Wearable, low-power CMOS ISFETs and compensation circuits for on-body sweat analysis

Complementary metal-oxide-semiconductor (CMOS) technology has been a key driver behind the trend of reduced power consumption and increased integration of electronics in consumer devices and sensors. In the late 1990s, the integration of ion-sensitive field-effect transistors (ISFETs) into unmodified CMOS helped to create advancements in lab-on-chip technology through highly parallelised and low-cost designs. Using CMOS techniques to reduce power and size in chemical sensing applications has already aided the realisation of portable, battery-powered analysis platforms, however the possibility of integrating these sensors into wearable devices has until recently remained unexplored. This thesis investigates the use of CMOS ISFETs as wearable electrochemical sensors, specifically for on-body sweat analysis. The investigation begins by evaluating the ISFET sensor for wearable applications, identifying the key advantages and challenges that arise in this pursuit. A key requirement for wearable devices is a low power consumption, to enable a suitable operational life and small form factor. From this perspective, ISFETs are investigated for low power operation, to determine the limitations when trying to push down the consumption of individual sensors. Batteryless ISFET operation is explored through the design and implementation of a 0.35 \si{\micro\metre} CMOS ISFET sensing array, operating in weak-inversion and consuming 6 \si{\micro\watt}. Using this application-specific integrated circuit (ASIC), the first ISFET array powered by body heat is demonstrated and the feasibility of using near-field communication (NFC) for wireless powering and data transfer is shown. The thesis also presents circuits and systems for combatting three key non-ideal effects experienced by CMOS ISFETs, namely temperature variation, threshold voltage offset and drift. An improvement in temperature sensitivity by a factor of three compared to an uncompensated design is shown through measured results, while adding less than 70 \si{\nano\watt} to the design. A method of automatically biasing the sensors is presented and an approach to using spatial separation of sensors in arrays in applications with flowing fluids is proposed for distinguishing between signal and sensor drift. A wearable device using the ISFET-based system is designed and tested with both artificial and natural sweat, identifying the remaining challenges that exist with both the sensors themselves and accompanying components such as microfluidics and reference electrode. A new ASIC is designed based on the discoveries of this work and aimed at detecting multiple analytes on a single chip. %Removed In the latter half of the thesis, Finally, the future directions of wearable electrochemical sensors is discussed with a look towards embedded machine learning to aid the interpretation of complex fluid with time-domain sensor arrays. The contributions of this thesis aim to form a foundation for the use of ISFETs in wearable devices to enable non-invasive physiological monitoring.Open Acces

Wearable System with Integrated Passive Microfluidics for Real-Time Electrolyte Sensing in Human Sweat

Wearable systems embodied as patches could offer noninvasive and real-time solutions for monitoring of biomarkers in human sweat as an alternative to blood testing, with applications in personalized and preventive healthcare. Sweat is considered to be a biofluid of foremost interest for analysis due the numerous biomarkers it contains. Recent studies have demonstrated that the concentration of some of these biomarkers in sweat, such as the electrolytes studied in this work, can be directly correlated to their concentrations in blood, making sweat a trusted biofluid candidate for non-invasive diagnostics. Until now, the biggest impediment to onâbody sweat monitoring was the lack of technology to analyze sweat composition in realâtime and mainly to continuously collect it. The goal of this work was to develop the building blocks of such wearable system for sweat electrolyte monitoring, with main emphasis on the passive microfluidics, the integrated miniaturized quasi-reference electrode and the functionalization of the sensing devices. The basic sensor technology is formed by Ion Sensitive Field Effect Transistors (ISFET) realized in FinFET and ultra-thin body Silicon on Insulator technology. This thesis shows the development of a state-of-the-art microsystem that allows multisensing of pH, Na+, K+ electrolyte concentrations in sweat, with high selectivity and high sensitivities (â50 mV/dec for all electrolytes), in a wearable fashion. The microsystem comprises a biocompatible skin interface that collects even infinitesimal quantities of sweat (of the order of hundreds of picoliters to tenths of nanoliters), which the body produces in periods of low physical effort. One of the main achievements of this work is the integration of Ion Sensing Fully Depleted FETs and zero power consumption microfluidics, enabling low power (less than 50 nWatts/sensor) wearable biosensing. The thesis presents the needed technological processes and optimizations, together with their characterization, in order to achieve a Lab-On-Skin system

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

A thermally powered ISFET array for on-body pH measurement

Recent advances in electronics and electrochemical sensors have led to an emerging class of next generation wearables, detecting analytes in biofluids such as perspiration. Most of these devices utilize ion-selective electrodes (ISEs) as a detection method; however, ion-sensitive field-effect transistors (ISFETs) offer a solution with improved integration and a low power consumption. This work presents a wearable, thermoelectrically powered system composed of an application-specific integrated circuit (ASIC), two commercial power management integrated circuits and a network of commercial thermoelectric generators (TEGs). The ASIC is fabricated in 0.35 μm CMOS and contains an ISFET array designed to read pH as a current, a processing module which averages the signal to reduce noise and encodes it into a frequency, and a transmitter. The output frequency has a measured sensitivity of 6 to 8 kHz/pH for a pH range of 7-5. It is shown that the sensing array and processing module has a power consumption 6 μW and, therefore, can be entirely powered by body heat using a TEG. Array averaging is shown to reduce noise at these low power levels to 104 μV (input referred integrated noise), reducing the minimum detectable limit of the ASIC to 0.008 pH units. The work forms the foundation and proves the feasibility of battery-less, on-body electrochemical for perspiration analysis in sports science and healthcare applications