Multiplexed Optical Sensors in Arrayed Islands of Cells for multimodal recordings of cellular physiology

Nat Commun. 2020 Aug 4;11(1):3881. doi: 10.1038/s41467-020-17607-5.


Cells typically respond to chemical or physical perturbations via complex signaling cascades which can simultaneously affect multiple physiological parameters, such as membrane voltage, calcium, pH, and redox potential. Protein-based fluorescent sensors can report many of these parameters, but spectral overlap prevents more than ~4 modalities from being recorded in parallel. Here we introduce the technique, MOSAIC, Multiplexed Optical Sensors in Arrayed Islands of Cells, where patterning of fluorescent sensor-encoding lentiviral vectors with a microarray printer enables parallel recording of multiple modalities. We demonstrate simultaneous recordings from 20 sensors in parallel in human embryonic kidney (HEK293) cells and in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), and we describe responses to metabolic and pharmacological perturbations. Together, these results show that MOSAIC can provide rich multi-modal data on complex physiological responses in multiple cell types.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Adrenergic beta-Antagonists / pharmacology
  • Biosensing Techniques / instrumentation
  • Biosensing Techniques / methods*
  • Calcium / chemistry
  • Green Fluorescent Proteins / metabolism
  • HEK293 Cells
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Hydrogen-Ion Concentration
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism*
  • Microscopy, Fluorescence / methods*
  • Mitochondria / metabolism
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / physiology
  • Optical Imaging / instrumentation
  • Optical Imaging / methods*
  • Oxidants / pharmacology
  • Oxidation-Reduction / drug effects
  • Propanolamines / pharmacology


  • Adrenergic beta-Antagonists
  • Oxidants
  • PHluorin
  • Propanolamines
  • Green Fluorescent Proteins
  • ICI 118551
  • Hydrogen Peroxide
  • Calcium