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Bioresorbable silicon electronic sensors for the brain

Abstract

Many procedures in modern clinical medicine rely on the use of electronic implants in treating conditions that range from acute coronary events to traumatic injury1,2. However, standard permanent electronic hardware acts as a nidus for infection: bacteria form biofilms along percutaneous wires, or seed haematogenously, with the potential to migrate within the body and to provoke immune-mediated pathological tissue reactions3,4. The associated surgical retrieval procedures, meanwhile, subject patients to the distress associated with re-operation and expose them to additional complications5,6,7,8. Here, we report materials, device architectures, integration strategies, and in vivo demonstrations in rats of implantable, multifunctional silicon sensors for the brain, for which all of the constituent materials naturally resorb via hydrolysis and/or metabolic action9,10,11,12, eliminating the need for extraction. Continuous monitoring of intracranial pressure and temperature illustrates functionality essential to the treatment of traumatic brain injury2,13; the measurement performance of our resorbable devices compares favourably with that of non-resorbable clinical standards. In our experiments, insulated percutaneous wires connect to an externally mounted, miniaturized wireless potentiostat for data transmission. In a separate set-up, we connect a sensor to an implanted (but only partially resorbable) data-communication system, proving the principle that there is no need for any percutaneous wiring. The devices can be adapted to sense fluid flow, motion, pH or thermal characteristics, in formats that are compatible with the body’s abdomen and extremities, as well as the deep brain, suggesting that the sensors might meet many needs in clinical medicine.

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Figure 1: Bioresorbable, silicon-based mechanical/physical/chemical sensors for biomedical applications.
Figure 2: Bioresorbable interfaces between intracranial sensors and external wireless data-communication modules with percutaneous wiring.
Figure 3: Wireless measurement of intracranial pressure and temperature with bioresorbable sensors implanted in live, freely moving animals.
Figure 4: Application of bioresorbable sensors to various body cavities, and demonstration of an injectable format for deep brain monitoring.

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Acknowledgements

S.-K.K. and co-workers are funded by the Defense Advanced Research Projects Agency. J.G.M. is supported by the National Institute of Mental Health, grant F31MH101956. The authors thank M. R. Bruchas at Washington University School of Medicine for providing immunohistochemistry facilities; M. R. MacEwan at Washington University School of Medicine for discussions on animal protocols; A. Manocchi at Transient Electronics Inc. for performing the dissolution test of polyanhydride; and H. Ning at Xerion Advanced Battery Corporation for assistance with running the BET measurements. H.C. was a Howard Hughes Medical Institute International Student Research Fellow. S.-W.H. was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (grant NRF-2015R1C1A1A02037560). G.P. and K.M.L. were supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future Planning (grants NRF-2007-00107 and NRF-2013M3A9D3045719).

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S.-K.K., S.-W.H., D.V.H., N.A.K., S.Y., J.S., H.Y., R.C.W., C.H.L., S.C., D.S.W., J.C., P.V.B. and J.A.R. designed and fabricated the sensors and interfaces. S.-K.K., S.M.L., J.S., J.K. S.H.L. and J.A.R. designed, fabricated and analysed the near-field communication system with the sensor. S.-K.K., R.K.J.M., S.M.L., D.V.H., H.C., P.G., S.Y., J.S., M.S., R.C.W., C.H.L., B.V., Z.L., Y.H., W.Z.R. and J.A.R. conceived the idea and performed the experiments and analysis. R.K.J.M., P.G., J.G.M., M.S., G.P., A.D.G., A.H.K., K.-M.L. and W.Z.R. analysed the immunohistochemistry. S.-K.K., R.K.J.M., S.-W.H., S.M.L., D.V.H., H.C., W.Z.R. and J.A.R. wrote the manuscript.

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Correspondence to Wilson Z. Ray or John A. Rogers.

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The authors declare no competing financial interests.

Extended data figures and tables

Extended Data Figure 1 Fully implantable near-field communication (NFC) system with bioresorbable interface and intracranial sensors.

a, Diagram of a fully implantable NFC system. This device uses a magnesium foil (~50 μm) for the inductive coil, interconnects and electrodes; patterned silicon nanomembranes (Si-NMs, ~300 nm) for resistors; conventional capacitors; and an advanced NFC microchip for data acquisition, processing and transmission. PLGA serves as the substrate and for encapsulation. The diameter of the entire device is about 15 mm. b, Image of this type of NFC system integrated with a bioresorbable pressure sensor. c, Diagram of the operational principles. d, Series of images showing accelerated dissolution of the NFC system inserted into an ACSF at 60 °C. e, Diagram of the implantation process. The bioresorbable sensors reside in the intracranial space, while the NFC system is located extracranially, on the outside surface of the skull, beneath the skin. Bioresorbable, thin metal wires interconnect the NFC system and the sensors. f, Real-time wireless measurements of ICP, showing transient increases induced by the Valsalva manoeuvre (red, data obtained from a transient ICP sensor; blue, data obtained from a commercial ICP sensor). g, Increase in ICT owing to application of a heating blanket around the head, as determined by bioresorbable (red) and commercial (blue) sensors. h, Demonstrations of implantation and suturing in a rat model. A biodegradable surgical glue (TISSEAL) seals the intracranial space.

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Kang, SK., Murphy, R., Hwang, SW. et al. Bioresorbable silicon electronic sensors for the brain. Nature 530, 71–76 (2016). https://doi.org/10.1038/nature16492

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