Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Soft and stretchable organic bioelectronics for continuous intraoperative neurophysiological monitoring during microsurgery

Nature Biomedical Engineering volume 7, pages 1270–1281 (2023)Cite this article

Subjects

Abstract

In microneurosurgery, it is crucial to maintain the structural and functional integrity of the nerve through continuous intraoperative identification of neural anatomy. To this end, here we report the development of a translatable system leveraging soft and stretchable organic-electronic materials for continuous intraoperative neurophysiological monitoring. The system uses conducting polymer electrodes with low impedance and low modulus to record near-field action potentials continuously during microsurgeries, offers higher signal-to-noise ratios and reduced invasiveness when compared with handheld clinical probes for intraoperative neurophysiological monitoring and can be multiplexed, allowing for the precise localization of the target nerve in the absence of anatomical landmarks. Compared with commercial metal electrodes, the neurophysiological monitoring system allowed for enhanced post-operative prognoses after tumour-resection surgeries in rats. Continuous recording of near-field action potentials during microsurgeries may allow for the precise identification of neural anatomy through the entire procedure.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Advantages of soft PEDOT electrodes over conventional handheld probes for intraoperative neurophysiological monitoring.
Fig. 2: Soft PEDOT electrodes for conformable neural interfaces.
Fig. 3: Soft PEDOT electrodes for intraoperative CNAP monitoring.
Fig. 4: Soft PEDOT electrodes for reliable and consistent long-term CNAP monitoring.
Fig. 5: Minimal invasiveness without nerve damage induced by the soft PEDOT electrodes.
Fig. 6: Improved post-operative prognosis using soft PEDOT electrodes.

Similar content being viewed by others

Data availability

All data supporting the results in this study are available within the paper and its Supplementary Information. Source data are provided with this paper.

References

  1. Buckner, J. C. et al. Central nervous system tumors. Mayo Clin. Proc. 82, 1271–1286 (2007).

    Article  PubMed  Google Scholar 

  2. Horbinski, C., Berger, T., Packer, R. J. & Wen, P. Y. Clinical implications of the 2021 edition of the WHO classification of central nervous system tumours. Nat. Rev. Neurol. 18, 515–529 (2022).

    Article  PubMed  Google Scholar 

  3. Miller, K. D. et al. Brain and other central nervous system tumor statistics, 2021. CA Cancer J. Clin. 71, 381–406 (2021).

    Article  PubMed  Google Scholar 

  4. Carlson, M. L. & Link, M. J. Vestibular schwannomas. N. Engl. J. Med. 384, 1335–1348 (2021).

    Article  PubMed  Google Scholar 

  5. Goldbrunner, R. et al. EANO guideline on the diagnosis and treatment of vestibular schwannoma. Neuro Oncol. 22, 31–45 (2020).

    Article  PubMed  Google Scholar 

  6. Sanai, N. & Berger, M. S. Surgical oncology for gliomas: the state of the art. Nat. Rev. Clin. Oncol. 15, 112–125 (2018).

    Article  PubMed  Google Scholar 

  7. Lapointe, S., Perry, A. & Butowski, N. A. Primary brain tumours in adults. Lancet 392, 432–446 (2018).

    Article  PubMed  Google Scholar 

  8. Betka, J. et al. Complications of microsurgery of vestibular schwannoma. Biomed. Res. Int. 2014, 315952 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Hirbe, A. C. & Gutmann, D. H. Neurofibromatosis type 1: a multidisciplinary approach to care. Lancet Neurol. 13, 834–843 (2014).

    Article  PubMed  Google Scholar 

  10. Gonzalez, A. A., Jeyanandarajan, D., Hansen, C., Zada, G. & Hsieh, P. C. Intraoperative neurophysiological monitoring during spine surgery: a review. Neurosurg. Focus 27, E6 (2009).

    Article  PubMed  Google Scholar 

  11. Rho, Y. J., Rhim, S. C. & Kang, J. K. Is intraoperative neurophysiological monitoring valuable predicting postoperative neurological recovery? Spinal Cord 54, 1121–1126 (2016).

