Biosensor Transducer Research Articles

Bio-functionalized conductive poly(acrylic acid):poly(3,4-Ethylenedioxythiophene)-Prussian blue hybrid transducer for biosensors and bioelectronics interfaces

This study presents an innovative organic-inorganic hybrid transducer of poly(acrylic acid) (PAA), poly(3,4-ethylenedioxythiophene) (PEDOT) and Prussian blue (PB) nanocatalysts. The transducer demonstrated functionality conducive to enzyme conjugation and exhibited favorable electrochemical properties for biosensor signal transduction. Fabricated by a one-tube chemical redox method, the PAA:PEDOT-PB transducer showed long-term electrocatalytic and structural stability. The performance of the transducer was characterized by high transduction activity and low charge transfer resistance, particularly for H2O2 reduction. It achieves a linear detection range from 1.0 μM to 4.0 mM, with a sensitivity of 494 ± 10 μA mM−1 cm−1 and a LOD of 0.34 μM. The PAA:PEDOT-PB transducer featured a high density of carboxyl groups (DCOOH = 14.64 ± 0.05 μmol cm−2) that promoted the immobilization of the H2O2-dependent oxidase enzyme lactate oxidase (LOx) with an EDC/S–NHS coupling agent. The LOx-PAA:PEDOT-PB transducer was developed for lactate biosensing. The transducer provided high LOx-enzyme affinity (KMapp = 1.47 ± 0.05 mM), and a rapid response time (10 s) for lactate detection across a concentration range of 5.0 μM to 4.0 mM, showing a sensitivity of 223 ± 3 μA mM−1 cm−1 and an LOD of 1.45 μM. The LOx-PAA:PEDOT-PB transducer was integrated with a flexible screen-printed electrode, incorporating a wireless, battery-free near-field communication potentiostat module to measure lactate in artificial sweat on a skin model via smartphone. The PAA:PEDOT-PB transducer could enable connections with multiple bio-recognition molecules through polycarboxylic acid groups, providing potential avenues for the development of advanced biosensors.

Biosensing Platforms for Cardiac Biomarker Detection.

Myocardial infarction (MI) is a cardiovascular disease that occurs when there is an elevated demand for myocardial oxygen as a result of the rupture or erosion of atherosclerotic plaques. Globally, the mortality rates associated with MI are steadily on the rise. Traditional diagnostic biomarkers employed in clinical settings for MI diagnosis have various drawbacks, prompting researchers to investigate fast, precise, and highly sensitive biosensor platforms and technologies. Biosensors are analytical devices that combine biological elements with physicochemical transducers to detect and quantify specific compounds or analytes. These devices play a crucial role in various fields including healthcare, environmental monitoring, food safety, and biotechnology. Biosensors developed for the detection of cardiac biomarkers are typically electrochemical, mass, and optical biosensors. Nanomaterials have emerged as revolutionary components in the field of biosensing, offering unique properties that significantly enhance the sensitivity and specificity of the detection systems. This review provides a comprehensive overview of the advancements and applications of nanomaterial-based biosensing systems. Beginning with an exploration of the fundamental principles governing nanomaterials, we delve into their diverse properties, including but not limited to electrical, optical, magnetic, and thermal characteristics. The integration of these nanomaterials as transducers in biosensors has paved the way for unprecedented developments in analytical techniques. Moreover, the principles and types of biosensors and their applications in cardiovascular disease diagnosis are explained in detail. The current biosensors for cardiac biomarker detection are also discussed, with an elaboration of the pros and cons of existing platforms and concluding with future perspectives.

DNA-modified Prussian blue nanozymes for enhanced electrochemical biosensing.

