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Trionic all-optical biological voltage sensing via quantum statistics

Nature Photonics volume 19, pages 540–548 (2025)Cite this article

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Abstract

Quantum confinement in monolayer semiconductors results in optical properties intricately linked to electrons, which can be manipulated by external electric fields. These optoelectronic features offer untapped potential for studying biological electrical activity. In addition to their relatively high quantum yields, picosecond level emission lifetimes make these materials particularly promising for monitoring biological voltages with high spatiotemporal resolution. Here we investigate exciton-to-trion conversion in ångström-thick semiconductors to experimentally demonstrate label-free, dual-polarity, all-optical detection of electrical activity, via changes in photoluminescence, in cardiomyocyte cultures with ultrahigh temporal resolution. We devise a physical model to demonstrate that this conversion process is inherently governed by the quantum statistics of the background electrons induced by biological activity. We show that the monolayer MoS2 enables completely bias-free tetherless operation due to its substantial trion density originating from intrinsic sulfur vacancies introduced during chemical vapour deposition. Our work opens up an unexplored avenue of opportunities for label-free all-optical voltage sensing using ångström-thick semiconductor materials whose applications have been elusive in the biological domain. This line of thinking at the intersection of biology and quantum science could lead to the discovery of non-ubiquitous quantum materials for detection of biological electrical activity.

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Fig. 1: Voltage-dependent trionic PL.
Fig. 2: Spatiotemporal characterization of MoS2 voltage responsivity.
Fig. 3: Simultaneous optical and electrical multimodal extracellular recording.
Fig. 4: All-optical intracellular imaging of porated cardiomyocytes.

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Data availability

All data are available in the Article and its Supplementary Information and via Zenodo at https://doi.org/10.5281/zenodo.14641718 (ref. 59).

Code availability

The code used to generate the figures for this work is available via Zenodo at https://doi.org/10.5281/zenodo.14641718 (ref. 59).

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Acknowledgements

We acknowledge funding from the National Science Foundation (NSF; grants ECCS-2139416 to E.C.; ECCS-2024776, ECCS-1752241 and ECCS-1734940 to D.K), National Institutes of Health (NIH; grants 1R21EY033676 to E.C.; 21EY029466, R21EB026180 and DP2 EB030992 to D.K.; and R01AG045428 to A.J.E.), Office of Naval Research (ONR; grants N000142012405, N000142312163 and N000141912545 to D.K.), G.G. acknowledges fellowships from the NSF GRFP, NIH (grant T32HL007444), the San Diego fellowship and the Seibel Scholars programme for financial support. Fabrication of the devices was performed at the San Diego Nanotechnology Infrastructure of UCSD, a member of the National Nanotechnology Coordinated Infrastructure, which is supported by the NSF (grant ECCS-1542148).

Author information

Author notes

  1. These authors contributed equally: Chawina De-Eknamkul, Fengyi Sun.

Authors and Affiliations

  1. Department of Chemical and Nano Engineering, University of California San Diego, La Jolla, CA, USA

    Yundong Ren, Chawina De-Eknamkul, Jake H. Schwab & Ertugrul Cubukcu

  2. Department of Electrical and Computer Engineering, University of California San Diego, La Jolla, CA, USA

    Fengyi Sun, Mehrdad Ramezani, Wenzhuo Huang, Madison N. Wilson, Duygu Kuzum & Ertugrul Cubukcu

  3. Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, CA, USA

    Gisselle Gonzalez & Adam J. Engler

  4. Sanford Consortium for Regenerative Medicine, La Jolla, CA, USA

    Gisselle Gonzalez & Adam J. Engler

  5. Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, USA

    Jake H. Schwab

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Contributions

E.C. and D.K. conceived the project. E.C. developed the theory. Y.R., C.D., F.S., J.H.S. and E.C. performed optical characterization. Y.R., C.D. and F.S. fabricated devices. W.H. performed the FEM simulations. Y.R., F.S., M.N.W., M.R. and D.K. performed electrical characterization. G.G. and A.J.E. cultured cells. Y.R., M.R., D.K. and E.C. analysed the experimental data. Y.R., D.K., E.C. and A.J.E. wrote the paper.

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Correspondence to Ertugrul Cubukcu.

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Nature Photonics thanks Fedor Jelezko, Daniel McCloskey, Milos Nesladek and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–23 and discussion.

Supplementary Video 1

Fluorescence wide-field microscope recording showing the MoS2’s PL being modulated by a 20 Hz square wave varying from 0 to −60 mV. The field of view is around 200 μm × 200 μm. The video was recorded at 60 frames per second and is played back six times slower. Such wide-field imaging capability demonstrated the MoS2 voltage imaging sensor’s potential of capturing electrophysiology signals at a high spatiotemporal resolution without compromising field of view.

Supplementary Video 2

Fluorescence wide-field microscope recording showing the MoS2’s PL being modulated by a 200 Hz square wave varying from −25 to 25 mV. The reduced field of view of 30 μm × 30 μm allowed the MoS2 PL image to be captured at a frame rate of 500 frames per second. The video is played back 50× slower than the actual recording frame rate.

Supplementary Video 3

The video was recorded at 30 frames per second. The arrows overlay on the video indicated the direction and amplitude of the cell displacement.

Supplementary Video 4

Fluorescence wide-field microscope video of the MoS2 PL recorded at 50 frames per second and played back at 100 frames per second.

Supplementary Video 5

Fluorescence wide-field microscope video of the MoS2 PL recorded at 100 frames per second and played back at 50 frames per second. The two bright spots are the locations of the porated cells. The MoS2 PL has become brighter after exposure to the high intensity laser used to porate the cells. The blinking of the PL at these two spots are due to the intracellular action potential of the cardiomyocytes.

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Ren, Y., De-Eknamkul, C., Sun, F. et al. Trionic all-optical biological voltage sensing via quantum statistics. Nat. Photon. 19, 540–548 (2025). https://doi.org/10.1038/s41566-025-01637-w

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