SBIR Phase II: Magnetic Quantum Dots for Cell Separation and Characterization

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The broader/commercial impact of this SBIR phase II project will develop magnetic and fluorescent reagents for the separation and analysis of cells from tissue samples stored in biobanks, central repositories for biological samples, including tissues, cells, blood, sera, and urine, and their associated patient data, used in research to identify new methods to diagnose and treat disease; this industry is currently $52 B/yr with a compound annual growth rate (CAGR) of 4.5%. Biobank samples typically consist of a mixture of pathologically normal and diseased cells and tissues, requiring separation. Sample quality is thus critical for biobanks. The cell separation market ($3.9 B/yr, CAGR 4.1%) is dominated by the flow cytometry segment ($3.1 B/yr, CAGR 3.6%); whereas magnetic cell separation is a growing market ($582 M/yr by 2020 CAGR of 6.4%). Most biobanks currently provide unpurified samples or samples purified via flow cytometry alone, with typical recoveries of 10% at purities of ~20%. This research will develop and commercialize reagents that combine magnetic separation with flow cytometry analysis for target cell purification from biobank tissue samples. In the company's Phase I research of cells in suspension, these reagents yielded ~100% recovery with purities 75%. This research will expand this technology to tissue homogenates with increased heterogeneity and viscosity, increasing purity of biobank samples and enhancing researcher ability to develop breakthrough medical technologies.This research will develop magnetic-fluorescent nanoparticle reagents for cell separation and subsequent flow cytometry analysis of heterogeneous clinical tissue samples from biobanks. Given the heterogeneous nature of biological specimens that may contain more normal than diseased components, purification technologies are critical to biobank operation. Based on the Phase I research, the company anticipates that this technology could increase recovery and purity to 75% (vs. 10-20% currently). This will be accomplished by: (1) developing an open magnetic separation system to reduce obstruction compared to existing commercial magnetic bead-packed columns; (2) optimization of reagent magnetic and fluorescent content to maximize cell separation and analysis signal while minimizing size and signal overlap with tissue autofluorescence; (3) protocol development for tissue homogenate analysis using commonly employed mechanical and enzymatic tissue digestion methods. This research will yield new tools for cell isolation from complex, viscous environments that will greatly enhance the utility of biobank samples in research and clinical investigations. Such improvements will also benefit applications with less rigorous engineering design requirements, including bio/pharma separations, bioprocessing (e.g., CAR T-cell therapy), and clinical diagnostics (e.g., circulating tumor cell recovery).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.