Field-effect transistor with a plasmonic fiber optic gate electrode as a multivariable biosensor device

A novel multivariable system, combining a transistor with fiber optic-based surface plasmon resonance spectroscopy with the gate electrode simultaneously acting as the fiber optic sensor surface, is reported. The dual-mode sensor allows for discrimination of mass and charge contributions for binding assays on the same sensor surface. Furthermore, we optimize the sensor geometry by investigating the influence of the fiber area to transistor channel area ratio and distance. We show that larger fiber optic tip diameters are favorable for electronic and optical signals and demonstrate the reversibility of plasmon resonance wavelength shifts after electric field application. As a proof of principle, a layer-by-layer assembly of polyelectrolytes is performed to benchmark the system against multivariable sensing platforms with planar surface plasmon resonance configurations. Furthermore, the biosensing performance is assessed using a thrombin binding assay with surface-immobilized aptamers as receptors, allowing for the detection of medically relevant thrombin concentrations

Optical and electronic signal stabilization of plasmonic fiber optic gate electrodes: towards improved real-time dual-mode biosensing

The use of multimodal readout mechanisms next to label-free real-time monitoring of biomolecular interactions can provide valuable insight into surface-based reaction mechanisms. To this end, the combination of an electrolyte-gated field-effect transistor (EG-FET) with a fiber optic-coupled surface plasmon resonance (FO-SPR) probe serving as gate electrode has been investigated to deconvolute surface mass and charge density variations associated to surface reactions. However, applying an electrochemical potential on such gold-coated FO-SPR gate electrodes can induce gradual morphological changes of the thin gold film, leading to an irreversible blue-shift of the SPR wavelength and a substantial signal drift. We show that mild annealing leads to optical and electronic signal stabilization (20-fold lower signal drift than as-sputtered fiber optic gates) and improved overall analytical performance characteristics. The thermal treatment prevents morphological changes of the thin gold-film occurring during operation, hence providing reliable and stable data immediately upon gate voltage application. Thus, the readout output of both transducing principles, the optical FO-SPR and electronic EG-FET, stays constant throughout the whole sensing time-window and the long-term effect of thermal treatment is also improved, providing stable signals even after 1 year of storage. Annealing should therefore be considered a necessary modification for applying fiber optic gate electrodes in real-time multimodal investigations of surface reactions at the solid-liquid interface

Dual monitoring of surface reactions in real time by combined surface-plasmon resonance and field-effect transistor interrogation

By combining surface plasmon resonance (SPR) and electrolyte gated field-effect transistor (EG-FET) methods in a single analytical device we introduce a novel tool for surface investigations, enabling simultaneous measurements of the surface mass and charge density changes in real time. This is realized using a gold sensor surface that simultaneously serves as a gate electrode of the EG-FET and as the SPR active interface. This novel platform has the potential to provide new insights into (bio)adsorption processes on planar solid surfaces by directly relating complementary measurement principles based on (i) detuning of SPR as a result of the modification of the interfacial refractive index profile by surface adsorption processes and (ii) change of output current as a result of the emanating effective gate voltage modulations. Furthermore, combination of the two complementary sensing concepts allows for the comparison and respective validation of both analytical techniques. A theoretical model is derived describing the mass uptake and evolution of surface charge density during polyelectrolyte multilayer formation. We demonstrate the potential of this combined platform through the observation of layer-bylayer assembly of PDADMAC and PSS. These simultaneous label-free and real-time measurements allow new insights into complex processes at the solid−liquid interface (like non-Fickian ion diffusion), which are beyond the scope of each individual tool.Fil: Aspermair, Patrik. Austrian Institute of Technology; Austria. CEST Competence Center for Electrochemical Surface Technologies; Austria. Centre National de la Recherche Scientifique; Francia. Universite Valencienne; Francia. Universite Lille; FranciaFil: Ramach, Ulrich. CEST Competence Center for Electrochemical Surface Technologies; AustriaFil: Reiner Rozman, Ciril. Austrian Institute of Technology; AustriaFil: Fossati, Stefan. Austrian Institute of Technology; AustriaFil: Lechner, Bernadette. Austrian Institute of Technology; AustriaFil: Moya, Sergio Enrique. Centro de Investigación Cooperativa en Biomateriales - CIC biomaGUNE; EspañaFil: Azzaroni, Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Dostalek, Jakub. Austrian Institute of Technology; AustriaFil: Szunerits, Sabine. Centre National de la Recherche Scientifique; Francia. Universite Valencienne; Francia. Universite Lille; FranciaFil: Knoll, Wolfgang. Austrian Institute of Technology; Austria. CEST Competence Center for Electrochemical Surface Technologies; AustriaFil: Bintinger, Johannes. Austrian Institute Of Technology; Austri

