Chronic intracortical neural recordings using microelectrode arrays coated with PEDOT–TFB
Open accessAbstract
Microelectrode arrays have been extensively utilized to record extracellular neuronal activity for brain-machine interface applications. Modifying the microelectrodes with conductive polymers such as poly(3,4-ethylenedioxythiophene) (PEDOT) has been reported to be advantageous because it increases the effective surface area of the microelectrodes, thereby decreasing impedance and enhancing charge transfer capacity. However, the long term stability and integrity of such coatings for chronic recordings remains unclear. Previously, our group has demonstrated that use of the smaller counter ion tetrafluoroborate (TFB) during electrodeposition increased the stability of the PEDOT coatings in vitro compared to the commonly used counter ion poly(styrenesulfonate) (PSS). In the current work, we examined the long-term in vivo performance of PEDOT-TFB coated microelectrodes. To do so, we selectively modified half of the microelectrodes on NeuroNexus single shank probes with PEDOT-TFB while the other half of the microelectrodes were modified with gold as a control. The modified probes were then implanted into the primary motor cortex of rats. Single unit recordings were observed on both PEDOT-TFB and gold control microelectrodes for more than 12 weeks. Compared to the gold-coated microelectrodes, the PEDOT-TFB coated microelectrodes exhibited an overall significantly lower impedance and higher number of units per microelectrode specifically for the first four weeks. The majority of PEDOT-TFB microelectrodes with activity had an impedance magnitude lower than 400 kΩ at 1 kHz. Our equivalent circuit modeling of the impedance data suggests stability in the polymer-related parameters for the duration of the study. In addition, when comparing PEDOT-TFB microelectrodes with and without long-term activity, we observed a distinction in certain circuit parameters for these microelectrodes derived from equivalent circuit modeling prior to implantation. This observation may prove useful in qualifying PEDOT-TFB microelectrodes with a greater likelihood of registering long-term activity. Overall, our findings confirm that PEDOT-TFB is a chronically stable coating for microelectrodes to enable neural recording.Statement of significance Microelectrode arrays have been extensively utilized to record extracellular neuronal activity for brain-machine interface applications. Poly(3,4-ethylenedioxythiophene) (PEDOT) has gained interest because of its unique electrochemical characteristics and its excellent intrinsic electrical conductivity. However, the long-term stability of the PEDOT film, especially for chronic neural applications, is unclear. In this manuscript, we report for the first time the use of highly stable PEDOT doped with tetrafluoroborate (TFB) for long-term neural recordings. We show that PEDOT-TFB coated microelectrodes on average register more units compared to control gold microelectrodes for at least first four weeks post implantation. We collected the in vivo impedance data over a wide frequency spectrum and developed an equivalent circuit model which helped us determine certain parameters to distinguish between PEDOT-TFB microelectrodes with and without long-term activity. Our findings suggest that PEDOT-TFB is a chronically stable coating for neural recording microelectrodes. As such, PEDOT-TFB could facilitate chronic recordings with ultra-small and high-density neural arrays.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
PEDOT is a conductive polymer known to exhibit low electrochemical impedance due to its porous film surface, can be modified by the addition of bioactive molecules, exhibits large charge injection capacity, and has proven to be stable in vivo without causing any toxic effect.
