Biosensor Applications Research Articles

Innovations in Biosensor Technologies for Healthcare Diagnostics and Therapeutic Drug Monitoring: Applications, Recent Progress, and Future Research Challenges.

This comprehensive review delves into the forefront of biosensor technologies and their critical roles in disease biomarker detection and therapeutic drug monitoring. It provides an in-depth analysis of various biosensor types and applications, including enzymatic sensors, immunosensors, and DNA sensors, elucidating their mechanisms and specific healthcare applications. The review highlights recent innovations such as integrating nanotechnology, developing wearable devices, and trends in miniaturisation, showcasing their transformative potential in healthcare. In addition, it addresses significant sensitivity, specificity, reproducibility, and data security challenges, proposing strategic solutions to overcome these obstacles. It is envisaged that it will inform strategic decision-making, drive technological innovation, and enhance global healthcare outcomes by synthesising multidisciplinary insights.

A highly sensitive dual-mode lateral flow immunoassay based on plasmonic hollow Ag/Au nanostars enhancing light absorption

The conventional lateral flow immunoassay (LFIA) based on gold nanoparticles (Au NPs) is limited by low sensitivity due to the insufficient brightness of Au NPs. To address this problem, noble metal nanomaterials with localized surface plasmon resonance (LSPR) and synthetic tunability are potential signal outputs for LFIA, which can achieve better optical properties by adjusting the preparation conditions. Herein, this study prepared the hollow silver/gold nano-stars (HAg/Au NSts) as LFIA signal output via the galvanic replacement method. HAg/Au NSts with anisotropic hollow alloy nanostructures exhibit a wide visible light absorption band and great NIR thermal conversion efficiency (η = 37.32 %), which endows them with enhanced colorimetric and photothermal signals. Further, we constructed a colorimetric-photothermal (CM-PT) dual-signal HAg/Au NSts-LFIA and chose staphylococcal enterotoxin B as the target analyte. The linear range of HAg/Au NSts-LFIA is 0.19–100 ng mL−1, and the limit of detection (LOD) is up to 0.29 ng mL−1 and 0.09 ng mL−1 in the colorimetric and photothermal modes respectively. Compared with the conventional Au NPs-LFIA, HAg/Au NSts-CM/PT-LFIA effectively improved the detection performance of LFIA. In addition, HAg/Au NSts-LFIA also showed satisfactory sensitivity (vLOD = 0.78 ng mL−1) and recovery (89.06–114.74 %) in milk and pork samples. Therefore, this work provides a new shape design idea for noble metal nanomaterials in biosensor applications.

Simulation analysis of a photonic crystal fiber refractive index sensor based on a double-layer film structure and surface plasmon resonance technology

A photonic crystal fiber surface plasmon resonance sensor based on a double-layer membrane structure is designed and analyzed. In the simple sensing structure with only one air hole size, TiO2 and Au layers with specific thicknesses are sequentially coated on the optical fiber to form a double-layer structure. The sensing characteristics of the double-layer membrane structure are studied by the finite element method. Compared to the single-layer membrane structure, the double-layer membrane sensor has significant sensing properties such as a better wavelength sensitivity and a smaller full width at half maximum in the loss spectrum. In the refractive index range between 1.37 and 1.43, the maximum wavelength sensitivity and average wavelength sensitivity of the sensor are 19,900 nm/RIU and 7417 nm/RIU, respectively, and the resolution can be up to 5.03×10−6RIU. The proposed photonic crystal fiber optic sensor achieves high performance with a simpler sensing structure than previous photonic crystal fiber optic sensors, and eliminates the step of polishing, which will greatly reduce the difficulty of actual fabrication and the error due to uneven polishing. The results show that the photonic crystal fiber optic sensor with a double-layer membrane structure has excellent performance. Due to its high sensitivity and resolution, it has great potential for applications in environmental monitoring, biosensing and chemical sensing.

