Biosensor Applications Research Articles

Advances in nanotechnological approaches for the detection of early markers associated with severe cardiac ailments.

Mortality from cardiovascular disease (CVD) accounts for over 30% of all deaths globally, necessitating reliable diagnostic tools. Prompt identification and precise diagnosis are critical for effective personalized treatment. Nanotechnology offers promising applications in diagnostics, biosensing and drug delivery for prevalent cardiovascular diseases. Its integration into cardiovascular care enhances diagnostic accuracy, enabling early intervention and tailored treatment plans. By leveraging nanoscale innovations, healthcare professionals can address the complexities of CVD progression and customize interventions based on individual patient needs. Ongoing advancements in nanotechnology continue to shape the landscape of cardiovascular medicine, offering potential for improved patient outcomes and reduced mortality rates from these pervasive diseases.

Automated Scanning Dielectric Microscopy Toolbox for Operando Nanoscale Electrical Characterization of Electrolyte‐Gated Organic Transistors

AbstractElectrolyte‐gated organic transistors (EGOTs) leveraging organic semiconductors' electronic and ionic transport characteristics are the key enablers for many biosensing and bioelectronic applications that can selectively sense, record, and monitor different biological and biochemical processes at the nanoscale and translate them into macroscopic electrical signals. Understanding such transduction mechanisms requires multiscale characterization tools to comprehensively probe local electrical properties and link them with device behavior across various bias points. Here, an automated scanning dielectric microscopy toolbox is demonstrated that performs operando in‐liquid scanning dielectric microscopy measurements on functional EGOTs and carries out extensive data analysis to unravel the evolution of local electrical properties in minute detail. This paper emphasizes critical experimental considerations permitting standardized, accurate, and reproducible data acquisition. The developed approach is validated with EGOTs based on blends of organic small molecule semiconductor and insulating polymer that work as accumulation‐mode field‐effect transistors. Furthermore, the degradation of local electrical characteristics at high gate voltages is probed, which is apparently driven by the destruction of local crystalline order due to undesirable electrochemical swelling of the organic semiconducting material near the source electrode edge. The developed approach paves the way for systematic probing of EGOT‐based technologies for targeted optimization and fundamental understanding.

Noise and sensitivity analysis of the dielectric modulated reconfigurable SiNW-SBT for biosensor applications

For the first time, we reported the noise and sensitivity analysis of the Dielectric Modulated Reconfigurable Silicon Nanowire-based Schottky Barrier Transistor (DMR SiNW-SBT) for biosensor applications. To validate the simulation, we present experimental calibration of the DMR SiNW-SBT biosensor. The biomolecules having different dielectric constants and charge densities are immobilized in the cavity region under the control gate. These biomolecules modulate the Schottky junction width at the source channel interface and enhance the drain current of the biosensor. The simulation results indicate that the proposed device ION and VTH sensitivity improved by 54.65 % and 85.71 %, respectively, with the state-of-the-art biosensors. Noise analysis shows that the NFmin decreased by 190.32 % and offers a low source impedance of 70Ω, which minimizes signal loss and distortion. Additionally, we investigate the linearity parameters that outperformed the FET-based biosensors. The gm3 experiences a reduction of 123.21 %, while the VIP3 sees an increase of 7.87 % and the IIP3 shows a rise of 7.21 %. Furthermore, we have conducted device optimization by varying the cavity length and thickness. We also outline potential fabrication steps for the DMR SiNW-SBT biosensor. Thus, results show that the proposed biosensor emerges as a promising candidate for advanced biosensing applications with high sensitivity, enhanced linearity, and robust noise resilience.

