Chemist
Chemist

Biography

Dr. Zhu is a senior bioanalytical scientist with the Instrument Development Lab team in the Environmental Molecular Sciences Division and the Environmental Molecular Sciences Laboratory (EMSL) user program. He also works closely with the Integrative Omics group in the Biological Sciences Division. 

Zhu’s research is focused on developing highly sensitive and high-throughput technologies for measuring proteins and small molecules from limited amounts of samples—as low as single cells. He co-invented the nanoPOTS (Nanodroplet Processing in One pot for Trace Samples) platform, which combined microfluidics, robotics, and ultrasensitive liquid chromatography-mass spectrometry (LC-MS) systems to achieve single cell analysis of protein expression in single cells. 

Research Interest

  • Microfluidic techniques for chemical and biological research 

  • Automation of liquid handling for sample preparation 

  • Ultrasensitive LC-MS instrumentation and methods 

  • Proteomic analysis of single cells

Education

  • PhD in Analytical Chemistry, Zhejiang University, 2010 

  • BS in Chemistry, Zhejiang University, 2001 

Awards and Recognitions

  • Pathway to Excellence Award for Intellectual Property Commercialization, PNNL (2020) 

  • BESTie Award, Earth and Biological Sciences Directorate, PNNL (2019) 

  • M.T. Thomas Award for Outstanding Postdoctoral Achievement, EMSL, PNNL 

  • Exceptional Contributions Award, PNNL (2018) 

  • BESTie Award, Earth and Biological Sciences Directorate, PNNL (2018) 

  • R&D 100 Finalist for NanoPOTS, R&D Magazine, (2018) 

  • Capability Development Award, Earth and Biological Sciences Directorate, PNNL (2017) 

  • Outstanding Performance Award, Earth and Biological Sciences Directorate, PNNL (2016) 

Publications

2020 

  • Cong, Y., Y. Liang, K. Motamedchaboki, R. Huguet, T. Truong, R. Zhao, Y. Shen, D. Lopez-Ferrer, Y. Zhu, and R. T. Kelly. 2020. “Improved Single-Cell Proteome Coverage Using Narrow-Bore Packed NanoLC Columns and Ultrasensitive Mass Spectrometry.” Analytical Chemistry 92 (3): 2665-2671. https://doi.org/10.1021/acs.analchem.9b04631. 

  • Liu W., and Y. Zhu. 2020. "Development and application of analytical detection techniques for droplet-based microfluidics-A Review." Analytica Chimica Acta 1113. PNNL-SA-150006. doi:10.1016/j.aca.2020.03.011 

  • Piehowski P.D., Y. Zhu, L.M. Bramer, K.G. Stratton, R. Zhao, D.J. Orton, and R.J. Moore, et al. 2020. "Automated mass spectrometry imaging of over 2000 proteins from tissue sections at 100-µm spatial resolution." Nature Communications 11, no. 1:Article No. 8. PNNL-SA-138884. doi:10.1038/s41467-019-13858-z 

  • Sigdel T.K., P.D. Piehowski, S. Roy, J. LIberto, J.R. Hansen, A.C. Swensen, and R. Zhao, et al. 2020. "Near-Single-Cell Proteomics Profiling of the Proximal Tubular and Glomerulus of the Normal Human Kidney." Frontiers in Medicine 7. PNNL-SA-145047. doi:10.3389/fmed.2020.00499 

  • Tsai C., R. Zhao, S.M. Williams, R.J. Moore, K.D. Schultz, W.B. Chrisler, and L. Pasa Tolic, et al. 2020. "An Improved Boosting to Amplify Signal with Isobaric Labeling (iBASIL) Strategy for Precise Quantitative Single-cell Proteomics." Molecular and Cellular Proteomics 19, no. 5:828-838. PNNL-SA-149183. doi:10.1074/mcp.RA119.001857 

  • Wang, X., A. C. Swensen, T. Zhang, P. D. Piehowski, M. J. Gaffrey, M. E. Monroe, Y. Zhu, H. Dong, and W. J. Qian. 2020. “Accurate Identification of Deamidation and Citrullination from Global Shotgun Proteomics Data Using a Dual-Search Delta Score Strategy.” Journal of Proteome Research 19 (4): 1863-1872. https://doi.org/10.1021/acs.jproteome.9b00766. 

