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

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 microcavitie...

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Bibliographic Details
Published in:	Nature communications Vol. 13; no. 1; p. 6685
Main Authors:	Wang, Yaping, Lang, Marion C., Lu, Jinsong, Suo, Mingqian, Du, Mengcong, Hou, Yubin, Wang, Xiu-Hong, Wang, Pu
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 05-11-2022 Nature Publishing Group Nature Portfolio
Subjects:	13 14 14/10 14/19 14/28 14/33 140/125 140/58 631/1647/2196/2197 639/624/1075/1083 639/624/1107/510 9/10 Biosensing Techniques - methods Biosensors Cell viability Energy Energy transfer Engineering research Fluorescence Resonance Energy Transfer Heterogeneity Humanities and Social Sciences Hypotheses Intracellular Lasers Lasing Manufacturing Microcavities Monitoring multidisciplinary Quantitative analysis Real time Science Science (multidisciplinary) Sensitivity enhancement Wavelengths
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Summary:	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. The authors introduce an active-mode optical microcavity sensor with enhanced sensitivity via Förster resonant energy transfer. Changes in lasing wavelengths of both donor and acceptor enable quantitative molecular analysis and real-time monitoring of intracellular molecules.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-022-34547-4