“Poly (3,4 – ethylene dioxytiophene) (PEDOT) is a conductive polymer known to exhibit low electrochemical impedance due to its porous film surface. PEDOT is interesting as it can be modified by the addition of bioactive molecules to e.g. promote cell adherence to the electrode surface. It exhibits large charge injection capacity and has proven to be stable in vivo without causing any toxic effect (”
From Realizing flexible bioelectronic medicines for accessing the peripheral nerves – technology considerations (2018) · cites this paper as Charkhar et al. 2015
Cites
Neural Stimulation and Recording Electrodes
Cogan, S. F. (2008) · Annual Review of Biomedical Engineering · doi:10.1146/annurev.bioeng.10.061807.160518 · Cited by 2,243 · see citing works
Response of brain tissue to chronically implanted neural electrodes
Polikov, V. S., Tresco, P. A., & Reichert, W. M. (2005) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2005.08.015 · Cited by 1,896 · see citing works
Brain–machine interfaces: past, present and future
Lebedev, M. A., & Nicolelis, M. A. L. (2006) · Trends in Neurosciences · doi:10.1016/j.tins.2006.07.004 · Cited by 1,875 · see citing works
Brain responses to micro-machined silicon devices
Szarowski, D. H., Andersen, M. D., Retterer, S. T., Spence, A. J., Isaacson, M. S., Craighead, H. G., Turner, J. N., & Shain, W. G. (2003) · Brain Research · doi:10.1016/s0006-8993(03)03023-3 · Cited by 798 · see citing works
Brain-Controlled Interfaces: Movement Restoration with Neural Prosthetics
Schwartz, A. B., Cui, X. T., Weber, D. J., & Moran, D. W. (2006) · Neuron · doi:10.1016/j.neuron.2006.09.019 · Cited by 792 · see citing works
Carbon nanotube coating improves neuronal recordings
Keefer, E. W., Botterman, B. R., Romero, M. I., Rossi, A. F., & Gross, G. W. (2008) · Nature Nanotechnology · doi:10.1038/nnano.2008.174 · Cited by 721 · see citing works
Kozai, T. D. Y., Langhals, N. B., Patel, P. R., Deng, X., Zhang, H., Smith, K. L., Lahann, J., Kotov, N. A., & Kipke, D. R. (2012) · Nature Materials · doi:10.1038/nmat3468 · Cited by 721 · see citing works
Conducting polymers for neural interfaces: Challenges in developing an effective long-term implant
Green, R. A., Lovell, N. H., Wallace, G. G., & Poole-Warren, L. A. (2008) · Biomaterials · doi:10.1016/j.biomaterials.2008.04.047 · Cited by 691 · see citing works
Impedance Characterization and Modeling of Electrodes for Biomedical Applications
Franks, W., Schenker, I., Schmutz, P., & Hierlemann, A. R. (2005) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.2005.847523 · Cited by 660 · see citing works
Ludwig, K. A., Uram, J. D., Yang, J., Martin, D. C., & Kipke, D. R. (2006) · Journal of Neural Engineering · doi:10.1088/1741-2560/3/1/007 · Cited by 638 · see citing works
Cui, X. T., & Martin, D. C. (2003) · Sensors and Actuators B Chemical · doi:10.1016/s0925-4005(02)00448-3 · Cited by 581 · see citing works
In vivo studies of polypyrrole/peptide coated neural probes
Cui, X. T. (2002) · Biomaterials · doi:10.1016/s0142-9612(02)00415-5 · Cited by 505 · see citing works
Richardson-Burns, S. M., Hendricks, J. L., Foster, B., Povlich, L. K., Kim, D., & Martin, D. C. (2006) · Biomaterials · doi:10.1016/j.biomaterials.2006.11.026 · Cited by 505 · see citing works
Implanted Neural Interfaces: Biochallenges and Engineered Solutions
Grill, W. M., Norman, S. E., & Bellamkonda, R. V. (2009) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-061008-124927 · Cited by 488 · see citing works
Chronic Neural Recording Using Silicon-Substrate Microelectrode Arrays Implanted in Cerebral Cortex
Vetter, R. J., Williams, J. C., Hetke, J. F., Nunamaker, E. A., & Kipke, D. R. (2004) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.2004.826680 · Cited by 477 · see citing works
The electrical properties of metal microelectrodes
Robinson, D. A. (1968) · Proceedings of the IEEE · doi:10.1109/proc.1968.6458 · Cited by 459 · see citing works
PEDOT Nanocrystal in Highly Conductive PEDOT:PSS Polymer Films
Takano, T., Masunaga, H., Fujiwara, A., et al. (2012) · Macromolecules · doi:10.1021/ma300120g · Cited by 426 · see citing works
