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    Laboratory of Molecular Probe Technology

     

     

     

     

    College of Future Technology,
    Institute of Molecular Medicine,

    National Biomedical Imaging Center,

    Peking-Tsinghua Center for Life Sciences,
    Peking University

     

     

     

     

     

  • Research Philosophy

    Tailored Molecules for Advanced Imaging and Biotechnology

    As an emerging yet interdisciplinary field, bioimaging is revolutionizing biological and medical research. Trained as a general chemist, Dr. Chen has been approaching this field from a molecular aspect. Our lab endeavors to develop novel molecular tools by integrating the essence of chemical synthesis, spectroscopy, polymer, and chemical biology. The molecular tools would be applied as cutting-edge technologies to various fields including biophysics, cell biology, physiology, and finally inspire drug discovery. Our research philosophy features: 1. based on chemical principles, we customize tailored molecules as enabling solutions; 2. we leverage the platforms of CFT and CLS as unique opportunities to bring modern molecular tools to the frontiers of biological sciences and molecular medicine. We believe our training in chemistry and biotechnology, our cross-disciplinary experience, and our problem-solving mindset would broaden the career path of trainees.

     

    Please refer to selected projects to see our accomplishments.

     

     

     

  • Meet Our Team

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    Dr. Zhixing Chen 陈知行 博士

    Principal Investigator

    • 2004-2008 BS in Chem. Biol., Tsinghua University
    • 2008-2009 Research Assistant, Peking University
    • 2009-2014 PhD in Chemistry, Columbia University
    • 2015 PostDoc, Columbia University
    • 2016-2018 Postdoc, Stanford University
    • 2018-2024 Assistant Professor, Peking University
    • 2024- Associate Professor, Peking University

    Affiliations:

    • College of Future Technology, Institute of Molecular Medicine & National Biomedical Imaging Center.
    • Academy for Advanced Interdisciplinary Studies, Biomed-X Center & Center for Life Sciences.
    • State Key Lab. of Membrane Biology

    Office: 417 Integrated Science Research Center #2

    Email: zhixingchen at pku.edu.cn

  • Dr. Zhixing Chen is a chemist with research experience spanning natural product synthesis, polymer mechano-chemistry, fluorescence and non-linear optical probes, bioconjugation, and live cell imaging. Zhixing believes in the enabling role of molecular technologies at the frontier of optical imaging, biotechnology, and life sciences. His current focus is to develop small and macro molecular tools for advanced imaging technologies. In the long term, Zhixing endeavors to unleash the synergy at the chemistry-biology-imaging interface in a collaborative manner, bringing new dimensions to the fields of molecular imaging and molecular medicine.

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    Cong Li 李聪

    PostDoc

    PhD. Integrated Biol. Sci.

    Peking University

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    TianYan Liu 刘天妍

    PostDoc (Boya Fellow)

    PhD. Integrated Biol. Sci.

    Peking University

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    JunWei Zhang 张钧维

    Graduate Student

    BE. Chemical Engineering

    Dalian Univ. Technology

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    Yuan Zhang 张源

    Graduate Student

    BS. Chemistry

    Tsinghua University

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    JingTing Chen 陈婧婷

    Graduate Student

    BS. Chemistry

    Wuhan University

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    ZhongTian Yang 杨中天

    Graduate Student

    BS. Chemical Biology

    Peking University

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    RunDong Yu 于润东

    Graduate Student

    BS. Chemistry

    Lanzhou University

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    KeCheng Zhang 张珂诚

    Graduate Student

    BS. Biological Sciences

    Beijing Normal Univ.

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    Zhe Yang 杨哲

    Graduate Student

    MS. Analytical Chemistry

    Fuzhou University

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    MingQiao Liu 刘明樵

    Graduate Student

    BS. Chemistry

    Beijing Institute of Technology

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    YiTong Liu 刘奕彤

    Graduate Student

    BS. Chemistry

    Nankai University

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    Dilizhatai Saimi
    迪丽扎泰·赛米

    Graduate Student

    MS. Immunology

    Peking Union Medical College

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    XiaoWen Shen 沈潇雯

    Graduate Student

    BS. Biological Sciences

    Xiamen University

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    ZhengZhao Chen 陈正昭

    Graduate Student

    BS. Chemistry

    Sichuan University

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    JiaSheng Du 杜佳晟

    Graduate Student

    MS. Material Engineering

    U Sci Tech Beijing

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    HaoLin Zhang 张昊霖

    Research Assistant

    MS. Integrated Biol. Sci.

