Abdelhamid Errachid

Ion-sensitive field-effect transistors fabricated in a commercial CMOS technology

Abstract The fabrication of pH-sensitive ISFET devices in an unmodified two-metal commercial CMOS technology (1.0 m from Atmel-ES2) is reported. The ISFET devices have a gate structure compatible with the CMOS process, with an electrically floating electrode consisting on polysilicon plus the two metals. The passivation oxynitride layer acts as the pH-sensitive material in contact with the liquid solution. The devices have shown good operating characteristics, with a 47 mV/pH response. The use of a commercial CMOS process allows the straightforward integration of signal-processing circuitry. An ISFET amplifier circuit has been integrated with the ISFET sensors.

A simple REFET for pH detection in differential mode

Abstract A simple reference field-effect transistor (REFET) for pH detection in differential mode measurements is described. The device is based on a pH-insensitive polymeric PVC membrane cast on the gate insulator of an ion-sensitive field-effect transistor (ISFET) device, that has been previously silylated. The REFET shows low pH sensitivity (1.8 mV/pH) and is only slightly affected by the concentration of Na + and K + . The pH response of a combined solid-state device consisting on a pH ISFET (of 45 mV/pH sensitivity), the REFET and a quasi-reference electrode (QRE) (Pt) is 43.7 mV/pH from pH 2 to 9.

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.

Impedimetric immunosensor for human serum albumin detection on a direct aldehyde-functionalized silicon nitride surface.

In this work we report the fabrication and characterization of a label-free impedimetric immunosensor based on a silicon nitride (Si(3)N(4)) surface for the specific detection of human serum albumin (HSA) proteins. Silicon nitride provides several advantages compared with other materials commonly used, such as gold, and in particular in solid-state physics for electronic-based biosensors. However, few Si(3)N(4)-based biosensors have been developed; the lack of an efficient and direct protocol for the integration of biological elements with silicon-based substrates is still one of its the main drawbacks. Here, we use a direct functionalization method for the direct covalent binding of monoclonal anti-HSA antibodies on an aldehyde-functionalized Si-p/SiO(2)/Si(3)N(4) structure. This methodology, in contrast with most of the protocols reported in literature, requires less chemical reagents, it is less time-consuming and it does not need any chemical activation. The detection capability of the immunosensor was tested by performing non-faradaic electrochemical impedance spectroscopy (EIS) measurements for the specific detection of HSA proteins. Protein concentrations within the linear range of 10(-13)-10(-7) M were detected, showing a sensitivity of 0.128 Ω μM(-1) and a limit of detection of 10(-14) M. The specificity of the sensor was also addressed by studying the interferences with a similar protein, bovine serum albumin. The results obtained show that the antibodies were efficiently immobilized and the proteins detected specifically, thus, establishing the basis and the potential applicability of the developed silicon nitride-based immunosensor for the detection of proteins in real and more complex samples.

Electrochemical detection of d-dimer as deep vein thrombosis marker using single-chain d-dimer antibody immobilized on functionalized polypyrrole

We describe a rapid and sensitive method for detection and quantification of d-dimer which is a biomarker present at elevated concentrations in patients with deep vein thrombosis (DVT) disorders. The method uses an immunosensor based on a single-chain antibody (ScAb) immobilized on a transducer surface and with a densely packed receptor layer. Detection is based on the redox activity of a N-alpha bis(carboxymethyl)-L-lysine (ANTA)/Cu2+ complex attached to a polypyrrole backbone. The resulting hybrid material: polypyrrole ANTA/metal complex/His-tag ScAb was characterized by AFM, surface plasmon resonance (SPR) and differential pulse voltammetry (DPV) for the optimization of the biosensor formation. The biosensor offers a promising template for antibody immobilization and for immunodetection of a specific D-dimer. The biosensor shows a remarkable variation in redox activity of the ANTA/Cu2+ complex after the D-dimer association with a binding constant Kd of 1 ng mL(-1). Electrochemical impedance spectroscopy (EIS) allows monitoring D-dimer association with a linear response between 0.1 ng mL(-1) and 500 ng mL(-1) and a detection limit of 100 pg mL(-1) in PBS is obtained. The biolayer exhibits the same sensitivity for the detection of d-dimer in human patient plasma samples. This assay method is versatile, offers enhanced performance for the evaluation of proteins association and could easily be extended to the detection of other proteins, present in serum human sample.

