An Integrated Platform for Differential Electrochemical and ISFET Sensing

A fully-integrated differential biosensing platform on CMOS is presented for miniaturized enzyme-based electrochemical sensing. It enables sensor background current elimination and consists of a differential sensor array and a differential readout IC (DiRIC). The sensor array includes a four-electrode sensor for amperometric electrochemical sensing, as well as a differential ISFET-based pH sensor to calibrate the biosensors. The ISFET is biased in weak inversion and co-designed with DiRIC to enable pH measurements from 1 to 14 with resolution of 0.1 pH. DiRIC enables differential current measurement in the range of ¿¿100 ¿¿A with more than 120dB dynamic range

An Implantable Bio-Micro-system for Drug Monitoring

Multi-target and continuous monitoring by wireless implantable devices is of increasing interest for personalized therapy. In this work an implantable system is presented which is capable of measuring different drugs with Cyclic Voltammetry (CV) method. The wireless microsystem consists of four modules, namely (i) The inductive coil; (ii) Power management IC; (iii) Readout and control IC; (iv) Biosensor array. The power management IC provides 1.8 V with as high as 2 mW power for the readout IC. The configurable readout IC is able to control the biosensor array and measure the sensor current in CV method. CV experiments performed with this microsystem well agree with a commercial equipment for two well known anti-cancer drugs, Etoposide and Mitoxantrone, detection

Full System for Translational Studies of Personalized Medicine with Free-Moving Mice (invited)

A full remotely powered system for metabolism monitoring of free-moving mice is presented here. The fully implantable sensing platform hosts two ASICs, one off-the-shelf micro-controller, four biosensors, two other sensors, a coil to receive power, and an antenna to transmit data. Proper enzymes ensure specificity for animal metabolites while Multi-Walled Carbon Nanotubes ensure the due sensitivity. The remote powering is indeed provided by inductive coils located under the floor of the mouse' cage. Two different approaches were investigated to ensure freedom of movement to the animal. The application to studies for personalized medicine is demonstrated by showing continuous monitoring of both glucose and paracetamol

Sub-mW Reconfigurable Interface IC for Electrochemical Sensing

The IronIC project has the aim of developing a fully implantable and remotely powered platform for the real- time monitoring of human metabolites. In this paper we present a mixed-signal interface IC for the electrochemical sensing data acquisition chain. The IC controls and reads out up to five biomolecular sensors, by receiving commands from a standard interface to conduct chronoamperometry (CA) and cyclic voltammetry (CV). Different voltage profiles are generated by using a single fully on-chip reconfigurable waveform generator, while the measured data are digitized. The IC is realized in 0.18 μm CMOS technology. Electrical measurements show that the linear readout current range is ±1650 nA with 8-bit resolution. The cyclic voltammetry of potassium ferricyanide and the chronoamperometry of hydrogen peroxide have been successfully performed with the interface. The IC consumes 0.92 mW from 1.8 V supply voltage, making it suitable for remotely powered and implantable applications

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 Flexible, Highly Integrated, Low Power pH Readout

Medical devices are widely employed in everyday life as wearable and implantable technologies make more and more technological breakthroughs. Implantable biosensors can be implanted into the human body for monitoring of relevant physiological parameters, such as pH value, glucose, lactate, CO2 [carbon dioxide], etc. For these applications the implantable unit needs a whole functional set of blocks such as micro- or nano-sensors, sensor signal processing and data generation units, wireless data transmitters etc., which require a well-designed implantable unit.Microelectronics technology with biosensors has caused more and more interest from both academic and industrial areas. With the advancement of microelectronics and microfabrication, it makes possible to fabricate a complete solution on an integrated chip with miniaturized size and low power consumption.This work presents a monolithic pH measurement system with power conditioning system for supply power derived from harvested energy. The proposed system includes a low-power, high linearity pH readout circuits with wide pH values (0-14) and a power conditioning unit based on low drop-out (LDO) voltage regulator. The readout circuit provides square-wave output with frequency being highly linear corresponding to the input pH values. To overcome the process variations, a simple calibration method is employed in the design which makes the output frequency stay constant over process, supply voltage and temperature variations. The prototype circuit is designed and fabricated in a standard 0.13-μm [micro-meter] CMOS process and shows good linearity to cover the entire pH value range from 0-14 while the voltage regulator provides a stable supply voltage for the system

Conception et fabrication d'un biocapteur à haute sensibilité pour la détection des neurotransmetteurs

