A Configurable IC to Control, Readout and Calibrate an Array of Biosensors

We present a novel integrated circuit for a biosensing data acquisition chain. The circuit controls and reads out five bimolecular sensors as well as pH and temperature sensors for biosensor calibration. The IC supports both chronoamperometry (CA) and cyclic voltammetry (CV) measurements, which are commonly used in biosensing. Different voltage waveforms are generated to control CV by using a single configurable waveform generator and programmable constant voltage levels are produced to enable CA. To reduce the area and power consumption of the interface electronics, a unified circuit is designed for CV, CA and pH readout. The biosensors produce currents that are converted by a 13.5-bit sigma delta analog to digital converter. The circuit has been designed and realized in 0.18 μm technology. It consumes 711 μW from a 1.8 V supply voltage, making it suitable for remotely powered and implantable applications

A Current-Mode Potentiostat for Multi-Target Detection Tested with Different Lactate Biosensors

Real-time and multi-target detection by wireless implantable devices is of increasing interest for chronic patients. In this work, electrode sharing is proposed to minimize the size of the implantable device when several three-electrode-based sensing sites are needed. An integrated potentiostat and readout circuit for a multi-target biosensor is presented. To realize this, the circuit reads out the sensor current through each working electrode in a current-mode scheme. The maximum detectable current is 8 μA and the simulated input referred current noise of the circuit is 125 pA/pHz at 1 Hz. The circuit was fabricated in 0.18 μm technology and tested for two lactate biosensors fabricated with a commercial lactate oxidase and an engineered one. Chronoamperometry experiments performed with the circuit agree well with a commercial equipment for lactate detection up to 1 mM

Empirical Study of Noise Dependence in Electrochemical Sensors

We report the experimental study of noise in electrochemical biosensors as related to voltage and concentration. A comparison with experiments is performed for H2O2 and Ferrocyanide with bare sensors and with sensors functionalized with Multi-Walled Carbon Nanotubes (MWCNT) modified electrodes. Chronoamperometry measurements at different voltages were carried out, followed by fast Fourier transform analysis of noise at different concentration of analyte to understand the effect of concentration and voltage on the noise Power Spectral Density (PSD) and the Signal over Noise (SNR) ratio. Experimental results demonstrate the presence of 1/f noise and its dependence on the state variables. The parameters of 1/f noise i.e. the amplitude coefficient and frequency power coefficients are extracted by curve fitting, and are characterized by comparing the coefficient in different molecules, electrodes, voltages and concentration

Electroless Au Plating of CMOS Microelectrodes: Fabrication, Characterisation and Electrochemical Measurement

An essential step in developing amperometric sensors directly on CMOS integrated circuits (ICs) is to cover the exposed uppermost metal layer (aluminium pads) with a thin layer of noble metal to form the basis of the sensing electrode. A simple and scalable method to achieve the gold layer is through electroless plating. Despite the popularity of electroless plating in e.g. PCB manufacturing, there is a lack of information on how it can be applied to Al microelectrodes, and what the electrochemical performances of Au-coated microelectrodes are. This paper presents a detailed process for electroless gold plating of CMOS microelectrodes, with a step-by-step characterisation of the surface roughness, thickness, and elemental composition to optimise the deposition parameters (e.g. deposition time and temperature) for achieving a smooth and uniform gold coverage of the microelectrodes. A gold layer with a rms surface roughness of 53.6 ± 7.9 nm is achieved on the microelectrodes and successfully characterised by cyclic voltammetry in a ferri/ferrocyanide solution. Sonication, oxygen plasma, and continuous cyclic voltammetry are applied to the Au-coated microelectrodes to determine their mechanical and electrochemical stability

An Integrated Platform for Advanced Diagnostics

Abstract—The objective of this work is the systematic study of the use of electrochemical readout for advanced diagnosis and drug monitoring. Whereas to date various electrochemical principles have been studied and successfully tested, they typically operate on a single target molecule and are not integrated in a full data analysis chain. The present work aims to view various sensing approaches and explore the design space for integrated realization of multi-target sensors and sensor arrays. Index Terms—biosensor, integrated circuit, metabolite, oxidase, cytochrome P450, potentiostat

Supplemental Material - Nociception related biomolecules in the adult human saliva: A scoping review with additional quantitative focus on cortisol

Supplemental Material for Nociception related biomolecules in the adult human saliva: A scoping review with additional quantitative focus on cortisol by Roxaneh Zarnegar, Angeliki Vounta, Qiuyuan Li and Sara S Ghoreishizadeh in Molecular Pain.</p

Full Fabrication and Packaging of an Implantable Multi-Panel Device for Monitoring of Metabolites in Small Animals

\u2014In this work, we show the realization of a fully-implantable device for monitoring free-moving small animals. The device integrates a microfabricated sensing platform, a coil for power and data transmission and two custom designed integrated circuits. The device is intended to be implanted in mice, free to move in a cage, to monitor the concentration of metabolites. We show the system level design of each block of the device, and we present the fabrication of the passive sensing platform and its employment for the electrochemical detection of endogenous and exogenous metabolites. Moreover, we describe the assembly of the device to test the biocompatibility of the materials used for the microfabrication. To ensure biocompatibility, an epoxy enhanced polyurethane membrane was used to cover the device. We proved through an in-vitro characterization that the membrane was capable to retain enzyme activity up to 35 days. After 30 days of implant in mice, in-vivo experiments proved that the membrane promotes the integration of the sensor with the surrounding tissue, as demonstrated by the low inflammation level at the implant site

Fabrication and packaging of a fully implantable biosensor

In this work, we showed the realization of a fully- implantable device that integrates a microfabricated sensing platform, a coil for power and data transmission and integrated circuits. We described a device intended to test the biocompati- bility of the materials used for the microfabrication. Therefore, electronics measurements for data communication and remote powering will be reported in another article [1]. To ensure biocompatibility an epoxy enhanced polyurethane membrane was used to cover the device. We proved through an in-vitro characterization that the membrane was capable to retain enzyme activity up to 35 days. After 30 days of implant in mice, in-vivo experiments proved that the membrane promotes the integration of the sensor with the surrounding tissue, as demonstrated by the low inflammation level at the implant sit