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.

Application of a new phosphadithiamacrocycle to ClO−4-selective CHEMFET and ion-selective electrode devices

Abstract A new dithiamacrocycle incorporating a phosphine donor group (I) has been synthesized and tested as neutral carrier in PVC membranes. ClO−4-selective CHEMFET and ISE devices based on these plasticized membranes have been developed. Both devices have shown Nernstian response and a wide working pH range. Most common anions, except BF−4, do not cause interferences. The response properties and selectivity found for perchlorate ions compare favourably with the commercial and conventional ClO−4 electrodes based on quaternary ammonium ion-exchange sites. This is probably the first example of perchlorate selective CHEMFETs.

Electrochemical boron-doped diamond film microcells micromachined with femtosecond laser: application to the determination of water framework directive metals.

Planar electrochemical microcells were micromachined in a microcrystalline boron-doped diamond (BDD) thin layer using a femtosecond laser. The electrochemical performances of the new laser-machined BDD microcell were assessed by differential pulse anodic stripping voltammetry (DPASV) determinations, at the nanomolar level, of the four heavy metal ions of the European Water Framework Directive (WFD): Cd(II), Ni(II), Pb(II), Hg(II). The results are compared with those of previously published BDD electrodes. The calculated detection limits are 0.4, 6.8, 5.5, and 2.3 nM, and the linearities go up to 35, 97, 48, and 5 nM for, respectively, Cd(II), Ni(II) Pb(II), and Hg(II). The detection limits meet with the environmental quality standard of the WFD for three of the four metals. It was shown that the four heavy metals could be detected simultaneously in the concentration ratio usually measured in sewage or runoff waters.

Impedimetric immunosensor based on SWCNT-COOH modified gold microelectrodes for label-free detection of deep venous thrombosis biomarker

Measurement of D-dimer has subsequently become an essential element in the diagnostics of deep vein thrombosis and pulmonary embolism; in this context microelectrodes with an area of 9×10(-4) cm(2) were used to develop impedimetric immunosensor for detecting deep venous thrombosis biomarker (D-dimer). The biosensor is based on functionalized carbon nanotubes (SWCNT-COOH) where the antibody (anti-D-dimer) was immobilized by covalent binding. The electrical properties and the morphology of the biolayer were characterized by electrochemical impedance spectroscopy (EIS), cyclic voltammetry and atomic force spectroscopy (AFM). Impedimetric microimmunosensor allows to obtain sensitivity of 40.1 kΩ μM(-1) and detection limit of 0.1 pg/mL (0.53 fM) with linear range from 0.1 pg/mL to 2 μg/mL (0.53 fM to 0.01 μM). We demonstrate that using carbon nanotubes and microelectrodes, high sensitivity and dynamic range were obtained. The biosensor exhibited a short response time of 10 min. Moreover, the studied immunosensor exhibits good reproducibility (R.S.D. 8.2%, n=4).

Microconductometric immunosensor for label-free and sensitive detection of Gram-negative bacteria

Blood safety is a global health goal. In developed countries, bacterial contamination of platelet concentrates is the highest infectious risk in transfusion despite the current preventive strategies. We aimed to develop a conductometric biosensor for the generic, rapid and sensitive detection of Gram-negative bacteria. Our strategy is based on immunosensors: addressable magnetic nanoparticles coupled with anti-LPS antibodies were used for the generic capture of Gram-negative bacteria. Bacterial capture was characterized by impedancemetric and microscopic measurements. The results obtained with conductometric measurements allowed real-time, sensitive detection of Escherichia coli or Serratia marcescens cultures from 1 to 10(3) CFU mL(-1). The ability of the immunosensor to detect Gram negative bacteria was also tested on clinically relevant strains. The conductometric immunosensor allowed the direct detection of 10-10(3) CFU mL(-1) of Pseudomonas aeruginosa and Acinetobacter baumannii strains that were undetectable using standard immunoblot methods. Results showed that the conductometric response was not inhibited in 1% serum.