Electrochemical Sensors and On-chip Optical Sensors

abstract: The microelectronics technology has seen a tremendous growth over the past sixty years. The advancements in microelectronics, which shows the capability of yielding highly reliable and reproducible structures, have made the mass production of integrated electronic components feasible. Miniaturized, low-cost, and accurate sensors became available due to the rise of the microelectronics industry. A variety of sensors are being used extensively in many portable applications. These sensors are promising not only in research area but also in daily routine applications. However, many sensing systems are relatively bulky, complicated, and expensive and main advantages of new sensors do not play an important role in practical applications. Many challenges arise due to intricacies for sensor packaging, especially operation in a solution environment. Additional problems emerge when interfacing sensors with external off-chip components. A large amount of research in the field of sensors has been focused on how to improve the system integration. This work presents new methods for the design, fabrication, and integration of sensor systems. This thesis addresses these challenges, for example, interfacing microelectronic system to a liquid environment and developing a new technique for impedimetric measurement. This work also shows a new design for on-chip optical sensor without any other extra components or post-processing.Dissertation/ThesisDoctoral Dissertation Electrical Engineering 201

A high performance ASIC for electrical and neurochemical traumatic brain injury monitoring

Traumatic Brain Injury (TBI) can be defined as a non-degenerative, non-congenital brain trauma due to an external mechanical force. TBI is a major cause of death and disability in all age groups and the leading cause of death and disability in working people and among young adults. This Thesis presents the first application specific integrated chip (ASIC) for monitoring patients suffering from TBI. The microelectronic chip was designed to meet the demands of processing physiological signals for an alternative method of TBI monitoring. It has been studied that by monitoring electrical (ECoG) and chemical (glucose, lactate and potassium) signals, the report of spreading depolarisation (SD) waves could be a good indicator for an upcoming secondary brain injury. The ultimate aim of this Thesis has been to support the idea of a “behind-the-ear” micro-platform, which could enable the monitoring of mobile (or mobilized) patients suffering a TBI who, currently, are not monitored. Switched-capacitor (SC) circuits have been adopted for the implementation of both current and voltage analogue front-ends (AFEs). Advanced techniques to minimise noise and improve the noise performance of the circuit were employed. Moreover, a digitally enabled automatic transimpedance gain control circuit, suitable for current analogue front-ends, was developed and tested in order to provide an automated way to adjust the gain and to counterbalance for the drop in sensitivity of the biosensors due to drift. Measured results confirming the operation of the TBI ASIC and its sub-circuits are reported. Finally, a novel circuit that mimics the Butler-Volmer dynamics is presented. The basic building blocks arise from the combination of Translinear (TL) Circuits and the Non- linear Bernoulli Cell Formalism (NBCF). The developed electrical equivalent circuit has been compared to an ideal model, which was developed in MATLAB. The robustness of the microelectronic system was evaluated by means of Monte Carlo simulations.Open Acces

Electrochemical noise limits of femtoampere-sensing, CMOS-integrated transimpedance amplifiers

Low-noise operational amplifiers are an important tool in the life sciences. Biosensor measurements typically rely on low-noise transimpedance amplifiers to record biological signals. Two different techniques were used to leverage the advantages of low-noise circuitry for bioelectronics. A CMOS-integrated system for measuring redox-active substrates using electrochemical read-out at very low noise levels is presented. The system incorporates 112 amplifier channels capable of current sensing with noise levels below 1 fArms in a 3.5-Hz bandwidth. The amplifier is externally connected to a gold microelectrode with a radius of 15 µm. The amplifier enables measurement of redox-couples such as potassium ferrocyanide/ferricyanide with concentrations down to 10 nM at current levels of only 300 fA. The electrochemical noise that sets the limits of detection is also measured and analyzed based on redox mass transfer equation and electrochemical impedance spectroscopy. Secondly, CMOS-integrated low noise junction field-effect transistors (JFETs) were developed in a standard 0.18-µm CMOS process. These JFETs reduce input referred flicker noise power by more than a factor of 10 when compared with equally sized n-channel MOS devices by eliminating oxide interfaces in contact with the channel. We show that this improvement in device performance translates into a factor-of-10 reduction in the input-referred noise of integrated CMOS operational amplifiers when JFET devices are used at the input