PH-Dependent Morphology of Copper (II) Oxide in Hydrothermal Process and Their Photoelectrochemical Application for Non-Enzymatic Glucose Biosensor

In this study, we investigated the influence of pH on the hydrothermal synthesis of copper (II) oxide CuO nanostructures with the aim of tuning their morphology. By varying the pH of the reaction medium, we successfully produced CuO nanostructures with three distinct morphologies including nanoparticles, nanorods, and nanosheets according to the pH levels of 4, 7, and 12, respectively. The observed variations in surface morphology are attributed to fluctuations in growth rates across different crystal facets, which are influenced by the presence of intermediate species within the reaction. This report also compared the structural and optical properties of the synthesized CuO nanostructures and explored their potential for photoelectrochemical glucose sensing. Notably, CuO nanoparticles and nanorods displayed exceptional performance with calculated limits of detection of 0.69 nM and 0.61 nM, respectively. Both of these morphologies exhibited a linear response to glucose within their corresponding concentration ranges (3–20 nM and 20–150 nM). As a result, CuO nanorods appear to be a more favorable photoelectrochemical sensing method because of the large surface area as well as the lowest solution resistance in electroimpedance analysis compared to CuO nanoparticles and nanosheets forms. These findings strongly suggest the promising application of hydrothermal-synthesized CuO nanostructures for ultrasensitive photoelectrochemical glucose biosensors.

Nitrogen doped carbon dots and gold nanoparticles mediated FRET for the detection of creatinine in human urine samples

Serum creatinine (CR) is regarded as one of the most sought out prognostic biomarkers in medical evaluation of chronic kidney disease (CKD). In light of the diagnostic significance of CR, the utility of a fluorescence biosensor for its detection in human urine specimens has been explored based on Förster resonance energy transfer (FRET) across nitrogen-doped carbon dots (N-CDs) and gold nanoparticles (GNPs). A straightforward microwave-assisted synthesis procedure has been adopted to prepare N-CDs (λexcitation = 400 nm, λemission = 540 ± 5 nm) with bright green emissions. On addition of pre-synthesized GNPs, the radiative emanation of the N-CDs is completely suppressed on account of FRET across the N-CDs and the GNPs. About 77 % of their fluorescence intensity is recovered after adding CR to GNPs@N-CDs nanocomposite. The limit of detection for CR sensing is estimated as 0.02 µg•mL−1. This biosensor is selective enough to recognize CR in the existence of potential interfering substances (e.g., ascorbic acid, glucose, glutathione, urea, and electrolytes). Its practical utility for CR detection has been validated further on the basis of satisfactory correlation with the benchmark Jaffe method, as observed in artificial/human urine specimens. Consequently, this manuscript marks a pioneering report on employing CDs and GNPs-based FRET for identifying CR in urine specimens of CKD patients.

Revolutionizing food safety with electrochemical biosensors for rapid and portable pathogen detection.

Foodborne diseases remain a worldwide concern, despite the advances made in sanitation, pathogen surveillance and food safety management systems. The methods routinely applied for detecting pathogens in foods are time consuming, labor intensive and usually require trained and qualified individuals. The objective of this review was to highlight the use of biosensors, with a focus on the electrochemical devices, as promising alternatives for detecting foodborne pathogens. These biosensors present high speed for obtaining results, with the possibility of evaluating foods in real time, at low cost, ease of use, in addition to being compact and portable. These aspects are considered advantageous and suitable for use in food safety management systems. This work also shows some limitations for the application of biosensors, and we present perspectives with the development and use of nanomaterials.

Dielectric crystal coupled with guided-mode resonance to enhance the magneto-optical Kerr effect and sensing behavior in transmission mode

In this study, we introduce a high-performance magneto-optical sensor that features enhanced amplitude and sensitivity, achieved through guided-mode resonance (GMR) excitations in an aluminum antimonide slab. This advancement is facilitated by a square, periodically arranged nanorod structure comprising dielectric materials. The electromagnetic field distributions were obtained along with the transmission spectra to elucidate the GMR mode in our proposed structure, thereby highlighting the enhancement of the transverse magneto-optical Kerr effect (TMOKE) signal in the transmitted mode and the corresponding sensing performance. The findings demonstrate that the position of the TMOKE resonance is remarkably responsive to variations in the background refractive index, yielding an impressive sensitivity of 188.7° per refractive index unit, coupled with a narrow linewidth owing to the inherent low loss of dielectric materials. This investigation lays the groundwork for novel advancements in linear optics, integrated optical circuits, and low-loss biosensing applications.

