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Bioresorbable photonic devices for the spectroscopic characterization of physiological status and neural activity

Abstract

Capabilities in real-time monitoring of internal physiological processes could inform pharmacological drug-delivery schedules, surgical intervention procedures and the management of recovery and rehabilitation. Current methods rely on external imaging techniques or implantable sensors, without the ability to provide continuous information over clinically relevant timescales, and/or with requirements in surgical procedures with associated costs and risks. Here, we describe injectable classes of photonic devices, made entirely of materials that naturally resorb and undergo clearance from the body after a controlled operational lifetime, for the spectroscopic characterization of targeted tissues and biofluids. As an example application, we show that the devices can be used for the continuous monitoring of cerebral temperature, oxygenation and neural activity in freely moving mice. These types of devices should prove useful in fundamental studies of disease pathology, in neuroscience research, in surgical procedures and in monitoring of recovery from injury or illness.

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Fig. 1: Bioresorbable Si photodetector with a bioresorbable fibre optic probe for spectroscopic characterization of biological tissues.
Fig. 2: Bioresorbable tri-colour Si photodetector with a bioresorbable fibre optic probe for spectroscopic characterization of biological tissues.
Fig. 3: Bioresorbable optical filter based on multilayer assemblies of films of SiOx and SiNy.
Fig. 4: In vivo evaluations of elemental biodistribution and biocompatibility of bioresorbable devices for spectroscopic characterization of biological tissues throughout their operational period and beyond.
Fig. 5: In vitro demonstrations of oxygenation, temperature, melanin and Ca2+ sensing via spectroscopic measurements using bioresorbable devices.
Fig. 6: Monitoring cerebral temperature, oxygenation and neural activity in freely moving animal models via spectroscopic measurements using bioresorbable devices.
Fig. 7: Representative confocal images of 30-µm horizontal striatal slices at various stages after implantation of the bioresorbable optical probes, compared with a control group.

Data availability

The main data supporting the results of this study are available within the paper and its Supplementary Information files. The raw and analysed datasets generated during the study are available for research purposes from the corresponding author on reasonable request.

References

  1. 1.

    Hotamisligil, G. S. Inflammation and metabolic disorders. Nature 444, 860–867 (2006).

    CAS  Article  Google Scholar 

  2. 2.

    Lo, E. H., Dalkara, T. & Moskowitz, M. A. Mechanisms, challenges and opportunities in stroke. Nat. Rev. Neurosci. 4, 399–414 (2003).

    CAS  Article  Google Scholar 

  3. 3.

    DeBerardinis, R. J. & Chandel, N. S. Fundamentals of cancer metabolism. Sci. Adv. 2, e1600200 (2016).

    Article  Google Scholar 

  4. 4.

    Tai, L.-C. et al. Methylxanthine drug monitoring with wearable sweat sensors. Adv. Mater. 30, 1707442 (2018).

    Article  Google Scholar 

  5. 5.

    Kim, H. et al. Single-neuronal cell culture and monitoring platform using a fully transparent microfluidic DEP device. Sci. Rep. 8, 13194 (2018).

    Article  Google Scholar 

  6. 6.

    Bettinger, C. J. Recent advances in materials and flexible electronics for peripheral nerve interfaces. Bioelectron. Med. 4, 6 (2018).

    Article  Google Scholar 

  7. 7.

    Hamaoka, T., McCully, K. K., Niwayama, M. & Chance, B. The use of muscle near-infrared spectroscopy in sport, health and medical sciences: recent developments. Phil. Trans. R. Soc. A Math. Phys. Eng. Sci. 369, 4591–4604 (2011).

    CAS  Article  Google Scholar 

  8. 8.

    Ferrari, M. & Quaresima, V. A brief review on the history of human functional near-infrared spectroscopy (fNIRS) development and fields of application. Neuroimage 63, 921–935 (2012).

    Article  Google Scholar 

  9. 9.