Crexens™: an expandable general-purpose electrochemical analyzer

2019 Fall.Includes bibliographical references.Electrochemical analysis has gained a great deal of attention of late due to its low-cost, easy-to-perform, and easy-to-miniaturize, especially in personal health care where accuracy and mobility are key factors to bring diagnostics to patients. According to data from Centers for Medicare & Medicaid Services (CMS) in the US, the share of health expenditure in the US has been kept growing in the past 3 decades and reached 17.9% of its overall Gross Domestic Product till 2016, which is equivalent to $10,348 for every person in the US per year. On the other hand, health care resources are often limited not only in rural area but also appeared in well-developed countries. The urgent need and the lack of health resource brings to front the research interest of Point-of-Care (PoC) diagnosis devices. Electrochemical methods have been largely adopted by chemist and biologist for their research purposes. However, several issues exist within current commercial benchtop instruments for electrochemical measurement. First of all, the current commercial instruments are usually bulky and do not have handheld feature for point-of-care applications and the cost are easily near$5,000 each or above. Secondly, most of the instruments do not have good integration level that can perform different types of electrochemical measurements for different applications. The last but not the least, the existing generic benchtops instruments for electrochemical measurements have complex operational procedures that require users to have a sufficient biochemistry and electrochemistry background to operate them correctly. The proposed Crexens™ analyzer platform is aimed to present an affordable electrochemical analyzerwhile achieving comparable performance to the existing commercial instruments, thus, making general electrochemical measurement applications accessible to general public. In this dissertation, the overall Crexens™ electrochemical analyzer architecture and its evolution are presented. The foundation of the Crexens™ architecture was derived from two separate but related research in electrochemical sensing. One of them is a microelectrode sensor array using CMOS for neurotransmitter sensing; the other one is a DNA affinity-based capacitive sensor for infectious disease, such as ZIKA. The CMOS microelectrode sensor array achieved a 320uM sensitivity for norepinephrine, whereas the capacitive sensor achieved a dynamic range of detection from 1 /uL to 105 /uL target molecules (20 to 2 million targets), which makes it be within the detection range in a typical clinical application environment. This dissertation also covers the design details of the CMOS microelectrode array sensor and the capacitive sensor design as a prelude to the development of the Crexens™ analyzer architecture. Finally, an expandable integrated electrochemical analyzer architecture (Crexens™) has been designed for mobile point-of-care (POC) applications. Electrochemical methods have been explored in detecting various bio-molecules such as glucose, lactate, protein, DNA, neurotransmitter, steroid hormone, which resulted in good sensitivity and selectivity. The proposed system is capable of running electrochemical experiments including cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), electrochemical capacitive spectroscopy (ECS), amperometry, potentiometry, and other derived electrochemical based tests. This system consist of a front-end interface to sensor electrodes, a back-end user interface on smart phone and PC, a base unit as master module, a low-noise add-on module, a high-speed add-on module, and a multi-channel add-on module. The architecture allows LEGO™-like capability to stack add-on modules on to the base-unit for performance enhancements in noise, speed or parallelism. The analyzer is capable of performing up to 1900 V/s CV with 10 mV step, up to 12 kHz EIS scan range and a limit of detection at 637 pA for amperometric applications with the base module. With high performance module, the EIS scan range can be extended upto 5 MHz. The limit of detection can be further improved to be at 333 fA using the low-noise module. The form factor of the electrochemical analyzer is designed for its mobile/point-of-care applications, integrating its entire functionality on to a 70 cm² area of surface space. A glutamine enzymatic sensor was used to valid the capability of the proposed electrochemical analyzer and turned out to give good linearity and reached a limit of detection at 50 uM

The development of an electrochemical sensing device for controlled drugs.

Forensic chemists can be faced with a wide array of substances to test when attending clandestine drug manufacture crime scenes. Whilst many techniques exist at their disposal - such as chemical colour test reagents and immunoassays - these methods are at best semi-quantitative and often subject to false positives. Electrochemical methods of detection offer a potential solution to this problem, as the equipment is portable, cheap and robust. The analysis is quantitative and, if the electrode/electrolyte combination is designed properly, it can be extremely sensitive and selective. The scientific literature contains many examples of voltammetric analyses of controlled drugs. A square wave voltammetric analysis of the novel psychoactive substance benzyl-piperazine is reported here, representing the first time this analysis has been established. A limit of detection of 6 μM was achieved, and resolution against the similar ecstasy-type drug 3-4-methylenedioxymethylamphetamine (MDMA) was demonstrated. Two innovative USB powered prototype potentiostats have been developed. As proof of concept, an ATMega328P microcontroller was used in conjunction with 12-bit digital-to-analog and analog-to-digital converters (MAX532 and MCP3304 respectively). Using ferricyanide for redox at a glassy carbon electrode, reversible cyclic voltammetric analyses and square wave linear calibration (2.7 to 13.7 μM, R2=0.998) were achieved by the first prototype. The second prototype extended the compliance range (from ±2.5 V to ±12 V) and improved the signal to noise ratio. The second prototype also achieved a linear calibration using square wave voltammetry of MDMA (41 to 82 μM, R2=0.995) at a carbon paste electrode

