Team Leader

Toshio Yanagida (Ph.D.)

One major goal in the life sciences is to directly observe how intracellular individual molecules behave when they cause changes in a cell's properties. While watching the dynamics of a single living cell using advanced microscopy, we have succeeded in using nanospray technology to extract intracellular molecules from organelles and analyze them with mass spectroscopy. In fact, our detection system is sufficiently sensitive that only 1 pL intracellular sample is needed to conduct the analysis in real-time. Based on this initial breakthrough, we envision a number of cellular applications to which our technique can be applied.

Research Topics

• Development of Live Single Cell Mass Spectrometry (Live MS)
• Application of live MS to cell molecular dynamism
• Application of live MS to Developmental Biology
• Pico-Medicine and Pico-Diagnosis
• Probe-imaging Single Cell Mass Spectrometry

Selected Publications

• Fujii, T., Matsuda, S., Tejedor, M. L., Esaki, T., Sakane, I., Mizuno, H., et al.
  "Direct metabolomics for plant cells by live single-cell mass spectrometry"
  Nat. Protoc. 10, 1445-1456 (2015) doi:10.1038/nprot.2015.084
• Shimizu, T., Miyakawa, S., Esaki, T., Mizuno, H., Masujima, T., Koshiba, T., et al.
  "Live Single-Cell Plant Hormone Analysis by Video-Mass Spectrometry"
  Plant and Cell Physiology 56, 1287-1296 (2015) doi:10.1093/pcp/pcv042
• Fujita, H., Esaki, T., Masujima, T., Hotta, A., Kim, S. H., Noji, H., et al.
  "Comprehensive chemical secretory measurement of single cells trapped in a micro-droplet array with mass spectrometry"
  RSC Adv. 5, 16968-16971 (2015) doi:10.1039/c4ra12021c
• Fukano, Y., Tsuyama, N., Mizuno, H., Date, S., Takano, M. & Masujima, T.
  "Drug metabolite heterogeneity in cultured single cells profiled by pico-trapping direct mass spectrometry"
  Nanomedicine 7, 1365-1374 (2012) doi:10.2217/nnm.12.34
• Tsuyama, N., Mizuno, H. & Masujima, T.
  "Molecular and Functional Analysis of Cellular Phenomena Using Single-Cell Mass Spectrometry"
  Biological & Pharmaceutical Bulletin 35, 1425-1431 (2012)
• Tejedor, M. L., Mizuno, H., Tsuyama, N., Harada, T. & Masujima, T.
  "In Situ Molecular Analysis of Plant Tissues by Live Single-Cell Mass Spectrometry"
  Anal. Chem. 84, 5221-5228 (2012) doi:10.1021/ac202447t
• Date, S., Mizuno, H., Tsuyama, N., Harada, T. & Masujima, T.
  "Direct Drug Metabolism Monitoring in a Live Single Hepatic Cell by Video Mass Spectrometry"
  Anal. Sci. 28, 201-203 (2012)