Bio-sensing 2.0 : Outils de mesure électriques et optiques pour le développement d'une plateforme d'investigation pour les interactions de bio-surface

Le choix entre les principes de détection optique et les concepts électriques pour un diagnostic biomédical n’a pas encore été décidée. Ces deux approches continuent à offrir des solutions pour une détection rapide, multiplexée, simple et peu coûteuse de molécules biologiques pertinentes. Toutefois, s’il s’agit de détecter de petits analytes et/ou si la densité de liaison d’analyte à la surface du transducteur est faible, les détections optiques sans marquages posent des problèmes. Dans ce travail, une plate-forme de détection innovante et polyvalente, combinant un dispositif de lecture électrique et optique pour comparer les signaux lors d’une reconnaissance biologique en temps réel, a été développée. Elle est basée sur le couplage de la lecture d'un transistor à effet de champ (gFET) à base de graphène avec celle de la résonance plasmonique de surface (SPR). Divers types de liaison dont la biotine/neutravidine, l’ANP/ADN et l’aptamère ssARN/ssADN pour la détection de protéines ont été étudiés et les résultats discutés.The race in biomedical diagnostics between optical detection principles and electrical concepts is not decided yet. Both approaches continue to offer solutions for fast, multiplexed, simple and cheap detection of biological relevant molecules. However, if it comes to the detection of small analytes and/or if the achievable analyte binding density at the transducer surface is low, label-free optical detection schemes have a problem because the change in the optical interfacial architecture induced by the mere binding of the analyte may be simply too minute to be detected. In this work, an innovative and versatile sensing platform, combining an electrical and optical read-out device to compare the different signal behaviors during a biological binding event in real time was developed. It is based in coupling the read out of a graphene-based field-effect transistor (gFET) with that of surface plasmon resonance (SPR). Various binding events including biotin/neutravidin, PNA/DNA and ssRNA/ssDNA aptamers for protein detection were investigated and the results discussed

Bio-sensing 2.0 : Outils de mesure électriques et optiques pour le développement d'une plateforme d'investigation pour les interactions de bio-surface

The race in biomedical diagnostics between optical detection principles and electrical concepts is not decided yet. Both approaches continue to offer solutions for fast, multiplexed, simple and cheap detection of biological relevant molecules. However, if it comes to the detection of small analytes and/or if the achievable analyte binding density at the transducer surface is low, label-free optical detection schemes have a problem because the change in the optical interfacial architecture induced by the mere binding of the analyte may be simply too minute to be detected. In this work, an innovative and versatile sensing platform, combining an electrical and optical read-out device to compare the different signal behaviors during a biological binding event in real time was developed. It is based in coupling the read out of a graphene-based field-effect transistor (gFET) with that of surface plasmon resonance (SPR). Various binding events including biotin/neutravidin, PNA/DNA and ssRNA/ssDNA aptamers for protein detection were investigated and the results discussed.Le choix entre les principes de détection optique et les concepts électriques pour un diagnostic biomédical n’a pas encore été décidée. Ces deux approches continuent à offrir des solutions pour une détection rapide, multiplexée, simple et peu coûteuse de molécules biologiques pertinentes. Toutefois, s’il s’agit de détecter de petits analytes et/ou si la densité de liaison d’analyte à la surface du transducteur est faible, les détections optiques sans marquages posent des problèmes. Dans ce travail, une plate-forme de détection innovante et polyvalente, combinant un dispositif de lecture électrique et optique pour comparer les signaux lors d’une reconnaissance biologique en temps réel, a été développée. Elle est basée sur le couplage de la lecture d'un transistor à effet de champ (gFET) à base de graphène avec celle de la résonance plasmonique de surface (SPR). Divers types de liaison dont la biotine/neutravidine, l’ANP/ADN et l’aptamère ssARN/ssADN pour la détection de protéines ont été étudiés et les résultats discutés

“Click” Chemistry on Gold Electrodes Modified with Reduced Graphene Oxide by Electrophoretic Deposition

