A Highly Sensitive Potentiometric Amphetamine Microsensor Based on All-Solid-State Membrane Using a New Ion-Par Complex, [3,3′-Co(1,2-closo-C2B9H11)2]− C9H13NH+

In the present work a highly sensitive ion-selective microelectrode for the detection of amphetamine is presented. For this purpose, a novel ion-par complex based on the metallocarborane, cobalt bis(dicarbollide) anion ([3,3′-Co(1,2-C2B9H11)2]−) coupled to amphetamonium cation has been prepared as the active site for amphetamine recognition. The prepared ion-par complex was incorporated to a PVC-type sensitive membrane. It was then drop-casted on the top of a gold microelectrode previously modified with a solid contact layer of polypyrrole. This novel amphetamine microsensor has provided excellent and quick response within the range 10−5 M to 10−3 M of amphetamine concentration, a limit of detection of 12 µM and a slope of 60.1 mV/decade. It was also found to be highly selective toward some potential interference compounds when compared to amphetamine.The authors acknowledge the financial support from the European Union’s Horizon 2020 research and innovation programme entitled MicroMole and HEARTEN grant agreement No. 653626 and No. 643694 respectivel

Low-Cost Impedance Measurements for Lab-on-a-Chip Architectures: Towards Potentiostat Miniaturization

The development of miniaturized potentiostats capable of measuring in a wide range of conditions and with full characteristics (e.g., wide bandwidth and capacitive/inductive contribution to sensor’s impedance) is still an unresolved challenge in bioelectronics. We present a simple analogue design coupled to a digital filter based on a lock-in amplifier as an alternative to complex architectures reported hitherto. A low-cost, miniaturized and fully integrated acquisition electronic system was developed, tested for a fully integrated three-lead electrochemical biosensor and benchmarked against a commercial potentiostat. The portable potentiostat was coupled to an array of miniaturized gold working electrodes to perform complex impedance analyses for tumor necrosis factor α (TNF-α) cytokine detection. This wearable potentiostat is very promising for the development of low-cost point-of-care (POC) with low power consumption.The research leading to these results has received funding from the European Union’s 7FP (SEA-on-a-CHIP, Grant Agreement No. 614168) and the European Union’s Horizon 2020 (HEARTEN, Grant Agreement No. 643694). R.P. acknowledges an FPU grant from the Spanish Ministerio de Educación, Cultura y Deporte

An aptasensor for ochratoxin A based on grafting of polyethylene glycol on a boron-doped diamond microcell

International audienceA novel strategy for the fabrication of an electrochemical label-free aptasensor for small-size molecules is proposed and demonstrated as an aptasensor for ochratoxin A (OTA). A long spacer chain of polyethylene glycol (PEG) was immobilized on a boron-doped diamond (BDD) microcell via electrochemical oxidation of its terminal amino groups. The amino-aptamer was then covalently linked to the carboxyl end of the immobilized PEG as a two-piece macromolecule, autoassembled at the BDD surface, forming a dense layer. Due to a change in conformation of the aptamer on the target analyte binding, a decrease of the electron transfer rate of the redox [Fe(CN)(6)](4-/3-) probe was observed. To quantify the amount of OTA, the decrease of the square wave voltammetry (SWV) peak maximum of this probe was monitored. The plot of the peak maximum against the logarithm of OTA concentration was linear along the range from 0.01 to 13.2 ng/L, with a detection limit of 0.01 ng/L. This concept was validated on spiked real samples of ric

Elaboration de microélectrodes par techniques originales basées sur la lithographie douce

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Novel Capacitance Biosensor Based on Hafnium Oxide for Interleukin-10 Protein Detection

International audienceIn this present study, we have analyzed one cytokine, interleukin-10 (IL-10), that plays a pivotal role in patients with chronic heart failure. For this purpose, a novel capacitance substrate, based on hafnium oxide (HfO2) grown by Atomic Layer Deposition on silicon, was applied to study the interaction between IL-10 with the corresponding antibody. HfO2 has been functionalized using an aldehyde monolayer, to directly immobilize the anti-human IL-10 monoclonal antibody. The interaction between antibody-antigen (Ab-An), was characterized by fluorescence patterning and electrochemical impedance spectroscopy (EIS). The preliminary results for fluorescence patterning, demonstrated bio-recognition of the recombinant protein, while Nyquist plots showed variation when we changed the concentration from 1-10 ng/mL. This demonstrated that the developed biosensor was sensitive to the detection of IL- 10

Development of a flexible microfluidic system based on a simple and reproducible sealing process between polymers and poly(dimethylsiloxane)

