title: Image-based cell-resolved screening assays in flow.
abstract: A parallel microfluidic cytometer (PMC) is based on a one-dimensional (1D) scanning detector, a parallel array of flow channels, and new multiparameter analysis algorithms that operate on low-pixel-count 1D images. In this article, we explore a series of image-based live- and fixed-cell screening assays, including two NF-kB nuclear translocations and T-cell capping. We then develop a new multiparametric linear weighted classifier that achieves a Z' factor sufficient for scaled pharmaceutical discovery with Jurkat cells in suspension. We conclude that the PMC should have the throughput and statistical power to permit a new capability for image-based high-sample-number pharmaceutical screening with suspension samples.
authors.affiliation: Department of Biomedical Engineering, Boston University, Massachusetts.
authors.forename: Man Ching
authors.initials: MC
authors.lastname: Cheung
authors.affiliation: Department of Biomedical Engineering, Boston University, Massachusetts.
authors.forename: Brian
authors.initials: B
authors.lastname: McKenna
authors.affiliation: Department of Biomedical Engineering, Boston University, Massachusetts.
authors.forename: Steve S
authors.initials: SS
authors.lastname: Wang
authors.affiliation: Department of Biomedical Engineering, Boston University, Massachusetts.
authors.forename: Dane
authors.initials: D
authors.lastname: Wolf
authors.affiliation: Department of Biomedical Engineering, Boston University, Massachusetts.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Ehrlich
mesh_terms: D000465:Algorithms; D000818:Animals; D016466:CHO Cells; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D045744:Cell Line, Tumor; D019295:Computational Biology / Q000379:methods; D003412:Cricetulus; D055808:Drug Discovery / Q000379:methods*; D005434:Flow Cytometry / Q000295:instrumentation / Q000379:methods*; D049452:Green Fluorescent Proteins; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D019169:Jurkat Cells; D008113:Liver Neoplasms / Q000188:drug therapy; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods*; D016328:NF-kappa B / Q000502:physiology; D049490:Systems Biology / Q000379:methods; D013601:T-Lymphocytes / Q000502:physiology
chemical_list: D016328:NF-kappa B; D049452:Green Fluorescent Proteins
keywords: HCA; high-content; high-throughput; imaging; live-cell assay; microfluidic; receptor capping; screening