A Low-Power, Highly Stabilized Three-Electrode Potentiostat Using Subthreshold Techniques

Implantable micro- and nano- sensors and implantable microdevices (IMDs) have demonstrated potential for monitoring various physiological parameters such as glucose, lactate, CO2 [carbon dioxide], pH, etc. Potentiostats are essential components of electrochemical sensors such as glucose monitoring devices for diabetic patients. Diabetes is a metabolic disorder associated with insufficient production or inefficient utilization of insulin. The most important role of this enzyme is to regulate the metabolic breakdown of glucose generating the necessary energy for human activities. Diabetic patients typically monitor their blood glucose levels by pricking a fingertip with a lancing device and applying the blood to a glucose meter. This painful process may need to be repeated once before each meal and once 1- 4 hour after meal. Patients may need to inject insulin manually to keep the blood glucose level at 3.9-6.7 mmol [mili mol] /liter. Frequent glucose measurement can help reduce the long term complication of this disease which includes kidney disease, nerve damage, heart and blood vessel diseases, gum disease, glaucoma and etc. Having an implanted close loop insulin delivery system can help increase the frequency of glucose measurement and the accuracy of insulin injection. The implanted close loop system consists of three main blocks: (1) an electrochemical sensor in conjunction with a potentiostat to measure the blood glucose level, (2) a control block that defines the level of insulin injection and (3) an implanted insulin pump. To provide a continuous health-care monitoring the implantable unit has to be powered up using wireless techniques. Minimizing the power consumption associated with the implantable system can improve the battery life times or minimize the power transfer through the human body. The focus of this work is on the design of low-power potentiostats for the implantable glucose monitoring system. This work addresses the conventional structures in potentiostat design and the problems associated with these designs. Based on this discussion a modification is made to improve the stability without increasing the complexity of the system. The proposed design adopts a subthreshold biasing scheme for the design of a highly-stabilized, low-power potentiostats

Next-Generation Diamond Electrodes for Neurochemical Sensing: Challenges and Opportunities

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. Carbon-based electrodes combined with fast-scan cyclic voltammetry (FSCV) enable neurochemical sensing with high spatiotemporal resolution and sensitivity. While their attractive electrochemical and conductive properties have established a long history of use in the detection of neurotransmitters both in vitro and in vivo, carbon fiber microelectrodes (CFMEs) also have limitations in their fabrication, flexibility, and chronic stability. Diamond is a form of carbon with a more rigid bonding structure (sp3-hybridized) which can become conductive when boron-doped. Boron-doped diamond (BDD) is characterized by an extremely wide potential window, low background current, and good biocompatibility. Additionally, methods for processing and patterning diamond allow for high-throughput batch fabrication and customization of electrode arrays with unique architectures. While tradeoffs in sensitivity can undermine the advantages of BDD as a neurochemical sensor, there are numerous untapped opportunities to further improve performance, including anodic pretreatment, or optimization of the FSCV waveform, instrumentation, sp2 /sp3 character, doping, surface characteristics, and signal processing. Here, we review the state-of-the-art in diamond electrodes for neurochemical sensing and discuss potential opportunities for future advancements of the technology. We highlight our team’s progress with the development of an all-diamond fiber ultramicroelectrode as a novel approach to advance the performance and applications of diamond-based neurochemical sensors

Wireless Amperometric Neurochemical Monitoring Using an Integrated Telemetry Circuit

Abstract—An integrated circuit for wireless real-time monitoring of neurochemical activity in the nervous system is described. The chip is capable of conducting high-resolution amperometric measurements in four settings of the input current. The chip architecture includes a first-order ∆Σ modulator (∆ΣM) and a frequency-shift-keyed (FSK) voltage-controlled oscillator (VCO) operating near 433 MHz. It is fabricated using the AMI 0.5 µm double-poly triple-metal n-well CMOS process, and requires only one off-chip component for operation. Measured dc current resolutions of ∼250 fA, ∼1.5 pA, ∼4.5 pA, and ∼17 pA were achieved for input currents in the range of ±5, ±37, ±150, and ±600 nA, respectively. The chip has been interfaced with a diamond-coated, quartz-insulated, microneedle, tungsten electrode, and successfully recorded dopamine concentration levels as low as 0.5 µM wirelessly over a transmission distance of ∼0.5 m in flow injection analysis experiments

