Ultra-sensitive digital quantification of proteins and mRNA in single cells

Jing Lin, Christian Jordi, Minjun Son, Hoang Phan, Nir Drayman, Mustafa Fatih Abasiyanik, Luke Vistain, Hsiung-Lin Tu and Savaş Tay ()
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Jing Lin: University of Chicago
Christian Jordi: University of Chicago
Minjun Son: University of Chicago
Hoang Phan: University of Chicago
Nir Drayman: University of Chicago
Mustafa Fatih Abasiyanik: University of Chicago
Luke Vistain: University of Chicago
Hsiung-Lin Tu: University of Chicago
Savaş Tay: University of Chicago

Nature Communications, 2019, vol. 10, issue 1, 1-10

Abstract: Abstract Simultaneous measurement of proteins and mRNA in single cells enables quantitative understanding and modeling of cellular functions. Here, we present an automated microfluidic system for multi-parameter and ultra-sensitive protein/mRNA measurements in single cells. Our technology improves the sensitivity of digital proximity ligation assay by up to 55-fold, with a detection limit of 2277 proteins per cell and with detection efficiency of as few as 29 protein molecules. Our measurements using this system reveal higher mRNA/protein correlation in single mammalian cells than previous estimates. Furthermore, time-lapse imaging of herpes simplex virus 1 infected epithelial cells enabled by our device shows that expression of ICP4 -a major transcription factor regulating hundreds of viral genes- is only partially correlated with viral protein counts, suggesting that many cells go through abortive infection. These results highlight the importance of high-sensitivity protein/mRNA quantification for understanding fundamental molecular mechanisms in individual cells.

Date: 2019
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DOI: 10.1038/s41467-019-11531-z

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