Nadia Zine

New technology for multi-sensor silicon needles for biomedical applications

Abstract A multi-sensor silicon needle including two ion-sensitive field effect transistor (ISFET) sensors, a platinum pseudo-reference electrode (Pt) and a temperature sensor has been fabricated by using a CMOS-compatible technology and silicon micromachining. This paper presents a summary of the fabrication process and results of the device characterisation. The feasibility of the fabrication technology has been demonstrated and all devices have operated satisfactorily, with a response showing good sensitivity and linearity. The multi-sensor has been developed for the detection of myocardial ischemia during cardiac surgery.

Hydrogen-selective microelectrodes based on silicon needles

The fabrication of hydrogen-selective microelectrodes on silicon needle-shaped substrates is described. The microelectrodes are based on an ion-selective poly(vinyl chloride) (PVC) membrane with an intrinsically conducting polymer (polypyrrole (PPy)) solid contact layer. The polypyrrole is prepared with the dopant anion cobaltbis(dicarbollide) [3,3 0 -Co(1,2-C2B9H11)2] � , which gives a high stability to the polymer layer. The performance of the resulting solid-contact ion-selective microelectrodes (SCISME) is investigated by using potentiometric measurement and electrochemical impedance spectrometry. The feasibility of the fabrication technology is demonstrated and the devices operate satisfactorily, with a response showing good sensitivity and selectivity against common interfering cations in background solutions. The SCISME has been developed for organ monitoring during cardiac surgery or during transportation for transplants. # 2003 Elsevier Science B.V. All rights reserved.

Analytical features of K+-sensitive membrane obtained by implantation in silicon dioxide films

Abstract Potassium (K + ) ion-sensitive membranes produced by the ion implantation technique are investigated. The sensing layers are fabricated by implanting K + and Al + ions into silicon dioxide on silicon with low energy in order to reduce the damage to the substrate during the process of implantation. The ion sensitivity of such ion-implanted layers was investigated by using C – V measurements. All devices tested have shown good sensitivities and linear responses over at least four decades of potassium activity, with good selectivity in the presence of interfering ions like NH 4 + , Li + and Mg 2+ .

Reactive magnetic poly(divinylbenzene-co-glycidyl methacrylate) colloidal particles for specific antigen detection using microcontact printing technique.

Epoxy-functionalized magnetic poly(divinylbenzene-co-glycidyl methacrylate) colloidal particles (mPDGs) were prepared by co-polymerization of 1,4-divinylbenzene and glycidyl methacrylate monomers. The reaction was conducted by batch emulsion polymerization in the presence of an oil in water magnetic emulsion as a seed. The chemical composition, morphology, iron oxide content, magnetic properties, particle size and colloidal stability of the prepared magnetic polymer particles were characterized using Fourier transform infrared spectroscopy, transmission electron microscopy, thermal gravimetric analysis, vibrating sample magnetometry, dynamic light scattering, and zeta potential determination, respectively. The prepared mPDGs were immobilized on a self-assembled monolayer of 3-aminopropyltriethoxysilane (APTES)/octadecyltrichlorosilane (OTS), which were patterned on glass using microcontact printing technique, forming mPDGs-APTES/OTS reactive surface. This construction (mPDGs-APTES/OTS) was used as a solid support for immunoassay. The immobilized magnetic particles were bioconjugated with monoclonal anti-human IL-10 antibody to provide specific and selective recognition sites for the recombinant human IL-10 protein (antigen). Fluorescence microscopic examination was carried out to follow this immunoassay using fluorescently labeled anti-human IL-10 antibody. The results obtained proved the successful use of mPDGs-APTES/OTS microcontact printed surfaces in an immunoassay, which can be exploited and integrated into microsystems in order to elaborate medical devices (e.g. biosensors) which could provide rapid analysis at high sensitivity with low volumes of analyte.

A fully integrated electrochemical biosensor platform fabrication process for cytokines detection.