Prussian blue nanoparticles exhibit the potential to be employed in bioanalytical applications due to their robust stability, peroxidase-like catalytic functionality, straightforward synthesis, and biocompatibility. An efficient approach is presented for the synthesis of nucleic acid-modified Prussian blue nanoparticles (DNA-PBNPs), utilizing nanoparticle porosity to adsorb nucleic acids (polyT). This strategic adsorption leads to the exposure of nucleic acid sequences on the particle surface while retaining catalytic activity. DNA-PBNPs further couple with functional nucleic acid sequences and aptamers through complementary base pairing to act as transducers in biosensors and amplify signal acquisition. Subsequently, we integrated a copper ion-dependent DNAzyme (Cu2+-DNAzyme) and a vascular endothelial growth factor aptamer (VEGF aptamer) onto screen-printed electrodes to serve as recognition elements for analytes. Significantly, our approach leverages DNA-PBNPs as a superior alternative to traditional enzyme-linked antibodies in electrochemical biosensors, thereby enhancing both the efficiency and adaptability of these devices. Our study conclusively demonstrates the application of DNA-PBNPs in two different biosensing paradigms: the sensitive detection of copper ions and vascular endothelial growth factor (VEGF). These results indicate the promising potential of DNA-modified Prussian blue nanoparticles in advancing bioanalytical sensing technologies.

Optical Properties of Nitride Cylindrical Quantum Dots as Biosensor Transducer

Optical Properties of Nitride Cylindrical Quantum Dots as Biosensor Transducer

Optical Biosensing Analysis of Spermine as Marker of Prostate Cancer with Help of Colloidal Gold and Anti-Spermine Antibody Modified Transducers

Prostate cancer (PC) is a deadly oncological disease spread all around the world among elderly men. Existing methods of analysis or detection of traditional biomarkers has proven to be expensive and in some cases less precise. That is why in recent years polyamines are studying as potential PC biomarkers. On the other hand biosensors have already proven themselves as precise and sensitive methods that can be used diagnostics, namely in detection of polyamines. Therefore, the aim of this research was to develop a new type of transducer for SPR biosensor based on use of colloidal gold and compare it with conventional antibody-antigen transducer to detect spermine as prostate cancer biomarker. The analysis was made with help of two biosensing devices Plasmontest and SPR-6 which were used detect spermine in range from 0.5 to 1000 nM During the research it was investigated that transducer treated with colloidal have higher sensivity to spermine comparing with antibody-treated transducer. It was observed that range of detected spermine concentration varies from 0.5 to 1000 nM and oplimum located in range 10-500 nM. This article presents data related to the development of the modern sensitive biosensor capable of detecting spermine as a potential marker of prostate cancer.

Graphene-based field-effect transistors for biosensing: where is the field heading to?

Two-dimensional (2D) materials hold great promise for future applications, notably their use as biosensing channels in thefield-effect transistor (FET) configuration. On the road to implementing one of the most widely used 2D materials, graphene, in FETs for biosensing, key issues such as operation conditions, sensitivity, selectivity, reportability, and economic viability have to be considered and addressed correctly. As the detection of bioreceptor-analyte binding events using a graphene-based FET (gFET) biosensor transducer is due to either graphene doping and/or electrostatic gating effects with resulting modulation of the electrical transistor characteristics, the gFET configuration as well as the surface ligands to be used have an important influence on the sensor performance. While the use of back-gating still grabs attention among the sensor community, top-gated and liquid-gated versions have started to dominate this area. The latest efforts on gFET designs for the sensing of nucleic acids, proteins and virus particles in different biofluids are presented herewith, highlighting the strategies presently engaged around gFET design and choosing the right bioreceptor for relevant biomarkers.

Enhanced cathodic electrogenerated chemiluminescence of luminol at a MXene–Nafion composite-modified electrode in neutral aqueous solution

Electrogenerated chemiluminescence (ECL) of luminol was studied on a two-dimensional titanium carbide (MXene)–Nafion composite-modified glassy carbon (GC) electrode in a neutral aqueous solution (pH 7). In the present work, Ti3C2Tx MXene was dispersed in a cation-exchange ionomer (Nation) and the resulting MXene–Nafion composite solution was drop-cast on the surface of GC electrode. Due to the strong electrocatalytic activity of the MXene towards the reduction reactions of oxygen and hydrogen peroxide, strong cathodic ECL emissions of luminol related to those reactions were obtained in a neutral aqueous solution. Based on the significant enhancement effect of hydrogen peroxide on the cathodic ECL, the present ECL sensor can detect hydrogen peroxide in the concentration range of 1.0 × 10−8 M ∼ 1.0 × 10−3 M with a detection limit of 3.1 × 10−9 M (S/N = 3). Furthermore, the present ECL sensor exhibits good selectivity towards hydrogen peroxide against interfering species such as glucose, ascorbic acid and uric acid. Therefore, the present ECL sensor could offer a good opportunity to be employed as an alternative transducer for the oxidase-based biosensors in biological fluids.

