Design, fabrication, and test of a sensor array for perspective biosensing in chronic pathologies

Biosensing for chronic pathologies requires the simultaneous monitoring of different parameters such as drug concentrations, inflammation status, temperature and pH. In this paper we discuss the design, fabrication and test of a sensor array hosting five biosensor platforms, a pH electrode and a temperature sensor. Different and reproducible nano-bio- functionalization can be obtained with high spatial resolution via selective electrodeposition of chitosan/MWCNT/enzyme solutions at the various electrodes. The array, completely fabricated with biocompatible materials, can be integrated with a CMOS integrated circuit and a remote powering coil for the realization of a fully implantable device

Design and Modeling of a Low-Power Multi-Channel Integrated Circuit for Infrared Gas Recognition

Peer reviewe

The Evaluation of Potentiostats: Electrochemical Detection Devices

This study evaluated the performance of three types of potentiostats; EmStat, CheapStat and UTMStat. EmStat is the smallest potentiostat available in the market. CheapStat is an open-source potentiostat suitable for educational applications. In addition, UTMStat is the extension of CheapStat, which was designed to overcome few weaknesses of CheapStat such as the input controller/ switch and data storage handling of the cyclic voltammogram. The cyclic voltammetry and amperometry measurements of ions ferrocyanide ([Fe(CN)6]4−) and chloride (Cl-) were carried out for each potentiostat. EmStat potentiostat is not only able to detect but also to measure ferrocyanide and chloride ions. However, CheapStat and UTMStat are only able to detect and measure ferrocyanide ions. The experiment is unable to be conducted due to limitation of waveform selection on both devices. Nevertheless, CheapStat and UTMStat could provide a reliable measurement to realize miniaturized lab-on-chip applications as shown in this study

Investigation of using potentiostats and microfluidic devices for continuous ions detection

In the light of the importance of the bedside patient monitoring system, a miniaturized, flexible, versatile, disposable and cost effective bedside patient continuous monitoring system is essential. Therefore, this research addresses the development of a cost effective and miniaturize continuous monitoring system. For electrochemical analysis, three potentiostats were used: EmStat, CheapStat and in house UTMStat. For lab-on-chip system, two models were proposed and their electrochemistry and pumping characteristics were studied. The 2 layers detection zone was developed through fused filament technology and replication moulding technique with a screen printed electrode attached together. It achieved the maximum flow rate of 0.30405 ml/min with resonance frequency of 20 Hz in micropump reverse direction. With the maximum frequency, the highest oxidation peak current of 15.86176 |iA in cyclic voltammetry measurement was achieved by 10 mM ferrocyanide ions at potential 0.25 V. The monolithic microfluidic device was developed through sticker masks fabrication and replication moulding technique with two screen printed electrodes attached beneath the inlets and the outlets of the micropump. It achieved the maximum flow rate of 0.19693 ml/min with resonance frequency of 10 Hz in micropump forward direction. With the maximum frequency, the highest oxidation peak current of 28.32518 |xA in cyclic voltammetry measurement was achieved by 10 mM ferrocyanide ions at potential 0.32 V. Additionally, the electrochemical investigation was extended by measuring the cyclic voltammetry measurements of chloride ions from a mixture by using EmStat and CheapStat. The highest oxidation peak was observed at 61.26875 |jA and 1.04400 |±A by using EmStat and CheapStat respectively at potential 0.13 V. Specifically, the monolithic microfluidic device is well integrated in lab-on-chip system with the advantage of miniaturize with the dimensions of 41 mm x 26 mm, cost effective by using sticker masks fabrication and replication moulding technique, disposability since it is inexpensive and meant for biomedical analysis, flexibility where it can be used for other ions detection just by changing the screen printed electrode and can measure the data during pumping. This research successfully provides an alternative approach for continuous monitoring of ferrocyanide and chloride ions detection via cyclic voltammetry and amperometry measurements

IEEE Trans Biomed Circuits Syst

Airborne pollutants are a leading cause of illness and mortality globally. Electrochemical gas sensors show great promise for personal air quality monitoring to address this worldwide health crisis. However, implementing miniaturized arrays of such sensors demands high performance instrumentation circuits that simultaneously meet challenging power, area, sensitivity, noise and dynamic range goals. This paper presents a new multi-channel CMOS amperometric ADC featuring pixel-level architecture for gas sensor arrays. The circuit combines digital modulation of input currents and an incremental \uce\ua3\ue2\u2c6\u2020 ADC to achieve wide dynamic range and high sensitivity with very high power efficiency and compact size. Fabricated in 0.5 [Formula: see text] CMOS, the circuit was measured to have 164 dB cross-scale dynamic range, 100 fA sensitivity while consuming only 241 [Formula: see text] and 0.157 [Formula: see text] active area per channel. Electrochemical experiments with liquid and gas targets demonstrate the circuit's real-time response to a wide range of analyte concentrations.R01 ES022302/ES/NIEHS NIH HHS/United StatesR01 OH009644/OH/NIOSH CDC HHS/United States2017-08-01T00:00:00Z27352395PMC505675

Design and Implementation of an Integrated Biosensor Platform for Lab-on-a-Chip Diabetic Care Systems