Interleukin-1b (IL-1b) and interleukin-10 (IL-10) biomarkers are one of many antigens that are secreted in acute stages of inflammation after left ventricle assisted device (LVAD) implantation for patients suffering from heart failure (HF). In the present study, we have developed a fully integrated electrochemical biosensor platform for cytokine detection at minute concentrations. Using eight gold working microelectrodes (WEs) the design will increase the sensitivity of detection, decrease the time of measurements, and allow a simultaneous detection of varying cytokine biomarkers. The biosensor platform was fabricated onto silicon substrates using silicon technology. Monoclonal antibodies (mAb) of anti-human IL-1b and anti-human IL-10 were electroaddressed onto the gold WEs through functionalization with 4-carboxymethyl aryl diazonium (CMA). Cyclic voltammetry (CV) was applied during the WE functionalization process to characterize the gold WE surface properties. Finally, electrochemical impedance spectroscopy (EIS) characterized the modified gold WE. The biosensor platform was highly sensitive to the corresponding cytokines and no interference with other cytokines was observed. Both cytokines: IL-10 and IL-1b were detected within the range of 1pgmL-1 to 15pgmL-1. The present electrochemical biosensor platform is very promising for multi-detection of biomolecules which can dramatically decrease the time of analysis. This can provide data to clinicians and doctors concerning cytokines secretion at minute concentrations and the prediction of the first signs of inflammation after LVAD implantation.

Submicron magnetic core conducting polypyrrole polymer shell: Preparation and characterization

Magnetic particles are of great interest in various biomedical applications, such as, sample preparation, in vitro biomedical diagnosis, and both in vivo diagnosis and therapy. For in vitro applications and especially in labs-on-a-chip, microfluidics, microsystems, or biosensors, the needed magnetic dispersion should answer various criteria, for instance, submicron size in order to avoid a rapid sedimentation rate, fast separations under an applied magnetic field, and appreciable colloidal stability (stable dispersion under shearing process). Then, the aim of this work was to prepare highly magnetic particles with a magnetic core and conducting polymer shell particles in order to be used not only as a carrier, but also for the in vitro detection step. The prepared magnetic seed dispersions were functionalized using pyrrole and pyrrole-2-carboxylic acid. The obtained core-shell particles were characterized in terms of particle size, size distribution, magnetization properties, FTIR analysis, surface morphology, chemical composition, and finally, the conducting property of those particles were evaluated by cyclic voltammetry. The obtained functional submicron highly magnetic particles are found to be conducting material bearing function carboxylic group on the surface. These promising conducting magnetic particles can be used for both transport and lab-on-a-chip detection.

Cancer Prognostics by Direct Detection of p53-Antibodies on Gold Surfaces by Impedance Measurements

The identification and measurement of biomarkers is critical to a broad range of methods that diagnose and monitor many diseases. Serum auto-antibodies are rapidly becoming interesting targets because of their biological and medical relevance. This paper describes a highly sensitive, label-free approach for the detection of p53-antibodies, a prognostic indicator in ovarian cancer as well as a biomarker in the early stages of other cancers. This approach uses impedance measurements on gold microelectrodes to measure antibody concentrations at the picomolar level in undiluted serum samples. The biosensor shows high selectivity as a result of the optimization of the epitopes responsible for the detection of p53-antibodies and was validated by several techniques including microcontact printing, self-assembled-monolayer desorption ionization (SAMDI) mass spectrometry, and adhesion pull-off force by atomic force microscopy (AFM). This transduction method will lead to fast and accurate diagnostic tools for the early detection of cancer and other diseases.

Novel strategy for sulfapyridine detection using a fully integrated electrochemical Bio-MEMS: Application to honey analysis.

