Polymer-fiber-coupled field-effect sensors for label-free deep brain recordings

Autoři: Yuanyuan Guo aff001;  Carl F. Werner aff002;  Andres Canales aff003;  Li Yu aff004;  Xiaoting Jia aff003;  Polina Anikeeva aff003;  Tatsuo Yoshinobu aff002
Působiště autorů: Frontier Research Institute for Interdisciplinary Sciences (FRIS), Graduate School of Medicine, Graduate School of Biomedical Engineering, Tohoku University, Sendai, Miyagi 9800845, Japan aff001;  Department of Electronic Engineering, Department of Biomedical Engineering, Tohoku University, Sendai, Miyagi, 9808579, Japan aff002;  Department of Materials Science and Engineering, Research Laboratory of Electronics, and McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 24139, United States of America aff003;  Bradley Department of Electrical and Computer Engineering, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, United States of America aff004
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0228076


Electrical recording permits direct readout of neural activity but offers limited ability to correlate it to the network topography. On the other hand, optical imaging reveals the architecture of neural circuits, but relies on bulky optics and fluorescent reporters whose signals are attenuated by the brain tissue. Here we introduce implantable devices to record brain activities based on the field effect, which can be further extended with capability of label-free electrophysiological mapping. Such devices reply on light-addressable potentiometric sensors (LAPS) coupled to polymer fibers with integrated electrodes and optical waveguide bundles. The LAPS utilizes the field effect to convert electrophysiological activity into regional carrier redistribution, and the neural activity is read out in a spatially resolved manner as a photocurrent induced by a modulated light beam. Spatially resolved photocurrent recordings were achieved by illuminating different pixels within the fiber bundles. These devices were applied to record local field potentials in the mouse hippocampus. In conjunction with the raster-scanning via the single modulated beam, this technology may enable fast label-free imaging of neural activity in deep brain regions.

Klíčová slova:

Brain electrophysiology – Electrophysiology – Fiber optics – Fibers – Light – Medical devices and equipment – Neuroimaging – Polymers


1. Buzsáki G, Stark E, Berényi A, Khodagholy D, Kipke DR, Yoon E, et al. Tools for probing local circuits: High-density silicon probes combined with optogenetics. Neuron. 2015;86:92–105. doi: 10.1016/j.neuron.2015.01.028 25856489

2. Kipke DR, Shain W, Buzsaki G, Fetz E, Henderson JM, Hetke JF, et al. Advanced Neurotechnologies for Chronic Neural Interfaces: New Horizons and Clinical Opportunities. Journal of Neuroscience. 2008;28:11830–11838. doi: 10.1523/JNEUROSCI.3879-08.2008 19005048

3. Viventi J, Kim DH, Vigeland L, Frechette ES, Blanco JA, Kim YS, et al. Flexible, foldable, actively multiplexed, high-density electrode array for mapping brain activity in vivo. Nature Neuroscience. 2011;14(12):1599–1605. doi: 10.1038/nn.2973 22081157

4. Wilt BA, Burns LD, Wei Ho ET, Ghosh KK, Mukamel EA, Schnitzer MJ. Advances in Light Microscopy for Neuroscience. Annual Review of Neuroscience. 2009;32:435–506. doi: 10.1146/annurev.neuro.051508.135540 19555292

5. Flusberg BA, Cocker ED, Piyawattanametha W, Jung JC, Cheung ELM, Schnitzer MJ. Fiber-optic fluorescence imaging. Nature Methods. 2005;2:941–950. doi: 10.1038/nmeth820 16299479

6. Flusberg BA, Jung JC, Cocker ED, Anderson EP, Schnitzer MJ. In vivo brain imaging using a portable 39?gram two-photon fluorescence microendoscope. Optics Letters. 2005;30:2272–2274. doi: 10.1364/ol.30.002272 16190441

7. Flusberg BA, Nimmerjahn A, Cocker ED, Mukamel EA, Barretto RPJ, Ko TH, et al. High-speed, miniaturized fluorescence microscopy in freely moving mice. Nature Methods. 2008;5:935–938. doi: 10.1038/nmeth.1256 18836457

8. Ghosh KK, Burns LD, Cocker ED, Nimmerjahn A, Ziv Y, Gamal AE, et al. Miniaturized integration of a fluorescence microscope. Nature Methods. 2011;8:871–878. doi: 10.1038/nmeth.1694 21909102

9. Lin MZ, Schnitzer MJ. Genetically encoded indicators of neuronal activity. Nature Neuroscience. 2016;19(9):1142–1153. doi: 10.1038/nn.4359 27571193

10. Grienberger C, Konnerth A. Imaging calcium in neurons. Neuron. 2012;73(5):862–885. doi: 10.1016/j.neuron.2012.02.011 22405199

11. Fromherz P. Joining microelectronics and microionics: Nerve cells and brain tissue on semiconductor chips. Solid-State Electronics. 2008;52:1364–1373. doi: 10.1016/j.sse.2008.04.024

12. Khodagholy D, Doublet T, Quilichini P, Gurfinkel M, Leleux P, Ghestem A, et al. In vivo recordings of brain activity using organic transistors. Nature Communications. 2013;4:1575. doi: 10.1038/ncomms2573 23481383

13. Poghossian A, Ingebrandt S, Offenhäusser A, Schöning MJ. Field-effect devices for detecting cellular signals. Seminars in Cell and Developmental Biology. 2009;20:41–48. doi: 10.1016/j.semcdb.2009.01.014 19429490

14. Hafeman DG, Parce JW, Mcconnell HM. Light-addressable potentiometric sensor for biochemical systems. Science. 1988;240:1182–1185.

