Biosensors and CMOS Interface Circuits

abstract: Analysing and measuring of biological or biochemical processes are of utmost importance for medical, biological and biotechnological applications. Point of care diagnostic system, composing of biosensors, have promising applications for providing cheap, accurate and portable diagnosis. Owing to these expanding medical applications and advances made by semiconductor industry biosensors have seen a tremendous growth in the past few decades. Also emergence of microfluidics and non-invasive biosensing applications are other marker propellers. Analyzing biological signals using transducers is difficult due to the challenges in interfacing an electronic system to the biological environment. Detection limit, detection time, dynamic range, specificity to the analyte, sensitivity and reliability of these devices are some of the challenges in developing and integrating these devices. Significant amount of research in the field of biosensors has been focused on improving the design, fabrication process and their integration with microfluidics to address these challenges. This work presents new techniques, design and systems to improve the interface between the electronic system and the biological environment. This dissertation uses CMOS circuit design to improve the reliability of these devices. Also this work addresses the challenges in designing the electronic system used for processing the output of the transducer, which converts biological signal into electronic signal.Dissertation/ThesisM.S. Electrical Engineering 201

Design and construction of a distributed sensor NET for biotelemetric monitoring of brain energetic metabolism using microsensors and biosensors

Neurochemical pathways involved in brain physiology or disease pathogenesis are mostly unknown either in physiological conditions or in neurodegenerative diseases. Nowadays the most frequent usage for biotelemetry is in medicine, in cardiac care units or step-down units in hospitals, even if virtually any physiological signal could be transmitted (FCC, 2000; Leuher, 1983; Zhou et al., 2002). In this chapter we present a wireless device connected with microsensors and biosensors capable to detect real-time variations in concentrations of important compounds present in central nervous system (CNS) and implicated in brain energetic metabolism (Bazzu et al., 2009; Calia et al., 2009)

A 64-channel, 1.1-pA-accurate on-chip potentiostat for parallel electrochemical monitoring

Electrochemical monitoring is crucial for both industrial applications, such as microbial electrolysis and corrosion monitoring as well as consumer applications such as personal health monitoring. Yet, state-of-the-art integrated potentiostat monitoring devices have few parallel channels with limited flexibility due to their channel architecture. This work presents a novel, widely scalable channel architecture using a switch capacitor based Howland current pump and a digital potential controller. An integrated, 64-channel CMOS potentiostat array has been fabricated. Each individual channel has a dynamic current range of 120dB with 1.1pA precision with up to 100kHz bandwidth. The on-chip working electrodes are post-processed with gold to ensure (bio)electrochemical compatibility

An integrated circuit for chip-based analysis of enzyme kinetics and metabolite quantification

We have created a novel chip-based diagnostic tools based upon quantification of metabolites using enzymes specific for their chemical conversion. Using this device we show for the first time that a solid-state circuit can be used to measure enzyme kinetics and calculate the Michaelis-Menten constant. Substrate concentration dependency of enzyme reaction rates is central to this aim. Ion-sensitive field effect transistors (ISFET) are excellent transducers for biosensing applications that are reliant upon enzyme assays, especially since they can be fabricated using mainstream microelectronics technology to ensure low unit cost, mass-manufacture, scaling to make many sensors and straightforward miniaturisation for use in point-of-care devices. Here, we describe an integrated ISFET array comprising 216 sensors. The device was fabricated with a complementary metal oxide semiconductor (CMOS) process. Unlike traditional CMOS ISFET sensors that use the Si3N4 passivation of the foundry for ion detection, the device reported here was processed with a layer of Ta2O5 that increased the detection sensitivity to 45 mV/pH unit at the sensor readout. The drift was reduced to 0.8 mV/hour with a linear pH response between pH 2 – 12. A high-speed instrumentation system capable of acquiring nearly 500 fps was developed to stream out the data. The device was then used to measure glucose concentration through the activity of hexokinase in the range of 0.05 mM – 231 mM, encompassing glucose’s physiological range in blood. Localised and temporal enzyme kinetics of hexokinase was studied in detail. These results present a roadmap towards a viable personal metabolome machine

Voltaje de referencia BandGap y módulo de comunicación serial para SAR ADC 10 bits de baja potencia para aplicaciones biomédicas

