SBIR-STTR Award

?Advances in reagents and analytical tools have improved characterization of cellular phenotypes. However, most studies are still performed on cell populations that are morphologically and genetically homogeneous, yet have important biological heterogeneity; with individual cells having unique phenotypic or `omic profiles. This leads to an average measurement of individual cells, none of which may actually be average. Single-cell analysis can define the scope of cell-to-cell variations within a population and provid in-depth analysis of single, exceptional cells in contexts such as stem cell differentiation or cancer, where these cells can give rise to clonal populations that drive the biology. While novel tools such as multiparameter flow cytometry, mass cytometry, and image-based cytometry provide in-depth analysis of individual cells, these technologies only provide a single time point "snapshot" and lack downstream molecular analysis. This project will develop a integrated cell-sorting and single-cell positioning device to allow single cells to be tracked and measured over time. This system will use a conventional multi-well plate format allowing the use of existing microscopy and analysis platforms.

Public Health Relevance Statement:


Public Health Relevance:
The advances proposed here will allow NanoCellect to achieve its mission: to advance single-cell technology that conforms to standard multiwell plate platforms. This will be achieved by integrating a microfluidic cell sorter and silicon-based plate-well insert that can arrange thousands of cells into hydrophilic zones, each containing a single cell.

NIH Spending Category:
Biotechnology

Project Terms:
Address; Air; analytical tool; Antibodies; base; Biological; Biology; Biopsy; Blood; cancer cell; Cell Cycle Kinetics; cell growth; Cell secretion; Cell Separation; Cell Survival; cell type; Cells; Collaborations; Communities; cost; cytokine; Cytometry; Devices; Diagnosis; Disease; Flow Cytometry; fluorescence activated cell sorter device; Fluorescence-Activated Cell Sorting; Gene Expression; Genome; Genomics; Glass; Health; Heterogeneity; Image Cytometry; improved; Individual; innovation; Island; Laboratories; laser capture microdissection; Link; Liquid substance; Logic; Maps; Measurement; Measures; Methods; Microfluidics; Microscopy; Mission; Molecular Analysis; novel; particle; Patients; Phenotype; Population; Positioning Attribute; Printing; Process; public health relevance; Reagent; Research Personnel; Resolution; Sampling; Silicon; single cell analysis; Sorting - Cell Movement; spatiotemporal; stem cell differentiation; Surface; System; Techniques; Technology; Time; tool; Variant

High-throughput single-cell sorting and kinetic analysis of secreted particles NanoCellect Biomedical, Inc. RESEARCH & RELATED Other Project Information 7. PROJECT SUMMARY Advances in reagents and analytical tools have improved characterization of cellular phenotypes. However, most studies are still performed on cell populations that are morphologically and genetically homogeneous, yet have important biological heterogeneity; with individual cells having unique phenotypic or `omic profiles. This leads to an average measurement of individual cells, none of which may actually be average. Single-cell analysis can define the scope of cell-to-cell variations within a population and provide in-depth analysis of single, exceptional cells in contexts such as stem cell differentiation or cancer, where these cells can give rise to clonal populations that drive the biology. While novel tools such as multiparameter flow cytometry, mass cytometry, and image-based cytometry provide in-depth analysis of individual cells, these technologies only provide a single time point “snapshot” and lack downstream molecular analysis. This project will develop for commercialization an integrated cell-sorting, cell dispensing, and single-cell positioning device to allow single cells to be tracked and measured over time. In addition, we will demonstrate a commercial prototype device that allows transfer of individual cells with desired phenotypic characteristics to 1536-well plates for downstream analysis in a standard format. This integrated system will be benchmarked with cells derived from glioblastoma that has been shown to have important exosome biological characteristics.

Public Health Relevance Statement:
High-throughput single-cell sorting and kinetic analysis of secreted particles NanoCellect Biomedical, Inc. RESEARCH & RELATED Other Project Information 8. PROJECT NARRATIVE The advances proposed here will allow NanoCellect to achieve its mission: to advance single-cell technology that conforms to standard multi-well plate platforms. This will be achieved by integrating a microfluidic cell sorter, dispenser, wells-in-a-well cell array and cell-selection screen to transfer cells of interest to 1536-well plates.

Project Terms:
Address; Air; Alpha Cell; analytical tool; Back; base; Benchmarking; Biologic Characteristic; Biological Assay; biological heterogeneity; Biology; Biopsy; Blood; Cancer Biology; cancer cell; Cell Cycle Kinetics; Cell Line; Cell Separation; Cell Survival; Cells; Characteristics; Collaborations; commercialization; Communities; Computer software; cost; cytokine; Cytometry; design; Devices; Diagnosis; Disease; exosome; Feedback; Flow Cytometry; Fluorescence-Activated Cell Sorting; Gene Expression; Generations; Genome; Genomics; Glioblastoma; Goals; Health; Image; improved; Individual; innovation; interest; Intervention; Laboratories; laser capture microdissection; Lead; Liquid substance; Logic; Measurement; Measures; Methods; Microfluidics; Mission; Molecular Analysis; Morphology; Neurosurgeon; novel; particle; Patients; personalized medicine; Phenotype; Population; Positioning Attribute; precision medicine; prototype; Reagent; Research Personnel; Resolution; Scientist; single cell analysis; single cell technology; Sorting - Cell Movement; stem cell differentiation; System; Techniques; Technology; Testing; Time; tool; Validation; Variant; Work