PFI-RP: Development of Delivery Devices to Enable Cell Transformation or Preservation

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The broader impact/commercial potential of this PFI project will arise from the development of new devices that efficiently and uniformly transport molecules to the inside of cells. Many large or charged molecules do not easily penetrate the outer layer of cells and are not able to access the components inside the cell. This is a problem because delivery of certain molecules (including sugars, proteins, DNA, or RNA) to the inside of cells would allow better methods for modifying and storing cells. Examples of how this could be useful include a nature-inspired process for preparing freeze-dried cells so they can be stored at room temperature and rehydrated on demand, which would be useful for both research (cell lines) and medical treatments (red blood cells). If successful, these activities will increase the economic competitiveness of the United States through new product development, company formation, and training opportunities. Our research could advance public health and support national defense by improving cancer therapy and providing dried blood for military field use, space travel, and emergency preparedness. This project is also designed specifically to enhance relationships between academia and industry, and to encourage participation of women and individuals from underrepresented groups in STEM research.The proposed project is expected to advance knowledge in many areas, including ultrasound-mediated sonoporation, microfluidics, and cryobiology. Our ultimate goal is to develop integrated ultrasound-microfluidic devices for optimal delivery of cell-impermeable molecules to a variety of cell types. Current methods are not ideal for numerous reasons including low transfection efficiency and toxicity. We plan to develop devices that can be used for the following applications: (1) intracellular delivery of cryoprotectant molecules (such as trehalose) to red blood cells or to cultured cell lines so that cells can be frozen, dehydrated, stored at ambient temperature, and then rehydrated without substantial loss of viability or function; and (2) intracellular delivery of biomolecules (DNA, RNA, or protein) to cultured cells or primary cells for use in research or therapy. Parameters to be optimized include microfluidic designs, flow rate, cryopreservation or transfection solutions, and methods for sonoporating, freezing, drying, and recovery. The success of our approach will be determined by evaluating multiple factors, such as loading, viability, and function. This is an academia-industry partnership project where university researchers and industry experts will work together to maximize the speed of development and the likelihood that the project will result in a commercially viable product.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.