. 2025 May 21;113(10):1491-1506.e6.

doi: 10.1016/j.neuron.2025.03.017. Epub 2025 Apr 10.

An integrated microfluidic and fluorescence platform for probing in vivo neuropharmacology

Sean C Piantadosi¹, Min-Kyu Lee², Mingzheng Wu³, Huong Huynh⁴, Raudel Avila⁵, Catalina A Zamorano⁶, Carina Pizzano¹, Yixin Wu⁷, Rachael Xavier⁸, Maria Stanslaski⁸, Jiheon Kang⁹, Sarah Thai¹, Youngdo Kim⁷, Jinglan Zhang¹⁰, Yonggang Huang¹¹, Yevgenia Kozorovitskiy¹², Cameron H Good¹³, Anthony R Banks¹³, John A Rogers¹⁴, Michael R Bruchas¹⁵

Affiliations

¹ Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA; Center of Excellence in Neurobiology of Addiction, Pain, and Emotion (NAPE), University of Washington, Seattle, WA, USA.
² Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA; Neurolux Inc., Northfield, IL 60093, USA; Shirley Ryan AbilityLab, Chicago, IL 60611, USA; Department of Physical Medicine and Rehabilitation, Northwestern University, Chicago, IL 60611, USA.
³ Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA; Department of Neurobiology, Northwestern University, Evanston, IL, USA.
⁴ Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA; Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA.
⁵ Department of Mechanical Engineering, Rice University, Houston, TX, USA; Department of Mechanical Engineering, Northwestern University, Evanston, IL 60208, USA.
⁶ Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA; Center of Excellence in Neurobiology of Addiction, Pain, and Emotion (NAPE), University of Washington, Seattle, WA, USA; Department of Pharmacology, University of Washington, Seattle, WA, USA.
⁷ Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA; Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208, USA.
⁸ Neurolux Inc., Northfield, IL 60093, USA.
⁹ Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA.
¹⁰ Department of Neurobiology, Northwestern University, Evanston, IL, USA.
¹¹ Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA; Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208, USA; Department of Mechanical Engineering, Northwestern University, Evanston, IL 60208, USA; Department of Civil and Environmental Engineering, Northwestern University, Evanston, IL 60208, USA.
¹² Department of Neurobiology, Northwestern University, Evanston, IL, USA; Chemistry of Life Processes Institutes, Northwestern University, Evanston, IL, USA.
¹³ Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA; Neurolux Inc., Northfield, IL 60093, USA.
¹⁴ Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA; Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208, USA; Department of Mechanical Engineering, Northwestern University, Evanston, IL 60208, USA; Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. Electronic address: jrogers@northwestern.edu.
¹⁵ Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA; Center of Excellence in Neurobiology of Addiction, Pain, and Emotion (NAPE), University of Washington, Seattle, WA, USA; Department of Pharmacology, University of Washington, Seattle, WA, USA; Department of Bioengineering, University of Washington, Seattle, WA, USA. Electronic address: mbruchas@uw.edu.

PMID: 40215966
PMCID: PMC12097939 (available on 2026-05-21)
DOI: 10.1016/j.neuron.2025.03.017

An integrated microfluidic and fluorescence platform for probing in vivo neuropharmacology

Sean C Piantadosi et al. Neuron. 2025.

. 2025 May 21;113(10):1491-1506.e6.

doi: 10.1016/j.neuron.2025.03.017. Epub 2025 Apr 10.

Authors

Affiliations

¹ Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA; Center of Excellence in Neurobiology of Addiction, Pain, and Emotion (NAPE), University of Washington, Seattle, WA, USA.
² Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA; Neurolux Inc., Northfield, IL 60093, USA; Shirley Ryan AbilityLab, Chicago, IL 60611, USA; Department of Physical Medicine and Rehabilitation, Northwestern University, Chicago, IL 60611, USA.
³ Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA; Department of Neurobiology, Northwestern University, Evanston, IL, USA.
⁴ Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA; Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA.
⁵ Department of Mechanical Engineering, Rice University, Houston, TX, USA; Department of Mechanical Engineering, Northwestern University, Evanston, IL 60208, USA.
⁶ Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA; Center of Excellence in Neurobiology of Addiction, Pain, and Emotion (NAPE), University of Washington, Seattle, WA, USA; Department of Pharmacology, University of Washington, Seattle, WA, USA.
⁷ Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA; Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208, USA.
⁸ Neurolux Inc., Northfield, IL 60093, USA.
⁹ Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA.
¹⁰ Department of Neurobiology, Northwestern University, Evanston, IL, USA.
¹¹ Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA; Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208, USA; Department of Mechanical Engineering, Northwestern University, Evanston, IL 60208, USA; Department of Civil and Environmental Engineering, Northwestern University, Evanston, IL 60208, USA.
¹² Department of Neurobiology, Northwestern University, Evanston, IL, USA; Chemistry of Life Processes Institutes, Northwestern University, Evanston, IL, USA.
¹³ Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA; Neurolux Inc., Northfield, IL 60093, USA.
¹⁴ Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA; Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208, USA; Department of Mechanical Engineering, Northwestern University, Evanston, IL 60208, USA; Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. Electronic address: jrogers@northwestern.edu.
¹⁵ Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA; Center of Excellence in Neurobiology of Addiction, Pain, and Emotion (NAPE), University of Washington, Seattle, WA, USA; Department of Pharmacology, University of Washington, Seattle, WA, USA; Department of Bioengineering, University of Washington, Seattle, WA, USA. Electronic address: mbruchas@uw.edu.