    Peking University

  • Past Members and their Next Destination

    Jing Ling (PhD 2019-2024), Postdoc at UCSD

    Yu Zhang (PhD/PostDoc 2018-2024), Postdoc at Weill Cornell Medicine

    Yihui Nie (Manager 2018-2024), Administrative staff at Hunan U.

    Zhibin Li (RA 2021-2023), PhD student at Westlake U.

    Xiaohong Peng (Joint PostDoc 2020-2022), PKU Medical School

    Jiaming Mo (MS 2018-2022), BGI

    Yabo Shi (RA 2018-2019), PhD student at PKU

    Yunxiang Wu (RA 2018-2019), PhD student at U. Wisc.

    Rui Sang (RA 2018-2019), PhD student at UNSW

    Zhaohong Wang (RA 2020-2021), PhD student at Cornell Univ.

    Zixuan Chen (UG 2019-2020)

     

    We look for talents at all levels to work together with us! Feel free to explore our mutual interests and the potential research opportunities. Our lab is affiliated to the PhD programs of Institute of Molecular Medicine and Center for Life Sciences. Postdoc and research staff candidates should contact Dr. Chen directly.

  • Selected Projects

    Our research achievements using elaborately tailored molecules to advance science at different frontiers

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    PK Mito Dyes: minimally phototoxic fluorophores for mitochondrial imaging/analysis in live & fixed cells

    with Christian Jüngst (Cologne), Stefan Jakobs lab (Max Planck), Liangyi Chen lab (PKU), & Kai Lei lab (Westlake U)

    Chem Sci 2020, PNAS 2022, PNAS 2024
     

    PNAS cover story

    Chemical Science Most popular 2019-2020 chemical biology articles

    News and Highlights: ScienceNet.cn （中国科学报）

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    Gentle Rhodamines: COT conjugation can generally reduce the phototoxicity of rhodamines for live cell imaging

    With Kai Johnsson lab (Max Planck) and Lu Wang Lab (Fudan)

    ACS Central Science 2024

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    PK Zinc Dyes: minimally phototoxic zinc indicators for multiplexed recording of insulin secretion

    with Liangyi Chen lab (PKU) & Chao Tang lab (PKU)

    ACIE 2021, Nat. Metabolism 2024, ChemEU 2022 (invited review)

     

    Angewandte Chemie Inside Cover

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    Cy-POD: The Cys-conjugated Cy dyes are more prone to photobleaching than those labeled through amide bonds. Here is our Why and How.

    with Chunlai Chen lab (THU)

    JACS 2023

    CurrOpinChemBio 2024 (invited review)

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    Gentle Voltage Sensors: long term imaging of membrane potentials in primary cells

    with Peng Zou lab (PKU)

    PNAS 2023

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    Covalent TMP-tag (Now 3rd generation): live cell protein labeling technology for advanced optical imaging

    A heritage of Prof. Virginia Cornish @Columbia

    ACIE 2022
    JACS 2012, CurrOpinChemBio 2013, ChemComm 2016

     

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    Vibrational palette: visualization of multiplexed molecular targets under stimulated Raman scattering microscopy

    @Columbia with Prof. Wei Min and colleagues

    JACS 2014, ACIE 2015, Nature 2017

     

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    Ladderene unzipping: transformation of an insulating polymer into a semiconductor by ultrasonic pulling force

    @Stanford with Prof. Yan Xia and colleagues

    Science 2017, NatChem 2020

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    Schindilactone A total synthesis: making a complex Chinese natural product from scratch

    @PKU with Profs. Zhen Yang, Jiahua Chen and colleagues

    ACIE 2011, ChemAsianJ 2012

  • Publications

    Selected papers highlighted. # equal contribution. * corresponding authors

    • (Preprint) Ling, J.#; Liu, Y.#; et al A gentle palette of plasma membrane dyes. bioRxiv May. 04 2024
       