    Article  CAS  PubMed  Google Scholar 

  12. Liu, Y. et al. Intraoperative monitoring of neuromuscular function with soft, skin-mounted wireless devices. NPJ Digit. Med. 1, 19 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Langguth, B., Kreuzer, P. M., Kleinjung, T. & De Ridder, D. Tinnitus: causes and clinical management. Lancet Neurol. 12, 920–930 (2013).

    Article  PubMed  Google Scholar 

  14. Watanabe, N. et al. Intraoperative cochlear nerve mapping with the mobile cochlear nerve compound action potential tracer in vestibular schwannoma surgery. J. Neurosurg. 130, 1568–1575 (2018).

    Article  Google Scholar 

  15. Nakatomi, H. et al. Improved preservation of function during acoustic neuroma surgery. J. Neurosurg. 122, 24–33 (2015).

    Article  PubMed  Google Scholar 

  16. Piccirillo, E. et al. Intraoperative cochlear nerve monitoring in vestibular schwannoma surgery—does it really affect hearing outcome? Audiol. Neurootol. 13, 58–64 (2008).

    Article  PubMed  Google Scholar 

  17. Legatt, A. D. Electrophysiology of cranial nerve testing: auditory nerve. J. Clin. Neurophysiol. 35, 25–38 (2018).

    Article  PubMed  Google Scholar 

  18. Yamakami, I., Yoshinori, H., Saeki, N., Wada, M. & Oka, N. Hearing preservation and intraoperative auditory brainstem response and cochlear nerve compound action potential monitoring in the removal of small acoustic neurinoma via the retrosigmoid approach. J. Neurol. Neurosurg. Psychiatry 80, 218–227 (2009).

    Article  CAS  PubMed  Google Scholar 

  19. Yamakami, I., Oka, N. & Yamaura, A. Intraoperative monitoring of cochlear nerve compound action potential in cerebellopontine angle tumour removal. J. Clin. Neurosci. 10, 567–570 (2003).

    Article  PubMed  Google Scholar 

  20. O’Doherty, J. E. et al. Active tactile exploration using a brain–machine–brain interface. Nature 479, 228–231 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Betzel, R. F. et al. Structural, geometric and genetic factors predict interregional brain connectivity patterns probed by electrocorticography. Nat. Biomed. Eng. 3, 902–916 (2019).

    Article  PubMed  Google Scholar 

  22. Miyazaki, H. & Caye-Thomasen, P. Intraoperative auditory system monitoring. Adv. Otorhinolaryngol. 81, 123–132 (2018).

    PubMed  Google Scholar 

  23. Khodagholy, D. et al. Organic electronics for high-resolution electrocorticography of the human brain. Sci. Adv. 2, e1601027 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  24. Jain, P. et al. Intra-operative cortical motor mapping using subdural grid electrodes in children undergoing epilepsy surgery evaluation and comparison with the conventional extra-operative motor mapping. Clin. Neurophysiol. 129, 2642–2649 (2018).

    Article  PubMed  Google Scholar 

  25. Sarnthein, J. et al. Evaluation of a new cortical strip electrode for intraoperative somatosensory monitoring during perirolandic brain surgery. Clin. Neurophysiol. 142, 44–51 (2022).

    Article  PubMed  Google Scholar 

  26. Yuk, H., Lu, B. & Zhao, X. Hydrogel bioelectronics. Chem. Soc. Rev. 48, 1642–1667 (2019).

    Article  CAS  PubMed  Google Scholar 

  27. Paulsen, B. D., Tybrandt, K., Stavrinidou, E. & Rivnay, J. Organic mixed ionic-electronic conductors. Nat. Mater. 19, 13–26 (2020).

    Article  CAS  PubMed  Google Scholar 

  28. Helbing, D. L., Schulz, A. & Morrison, H. Pathomechanisms in schwannoma development and progression. Oncogene 39, 5421–5429 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Ammoun, S. & Hanemann, C. O. Emerging therapeutic targets in schwannomas and other merlin-deficient tumors. Nat. Rev. Neurol. 7, 392–399 (2011).

    Article  CAS  PubMed  Google Scholar 

  30. Matthies, C. & Samii, M. Management of 1000 vestibular schwannomas (acoustic neuromas): clinical presentation. Neurosurgery 40, 1–10 (1997).