International audienceThe coating of electrical interfaces with reduced graphene oxide (rGO) films and their subsequent chemical modification are essential steps in the fabrication of graphene-based sensing platforms. In this work, electrophoretic deposition (EPD) of graphene oxide at 2.5 V for 300 s followed by vapor treatment were employed to coat gold electrodes uniformly with rGO. These interfaces showed excellent electron transfer characteristics for redox mediators such as ferrocene methanol and potassium ferrocyanide. Functional groups were integrated onto the Au/rGO electrodes by the electro-reduction of an aryldiazonium salt, 4-((triisopropylsilyl)ethylenyl)benzenediazonium tetrafluoroborate (TIPS-Eth-ArN) in our case. Chemical deprotection of the triisopropylsilyl function resulted in propargyl-terminated Au/rGO electrodes to which azidomethylferrocene was chemically linked using the Cu(I) catalyzed “click” chemistry

Field-effect transistor with a plasmonic fiber optic gate electrode as a multivariable biosensor device

Detailed information about the data set see "dataset description.txt" file

Controlled covalent functionalization of a graphene-channel of a field effect transistor as an ideal platform for (bio)sensing applications

International audienceThe controlled covalent functionalization of the graphene channel of a field effect transistor, based on interdigitated gold electrodes (source and drain), via electrochemical grafting, using specifically designed aryl diazonium species is demonstrated to allow the simple fabrication of a general platform for (bio)sensing applications. The electrochemical grafting of a protected ethynylphenyl diazonium salt leads to the deposition of only a monolayer on the graphene channel. This controlled covalent functionalization of the graphene channel results in a charge mobility of the GFET of 1739 ± 376 cm2 V−1 s−1 and 1698 ± 536 cm2 V−1 s−1 for the holes and electrons, respectively, allowing their utilization as (bio)sensors. After deprotection, a dense and compact ethynylphenyl monolayer is obtained and allows the immobilization of a wide range of (bio)molecules by a “click” chemistry coupling reaction (Huisgen 1,3-dipolar cycloaddition). This finding opens promising options for graphene-based (bio)sensing applications

Electrochemical and electronic detection of biomarkers in serum: a systematic comparison using aptamer-functionalized surfaces

International audienceSensitive and selective detection of biomarkers in serum in a short time has a significant impact on health. The enormous clinical importance of developing reliable methods and devices for testing serum levels of cardiac troponin I (cTnI), which are directly correlated to acute myocardial infarction (AMI), has spurred an unmatched race among researchers for the development of highly sensitive and cost-effective sensing formats to be able to differentiate patients with early onset of cardiac injury from healthy individuals with a mean cTnI level of 26 pg mL-1. Electronic- and electrochemical-based detection schemes allow for fast and quantitative detection not otherwise possible at the point of care. Such approaches rely largely on voltammetric and field-effect-based readouts. Here, we systematically investigate electric and electrochemical point-of-care sensors for the detection of cTnI in serum samples by using the same surface receptors, cTnI aptamer-functionalized CVD graphene-coated interdigated gold electrodes. The analytical performances of both sensors are comparable with a limit of detection (LoD) of 5.7 ± 0.6 pg mL-1(electrochemical) and 3.3 ± 1.2 pg mL-1 (electric). However, both sensors exhibit different equilibrium dissociation constant (KD) values between the aptamer-linked surface receptor and the cTnI analyte, being 160 pg mL-1 for the electrochemical and about three times lower for the electrical approach with KD = 51.4 pg mL-1. This difference is believed to be related to the use of a redox mediator in the electrochemical sensor for readout. The ability of the redox mediator to diffuse from the solution to the surface via the cTnI/aptamer interface is hindered, correlating to higher KD values. In contrast, the electric readout has the advantage of being label-free with a sensing limitation due to ionic strength effects, which can be limited using poly(ethylene) glycol surface ligands

Polyclonal aptamer libraries as binding entities on a graphene FET based biosensor for the discrimination of apo- and holo- retinol binding protein 4

Oligonucleotide DNA aptamers represent an emergently important class of binding entities towards as different analytes as small molecules or even whole cells. Without the canonical isolation of individual aptamers following the SELEX process already the focused polyclonal libraries prepared by this in vitro evolution and selection can directly be used to label their dedicated analytes and to serve as binding molecules on surfaces. Here we report the first instance of a sensor able to discriminate between loaded and unloaded retinol binding protein 4 (RBP4), an important biomarker for the prediction of diabetes and kidney disease. The sensor relies purely on two aptamer libraries tuned such, that they discriminate between the protein isoforms, requiring no further sample labelling to detect RBP4 in both state. The evolution, binding properties of the libraries and the functionalization of graphene FET sensor chips are presented as well as the functionality of the resulting biosensor