More Than One Enzyme: Exploring Alternative FMN-Dependent L-Lactate Oxidases for Biosensor Development.

The α-hydroxy acid oxidoreductase (HAOx) family contains a diverse group of enzymes that can be applied in biosensors for L-lactate detection, most prominently lactate oxidase (LOx). The limited availability and a lack of diversity of L-lactate-oxidizing enzymes have currently hindered advancements in L-lactate biosensor development. Until now, the field has mostly relied on a single, commercially available enzyme, namely Aerococcus viridans L-lactate oxidase (AvLOx). In this study, we present newly discovered alternative L-lactate oxidases that exhibit a narrow substrate specificity and varied kinetic efficiencies toward L-lactate, making them suitable for integration into existing biosensor configurations. Some of these FMN-dependent L-lactate oxidases could be obtained in substantial amounts from routine E. coli expression, potentially facilitating commercial production. Using electrochemical characterization with a mediated biosensor setup, we present 7 enzymes that perform comparable or even better than commercial AvLOx. Finally, we show that their electrochemical performance is not directly correlating with their biochemical performance, making predictions of the suitability of enzymes for biosensor applications extremely difficult. Our research emphasizes the significance of expanding the enzyme toolbox of L-lactate oxidases for the development of improved L-lactate biosensors.

Recent advances and trends in innovative biosensor-based devices for heavy metal ion detection in food.

Low-cost, reliable, and efficient biosensors are crucial in detecting residual heavy metal ions (HMIs) in food products. At present, based on distance-induced localized surface plasmon resonance of noble metal nanoparticles, enzyme-mimetic reaction of nanozymes, and chelation reaction of metal chelators, the constructed optical sensors have attracted wide attention in HMIs detection. Besides, based on the enrichment and signal amplification strategy of nanomaterials on HMIs and the construction of electrochemical aptamer sensing platforms, the developed electrochemical biosensors have overcome the plague of low sensitivity, poor selectivity, and the inability of multiplexed detection in the optical strategy. Moreover, along with an in-depth discussion of these different types of biosensors, a detailed overview of the design and application of innovative devices based on these sensing principles was provided, including microfluidic systems, hydrogel-based platforms, and test strip technologies. Finally, the challenges that hinder commercial application have also been mentioned. Overall, this review aims to establish a theoretical foundation for developing accurate and reliable sensing technologies and devices for HMIs, thereby promoting the widespread application of biosensors in the detection of HMIs in food.

Development of Spiropyran Immobilization and Characterization Protocols for Reversible Photopatterning of SiO2 Surfaces.

Spiropyran is a dynamic organic compound that is distinguished by its reversible conversion between two forms: the colorless closed spiropyran (SP) form and the purple open merocyanine (MC) form. Typically triggered by UV light and reversed by visible light, spiropyran-functionalized surfaces offer reversible conversion in properties including color, polarity, reactivity, and fluorescence, making them applicable to diverse applications in chemical sensors, biosensors, drug delivery, and heavy metal extraction. While spiropyran has been successfully incorporated into various material platforms with SiO2 surfaces, its application on flat surfaces has been limited due to surface area constraints and a lack of standardized evaluation methods, which largely depend on the integration approach and substrate type used. In this study, we systematically review the existing literature and categorize integration methods and substrate types first and then report on our experimental work, in which we developed a streamlined three-step immobilization protocol, which includes surface activation, amination with (3-aminopropyl) triethoxysilane (APTES), and subsequent functionalization with carboxylic spiropyran (SP-COOH). Using SiO2 surfaces as a demonstration, we have also established a robust characterization protocol, consisting of contact angle measurements, X-ray photoelectron spectroscopy (XPS), ellipsometry, and fluorometric analysis. Our results evaluate the newly developed immobilization protocol, demonstrating effective activation and optimal amination using a 2% APTES solution, achieved in 5 min at room temperature. Fluorescence imaging provided clear contrast between the SP and the MC forms. Furthermore, we discuss limitations in the surface density of functional groups and steric hindrance and propose future improvements. Our work not only underscores the versatility of spiropyran in surface patterning but also provides optimized protocols for its immobilization and characterization on SiO2 surfaces, which may be adapted for use on other substrates. These advancements lay the groundwork for on-chip sensing technologies and other applications.