International audienceIn this paper, we describe a novel technique to bond a poly(dimethylsiloxane) (PDMS) microfluidic device onto various thermoplastic films such as polyimide (PI), polyethylene naphthalate (PEN), and polyethylene terephthalate (PET) using (3-mercaptopropyl)trimethoxysilane (MPS) silane reagent. To our knowledge this is the first reported application of MPS to formulate the PDMS-polymer bonding. For the development of such devices, first, the polymers (PI, PEN, and PET) were hydrolyzed by potassium hydroxide (KOH) to generate hydrophilic groups on the polymer surface. This was followed by polymer immersion in MPS (0.3 M) solution which required a short incubation time at room temperature. Finally, a post-treatment by oxygen plasma was made to substitute the propyl-thiol chain with hydroxyl groups by cleaving the terminal groups on the MPS treated polymers. This created the required silanol groups (Si-OH) for PDMS adhesion, where an irreversible bond was formed without any pressure or high temperatures to initiate bonding. The polymer film surfaces were successfully modified by MPS and this was confirmed by surface characterization using contact angle measurement (CAM) and X-ray photoelectron spectroscopy (XPS) analysis. The PDMS-polymer bonding was observed by injection of a dye, and the liquid circulated inside the microchannel of the microfluidic device without any leakage. The device was also tested for longevity and the liquid remained inside the microchannel for one month without any noticeable deterioration

Development of an impedimetric biosensor sensitive to human interluekin-10 based on electrically addressable diazonium functionalized antibodies.

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Polymer micromixers bonded to thermoplastic films combining soft-lithography with plasma and aptes treatment processes

International audienceOver the past few years, a growing interest on covalent bonding of polydimethylsiloxane (PDMS) microfluidic devices to thermoplastic films has developed due to reduced costs, biocompatibility, and flexibility. The silane reagent, 3-aminopropyltriethoxysilane (APTES) has been applied to create this bonding. Here, we report on the fabrication of replica PDMS micromixer devices from a silicon mold using soft lithography that is rapid, facile, and cost-effective to manufacture. After replica molding, the PDMS micromixer devices were bonded to the APTES-activated thermoplastic films of polyimide, polyethylene terephthalate, and polyethylene naphthalate. Characterization of these thermoplastic surfaces was analyzed by contact angle measurement, surface free energy, and X-ray photoelectron spectroscopy. To demonstrate the functionality of this technology, we have analyzed the PDMS micromixers by a peel test, nonleakages, and mixing with the injection of inks, a surfactant, and varying pH solutions. To our knowledge, this is the first reported example in literature of the PDMSAPTESthermoplastic films preparation that integrates a complex micromixer device. Here, we have established that the hydrophobicity of both sealed polymers required alteration in order for dispersion of a polar liquid in the mixing loops. The application of a polar solvent before injection can remedy this ill effect formulating a hydrophilic micromixer. These preliminary results demonstrate the feasibility of the fabrication technology, bonding technique, and application of the micromixer that, once optimized, can eventually integrate more components to formulate a lab-on-a-chip with the fabrication of gold microelectrodes for biological analysis of blood or plasma

Development of a flexible Lab-on-Chip: Application for the detection of biomarkers in heart failure patients.

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A novel biosensor based on hafnium oxide: Application for early stage detection of human interleukin-1

International audienceMeasurement of interleukin-10 (IL-10) has subsequently become a crucial tool to identify end-stage heart failure (ESHF) patients prone to adverse outcomes during the early phase of left ventricular assisted device (LVAD) implantation. In this context, label-free detection using a novel substrate based on hafnium oxide (HfO2) grown by atomic layer deposition (ALD) on silicon was applied. Here, we studied the interaction between recombinant human (rh) IL-10 with the corresponding monoclonal antibody (mAb) for early cytokine detection of an anti-inflammatory response due to LVAD implantation. For this purpose, HfO2 has been functionalized using an aldehyde-silane ((11-(triethoxysilyl) unclecanal (TESUD)) self-assembled monolayer (SAMs), to directly immobilize the anti-human IL-10 mAb by covalent bonding. The interaction between the antibody-antigen (Ab-Ag) was characterized by fluorescence patterning and electrochemical impedance spectroscopy (EIS). Confirmation for the bio-recognition of the protein was achieved by fluorescence patterning, while Nyquist plots have shown a stepwise variation due to the polarization resistance (R-p) between the Ab activated surfaces with the detection of the protein. For early expression monitoring, commercial proteins of rh IL-10 were analyzed between 0.1 pg/mL and 50 ng/mL Protein concentrations within the linear range of 0.1-20 pg/mL were detected, and these values formulated a sensitivity of 0.49 (ng/mL)(-1). These preliminary results demonstrated that the developed biosensor was sensitive to the detection of rh IL-10, and the measured limit of 0 1 pg/mL in phosphate buffered saline (PBS) was clearly detectable, which displays the high sensitivity of EIS. On analysis of an interference attributable to non-specific binding of other cytokine biomarkers; tumor necrosis factor-alpha (TNF-alpha) and IL-1 beta were analyzed without causing an interference to the IL-10 mAb. This established that selective sensitivity was responsive only to rh IL-10. To our knowledge, this is tie first biosensor that has been based on HfO2 for Ag detection by EIS. In time, the HfO2 insulator will be incorporated into the gate of silicon-based ion-sensitive field-effect transistors (ISFETs) and developed as a portable real time detection system for the IL family of biomarkers in human serum