Low-power Wearable Healthcare Sensors

Advances in technology have produced a range of on-body sensors and smartwatches that can be used to monitor a wearer’s health with the objective to keep the user healthy. However, the real potential of such devices not only lies in monitoring but also in interactive communication with expert-system-based cloud services to offer personalized and real-time healthcare advice that will enable the user to manage their health and, over time, to reduce expensive hospital admissions. To meet this goal, the research challenges for the next generation of wearable healthcare devices include the need to offer a wide range of sensing, computing, communication, and human–computer interaction methods, all within a tiny device with limited resources and electrical power. This Special Issue presents a collection of six papers on a wide range of research developments that highlight the specific challenges in creating the next generation of low-power wearable healthcare sensors

Integrated Electronics to Control and Readout Electrochemical Biosensors for Implantable Applications

Biosensors can effectively be used to monitor multiple metabolites such as glucose, lactate, ATP and drugs in the human body. Continuous monitoring of these metabolites is essential for patients with chronic or critical conditions. Moreover, this can be used to tune the dosage of a drug for each individual patient, in order to achieve personalized therapy. Implantable medical devices (IMDs) based on biosensors are emerging as a valid alternative for blood tests in laboratories. They can provide continuous monitoring while reduce the test costs. The potentiostat plays a fundamental role in modern biosensors. A potentiostat is an electronic device that controls the electrochemical cell, using three electrodes, and runs the electrochemical measurement. In particular the IMDs require a low-power, fully-integrated, and autonomous potentiostats to control and readout the biosensors. This thesis describes two integrated circuits (ICs) to control and readout multi-target biosensors: LOPHIC and ARIC. They enable chronoamperometry and cyclic voltammetrymeasurements and consume sub-mW power. The design, implementation, characterisation, and validation with biosensors are presented for each IC. To support the calibration of the biosensors with environmental parameters, ARIC includes circuitry to measure the pHand temperature of the analyte through an Iridiumoxide pH sensor and an off-chip resistor-temperature detector (RTD). In particular, novel circuits to convert resistor value into digital are designed for RTD readout. ARIC is integrated into two IMDs aimed for health-care monitoring and personalized therapy. The control and readout of the embedded sensor arrays have been successfully achieved, thanks to ARIC, and validated for glucose and paracetamol measurements while it is remotely powered through an inductive link. To ensure the security and privacy of IMDs, a lightweight cryptographic system (LCS) is presented. This is the first ASIC implementation of a cryptosystem for IMDs, and is integrated into ARIC. The resulting system provides a unique and fundamental capability by immediately encrypting and signing the sensor data upon its creation within the body. Nano-structures such as Carbon nanotubes have been widely used to improve the sensitivity of the biosensors. However, in most of the cases, they introduce more noise into the measurements and produce a large background current. In this thesis the noise of the sensors incorporating CNTs is studied for the first time. The effect of CNTs as well as sensor geometry on the signal to noise ratio of the sensors is investigated experimentally. To remove the background current of the sensors, a differential readout scheme has been proposed. In particular, a novel differential readout IC is designed and implemented that measures inputcurrents within a wide dynamic range and produces a digital output that corresponds to the -informative- redox current of the biosensor

Abstracts of National PhD Students Days 2018 (NPSD’2018) 1st Edition, May 4-5, 2018, Université Ibn Zohr Agadir Maroc, Ouarzazate, Morocco

Abstracts of National PhD Students Days 2018 (NPSD’2018) 1st Edition, May 4-5, 2018, Université Ibn Zohr Agadir Maroc, Ouarzazate, Morocc

A Rapid and Ultra-sensitive Biosensing Platform based on Tunable Dielectrophoresis for Robust POC Applications

With the ongoing pandemic, there have been increasing concerns recently regarding major public health issues such as abuse of organophosphorus compounds, pathogenic bacterial infections, and biosecurity in agricultural production. Biosensors have long been considered a kernel technology for next-generation diagnostic solutions to improve food safety and public health. Significant amounts of effort have been devoted to inventing novel sensing mechanisms, modifying their designs, improving their performance, and extending their application scopes. However, the reliability and selectivity of most biosensors still have much to be desired, which holds back the development and commercialization of biosensors, especially for on-site and point-of-care (POC) usages. Herein, we introduce an innovative two-phase sensing strategy based on tunable AC electrokinetics and capacitive sensing. By dividing the detection process into a sensitivity-priority step and a selectivity-priority step, the specificity and sensitivity of a biosensor can be significantly improved. A capacitive POC aptasensor is fabricated for the implementation of the 2-phase detection and a quasi-single-cell level detection of limit together with an excellent selectivity is achieved simultaneously. The sensor is capable of handling real-world clinic samples without sophisticated pretreatment. Just after a simple one-step dilution, the developed sensor can detect bacteria no less than 2~3 bacteria/10 µL in raw milk samples within 100 s. Alongside whole bacteria detection, the biosensor can also detect endotoxin, the lipopolysaccharide, in bovine serum samples, with a limit of detection of 10 pg/mL. The biosensor is low-cost and easy to use. This work not only demonstrates a biosensor with significant advantages in sensitivity, selectivity and assay time but also opens up a new horizon for further research of all affinity-based biosensors