Novel self-powered sandwich type Aptamer sensor for estrogen detection assisted with peroxidase mimic Cu-MOF

A novel self-powered and flexible enzymatic biofuel cell (EBFC)-based aptasensor was developed for the sensitive and selective detection of 17 β-estradiol (E2). A flexible polyvinyl alcohol (PVA)-tannic acid‑carbon nanotube/reduced graphene oxide (PTCR) substrate was modified with gold nanoparticles (AuNPs) and thiolated aptamer 1 (Apt1) to yield Apt1@AuNPs/PTCR. A copper-based metal-organic framework (Cu-MOF) with peroxidase mimicking activity was employed to anchor glucose oxidase (GOD) and Apt2, forming the Cu-MOF@GOD/Apt2 tag. When E2 was recognized by Apt1, the anchored E2 quantitatively recognized Cu-MOF@GOD/Apt2 to create a Cu-MOF@GOD/Apt2-E2-Apt1 sandwich structure for glucose oxidation to generate electrical power. Increased E2 concentrations enhanced Cu-MOF@GOD/Apt2 capture and amplified the electrical signal. The electrical power increased linearly as the E2 concentration increased from 1.0 pM to 1.0 nM. The sensor was successfully applied to various food samples and blood serum detection. This work promoted the application of novel self-powered biosensors for food safety analysis.

Complementary Cost‐Effective Electrochemical Platforms for Point‐Of‐Use Biosensing

AbstractThe COVID‐19 pandemic has illustrated the urgent need for rapid and affordable point‐of‐use diagnostics. Electrochemical biosensors are useful for such applications because they enable quantitative readout and show drastically improved sensitivity compared to prevalent lateral flow technologies. However, to‐date, the poor quality of commercially‐available, mass‐produced electrodes has prohibited the scaled production and commercialization of such biosensors beyond glucose sensing. Low‐cost gold leaf electrodes have previously been developed that can be fabricated with no specialized equipment at the point‐of‐use. These electrodes are more effective for biosensing than prevalent commercially‐available systems. Yet, their manual fabrication can be tedious and is not scalable in its current form. Here, performance of mass‐produced gold electrodes generated using roll‐to‐roll manufacturing is evaluated, offering the potential to scale production. Upon comparison of these electrodes with the gold leaf, it is found that these electrodes are high quality, equivalent to the gold leaf electrodes, and support biosensing applications through the detection of both DNase I and BtsI‐v2 activity with comparable performance. These results demonstrate the role of complementary technologies to achieve point‐of‐use sensing by enabling flexibility between mass‐produced manufacture and on‐site production.

Opto-electrochemical transducers for molecular sensing utilizing nanozyme-based sensing technologies

As a potential substitute for naturally occurring enzymes, nanozymes (nanomaterials with enzyme-mimicking catalytic activity) have emerged in recent years. Natural enzymes have a number of intrinsic shortcomings that could be addressed by nanozymes, including their expensive price, poor stability, storage complexities, and reliance on particular working conditions (e.g., restricted substrate, pH, and temperature ranges). Therefore, the creation and deployment of sophisticated nanozymes has the potential to drastically alter the state of biosensor applications and the life sciences as they exist today. Biosensors have been utilized for quite some time as a streamlined method to quantitatively detect biomarkers (analytes) of interest. Therefore, the utilization of nanozymes in such biosensors assumes significant importance in the pursuit of cost-effective and dependable biosensors for therapeutic monitoring, disease prognosis, and diagnostics. Nanozymes have been investigated for a wide range of biosensing applications throughout the last few years. However, only few of such initiatives have produced platforms and devices that may be used for point-of-care and on-site monitoring. Hence, by providing a thorough overview of current developments in the classification of common nanozymes, this review seeks to guide and support the future development of biosensor technologies based on nanozymes, with an emphasis on their applications in the biosensing sector. We envision that this review will promote coordinated efforts across disciplines and sectors, helping to bridge the gap that keeps nanozyme-based biosensor technology confined to lab settings rather than being used in real-world situations.

Synthesis of varied oleic acid-coated Fe3O4 nanoparticles using the co-precipitation technique for biosensor applications

This study successfully synthesized oleic acid (OA)-coated Fe3O4 nanoparticles using the coprecipitation method for the needs of biosensor applications, as shown through the characterization of structure and morphology using XRD and TEM. This observation used 0.75 ml of OA (Fe3O4-OA(0.75)) and 1.25 ml of OA (Fe3O4-OA(1.25). A decrease in particle size distribution from 18.55 nm to 16.30 nm was observed, which means a reduction in agglomeration and increased dispersibility. Vibrating Sample Magnetometer (VSM) observations showed that the saturation magnetization of Fe3O4 particles modified with OA decreased from 47.71 emu/g to 45.90 emu/g at Fe3O4-OA(0.75) and decreased again to 42.29 emu/g at Fe3O4-OA(1.25). But they all show soft ferromagnetic properties with very low coercivity, making them suitable for Giant Magnetoresistance (GMR) biosensor applications. A series of concentrations in ethanol solution were performed to evaluate the detection sensitivity of GMR for these pure and oleic acid-modified Fe3O4 samples. Concentrations of 2, 5, 10, 15, 25, and 35 mg/ml were integrated at 2 μL each onto the surface of the GMR chip. A decrease in sensitivity was observed due to the change in saturation. Pure Fe3O4 with a sensitivity of 5.07 mV (mg/ml) decreased to 4.49 mV (mg/ml) and 3.35 mV (mg/ml) after oleic acid coating. Thus, although adding a proportional amount of oleic acid can slightly decrease the saturation magnetization, it can be a valuable method for applications such as GMR biosensors that demand high dispersibility and sensitivity that remains strong.

