Hideo Oi

Nanoscale‐Tipped High‐Aspect‐Ratio Vertical Microneedle Electrodes for Intracellular Recordings

Intracellular recording nanoscale electrode devices provide the advantages of a high spatial resolution and high sensitivity. However, the length of nanowire/nanotube-based nanoelectrodes is currently limited to <10 μm long due to fabrication issues for high-aspect-ratio nanoelectrodes. The concept reported here can address the technological limitations by fabricating >100 μm long nanoscale-tipped electrodes, which show intracellular recording capability.

Dissolvable Base Scaffolds Allow Tissue Penetration of High-Aspect-Ratio Flexible Microneedles

Microscale needle technology is important in electrophysiological studies, drug/chemical delivery systems, optogenetic applications, and so on. In this study, dissolvable needle-base scaffold realizes penetration of high-aspect-ratio flexible microneedles (e.g., <5 μm diameter and >500 μm length) into biological tissues. This methodology, which is applicable to numerous high-aspect-ratio flexible microneedles, should reduce the invasiveness and provide safer tissue penetrations than conventional approaches.

Single 5 μm diameter needle electrode block modules for unit recordings in vivo

Investigations into mechanisms in various cortical areas can be greatly improved and supported by stable recording of single neuronal activity. In this study, fine silicon wire electrodes (diameter 3 μm, length 160 μm) are fabricated by vapor–liquid–solid (VLS) growth with the aim of stabilizing recording and reducing the invasiveness on the measurement procedure. The electrode is fabricated on a modular 1 ×  1 mm2 conductive silicon block that can be assembled into a number of different device packages, for example on rigid or flexible printed circuit boards (PCB). After plating with a 5 μm diameter platinum black, the needle exhibits an electrical impedance of ~100 kΩ at 1 kHz in saline. The in vivo recording capability of the device is demonstrated using mice, and spike signals with peak-to-peak amplitudes of 200−300 μV in the range 0.5−3 kHz are stably detected, including single-unit activities in cortical layer 2/3. In addition, the device packaged with a flexible PCB shows stable unit recordings for 98.5 min (n = 4). Consequently, our modular, low-invasive needle electrode block devices present an effective route for single-unit recordings in vivo, as well as demonstrating adaptability in device design for a diverse range of experiments.

A vertically integrated nanoscale tipped microprobe intracellular electrode array

Here we report integration of nanoscale tipped 120-μm-long vertical microprobe electrode (NTE) array and intracellular recordings using a gastrocnemius muscle of a mouse. The tip diameter and curvature radius of the NTE was <; 200 nm, respectively, and the controlled height of the exposed tip section was 4 μm. The impedance of the fabricated NTE exhibited 3.1 MΩ at 1 kHz in saline, with the output/input signal amplitude ratio of 50%. The penetrated NTE into the muscle of a mouse detected the resting membrane potentials with the amplitude of ~ -200 mV, indicating that the NTE device detected intracellular signals from the mouses muscle. Although we have demonstrated the intracellular recording capability using a muscle, such nanoscale electrodes with a high aspect ratio can be used for multisite intracellular recordings within numerous neuronal tissues including brain slice.

Dissolvable material for high-aspect-ratio flexible silicon-microwire penetrations

High-aspect-ratio microwire array devices, which penetrates into a biological tissue, have widely been used in neuroscience, offering in vivo/in vitro electrophysiological stimulation and recording, drug delivery (e.g., DNA), and optogenetics applications. As low invasive and safe penetrations, these microwire devices are required to be further miniaturized and flexibility. However, tissue penetration with such high-aspect-ratio and flexible wires is problematic, because the wire buckles during the penetration. Here, we improve the penetration capability of high-aspect-ratio flexible wires by coating a dissolvable material of “silk fibroin” (Fig.1). The silk-fibroin is a material, which dissolves when the surface contacts with a wet biological tissue, resulting in that embedded wires are appeared and penetrated. We demonstrated the silk fibroin coating over high-aspect-ratio silicon-microwires (~720 μm in length), which was fabricated by vapor-liquid-solid (VLS) growth. The 420-μm-long silicon-wire with a ~200-μm-thick silk film exited the stiffness of 4.03 N/m, which is 72% improved value compared to that of the silicon-wires without silk (2.34 N/m). The effects of the silk support on the wire penetration were confirmed by demonstrating the gelatin penetrations. These results suggest that the numerous high-aspect-ratio flexible bioprobes can be penetrated by using the silk support.

Verification of bending strength of vapor-liquid-solid grown high-aspect-ratio silicon-neuroprobes

MEMS-based penetrating probe electrode devices have opened a new class of multi-site electrophysiological recordings of neurons/cells in a tissue with a high spatial resolution. Although these probes becomes a powerful tool in electrophysiology, the challenge still remains the tissue penetrations with small diameter probes for further low-invasive and safe tissue penetrations. However, it is difficult to penetrate small diameter probes with a high aspect ratio (e.g., a micro-scale diameter probe with the length of several hundred microns or more), due to the buckling of the probe during the tissue penetration (Fig.1). To realize the tissue penetration with small diameter needle with a high aspect ratio, quantitative discussions of the penetration force and the buckling/bending properties of the probe are further required. Here we verify the bending strength of silicon-microprobe with a high aspect ratio using in situ force-measurement-system (FMS) inside the SEM. In addition, these silicon probes are coated with a metal of iridium (Ir) with a high Youngs modulus as the exoskeleton (shell), quantitatively confirming the increased stiffness of the probe. Such data can be used to design stiff probes and realize the minimization of the probe diameter, enhancing the penetrating capability of small probes for further low-invasive and safe tissue penetrations.