Responsive Acrylamide-Based Hydrogels: Advances in Interpenetrating Polymer Structures.

Hydrogels, composed of hydrophilic homopolymer or copolymer networks, have structures similar to natural living tissues, making them ideal for applications in drug delivery, tissue engineering, and biosensors. Since Wichterle and Lim first synthesized hydrogels in 1960, extensive research has led to various types with unique features. Responsive hydrogels, which undergo reversible structural changes when exposed to stimuli like temperature, pH, or specific molecules, are particularly promising. Temperature-sensitive hydrogels, which mimic biological processes, are the most studied, with poly(N-isopropylacrylamide) (PNIPAm) being prominent due to its lower critical solution temperature of around 32 °C. Additionally, pH-responsive hydrogels, composed of polyelectrolytes, change their structure in response to pH variations. Despite their potential, conventional hydrogels often lack mechanical strength. The double-network (DN) hydrogel approach, introduced by Gong in 2003, significantly enhanced mechanical properties, leading to innovations like shape-deformable DN hydrogels, organic/inorganic composites, and flexible display devices. These advancements highlight the potential of hydrogels in diverse fields requiring precise and adaptable material performance. In this review, we focus on advancements in the field of responsive acrylamide-based hydrogels with IPN structures, emphasizing the recent research on DN hydrogels.

Study of ISFET for KCl sensing

This work presents the fabrication and electrical characterization of the Ion Sensitive Field Effect Transistor (ISFET) exposed to potassium chloride (KCl) solutions. The focus of the study is to compare two measurements methods and verify the effects of these methods in the device threshold voltage (VTH) sensitivity to the different KCl concentrations. First, a reference electrode (a platinum needle) is placed in the sample solution over the gate area of the device, demonstrating that the threshold voltage decreases with the increase of the KCl concentration. The method shows a sensitivity of 10.44 mV/mM for the low KCl concentration range (0 to 10 mM) and 0.5 mV/mM for the higher KCl concentration range (10 to 100 mM). The second method involves inserting a second platinum electrode into the solution on the field oxide. This method proposes the KCl electrolysis to increase the selectivity for potassium ions. The result allows the next steps for potassium sensing biosensor application with selective membranes.

Next-generation of a Fe-Ce double variable-valence metals modulated high-efficiency nanozyme

High catalytic efficiency is the continuous pursuit for the preparation of high-performance nanozymes. In this work, a Fe-Ce double variable-valence metals nanozyme (Fe-Ce-MOL) was constructed based on metal–organic layers (MOLs), a class of two-dimensional metal–organic frameworks with ultra-thin structure, for peroxidase (POD) mimicking. Fe-Ce-MOL exhibited significantly enhanced catalytic activity in comparison with that of natural horseradish peroxidase and single variable-valence metal nanozyme (Fe-Zr-MOL). Density functional theory calculations demonstrated that the Fe site of Fe-Ce-MOL had a stronger adsorption effect on H2O2 compared to Fe-Zr-MOL and more heat was released in the catalytic reaction of H2O2, making the reaction easier to occur. Moreover, there was more electron transfer between Fe and Ce double variable-valence metals, also accelerating the catalytic process. These results indicated that the ultra-thin structure of Fe-Ce-MOL provided more catalytic sites and Fe and Ce double variable-valence metals could regulate the process of oxidation–reduction and promote the efficiency of electron transfer synergistically. As a proof of concept, the proposed Fe-Ce-MOL was used in biosensing and antibacterial applications. These results suggested that Fe-Ce-MOL had great potential as a new-generation nanozyme. This work pioneers a new approach for the rational design of highly efficient nanozymes.

