A 3D flexible neural interface based on a microfluidic interconnection cable capable of chemical delivery

The demand for multifunctional neural interfaces has grown due to the need to provide a better understanding of biological mechanisms related to neurological diseases and neural networks. Direct intracerebral drug injection using microfluidic neural interfaces is an effective way to deliver drugs to the brain, and it expands the utility of drugs by bypassing the blood–brain barrier (BBB). In addition, uses of implantable neural interfacing devices have been challenging due to inevitable acute and chronic tissue responses around the electrodes, pointing to a critical issue still to be overcome. Although neural interfaces comprised of a collection of microneedles in an array have been used for various applications, it has been challenging to integrate microfluidic channels with them due to their characteristic three-dimensional structures, which differ from two-dimensionally fabricated shank-type neural probes. Here we present a method to provide such three-dimensional needle-type arrays with chemical delivery functionality. We fabricated a microfluidic interconnection cable (µFIC) and integrated it with a flexible penetrating microelectrode array (FPMA) that has a 3-dimensional structure comprised of silicon microneedle electrodes supported by a flexible array base. We successfully demonstrated chemical delivery through the developed device by recording neural signals acutely from in vivo brains before and after KCl injection. This suggests the potential of the developed microfluidic neural interface to contribute to neuroscience research by providing simultaneous signal recording and chemical delivery capabilities. © 2021, The Author(s).1

A Multimodal Neural Activity Readout Integrated Circuit for Recording Fluorescence and Electrical Signals

Monitoring the electrical neural signals is an important method for understanding the neuronal mechanism. In particular, in order to perform a cell-type-specific study, it is necessary to observe the concentration of calcium ions using fluorescent indicators in addition to measuring the electrical neural signal. This paper presents a multimodal multichannel neural activity readout integrated circuit that can perform not only electrical neural recording but also fluorescence recording of neural activity for the cell-type-specific study of heterogeneous neuronal cell populations. For monitoring the calcium ions, the photodiode generates the current according to the fluorescence expressed by the reaction between the genetically encoded calcium indicators and calcium ions. The time-based fluorescence recording circuit then records the photodiode current. The electrical neural signal captured by the microelectrode is recorded through the low-noise amplifier, variable gain amplifier, and analog-to-digital converter. The proposed integrated circuit is fabricated in a 1-poly 6-metal (1P6M) 0.18- ??m CMOS process. The fluorescence recording circuit achieves a recording range of 81 dB (75 pA to 860 nA) and consumes a power of 724 nW/channel. The electrical recording circuit achieves an input-referred noise of 2.7 ??Vrms over the bandwidth of 10 kHz, while consuming the power of 4.9 ??W /channel. The functionality of the proposed circuits is verified through the in vivo and in vitro experiments. Compared to the conventional neuroscience tools, which consist of bulky off-chip components, this neural interface is implemented in a compact size to perform multimodal neural recording while consuming low power

Long-term characterization of neural electrodes based on parylene-caulked polydimethylsiloxane substrate

This study investigates the mechanical and long-term electrical properties of parylene-caulked polydimethylsiloxane (PDMS) as a substrate for implantable electrodes. The parylene-caulked PDMS is a structure where particles of parylene fill the porous surface of PDMS. This material is expected to have low water absorption and desirable mechanical properties such as flexibility and elasticity that are beneficial in many biomedical applications. To evaluate the mechanical property and electrical stability of parylene-caulked PDMS for potential in-vivo uses, tensile tests were conducted firstly, which results showed that the mechanical strength of parylene-caulked PDMS was comparable to that of native PDMS. Next, surface electrodes based on parylene-caulked PDMS were fabricated and their impedance was measured in phosphate-buffered saline (PBS) solution at 36.5 °C over seven months. The electrodes based on parylene-caulked PDMS exhibited the improved stability in impedance over time than native PDMS. Thus, with improved electrical stability in wet environment and preserved mechanical properties of PDMS, the electrodes based on parylene-caulked PDMS are expected to be suitable for long-term in-vivo applications. © 2016, Springer Science+Business Media New York.

A Method to Pattern Silver Nanowires Directly on Wafer-Scale PDMS Substrate and Its Applications

This study describes a fabrication method of microsized AgNW patterns based on poly dimethylsiloxane (PDMS) substrate using a poly(p-xylylene) (parylene) stencil technique. Various patterns of AgNW conductive sheets were created on the wafer scale area in the forms of straight and serpentine lines, texts, and symbols, which dimensions ranged from a few tens of micrometers to hundreds of micrometers. We demonstrated the electrical performance of straight line and serpentine line patterned AgNW electrodes when subjected to mechanical strains. The gauge factor and stretchability ranged from 0.5 to 55.2 at 2% uniaxial strain and from 4.7 to 55.7%, respectively, depending on the shapes and structures of the AgNW electrodes. Using the developed AgNW patterning technique, we fabricated strain sensors to detect small body signals epidermally such as hand motion, eye blink and heart rate. Also, tactile sensors were fabricated and exhibited the sensitivity of 3.91 MPa-1 in the pressure range lower than 50 kPa, and 0.28 MPa-1 in the pressure range greater than 50 kPa up to 1.3 MPa. From these results, we concluded that the proposed technique enables the fabrication of reliable AgNW patterns on wafer-scale PDMS substrate and the potential applications for various flexible electronic devices. © 2016 American Chemical Society.FALS

