Monitoring contractility in cardiac tissue with cellular resolution using biointegrated microlasers

Marcel Schubert; Lewis Woolfson; Isla Rose Mary Barnard; Amy Dorward; Becky  Casement; Andrew Morton; Gavin Bruce Robertson; Paul L. Appleton; Gareth Brian Miles; Carl S Tucker; Samantha J. Pitt; Malte Christian Gather

doi:10.1038/s41566-020-0631-z

Monitoring contractility in cardiac tissue with cellular resolution using biointegrated microlasers

Marcel Schubert^*
, Lewis Woolfson
, Isla Rose Mary Barnard
, Amy Dorward
, Becky Casement
, Andrew Morton
, Gavin Bruce Robertson
, Paul L. Appleton
, Gareth Brian Miles
, Carl S Tucker
, Samantha J. Pitt
, Malte Christian Gather^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

The contractility of cardiac cells is a key parameter that describes the biomechanical characteristics of the beating heart, but functional monitoring of three-dimensional cardiac tissue with single-cell resolution remains a major challenge. Here, we introduce microscopic whispering-gallery-mode lasers into cardiac cells to realize all-optical recording of transient cardiac contraction profiles with cellular resolution. The brilliant emission and high spectral sensitivity of microlasers to local changes in refractive index enable long-term tracking of individual cardiac cells, monitoring of drug administration, accurate measurements of organ-scale contractility in live zebrafish, and robust contractility sensing through hundreds of micrometres of rat heart tissue. Our study reveals changes in sarcomeric protein density as an underlying factor to cardiac contraction. More broadly, the use of novel micro- and nanoscopic lasers as non-invasive, biointegrated optical sensors brings new opportunities to monitor a wide range of physiological parameters with cellular resolution.

Original language	English
Pages (from-to)	452–458
Number of pages	12
Journal	Nature Photonics
Volume	14
Issue number	7
Early online date	15 Jun 2020
DOIs	https://doi.org/10.1038/s41566-020-0631-z
Publication status	Published - Jul 2020

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schubert m et al, Main text_archive
Copyright © 2020 The Author(s), under exclusive licence to Springer Nature Limited 2020. This work has been made available online in accordance with publisher policies or with permission. Permission for further reuse of this content should be sought from the publisher or the rights holder. This is the author created accepted manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at https://doi.org/10.1038/s41566-020-0631-z
Accepted author manuscript, 3.65 MBLicence: Unspecified

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Beating Lasers: Long-term monitoring: Beating Lasers: Long Term monitoring of cardiac cells with intracellular lasers
Schubert, M. (PI)
31/03/18 → 30/03/22
Project: Standard
Resonant and shaped photonics for under: Resonant and shaped photonics for understanding the physical and biomedical world
Dholakia, K. (PI) & Gather, M. (CoI)
1/08/17 → 31/07/22
Project: Standard
ISSF3 Wellcome Trust Award: Institutional Strategic Support Fund (ISSF3)
Brown, C. T. A. (PI)
The Wellcome Trust
1/03/17 → 29/02/20
Project: Standard

Samantha J. Pitt
- sjp24st-andrews.acuk
Person: Academic

Monitoring contractility in cardiac tissue with cellular resolution using biointegrated microlasers (dataset)
Schubert, M. (Creator), Woolfson, L. (Creator), Barnard, I. R. M. (Creator), Dorward, A. (Creator), Casement, B. (Creator), Morton, A. (Creator), Robertson, G. B. (Creator), Appleton, P. L. (Creator), Miles, G. B. (Creator), Tucker, C. S. (Creator), Pitt, S. J. (Creator) & Gather, M. C. (Creator), University of St Andrews, 15 Jun 2020
DOI: 10.17630/97927f1f-a111-46d0-8d41-038771733b73
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title = "Monitoring contractility in cardiac tissue with cellular resolution using biointegrated microlasers",

abstract = "The contractility of cardiac cells is a key parameter that describes the biomechanical characteristics of the beating heart, but functional monitoring of three-dimensional cardiac tissue with single-cell resolution remains a major challenge. Here, we introduce microscopic whispering-gallery-mode lasers into cardiac cells to realize all-optical recording of transient cardiac contraction profiles with cellular resolution. The brilliant emission and high spectral sensitivity of microlasers to local changes in refractive index enable long-term tracking of individual cardiac cells, monitoring of drug administration, accurate measurements of organ-scale contractility in live zebrafish, and robust contractility sensing through hundreds of micrometres of rat heart tissue. Our study reveals changes in sarcomeric protein density as an underlying factor to cardiac contraction. More broadly, the use of novel micro- and nanoscopic lasers as non-invasive, biointegrated optical sensors brings new opportunities to monitor a wide range of physiological parameters with cellular resolution.",

author = "Marcel Schubert and Lewis Woolfson and Barnard, \{Isla Rose Mary\} and Amy Dorward and Becky Casement and Andrew Morton and Robertson, \{Gavin Bruce\} and Appleton, \{Paul L.\} and Miles, \{Gareth Brian\} and Tucker, \{Carl S\} and Pitt, \{Samantha J.\} and Gather, \{Malte Christian\}",