Immobilized Multi-Enzyme/Nanozyme Biomimetic Cascade Catalysis for Biosensing Applications.

Multiple enzyme-induced cascade catalysis has an indispensable role in the process of complex life activities, and is widely used to construct robust biosensors for analyzing various targets. The immobilized multi-enzyme cascade catalysis system is a novel biomimetic catalysis strategy that immobilizes various enzymes with different functions in stable carriers to simulate the synergistic catalysis of multiple enzymes in biological systems, which enables high stability of enzymes and efficiency enzymatic cascade catalysis. Nanozymes, a type of nanomaterial with intrinsic enzyme-like characteristics and excellent stabilities, are also widely applied instead of enzymes to construct immobilized cascade systems, achieving better catalytic performance and reaction stability. Due to good stability, reusability, and remarkably high efficiency, the immobilized multi-enzyme/nanozyme biomimetic cascade catalysis systems show distinct advantages in promoting signal transduction and amplification, thereby attracting vast research interest in biosensing applications. This review focuses on the research progress of the immobilized multi-enzyme/nanozyme biomimetic cascade catalysis systems in recent years. The construction approaches, factors affecting the efficiency, and applications for sensitive biosensing are discussed in detail. Further, their challenges and outlooks for future study are also provided.

Ultra-high sensitivity pH sensor based on vertical organic electrochemical transistors with extended gate.

Anultra-high sensitivity pH sensor based on vertical organic electrochemical transistors (vOECT) with extended gate was proposed. The vOECT, which exhibited high transconductance (gm), was forthe first time used in the preparation of apH sensor. The extended gate was modified by electrochemical deposition of polyaniline (PANI) using the cyclic voltammetry (CV) technique. Open circuit potential (OCP) measurements were used to optimize the scan rate, showing a super-Nernstian sensitivity at all scan rates. The pH sensor based on vOECT with extended gate was investigated at different pH levels, and it exhibited an ultra-high sensitivity of 3363.6 µA/pH in the pH range 5-9, which was about 36 times greater than the maximum current sensitivity (91 µA/pH) of other transistor-based pH sensors, to the best of our knowledge. This pH sensor performed excellently in terms of reversibility, long-term stability, and selectivity. To confirm the reliability of the pH sensor, we conducted measurements on real samples using this pH sensor and compared the results with those obtained from a standard pH meter. The ultra-high sensitivity pH sensor based on vOECT with extended gate offers a sensitive and promising alternative in environmental monitoring, food safety, chemistry, clinical diagnostics, and bio-sensing applications.

Absorption enhancement in silicon-based dielectric resonator for quad-band terahertz biosensing

A technique is implemented to obtain the multi-band perfect absorption (nearly 100%) in an ultrathin silicon-based dielectric resonator (DR) using perturbation. A silicon-based plus-shaped resonator is utilized to design the proposed absorber which provides the four narrow-band absorptions at frequencies of around 5.75, 6.14, 6.48, and 7.24 THz with the level of absorption 54%, 20%, 95%, and 96%, respectively. The plus-shaped resonator is perturbed by cutting slot of plus shape in such a way that it obtains perfect absorption with sufficient guard-band to prevent the multi-band interference in each band. This perturbation provides four absorption peaks at frequencies of around 5.80, 6.27, 6.80, and 7.23 THz, with highly improved absorption in all the bands, i.e., 99.84%, 99.78%, 99.51%, 98.42%, respectively. The ultranarrow absorption peaks with narrow FWHM are suitable for the application of THz biosensing and refractive index analysis. The performance of the proposed absorber is studied with the variation in refractive index of sample. It is found that the proposed absorber provides the high sensitivity 0.186, 0.29, 0.2485, 0.43 THz RIU−1 and quality factor 280, 185.79, 320.42, and 131.51 for different bands, respectively. The proposed absorber performance is also studied for various THz biosensing applications like the detection of various viruses, malaria, and cancer in the human body at various stages.

Electrochemical Investigation of PEDOT:PSS/Graphene Aging in Artificial Sweat.

