Thin-film implants for bioelectronic medicine

Abstract

This article is based on the MRS Mid-Career Researcher Award "for outstanding contributions to the fundamentals and development of organic electronic materials and their application in biology and medicine" presentation given by George G. Malliaras, University of Cambridge, at the 2023 MRS Spring Meeting in San Francisco, Calif.Bioelectronic medicine offers a revolutionary approach to treating disease by stimulating the body with electricity. While current devices show safety and efficacy, limitations, including bulkiness, invasiveness, and scalability, hinder their wider application. Thin-film implants promise to overcome these limitations. Made using microfabrication technologies, these implants conform better to neural tissues, reduce tissue damage and foreign body response, and provide high-density, multimodal interfaces with the body. This article explores how thin-film implants using organic materials and novel designs may contribute to disease management, intraoperative monitoring, and brain mapping applications. Additionally, the technical challenges to be addressed for this technology to succeed are discussed.

Keywords: Bioelectronic; Biomedical; Devices; Thin film.

Figure 1

(a, b) Fabrication of current implants for bioelectronic medicine. The process involves a manual assembly line. Reprinted with permission from Reference . © 2016 MED-L. (c) Postoperative lateral x-ray shows deep brain stimulation leads implanted in the left and right subcallosal cingulate region. Reprinted with permission from Reference . © 2019 Proceedings of the National Academy of Sciences.

Figure 2

Value proposition for thin-film devices in bioelectronic medicine. The middle darker blue circle highlights the recent achievements of thin-film bioelectronics, and the lighter blue outer circle highlights the benefits these new devices offer compared to traditional bioelectronic devices.

Figure 3

Two examples of assembled flexible and stretchable thin-film devices. (a) The transversal intrafascicular multichannel electrode-3 electrode for interfacing with peripheral nerves. Reprinted with permission from Reference . © 2019 Taylor & Francis. (b) E-dura: a flexible and stretchable thin-film device for interfacing with tissue. Reprinted with permission from Reference . © 2015 AAAS.

Figure 4

Examples of miniaturized thin-film devices. (a) Schematic showing PEDOT:PSS/electrolyte interface and structure. Reprinted with permission from Reference . © 2013 American Chemical Society. (b) Volumetric capacitance of PEDOT:PSS. Reprinted with permission from Reference . © 2015 AAAS. (c) Pt/Ir contacts, 5-mm diameters with nine electrodes. (d) PEDOT:PSS thin-film electrodes, 10-µm diameters with 256 electrodes. Reprinted with permission from Reference . © 2015 Springer Nature. (e) NeuroGrid: flexible device conforms to orchid petal. Scale bar = 5 mm. Inset: High-density electrodes (256) on NeuroGrid. Scale bar = 100 μm. (f) Brain Interface: NeuroGrid integrates with rat somatosensory cortex. Scale bar = 1 mm. Reprinted with permission from Reference . © 2015 Springer Nature. (g, h) Neuralink’s thin-film brain implant has more than 1000 channels. Reprinted with permission from Reference . © 2019 JMIR Publications. REF, reference, GND, ground.

Figure 5

Examples of multimodal devices. (a) Example of a microfluidic drug delivery device integrated into a thin-film electrode. Inset scale bar: 100 µm; Main image scale bar = 1 mm. Reprinted with permission from Reference . © 2018 AAAS. (b) Example of a microfluidic device for drug delivery combined with light-emitting diodes (LEDs) to perform optical stimulation of specific neuronal populations. Row 1, Image 2: Inset scale bar: 100 µm. Row 2, Image 2: Inset scale bar: 100 µm. Row 2, Image 3: Inset scale bar: 50 µm. Reprinted with permission from Reference . © 2015 Cell Press. ILED, inorganic light-emitting diode.

Figure 6

Biosensing thin-film devices. (a, b) Schematics of a thin-film neural probe with a capillary integrated into the lead wire for the collection of biological samples for further chemical analysis. Reprinted with permission from Reference . © 2017 Springer Nature. (c) Example of a thin-film organic electrochemical transistor (OECT) device for biosensing. Reprinted with permission from Reference . © 2020 MDPI. (d) Example of another OECT-based device, with examples of sensing different concentrations of dopamine. Row 1: Left image: Scale bar: 5 mm; Middle image scale bar: 200 µm. Reprinted with permission from Reference . © 2020 Wiley.

Figure 7

Transparent devices for simultaneous imaging and electrophysiology. (a) Schematic and realization of a fully PEDOT:PSS-based device for multimodal neural electrodes. Reprinted with permission from Reference . © 2021 Wiley. (b) Schematic and optical micrographs of another fully PEDOT:PSS thin-film device. Middle image scale bar: 1 cm; Right image scale bar: 100 µm. Reprinted with permission from Reference . © 2016 Frontiers Media. (c) Application of a PEDOT:PSS device for calcium imaging and subsequent fluorescence analysis. Left image scale bar: 50 µm; Right image scale bars: 5 µm. Reprinted with permission from Reference . © 2016 Frontiers Media.

Figure 8

Shape-actuated devices. (a) Design and fabrication aspects of a minimally invasive spinal-cord device. Reprinted with permission from Reference . © 2021 AAAS. (b) Visualization of a nitinol-based minimally invasive brain implant in both the compressed and deployed state. Row 2: Middle image scale bar: 5 mm; Right image scale bar: 5 mm. Reprinted with permission from Reference . © 2015 Cell Press. IPG, implantable pulse generator, CNT, carbon nanotube, MEA, microelectrode array.

Figure 9

Biohybrid devices. (a) Biohybrid device for peripheral nerve repair design and fabrication. (b) Thin-film devices with cells cultured on top. Left image scale bar: 60 µm; Middle image scale bar: 465 µm; Right image scale bar: 230 µm. Reprinted with permission from Reference . © 2023 Wiley. (c) Construction of a hybrid implant system for creating long‐term interfaces with tissue. Left image scale bar: 5 mm; Top right image scale bar: 1 mm; Bottom right image scale bar: 50 µm. (d) Implants are created by combining a microelectrode array with a bioresorbable and remodelable collagen gel. Left image scale bar: 5 mm; Top right image scale bar: 1 mm; Bottom right image scale bar: 100 µm. Reprinted with permission from Reference . © 2023 Wiley. iPSC, induced pluripotent stem cell.