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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The authors declare that all data supporting the results in this study are available within the paper and its Supplementary Information.
All BLE firmware is available in the Supplementary Information.
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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.
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.
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary methods, figures, tables and video captions.
Highly precise and wirelessly reprogrammable temporal control for the sequenced delivery of two distinct fluids, with a 1 s delay in between.
Wireless operation of the plug-n-play optofluidic device.
Spatiotemporal heat analysis during fluid actuation using the IR camera.
Smartphone App Graphical User Interface for the wireless, selective and programmable control of multimodal plug-n-play optofluidic devices.
Demonstration of a dependent closed-loop concept through the SimbleeCOM Protocol, using model mice.
Wireless chronic drug delivery in a freely moving mouse.
Wireless selective control triggering of intra-VTA DAMGO release in a group of four mice during a 60-min open-field test.