    CAS  PubMed  Google Scholar 

  31. Kirchmann, M. et al. Ten-year follow-up on tumor growth and hearing in patients observed with an intracanalicular vestibular schwannoma. Neurosurgery 80, 49–56 (2017).

    Article  PubMed  Google Scholar 

  32. Propp, J. M., McCarthy, B. J., Davis, F. G. & Preston-Martin, S. Descriptive epidemiology of vestibular schwannomas. Neuro Oncol. 8, 1–11 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  33. Deletis, V., Shils, J., Sala, F. & Seidel, K. Neurophysiology in Neurosurgery: A Modern Approach 2nd edn (Elsevier, 2020).

  34. Rampp, S., Rahne, T., Plontke, S. K., Strauss, C. & Prell, J. Intraoperative monitoring of cochlear nerve function during cerebello-pontine angle surgery. HNO 65, 413–418 (2017).

    Article  CAS  PubMed  Google Scholar 

  35. Akil, O., Oursler, A. E., Fan, K. & Lustig, L. R. Mouse auditory brainstem response testing. Bio Protoc. 6, e1768 (2016).

    PubMed  Google Scholar 

  36. Møller, A. R. Intraoperative Neurophysiological Monitoring 3rd edn (Springer, 2011).

  37. Ochal-Choinska, A., Lachowska, M., Kurczak, K. & Niemczyk, K. Audiologic prognostic factors for hearing preservation following vestibular schwannoma surgery. Adv. Clin. Exp. Med. 28, 747–757 (2019).

    Article  PubMed  Google Scholar 

  38. Zhou, W. et al. A novel imaging grading biomarker for predicting hearing loss in acoustic neuromas. Clin. Neuroradiol. 31, 599–610 (2021).

    Article  PubMed  Google Scholar 

  39. Someya, T., Bao, Z. & Malliaras, G. G. The rise of plastic bioelectronics. Nature 540, 379–385 (2016).

    Article  CAS  PubMed  Google Scholar 

  40. Liu, Y. et al. Soft and elastic hydrogel-based microelectronics for localized low-voltage neuromodulation. Nat. Biomed. Eng. 3, 58–68 (2019).

    Article  CAS  PubMed  Google Scholar 

  41. Khodagholy, D. et al. NeuroGrid: recording action potentials from the surface of the brain. Nat. Neurosci. 18, 310–315 (2015).

    Article  CAS  PubMed  Google Scholar 

  42. Jiang, Y. et al. Topological supramolecular network enabled high-conductivity, stretchable organic bioelectronics. Science 375, 1411–1417 (2022).

    Article  CAS  PubMed  Google Scholar 

  43. Yamakami, I., Ito, S. & Higuchi, Y. Retrosigmoid removal of small acoustic neuroma: curative tumor removal with preservation of function. J. Neurosurg. 121, 554–563 (2014).

    Article  PubMed  Google Scholar 

  44. Lacour, S. P., Chan, D., Wagner, S., Li, T. & Suo, Z. Mechanisms of reversible stretchability of thin metal films on elastomeric substrates. Appl. Phys. Lett. 88, 204103 (2006).

    Article  Google Scholar 

  45. Gao, X. et al. Anti-VEGF treatment improves neurological function and augments radiation response in NF2 schwannoma model. Proc. Natl Acad. Sci. USA 112, 14676–14681 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Wu, L. et al. Losartan prevents tumor-induced hearing loss and augments radiation efficacy in NF2 schwannoma rodent models. Sci. Transl. Med. 13, 4816 (2021).

    Article  Google Scholar 

  47. de Medinaceli, L., Freed, W. J. & Wyatt, R. J. An index of the functional condition of rat sciatic nerve based on measurements made from walking tracks. Exp. Neurol. 77, 634–643 (1982).

    Article  PubMed  Google Scholar 

  48. Leong, S. C. & Lesser, T. H. A national survey of facial paralysis on the quality of life of patients with acoustic neuroma. Otol. Neurotol. 36, 503–509 (2015).