Multifunctional Nanobiomaterials for Neural Interfaces
Abidian, M. R., & Martin, D. C. (2009) · Advanced Functional Materials · doi:10.1002/adfm.200801473 · Cited by 416 · see citing works
Suner, S., Fellows, M. R., Vargas-Irwin, C., Nakata, G. K., & Donoghue, J. P. (2005) · IEEE Transactions on Neural Systems and Rehabilitation Engineering · doi:10.1109/tnsre.2005.857687 · Cited by 415 · see citing works
Using a Common Average Reference to Improve Cortical Neuron Recordings From Microelectrode Arrays
Ludwig, K. A., Miriani, R. M., Langhals, N. B., Joseph, M. D., Anderson, D. J., & Kipke, D. R. (2008) · Journal of Neurophysiology · doi:10.1152/jn.90989.2008 · Cited by 410 · see citing works
Stability of polypyrrole and poly(3,4-ethylenedioxythiophene) for biosensor application
Yamato, H., Ohwa, M., & Wernet, W. (1995) · Journal of Electroanalytical Chemistry · doi:10.1016/0022-0728(95)04156-8 · Cited by 360 · see citing works
The brain–computer interface cycle
van Gerven, M. A. J., Farquhar, J. D. R., Schaefer, R. S., Vlek, R. J., Geuze, J., Nijholt, A., Ramsey, N. F., Haselager, P., Vuurpijl, L. G., Gielen, S. C. A. M., et al. (2009) · Journal of Neural Engineering · doi:10.1088/1741-2560/6/4/041001 · Cited by 328 · see citing works
In Vitro and In Vivo Evaluation of PEDOT Microelectrodes for Neural Stimulation and Recording
Venkatraman, S., Hendricks, J., King, Z. A., Sereno, A. J., Richardson-Burns, S., Martin, D., & Carmena, J. M. (2011) · IEEE Transactions on Neural Systems and Rehabilitation Engineering · doi:10.1109/tnsre.2011.2109399 · Cited by 319 · see citing works
Toward a comparison of microelectrodes for acute and chronic recordings
Ward, M. P., Rajdev, P., Ellison, C., & Irazoqui, P. P. (2009) · Brain Research · doi:10.1016/j.brainres.2009.05.052 · Cited by 296 · see citing works
Ludwig, K. A., Langhals, N. B., Joseph, M. D., Richardson-Burns, S. M., Hendricks, J. L., & Kipke, D. R. (2011) · Journal of Neural Engineering · doi:10.1088/1741-2560/8/1/014001 · Cited by 283 · see citing works
Mechanically-compliant intracortical implants reduce the neuroinflammatory response
Nguyen, J. K., Park, D. J., Skousen, J. L., Hess-Dunning, A. E., Tyler, D. J., Rowan, S. J., Weder, C., & Capadona, J. R. (2014) · Journal of Neural Engineering · doi:10.1088/1741-2560/11/5/056014 · Cited by 274 · see citing works
Abidian, M. R., Ludwig, K. A., Marzullo, T., Martin, D. C., & Kipke, D. R. (2009) · Advanced Materials · doi:10.1002/adma.200900887 · Cited by 256 · see citing works
Organic electrode coatings for next-generation neural interfaces
Robles, U. A. A., Woolley, A. J., Poole-Warren, L. A., Lovell, N. H., & Green, R. A. (2014) · Frontiers in Neuroengineering · doi:10.3389/fneng.2014.00015 · Cited by 255 · see citing works
Potter, K. A., Buck, A. C., Self, W. K., & Capadona, J. R. (2012) · Journal of Neural Engineering · doi:10.1088/1741-2560/9/4/046020 · Cited by 239 · see citing works
Kozai, T. D. Y., Gugel, Z., Li, X., Gilgunn, P. J., Khilwani, R., Ozdoganlar, O. B., Fedder, G. K., Weber, D. J., & Cui, X. T. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2014.07.039 · Cited by 193 · see citing works
Chronic In Vivo Evaluation of PEDOT/CNT for Stable Neural Recordings
Kozai, T. D. Y., Catt, K. A., Du, Z. J., Na, K., Srivannavit, O., Haque, R., Seymour, J. P., Wise, K. D., Yoon, E., & Cui, X. T. (2015) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.2015.2445713 · Cited by 192 · see citing works
Mechanically adaptive intracortical implants improve the proximity of neuronal cell bodies
Harris, J. P., Capadona, J. R., Miller, R. H., Healy, B. C., Shanmuganathan, K., Rowan, S. J., Weder, C., & Tyler, D. J. (2011) · Journal of Neural Engineering · doi:10.1088/1741-2560/8/6/066011 · Cited by 190 · see citing works
Scaling limitations of silicon multichannel recording probes
Najafi, K., Ji, J., & Wise, K. D. (1990) · IEEE Transactions on Biomedical Engineering · doi:10.1109/10.43605 · Cited by 163 · see citing works
Cui, X., & Martin, D. C. (2003) · Sensors and Actuators A: Physical · doi:10.1016/s0924-4247(02)00427-2 · Cited by 160 · see citing works