    Lloyd-Fox, S., Blasi, A. & Elwell, C. E. Illuminating the developing brain: the past, present and future of functional near infrared spectroscopy. Neurosci. Biobehav. Rev. 34, 269–284 (2010).

    CAS  Article  Google Scholar 

  10. 10.

    Hwang, S.-W. et al. A physically transient form of silicon electronics. Science 337, 1640–1644 (2012).

    CAS  Article  Google Scholar 

  11. 11.

    Kang, S. et al. Bioresorbable silicon electronic sensors for the brain. Nature 530, 71–76 (2016).

    CAS  Article  Google Scholar 

  12. 12.

    Tao, H. et al. Silk-based resorbable electronic devices for remotely controlled therapy and in vivo infection abatement. Proc. Natl Acad. Sci. USA 111, 17385–17389 (2014).

    CAS  Article  Google Scholar 

  13. 13.

    Luo, M., Martinez, A. W., Song, C., Herrault, F. & Allen, M. G. A microfabricated wireless RF pressure sensor made completely of biodegradable materials. J. Micro. Syst. 23, 4–13 (2014).

    CAS  Article  Google Scholar 

  14. 14.

    Lu, L. et al. Biodegradable monocrystalline silicon photovoltaic microcells as power supplies for transient biomedical implants. Adv. Energy Mater. 8, 1703035 (2018).

    Article  Google Scholar 

  15. 15.

    Bai, W. et al. Flexible transient optical waveguides and surface-wave biosensors constructed from monocrystalline silicon. Adv. Mater. 30, 1801584 (2018).

    Article  Google Scholar 

  16. 16.

    Nizamoglu, S. et al. Bioabsorbable polymer optical waveguides for deep-tissue photomedicine. Nat. Commun. 7, 10374 (2016).

    CAS  Article  Google Scholar 

  17. 17.

    Yu, K. J. et al. Bioresorbable silicon electronics for transient spatiotemporal mapping of electrical activity from the cerebral cortex. Nat. Mater. 15, 782–791 (2016).

    CAS  Article  Google Scholar 

  18. 18.

    Fang, H. et al. Capacitively coupled arrays of multiplexed flexible silicon transistors for long-term cardiac electrophysiology. Nat. Biomed. Eng. 1, 0038 (2017).

    Article  Google Scholar 

  19. 19.

    Son, D. et al. Bioresorbable electronic stent integrated with therapeutic nanoparticles for endovascular diseases. ACS Nano 9, 5937–5946 (2015).

    CAS  Article  Google Scholar 

  20. 20.

    Karliczek, A. et al. Intraoperative assessment of microperfusion with visible light spectroscopy for prediction of anastomotic leakage in colorectal anastomoses. Color. Dis. 12, 1018–1025 (2010).

    CAS  Article  Google Scholar 

  21. 21.

    Bogomolov, A. et al. Development and testing of an LED-based near-infrared sensor for human kidney tumor diagnostics. Sensors 17, 1914 (2017).

    Article  Google Scholar 

  22. 22.

    Yun, S. H. & Kwok, S. J. J. Light in diagnosis, therapy and surgery. Nat. Biomed. Eng. 1, 0008 (2017).

    Article  Google Scholar 

  23. 23.

    Du, Q. et al. Chip-scale broadband spectroscopic chemical sensing using an integrated supercontinuum source in a chalcogenide glass waveguide. Photonics Res. 6, 506–510 (2018).

    CAS  Article  Google Scholar 

  24. 24.

    Warden, M. R., Cardin, J. A. & Deisseroth, K. Optical neural interfaces. Annu. Rev. Biomed. Eng. 16, 103–129 (2014).

    CAS  Article  Google Scholar 

  25. 25.

    Kang, S.-K. et al. Dissolution behaviors and applications of silicon oxides and nitrides in transient electronics. Adv. Funct. Mater. 24, 4427–4434 (2014).

    CAS  Article  Google Scholar 

  26. 26.