    Article  PubMed  Google Scholar 

  49. Owusu, J. A., Stewart, C. M. & Boahene, K. Facial nerve paralysis. Med. Clin. North Am. 102, 1135–1143 (2018).

    Article  PubMed  Google Scholar 

  50. Abramson, A. et al. A flexible electronic strain sensor for the real-time monitoring of tumor regression. Sci. Adv. 8, eabn6550 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Park, C. et al. Protective effect of baicalein on oxidative stress-induced DNA damage and apoptosis in RT4-D6P2T Schwann cells. Int. J. Med. Sci. 16, 8–16 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Wong, H. K. et al. Anti-vascular endothelial growth factor therapies as a novel therapeutic approach to treating neurofibromatosis-related tumors. Cancer Res. 70, 3483–3493 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 82071996). Part of the work was supported by the Wu Tsai Neuroscience Institute at Stanford University. Part of this work was performed at the Stanford Nano Shared Facilities (SNSF), supported by the National Science Foundation under award ECCS-2026822. We thank G. Jia and Z. Xue for administrative support; L. Yang for instrument support of CINM measurements; and D. Zhang, C. Zhang, X. Wang and Y. Wang for guidance with the project.

Author information

Author notes

  1. These authors contributed equally: Wenjianlong Zhou, Yuanwen Jiang.

Authors and Affiliations

  1. Department of Neurosurgery, Beijing Tiantan Hospital, National Center for Neurological Disorders, Capital Medical University, Beijing, China

    Wenjianlong Zhou, Qin Xu, Liangpeng Chen, Yuan Zhang, Xiudong Guan, Shunchang Ma, Peng Kang, Linhao Yuan, Deling Li & Wang Jia

  2. Department of Chemical Engineering, Stanford University, Stanford, CA, USA

    Yuanwen Jiang, Jian-Cheng Lai, Donglai Zhong, Jeffrey B.-H. Tok & Zhenan Bao

  3. Department of Neurophysiology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China

    Hui Qiao

  4. Tianjin Key Laboratory of Molecular Optoelectronic Sciences, Department of Chemistry, School of Science, Tianjin University, Tianjin, China

    Yi-Xuan Wang

  5. Department of Electronic Engineering, Tsinghua University, Beijing, China

    Weining Li, Xuecheng Wang, Jiaxin Lei & Milin Zhang

  6. Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

    Yanru Du & Gehong Dong

  7. Department of Neurotomy, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China

    Shunchang Ma & Wang Jia

  8. China National Clinical Research Center for Neurological Diseases (NCRC-ND), Beijing, China

    Deling Li & Wang Jia

  9. Beijing Neurosurgical Institute, Capital Medical University, Beijing, China

    Deling Li

Authors
  1. Wenjianlong Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuanwen Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qin Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Liangpeng Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hui Qiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yi-Xuan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jian-Cheng Lai
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Donglai Zhong
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yuan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Weining Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Yanru Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Xuecheng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Jiaxin Lei
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Gehong Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Xiudong Guan
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Shunchang Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Peng Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Linhao Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Milin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Jeffrey B.-H. Tok
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Deling Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Zhenan Bao
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Wang Jia
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

W.Z., Y.J., D.L., Z.B. and W.J. designed the study. Y.J., J.-C.L., D.Z. and Y.-X.W. performed material synthesis and characterizations. W.Z., Q.X., L.C., H.Q., Y.Z., W.L., X.W., J.L., X.G., S.M., P.K., L.Y. and M.Z. performed the animal experiments and cell culture. Y.D. and G.D. performed the histological staining. W.Z., Y.J., J.B.-H.T., D.L. and Z.B. wrote the manuscript with input from all co-authors.

Corresponding authors

Correspondence to Deling Li, Zhenan Bao or Wang Jia.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Biomedical Engineering thanks Nick Donaldson, Peter Nakaji and Bozhi Tian for their contribution to the peer review of this work.

Additional information

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

Extended data

Extended Data Fig. 1 Schematic (a) and photo (b) of the PEDOT electrodes wrapped around the facial-acoustic nerve complex.

The PEDOT device was implanted in a human cadaver skull via retrosigmoid approach from superior view of axial cross section. CN V: Trigeminal nerve; CN VII-VIII: Facial-acoustic nerve complex.

