Precision Microfluidic Design Advances Targeted Proteomics to Single Cell Resolution
Lester John & Lynne Dewar Lloyd Distinguished Professor, Bioengineering
University of California Berkeley
March 31, 2016
Foege N130A, Wallace H. Coulter Seminar Room
Biology is becoming quantitative. Measurement advances have driven a genomics revolution with sweeping impact on our understanding of life processes. Yet, when researchers and clinicians seek to measure unmodified, endogenous proteins, the immunoassay remains the de facto standard. While certainly powerful in assays ranging from ELISA to immunohistochemistry to mass cytometry, numerous protein targets lack an antibody probe with adequate specificity. Insufficient immunoprobe specificity translates into less-than-ideal assays for protein isoforms, complexes, and even multiplexing (owing to background cross-reactivity). To this end, I will detail our research surrounding microengineering design strategies for critical multi-stage protein assays — where selectivity is enhanced by concatenating multiple independent assays. New tunable photopatterned materials for switchable function will be described, as will microfluidic architectures for seamless integration of discrete stages, and multiplexed readouts for quantitation. As specific case studies, I will discuss a spectrum of translational measurements my group is making possible: from near-patient diagnostics for HIV confirmation to biomarker validation of cancer signaling isoforms to single-cell Western blotting of pathway activation during neural stem cell differentiation. Microfluidic design further brings multi-stage separations to single-cell and sub-cellular resolution. Performance and operational gains will be discussed, as well as a forward-looking view on where the tools can make an impact. Ultimately, our work infuses protein measurement advances into the biological and biomedical sciences.
Amy E. Herr is the Lester John & Lynne Dewar Lloyd Distinguished Professor in Bioengineering at the University of California, Berkeley. She received her BS degree from Caltech and her MS and PhD degrees from Stanford in Mechanical Engineering. From 2002-2007, Dr. Herr was a Biosystems Research staff member at Sandia National Laboratories (Livermore). At UC Berkeley since 2007, Prof. Herr’s research focuses on instrumentation innovation to advance quantitation in life sciences and clinical problems – impact spans from tools for fundamental research (cell signaling) to near-patient disease diagnostics. Her major awards include: the 2015 George Guiochon Award from HPLC, the 2012 Young Innovator Award from Analytical Chemistry and the Chemical & Biological Microsystems Society, the 2012 Ellen Weaver Award from the Association for Women in Science (AWIS), a 2012 Bakar Fellowship at UC Berkeley, a 2011 NSF CAREER Award, the 2011 Eli Lilly & Co. New Investigator Award in analytical chemistry, a 2010 NIH New Innovator Award, a 2010 Alfred P. Sloan Research Fellowship (chemistry), and a 2009 DARPA Young Faculty Award. She Chaired (2009) & vice-chaired (2007) the Gordon Research Conference (GRC) on the Physics & Chemistry of Microfluidics, will Chair the 2020 microTAS conference, and has served on the technical program committee for several international conferences. Prof. Herr is an elected Fellow of the American Institute of Medical and Biological Engineering (AIMBE), serves on the Editorial Advisory Boards of the journals Analytical Chemistry and ACS Sensors, and the Board of the international Chemical & Biological Microsystems Society (CBMS), which oversees the microTAS conference