A Batteryless, Wireless Strain Sensor Using Resonant Frequency Modulation

In this study, we demonstrated the feasibility of a wireless strain sensor using resonant frequency modulation through tensile impedance test and wireless sensing test. To achieve a high stretchability, the sensor was fabricated by embedding a copper wire with high conductivity in a silicone rubber with high stretchability, in which the resonant frequency can be modulated according to changes in strain. The characteristics of the sensor and the behavior of wireless sensing were calculated based on equations and simulated using finite element method. As the strain of the sensor increased, the inductance increased, resulting in the modulation of resonant frequency. In experimental measurement, as the strain of the sensor increased from 0% to 110%, its inductance was increased from 192 nH to 220 nH, changed by 14.5%, and the resonant frequency was shifted from 13.56 MHz to 12.72 MHz, decreased by 6.2%. It was demonstrated that using the proposed sensor, strains up to 110% could be detected wirelessly up to a few centimeters

Annealing Effects of Parylene-Caulked Polydimethylsiloxane as a Substrate of Electrodes

This paper investigates the effects of annealing of the electrodes based on parylene-caulked polydimethylsiloxane (pc-PDMS) in terms of mechanical strength and long-term electrical property. Previously, the electrodes based on pc-PDMS showed a better ability to withstand in vivo environments because of the low water absorption and beneficial mechanical properties of the substrate, compared to native PDMS. Moreover, annealing is expected to even strengthen the mechanical strength and lower the water absorption of the pc-PDMS substrate. To characterize the mechanical strength and water absorption of the annealed pc-PDMS, tensile tests were carried out and infrared (IR) spectra were measured using Fourier transform infrared spectroscopy over a month. The results showed that annealed pc-PDMS had higher mechanical strength and lower water absorption than non-annealed pc-PDMS. Then, electrochemical impedance spectroscopy was measured to evaluate the electrical stability of the electrodes based on annealed pc-PDMS in phosphate-buffered saline solution at 36.5 °C. The impedance magnitude of the electrodes on annealed pc-PDMS was twice higher than that of the electrodes on non-annealed pc-PDMS in the initial days, but the impedance magnitude of the electrodes based on two different substrates converged to a similar value after eight months, indicating that the annealing effects disappear after a certain period of time in a physiological environment

Interfacial and surface analysis of parylene C-modified PDMS substrates for soft bioelectronics

Parylene C-modified polydimethylsiloxane (PDMS) substrates such as parylene C-deposited PDMS and parylene C-filled PDMS have been developed for the microfabrication of soft electronic devices with mechanically and electrically stable metal patterns. In previous studies, we performed oxygen plasma etching to etch parylene C away from the PDMS surface of parylene C-deposited PDMS to maximize the benefits of soft and stretchable properties of PDMS. However, the resultant parylene C-filled PDMS exhibited microcracks during thin film metal patterning as the etching time increased. In this study, to analyze this cracking phenomenon precisely, the penetration depth of parylene C into PDMS was quantitatively investigated according to the thickness of deposited parylene C, and the amount of parylene C on the surface as well as in the interfacial region formed by parylene C and PDMS was analyzed depending on the etching time. It was observed that residual parylene C remained in the PDMS pores even after parylene C was etched away from the PDMS surface. In addition, we confirmed that only the amount of parylene C on the PDMS surface was reduced by excessive etching, and parylene C inside the PDMS pores was not significantly affected. From these results, we could confirm that the optimal condition to fabricate the parylene C-filled PDMS substrate was to etch parylene C just from the surface of PDMS without over-etching. The parylene C-filled PDMS substrate would enable the wafer-scale high-yield fabrication of soft bioelectronics for diverse applications. © 2021 Elsevier B.V.1

Transformation of 2D Planes into 3D Soft and Flexible Structures with Embedded Electrical Functionality

Three-dimensional (3D) structures composed of flexible and soft materials have been in demand for implantable biomedical devices. However, the fabrication of 3D structures using microelectromechanical system (MEMS) techniques has limitations in terms of the materials and the scale of the structures. Here, a technique to selectively bond polydimethylsiloxane (PDMS) and parylene-C by plasma treatment is reported, with which two-dimensional structures that are fabricated using MEMS techniques are turned into 3D structures by the inflation of selectively non-bonded patterns. The bonding strength and the bonding mechanism were analyzed by mechanical tests and chemical analyses, respectively. We fabricated soft and flexible 3D structures with various patterns and dimensions, even with embedded electrical functions, including light emitting diodes and electrocorticogram electrodes. Based on these results, the flexible, soft, and MEMS-capable 3D structures that are obtained by the developed selective bonding technique are promising for applications in a wide range of biomedical applications. © 2019 American Chemical Society.FALS

An Intrafascicular Neural Interface with Enhanced Interconnection for Recording of Peripheral Nerve Signals

For implantable devices, Parylene C (hereafter referred to as Parylene) has shown promising properties such as flexibility, biocompatibility, biostability, and good barrier properties. Parylene-based flexible interconnection cable (FIC) was previously developed to connect a flexible penetrating microelectrode array (FPMA) with a recording system. However, Parylene-based FIC was difficult to handle and prone to damage during the implantation surgery because of its low mechanical strength. To improve the mechanical properties of the FIC, we suggest a mechanically enhanced flexible interconnection cable (enhanced FIC) obtained using a combination of Parylene and polyimide. To investigate the long-term stability of the enhanced FIC, Parylene-only FIC, and enhanced FIC were tested and their mechanical properties were compared under an accelerated aging condition. During the course of six months of soaking, the maximum strength of the enhanced FIC remained twice as high as that of the Parylene-only FIC throughout the experiment, although the mechanical strength of both FICs decreased over time. To show the capability of the enhanced FIC in the context of nerve signal recording as a part of a neural interfacing device, it was assembled together with the FPMA and custom-made wireless recording electronics. We demonstrated the feasibility of the enhanced FIC in an in vivo application by recording acute nerve signals from canine sciatic nerves.1