    • (42) Liu, T.#; Kompa, J.#; Ling, J.#; Lardon, N.; Zhang, Y.; Chen, J.; Reymond, L.; Chen, P.; Tran, M.; Yang, Z.; Zhang, H.; Liu, Y.; Pitsch, S.; Zou, P.; Wang, L.; Johnsson, K.; Chen, Z.* Gentle rhodamines for live-cell fluorescence microscopy. ACS Cent. Sci. 2024, 10, 1933-44.
    • (41) Chen, J.; Stephan, T.; Gaedke, F.; Liu, T.; Li, Y. Schauss, A.; Chen, P.; Wulff, V.; Jakobs, S.; Jüngst, C.*; Chen, Z.* An aldehyde-crosslinking mitochondrial probe for STED imaging in fixed cells. PNAS 2024, 121, e2317703121.
    • (40) Zhang, Y.; Yang, Z.; Dilizhatai, S.; Shen, X.; Ye, J.; Yu, B.; Pefaur, N.; Scheer, J. M.; Nixon, A. E.*; Chen, Z.* Geometric Antibody Engineering Reveals the Spatial Factor on the Efficacy of Bispecific T Cell Engagers. ACS Chem. Biol. 2024, 19, 916-25
    • (39) Zhang, Y.;Ling, J.; Liu, T.; Chen, Z.* Lumos maxima – How robust fluorophores resist photobleaching? Curr. Opin. Chem. Biol. 2024, 79, 102439 [invited review]
    • (38) Peng, X.#; Ren, H.#; Yang, L.#; Tong, S.#; et al.; Chen, Z.; Liu, H.*; Chen, L*. Readily releasable β cells with tight Ca2+–exocytosis coupling dictate biphasic glucose-stimulated insulin secretion. Nat. Metablism 2024, 6, 238-53
    • (37) Li, C.#; Cheng, K.#; Zhao, Q.#; et al.; Quan, L.*; Chen, Z.* Diazo-carboxyl Click Derivatization Enables Sensitive Analysis of Carboxylic Acid Metabolites in Biosamples. Anal. Chem. 2023, 95, 16976.
    • (36) Dilizhatai, S.; Chen, Z.* Chemical tags and beyond: Live-cell protein labeling technologies for modern optical imaging. Smart Molecules. 2023, 1, e20230002.
    • (35) Liu, S.#; Ling, J.#; et al.; Zou, P.*; Chen, Z.* Orange/far-red hybrid voltage indicators with reduced phototoxicity enable reliable long-term imaging in neurons and cardiomyocytes. PNAS 2023, 120, e2306950120.
    • (34) Yang, X.; Chen, D.; Sun, Q. et al.; Chen, Z.; Liu, Y.*; Zhang, J.*; Zhao, Y.* A live-cell image-based machine learning strategy for reducing variability in PSC differentiation systems. Cell Discov. 2023, 9, 53.
    • (33) Yu, Q.; Yao, Z.; Zhang, H.; Li, Z.; Chen, Z.; Xiong, H.* Transient Stimulated Raman Excited Fluorescence Spectroscopy. J. Am. Chem. Soc. 2023, 145, 7758-62.
    • (32) Zhang, Y.#; Yang, C.#; Peng, S.; Ling, J.; Chen, P.; Ma, Y.; Wang, W.; Chen, Z.*; Chen, C.* General Strategy To Improve the Photon Budget of Thiol-Conjugated Cyanine Dyes. J. Am. Chem. Soc. 2023, 145, 4187-98.
    • (31) Liu, T.#; Stephan, T.#; Chen, P.; Keller-Findeisen, J.; Chen, J.; Riedel, D.; Yang, Z.; Jakobs, S.; Chen, Z.* Multi-color live-cell STED nanoscopy of mitochondria with a gentle inner membrane stain. PNAS 2022, 119, e2215799119 [Cover]
    • (30) Mo, J.#; Chen, J.#; Shi, Y.; Sun, J.; Wu, Y.; Liu, T.; Zhang, J.; Zheng, Y.; Li, Y.; Chen, Z.* Third-Generation Covalent TMP-Tag for Fast Labeling and Multiplexed Imaging of Cellular Proteins. Angew. Chem. Int. Ed. 2022, 61, e202207905
    • (29) Liu, M.#; Zhang, J.#; Chen, Z.* Emerging trends in fluorescence bioimaging of divalent metal cations using small-molecule indicators. Chem. Eur. J. 2022, 28, e202200587. [Invited Review]
    • (28) Du, J.; Zheng, L.; Gao, P.; Yang, H.; Yang, W.-J.; Guo, F.; Liang, R.; Feng, M.; Wang, Z.; Zhang, Z.; Bai, L.; Bu, Y.; Xing, S.; Zheng, W.; Wang, X.; Quan, L.; Hu, X.; Wu, H.; Chen, Z.; Chen, L.; Wei, K.; Zhang, Z.; Zhu, X.; Zhang, X.; Tu, Q.; Zhao, S.-M.*; Lei, X.*; Xiong, J.-W.* A small-molecule cocktail promotes mammalian cardiomyocyte proliferation and heart regeneration. Cell Stem Cell 2022, 29, 545-58.
    • (27) Niu, Y.; Liu, R.; Guan, C.; Zhang, Y.; Chen, Z.; Hoerer, S.; Nar, H.; Chen, L.* Structural basis of inhibition of the human SGLT2–MAP17 glucose transporter. Nature 2022, 601, 280-4.
    • (26) Zhang, J.#; Peng, X.#; Wu, Y.#; Ren, H.#; Sun, J.; Tong, S.; Liu, T.; Zhao, Y.; Wang, S.; Tang, C.; Chen, L.; Chen, Z.* Red- and Far-Red-Emitting Zinc Probes with Minimal Phototoxicity for Multiplexed Recording of Orchestrated Insulin Secretion. Angew. Chem. Int. Ed. 2021, 60, 25846-55. [Inside Cover]
    • (25) Yang, Z.#; Li, L.#; Ling, J.; Liu, T.; Huang, X.; Ying, Y.; Zhao, Y.; Zhao, Y.; Lei, K.*; Chen, L.*; Chen, Z.* Cyclooctatetraene-conjugated cyanine mitochondrial probes minimize phototoxicity in fluorescence and nanoscopic imaging. Chem. Sci. 2020, 11, 8506-8516.

