Viable cell concentration is one of the most important key performance indicator during upstream technologies in mammalian cell culture. Customer Discovery discussions with biopharma execs and R&D specialists revealed there is an unmet need for on-line/in-line monitoring of cell viability in pharma bioreactors driven by compliance with real-time product quality assurance as described in Process Analytical Technology (PAT) and Quality by Design initiatives. Preliminary work equivalent to Phase I effort has resulted in a cell imaging system including a flow cell setup that simulates an on-line stirring bioreactor sampling route. Proof-of-concept was also established for detection and classification of live/dead assays using digital staining via PICS (Phase Imaging with Computational Specificity). This Small Business Innovation Research project proposes to build a commercial prototype instrument for real time, quantitative and high-throughput cell viability scoring for on-line/in-line bioreactor monitoring that meets the metrics of interest for pharma R&D applications. During this effort the standard operation of the QPI+PICS instrument will be refined and the automated software detection and classification of live/dead assays will be completed. At the end of this Direct Phase II project we will deliver a commercial prototype -a "push-of-a-button" viability scanner with the above capabilities built in.
Public Health Relevance Statement: Project Narrative Phi Optics proposes to develop an optical instrument for performing real time, quantitative high-throughput viability classification and direct growth monitoring using label-free quantitative imaging combined with novel AI algorithms. The instrument will allow novel bioreactor optimization strategies that could circumvent growth rate limitations and optimize feeding.
Project Terms: Biological Assay; Assay; Bioassay; Biologic Assays; Cell Count; Cell Number; Cell Culture Techniques; cell culture; cell cultures; Cell Cycle; Cell Division Cycle; cell growth; Cellular Expansion; Cellular Growth; Cell Line; CellLine; Strains Cell Lines; cultured cell line; Cell Survival; Cell Viability; Cells; Cell Body; Classification; Systematics; Data Analyses; Data Analysis; data interpretation; DNA; Deoxyribonucleic Acid; Escherichia coli; E coli; E. coli; Feasibility Studies; Fluorescence; Goals; Growth; Generalized Growth; Tissue Growth; ontogeny; Investments; Learning; Microscopy; optical; Optics; Patents; Legal patent; Hansenula; Pichia; Production; Reagent; Recombinant Proteins; Research; Development and Research; R & D; R&D; research and development; Saccharomyces; Sales; Software; Computer software; Computer Software Tools; software toolkit; Software Tools; Specificity; Staining method; Stains; Stress; Suspension substance; Suspensions; Technology; Testing; Time; tomography; Trypan Blue; Benzamine Blue; Work; Agitation; Psychomotor Agitation; Psychomotor Excitement; Psychomotor Hyperactivity; Psychomotor Restlessness; Restlessness; Businesses; Specialist; base; quality assurance; Label; Microscope; Pump; Procedures; Phase; Ensure; Chemicals; Training; Stimulus; Measurement; Funding; R-Series Research Projects; R01 Mechanism; R01 Program; Research Grants; Research Projects; Research Project Grants; Letters; fluid; liquid; Liquid substance; Morphology; instrument; Research Specimen; Specimen; microbioreactor; Bioreactors; mechanical; Mechanics; Hour; Route; 3-D; 3D; three dimensional; 3-Dimensional; interest; experience; membrane structure; Membrane; Performance; fluorophore; Cellular injury; cell damage; cellular damage; damage to cells; injury to cells; cell injury; Structure; novel; Agreement; Modality; Modeling; Sampling; develop software; developing computer software; software development; monolayer; Staining and Labeling; Photobleaching; Molecular Interaction; Binding; Pharmaceutical Agent; Pharmaceuticals; Pharmacological Substance; Pharmacologic Substance; image-based method; imaging method; imaging modality; Data; Detection; Imaging Instrument; Imaging Tool; Imaging Device; Mammalian Cell; Cellular Assay; cell assay; Optical Instrument; Optics/Optical Instrument; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Monitor; Process; Development; developmental; Phototoxicity; cellular imaging; cell imaging; Image; imaging; Output; feeding; digital; design; designing; Population; Consumption; fluorescence imaging; fluorescent imaging; prototype; high risk; operation; Geometry; quantitative imaging; imaging system; deep neural network; deep learning based neural network; deep learning neural network; deep neural net; deep learning; deep learning algorithm; artificial intelligence algorithm; AI algorithm