    Fu, R. et al. Implantable and biodegradable poly(l-lactic acid) fibers for optical neural interfaces. Adv. Opt. Mater. 6, 1700941 (2018).

    Article  Google Scholar 

  27. 27.

    Lee, Y. K. et al. Dissolution of monocrystalline silicon nanomembranes and their use as encapsulation layers and electrical interfaces in water-soluble electronics. ACS Nano 11, 12562–12572 (2017).

    CAS  Article  Google Scholar 

  28. 28.

    Yin, L. et al. Dissolvable metals for transient electronics. Adv. Funct. Mater. 24, 645–658 (2014).

    CAS  Article  Google Scholar 

  29. 29.

    Yin, L. et al. Mechanisms for hydrolysis of silicon nanomembranes as used in bioresorbable electronics. Adv. Mater. 27, 1857–1864 (2015).

    CAS  Article  Google Scholar 

  30. 30.

    Kang, S. K. et al. Dissolution chemistry and biocompatibility of silicon- and germanium-based semiconductors for transient electronics. ACS Appl. Mater. Interfaces 7, 9297–9305 (2015).

    CAS  Article  Google Scholar 

  31. 31.

    Brown, J. Q., Vishwanath, K., Palmer, G. M. & Ramanujam, N. Advances in quantitative UV-visible spectroscopy for clinical and pre-clinical application in cancer. Curr. Opin. Biotechnol. 20, 119–131 (2009).

    CAS  Article  Google Scholar 

  32. 32.

    Menon, L. et al. Transferred flexible three-color silicon membrane photodetector arrays. IEEE Photonics J. 7, 1–6 (2015).

    Article  Google Scholar 

  33. 33.

    Liu, C. et al. High performance, biocompatible dielectric thin-film optical filters integrated with flexible substrates and microscale optoelectronic devices. Adv. Opt. Mater. 6, 1800146 (2018).

    Article  Google Scholar 

  34. 34.

    Macleod, H. A. & Hugh, A. Thin-Film Optical Filters (CRC Press/Taylor & Francis, 2010).

  35. 35.

    Chen, T.-W. et al. Ultrasensitive fluorescent proteins for imaging neuronal activity. Nature 499, 295–300 (2013).

    CAS  Article  Google Scholar 

  36. 36.

    Besser, R. S., Louris, P. J. & Musket, R. G. Chemical etch rate of plasma-enhanced chemical vapor deposited SiO2 films. J. Electrochem. Soc. 144, 2859–2864 (1997).

    CAS  Article  Google Scholar 

  37. 37.

    Kraitl, J., Timm, U. & Ewald, H. Non-invasive measurement of blood and tissue parameters based on VIS-NIR spectroscopy. In Proc. SPIE 8591 (SPIE, 2013).

  38. 38.

    Lu, G. & Fei, B. Medical hyperspectral imaging: a review. J. Biomed. Opt. 19, 010901 (2014).

    Article  Google Scholar 

  39. 39.

    Ciurczak, E. W. & Igne, B. Pharmaceutical and Medical Applications of Near-Infrared Spectroscopy 2nd edn (CRC Press, 2014).

  40. 40.

    Durduran, T., Choe, R., Baker, W. B. & Yodh, A. G. Diffuse optics for tissue monitoring and tomography. Rep. Prog. Phys. 73, 076701 (2010).

    Article  Google Scholar 

  41. 41.

    Mrozek, S., Vardon, F. & Geeraerts, T. Brain temperature: physiology and pathophysiology after brain injury. Anesthesiol. Res. Pract. 2012, 989487 (2012).

    PubMed  PubMed Central  Google Scholar 

  42. 42.

    Wang, H. et al. Brain temperature and its fundamental properties: a review for clinical neuroscientists. Front. Neurosci. 8, 307 (2014).

    PubMed  PubMed Central  Google Scholar 

  43. 43.

    Ho, C. L., Wang, C. M., Lee, K. K., Ng, I. & Ang, B. T. Cerebral oxygenation, vascular reactivity, and neurochemistry following decompressive craniectomy for severe traumatic brain injury. J. Neurosurg. 108, 943–949 (2008).

