Demonstration of intracellular real-time molecular quantification via FRET-enhanced optical microcavity

Yaping Wang, Marion C. Lang, Jinsong Lu, Mingqian Suo, Mengcong Du, Yubin Hou, Xiu-Hong Wang () and Pu Wang
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Yaping Wang: Beijing University of Technology
Marion C. Lang: Beijing University of Technology
Jinsong Lu: Beijing University of Technology
Mingqian Suo: Beijing University of Technology
Mengcong Du: Beijing University of Technology
Yubin Hou: Beijing University of Technology
Xiu-Hong Wang: Beijing University of Technology
Pu Wang: Beijing University of Technology

Nature Communications, 2022, vol. 13, issue 1, 1-10

Abstract: Abstract Single cell analysis is crucial for elucidating cellular diversity and heterogeneity as well as for medical diagnostics operating at the ultimate detection limit. Although superbly sensitive biosensors have been developed using the strongly enhanced evanescent fields provided by optical microcavities, real-time quantification of intracellular molecules remains challenging due to the extreme low quantity and limitations of the current techniques. Here, we introduce an active-mode optical microcavity sensing stage with enhanced sensitivity that operates via Förster resonant energy transferring (FRET) mechanism. The mutual effects of optical microcavity and FRET greatly enhances the sensing performance by four orders of magnitude compared to pure Whispering gallery mode (WGM) microcavity sensing system. We demonstrate distinct sensing mechanism of FRET-WGM from pure WGM. Predicted lasing wavelengths of both donor and acceptor by theoretical calculations are in perfect agreement with the experimental data. The proposed sensor enables quantitative molecular analysis at single cell resolution, and real-time monitoring of intracellular molecules over extended periods while maintaining the cell viability. By achieving high sensitivity at single cell level, our approach provides a path toward FRET-enhanced real-time quantitative analysis of intracellular molecules.

Date: 2022
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DOI: 10.1038/s41467-022-34547-4

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