Repeated voltage biasing improves unit recordings by reducing resistive tissue impedances
Johnson, M. D., Otto, K. J., & Kipke, D. R. (2005) · IEEE Transactions on Neural Systems and Rehabilitation Engineering · doi:10.1109/tnsre.2005.847373 · Cited by 131 · see citing works
Thiol‐ene/acrylate substrates for softening intracortical electrodes
Ware, T. H., Simon, D., Liu, H. C., Musa, T., Vasudevan, S., Sloan, A. M., Keefer, E. W., Rennaker, R. L., & Voit, W. E. (2013) · Journal of Biomedical Materials Research Part B Applied Biomaterials · doi:10.1002/jbmb.32946 · Cited by 126 · see citing works
Minnikanti, S., Diao, G., Pancrazio, J. J., Xie, X., Rieth, L. W., Solzbacher, F., & Peixoto, N. (2013) · Acta Biomaterialia · doi:10.1016/j.actbio.2013.10.031 · Cited by 107 · see citing works
Self-citationMicroporous conducting polymers on neural microelectrode arrays
Yang, J., & Martin, D. C. (2004) · Sensors and Actuators A Physical · doi:10.1016/j.sna.2004.02.029 · Cited by 104 · see citing works
Electrochemical polymerization and properties of PEDOT/S-EDOT on neural microelectrode arrays
Xiao, Y., Cui, X. T., & Martin, D. C. (2004) · Journal of Electroanalytical Chemistry · doi:10.1016/j.jelechem.2004.06.024 · Cited by 103 · see citing works
King, Z. A., Shaw, C. M., Spanninga, S. A., & Martin, D. C. (2011) · Polymer · doi:10.1016/j.polymer.2011.01.042 · Cited by 98 · see citing works
Novel multi-sided, microelectrode arrays for implantable neural applications
Seymour, J. P., Langhals, N. B., Anderson, D. J., & Kipke, D. R. (2011) · Biomedical Microdevices · doi:10.1007/s10544-011-9512-z · Cited by 95 · see citing works
Lu, Y., Li, Y., Pan, J., Wei, P., Liu, N., Wu, B., Cheng, J., Lu, C., & Wang, L. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2011.09.083 · Cited by 94 · see citing works
PEDOT/MWCNT composite film coated microelectrode arrays for neural interface improvement
Chen, S., Pei, W., Gui, Q., Tang, R., Chen, Y., Zhao, S., Wang, H., & Chen, H. (2013) · Sensors and Actuators A Physical · doi:10.1016/j.sna.2013.01.033 · Cited by 87 · see citing works
Quartz crystal microbalance analysis
Naoi, K., Lien, M. M., & Smyrl, W. H. (1989) · Journal of Electroanalytical Chemistry · doi:10.1016/0022-0728(89)87088-3 · Cited by 84 · see citing works
Mandal, H. S., Knaack, G. L., Charkhkar, H., McHail, D. G., Kastee, J. S., Dumas, T. C., Peixoto, N., Rubinson, J. F., & Pancrazio, J. J. (2014) · Acta Biomaterialia · doi:10.1016/j.actbio.2014.02.029 · Cited by 72 · see citing works
Self-citationPolymer Hydrogel Microelectrodes for Neural Communication
Nyberg, T., Inganäs, O., & Jerregård, H. (2002) · Biomedical Microdevices · doi:10.1023/a:1014219828983 · Cited by 68 · see citing works
Gutowski, S. M., Shoemaker, J. T., Templeman, K. L., Wei, Y., Latour, R. A., Bellamkonda, R. V., LaPlaca, M. C., & Garcı́a, A. J. (2015) · Biomaterials · doi:10.1016/j.biomaterials.2014.12.009 · Cited by 68 · see citing works
Bioimpedance modeling to monitor astrocytic response to chronically implanted electrodes
McConnell, G. C., Butera, R. J., & Bellamkonda, R. V. (2009) · Journal of Neural Engineering · doi:10.1088/1741-2560/6/5/055005 · Cited by 67 · see citing works
Electrochemical Processing of Conducting Polymer Fibers
Li, S., Macosko, C. W., & White, H. S. (1993) · Science · doi:10.1126/science.259.5097.957 · Cited by 62 · see citing works
Noise Characterization, Modeling, and Reduction for In Vivo Neural Recording
Yang, Z. Q., Zhao, Q., Keefer, E. W., et al. (2009) · CaltechAUTHORS (California Institute of Technology) · Cited by 44 · see citing works
Improved Poly(3,4-Ethylenedioxythiophene) (PEDOT) for Neural Stimulation
Mandal, H. S., Kastee, J. S., McHail, D. G., Rubinson, J. F., Pancrazio, J. J., & Dumas, T. C. (2015) · Neuromodulation Technology at the Neural Interface · doi:10.1111/ner.12285 · Cited by 43 · see citing works
Self-citationSmectic structures in electrochemically prepared poly(3,4‐ethylenedioxythiophene) films
Breiby, D. W., Samuelsen, E. J., Groenendaal, L., et al. (2003) · Journal of Polymer Science Part B Polymer Physics · doi:10.1002/polb.10412 · Cited by 41 · see citing works
