Nanodroplet processing platform for deep and quantitative proteome profiling of 10-100 mammalian cells

Nat Commun. 2018 Feb 28;9(1):882. doi: 10.1038/s41467-018-03367-w.


Nanoscale or single-cell technologies are critical for biomedical applications. However, current mass spectrometry (MS)-based proteomic approaches require samples comprising a minimum of thousands of cells to provide in-depth profiling. Here, we report the development of a nanoPOTS (nanodroplet processing in one pot for trace samples) platform for small cell population proteomics analysis. NanoPOTS enhances the efficiency and recovery of sample processing by downscaling processing volumes to <200 nL to minimize surface losses. When combined with ultrasensitive liquid chromatography-MS, nanoPOTS allows identification of ~1500 to ~3000 proteins from ~10 to ~140 cells, respectively. By incorporating the Match Between Runs algorithm of MaxQuant, >3000 proteins are consistently identified from as few as 10 cells. Furthermore, we demonstrate quantification of ~2400 proteins from single human pancreatic islet thin sections from type 1 diabetic and control donors, illustrating the application of nanoPOTS for spatially resolved proteome measurements from clinical tissues.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Gene Expression Profiling
  • Humans
  • Islets of Langerhans / chemistry
  • Islets of Langerhans / metabolism*
  • Mass Spectrometry
  • Proteins / chemistry
  • Proteins / genetics*
  • Proteins / metabolism
  • Proteome / chemistry
  • Proteome / genetics*
  • Proteome / metabolism
  • Proteomics


  • Proteins
  • Proteome