Extended Data Fig. 2 Microanatomy and structures affected by vestibular schwannomas (VS).

a, Schematic showing the relevant microanatomy of the cerebellopontine angle (CPA). b-c, Schematic (b) and MRI image (c) showing the effect of tumour growth on the adjacent cranial nerves, the brainstem, and the cerebellum. VS characteristically arise within the internal auditory canal, from one of the two vestibular divisions of the vestibulocochlear nerve. CN V: Trigeminal nerve; CN VII-VIII: Facial-acoustic nerve complex; CN IX-XI: Glossopharyngeal nerve, vagus nerve and accessory nerve.

Extended Data Fig. 3 The whole process of retrosigmoid craniotomy in a rabbit model.

a-c, A linear, vertically oriented occipital incision was used in the surgery. d, After removing the bone, the dura was exposed. e, The dura was then opened, exposing the facial-acoustic nerve complex with the cerebellum retracted. f, Soft PEDOT electrodes were wrapped around the facial-acoustic nerve complex for subsequent neurophysiological monitoring. CN VII-VIII: Facial-acoustic nerve complex.

Extended Data Fig. 4 PEDOT electrodes can be multiplexed for nerve for facial-acoustic nerve complex identification.

Three groups of unidentified nerves were exposed after retracting the cerebellum of an anesthetized rabbit. Soft PEDOT electrodes were wrapped around each visible nerve for facial-acoustic nerve complex identification. Electromyography (EMG, 1 mA, single stimulation) was used in CN V, CN VII and CN XI identification, cochlear nerve action potentials (CNAP) was used in CN VIII identification. The P values for comparison of the amplitudes are as follows: for the CN V (n = 3 rabbits), P < 0.001 compared with the rest; for the CN VII (n = 3 rabbits), P < 0.001 compared with the rest; for the CN VIII (n = 3 rabbits), P < 0.001 compared with the rest; for the CN XI (n = 3 rabbits), P < 0.001 compared with the rest. All error bars denote s.d. *P < 0.05; **P < 0.01; ***P < 0.001; unpaired, two-tailed student’s t-test was used. CN V: Trigeminal nerve; CN VII-VIII: Facial-acoustic nerve complex; CN IX-XI: Lower cranial nerves (Glossopharyngeal nerve, vagus nerve and accessory nerve).

Source data

Extended Data Fig. 5 Soft PEDOT electrode for intra-operative cochlear nerve action potentials (CNAP) monitoring.

a, Photos of the PEDOT (left) and Au (left) electrodes wrapped around the facial-cochlear nerve complex for CNAP recording. b, CNAP values were measured from the PEDOT (up) and Au (down) device. c, PEDOT electrode could consistently record higher CNAP amplitudes than those from the Au electrode. (n = 11 nerves, P < 0.001). All error bars denote s.d. *P < 0.05; **P < 0.01; ***P < 0.001; unpaired, two-tailed student’s t-test was used for c. CN VII-VIII: Facial-acoustic nerve complex.

Source data

Extended Data Fig. 6 PEDOT electrodes for real-time auditory monitoring.

a, Schematic and variation of cochlear nerve action potentials (CNAP) waveforms measured by PEDOT electrodes during nerve tugging. * denotes the time point of nerve tugging. b, Schematic and variation of CNAP waveforms measured by Au during nerve tugging. * denotes the time point of nerve tugging. c, Comparison of response latencies of CNAP recorded by PEDOT or Au electrodes during nerve tugging. (n = 4 rabbits, P = 0.427). d, Comparison of recovery latencies of CNAP recorded by Au or PEDOT electrodes during nerve tugging. (n = 4 rabbits, P < 0.001). e, Percentage of CNAP amplitude after physical nerve tugging recorded by Au or PEDOT electrodes. (n = 4 rabbits, P < 0.001). All error bars denote s.d. *P < 0.05; **P < 0.01; ***P < 0.001; unpaired, two-tailed student’s t-test was used for c-e. Schematics in a and b were created with BioRender.com.

