title: Stand-Sit Microchip for High-Throughput, Multiplexed Analysis of Single Cancer Cells.
abstract: Cellular heterogeneity in function and response to therapeutics has been a major challenge in cancer treatment. The complex nature of tumor systems calls for the development of advanced multiplexed single-cell tools that can address the heterogeneity issue. However, to date such tools are only available in a laboratory setting and don't have the portability to meet the needs in point-of-care cancer diagnostics. Towards that application, we have developed a portable single-cell system that is comprised of a microchip and an adjustable clamp, so on-chip operation only needs pipetting and adjusting of clamping force. Up to 10 proteins can be quantitated from each cell with hundreds of single-cell assays performed in parallel from one chip operation. We validated the technology and analyzed the oncogenic signatures of cancer stem cells by quantitating both aldehyde dehydrogenase (ALDH) activities and 5 signaling proteins in single MDA-MB-231 breast cancer cells. The technology has also been used to investigate the PI3K pathway activities of brain cancer cells expressing mutant epidermal growth factor receptor (EGFR) after drug intervention targeting EGFR signaling. Our portable single-cell system will potentially have broad application in the preclinical and clinical settings for cancer diagnosis in the future.
authors: Multiplex Biotechnology Laboratory, Department of Chemistry, University at Albany, State University of New York, Albany, NY 12222, USA.
authors: Lisa
authors: L
authors: Ramirez
authors: Cancer Research Center, University at Albany, State University of New York, Rensselaer, NY 12144, USA.|Department of Biomedical Sciences, University at Albany, State University of New York, Albany, NY 12222, USA.
authors: Jason I
authors: JI
authors: Herschkowitz
authors: Multiplex Biotechnology Laboratory, Department of Chemistry, University at Albany, State University of New York, Albany, NY 12222, USA.|Cancer Research Center, University at Albany, State University of New York, Rensselaer, NY 12144, USA.
authors: Jun
authors: J
authors: Wang
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D057166:High-Throughput Screening Assays / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D056656:Lab-On-A-Chip Devices; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D019095:Point-of-Care Systems; D015398:Signal Transduction; D059010:Single-Cell Analysis / Q000295:instrumentation / Q000379:methods*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D000444:Aldehyde Dehydrogenase; D019869:Phosphatidylinositol 3-Kinases; C512478:EGFR protein, human; D066246:ErbB Receptors