PMID: 40215966
PMCID: PMC12097939 (available on 2026-05-21)
DOI: 10.1016/j.neuron.2025.03.017

Abstract

Neurotechnologies and genetic tools for dissecting neural circuit functions have advanced rapidly over the past decade although the development of complementary pharmacological methodologies has comparatively lagged. Understanding the precise pharmacological mechanisms of neuroactive compounds is critical for advancing basic neurobiology and neuropharmacology, as well as for developing more effective treatments for neurological and neuropsychiatric disorders. However, integrating modern tools for assessing neural activity in large-scale neural networks with spatially localized drug delivery remains a major challenge. Here, we present a dual microfluidic-photometry platform that enables simultaneous intracranial drug delivery with neural dynamics recording in the rodent brain. The integrated platform combines a wireless, battery-free, miniaturized fluidic microsystem with optical probes, allowing for spatially and temporally restricted drug delivery while sensing activity-dependent fluorescence using genetically encoded calcium indicators (GECIs), neurotransmitter sensors, and neuropeptide sensors. We demonstrate the performance of this platform for investigating neuropharmacological mechanisms in vivo in behaving mice.

Keywords: biosensor; fiber photometry; intracranial drug delivery; microfluidic; neuropharmacology; optogenetics; rodent behavior.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests M.R.B., J.A.R., and A.R.B. are co-founders of NeuroLux, Inc., which has a potential commercial interest in this technology. M.-K.L., R.X., M.S., and C.H.G. are employees of NeuroLux, Inc.

Update of

An integrated microfluidic and fluorescence platform for probing in vivo neuropharmacology.
Piantadosi SC, Lee MK, Wu M, Huynh H, Avila R, Pizzano C, Zamorano CA, Wu Y, Xavier R, Stanslaski M, Kang J, Thai S, Kim Y, Zhang J, Huang Y, Kozorovitskiy Y, Good CH, Banks AR, Rogers JA, Bruchas MR. Piantadosi SC, et al. bioRxiv [Preprint]. 2024 May 14:2024.05.14.594203. doi: 10.1101/2024.05.14.594203. bioRxiv. 2024. Update in: Neuron. 2025 May 21;113(10):1491-1506.e6. doi: 10.1016/j.neuron.2025.03.017. PMID: 38798493 Free PMC article. Updated. Preprint.

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Microfluidic technologies for wearable and implantable biomedical devices.
Wang Z, Shah A, Lee H, Lee CH. Wang Z, et al. Lab Chip. 2025 Aug 21. doi: 10.1039/d5lc00499c. Online ahead of print. Lab Chip. 2025. PMID: 40836841 Free PMC article. Review.

References

1. Boyden ES, Zhang F, Bamberg E, Nagel G, and Deisseroth K (2005). Millisecond-timescale, genetically targeted optical control of neural activity. Nature neuroscience 8, 1263–1268. 10.1038/nn1525. - DOI - PubMed
1. Deisseroth K, and Schnitzer MJ (2013). Engineering approaches to illuminating brain structure and dynamics. Neuron 80, 568–577. 10.1016/j.neuron.2013.10.032. - DOI - PMC - PubMed
1. Cui G, Jun SB, Jin X, Luo G, Pham MD, Lovinger DM, Vogel SS, and Costa RM (2014). Deep brain optical measurements of cell type-specific neural activity in behaving mice. Nature protocols 9, 1213–1228. 10.1038/nprot.2014.080. - DOI - PMC - PubMed
1. Chen TW, Wardill TJ, Sun Y, Pulver SR, Renninger SL, Baohan A, Schreiter ER, Kerr RA, Orger MB, Jayaraman V, et al. (2013). Ultrasensitive fluorescent proteins for imaging neuronal activity. Nature 499, 295–300. 10.1038/nature12354. - DOI - PMC - PubMed
1. Simpson EH, Akam T, Patriarchi T, Blanco-Pozo M, Burgeno LM, Mohebi A, Cragg SJ, and Walton ME (2024). Lights, fiber, action! A primer on in vivo fiber photometry. Neuron 112, 718–739. 10.1016/j.neuron.2023.11.016. - DOI - PMC - PubMed

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An integrated microfluidic and fluorescence platform for probing in vivo neuropharmacology

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An integrated microfluidic and fluorescence platform for probing in vivo neuropharmacology

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