Wireless optofluidic brain probes for chronic neuropharmacology and photostimulation

Abstract

Both in vivo neuropharmacology and optogenetic stimulation can be used to decode neural circuitry, and can provide therapeutic strategies for brain disorders. However, current neuronal interfaces hinder long-term studies in awake and freely behaving animals, as they are limited in their ability to provide simultaneous and prolonged delivery of multiple drugs, are often bulky and lack multifunctionality, and employ custom control systems with insufficiently versatile selectivity for output mode, animal selection and target brain circuits. Here, we describe smartphone-controlled, minimally invasive, soft optofluidic probes with replaceable plug-like drug cartridges for chronic in vivo pharmacology and optogenetics with selective manipulation of brain circuits. We demonstrate the use of the probes for the control of the locomotor activity of mice for over four weeks via programmable wireless drug delivery and photostimulation. Owing to their ability to deliver both drugs and photopharmacology into the brain repeatedly over long time periods, the probes may contribute to uncovering the basis of neuropsychiatric diseases.

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Fig. 1: Design and operation principles of soft optofluidic probe system with replaceable plug-n-play drug cartridges.
Fig. 2: Thermal, fluidic and mechanical characteristics of wireless plug-n-play optofluidic neural implants.
Fig. 3: Smartphone control of wireless plug-n-play optofluidic neural implants.
Fig. 4: Chronic, wireless drug delivery produces repeatable behavioural changes in mice.
Fig. 5: Wireless, selective control of drug delivery within a group of simultaneously behaving mice.
Fig. 6: Incorporation of wireless photostimulation and wireless pharmacology in awake, behaving mice.

Data availability

The authors declare that all data supporting the results in this study are available within the paper and its Supplementary Information.

Code availability

All BLE firmware is available in the Supplementary Information.

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Acknowledgements

This work was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science and ICT (grant nos. NRF-2018R1C1B6001706 and NRF-2018025230, J.-W.J.). This work was also supported by Mallinckrodt Professorship (M.R.B.), NIH (grant no. R01DA037152), NIDA Diversity Supplement (grant no. R01DA033396-S1, M.R.B. and A.G.), and grant no. NIDA F32DA043999 (D.C.C). Support was also provided by the Hope Center Viral Vectors Core. We thank J.-W. Yu (KAIST) for providing equipment to conduct BLE wireless transmission tests.

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Authors

Contributions

R.Q., A.G., M.R.B. and J.-W.J. conceptualized the project and designed the experiments with methodology. R.Q., J.A. and A.A. fabricated and prepared the devices for behavioural tests. R.Q., A.G. and D.C.C. performed the in vivo behavioural, tracing and imaging experiments. R.Q., A.G., Z.Z., J.X., J.Y.S., C.Y.K., S.-H.B., B.C.L., K.I.J., J.X., M.R.B. and J.-W.J. performed the investigation, analysed the data and wrote up the modelling results. R.Q., Y.X., A.A. and F.L., designed the firmware and software. R.Q., A.G., D.C.C, M.R.B. and J.-W.J. wrote the paper. M.R.B. and J.-W.J. acquired funding and supervised the project. M.R.B. and J.-W.J. are co-senior authors.

Corresponding authors

Correspondence to Michael R. Bruchas or Jae-Woong Jeong.

Ethics declarations

Competing interests

M.R.B. is a co-founder and scientific advisor for Neurolux, Inc., a neurotechnology company that offers neuroscience tools. The device described in this study is not currently sold or manufactured by this company.

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Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

Supplementary methods, figures, tables and video captions.

Reporting Summary

Supplementary Video 1

Highly precise and wirelessly reprogrammable temporal control for the sequenced delivery of two distinct fluids, with a 1 s delay in between.

Supplementary Video 2

Wireless operation of the plug-n-play optofluidic device.

Supplementary Video 3

Spatiotemporal heat analysis during fluid actuation using the IR camera.

Supplementary Video 4

Smartphone App Graphical User Interface for the wireless, selective and programmable control of multimodal plug-n-play optofluidic devices.

Supplementary Video 5

Demonstration of a dependent closed-loop concept through the SimbleeCOM Protocol, using model mice.

Supplementary Video 6

Wireless chronic drug delivery in a freely moving mouse.

Supplementary Video 7

Wireless selective control triggering of intra-VTA DAMGO release in a group of four mice during a 60-min open-field test.

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Qazi, R., Gomez, A.M., Castro, D.C. et al. Wireless optofluidic brain probes for chronic neuropharmacology and photostimulation. Nat Biomed Eng 3, 655–669 (2019). https://doi.org/10.1038/s41551-019-0432-1

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