Electrochemical polymerization and properties of PEDOT/S-EDOT on neural microelectrode arrays
Xiao, Y., Cui, X. T., & Martin, D. C. (2004) · Journal of Electroanalytical Chemistry · doi:10.1016/s0022-0728(04)00336-5 · Cited by 31 · see citing works
Kayinamura, Y. P., Ovadia, M., Zavitz, D. H., et al. (2010) · ACS Applied Materials & Interfaces · doi:10.1021/am100480s · Cited by 25 · see citing works
Abidian, M. R., Salas, L. G., Yazdan-Shahmorad, A., Marzullo, T., Martin, D. C., & Kipke, D. R. (2007) · International IEEE/EMBS Conference on Neural Engineering · doi:10.1109/cne.2007.369612 · Cited by 24 · see citing works
In Vivo Electrochemical Characterization of a Tissue–Electrode Interface During Metamorphic Growth
Bozkurt, A. Y., Gilmour, R. F., & Lal, A. (2011) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.2011.2158822 · Cited by 12 · see citing works
Kayinamura, Y. P., Roberts, J. H., & Rubinson, J. F. (2012) · ACS Applied Materials & Interfaces · doi:10.1021/am2017706 · Cited by 12 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Bioinspired neuron-like electronics
Yang, X., Zhou, T., Zwang, T. J., Hong, G., Zhao, Y., Viveros, R. D., Fu, T.-M., Gao, T., & Lieber, C. M. (2019) · Nature Materials · doi:10.1038/s41563-019-0292-9 · Cited by 384 · see citing works
Ferlauto, L., D’Angelo, A. N., Vagni, P., Airaghi Leccardi, M. J. I., Mor, F. M., Cuttaz, E. A., Heuschkel, M. O., Stoppini, L., & Ghezzi, D. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00648 · Cited by 74 · see citing works
Neural interfaces engineered via micro- and nanostructured coatings
Chen, N., Tian, L., Patil, A. C., Peng, S., Yang, I. H., Thakor, N. V., & Ramakrishna, S. (2017) · Nano Today · doi:10.1016/j.nantod.2017.04.007 · Cited by 74 · see citing works
Giagka, V., & Serdijn, W. A. (2018) · Bioelectronic Medicine · doi:10.1186/s42234-018-0010-y · Cited by 58 · see citing works
Niederhoffer, T., Vanhoestenberghe, A., & Lancashire, H. T. (2023) · Journal of Neural Engineering · doi:10.1088/1741-2552/acb084 · Cited by 38 · see citing works
Transient neurovascular interface for minimally invasive neural recording and stimulation
Fanelli, A., Ferlauto, L., Zollinger, E. G., Brina, O., Reymond, P., Machi, P., & Ghezzi, D. (2022) · Advanced Materials Technologies · doi:10.1002/admt.202100176 · Cited by 22 · see citing works
- Authors
- Charkhkar, H., Knaack, G. L., McHail, D. G., Mandal, H. S., Peixoto, N., Rubinson, J. F., Dumas, T. C., & Pancrazio, J. J.
- Affiliations
- George Mason University (US)
- United States Food and Drug Administration (US)
- Blackrock Microsystems (United States) (US)
- Georgetown University (US)
- Corresponding author
- Charkhkar, Hamid
- ORCID
- Venue
- Acta Biomaterialia
- Publisher
- Elsevier BV
- Published
- 2016-03
- Volume
- 32
- Pages
- 57-67
- ISSN
- 1742-7061 (ISSN-L)
- OpenAlex
- W2195914328
- Cited by
- 68
- References
- 57
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 3 · 2023: 9 · 2022: 5 · 2021: 10 · 2020: 6 · 2019: 7 · 2018: 8 · 2017: 6 · 2016: 4
- FWCI
- 2.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Acta Biomaterialia (acceptedVersion)
- PubMed (publishedVersion)
- Funders
- Defense Advanced Research Projects Agency
- Space and Naval Warfare Systems Command
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
- Physical Sciences › Materials Science › Polymers and Plastics › Conducting polymers and applications
- Physical Sciences › Engineering › Electrical and Electronic Engineering › Electrochemical sensors and biosensors
- Keywords
- microelectrode arrays, chronic neural recording, conducting polymer coatings, electrode impedance, primary motor cortex, single-unit recording, equivalent circuit model, electrode stability, brain-computer interface, rat model
- MeSH terms
- Animals, Borates, Boric Acids, Cerebral Cortex, Electrodes, Implanted, Female, Gold, Microelectrodes, Neurons, Polymers, Electric Impedance, Bridged Bicyclo Compounds, Heterocyclic, Coated Materials, Biocompatible, Rats, Long-Evans, Dielectric Spectroscopy
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review