Miniaturized Wirelessly Powered and Controlled Implants for Multisite Stimulation.

This paper presents a miniaturized implant with a diameter of only 14 mm, which houses a novel System on Chip (SoC) enabling two voltage level stimulation of up to 16 implants using a single Tx coil. Each implant can operate at a distance of 80 mm in the air through the inductive resonant link. The SoC consumes only 27 µW static power and enables two channels with stimulation amplitudes of 1.8 V and 3.3 V and timing resolution of 100 µs. The SoC is implemented in the standard 180 nm complementary metal oxide semiconductor (CMOS) technology and has an area of 0.75 mm × 1.6 mm. The SoC comprises an RF rectifier, low drop-out regulator (LDO), error detection block, clock data recovery, finite state machine (FSM), and output stage. Each implant has a PCB-defined passcode, which enables the individual addressability of the implants for synchronized therapies. The implantable device weighs only 80 mg and sizes 20.1 mm3. Tolerance of up to 70° to angular misalignment was measured at a distance of 50 mm. The efficacy of bilateral stimulation was further verified by implanting two devices on two sides of a pig's neck and performing bilateral vagus nerve stimulation (VNS), while monitoring the heart rate.

Vagus nerve stimulation using a miniaturized wirelessly powered stimulator in pigs.

Neuromodulation of peripheral nerves has been clinically used for a wide range of indications. Wireless and batteryless stimulators offer important capabilities such as no need for reoperation, and extended life compared to their wired counterparts. However, there are challenging trade-offs between the device size and its operating range, which can limit their use. This study aimed to examine the functionality of newly designed wirelessly powered and controlled implants in vagus nerve stimulation for pigs. The implant used near field inductive coupling at 13.56 MHz industrial, scientific, and medical band to harvest power from an external coil. The circular implant had a diameter of 13 mm and weighed 483 mg with cuff electrodes. The efficiency of the inductive link and robustness to distance and misalignment were optimized. As a result, the specific absorption rate was orders of magnitude lower than the safety limit, and the stimulation can be performed using only 0.1 W of external power. For the first time, wireless and batteryless VNS with more than 5 cm operation range was demonstrated in pigs. A total of 84 vagus nerve stimulations (10 s each) have been performed in three adult pigs. In a quantitative comparison of the effectiveness of VNS devices, the efficiency of systems on reducing heart rate was similar in both conventional (75%) and wireless (78.5%) systems. The pulse width and frequency of the stimulation were swept on both systems, and the response for physiological markers was drawn. The results were easily reproducible, and methods used in this study can serve as a basis for future wirelessly powered implants.

Subthreshold electrical stimulation as a low power electrical treatment for stroke rehabilitation.

As a promising future treatment for stroke rehabilitation, researchers have developed direct brain stimulation to manipulate the neural excitability. However, there has been less interest in energy consumption and unexpected side effect caused by electrical stimulation to bring functional recovery for stroke rehabilitation. In this study, we propose an engineering approach with subthreshold electrical stimulation (STES) to bring functional recovery. Here, we show a low level of electrical stimulation boosted causal excitation in connected neurons and strengthened the synaptic weight in a simulation study. We found that STES with motor training enhanced functional recovery after stroke in vivo. STES was shown to induce neural reconstruction, indicated by higher neurite expression in the stimulated regions and correlated changes in behavioral performance and neural spike firing pattern during the rehabilitation process. This will reduce the energy consumption of implantable devices and the side effects caused by stimulating unwanted brain regions.

A 540-[Formula: see text] Duty Controlled RSSI With Current Reusing Technique for Human Body Communication.

An ultra-low-power duty controlled received signal strength indicator (RSSI) is implemented for human body communication (HBC) in 180 nm CMOS technology under 1.5 V supply. The proposed RSSI adopted 3 following key features for low-power consumption; 1) current reusing technique (CR-RSSI) with replica bias circuit and calibration unit, 2) duty controller, and 3) reconfigurable gm-boosting LNA. The CR-RSSI utilizes stacked amplifier-rectifier-cell (AR-cell) to reuse the supply current of each blocks. As a result, the power consumption becomes 540 [Formula: see text] with +/-2 dB accuracy and 75 dB dynamic range. The replica bias circuit and calibration unit are adopted to increase the reliability of CR-RSSI. In addition, the duty controller turns off the RSSI when it is not required, and this function leads 70% power reduction. At last, the gm-boosting reconfigurable LNA can adaptively vary its noise and linearity performance with respect to input signal strength. Fro current reusing technique m this feature, we achieve 62% power reduction in the LNA. Thanks to these schemes, compared to the previous works, we can save 70% of power in RSSI and LNA.

Identification and functional assessment of BCRP polymorphisms in a Korean population.

The breast cancer resistance protein (BCRP) is a member of the ATP-binding cassette transporters. The aim of the present study was to identify genetic variants of BCRP in Koreans and to assess the functional consequences of BCRP polymorphisms. Twenty single nucleotide polymorphisms (SNP), including four nonsynonymous SNP, were identified by DNA sequencing of the BCRP gene in 92 Korean subjects. BCRP V12M, Q141K, P269S, and Q126Stop were detected at frequencies of 23, 28, 0.2, and 1.9%, respectively. These four coding variants were also screened in Chinese and Vietnamese subjects; the allelic frequencies among the three populations were compared; and predictions were made as to the potential frequency of each variant. In vitro functional analyses of the P269S protein and the promoter SNP -19031C>T (mutated in the hypoxia-inducible factor-1alpha binding site) were performed and compared with those of the wild type. P269S exhibited a 35 to 40% decrease in vesicular uptake of [(3)H]estrone-3-sulfate and [(3)H]methotrexate compared with the wild type. The promoter SNP -19031C>T did not affect BCRP promoter activity in either the presence or absence of chemical-induced hypoxic stress. Our results suggest that the P269S variant could be a functionally altered variant. Genotyping of this variant in clinical studies is needed to address its phenotypic role. Genetic polymorphisms of BCRP were found to be very common in Koreans, as well as in other ethnic groups. Comparative analyses among three Asian populations revealed different frequencies for the four functional BCRP variants.