Dans ce mémoire, nous présentons de nouvelles architectures de différents biocapteurs électrochimiques discrets et intégrés appelés potentiostats. Tous les potentiostats développés sont basés sur une structure entièrement différentielle pour une meilleure sensibilité et une meilleure précision. Deux conceptions discrètes à un et quatre canaux ont été proposées. La conception discrète à un canal détecte la molécule de dopamine avec un courant de l’ordre du nA et une consommation électrique de 120 mW. Cette architecture a été développée sur une carte de circuit imprimé (PCB) de 20 mm x 35 mm. L’architecture discrète à quatre canaux est la version améliorée de la précédente en termes de superficie, de sensibilité et de consommation électrique. Une autre version du potentiostat, implémentée sur un PCB de 15 mm x 15 mm, peut mesurer les courants d’oxydoréduction dans la plage du pA avec une consommation de puissance de 60 mW. L’avantage de la structure à multicanaux est qu’elle offre des sensibilités différentes allant du pA au mA pour chaque canal. Une chambre microfluidique de 7,5 mm x 5 mm avec deux entrées et une sortie a été déposée sur le PCB. Une solution saline tampon au phosphate (PBS) avec une solution de ferrocyanure a été utilisée pour tester la fonctionnalité du système réalisé. La voltampérométrie cyclique a été utilisée comme technique de détection. Un comportement linéaire a été observé lorsque la concentration des neurotransmetteurs change. De plus, un potentiostat intégré a été proposé et fabriqué en technologie CMOS 180 nm, basé sur une structure entièrement « différentiel de différence » (Fully Differential Diffrence Amplifier FDDA) pour une faible consommation de puissance et un système à haute sensibilité. Cette nouvelle configuration a été conçue pour la détection des neurotransmetteurs en très faible concentration avec un faible bruit et une plage dynamique élevée. Cette architecture intégrée peut détecter les courants dans une plage inférieure au pA avec un bruit d’entrée faible de 6,9 μVrms tout en consommant seulement 53,9 μW. Le potentiostat proposé est dédié aux dispositifs implantables à faible consommation de puissance et à sensibilité et linéarité élevées.In this thesis, we present different discrete and integrated electrochemical biosensors. All these designed potentiostats are based on fully-differential architecture to enhance sensitivity and accuracy. Two complete single channel and four-channel discrete designs were fabricated. The single channel discrete design imaged the dopamine neurotransmitter with the sensed current of approximately low nano-ampere and power consumption of 120 mW implemented on a 20 x 35 mm PCB. The four-channel discrete design was the improved version of previous one in terms of area, sensitivity and power consumption. The 15 x 15 mm PCB was able to measure the reduction-oxydation currents in the range of high pico-ampere while consuming 60 mW. The advantage of the multichannel architecture is to provide a system with different sensitivity going from pA to mA for each channel. A microfluidic 7.5 x 5 mm chamber with two inlets and one outlet was bonded to the PCB. A phosphate buffered saline (PBS) with ferrocyanide solution was used to test the functionality of the implemented system. Cyclic voltammetry has been used as a detection technique. A linear behavior had been observed when the neurotransmitter concentration changed. An integrated CMOS potentiostat was designed and fabricated in 180 nm technology based on a fully-differential-difference architecture for a low power consumption and also high sensitivity system. This new architecture was designed in order to sense ultra-low concentration of neurotransmitters with low noise and high dynamic range. This integrated design was able to image currents in the range of sub-pA with low input-referred noise of 6.9 µVrms while consuming only 53.9 µW. The proposed potentiostat is dedicated for implantable devices with low power consumption and high sensitivity and linearity

An Integrated Control and Readout Circuit for Implantable Multi-Target Electrochemical Biosensing

We describe an integrated biosensor capable of sensing multiple molecular targets using both cyclic voltammetry (CV) and chronoamperometry (CA). In particular, we present our custom IC to realize voltage control and current readout of the biosensors. A mixed-signal circuit block generates sub-Hertz triangular waveform for the biosensors by means of a direct-dig- ital-synthesizer to control CV. A current to pulse-width converter is realized to output the data for CA measurement. The IC is fabricated in 0.18 μm technology. It consumes 220 μW from 1.8 V supply voltage, making it suitable for remotely-powered applications. Electrical measurements show excellent linearity in sub-μA current range. Electrochemical measurements including CA measurements of glucose and lactate and CV measurements of the anti-cancer drug Etoposide have been acquired with the fabricated IC and compared with a commercial equipment. The results obtained with the fabricated IC are in good agreement with those of the commercial equipment for both CV and CA measurements