     

    • (24) Chen, Z.#; Zhu, X.#; Yang, J.; Mercer, J. A. M.; Burns, N. Z.; Martinez, T. J.; Xia, Y. The cascade unzipping of ladderane reveals dynamic effects in mechanochemistry. Nat. Chem. 2020, 12, 302-309.
    • (23) Su, J. K.; Feist, J. D.; Yang, J.; Mercer, J. A. M.; Romaniuk, J. A. H.; Chen, Z.; Cegelski, L.; Burns, N. Z.; Xia, Y. Synthesis and Mechanochemical Activation of Ladderene–Norbornene Block Copolymers. J. Am. Chem. Soc. 2018, 140, 12388.
    • (22) Shi, L.; Zheng, C.; Shen, Y.; Chen, Z.; Silveira, E. S.; Zhang, L.; Wei, M.; Liu, C.; de Sena-Tomas, C.; Targoff, K.; Min, W. Optical imaging of metabolic dynamics in animals. Nature Communications 2018, 9, 2995.
    • (21) Qiao, Y.; Zhou, Z.; Chen, Z.; Du, S.; Cheng, Q.; Zhai, H.; Fritz, N. J.; Du, Q.; Yang, Y. Visualizing ion diffusion in battery systems by fluorescence microscopy: A case study on the dissolution of LiMn2O4. Nano Energy 2018, 45, 68.
    • (20) Chen, Z.; Mercer, J. A. M.; Zhu, X.; Romaniuk, J. A. H.; Pfattner, R.; Cegelski, L.; Martinez, T. J.; Burns, N. Z.; Xia, Y. Mechanochemical unzipping of insulating polyladderene to semiconducting polyacetylene. Science 2017, 357, 475-479 [Front Cover].
    • (19) Wei, L.; Chen, Z.; Shi, L.; Long, R.; Anzalone, A. V.; Zhang, L.; Hu, F.; Yuste, R.; Cornish, V. W.; Min, W. Super-multiplex vibrational imaging. Nature 2017, 544, 465-470.
    • (18) Wei, L.; Hu, F.; Chen, Z.; Shen, Y.; Zhang, L.; Min, W., Live-Cell Bioorthogonal Chemical Imaging: Stimulated Raman Scattering Microscopy of Vibrational Probes. Acc. Chem. Res. 2016, 49, 1494-1502
    • (17) Anzalone, A. V; Chen, Z.; Cornish, V. W. Synthesis of Photoactivatable Azido-acyl Caged Oxazine Fluorophores for Live-cell Imaging. Chem. Commun. (Camb). 2016, 52, 9442-9445
    • (16) Freyer, J. L.; Brucks, S. D.; Gobieski, G. S.; Russell, S. T.; Yozwiak, C. E.; Sun, M.; Chen, Z.; Jiang, Y.; Bandar, J. S.; Stockwell, B. R.; Lambert, T. H.; Campos, L. M., Clickable Poly(ionic liquids): A Materials Platform for Transfection. Angew. Chem. Int. Ed. 2016, 55, 12382-12386
    • (15) Hu, F.; Chen, Z.; Zhang, L.; Shen, Y.; Wei, L.; Min, W. Vibrational Imaging of Glucose Uptake Activity in Live Cells and Tissues by Stimulated Raman Scattering. Angew. Chem. Intl. Ed. 2015, 54, 9821-9825
    • (14) Chen, Z.; Paley, D. W.; Wei, L.; Weisman, A. L.; Friesner, R. A.; Nuckolls, C.; Min, W. Multicolor Live-Cell Chemical Imaging by Isotopically Edited Alkyne Vibrational Palette. J. Am. Chem. Soc. 2014, 136, 8027–8033.
    • (13) Wei, L.; Hu, F.; Shen, Y.; Chen, Z.; Yu, Y.; Lin, C.-C.; Wang, M. C.; Min, W. Live-Cell Imaging of Alkyne-Tagged Small Biomolecules by Stimulated Raman Scattering. Nat. Methods 2014, 11, 410–412.
    • (12) Chen, Z.; Cornish, V. W.; Min, W. Chemical Tags: Inspiration for Advanced Imaging Techniques. Curr. Opin. Chem. Biol. 2013, 17, 637–643.
