Anti-artifacts techniques for neural recording front-ends in closed-loop brain-machine interface ICs.

In recent years, thanks to the development of integrated circuits, clinical medicine has witnessed significant advancements, enabling more efficient and intelligent treatment approaches. Particularly in the field of neuromedical, the utilization of brain-machine interfaces (BMI) has revolutionized the treatment of neurological diseases such as amyotrophic lateral sclerosis, cerebral palsy, stroke, or spinal cord injury. The BMI acquires neural signals via recording circuits and analyze them to regulate neural stimulator circuits for effective neurological treatment. However, traditional BMI designs, which are often isolated, have given way to closed-loop brain-machine interfaces (CL-BMI) as a contemporary development trend. CL-BMI offers increased integration and accelerated response speed, marking a significant leap forward in neuromedicine. Nonetheless, this advancement comes with its challenges, notably the stimulation artifacts (SA) problem inherent to the structural characteristics of CL-BMI, which poses significant challenges on the neural recording front-ends (NRFE) site. This paper aims to provide a comprehensive overview of technologies addressing artifacts in the NRFE site within CL-BMI. Topics covered will include: (1) understanding and assessing artifacts; (2) exploring the impact of artifacts on traditional neural recording front-ends; (3) reviewing recent technological advancements aimed at addressing artifact-related issues; (4) summarizing and classifying the aforementioned technologies, along with an analysis of future trends.

A Low Noise Neural Recording Frontend IC With Power Management for Closed-Loop Brain-Machine Interface Application.

Brain-machine Interface (BMI) with implantable bioelectronics systems can provide an alternative way to cure neural diseases, while a power management system plays an important role in providing a stable voltage supply for the implanted chip. a prototype system of power management integrated circuit (PMIC) with heavy load capability supplying artifacts tolerable neural recording integrated circuit (ATNR-IC) is presented in this work. A reverse nested miller compensation (RNMC) low dropout regulator (LDO) with a transient enhancer is proposed for the PMIC. The power consumption is 0.55 mW and 22.5 mW at standby (SB) and full stimulation (ST) load, respectively. For a full load transition, the overshoot and downshoot of the LDO are 110 mV and 71 mV, respectively, which help improve the load transient response during neural stimulation. With the load current peak-to-peak range is about 560 µA supplied by a 4-channel stimulator, the whole PMIC can output a stable 3.3 V supply voltage, which indicates that this PMIC can be extended for more stimulating channels' scenarios. When the ATNR-IC is supplied for presented PMIC through a voltage divider network, it can amplify the signal consisting of 1 mVpp simulated neural signal and 20 mVpp simulated artifact by 28 dB with no saturation.

A 4-Channel Neural Stimulation IC Design With Charge Balancing and Multiple Current Output Modes.

This article proposes a neural stimulation integrated circuit design with multiple current output modes. In the cathodic stimulation phase and anodic stimulation phase, each output current waveform can be independently selected to either exponential waveform or square wave, so the stimulator holds four stimulation modes. To minimize the headroom voltage of the output stage and enhance the power efficiency of the proposed stimulator, we introduce the exponentially decaying current which is realized by the exponential current generation circuit in this work. It can enhance the longer duration of the stimulation pulse as well. In case the residual charge may cause harm to patients, a charge balancing technique is implemented in this work for all operation modes. The four-channel stimulator IC is implemented in a 180-nm CMOS process, occupying a core area of 1.93 mm2. The measurement results show that the proposed stimulator realized a maximum power efficiency of 91.3% and the maximum stimulation duration is 3 times larger than previous works. Moreover, even in exponential output waveform mode, the maximum residual charge in a single cycle is only 255 pC due to the proposed charge balancing technique. The experiment results based on the PBS solution also show that the stimulator IC can remove residual charges within 60 µs, and the electrode voltage remains stable within a safe range under multicycle stimulation.

Biodegradable Ru-Containing Polycarbonate Micelles for Photoinduced Anticancer Multitherapeutic Agent Delivery and Phototherapy Enhancement.

The lack of selectivity between tumor and healthy cells, along with inefficient reactive oxygen species production in solid tumors, are two major impediments to the development of anticancer Ru complexes. The development of photoinduced combination therapy based on biodegradable polymers that can be light activated in the "therapeutic window" would be beneficial for enhancing the therapeutic efficacy of Ru complexes. Herein, a biodegradable Ru-containing polymer (poly(DCARu)) is developed, in which two different therapeutics (the drug and the Ru complex) are rationally integrated and then conjugated to a diblock copolymer (MPEG-b-PMCC) containing hydrophilic poly(ethylene glycol) and cyano-functionalized polycarbonate with good degradability and biocompatibility. The polymer self-assembles into micelles with high drug loading capacity, which can be efficiently internalized into tumor cells. Red light induces the generation of singlet oxygen and the release of anticancer drug-Ru complex conjugates from poly(DCARu) micelles, hence inhibiting tumor cell growth. Furthermore, the phototherapy of polymer micelles demonstrates remarkable inhibition of tumor growth in vivo. Meanwhile, polymer micelles exhibit good biocompatibility with blood and healthy tissues, which opens up opportunities for multitherapeutic agent delivery and enhanced phototherapy.