Signal amplification strategies for optical biodetection at the liquid crystal–solid interface

ABSTRACTLiquid crystals (LCs) are reliable signal transducers for biosensors with chemical and biological sensing potentials demonstrated on the basis of their anisotropy. Thanks to the high sensitivity and fast response to analytes, the LC–solid, LC–aqueous and LC droplet interfaces facilitate sensing platforms to be established without the requirement of sophisticated and costly analytical instruments. In this mini-review, we summarise strategies of optical signal amplification to improve the detection limit of biological analytes at the LC–solid interface. Because approaches towards signal amplification for a single target analyte are seldom compared by discussing various LC-based biosensing platforms, this mini-review may provide implications for integrating current technologies to promote the development of multiplex platforms based on the LC–solid interface.

The Platinization of Graphite Composites Turns Widespread and Low-Cost Materials into Hydrogen Peroxide Sensors and High-Value Biosensor Transducers

Electrochemical microsensors and biosensors have been widely used in many fields, in particular neurochemical monitoring, because of their features. Usually, hydrogen peroxide (HP), obtained as a by-product of an enzymatic reaction, is the detected compound on transducers made of precious metals, in particular platinum. The over-time increase in the price of platinum and its alloys requires the use of miniaturizable low-cost supports that can be suitably modified with the deposition of Pt particles; among them, graphite is the most widespread. In the present paper, carbon-composition resistors (CCRs) and pencil leads (PLs) of different diameters (0.3, 0.5 and 2.0 mm), mainly made up of graphite, clay and some other components were used as carbonaceous support for the deposition of platinum. Platinizations were carried out by means of cyclic voltammetry (CV) and constant potential amperometry (CPA) techniques. On the platinized supports, hydrogen peroxide (HP) and ascorbic acid (AA) sensitivity were assessed in order to verify the possibility of using them as transducers of amperometric biosensors. All the used protocols determined the occurrence of HP monitoring, not appreciable on carbonaceous surfaces. We chose 0.3 mm Ø PLs for the construction of glucose biosensors by appropriately modifying the platinum surface layering, a permselective polymer, an enzyme booster, the glucose oxidase (GOx) enzyme and a containing network. The biosensor constructed in this way demonstrated a behavior comparable to that obtained using classic platinum wires.

Single Printing Step Prussian Blue Bulk-Modified Transducers for Oxidase-Based Biosensors

We report on hydrogen peroxide sensors made through a single printing step with carbon ink containing catalytically synthesized Prussian blue nanoparticles. Despite their reduced sensitivity, the resulting bulk-modified sensors displayed both a wider linear calibration range (5 × 10-7-1 × 10-3 M) and an approximately four times lower detection limit versus the surface-modified sensors due to the dramatically decreased noise resulting in, on average, a six times higher signal-to-noise ratio. The corresponding glucose and lactate biosensors demonstrated similar and even higher sensitivities compared to those of biosensors based on surface-modified transducers. The biosensors have been validated through analysis of human serum. The decreased time and cost for production of single printing step bulk-modified transducers, as well as their analytical performance characteristics, which are advantageous over conventional surface-modified ones, would be expected to enable their wide use in (bio)sensorics.

Comparative Surface Interaction Study to Detect Brucella melitensis 16M Using Biosensor Transducer Modifications with 4-MBA, ZnONPs/AuNPs, ZnONPs/AuNPs/4-MBA