  • Williams S.M., A.V. Liyu, C. Tsai, R.J. Moore, D.J. Orton, W.B. Chrisler, and M.J. Gaffrey, et al. 2020. "Automated coupling of nanodroplet sample preparation with liquid chromatography-mass spectrometry for high-throughput single-cell proteomics." Analytical Chemistry 92, no. 15:10588-10596. PNNL-SA-152553. doi:10.1021/acs.analchem.0c01551 

  • Xiang P., Y. Zhu, Y. Yang, Z. Zhao, S.M. Williams, R.J. Moore, and R.T. Kelly, et al. 2020. "Picoflow Liquid Chromatography-Mass Spectrometry for Ultrasensitive Bottom-up Proteomics using 2-µm i.d. Open Tubular Columns." Analytical Chemistry 92, no. 7:4711-4715. PNNL-SA-150120. doi:10.1021/acs.analchem.9b05639 

  • Zhou M., N.O. Uwugiaren, S.M. Williams, R.J. Moore, R. Zhao, D. Goodlett, and I. Dapic, et al. 2020. "Sensitive Top-Down Proteomics Analysis of Low Number of Mammalian Cells Using a Nanodroplet Sample Processing Platform." Analytical Chemistry 92, no. 10:7087-7095. PNNL-SA-149823. 

2019 

  • Couvillion, S. P., Y. Zhu, G. Nagy, J. N. Adkins, C. Ansong, R. S. Renslow, P. D. Piehowski, Y. M. Ibrahim, R. T. Kelly, and T. O. Metz. 2019. “New Mass Spectrometry Technologies Contributing Towards Comprehensive and High Throughput Omics Analyses of Single Cells.” Analyst 144 (3): 794-807. https://doi.org/10.1039/c8an01574k. 

  • Dou M., C. Tsai, P.D. Piehowski, Y. Wang, T.L. Fillmore, R. Zhao, and R.J. Moore, et al. 2019. "Automated Nanoflow Two-Dimensional Reversed-Phase Liquid Chromatography System Enables In-Depth Proteome and Phosphoproteome Profiling of Nanoscale Samples." Analytical Chemistry 91, no. 15:9707-9715. PNNL-SA-141437. doi:10.1021/acs.analchem.9b01248 

  • Dou, M., G. Clair, C. F. Tsai, K. Xu, W. B. Chrisler, R. L. Sontag, R. Zhao, R. J. Moore, T. Liu, L. Pasa-Tolic, R. D. Smith, T. Shi, J. N. Adkins, W. J. Qian, R. T. Kelly, C. Ansong, and Y. Zhu. 2019. “High-Throughput Single Cell Proteomics Enabled by Multiplex Isobaric Labeling in a Nanodroplet Sample Preparation Platform.” Analytical Chemistry 91 (20): 13119-13127. https://doi.org/10.1021/acs.analchem.9b03349. 

  • Dou M., C.D. Chouinard, Y. Zhu, G. Nagy, A.V. Liyu, Y.M. Ibrahim, and R.D. Smith, et al. 2019. "Nanowell-mediated multidimensional separations combining nanoLC with SLIM IM-MS for rapid, high-peak-capacity proteomic analyses." Analytical and Bioanalytical Chemistry 411, no. 21:5363-5372. PNNL-SA-146403. doi:10.1007/s00216-018-1452-5 

  • Kelly R.T., and Y. Zhu. 2019. "Ultrasmall sample biochemical analysis." Analytical and Bioanalytical Chemistry 411, no. 21:5349-5350. PNNL-SA-146523. doi:10.1007/s00216-019-01957-1 

  • Snyder M., S. Lin, A. Posgai, M.A. Atkinson, A. Regev, J. Rood, and O. Rozenblatt-Rosen, et al. 2019. "The human body at cellular resolution: the NIH Human Biomolecular Atlas Program." Nature 574, no. 7777:187-192. PNNL-SA-146510. doi:10.1038/s41586-019-1629-x 

  • Wei, Y., Y. Zhu, and Q. Fang. 2019. “Nanoliter Quantitative High-Throughput Screening with Large-Scale Tunable Gradients Based on a Microfluidic Droplet Robot under Unilateral Dispersion Mode.” Analytical Chemistry 91 (8): 4995-5003. https://doi.org/10.1021/acs.analchem.8b04564. 

