Redox-Reactive Field-Effect Transistor Nanodevices for the Direct Monitoring of Small Metabolites in Biofluids toward Implantable Nanosensors Arrays

Abstract

Chemically modified field-effect transistor (FET) nanodevices were shown to be a selective and extremely sensitive detection platform. In FET-based sensors, signal amplification and transduction is based on electrostatic gating of the nanometric semiconductor channel by analyte–receptor interactions, which measurably affect the transconductance of the device. However, chemically modified FETs must overcome several fundamental limitations before they can be effectively deployed as real-time sensors for bioevents occurring on their surface in complex biofluids. Here, we demonstrate the development of amperoFET devices for the real-time continuous monitoring of small molecular metabolites in biofluids. The surface of the nanowires is covalently modified with a redox reversible moiety, which is easily oxidized in the presence of H 2 O 2 . The reversible redox transformation of the surface-confined molecules is carried out by a hot electron injection mechanism, conducted simply by the modulation of the source–drain current through the nanoFET sensing device. By this approach, electrons may be injected by the nanowire element into the surface-confined redox moiety and thus maintain a whole-electrically actuated redox system in which the oxidation state is completely controlled by the current applied to the amperoFET system. The modulation of the source–drain current allows the control of the reduced versus oxidized redox moieties population on the nanowire surface, and this, in turn, is applied as the main sensing mechanism. At a given constant source–drain and gate voltage, the chemical perturbation exerted by the presence of chemical oxidants in the tested biofluid will lead to a measurable conductance change. Alteration in the concentration of the specific metabolite will chemically regulate the extent of perturbation applied to the redox system, which can be utilized for the quantification of the molecular metabolite of interest. These ‘equilibrium’-type sensors are fully electrically operated and can be further used in implantable sensing applications.

Real-time Monitoring of Bacterial Biofilms Metabolic Activity by a Redox-Reactive Nanosensors Array

“…This layer of an active redox system alternates from oxidized to reduced states and contributes charge carriers which are followed by electrical changes on the surface of the SiNW FETs. Moreover, SiNW FETs modified with active redox systems enable monitoring of metabolites without any preprocessing of the sample [12,26], including desalting, directly from the extracellular medium of the bacterial biofilm, and offer the reuse of the nanosensor because of the unique reversible redox system. Detection and monitoring of extracellular metabolites of bacterial biofilms have a considerable advantage, since it is much easier to detect changes in metabolite concentrations extracellularly, as the device does not have to be in contact with the biofilm (Fig.…”

“…Since glucose metabolism can provide critical information reflecting the living state of bacteria, an ultrasensitive, real-time, label-free sensor based on SiNW FETs was developed to monitor glucose consumption by living cells. A unique redox-reactive modification on the surface of the SiNW devices was shown to be a powerful tool for glucose sensing in high-ionic-strength solution [12,26]. Based on this work, we developed a platform that enables label-free and real-time monitoring of the metabolic activity of biofilms based on glucose consumption, testing their susceptibility to drugs and other eradication efforts, to adjust the proper medical treatment to overcome biofilm infections.…”

Real-time Monitoring of Bacterial Biofilms Metabolic Activity by a Redox-Reactive Nanosensors Array

“…This layer of an active redox system alternates from oxidized to reduced states and contributes charge carriers which are followed by electrical changes on the surface of the SiNW FET. Moreover, SiNW FETs modi ed with active redox systems enable the monitoring of metabolites without any preprocessing of the sample [13,27], including desalting, directly from the extracellular medium of the bacterial bio lm, and offer the reuse of the nanosensor because of the unique reversible redox system. Detection and monitoring of the extracellular composition of bacterial bio lm have a considerable advantage since it is much easier to detect changes in metabolite concentrations extracellularly, as the device does not have to be in contact with the bio lm (Figure 1a right panel).…”

“…More speci cally, the inhibition of bacterial metabolism of glucose consumption can be used as an index of bacterial susceptibility to drugs [43,44]. A unique redox-reactive modi cation on the surface of the SiNW FET devices was previously shown to be a powerful tool for glucose sensing in high-ionic-strength solution [13,27]. The redox system's functional group comprising 9,10-dihydroxyanthracene (AQ), that can be oxidized or reduced in a reversible manner, which involves a signi cant change in the charge [13,45], and in uences the conductivity of the FET.…”

Real-time monitoring of bacterial biofilms metabolic activity by a redox-reactive nanosensors array

“…More specifically, the inhibition of bacterial metabolism of glucose consumption can be used as an index of bacterial susceptibility to drugs [43,44]. A unique redox-reactive modification on the surface of the SiNW FET devices was previously shown to be a powerful tool for glucose sensing in high-ionic-strength solution [13,27]. The redox system's functional group comprising 9,10-dihydroxyanthracene (AQ), that can be oxidized or reduced in a reversible manner, which involves a significant change in the charge [13,45], and influences the conductivity of the FET.…”