    Article  Google Scholar 

  44. 44.

    Leal-Noval, S. R. et al. Invasive and noninvasive assessment of cerebral oxygenation in patients with severe traumatic brain injury. Intensive Care Med. 36, 1309–1317 (2010).

    CAS  Article  Google Scholar 

  45. 45.

    Toet, M. C., Lemmers, P. M. A., van Schelven, L. J. & van Bel, F. Cerebral oxygenation and electrical activity after birth asphyxia: their relation to outcome. Pediatrics 117, 333–339 (2006).

    Article  Google Scholar 

  46. 46.

    Brassard, P., Ainslie, P. N. & Secher, N. H. Cerebral oxygenation in health and disease. Front. Physiol. 5, 458 (2014).

    Article  Google Scholar 

  47. 47.

    Van Bel, F. & Mintzer, J. P. Monitoring cerebral oxygenation of the immature brain: a neuroprotective strategy? Pediatr. Res. 84, 159–164 (2018).

    Article  Google Scholar 

  48. 48.

    Tye, K. M. & Deisseroth, K. Optogenetic investigation of neural circuits underlying brain disease in animal models. Nat. Rev. Neurosci. 13, 251–266 (2012).

    CAS  Article  Google Scholar 

  49. 49.

    Cui, G. et al. Concurrent activation of striatal direct and indirect pathways during action initiation. Nature 494, 238–242 (2013).

    CAS  Article  Google Scholar 

  50. 50.

    Thrane, A. S. et al. General anesthesia selectively disrupts astrocyte calcium signaling in the awake mouse cortex. Proc. Natl Acad. Sci. USA 109, 18974–18979 (2012).

    CAS  Article  Google Scholar 

  51. 51.

    Siuda, E. R., Al-Hasani, R., McCall, J. G., Bhatti, D. L. & Bruchas, M. R. Chemogenetic and optogenetic activation of Gαs signaling in the basolateral amygdala induces acute and social anxiety-like states. Neuropsychopharmacology 41, 2011–2023 (2016).

    CAS  Article  Google Scholar 

  52. 52.

    Jeong, J.-W. et al. Wireless optofluidic systems for programmable in vivo pharmacology and optogenetics. Cell 162, 662–674 (2015).

    CAS  Article  Google Scholar 

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Acknowledgements

W.Z. acknowledges support from the Army Research Office under grant W911NF-15-1-0035. This work utilized the Northwestern University Micro/Nano Fabrication Facility, which is partially supported by the Soft and Hybrid Nanotechnology Experimental Resource (NSF ECCS-1542205), Materials Research Science and Engineering Center (NSF DMR-1121262), State of Illinois, Northwestern University and Center for Bio-Integrated Electronics (Simpson Querrey Institute). The Center for Developmental Therapeutics is supported by Cancer Center Support Grant P30 CA060553 from the National Cancer Institute, awarded to the Robert H. Lurie Comprehensive Cancer Center.

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W.B., R.F., J.S., D.L., X.N., Y.P., Z.L., T.H., Y.L., D.W., H.Z., X.S., L.Y., W.Z. and J.A.R. designed and fabricated the devices, and performed the analysis. W.B., I.K., J.S., D.L., X.N., Y.P., I.S. and F.A. performed the animal study. C.R.H. and A.B. performed the computed tomography imaging. W.B., I.K, J.S., D.W., X.N., Q.Y., J.Z., K.M. and M.P. performed the study of bioresorption, biodistribution and toxicity. W.B., J.S., I.K., R.F., W.Z. and J.A.R wrote the manuscript with input from all authors.

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Correspondence to John A. Rogers.

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Bai, W., Shin, J., Fu, R. et al. Bioresorbable photonic devices for the spectroscopic characterization of physiological status and neural activity. Nat Biomed Eng 3, 644–654 (2019). https://doi.org/10.1038/s41551-019-0435-y

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