  • Xu K., Y. Liang, P.D. Piehowski, M. Dou, K.C. Schwarz, R. Zhao, and R.L. Sontag, et al. 2019. "Benchtop-compatible sample processing workflow for proteome profiling of <100 mammalian cells." Analytical and Bioanalytical Chemistry 411, no. 19:4587-4596. PNNL-SA-146641. doi:10.1007/s00216-018-1493-9 

  • Zhang P., M.J. Gaffrey, Y. Zhu, W.B. Chrisler, T.L. Fillmore, L. Yi, and C.D. Nicora, et al. 2019. "Carrier-assisted single-tube processing approach for targeted proteomics analysis of low numbers of mammalian cells." Analytical Chemistry 91, no. 2:1441-1451. PNNL-SA-138130. doi:10.1021/acs.analchem.8b04258 

  • Zhu Y., M. Scheibinger, D.C. Ellwanger, J.F. Krey, D. Choi, R.T. Kelly, and S. Heller, et al. 2019. "Single-cell proteomics reveals changes in expression during hair-cell development." eLife 8. PNNL-SA-144744. doi:10.7554/eLife.50777 

2018 

  • Dou, M., Y. Zhu, A. Liyu, Y. Liang, J. Chen, P. D. Piehowski, K. Xu, R. Zhao, R. J. Moore, M. A. Atkinson, C. E. Mathews, W. J. Qian, and R. T. Kelly. 2018. “Nanowell-Mediated Two-Dimensional Liquid Chromatography Enables Deep Proteome Profiling of <1000 Mammalian Cells.” Chemical Science 9 (34): 6944-6951. https://doi.org/10.1039/c8sc02680g.  

  • Du, G. S., J. Z. Pan, S. P. Zhao, Y. Zhu, J. M. J. den Toonder, and Q. Fang. 2018. A Microfluidic Droplet Array System for Cell-Based Drug Combination Screening. Methods in Molecular Biology 1771: 203-211. https://doi.org/10.1007/978-1-4939-7792-5_16  

  • Guo, X. L., Y. Wei, Q. Lou, Y. Zhu, and Q. Fang. 2018. “Manipulating Femtoliter to Picoliter Droplets by Pins for Single Cell Analysis and Quantitative Biological Assay.” Analytical Chemistry 90 (9): 5810-5817. https://doi.org/10.1021/acs.analchem.8b00343.  

  • Li, Z. Y., M. Huang, X. K. Wang, Y. Zhu, J. S. Li, C. C. L. Wong, and Q. Fang. 2018. “Nanoliter-Scale Oil-Air-Droplet Chip-Based Single Cell Proteomic Analysis.” Analytical Chemistry 90 (8): 5430-5438. https://doi.org/10.1021/acs.analchem.8b00661. 

  • Liang Y., Y. Zhu, M. Dou, K. Xu, R.K. Chu, W.B. Chrisler, and R. Zhao, et al. 2018. "Spatially resolved proteomic profiling of <200 cells from tomato fruit pericarp by integrating laser-capture microdissection with nanodroplet sample preparation." Analytical Chemistry 90, no. 18:11106-11114. PNNL-SA-134717. doi:10.1021/acs.analchem.8b03005 

  • Zhu Y., G. Clair, W.B. Chrisler, Y. Shen, R. Zhao, A.K. Shukla, and R.J. Moore, et al. 2018. "Proteomic Analysis of Single Mammalian Cells Enabled by Microfluidic Nanodroplet Sample Preparation and Ultrasensitive NanoLC-MS." Angewandte Chemie International Edition 57, no. 38:12370-12374. PNNL-SA-132946. doi:10.1002/anie.201802843 

