Sara S. Ghoreishizadeh

Full fabrication and packaging of an implantable multi-panel device for monitoring of metabolites in small animals.

In 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.

An integrated platform for advanced diagnostics

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.

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.

A System for Wireless Power Transfer and Data Communication of Long-Term Bio-Monitoring

A system for wireless power transfer and data communication of implantable bio-monitoring systems is presented. The proposed solution uses a servo-controlled power transmitter moved under the animal moving space. An x-y movable magnetic coil transmits the required power with a level able to keep constant the received energy by the bio-sensor system. The power is transferred via the optimized remote powering link at 13.56 MHz. The received ac signal is converted to dc voltage with a passive full-wave integrated rectifier and the voltage regulator supplies 1.8 V for the implantable sensor system. The sensor control and readout circuit measures the current on the bio-sensors and transmit the data to the transmitter. The sensor data are transmitted to an external reader by a low-power OOK transmitter and received by a custom designed receiver at 869 MHz. The results are shown in a tablet computer in real time continuously. The long-term characterization of the implantable system is verified by a fully bio-compatible packaged implant with 30 days measurement. A complete prototype is also presented to prove the overall system performance with the experimental in vitro measurement.

A configurable IC to contol, 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 chronoamper-ometry (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 μW technology. It consumes 711 μW from a 1.8 V supply voltage, making it suitable for remotely powered and implantable applications.

Developing highly-integrated subcutaneous biochips for remote monitoring of human metabolism

A highly integrated system for remote monitoring of several human metabolites is proposed. It is obtained by integrating several components, such as: bio-probes, carbon nanotubes, micro-fabricated gold-electrodes, temperature and pH sensors, extremely small CMOS IC and multilayer coil for remote powering data acquisition and transmission. The entire system has final sizes of only 2.2 mm in width and thick and it is long 1.5 cm. In this paper, results on sensors micro-fabrication, sensing tests, IC design, and power transmission are presented. These results confirmed that the proposed approach is suitable for minimally invasive monitoring of multi-metabolites in humans.

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.

A lightweight cryptographic system for implantable biosensors

This paper presents a lightweight cryptographic system integrated onto a multi-function implantable biosensor prototype. The resulting heterogeneous system provides a unique and fundamental capability by immediately encrypting and signing the sensor data upon its creation within the body. By providing these security services directly on the implantable sensor, a number of low-level attacks can be prevented. This design uses the recently standardized SHA-3 Keccak secure hash function implemented in an authenticated encryption mode. The security module consists of the DuplexSponge security core and the interface wrapper. The security core occupies only 1550 gate-equivalents, which is the smallest authenticated encryption core reported to date. The circuit is fabricated using 0.18 μm CMOS technology and uses a supply voltage of 1.8 V. The simulated power consumption of the complete cryptosystem with a 500 KHz clock is below 7 μW.

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.

Fabrication and packaging of a fully implantable biosensor array

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 biocompatibility 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 site.