A Force-controlled Probe Based Platform for Single Cell Biomolecular Delivery

DESCRIPTION (provided by applicant): Application of nanotechnology in medicine, nanomedicine, has provided numerous emerging opportunities in healthcare, particularly given ever increasing demand for in vitro toxicology and diagnostics towards personalized medicine. With increasing demand for personalized medicine, pharmaceutical companies strive in taking advantage of the potential of nanotechnology tools in search of next generation therapeutics. Such efforts require systematic incorporation of genetic information from each individual in optimizing preventive and therapeutic care, which evidently would require much more efficient biomedical tools. The so-called nanofountain probe (NFP), which was developed at Northwestern University and is currently commercialized by iNfinitesimal LLC, is a nanotechnology tool that enables such endeavors. These probes have been used to investigate drug delivery through substrate nanopatterning and direct cell injection. In this regard, unique attributes of the NFP technology are: Easy integration with bio-AFMs and inverted fluorescent microscopes. Ultra-low mechanical stiffness of the probe allowing force-controlled injection to ensure minimal cell damage, i.e., high cell viability. Special probe morphology with a sharp tip that creates a small rupture in the cell membrane while the outer shell guides biomolecules to the point of injection. Picoliter control in fluid injection Large scale genomic and proteomic studies require delivery of drugs, conjugated nanoparticles, DNA, siRNA, and proteins into living cells to study spatial and temporal molecular regulatory mechanisms within the cell in response to a particular treatment. For direct drug delivery, micropipette based injection has been used for many years. However, its viability (cell survival) and limited automation limit its extensive application. This STTR Phase I project aims at developing and commercializing a cost effective and high-throughput cell injection system based on the nanofountain probe technologythat can potentially be automated towards much faster drug delivery to individual cell with high viability. Leveraging probe-cell force control and fluidic handling capabilities of nanofountain probes are the core of the new proposed tool. These attributeswould greatly enhance its potential to be the instrument of choice for viable cell injection in research labs and pharmaceutical companies, allowing them to have access to state-of-the-art nanotechnology tools in their endeavor toward patient-centered healthcare system. Key words: Single cell Injection, Drug delivery, Nanofountain Probes, Personalized medicine, Atomic force microscopy, Fluorescent microscopy, Cell viability, Force control. PUBLIC HEALTH RELEVANCE: This STTR Phase I project aims atdeveloping and commercializing a cost effective, high- throughput, and potentially automated single cell injection system towards much faster drug delivery to individual cells. The system will be applicable to large scale genomic and proteomic studies required for the ever increasing demand for personalized medicine .