  • Zhu Y., J. Podolak, R. Zhao, A.K. Shukla, R.J. Moore, G.V. Thomas, and R.T. Kelly. 2018. "Proteome Profiling of 1 to 5 Spiked Circulating Tumor Cells Isolated from Whole Blood Using Immunodensity Enrichment, Laser Capture Microdissection, Nanodroplet Sample Processing, and Ultrasensitive nanoLC-MS." Analytical Chemistry 90, no. 20:11756-11759. PNNL-SA-140551. doi:10.1021/acs.analchem.8b03268 

  • Zhu Y., P.D. Piehowski, R. Zhao, J. Chen, Y. Shen, R.J. Moore, and A.K. Shukla, et al. 2018. "Nanodroplet processing platform for deep and quantitative proteome profiling of 10-100 mammalian cells." Nature Communications 9, no. 1:882. PNNL-SA-125235. doi:10.1038/s41467-018-03367-w 

  • Zhu Y., P.D. Piehowski, R.T. Kelly, and W. Qian. 2018. "Nanoproteomics Comes of Age." Expert Review of Proteomics 15, no. 11:865-871. PNNL-SA-136396. doi:10.1080/14789450.2018.1537787 

  • Zhu Y., R. Zhao, P.D. Piehowski, R.J. Moore, S. Lim, V.J. Orphan, and L. Pasa Tolic, et al. 2018. "Subnanogram proteomics: impact of LC column selection, MS instrumentation and data analysis strategy on proteome coverage for trace samples." International Journal of Mass Spectrometry 427. PNNL-SA-125645. doi:10.1016/j.ijms.2017.08.016 

2017 

  • Geng T., C.R. Smallwood, Y. Zhu, E.L. Bredeweg, S.E. Baker, J.E. Evans, and R.T. Kelly. 2017. "Multimodal Microchannel and Nanowell-Based Microfluidic Platforms for Bioimaging." In Proceedings of the 10th IEEE International Conference on Nano/Molecular Medicine and Engineering (NANOMED 2016), October 30- November 2, 2016, Macau, China, 155-158. Piscataway, New Jersey:IEEE. PNNL-SA-124699. doi:10.1109/NANOMED.2016.7883480 

  • Huang C., Y. Zhu, D. Jin, R.T. Kelly, and Q. Fang. 2017. "Direct Surface and Droplet Microsampling for Electrospray Ionization Mass Spectrometry Analysis with an Integrated Dual-Probe Microfluidic Chip." Analytical Chemistry 89, no. 17:9009-9016. PNNL-SA-128967. doi:10.1021/acs.analchem.7b01679 

2016 

  • Jin, D. Q., Y. Zhu, and Q. Fang. 2016. “Non-Tapered PTFE Capillary as Robust and Stable Nanoelectrospray Emitter for Electrospray Ionization Mass Spectrometry.” Rapid Communications in Mass Spectrometry: 62-67. https://doi.org/10.1002/rcm.7623.  

  • Li, Q., Y. Zhu, N. Q. Zhang, and Q. Fang. 2016. “Automatic Combination of Microfluidic Nanoliter-Scale Droplet Array with High-Speed Capillary Electrophoresis.” Scientific Reports 6. https://doi.org/10.1038/srep26654.  

  • Liang, Y., Y. Zhu, and Q. Fang. 2016. “Advances in High-Throughput, Automated Techniques and Instrumentation for Protein Crystallization Screening.” Chinese Journal of Chromatography (Se Pu) 34 (12): 1137-1144. https://doi.org/10.3724/SP.J.1123.2016.08009.  

  • Ma, Y., J. Z. Pan, S. P. Zhao, Q. Lou, Y. Zhu, and Q. Fang. 2016. “Microdroplet Chain Array for Cell Migration Assays.” Lab on a Chip 16 (24): 4658-4665. https://doi.org/10.1039/C6LC00823B.