Conference PaperPDF Available

Soft, flexible and transparent graphene-based active spinal cord implants for optogenetic studies

Authors:

Abstract and Figures

Patients affected by spinal cord injuries (SCI) are usually unable to perform trivial motor activities and thus, for therapeutic purposes, epidural spinal cord stimulation (ESCS) is currently used. Moreover, more exploratory research, using optogenetics, is being conducted in rodents for a better understanding of the mechanisms that occur while delivering specific therapies. However, the availability of tailored neurotechnologies for such experiments is limited. This work reports the development and characterization of flexible, active spinal cord implants with optogenetic compatibility 1,2 (Fig.1). A scalable and reproducible microfabrication process has been developed, using graphene 3 , a transparent, flexible and conductive material, to form the electrodes and interconnects of the implant. Small and thin 4 electronic chips were assembled via flip-chip bonding processes either on graphene or on metal-on-graphene layers. Soft, polymeric encapsulation was employed to sustain the high flexibility and transparency of the implant. The result is an active prototype consisting of a multi-layered graphene structure between two polymeric-based encapsulation layers, with thin chips integrated on the implant and test pads for interconnection to the outside world. Raman spectroscopy and optical transmittance were employed for the characterization of the graphene layer while cyclic voltammetry and electrochemical impedance spectroscopy were performed to benchmark the electrical properties of the device. The assembly process of the chips was evaluated using four-point electrical measurements. In this work, the first transparent, graphene-based active implants have been developed (Fig. 2 and Fig. 3). The prototypes were extensively characterized and the results showed a transparency of ~80 % as well as no deterioration over time when soaked in saline solution or when bent under various angles. The graphene electrodes showed an impedance of ~8 kΩ at 1 kHz frequencies and the resistance after the bonding process ranged from 10 mΩ up to 16 Ω for individual connections, depending on the substrate used. Fig.
Content may be subject to copyright.
13th International Symposium on Flexible Organic Electronics (ISFOE20)
6-9 July 2020, Thessaloniki, Greece
Soft, flexible and transparent graphene-based active spinal cord implants for
optogenetic studies
A. I. Velea1,2,3, S. Vollebregt2, V. Giagka1,3
1Bioelectronics Section and 2Electronic Components, Technology and Materials section,
Department of Microelectronics, Faculty of Electrical Engineering, Mathematics and Computer
Science, Delft University of Technology
Mekelweg 4, 2628 CD, Delft, The Netherlands
3Technologies for Bioelectronics Group, Department of System Integration and Interconnection
Technologies, Fraunhofer Institute for Reliability and Microintegration IZM
Gustav-Meyer-Allee 25, 13355, Berlin, Germany
e-mail: a.velea-1@tudelft.nl; andrada.iulia.velea@izm.fraunhofer.de
Patients affected by spinal cord injuries (SCI) are usually unable to perform trivial motor activities and thus,
for therapeutic purposes, epidural spinal cord stimulation (ESCS) is currently used. Moreover, more exploratory
research, using optogenetics, is being conducted in rodents for a better understanding of the mechanisms that
occur while delivering specific therapies. However, the availability of tailored neurotechnologies for such
experiments is limited.
This work reports the development and characterization of flexible, active spinal cord implants with
optogenetic compatibility1,2 (Fig.1). A scalable and reproducible microfabrication process has been developed,
using graphene3, a transparent, flexible and conductive material, to form the electrodes and interconnects of
the implant. Small and thin4 electronic chips were assembled via flip-chip bonding processes either on
graphene or on metal-on-graphene layers. Soft, polymeric encapsulation was employed to sustain the high
flexibility and transparency of the implant. The result is an active prototype consisting of a multi-layered
graphene structure between two polymeric-based encapsulation layers, with thin chips integrated on the
implant and test pads for interconnection to the outside world.
Raman spectroscopy and optical transmittance were employed for the characterization of the graphene
layer while cyclic voltammetry and electrochemical impedance spectroscopy were performed to benchmark the
electrical properties of the device. The assembly process of the chips was evaluated using four-point electrical
measurements.
In this work, the first transparent, graphene-based active implants have been developed (Fig. 2 and Fig. 3).
The prototypes were extensively characterized and the results showed a transparency of ~80 % as well as no
deterioration over time when soaked in saline solution or when bent under various angles. The graphene
electrodes showed an impedance of ~8 kΩ at 1 kHz frequencies and the resistance after the bonding process
ranged from 10 mΩ up to 16 Ω for individual connections, depending on the substrate used.