Sulfapyridine (SPy) is a sulfonamide antibiotic largely employed as veterinary drugs for prophylactic and therapeutic purposes. Therefore, its spread in the food products has to be restricted. Herein, we report the synthesis and characterization of a novel electrochemical biosensor based on gold microelectrodes modified with a new structure of magnetic nanoparticles (MNPs) coated with poly(pyrrole-co-pyrrole-2-carboxylic acid) (Py/Py-COOH) for high efficient detection of SPy. This analyte was quantified through a competitive detection procedure with 5-[4-(amino)phenylsulfonamide]-5-oxopentanoic acid-BSA (SA2-BSA) antigens toward polyclonal antibody (Ab-155). Initially, gold working electrodes (WEs) of integrated biomicro electro-mechanical system (BioMEMS) were functionalized by Ppy-COOH/MNPs, using a chronoamperometric (CA) electrodeposition. Afterward, SA2-BSA was covalently bonded to Py/Py-COOH/MNP modified gold WEs through amide bonding. The competitive detection of the analyte was made by a mixture of a fixed concentration of Ab-155 and decreasing concentrations of SPy from 50µgL-1 to 2ngL-1. Atomic Force Microscopy characterization was performed in order to ensure Ppy-COOH/MNPs electrodeposition on the microelectrode surfaces. Electrochemical measurements of SPy detection were carried out using electrochemical impedance spectroscopy (EIS). This biosensor was found to be highly sensitive and specific for SPy, with a limit of detection of 0.4ngL-1. This technique was exploited to detect SPy in honey samples by using the standard addition method. The measurements were highly reproducible for detection and interferences namely, sulfadiazine (SDz), sulfathiazole (STz) and sulfamerazine (SMz). Taking these advantages of sensitivity, specificity, and low cost, our system provides a new horizon for development of advanced immunoassays in industrial food control.

A durable solid contact sulfide sensor based on a ceric acrylohydrazide ionophore attached to polyacrylamide with a nanomolar detection limit

A durable sulfide selective solid-contact sensor based on a newly synthesized ceric complex of N′-acetyl-2-(benzothiazol-2yl)-3-(3-chloro-5-methyl-4H-pyrazol-4-yl)acrylo hydrazide (ABPAH) covalently attached to polyacrylamide (PAA) as the ionophore has been developed and potentiometrically evaluated. The all solid-contact sensor was constructed by the application of a thin film of the selective membrane cocktail onto the surface of a gold electrode, which was pre-coated with conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) as an ion and electron transducer. The cocktail was composed of poly(butyl methacrylate-co-dodecyl methacrylate) (PBDA) copolymer as a plasticizer-free matrix and the covalently attached acrylohydrazide ionophore. The sensor containing 12.5% of the Ce–ABPAH–PAA (ionophore II) showed a Nernstian slope of −29.42 mV per conc. decade with a linear range of 1.0 × 10−8–1.0 × 10−2 mol L−1 and a detection limit of 2.0 × 10−9 mol L−1 in a sulfide anti-oxidant buffer (SAOB) solution with a pH value 13.0. The fast response time of >10 seconds for the proposed sulfide sensor allowed its utilization as a detector for the flow injection potentiometric (FIP) determination of sulfide ions in various water samples.

Human olfactory receptor 17-40 as an active part of a nanobiosensor: a microscopic investigation of its electrical properties

Increasing attention has recently been devoted to protein-based nanobiosensors. The main reason is the huge number of possible technological applications, ranging from drug detection to early cancer diagnosis. Their operating model is based on protein activation and the corresponding conformational change due to the capture of an external molecule, the so-called ligand. Recent measurements, performed with different techniques on the human 17-40 olfactory receptor, revealed a very narrow window of response in respect to the odour concentration. This is a crucial point for understanding whether the use of this olfactory receptor as a sensitive part of a nanobiosensor is a good choice. In this paper we investigate the topological and electrical properties of the human olfactory receptor 17-40 with the objective of providing a microscopic interpretation of available experiments. To this purpose, we model the protein by means of a graph that is able to capture the mean features of the 3D backbone structure. The graph is then associated with an equivalent impedance network, able to evaluate the impedance spectra of the olfactory receptor in its native and activated state. We assume a topological origin of the different protein electrical responses to different ligand concentrations: In this perspective all the experimental data are collected and interpreted satisfactorily within a unified scheme, also useful for application to other proteins.