Brucellosis is a zoonotic disease endemic in developing countries and caused by gram-negative bacteria of genus Brucella infecting both livestock and humans. Brucella melitensis and Brucella abortus are important species representing largest biotypes world-wide. Therefore, modified detection strategies and advancement in potential analytical tools are required to monitor its rapid prevalence. In this study, we aim to modify gold-transducer of Surface Plasmon Resonance biosensor with combination of metal oxide nanomaterials and chemical probe to detect recombinant outer membrane ‘rOmp28’ protein antigen of Brucella melitensis 16M in concentration-dependent surface interactions. We synthesized Zinc (ZnONPs) and Gold (AuNPs) nanoparticles using standard ‘Hydrothermal and Turkevich Methods’ and their crystalline structure, chemical property and morphology were analysed using UV-Visible Spectrophotometry, FT-IR, Powder-XRD, SEM-EDX and TEM-SAED. For immobilizing specific rOmp28 derived IgG-pAbs on modified Au-transducer, rOmp28 protein was expressed and purified using Ni-NTA gel affinity chromatography for producing pAbs in BALB/c mice. Three modifications of Au-transducer with 4-MBA, ZnONPs/AuNPs and ZnONPs/AuNPs/4-MBA were subjected for immobilization and SPR biosensing was performed with rOmp28 Ag at detection range of 0.1 μg mL-1 to 0.01 fg mL-1. Limit of detection observed with ZnONPs/AuNPs/4-MBA combination was 0.1 fg mL-1 by relative increase in SPR response angle at 0.1 μg mL-1 in the order 83.7° < 98.9° < 179.2° for 4-MBA < ZnONPs/AuNPs < ZnONPs/AuNPs/4-MBA respectively. In conclusion, metal oxide nanomaterials in combination with biosensor are suitable in sensitive and specific interaction of antigen displaying lowest LODs and enhanced biosensor response for on-field real-time Brucella detection in both clinical and non-clinical disease scenario.

Modular conductive MOF-gated field-effect biosensor for sensitive discrimination on the small molecular scale

Field-effect transistors (FETs) are a promising transducer for biosensors owing to their drastic signal amplification, showing a high sensitivity enough to detect ultra-low concentrations of small-molecular biomarkers in biofluids. However, the discrimination of small molecules from their structural analogues in biofluids using a FET is challenging; because of the 1) Debye screening in high-ionic-strength conditions, 2) few or no charges of the analytes, and 3) lack of target-specific receptors for small molecules. To overcome these limitations, we report a modular conductive MOF (c-MOF)-gated FET biosensor array that discriminates small-molecular neurotransmitters in biofluids. Adsorption and oxidation of analytes inside the pore of catalytic c-MOF films allow the sensitive detection of small molecules close to the clinically relevant concentration, regardless of the ionic strength of the media. The hierarchical screening ability of c-MOF attributed to their tunable pore size, surface charge, and host–guest interactions induces differentiated adsorption of small molecules. The cross-reaction intended by c-MOF design of our biosensor could provide discriminatory information of each neurotransmitter corresponding to the differences of one functional group in the molecule. Using our system, we also demonstrate discrimination capability under the interference of biologically relevant substances and artificial cerebrospinal fluid.

Pulsed transistor operation enables miniaturization of electrochemical aptamer-based sensors.

By simultaneously transducing and amplifying, transistors offer advantages over simpler, electrode-based transducers in electrochemical biosensors. However, transistor-based biosensors typically use static (i.e., DC) operation modes that are poorly suited for sensor architectures relying on the modulation of charge transfer kinetics to signal analyte binding. Thus motivated, here, we translate the AC "pulsed potential" approach typically used with electrochemical aptamer-based (EAB) sensors to an organic electrochemical transistor (OECT). Specifically, by applying a linearly sweeping square-wave potential to an aptamer-functionalized gate electrode, we produce current modulation across the transistor channel two orders of magnitude larger than seen for the equivalent, electrode-based biosensor. Unlike traditional EAB sensors, our aptamer-based OECT (AB-OECT) sensors critically maintain output current even with miniaturization. The pulsed transistor operation demonstrated here could be applied generally to sensors relying on kinetics-based signaling, expanding opportunities for noninvasive and high spatial resolution biosensing.

Transducer Technologies for Biosensors and Their Wearable Applications.

The development of new biosensor technologies and their active use as wearable devices have offered mobility and flexibility to conventional western medicine and personal fitness tracking. In the development of biosensors, transducers stand out as the main elements converting the signals sourced from a biological event into a detectable output. Combined with the suitable bio-receptors and the miniaturization of readout electronics, the functionality and design of the transducers play a key role in the construction of wearable devices for personal health control. Ever-growing research and industrial interest in new transducer technologies for point-of-care (POC) and wearable bio-detection have gained tremendous acceleration by the pandemic-induced digital health transformation. In this article, we provide a comprehensive review of transducers for biosensors and their wearable applications that empower users for the active tracking of biomarkers and personal health parameters.

