Monitoring contractility in cardiac tissue with cellular resolution using biointegrated microlasers

Schubert, Marcel; Woolfson, Lewis; Barnard, Isla Rose Mary; Dorward, Amy M; Casement, Becky; Morton, Andrew; Robertson, Gavin B.; Appleton, Paul L.; Miles, Gareth B.; Tucker, Carl; Pitt, Samantha J.; Gather, Malte C.

doi:10.1038/s41566-020-0631-z

Cited by 100 publications

(117 citation statements)

References 52 publications

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“…The second was the slicing of tissue blocks in the epicardium-tangential plane, which ensures optimal alignment of cardiomyocytes with the slicing blade and results in substantially reduced cell damage [ 31 , 47 ]. LMS are now prepared from almost all of the animal species including mice [ 20 , 39 , 40 , 52], rats [ 4 – 7 , 11 , 29 , 35 , 39 49, 50, 53], guinea pigs [ 6 , 7 , 48], rabbits [48], dogs [ 8 , 38 , 39 ] and pigs [ 36 ]). LMS can also be prepared from human specimens [ 3 , 9 , 29 , 41 , 43 , 44 ] providing great potential for translational studies.…”

Section: Lms Preparationmentioning

confidence: 99%

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A practical guide for investigating cardiac physiology using living myocardial slices

Watson

Dendorfer²,

Thum

et al. 2020

Basic Res Cardiol

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Ex vivo multicellular preparations are essential tools to study tissue physiology. Among them, the recent methodological and technological developments in living myocardial slices (LMS) are attracting increasing interest by the cardiac research field. Despite this, this research model remains poorly perceived and utilized by most research laboratories. Here, we provide a practical guide on how to use LMS to interrogate multiple aspects of cardiac function, structure and biochemistry. We discuss issues that should be considered to conduct successful experiments, including experimental design, sample preparation, data collection and analysis. We describe how laboratory setups can be adapted to accommodate and interrogate this multicellular research model. These adaptations can often be achieved at a reasonable cost with off-the-shelf components and operated reliably using well-established protocols and freely available software, which is essential to broaden the utilization of this method. We will also highlight how current measurements can be improved to further enhance data quality and reliability to ensure inter-laboratory reproducibility. Finally, we summarize the most promising biomedical applications and envision how living myocardial slices can lead to further breakthroughs.

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Section: Lms Preparationmentioning

confidence: 99%

“…In a recent study by Schubert et al . , micro- and nanoscopic lasers were used for optical recording of transient cardiac contraction profiles [ 39 ]. These recordings were not restricted to the tissue surface, but could sense though hundreds of micrometers of rat heart tissue.…”

Section: Contractile Functionmentioning

confidence: 99%

A practical guide for investigating cardiac physiology using living myocardial slices

Watson

Dendorfer²,

Thum

et al. 2020

Basic Res Cardiol

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“…During the last few years, the application of microlasers, especially whispering-gallery mode (WGM) microlasers, in chemical and biological sensing has increased due to advances made in reducing the gap between laboratory experiments and their real-world application. A number of exciting applications of WGM lasers in biosensing have been reported, such as lasing within living cells 4 , monitoring contractility in cardiac tissue 5 , detection of molecular electrostatic changes at biointerfaces 6 , label-free detection of single virus particles 7 and advancement of in vivo sensing 4 , 8 , 9 . WGM microlasers with a liquid-core optical ring resonator (LCORR) can probe the properties of a gain medium introduced as a fluid into the core of a thin-walled glass capillary, thereby providing good sensitivity for the detection of health biomarkers such as DNA and protein molecules 10 , 11 .…”

Section: Introductionmentioning

confidence: 99%

Review of biosensing with whispering-gallery mode lasers

et al. 2021

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Lasers are the pillars of modern optics and sensing. Microlasers based on whispering-gallery modes (WGMs) are miniature in size and have excellent lasing characteristics suitable for biosensing. WGM lasers have been used for label-free detection of single virus particles, detection of molecular electrostatic changes at biointerfaces, and barcode-type live-cell tagging and tracking. The most recent advances in biosensing with WGM microlasers are described in this review. We cover the basic concepts of WGM resonators, the integration of gain media into various active WGM sensors and devices, and the cutting-edge advances in photonic devices for micro- and nanoprobing of biological samples that can be integrated with WGM lasers.

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“…Biological laser, which embeds biological materials into the gain medium and optical cavity, is an emerging technology that offers new ways of using laser light in biomedical applications [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] . Thanks to the strong light-matter interactions provided by an optical cavity, subtle changes in biological gain media could be amplified, leading to distinctive output lasing characteristics.…”

Section: Introductionmentioning

confidence: 99%

Single Cell Biological Microlasers Powered by Deep Learning

Qiao

Zhang

Jie

et al. 2021

Preprint

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Cellular lasers are cutting-edge technologies for biomedical applications. Due to the enhanced interactions between light and cells in microcavities, cellular properties and subtle changes of cells can be significantly reflected by the laser emission characteristics. In particular, transverse laser modes from single-cell lasers which utilize Fabry–Pérot cavities are highly correlated to the spatial biophysical properties of cells. However, the high chaotic and complex variation of laser modes limits their practical applications for cell detections. Deep learning technique has demonstrated its powerful capability in solving complex imaging problems, which is expected to be applied for cell detections based on laser mode imaging. In this study, deep learning technique was applied to analyze laser modes generated from single-cell lasers, in which a correlation between laser modes and physical properties of cells was built. As a proof-of-concept, we demonstrated the predictions of cell sizes using deep learning based on laser mode imaging. In the first part, bioinspired cell models were fabricated to systematically study how cell sizes affect the characteristics of laser modes. By training a convolutional neuron network (CNN) model with laser mode images, predictions of cell model diameters with a sub-wavelength accuracy were achieved. In the second part, deep learning was employed to study laser modes generated from biological cells. By training a CNN model with laser mode images acquired from astrocyte cells, predictions of cell sizes with a sub-wavelength accuracy were also achieved. The results show the great potential of laser mode imaging integrated with deep learning for cell analysis and biophysical studies.

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Monitoring contractility in cardiac tissue with cellular resolution using biointegrated microlasers

Cited by 100 publications

References 52 publications

A practical guide for investigating cardiac physiology using living myocardial slices

A practical guide for investigating cardiac physiology using living myocardial slices

Review of biosensing with whispering-gallery mode lasers

Single Cell Biological Microlasers Powered by Deep Learning

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