Along with the increasing popularity of larval zebrafish as an experimental animal in the fields of drug screening, neuroscience, genetics, and developmental biology, the need for tools to deal with multiple larvae has emerged. Microfluidic channels have been employed to handle multiple larvae simultaneously, even for sensing electroencephalogram (EEG). In this study, we developed a microfluidic chip capable of uniform and continuous drug infusion across all microfluidic channels during EEG recording. Owing to the modular design of the microfluidic channels, the number of animals under investigation can be easily increased. Using the optimized design of the microfluidic chip, liquids could be exchanged uniformly across all channels without physically affecting the larvae contained in the channels, which assured a stable environment maintained all the time during EEG recording, by eliminating environmental artifacts and leaving only biological effects to be seen. To demonstrate the usefulness of the developed system in drug screening, we continuously measured EEG from four larvae without and with pentylenetetrazole application, up to 60 min. In addition, we recorded EEG from valproic acid (VPA)-treated zebrafish and demonstrated the suppression of seizure by VPA. The developed microfluidic system could contribute to the mass screening of EEG for drug development to treat neurological disorders such as epilepsy in a short time, owing to its handy size, cheap fabrication cost, and the guaranteed uniform drug infusion across all channels with no environmentally induced artifacts.

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.

Objective. Magnetic stimulation using implantable devices may offer a promising alternative to other stimulation methods such as transcranial magnetic stimulation (TMS) or electric stimulation using implantable devices. This alternative may increase the selectivity of stimulation compared to TMS, and eliminate the need to expose tissue to metals in the body, as is required in electric stimulation using implantable devices. However, previous studies of magnetic stimulation of the sciatic nerve used large coils, with a diameter of several tens of mm, and a current intensity in the order of kA. Approach. Since such large coils and high current intensity are not suitable for implantable devices, we investigated the feasibility of using a smaller implantable coil and lower current to elicit neuronal responses. A coil with a diameter of 3 mm and an inductance of 1 mH was used as the implantable stimulator. Main results. Before in vivo experiments, we used 3D computational models to estimate the minimum stimulus intensity required to elicit neuronal responses, resulting in a threshold current above 3.5 A. In in vivo experiments, we observed successful nerve stimulation via compound muscle action potentials elicited in hind-limb muscles when the applied current was above 3.8 A, a significantly reduced current than that used in conventional magnetic stimulation. Significance. We report the feasibility of magnetic stimulation using an implantable millimeter-sized coil and low current of a few amperes to elicit neural responses in peripheral nerves. The proposed method is expected to be an alternative to TMS, with the merit of improved selectivity in stimulation, and to electrical stimulation based on implantable devices, with the merit of avoiding the exposure of conducting metals to neural tissues.

Magnetic stimulation, represented by transcranial magnetic stimulation, is used to treat neurological diseases. Various strategies have been explored to improve the spatial resolution of magnetic stimulation. While reducing the coil size is the most impactful approach for increasing the spatial resolution, it decreases the stimulation intensity and increases heat generation. We aim to demonstrate the feasibility of magnetic stimulation using an epidurally implanted millimeter-sized coil and that it does not damage the cortical tissue via heating even when a repetitive stimulation protocol is used. A coil with dimensions of 3.5 × 3.5 × 2.6 mm³ was epidurally implanted on the left motor cortex of rat, corresponding to the right hindlimb. Before and after epidural magnetic stimulation using a quadripulse stimulation (QPS) protocol, changes in the amplitude of motor evoked potentials (MEPs) elicited by a transcranial magnetic stimulation (TMS) coil were compared. The experimental group showed an average increase of 88% in MEP amplitude in the right hindlimb after QPS, whereas the MEP amplitude in the left hindlimb increased by 18% on average. The control group showed no significant change in MEP amplitude after QPS in either hindlimb. The temperature changes at the coil surface remained <2°C during repetitive stimulation, meeting the thermal safety limit for implantable medical devices. These results demonstrate the feasibility of epidural magnetic stimulation using an implantable coil to induce neuromodulation effects. This novel method is expected to be a promising alternative for focal magnetic stimulation with an improved spatial resolution and lowered stimulus current than previous magnetic stimulation methods.

Peripheral nerve electrical stimulation is widely used for the treatment of neuropathic pain and neural regeneration. However, it often induces adverse biological reactions and unintended activation of surrounding neural tissues. As an alternative, peripheral nerve magnetic stimulation offers a promising, less invasive approach that enables targeted nerve stimulation without direct tissue contact. Despite its potential, it is constrained by the bulkiness of coils and excessive heat generation due to the high currents required. To address these limitations, we conducted a study on coil design optimized for peripheral nerve modulation. Our approach, supported by simulations and animal experiments, focused on optimizing coil geometry to maximize the induced electric field gradient. Among various designs, a four-leaf rhombus-shaped coil demonstrated the highest gradient at the center of the interface. In rat sciatic nerve experiments, this coil, driven by a rectangular pulse with a 200 μs rise time and 25 V amplitude, successfully elicited compound muscle action potentials in both the tibial anterior and gastrocnemius muscles. This study presents design guidelines for peripheral nerve stimulation (PNS) coils based on magnetic stimulation as an alternative to conventional electrical stimulation. The proposed approach may serve as a foundation for the development of advanced, miniaturized, and energy-efficient neural stimulation coils.