Fig. 1. Envisioned structure of the proposed system
Fig. 2. Active prototypes developed
on a silicon wafer
Fig. 3. Soft, flexible,
graphene-based implants
1. A. I. Velea, S. Vollebregt, G. K. Wardhana, and V. Giagka, Wafer-scale graphene-based soft implant with optogenetic
compatibility,” in Proc. IEEE MEMS 2020, Vancouver, Canada, Jan. 2020.
2. A. I. Velea, S. Vollebregt, Tim Hosman, A. Pak, and V. Giagka, “Towards a Microfabricated Flexible Graphene-Based Active
Implant for Tissue Monitoring During Optogenetic Spinal Cord Stimulation,” in Proc. IEEE Nanotech. Mater. Dev. Conf.
(NMDC) 2019, Stockholm, Sweden, Oct. 2019.
3. S. Vollebregt et al., “A transfer-free wafer-scale CVD graphene fabrication process for MEMS/NEMS sensors”, in Proc. IEEE
MEMS 2016, pp.17 20, Shanghai, China, Jan. 2016.
4. V. Giagka, N. Saeidi, A. Demosthenous, and N. Donaldson, “Controlled silicon IC thinning on individual die level for active
implant integration using a purely mechanical process,” in Proc. ECTC 2014, Orlando, FL, USA, May 2014, pp. 2213 2219.
ResearchGate has not been able to resolve any citations for this publication.
Conference Paper
Full-text available
This paper reports on the characterization of a microfabricated wafer-scale, graphene-based, soft implant for spinal cord applications. Graphene is used because of its high transparency and good conductivity, making it suitable for optogenetic applications. Moreover it has a high mechanical strength and is potentially biocompatible. The implant consists of multi-layered chemical vapor deposited graphene, in the form of electrodes and tracks, encapsulated between 2 layers of silicone. Methods such as Raman spectroscopy, optical transmittance, and electrical measurements combined with bending tests and in-vitro experiments, using phosphate-buffered saline (PBS) solution, were employed to characterize the device. The results have shown high bendability and no critical damage of the graphene after immersing the device in PBS solution up to 7 days. To the authors' best knowledge, this is the first work that presents a soft and fully scalable optogenetics-compatible graphene-based spinal cord electrode array.
Conference Paper
Full-text available
This work aims to develop a smart neural interface with transparent electrodes to allow for electrical monitoring of the site of interest during optogenetic stimulation of the spinal cord. In this paper, a microfabrication process for the wafer-level development of such a compact, active, transparent and flexible implant is presented. Graphene has been employed to form the transparent array of electrodes and tracks, on top of which chips have been bonded using flip-chip bonding techniques. To provide high flexibility, soft encapsulation, using polydimethylsiloxane (PDMS) has been used. Making use of the "Flex-to-Rigid" (F2R) technique, cm-size graphene-on-PDMS structures have been suspended and characterized using Raman spectroscopy to qualitatively evaluate the graphene layer, together with 2-point measurements to ensure the conductivity of the structure. In parallel, flip-chip bonding processes of chips on graphene structures were employed and the 2-point electrical measurement results have shown resistance values in the range of kΩ for the combined tracks and ball-bonds.
Conference Paper
Full-text available
In this paper we report a novel transfer-free graphene fabrication process, which does not damage the graphene layer. Uniform graphene layers on 4" silicon wafers were deposited by chemical vapor deposition using the CMOS compatible Mo catalyst. Removal of the Mo layer after graphene deposition results in a transfer-free and controlled placement of the graphene on the underlying SiO2. Moreover, pre-patterning the Mo layer allows customizable graphene geometries to be directly obtained, something that has never been achieved before. This process is extremely suitable for the large-scale fabrication of MEMS/NEMS sensors, especially those benefitting from specific properties of graphene, such as gas sensing.
Conference Paper
Full-text available
We are developing an electrode array for epidural spinal cord stimulation and a thin integrated circuit (IC) is to be embedded in it. This paper focuses on the development and characterization of a manual process for thinning individual IC die and discusses the issues associated with thinning small dice by a manual process. The procedure allows easy and controlled post-separation thinning of small (about 1 mm2) silicon chips by grinding. A systematic approach was followed to characterize the technique and repeatability of the results. With the setup we introduced we were able to control the final thickness of the IC with a standard deviation of 9.2 μm. Although no chemical processing is used, a small grit size film can create smooth surfaces, with roughness comparable to reported values after etching, acting as the so-called “stress-relief” step. Electrical tests performed on a thinned stimulator output stage IC indicated that no die damage was caused by the procedure. Some issues regarding the integration of thinned ICs on flexible substrates and the reliability of gold ball rivet bonds on the ICs' aluminium pads are also discussed.