Herein, we investigate the potential application of a composite consisting of PEDOT:PSS/Graphene, deposited via spray coating on a flexible substrate, as an autonomous conducting film for applications in wearable biosensor devices. The stability of PEDOT:PSS/Graphene is assessed through electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and linear polarization (LP) during exposure to an artificial sweat electrolyte, while scanning electron microscopy (SEM) was employed to investigate the morphological changes in the layer following these. The results indicate that the layers exhibit predominant capacitive behavior in the potential range of -0.3 to 0.7 V vs. Ag/AgCl, with a cut-off frequency of approximately 1 kHz and retain 90% capacity after 500 cycles. Aging under exposure to air for 6 months leads only to a minor increase in impedance, demonstrating potential for storage under non-demanding conditions. However, prolonged exposure (>48 h) to the artificial sweat causes significant degradation, resulting in an impedance increase of over 1 order of magnitude. The observed degradation raises important considerations for the long-term viability of these layers in wearable biosensor applications, prompting the need for additional protective measures during prolonged use. These findings contribute to ongoing efforts to enhance the stability and reliability of conducting materials for biosensors in health care and biotechnology applications.

Recent Progress of Fluorescent Carbon Dots and Graphene Quantum Dots for Biosensors: Synthesis of Solution Methods and their Medical Applications.

In the fields of health and biology, fluorescent nanomaterials have emerged as highly potential and very useful candidates for use in biosensor applications. These typical highly powerful nanomaterials are carbon dots (CDs) and graphene quantum dots (GQDs) among many other metallic nanomaterials. In the context of medical biosensors, this review article investigates the techniques of synthesis, and many uses of these nanomaterials, the obstacles that they face, and the potential for their future. We cover the significance of fluorescent nanomaterials, their use in the medical field, as well as the several techniques of synthesis for CDs and GQDs, including ultrasonication, hydrothermal, electrochemical method, surface modification, and solvothermal. In addition, we also discuss their biomedical applications, which include biomolecule detection, disease diagnosis and examine the obstacles and prospective possibilities for development of ultra-bright, ultra-sensitive, and selective biosensors for use in in-vivo research.Fluorescent carbon dots and graphene quantum dots is synthesized by using several types of raw material and methods. These Carbon dots and graphene quantum dots are used in the medical field includes detection of biomaterials, detection of cancer, virus and mutation in DNA.

β-Cyclodextrin-Tethered Butein, a Greener Redox-Active Biomaterial for Electrochemical Enzymatic Sensing of Sialic Acid.

Biocompatible, industrially scalable, and opto/electrochemically active biomaterials are promising for biosensor platform design and application. Herein, cyclic oligosaccharide, β-cyclodextrin (BCD), is conjugated with Butein, a chalcone-type polyphenol, via dehydration reaction of the hydroxyl groups of BCD and the benzoyl ring of Butein. Functional group changes in the conjugated BCD-Butein were comprehensively studied using UV-visible absorbance, Fourier transform-infrared, and X-ray photoelectron spectroscopic techniques. The electrochemical characteristics of BCD-Butein were explored using cyclic voltammetry, showing the reversible redox behavior (2e-/2H+) attributed to the catecholic OH group of Butein. The BCD-Butein-modified electrode exhibits a surface-confined redox process (R2 = 0.99, Ipa and Ipc) at the interface, suitable for external mediatorless sensor studies. An enzymatic biomolecular sensor has been constructed using BCD-Butein-modified glassy carbon and a screen-printed electrode targeting sialic acid as the model clinical biomarker. With the enzyme sialic acid aldolase, BCD-Butein-modified substrate exhibited a selective conversion of sialic acid to N-acetyl-d-mannosamine and pyruvate, with a wide linear detection range (1-100 nM), the lowest detection limit of 0.2 nM, and a quantification limit of 0.69 nM, convenient for clinical threshold diagnosis.

Advanced design and sensitivity analysis of hollow-core fiber Bragg rating for enhanced biosensing applications

Advanced design and sensitivity analysis of hollow-core fiber Bragg rating for enhanced biosensing applications