Recent advances in semiconductor processing and microfabrication techniques allow the implementation of complex microstructures in a single platform or lab on chip. These devices require fewer samples, allow lightweight implementation, and offer high sensitivities. However, the use of these microstructures place stringent performance constraints on sensor readout architecture. In glucose sensing for diabetic patients, portable handheld devices are common, and have demonstrated significant performance improvement over the last decade. Fluctuations in glucose levels with patient physiological conditions are highly unpredictable and glucose monitors often require complex control algorithms along with dynamic physiological data. Recent research has focused on long term implantation of the sensor system. Glucose sensors combined with sensor readout, insulin bolus control algorithm, and insulin infusion devices can function as an artificial pancreas. However, challenges remain in integrated glucose sensing which include degradation of electrode sensitivity at the microscale, integration of the electrodes with low power low noise readout electronics, and correlation of fluctuations in glucose levels with other physiological data. This work develops 1) a low power and compact glucose monitoring system and 2) a low power single chip solution for real time physiological feedback in an artificial pancreas system. First, glucose sensor sensitivity and robustness is improved using robust vertically aligned carbon nanofiber (VACNF) microelectrodes. Electrode architectures have been optimized, modeled and verified with physiologically relevant glucose levels. Second, novel potentiostat topologies based on a difference-differential common gate input pair transimpedance amplifier and low-power voltage controlled oscillators have been proposed, mathematically modeled and implemented in a 0.18μm [micrometer] complementary metal oxide semiconductor (CMOS) process. Potentiostat circuits are widely used as the readout electronics in enzymatic electrochemical sensors. The integrated potentiostat with VACNF microelectrodes achieves competitive performance at low power and requires reduced chip space. Third, a low power instrumentation solution consisting of a programmable charge amplifier, an analog feature extractor and a control algorithm has been proposed and implemented to enable continuous physiological data extraction of bowel sounds using a single chip. Abdominal sounds can aid correlation of meal events to glucose levels. The developed integrated sensing systems represent a significant advancement in artificial pancreas systems

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

A Current-Mode Multi-Channel Integrating Analog-to-Digital Converter

Multi-channel analog to digital converters (ADCs) are required where signals from multiple sensors can be digitized. A lower power per channel for such systems is important in order that when the number of channels is increased the power does not increase drastically. Many applications require signals from current output sensors, such as photosensors and photodiodes to be digitized. Applications for these sensors include spectroscopy and imaging. The ability to digitize current signals without converting currents to voltages saves power, area, and the design time required to implement I-to-V converters. This work describes a novel and unique current-mode multi-channel integrating ADC which processes current signals from sensors and converts it to digital format. The ADC facilitates the processing of current analog signals without the use of transconductors. An attempt has been made also to incorporate voltage-mode techniques into the current-mode design so that the advantages of both techniques can be utilized to augment the performance of the system. Additionally since input signals are in the form of currents, the dynamic range of the ADC is less dependant on the supply voltage. A prototype 4-channel ADC design was fabricated in a 0.5-micron bulk CMOS process. The measurement results for a 10Ksps sampling rate include a DNL, which is less than 0.5 LSB, and a power consumption of less than 2mW per channel

Integrated Microsystems for Wireless Sensing Applications

Personal health monitoring is being considered the future of a sustainable health care system. Biosensing platforms are a very important component of this system. Real-time and accurate sensing is essential for the success of personal health care model. Currently, there are many efforts going on to make these sensors practical and more useful for such measurements. Implantable sensors are considered the most widely applicable and most reliable sensors for such accurate health monitoring applications. However, macroscopic (cm scale) size has proved to be a limiting factor for successful use of these systems for long time and in large numbers. This work is focused to resolve the issues related with miniaturizing these devices to a microscopic (mm scale) size scale which can minimize many practical difficulties associated with their larger counterparts currently. To accomplish this goal of miniaturization while retaining or even improving on the necessary capabilities for such sensing platforms, an integrated approach is presented which focuses on system-level miniaturization using standard fabrication procedures. First, it is shown that a completely integrated and wireless system is the best solution to achieve desired miniaturization without sacrificing the functionality of the system. Hence, design and implementation of the different components comprising the complete system needs to be done according to the requirements of the overall integrated system. This leads to the need of on-chip functional sensors, integrated wireless power supply, integrated wireless communication and integrated control system for realization of such system. In this work, different options for implementation of each of these subsystems are compared and an optimal solution is presented for each subsystem. For such complex systems, it is imperative to use a standard fabrication process which can provide the required functionality for all subsystems at smallest possible size scale. Complementary Metal Oxide Semiconductor (CMOS) process is the most appropriate of the technologies in this regard and has enabled incredible miniaturization of the computing industry. It also provides options for designing different subsystems on the same platform in a monolithic process with very high yield. This choice then leads to actual designs of subsystems in the CMOS technology using different possible methods. Careful comparison of these subsystems provides insights into different design adjustments that are made until the desired functions are achieved at the desired size scale. Integration of all these compatible subsystems in the same platform is shown to provide the smallest possible sensing platform to date. The completely wireless system can measure a host of different important analyte and can transmit the data to an external device which can use it for appropriate purpose. Results on measurements in phosphate buffer solution, blood serum and whole blood along with wireless communication in real biological tissues are provided. Specific examples of glucose and DNA sensors are presented and the use for many other relevant applications is also proposed. Finally, insights into animal model studies and future directions of the research are discussed. </p