Biosensor Applications Research Articles

Progresses and Developments in Chitosan-based Materials and its Derivatives for Biomedical and Biosensing Applications

Abstract: This extensive review highlights the different techniques used to extract chitosan, its antibacterial characteristics, and its wide range of applications across various industries. Thanks to its exceptional solubility and notable chemical and biological properties, it has been used in several applications. It is biodegradable, and biocompatible, and has numerous reactive amino side groups that enable chemical modification and the development of various practical derivatives. Several academic publications have extensively covered many characteristics of chitosan and its applications in different industries, such as medicine. Chitosan can impart different functions in multiple fields, such as antibacterial, antiviral, and other biological features. Chitosan has various applications across various industries. Due to its exceptional solubility and significant chemical and biological properties, it has been utilized in numerous applications. Chitosan is biodegradable and biocompatible, and its multiple reactive amino side groups enable chemical modification and the development of various practical derivatives. Chitosan can provide different functions in numerous fields, such as antibacterial, antiviral, and other biological features. This review primarily focuses on chitosan's sources and extraction methods, providing an up-to-date overview of its properties. Additionally, the review highlights the diverse applications of chitosan, whether in its original state or modified and incorporated into nanocomposites, in various fields, making it a highly versatile and commonly used material in the biomedical industry.

Spatially confined dual-emission nanoprobes assembled from silicon nanoparticles and gold nanoclusters for ratiometric biosensing.

Gold nanoclusters (AuNCs) possess weak intrinsic fluorescence, limiting their sensitivity in biosensing applications. This study addresses these limitations by developing a spatially confined dual-emission nanoprobe composed of silicon nanoparticles (SiNPs) and AuNCs. This amplified and stabilized fluorescence mechanism overcomes the limitations associated with using AuNCs alone, achieving superior sensitivity in the sensing platform. The nanoprobe was successfully employed for ratiometric detection of bleomycin (BLM) in serum samples, operating at an excitation wavelength of 365nm, with emission wavelengths at 480nm and 580nm. The analytical performance of the system is distinguished by a linear detection range of 0-3.5μM, an impressive limit of detection (LOD) of 35.27nM, and exceptional recoveries ranging from 96.80 to 105.9%. This innovative approach significantly enhances the applicability and reliability of AuNC-based biosensing in complex biological media, highlighting its superior analytical capabilities.

Gold Nanoparticles in Nanobiotechnology: From Synthesis to Biosensing Applications.

Nanobiotechnology has ushered in a new era of scientific discovery where the unique properties of nanomaterials, such as gold nanoparticles, have been harnessed for a wide array of applications. This review explores gold nanoparticles' synthesis, properties, and multidisciplinary applications, focusing on their role as biosensors. Gold nanoparticles possess exceptional physicochemical attributes, including size-dependent optical properties, biocompatibility, and ease of functionalization, making them promising candidates for the development of biosensing platforms. The review begins by providing a comprehensive overview of gold nanoparticle synthesis techniques, highlighting the advantages and disadvantages of various approaches. It then delves into the remarkable properties that underpin their success in biosensing, such as localized surface plasmon resonance and enhanced surface area. The discussion also includes the functionalization strategies that enable specific binding to biomolecules, enhancing the sensitivity and selectivity of gold-nanoparticle-based biosensors. Furthermore, this review surveys the diverse applications of gold nanoparticles in biosensing, encompassing diagnostics, environmental monitoring, and drug delivery. The multidisciplinary nature of these applications underscores the versatility and potential of gold nanoparticles in addressing complex challenges in healthcare and environmental science. The review emphasizes the pressing need for further exploration and research in the field of nanobiotechnology, particularly regarding the synthesis, properties, and biosensing applications of gold nanoparticles. With their exceptional physicochemical attributes and versatile functionalities, gold nanoparticles present a promising avenue for addressing complex challenges in healthcare and environmental science, making it imperative to advance our understanding of their synthesis, properties, and applications for enhanced biosensing capabilities and broader scientific innovation.

In Situ Growth of Columnar PEG on PEDOT and Its Antifouling Properties.

The antifouling properties of conductive polymers have received extensive attention for biosensor and bioelectronic applications. Polyethylene glycol (PEG) is a well-known antifouling material, but the controlled regulation of the surface topography of PEG without a template remains a challenge. Here, we show a columnar structure antifouling conductive polymer brush with enhanced antifouling properties and considerable conductivity. The method involves synthesizing the 3,4-ethylenedioxythiophene monomer modified with azide (EDOT-N3), the electropolymerization of PEDOT-N3, and the in situ growth of PEG polymer brushes on PEDOT through double-click reactions. The resultant columnar structure polymer brush exhibits high electrical conductivity (3.5 Ω·cm2), ultrahigh antifouling property, electrochemical stability (capacitance retention was 93.8% after 2000 cycles of CV scans in serum), and biocompatibility.