Solution processed low power organic field-effect transistor bio-chemical sensor of high transconductance efficiency

Developing organic field-effect transistor (OFET) biosensors for customizable detection of biomarkers for many diseases would provide a low-cost and convenient tool for both biological studies and clinical diagnosis. In this work, design principles of the OFET transducer for biosensors were derived to relate the signal-to-noise ratio (SNR) to the device-performance parameters. Steep subthreshold swing (SS), proper threshold voltage (Vth), good-enough bias-stress stability, and mechanical durability are shown to be the key prerequisites for realizing OFET bio-sensors of high transconductance efficiency (gm/ID) for large SNR. Combining a low trap-density channel and a high-k/low-k gate dielectric layer, low-temperature (<100 °C) solution-processed flexible OFETs can meet the performance requirements to maximize the gm/ID. An extended gate-structure OFET biosensor was further implemented for label-free detection of miR-21, achieving a detection limit below 10 pM with high selectivity at a low operation voltage (<1 V).

ZnO Transducers for Photoluminescence-Based Biosensors: A Review

Zinc oxide (ZnO) is a wide bandgap semiconductor material that has been widely explored for countless applications, including in biosensing. Among its interesting properties, its remarkable photoluminescence (PL), which typically exhibits an intense signal at room temperature (RT), arises as an extremely appealing alternative transduction approach due to the high sensitivity of its surface properties, providing high sensitivity and selectivity to the sensors relying on luminescence output. Therefore, even though not widely explored, in recent years some studies have been devoted to the use of the PL features of ZnO as an optical transducer for detection and quantification of specific analytes. Hence, in the present paper, we revised the works that have been published in the last few years concerning the use of ZnO nanostructures as the transducer element in different types of PL-based biosensors, namely enzymatic and immunosensors, towards the detection of analytes relevant for health and environment, like antibiotics, glucose, bacteria, virus or even tumor biomarkers. A comprehensive discussion on the possible physical mechanisms that rule the optical sensing response is also provided, as well as a warning regarding the effect that the buffer solution may play on the sensing experiments, as it was seen that the use of phosphate-containing solutions significantly affects the stability of the ZnO nanostructures, which may conduct to misleading interpretations of the sensing results and unreliable conclusions.

The impact of physiological buffer solutions on zinc oxide nanostructures: zinc phosphate conversion

Zinc oxide (ZnO) nanostructures have been widely used in biosensor applications. However, little attention has been given to the interaction of ZnO structures with physiological buffer solutions. In the present work, it is shown that the use of buffers containing phosphate ions leads to the modification of the ZnO tetrapodal micro/nanostructures when immersed in such solutions for several hours, even at the physiological pH (7.4). ZnO samples designed to be used as transducers in biosensors were immersed in phosphate buffers for several durations at pH = 5.8 and pH = 7.4. Their detailed morphological, structural and optical characterization was carried out to demonstrate the effect of the ZnO interaction with the phosphate ions. The pH had an important role in the ZnO conversion into zinc phosphate, with lower pH promoting a more pronounced effect. After 72 h and at pH = 5.8, a significant amount of the ZnO structures were converted into crystalline zinc phosphate, while immersion during the same time at pH = 7.4 resulted predominantly in amorphous zinc phosphate particles mixed with the original ZnO tetrapods. Photoluminescence spectra show remarkable changes with prolonged immersion times, particularly when the luminescence of the sample was investigated at 14 K. These findings highlight the importance of a careful analysis of the sensing results when phosphate-based buffer solutions are in contact with the ZnO transducers, as the changes observed on the transduction signal during sensing experiments may also comprise a non-negligible contribution from a phosphate-induced transformation of ZnO, which can hamper an accurate assessment of the sensing behavior.

MOF@COF Heterostructure Hybrid for Dual-Mode Photoelectrochemical-Electrochemical HIV-1 DNA Sensing.