Non-planar diamond electrodes for biomedical neural sensing and stimulating

Abstract Conductive diamond has exceptional chemical stability, making it an appealing candidate material for long-term medical device implants. This work describes the characterization, and fabrication of four diamond-based neural devices. A previously developed 30 µm diamond-disk in vitro needle electrode was characterized. The device could detect 1 nM concentration analytes in a flow cell using fast scan cyclic voltammetry, but the fabrication was not reproducible. A novel in vitro diamond device was developed with diamond selectively grown at the tip of a hollow quartz capillary, resulting in a 2-4 µm tip diameter. The diamond tip shape and size were geometrically reproducible, although an electrical connection to these tips is still needed. Two novel in vivo diamond based devices were also fabricated. The first generation in vivo diamond electrode was assembled by attaching a brittle diamond electrode to a flexible insulated substrate. The device fabrication time was 6 hrs of hands-on activity, but it was successfully implanted in a freely behaving Aplysia californica. Electrical recordings were compared to a stainless steel standard for two surgeries, respectively 8 days post surgery and 12 days post surgery. However, external electrical connections to equipment had sufficiently large noise and signal variability. No definitive conclusions could be reached about differences in recordings by diamond and steel.A second generation in vivo diamond electrode was fabricated on a substrate that remained flexible after diamond growth, also reducing the fabrication time by 4 hrs. Substrates typically become embrittled during diamond growth because of surface carbide formation. Two rhenium alloys, 75% tungsten / 25% rhenium (v/v) and 47.5% molybdenum / 52.5% rhenium (v/v), were investigated as flexible substrates that might not form carbides during diamond growth but adhere strongly to diamond. Three growth times were explored, with the rhenium alloys compared to a traditional tungsten substrate. Diamond grown for 20 hours on 47.5% molybdenum / 52.5% rhenium alloy had the highest diamond quality (crystal size, sp3 content, and good electrochemical activity), with the substrate remaining flexible after the diamond growth. This device has not yet been insulated with a biocompatible material; however, in vitro recordings were obtained with Aplysia

Non-planar diamond electrodes for biomedical neural sensing and stimulating

Abstract Conductive diamond has exceptional chemical stability, making it an appealing candidate material for long-term medical device implants. This work describes the characterization, and fabrication of four diamond-based neural devices. A previously developed 30 µm diamond-disk in vitro needle electrode was characterized. The device could detect 1 nM concentration analytes in a flow cell using fast scan cyclic voltammetry, but the fabrication was not reproducible. A novel in vitro diamond device was developed with diamond selectively grown at the tip of a hollow quartz capillary, resulting in a 2-4 µm tip diameter. The diamond tip shape and size were geometrically reproducible, although an electrical connection to these tips is still needed. Two novel in vivo diamond based devices were also fabricated. The first generation in vivo diamond electrode was assembled by attaching a brittle diamond electrode to a flexible insulated substrate. The device fabrication time was 6 hrs of hands-on activity, but it was successfully implanted in a freely behaving Aplysia californica. Electrical recordings were compared to a stainless steel standard for two surgeries, respectively 8 days post surgery and 12 days post surgery. However, external electrical connections to equipment had sufficiently large noise and signal variability. No definitive conclusions could be reached about differences in recordings by diamond and steel.A second generation in vivo diamond electrode was fabricated on a substrate that remained flexible after diamond growth, also reducing the fabrication time by 4 hrs. Substrates typically become embrittled during diamond growth because of surface carbide formation. Two rhenium alloys, 75% tungsten / 25% rhenium (v/v) and 47.5% molybdenum / 52.5% rhenium (v/v), were investigated as flexible substrates that might not form carbides during diamond growth but adhere strongly to diamond. Three growth times were explored, with the rhenium alloys compared to a traditional tungsten substrate. Diamond grown for 20 hours on 47.5% molybdenum / 52.5% rhenium alloy had the highest diamond quality (crystal size, sp3 content, and good electrochemical activity), with the substrate remaining flexible after the diamond growth. This device has not yet been insulated with a biocompatible material; however, in vitro recordings were obtained with Aplysia

A Low-Power Wireless Multichannel Microsystem for Reliable Neural Recording.

This thesis reports on the development of a reliable, single-chip, multichannel wireless biotelemetry microsystem intended for extracellular neural recording from awake, mobile, and small animal models. The inherently conflicting requirements of low power and reliability are addressed in the proposed microsystem at architectural and circuit levels. Through employing the preliminary microsystems in various in-vivo experiments, the system requirements for reliable neural recording are identified and addressed at architectural level through the analytical tool: signal path co-optimization. The 2.85mm×3.84mm, mixed-signal ASIC integrates a low-noise front-end, programmable digital controller, an RF modulator, and an RF power amplifier (PA) at the ISM band of 433MHz on a single-chip; and is fabricated using a 0.5µm double-poly triple-metal n-well standard CMOS process. The proposed microsystem, incorporating the ASIC, is a 9-channel (8-neural, 1-audio) user programmable reliable wireless neural telemetry microsystem with a weight of 2.2g (including two 1.5V batteries) and size of 2.2×1.1×0.5cm3. The electrical characteristics of this microsystem are extensively characterized via benchtop tests. The transmitter consumes 5mW and has a measured total input referred voltage noise of 4.74µVrms, 6.47µVrms, and 8.27µVrms at transmission distances of 3m, 10m, and 20m, respectively. The measured inter-channel crosstalk is less than 3.5% and battery life is about an hour. To compare the wireless neural telemetry systems, a figure of merit (FoM) is defined as the reciprocal of the power spent on broadcasting one channel over one meter distance. The proposed microsystem’s FoM is an order of magnitude larger compared to all other research and commercial systems. The proposed biotelemetry system has been successfully used in two in-vivo neural recording experiments: i) from a freely roaming South-American cockroach, and ii) from an awake and mobile rat.PhDElectrical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/91542/1/aborna_1.pd