note = "Funding: This research was financially supported by the European Research Council under the European Union{\textquoteright}s Horizon 2020 Framework Programme (FP/2014-2020)/ERC grant agreement no. 640012 (ABLASE), by EPSRC (grant no. EP/P030017/1) and by the RS Macdonald Charitable Trust. S.J.P. acknowledges funding by the Royal Society of Edinburgh (Biomedical Fellowship) and the British Heart Foundation (grant no. FS/17/9/32676). S.J.P. and G.B.R. acknowledge support from The Wellcome Trust Institutional Strategic Support Fund to the University of St Andrews (grant no. 204821/Z/16/A). M.S. acknowledges funding by the European Commission (Marie Sk{\l}odowska-Curie Individual Fellowship, 659213) and the Royal Society (Dorothy Hodgkin Fellowship, DH160102; grant no. RGF\textbackslash{}R1\textbackslash{}180070).",

year = "2020",

month = jul,

doi = "10.1038/s41566-020-0631-z",

language = "English",

volume = "14",

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T1 - Monitoring contractility in cardiac tissue with cellular resolution using biointegrated microlasers

AU - Schubert, Marcel

AU - Woolfson, Lewis

AU - Barnard, Isla Rose Mary

AU - Dorward, Amy

AU - Casement , Becky

AU - Morton, Andrew

AU - Robertson, Gavin Bruce

AU - Appleton, Paul L.

AU - Miles, Gareth Brian

AU - Tucker, Carl S

AU - Pitt, Samantha J.

AU - Gather, Malte Christian

N1 - Funding: This research was financially supported by the European Research Council under the European Union’s Horizon 2020 Framework Programme (FP/2014-2020)/ERC grant agreement no. 640012 (ABLASE), by EPSRC (grant no. EP/P030017/1) and by the RS Macdonald Charitable Trust. S.J.P. acknowledges funding by the Royal Society of Edinburgh (Biomedical Fellowship) and the British Heart Foundation (grant no. FS/17/9/32676). S.J.P. and G.B.R. acknowledge support from The Wellcome Trust Institutional Strategic Support Fund to the University of St Andrews (grant no. 204821/Z/16/A). M.S. acknowledges funding by the European Commission (Marie Skłodowska-Curie Individual Fellowship, 659213) and the Royal Society (Dorothy Hodgkin Fellowship, DH160102; grant no. RGF\R1\180070).

PY - 2020/7

Y1 - 2020/7

N2 - The contractility of cardiac cells is a key parameter that describes the biomechanical characteristics of the beating heart, but functional monitoring of three-dimensional cardiac tissue with single-cell resolution remains a major challenge. Here, we introduce microscopic whispering-gallery-mode lasers into cardiac cells to realize all-optical recording of transient cardiac contraction profiles with cellular resolution. The brilliant emission and high spectral sensitivity of microlasers to local changes in refractive index enable long-term tracking of individual cardiac cells, monitoring of drug administration, accurate measurements of organ-scale contractility in live zebrafish, and robust contractility sensing through hundreds of micrometres of rat heart tissue. Our study reveals changes in sarcomeric protein density as an underlying factor to cardiac contraction. More broadly, the use of novel micro- and nanoscopic lasers as non-invasive, biointegrated optical sensors brings new opportunities to monitor a wide range of physiological parameters with cellular resolution.

AB - The contractility of cardiac cells is a key parameter that describes the biomechanical characteristics of the beating heart, but functional monitoring of three-dimensional cardiac tissue with single-cell resolution remains a major challenge. Here, we introduce microscopic whispering-gallery-mode lasers into cardiac cells to realize all-optical recording of transient cardiac contraction profiles with cellular resolution. The brilliant emission and high spectral sensitivity of microlasers to local changes in refractive index enable long-term tracking of individual cardiac cells, monitoring of drug administration, accurate measurements of organ-scale contractility in live zebrafish, and robust contractility sensing through hundreds of micrometres of rat heart tissue. Our study reveals changes in sarcomeric protein density as an underlying factor to cardiac contraction. More broadly, the use of novel micro- and nanoscopic lasers as non-invasive, biointegrated optical sensors brings new opportunities to monitor a wide range of physiological parameters with cellular resolution.

U2 - 10.1038/s41566-020-0631-z

DO - 10.1038/s41566-020-0631-z

M3 - Article

SN - 1749-4885

VL - 14

SP - 452

EP - 458

JO - Nature Photonics

JF - Nature Photonics

IS - 7

ER -

Monitoring contractility in cardiac tissue with cellular resolution using biointegrated microlasers

Abstract

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Projects

Beating Lasers: Long-term monitoring: Beating Lasers: Long Term monitoring of cardiac cells with intracellular lasers

Resonant and shaped photonics for under: Resonant and shaped photonics for understanding the physical and biomedical world

ISSF3 Wellcome Trust Award: Institutional Strategic Support Fund (ISSF3)

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Samantha J. Pitt

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Monitoring contractility in cardiac tissue with cellular resolution using biointegrated microlasers (dataset)

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