Source data

Extended Data Fig. 7 Hearing preservation without nerve damage after continuous intra-operative neurophysiological monitoring by soft PEDOT electrodes.

a-b, Comparison of brainstem auditory evoked potentials (BAEP) amplitude (a) and latency (b) with and without soft PEDOT electrodes wrapping. P values for comparing the BAEP amplitudes and latencies are as follows: I, pre-operation (n = 8 rabbits) vs post-operation (n = 6 rabbits), P = 0.549; II, pre-operation (n = 8 rabbits) versus post-operation (n = 6 rabbits), P = 0.025; III, pre-operation (n = 8 rabbits) versus post-operation (n = 6 rabbits), P = 0.742; IV, pre-operation (n = 8 rabbits) versus post-operation (n = 6 rabbits), P < 0.001; V, pre-operation (n = 8 rabbits) versus post-operation (n = 6 rabbits), P = 0.258; 0 - I, pre-operation (n = 8 rabbits) versus post-operation (n = 6 rabbits), P = 0.676; I - II, pre-operation (n = 8 rabbits) versus post-operation (n = 6 rabbits), P = 0.076; II - III, pre-operation (n = 8 rabbits) versus post-operation (n = 6 rabbits), P = 0.299; III - IV, pre-operation (n = 8 rabbits) versus post-operation (n = 6 rabbits), P = 0.035; IV - V, pre-operation (n = 8 rabbits) versus post-operation (n = 6 rabbits), P = 0.154. c-d, Comparison of BAEP amplitude (c) and latency (d) with and without rigid electrodes wrapping. P values for comparing the BAEP amplitudes and latencies are as follows: I, pre-operation (n = 8 rabbits) versus post-operation (n = 8 rabbits), P = 0.005; II, pre-operation (n = 8 rabbits) versus post-operation (n = 8 rabbits), P < 0.001; III, pre-operation (n = 8 rabbits) versus post-operation (n = 8 rabbits), P = 0.058; IV, pre-operation (n = 8 rabbits) versus post-operation (n = 8 rabbits), P < 0.001; V, pre-operation (n = 8 rabbits) versus post-operation (n = 8 rabbits), P = 0.002; 0 - I, pre-operation (n = 8 rabbits) versus post-operation (n = 8 rabbits), P < 0.001; I - II, pre-operation (n = 8 rabbits) versus post-operation (n = 8 rabbits), P < 0.001; II - III, pre-operation (n = 8 rabbits) versus post-operation (n = 8 rabbits), P < 0.001; III - IV, pre-operation (n = 8 rabbits) versus post-operation (n = 8 rabbits), P = 0.987; IV - V, pre-operation (n = 8 rabbits) versus post-operation (n = 8 rabbits), P = 0.236. e, Comparison of BAEP amplitude with soft PEDOT electrodes wrapping and with rigid electrodes wrapping. P values for comparing the BAEP amplitudes are as follows: I, PEDOT electrodes (n = 6 rabbits) versus rigid electrodes (n = 8 rabbits), P = 0.049; II, PEDOT electrodes (n = 6 rabbits) versus rigid electrodes (n = 8 rabbits), P < 0.001; III, PEDOT electrodes (n = 6 rabbits) versus rigid electrodes (n = 8 rabbits), P = 0.206; IV, PEDOT electrodes (n = 6 rabbits) versus rigid electrodes (n = 8 rabbits), P = 0.820; V, PEDOT electrodes (n = 6 rabbits) versus rigid electrodes (n = 8 rabbits), P = 0.009. All error bars denote s.d. *P < 0.05; **P < 0.01; ***P < 0.001; NS, not significant; unpaired, two-tailed student’s t-test was used for a-e. I: wave I – potentials in the auditory nerve (distal part); II: wave II – potentials at proximal part of cochlear nucleus; III: wave III – potentials at lower pons, superior olivary nucleus; IV: wave IV - potentials at upper pons; V: wave V - potentials at lower midbrain.