    • (11) Anzalone, A. V; Wang, T. Y.; Chen, Z.; Cornish, V. W. A Common Diaryl Ether Intermediate for the Gram-Scale Synthesis of Oxazine and Xanthene Fluorophores. Angew. Chem. Int. Ed. Engl. 2013, 52, 650–654.
    • (10) Xu, F.; Wei, L.; Chen, Z.; Min, W. Frustrated FRET for High-Contrast High-Resolution Two-Photon Imaging. Opt. Express 2013, 21, 14097–14108.
    • (9) Zhang, L.; Xu, F.; Chen, Z.; Zhu, X.; Min, W. Bioluminescence Assisted Switching and Fluorescence Imaging (BASFI). J. Phys. Chem. Lett. 2013, 4, 3897–3902.
    • (8) Chen, Z.; Jing, C.; Gallagher, S. S.; Sheetz, M. P.; Cornish, V. W. Second-Generation Covalent TMP-Tag for Live Cell Imaging. J. Am. Chem. Soc. 2012, 134, 13692–13699.
    • (7) Gatzogiannis, E.#; Chen, Z.#; Wei, L.; Wombacher, R.; Kao, Y.-T.; Yefremov, G.; Cornish, V. W.; Min, W. Mapping Protein-Specific Micro-Environments in Live Cells by Fluorescence Lifetime Imaging of a Hybrid Genetic-Chemical Molecular Rotor Tag. Chem. Commun. (Camb). 2012, 48, 8694–8696.
    • (6) Chen, Z.#; Wei, L.#; Zhu, X.#; Min, W. Extending the Fundamental Imaging-Depth Limit of Multi-Photon Microscopy by Imaging with Photo-Activatable Fluorophores. Opt. Express 2012, 20, 18525–18536.
    • (5) Wei, L.; Chen, Z.; Min, W. Stimulated Emission Reduced Fluorescence Microscopy: A Concept for Extending the Fundamental Depth Limit of Two-Photon Fluorescence Imaging. Biomed. Opt. Express 2012, 3, 1465–1475.
    • (4) Li, Y.; Chen, Z.-X.; Xiao, Q.; Ye, Q.-D.; Sun, T.-W.; Meng, F.-K.; Ren, W.-W.; You, L.; Xu, L.-M.; Wang, Y.-F.; et al. Diastereoselective Total Synthesis of (±)-Schindilactone A, Part 2: Construction of the Fully Functionalized CDEFGH Ring System. Chem. Asian J. 2012, 7, 2334–2340.
    • (3) Ren, W.-W.; Chen, Z.-X.; Xiao, Q.; Li, Y.; Sun, T.-W.; Zhang, Z.-Y.; Ye, Q.-D.; Meng, F.-K.; You, L.; Zhao, M.-Z.; et al. Diastereoselective Total Synthesis of (±)-Schindilactone A, Part 3: The Final Phase and Completion. Chem. Asian J. 2012, 7, 2341–2350.
    • (2) Xiao, Q.#; Ren, W.-W.#; Chen, Z.-X.; Sun, T.-W.; Li, Y.; Ye, Q.-D.; Gong, J.-X.; Meng, F.-K.; You, L.; Liu, Y.-F.; et al. Diastereoselective Total Synthesis of (±)-Schindilactone A. Angew. Chem. Int. Ed. Engl. 2011, 50, 7373–7377 [Front Cover].
    • (1) Wang, L.; Gong, J.; Deng, L.; Xiang, Z.; Chen, Z.; Wang, Y.; Chen, J.; Yang, Z. Formal Total Synthesis of N-Methylmaysenine. Org. Lett. 2009, 11, 1809–1812.

  • Samples

    It's our pleasure to distribute our products to promote your research, contact Dr. Chen for material requests

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    PK Mito Red/DeepRed/Orange


    PK Mito dyes feature reduced phototoxicity and stem-cell biocompatibility, enabling STED and Hessian-SIM imaging under super-resolution.

     

    Refer to publications #25 and #31 for details.

     

    Commercial Sources:

     

    China:

    http://www.genvivotech.com/products

     

    International:

    https://spirochrome.com/

     

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