Google Glass-Directed Monitoring and Control of Microfluidic Biosensors and Actuators.

Google Glass is a recently designed wearable device capable of displaying information in a smartphone-like hands-free format by wireless communication. The Glass also provides convenient control over remote devices, primarily enabled by voice recognition commands. These unique features of the Google Glass make it useful for medical and biomedical applications where hands-free experiences are strongly preferred. Here, we report for the first time, an integral set of hardware, firmware, software, and Glassware that enabled wireless transmission of sensor data onto the Google Glass for on-demand data visualization and real-time analysis. Additionally, the platform allowed the user to control outputs entered through the Glass, therefore achieving bi-directional Glass-device interfacing. Using this versatile platform, we demonstrated its capability in monitoring physical and physiological parameters such as temperature, pH, and morphology of liver- and heart-on-chips. Furthermore, we showed the capability to remotely introduce pharmaceutical compounds into a microfluidic human primary liver bioreactor at desired time points while monitoring their effects through the Glass. We believe that such an innovative platform, along with its concept, has set up a premise in wearable monitoring and controlling technology for a wide variety of applications in biomedicine.

In-Vivo Validation of Fully Implantable Multi-Panel Devices for Remote Monitoring of Metabolism.

This paper presents the in-vivo tests on a Fully Implantable Multi-Panel Devices for Remote Monitoring of endogenous and exogenous analytes. To investigate issues on biocompatibility, three different covers have been designed, realized and tested in mice for 30 days. ATP and neutrophil concentrations have been measured, at the implant site after the device was explanted, to assess the level of biocompatibility of the device. Finally, fully working prototypes of the device were implanted in mice and tested. The implanted devices were used to detect variations in the physiological concentrations of glucose and paracetamol. Data trends on these analytes have been successfully acquired and transmitted to the external base station. Glucose and paracetamol (also named acetaminophen) have been proposed in this research as model molecules for applications to personalized and translational medicine.

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 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-digital-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.

Memristive biosensors under varying humidity conditions.

We attempt to examine the potential of silicon nanowire memristors in the field of nanobiosensing. The memristive devices are crystalline Silicon (Si) Nanowires (NWs) with Nickel Silicide (NiSi) terminals. The nanowires are fabricated on a Silicon-on-Insulator (SOI) wafer by an Ebeam Lithography Technique (EBL) process that allows high resolution at the nanoscale. A Deep Reactive Ion Etching (DRIE) technique is used to define free-standing nanowires. The close alignment between Silicon (Si) and Nickel-Silicide (NiSi) terminals forms a Schottky-barrier at their junction. The memristive effect of the fabricated devices matches well with the memristor theory. An equivalent circuit reproducing the memristive effect in current-voltage (I-V) characteristics of our silicon nanowires is presented too. The memristive silicon nanowire devices are then functionalized with anti-human VEGF (Vascular Endothelial Growth Factor) antibody and I-V characteristics are examined for the nanowires prior to and after protein functionalization. The uptake of bio-molecules linked to the surface of the memristive NWs is confirmed by the increased voltage gap in the hysteresis curve. The effects of varying humidity conditions on the conductivity of bio-modified memristive silicon nanowires are deeply investigated.

Electrochemical biochip for applications to wireless and batteryless monitoring of free-moving mice.

A multi-sensing platform for applications in wireless and batteryless monitoring of free-moving small animals is presented in this paper. The proposed platform hosts six sensors: four biosensors for sensing of both disease biomarkers and therapeutic compounds, and two further sensors (T and pH) for biosensor calibration. Electrodeposition of Multi-Walled Carbon Nanotubes (MWCNTs) and the subsequent function-alization with proper enzymes is used to assure sensitivity and specificity in electrochemical biosensing. The realized sensors are demonstrated to be capable of measuring several parameters: lactate with a sensitivity of 77±26 µA/mM· cm(2) and a limit of detection (LOD) of 4±1 µM; glucose with a sensitivity of 63±15 µA/mM· cm(2) and a LOD of 8±2 µM; Etoposide (a well known anti-cancer agent) with a sensitivity of 0.15±0.04 mA/mM· cm(2) and a LOD of 4±1 µM; Open Circuit Potential (OCP) measurements are used on a Pt/IrOx junction to sense pH with a sensitivity of around -75±5mV/pH; while a Pt resistive thermal device is used to measure physiological temperature-range with an average sensitivity of 0.108±0.001 kΩ/°C.

Fully integrated biochip platforms for advanced healthcare.

Recent advances in microelectronics and biosensors are enabling developments of innovative biochips for advanced healthcare by providing fully integrated platforms for continuous monitoring of a large set of human disease biomarkers. Continuous monitoring of several human metabolites can be addressed by using fully integrated and minimally invasive devices located in the sub-cutis, typically in the peritoneal region. This extends the techniques of continuous monitoring of glucose currently being pursued with diabetic patients. However, several issues have to be considered in order to succeed in developing fully integrated and minimally invasive implantable devices. These innovative devices require a high-degree of integration, minimal invasive surgery, long-term biocompatibility, security and privacy in data transmission, high reliability, high reproducibility, high specificity, low detection limit and high sensitivity. Recent advances in the field have already proposed possible solutions for several of these issues. The aim of the present paper is to present a broad spectrum of recent results and to propose future directions of development in order to obtain fully implantable systems for the continuous monitoring of the human metabolism in advanced healthcare applications.

Electrochemical detection of anti-breast-cancer agents in human serum by cytochrome P450-coated carbon nanotubes.

We report on the electrochemical detection of anti-cancer drugs in human serum with sensitivity values in the range of 8-925 nA/µM. Multi-walled carbon nanotubes were functionalized with three different cytochrome P450 isoforms (CYP1A2, CYP2B6, and CYP3A4). A model used to effectively describe the cytochrome P450 deposition onto carbon nanotubes was confirmed by Monte Carlo simulations. Voltammetric measurements were performed in phosphate buffer saline (PBS) as well as in human serum, giving well-defined current responses upon addition of increasing concentrations of anti-cancer drugs. The results assert the capability to measure concentration of drugs in the pharmacological ranges in human serum. Another important result is the possibility to detect pairs of drugs present in the same sample, which is highly required in case of therapies with high side-effects risk and in anti-cancer pharmacological treatments based on mixtures of different drugs. Our technology holds potentials for inexpensive multi-panel drug-monitoring in personalized therapy.