The document presents two designs a BandGap Reference Voltage, and a Communication Serial Module for a 10 bits SAR ADC for low-power applications. Designs were implemented using TSMC 0.18 µm CMOS technology with 1.8 V supply voltage. The BandGap Reference Voltage was designed to provide a reference voltage of 900 mV ±500 µV. The bandgap was tested at simulation level under different temperature conditions to ensure constant output in a temperature range from –40 °C to 85 °C. The Communication Serial Module is designed using the hardware description language Verilog. This module receives the 10 bits parallel output of the SAR ADC and retransmits the conversion result into a serial format using the SPI format. The Communication Serial Module was tested under a simulator, where multiple test cases were applied to stimulate in different ways the module. Both circuits were designed to accomplish the SAR ADC requirements in which BandGap supplies the reference voltage to the capacitor array in the SAR ADC and the Serial Module sends the data values after the conversion is finalized.ITESO, A. C

A programmable microsystem using system-on-chip for real-time biotelemetry

A telemetry microsystem, including multiple sensors, integrated instrumentation and a wireless interface has been implemented. We have employed a methodology akin to that for System-on-Chip microelectronics to design an integrated circuit instrument containing several "intellectual property" blocks that will enable convenient reuse of modules in future projects. The present system was optimized for low-power and included mixed-signal sensor circuits, a programmable digital system, a feedback clock control loop and RF circuits integrated on a 5 mm × 5 mm silicon chip using a 0.6 μm, 3.3 V CMOS process. Undesirable signal coupling between circuit components has been investigated and current injection into sensitive instrumentation nodes was minimized by careful floor-planning. The chip, the sensors, a magnetic induction-based transmitter and two silver oxide cells were packaged into a 36 mm × 12 mm capsule format. A base station was built in order to retrieve the data from the microsystem in real-time. The base station was designed to be adaptive and timing tolerant since the microsystem design was simplified to reduce power consumption and size. The telemetry system was found to have a packet error rate of 10<sup>-</sup><sup>3</sup> using an asynchronous simplex link. Trials in animal carcasses were carried out to show that the transmitter was as effective as a conventional RF device whilst consuming less power

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

Dynamic Comparator, SR Latch and Bootstrap Switch for 10 Bits SAR ADC for Biomedical Applications

This document presents the design of a Dynamic Comparator, a SR Latch and a Sample and Hold circuit for a 10 bits SAR ADC. Designs are performed using TSMC 0.18 um CMOS technology with 1.8 V supply voltage. The Dynamic comparator with Strong Arm topology is chosen to fulfill the requirements of SAR ADC. Its performance is tested at simulation level with a clock frequency of 10 KHz to 310 MHz, using typical parameter of process, nominal supply voltage and room temperature. Although, results are presented only at clock frequency of 100 KHz. This analysis showed that comparator has an input offset of 17.8 mV and power consumption of 36.27 nW. Power consumption is in the power budget of SAR ADC however, the input offset voltage has limited the resolution of SAR ADC. The SR latch is designed at transistor level using NAND gates. The circuit has additional digital logic and an external reset pin in order to avoid the prohibited condition. After implementing this modification, it shows a correct functionality at a clock frequency of 100 KHz. The sample and hold circuit is designed with a bootstrap switch for a load capacitance of 300 pF which is the total capacitance of the circuit when it is integrated to the SAR ADC.ITESO, A. C

Silicon-based Integrated Microarray Biochips for Biosensing and Biodetection Applications

The silicon-based integrated microarray biochip (IMB) is an inter-disciplinary research direction of microelectronics and biological science. It has caught the attention of both industry and academia, in applications such as deoxyribonucleic acid (DNA) and immunological detection, medical inspection and point-of-care (PoC) diagnosis, as well as food safety and environmental surveillance. Future biodetection strategies demand biochips with high sensitivity, miniaturization, integration, parallel, multi-target and even intelligence capabilities. In this chapter, a comprehensive investigation of current research on state-of-the-art silicon-based integrated microarray biochips is presented. These include the electrochemical biochip, magnetic tunnelling junction (MTJ) based biochip, giant magnetoresistance (GMR) biochip and integrated oscillator-based biochip. The principles, methodologies and challenges of the aforementioned biochips will also be discussed and compared from all aspects, e.g., sensitivity, fabrication complexity and cost, compatibility with silicon-based complementary metal-oxide-semiconductor (CMOS) technology, multi-target detection capabilities, signal processing and system integrations, etc. In this way, we discuss future silicon-based fully integrated biochips, which could be used for portable medical detection and low cost PoC diagnosis applications