Ureido-Ionic Liquid Mediated Conductive Hydrogel: Superior Integrated Properties for Advanced Biosensing Applications.

Ionic conductive hydrogels (ICHs) have recently gained prominence in biosensing, indicating their potential to redefine future biomedical applications. However, the integration of these hydrogels into sensor technologies and their long-term efficacy in practical applications pose substantial challenges, including a synergy of features, such as mechanical adaptability, conductive sensitivity, self-adhesion, self-regeneration, and microbial resistance. To address these challenges, this study introduces a novel hydrogel system using an imidazolium salt with a ureido backbone (UL) as the primary monomer. Fabricated via a straightforward one-pot copolymerization process that includes betaine sulfonate methacrylate (SBMA) and acrylamide (AM), the hydrogel demonstrates multifunctional properties. The innovation of this hydrogel is attributed to its robust mechanical attributes, outstanding strain responsiveness, effective water retention, and advanced self-regenerative and healing capabilities, which collectively lead to its superior performance in various applications. Moreover, this hydrogel exhibited broad-spectrum antibacterial activity. Its potential for biomechanical monitoring, especially in tandem with contact and noncontact electrocardiogram (ECG) devices, represents a noteworthy advancement in precise real-time cardiac monitoring in clinical environments. In addition, the conductive properties of the hydrogel make it an ideal substrate for electrophoretic patches aimed at treating infected wounds and consequently enhancing the healing process.

Designing Nanocomposite-Based Electrochemical Biosensors for Diabetes Mellitus Detection: A Review.

This review will unveil the development of a new generation of electrochemical sensors utilizing a transition-metal-oxide-based nanocomposite with varying morphology. There has been considerable discussion on the role of transition metal oxide-based nanocomposite, including iron, nickel, copper, cobalt, zinc, platinum, manganese, conducting polymers, and their composites, in electrochemical and biosensing applications. Utilizing these materials to detect glucose and hydrogen peroxide selectively and sensitively with the correct chemical functionalization is possible. These transition metals and their oxide nanoparticles offer a potential method for electrode modification in sensors. Nanotechnology has made it feasible to develop nanostructured materials for glucose and H2O2 biosensor applications. Highly sensitive and selective biosensors with a low detection limit can detect biomolecules at nanomolar to picomolar (10-9 to 10-12 molar) concentrations to assess physiological and metabolic parameters. By mixing carbon-based materials (graphene oxide) with inorganic nanoparticles, nanocomposite biosensor devices with increased sensitivity can be made using semiconducting nanoparticles, quantum dots, organic polymers, and biomolecules.

Anti-IgG Doped Melanin Nanoparticles Functionalized Quartz Tuning Fork Immunosensors for Immunoglobulin G Detection: In Vitro and In Silico Study.

The quartz tuning fork (QTF) is a promising instrument for biosensor applications due to its advanced properties such as high sensitivity to physical quantities, cost-effectiveness, frequency stability, and high-quality factor. Nevertheless, the fork's small size and difficulty in modifying the prongs' surfaces limit its wide use in experimental research. Our study presents the development of a QTF immunosensor composed of three active layers: biocompatible natural melanin nanoparticles (MNPs), glutaraldehyde (GLU), and anti-IgG layers, for the detection of immunoglobulin G (IgG). Frequency shifts of QTFs after MNP functionalization, GLU activation, and anti-IgG immobilization were measured with an Asensis QTF F-master device. Using QTF immunosensors that had been modified under optimum conditions, the performance of QTF immunosensors for IgG detection was evaluated. Accordingly, a finite element method (FEM)-based model was produced using the COMSOL Multiphysics software program (COMSOL License No. 2102058) to simulate the effect of deposited layers on the QTF resonance frequency. The experimental results, which demonstrated shifts in frequency with each layer during QTF surface functionalization, corroborated the simulation model predictions. A modelling error of 0.05% was observed for the MNP-functionalized QTF biosensor compared to experimental findings. This study validated a simulation model that demonstrates the advantages of a simulation-based approach to optimize QTF biosensors, thereby reducing the need for extensive laboratory work.

Proximity-Dependent Activation of Split DNAzyme Kinase.

Binary (also known as split) nucleic acid enzymes have emerged as novel tools in biosensors. We report a new split strategy to split the DNAzyme kinase into two independent and non-functional fragments, denoted Dk1sub and Dk1enz. In the presence of the specific target, their free ends are brought sufficiently close to interact with each other without the formation of Watson-Crick base pairings between Dk1sub and Dk1enz, thus allowing the DNA phosphorylation reaction. We term this approach proximity-dependent activation of split DNAzyme kinase (ProxSDK). The utility of ProxSDK is demonstrated by engineering a biosensing system that is capable of measuring specific DNA-protein interactions. We envision that the approach described herein will find useful applications in biosensing, imaging, and clinical diagnosis.

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.