Source data

Extended Data Fig. 8 Long term biocompatibility.

a, Schematic of the biocompatibility study and longitudinal-section slice of sciatic nerve labelled by the inflammatory biomarker ER-HR3 for soft PEDOT, rigid and sham control. Soft PEDOT electrodes or rigid electrodes were wrapped around the sciatic nerve of the rats for 2 weeks, respectively. b, Histogram showing the mean fluorescence intensity of ER-HR3 for soft PEDOT, rigid and sham control (n = 4 nerves). The P values for comparison of the ER-HR3 intensities are as follows: for sham and the soft PEDOT electrodes, P < 0.001; for sham and the rigid electrodes, P < 0.001. for soft PEDOT and rigid electrodes, P < 0.001. All error bars denote s.d. *P < 0.05; **P < 0.01; ***P < 0.001; unpaired, two-tailed student’s t-test was used for b. Schematics in a were created with BioRender.com.

Source data

Extended Data Fig. 9 Correlation between cochlear nerve action potentials (CNAP) signals and degrees of nerve damage.

a-f, Photos of the same rabbit sciatic nerve under various degrees of sharp damage using micro-scissors and corresponding evoked Electromyography (EMG) signals. g, Comparison of evoked EMG amplitudes with soft PEDOT electrodes under various degrees of sharp damage. P values for comparing the EMG amplitudes are as follows: G 0 (n = 4 nerves) versus G I (n = 4 nerves), P = 0.007; G I (n = 4 nerves) versus G II (n = 4 nerves), P = 0.005; G II (n = 4 nerves) versus G III (n = 4 nerves), P = 0.007; G III (n = 4 nerves) versus G IV (n = 4 nerves), P = 0.011; h, Amplitudes of Brainstem auditory evoked potentials (BAEP) and CNAP under various degrees of cochlear nerve damage. CNAP was recorded from soft PEDOT electrodes wrapping around the nerve. P values for comparing the amplitudes are as follows: CNAP: No damage (n = 4 nerves) versus Severe damage (n = 4 nerves), P < 0.001; BAEP (V I): No damage (n = 4 nerves) versus Severe damage (n = 4 nerves), P < 0.001; BAEP (V I): No damage (n = 4 nerves) versus Severe damage (n = 4 nerves), P < 0.001. All error bars denote s.d. *P < 0.05; **P < 0.01; ***P < 0.001; paired, two-tailed student’s t-test was used for g; unpaired, two-tailed student’s t-test was used for h.

Source data

Extended Data Fig. 10 Neural stimulation for facial nerve evaluation.

a, Schematic of neural stimulation for facial nerve evaluation. b-c, Schematic and evoked electromyography (EMG) waveforms by stimulating the facial nerves using PEDOT electrodes (b) and commercial metal electrodes (c) at 4 mA. d, Comparison of evoked EMG amplitudes by PEDOT electrodes and conventional metal electrodes at 4 mA (n = 9 nerves, P < 0.001). All error bars denote s.d. *P < 0.05; **P < 0.01; ***P < 0.001; unpaired, two-tailed student’s t-test was used for d. Schematics in a, b and c were created with BioRender.com.

Source data

Supplementary information

Supplementary Information

Supplementary Figs. 1–12, Table 1 and video captions.

Reporting Summary

Supplementary Video 1

BAEP monitoring.

Supplementary Video 2

CNAP monitoring.

Supplementary Video 3

Comparison of response (recovery) latency between BAEP and CNAP signals under single cochlear nerve tugging.

Supplementary Video 4

The slow response and long recovery latency of BAEP signals under repeated nerve tugging.

Supplementary Video 5

Temporal cochlear nerve tugging under continuous CNAP monitoring.

Supplementary Video 6

Gait study of sciatic nerve schwannoma model.

Supplementary Video 7

Gait comparison between rat monitored with PEDOT electrodes and commercial metal electrodes.

Supplementary Video 8

Electrical stimulations with PEDOT electrodes.

Supplementary Video 9

Comparison of electrical-stimulation efficiency between soft PEDOT electrodes and conventional metal electrodes.

Source data

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhou, W., Jiang, Y., Xu, Q. et al. Soft and stretchable organic bioelectronics for continuous intraoperative neurophysiological monitoring during microsurgery. Nat. Biomed. Eng 7, 1270–1281 (2023). https://doi.org/10.1038/s41551-023-01069-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41551-023-01069-3

Search

Advanced search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer