microfluidic platform for intracellular delivery of biomolecules in order to increase efficacy, and improve ease-of-use. The platform uses a novel method based on rapid, transient deformation of cells ("cell squeezing") as they pass through a microfluidic constriction. The squeezing process causes temporary disruption of the cell membrane and facilitates passive transport of target delivery materials into the cytoplasm. The proposed work aims to introduce automated, closed-loop control of key parameters (pressure, temperature, and flow rate) that govern the delivery process. These additions will allow users to precisely tune the amount of material delivered to cells and the resultant viability. By developing this hardware, the technology will be well-positioned for increased adoption and commercialization by the end of Phase I. The proposed hardware controllers will be verified and validated through relevant studies using primary immune cells, a disease-relevant subset of cells that are recalcitrant to existing delivery methods. Finally, the proposed work would facilitate the launch of a robust prototype system for early-stage testing in high-impact applications.