Irene Taurino

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.

Fast synthesis of platinum nanopetals and nanospheres for highly-sensitive non-enzymatic detection of glucose and selective sensing of ions

Novel methods to obtain Pt nanostructured electrodes have raised particular interest due to their high performance in electrochemistry. Several nanostructuration methods proposed in the literature use costly and bulky equipment or are time-consuming due to the numerous steps they involve. Here, Pt nanostructures were produced for the first time by one-step template-free electrodeposition on Pt bare electrodes. The change in size and shape of the nanostructures is proven to be dependent on the deposition parameters and on the ratio between sulphuric acid and chloride-complexes (i.e., hexachloroplatinate or tetrachloroplatinate). To further improve the electrochemical properties of electrodes, depositions of Pt nanostructures on previously synthesised Pt nanostructures are also performed. The electroactive surface areas exhibit a two order of magnitude improvement when Pt nanostructures with the smallest size are used. All the biosensors based on Pt nanostructures and immobilised glucose oxidase display higher sensitivity as compared to bare Pt electrodes. Pt nanostructures retained an excellent electrocatalytic activity towards the direct oxidation of glucose. Finally, the nanodeposits were proven to be an excellent solid contact for ion measurements, significantly improving the time-stability of the potential. The use of these new nanostructured coatings in electrochemical sensors opens new perspectives for multipanel monitoring of human metabolism.

Bubble electrodeposition of gold porous nanocorals for the enzymatic and non-enzymatic detection of glucose.

Au nanocorals are grown on gold screen-printed electrodes (SPEs) by using a novel and simple one-step electrodeposition process. Scanning electron microscopy was used for the morphological characterization. The devices were assembled on a three-electrode SPE system, which is flexible and mass producible. The electroactive surface area, determined by cyclic voltammetry in sulphuric acid, was found to be 0.07±0.01cm(2) and 35.3±2.7cm(2) for bare Au and nanocoral Au, respectively. The nanocoral modified SPEs were used to develop an enzymatic glucose biosensor based on H2O2 detection. Au nanocoral electrodes showed a higher sensitivity of 48.3±0.9μA/(mMcm(2)) at +0.45V vs Ag|AgCl compared to a value of 24.6±1.3μA/(mMcm(2)) at +0.70V vs Ag|AgCl obtained with bare Au electrodes. However, the modified electrodes have indeed proven to be extremely powerful for the direct detection of glucose with a non-enzymatic approach. The results confirmed a clear peak observed by using nanocoral Au electrode even in the presence of chloride ions at physiological concentration. Amperometric study carried out at +0.15V vs Ag|AgCl in the presence of 0.12M NaCl showed a linear range for glucose between 0.1 and 13mM.

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.

High-Performance Multipanel Biosensors Based on a Selective Integration of Nanographite Petals

We report the first selective growth of nanographite petals and various carbon nanomaterials onto a multipanel electrochemical platform. Different types of nanomaterials can be obtained by fine-tuning the growth parameters of the chemical vapor deposition (CVD) process. First, absolute novelty is the catalytic CVD selective growth of different carbon nanomaterials only on the working electrodes of the platform. A second novelty is the growth obtained at complementary metal-oxide-semiconductor compatible temperatures. These novel electrodes have been incorporated in sensors in which performance characteristics improve with the content of nanostructures. Unprecedented sensing parameters with respect to both direct and enzyme-mediated electrochemical biodetection have been obtained.

Efficient voltammetric discrimination of free bilirubin from uric acid and ascorbic acid by a CVD nanographite-based microelectrode

We report a novel electrochemical sensor based on nanographite grown on platinum microelectrodes for the determination of bilirubin in the presence of normal concentrations of albumin. The albumin is a protein with an intrinsic ability to bind the bilirubin therefore reducing the concentration of the free electroactive metabolite in human fluids. In addition, the proposed device permits the discrimination of free bilirubin from two interferents, uric acid and ascorbic acid, by the separation of their oxidation peaks in voltammetry. Preliminary measurements in human serum prove that the proposed nanostructured platform can be used to detect bilirubin.