15. Owicki JC, Bousse LJ, Hafeman DG, Kirk GL, Olson JD, Wada HG, et al. The Light-Addressable Potentiometric Sensor: Principles and Biological Applications. Annual Review of Biophysics and Biomolecular Structure. 1994;23(1):87–114. doi: 10.1146/annurev.bb.23.060194.000511 7919801

16. Yoshinobu T, Iwasaki H, Ui Y, Furuichi K, Ermolenko Y, Mourzina Y, et al. The light-addressable potentiometric sensor for multi-ion sensing and imaging. Methods. 2005;37:94–102. doi: 10.1016/j.ymeth.2005.05.020 16199169

17. Yoshinobu T, Miyamoto KI, Wagner T, Schöning MJ. Recent developments of chemical imaging sensor systems based on the principle of the light-addressable potentiometric sensor. Sensors and Actuators, B: Chemical. 2015;207:926–932. doi: 10.1016/j.snb.2014.09.002

18. Stein B, George M, Gaub HE, Parak WJ. Extracellular measurements of averaged ionic currents with the light-addressable potentiometric sensor (LAPS). Sensors and Actuators, B: Chemical. 2004. doi: 10.1016/j.snb.2003.10.034

19. Parak WJ, George M, Domke J, Radmacher M, Behrends JC, Denyer MC, et al. Can the light-addressable potentiometric sensor (LAPS) detect extracellular potentials of cardiac myocytes. IEEE Transactions on Biomedical Engineering. 2000. doi: 10.1109/10.855939 10943060

20. ichiro Miyamoto K, Yu B, Isoda H, Wagner T, Schöning MJ, Yoshinobu T. Visualization of the recovery process of defects in a cultured cell layer by chemical imaging sensor. Sensors and Actuators, B: Chemical. 2016.

21. Miyamoto KI, Itabashi A, Wagner T, Schöning MJ, Yoshinobu T. High-speed chemical imaging inside a microfluidic channel. Sensors and Actuators, B: Chemical. 2014. doi: 10.1016/j.snb.2013.12.090

22. Abouraddy AF, Bayindir M, Benoit G, Hart SD, Kuriki K, Orf N, et al. Towards multimaterial multifunctional fibres that see, hear, sense and communicate. Nature Materials. 2007;7:336–347. doi: 10.1038/nmat1889

23. Canales A, Jia X, Froriep UP, Koppes RA, Tringides CM, Selvidge J, et al. Multifunctional fibers for simultaneous optical, electrical and chemical interrogation of neural circuits in vivo. Nature Biotechnology. 2015;33:277–284. doi: 10.1038/nbt.3093 25599177

24. Park S, Guo Y, Jia X, Choe HK, Grena B, Kang J, et al. One-step optogenetics with multifunctional flexible polymer fibers. Nature Neuroscience. 2017;20:612–619. doi: 10.1038/nn.4510 28218915

25. Guo Y, Miyamoto KI, Wagner T, Schöning MJ, Yoshinobu T. Device simulation of the light-addressable potentiometric sensor for the investigation of the spatial resolution. Sensors and Actuators, B: Chemical. 2014;204:659–665. doi: 10.1016/j.snb.2014.08.016

26. Guo Y, Miyamoto KI, Wagner T, Schöning MJ, Yoshinobu T. Theoretical study and simulation of light-addressable potentiometric sensors. Physica Status Solidi (A) Applications and Materials Science. 2014;211:1467–1472. doi: 10.1002/pssa.201330354

27. Chauvette S, Crochet S, Volgushev M, Timofeev I. Properties of Slow Oscillation during Slow-Wave Sleep and Anesthesia in Cats. Journal of Neuroscience. 2011;31:14998–5008. doi: 10.1523/JNEUROSCI.2339-11.2011 22016533

28. Wagner T, Miyamoto K, Werner CF, Schöning MJ, Yoshinobu T. Utilising Digital Micro-Mirror Device (DMD) as Scanning Light Source for Light-Addressable Potentiometric Sensors (LAPS). Sensor Letters. 2011;9:812–815. doi: 10.1166/sl.2011.1620

29. Wagner T, Werner CF, Miyamoto KI, Schöning MJ, Yoshinobu T. Development and characterisation of a compact light-addressable potentiometric sensor (LAPS) based on the digital light processing (DLP) technology for flexible chemical imaging. Sensors and Actuators, B: Chemical. 2012;170:34–39. doi: 10.1016/j.snb.2010.12.003

30. Miyamoto KI, Kaneko K, Matsuo A, Wagner T, Kanoh S, Schöning MJ, et al. Miniaturized chemical imaging sensor system using an OLED display panel. Sensors and Actuators, B: Chemical. 2012;170:82–87. doi: 10.1016/j.snb.2011.02.029

31. Soref R. The past, present, and future of silicon photonics. IEEE Journal on Selected Topics in Quantum Electronics. 2006;12:1678–1687. doi: 10.1109/JSTQE.2006.883151

32. Canales A, Park S, Kilias A, Anikeeva P. Multifunctional Fibers as Tools for Neuroscience and Neuroengineering. Accounts of Chemical Research. 2018;51:829–838. doi: 10.1021/acs.accounts.7b00558 29561583

33. Meng C, Zhou J, Papaneri A, Peddada T, Xu K, Cui G. Spectrally Resolved Fiber Photometry for Multi-component Analysis of Brain Circuits. Neuron. 2018;98:707–717. doi: 10.1016/j.neuron.2018.04.012 29731250

34. Bucher ES, Wightman RM. Electrochemical Analysis of Neurotransmitters. Annual Review of Analytical Chemistry. 2015;8(1):239–261. doi: 10.1146/annurev-anchem-071114-040426 25939038

Článek vyšel v časopise


2020 Číslo 1