We developed a novel metal-organic framework (MOF)@covalent-organic framework (COF) hybrid with a hierarchical nanostructure and excellent photoactivity, which further acted as the bifunctional platform of a dual-mode photoelectrochemical (PEC) and electrochemical (EC) biosensor for detecting HIV-1 DNA via immobilizing the HIV-1 DNA probe. First, the presynthesized Cu-MOF nanoellipsoids were used as the template for the in situ growth of the COF network, which was synthesized using copper-phthalocyanine tetra-amine (CoPc-TA) and 2,9-bis[p-(formyl)phenyl]-1,10-phenanthroline as building blocks through the Schiff base condensation. In view of the large specific surface area, abundant reserved amino group, excellent electrochemical activity, and high photoactivity, the obtained Cu-MOF@CuPc-TA-COF heterostructure not only can serve as the sensitive platform for anchoring the HIV-1 DNA probe strands but also can be utilized as the signal transducers for PEC and EC biosensors. Thereby, the constructed biosensor shows the sensitive and selective analysis ability toward the HIV-1 target DNA via the complementary hybridization between probe and target DNA strands. The dual-mode PEC and EC measurements revealed that the Cu-MOF@CuPc-TA-COF-based biosensor displayed a wide linear detection range from 1 fM to 1 nM and an extremely low limit of detection (LOD) of 0.07 and 0.18 fM, respectively. In addition, the dual-mode PEC-EC biosensor also demonstrated remarkable selectivity, high stability, good reproducibility, and preferable regeneration ability, as well as acceptable applicability, for which the detected HIV-1 DNA in human serum showed good consistency with real concentrations. Thereby, the present work can open a new dual-mode PEC-EC platform for detecting HIV-1 DNA based on the porous-organic framework heterostructure.

Conducting Polymer-Reinforced Laser-Irradiated Graphene as a Heterostructured 3D Transducer for Flexible Skin Patch Biosensors.

Flexible skin patch biosensors are promising for the noninvasive determination of physiological parameters in perspiration for fitness and health monitoring. However, various prerequisites need to be met for the development of such biosensors, including the creation of a flexible conductive platform, bending/contact stability, fast electrochemical kinetics, and immobilization of biomolecules. Here, we describe a conducting polymer-reinforced laser-irradiated graphene (LIG) network as a heterostructured three-dimensional (3D) transducer for flexible skin patch biosensors. LIG with a hierarchically interconnected graphene structure is geometrically patterned on polyimide via localized laser irradiation as a flexible conductive platform, which is then reinforced by poly(3,4-ethylenedioxythiophene) (PEDOT) as a conductive binder (PEDOT/LIG) with improved structural/contact stability and electrochemical kinetics. The interconnected pores of the reinforced PEDOT/LIG function as a 3D host matrix for high loading of “artificial” (Prussian blue, PB) and natural enzymes (lactate oxidase, LOx), forming a compact and heterostructured 3D transducer (LOx/PB-PEDOT/LIG) for lactate biosensing with excellent sensitivity (11.83 μA mM–1). We demonstrated the fabrication of flexible skin patch biosensors comprising a custom-built integrated three-electrode system achieve amperometric detection of lactate in artificial sweat over a wide physiological linear range of 0–18 mM. The advantage of this facile and versatile transducer is further illustrated by the development of a folded 3D wristband lactate biosensor and a dual channel biosensors for simultaneous monitoring of lactate and glucose. This innovative design concept of a heterostructured transducer for flexible biosensors combined with a versatile fabrication approach could potentially drive the development of new wearable and skin-mountable biosensors for monitoring various physiological parameters in biofluids for noninvasive fitness and health management.

Flow-Through Electrochemical Biosensor with a Replaceable Enzyme Reactor and Screen-Printed Electrode for the Determination of Uric Acid and Tyrosine

A flow-through biosensor has been developed and manufactured by 3D printing from poly(lactic acid). Uricase or tyrosinase were immobilized on the inner walls of the reactor cell and the concentrations of the reaction products, i.e., hydrogen peroxide in the case of uricase and quinone product of the tyrosine oxidation in the case of tyrosinase, were monitored in the amperometric mode. The screen-printed electrode modified with carbon black, pillar[5]arene and electropolymerized thionine and methylene blue was separated from the enzyme layer by 0.1 mm gap and used as a biosensor transducer. The components of the modifier layer exerted a synergetic effect and increased the cathodic current up to seven times compared to electrodes modified with individual components, increasing the sensitivity of the analysis. In the optimal conditions, biosensor allowed the determination of 1 × 10−7 to 1 × 10−5 M uric acid and 2 × 10−7 to 1 × 10−5 M tyrosine. The biosensors analyzed spiked samples of blood serum and urine and provided recoveries from 95 to 110%. Easy mounting of the flow-through cell and low cost of the replaceable parts make promising future application of the biosensor for routine clinical assays.