Direct growth of nanotubes and graphene nanoflowers on electrochemical platinum electrodes

Multi-walled carbon nanotubes and graphene nanoflowers were grown by a catalytic chemical vapor deposition process on metal surfaces. Electrodeposition was used as a versatile technique to obtain three different iron catalyst coatings on platinum microelectrodes. The influence of growth parameters on carbon deposits was investigated. Characterization was carried out by scanning electron microscopy and Raman spectroscopy. A chemical treatment in sulphuric acid produced an increased voltammetric background current. In Raman spectra, the effect of the chemical treatment is seen as a more pronounced sp(3) hybridisation mode of C resulting from surface functionalization of the C nanomaterials. Overall, the hybrid electrodes we produced exhibit a promising performance for oxidase-based array biosensors. Therefore, our study opens the possibility of integrating the hybrid electrodes in biochip applications.

Wireless Monitoring of Endogenous and Exogenous Biomolecules on an Android Interface

Monitoring patients in intensive care units is generally expensive and time consuming. A prompter medical intervention for those critical patients is a key factor for their safety. Therefore, a system that offers immediate visualization of the monitored data represents a great advance in the field. In this paper, the design, the development, and the validation of an android interface for the continuous and wireless monitoring of up to five compounds are described. Continuous monitoring of the biomolecules is addressed by using a fully integrated hardware platform consisting of biosensors connected to a read-out circuit on a printed circuit board. The electrochemical platform uses Rovings Bluetooth module RN-42 to send the measured data to the mobile device. For the validation of the system, some biomolecules are taken as reference: glucose and lactate for endogenous metabolites and paracetamol for exogenous biomolecules. Chronoamperometries are performed at +650 mV for glucose and lactate and at +450 mV for paracetamol. Multi-walled carbon nanotubes are deposited on working electrodes for glucose and lactate for enhanced signal. Instead, for paracetamol, bare working electrodes are used. The measured data are continuously displayed on the screen of the mobile device because of the android interface. Current step for every variation of glucose, lactate, or paracetamol is clearly visible by the trend of the graphs.

Wireless monitoring in intensive care units by a 3D-printed system with embedded electronic

In this paper, the design, realization, and preliminary testing of a portable wireless system for measuring key metabolites (e.g., glucose, lactate, calcium, potassium) in intensive care monitoring is presented. The system consists of a 3D-Printed case, which includes the fluidic system that drives the monitored human fluids on top of the sensing devices. The case fully integrates a hardware platform on PCB (Printed Circuit Board) that connects the biosensors to the read-out font-end and to a Bluetooth® module for the data transmission to a mobile Android interface. Two metabolites, glucose and lactate, that are important to monitor in critical patients, were measured in the range of clinical interest.

Electrochemical nanostructured biosensors: carbon nanotubes versus conductive and semi-conductive nanoparticles

The aim of this work was to demonstrate that various types of nanostructures provide different gains in terms of sensitivity or detection limit albeit providing the same gain in terms of increased area. Commercial screen printed electrodes (SPEs) were functionalized with 100 µg of bismuth oxide nanoparticles (Bi2O3 NPs), 13.5 µg of gold nanoparticles (Au NPs), and 4.8 µg of multi-wall carbon nanotubes (MWCNTs) to sense hydrogen peroxide (H2O2). The amount of nanomaterials to deposit was calculated using specific surface area (SSA) in order to equalize the additional electroactive surface area. Cyclic voltammetry (CV) experiments revealed oxidation peaks of Bi2O3 NPs, Au NPs, and MWCNTs based electrodes at (790 ± 1) mV, (386 ± 1) mV, and (589 ± 1) mV, respectively, and sensitivities evaluated by chronoamperometry (CA) were (74 ± 12) µA mM−1 cm−2, (129 ± 15) ±A mM−1 cm−2, and (54 ± 2) ±A mM−1 cm−2, respectively. Electrodes functionalized with Au NPs showed better sensing performance and lower redox potential (oxidative peak position) compared with the other two types of nanostructured SPEs. Interestingly, the average size of the tested Au NPs was 4 nm, under the limit of 10 nm where the quantum effects are dominant. The limit of detection (LOD) was (11.1 ± 2.8) ±M, (8.0 ± 2.4) ±M, and (3.4 ± 0.1) ±M for Bi2O3 NPs, Au NPs, and for MWCNTs based electrodes, respectively.