Application of advanced biosensors in nervous system diseases

AbstractNervous system diseases are among the most common diseases globally, posing a severe threat to patients' quality of life and placing a considerable burden on families and society. With improvements in miniaturization, intelligence, and the safety of biosensors, the combination of machinery and organisms is becoming increasingly common. In neuroscience research, biosensors of different macroscopic dimensions have been uniquely utilized to harness their relevant properties. One‐dimensional (1D) biosensors can achieve in situ real‐time monitoring of neural markers at the subcellular, single‐cell, ex vivo, and in vivo levels, with reduced impacts on organisms. Two‐dimensional (2D) biosensors can monitor the chemical behavior of cells and the neural activity of living animals. They are helpful for objectively identifying the characteristics of cells in response to external stimuli and studying the neural circuits of living animals. Three‐dimensional (3D) biosensors have shown unique advantages in point‐of‐care testing, liquid biopsy, drug screening, and mechanistic research. In clinical practice, brain‐computer interfaces (BCIs) and wearable devices have become important tools for monitoring and treatment. To date, there has been widespread adoption of BCIs in clinical practice. BCIs not only exhibit good efficacy in severe neurological and mental diseases but also provide a method for early diagnosis and treatment of these diseases. Wearable sensor devices can accurately assess the symptoms of movement disorders and play an active role in rehabilitation and treatment. In this review, we summarize the application of advanced biosensors in neuroscience research and clinical practice. The challenges and prospects of biosensors as applied to nervous system diseases under interdisciplinary promotion are also discussed in depth.

Therapeutic Voyage of Graphene-based Biosensor

: The study of carbon-based materials and nanoparticles is currently an exciting field of study in the domain of material science. One of the most prominent of these materials is graphene, along with its related components graphene oxide and reduced graphene oxide. A single-layer, twodimensional nanomaterial called graphene (GN) is employed in many different industries, such as electronics and biology. Graphene is a remarkable two-dimensional substance that has earned the title of "wonder material." Its remarkable electrical, optical, thermal, and mechanical qualities have attracted significant attention. Graphene's intriguing characteristics have led to its integration into numerous biosensing applications. Graphene possesses remarkable chemical, electrical, and physical qualities. The distinctive properties of graphene, particularly its electrical conductivity, large surface area, and significant electron mobility, are focusing more attention on applications in biomedicine that facilitate easier health monitoring. Biosensors with high sensitivity and precision can enhance patient care, and offer an opportunity for an early illness diagnosis and clinical pathogen identification. Additionally, a wide range of biological molecules, including glucose, hydrogen peroxide, cholesterol, dopamine, etc., can be detected using graphene-based biosensors. This study evaluates contemporary developments regarding graphene-based biosensors and their prospects and difficulties in this rapidly developing profession in the coming era. Graphene-based nanomaterials are appropriate to be employed in various biological and sensory contexts, including medicine and gene transfer, because of their unusual topologies and extraordinary properties. Graphene's outstanding characteristics enable biosensing applications to obtain the appropriate sensitivity, selectivity, and repeatability for a range of targets.

Conformation-Dependent Hydrogen-Bonding Interactions in a Switchable Artificial Metalloprotein.

Hydrogen-bonding (H-bonding) interactions in metalloprotein active sites can critically regulate enzyme function. Changes in the protein structure triggered by interplay with substrates, products, and partner proteins are often translated to the metallocofactor by way of specific changes in H-bond networks connected to the active site. However, the complexities of metalloprotein architecture and mechanism often preclude our ability to define the precise molecular interactions giving rise to these intricate regulatory pathways. To address this shortcoming, we have developed conformationally switchable artificial metalloproteins (swArMs) in which allosteric Gln-binding triggers protein conformational changes that impact the microenvironment surrounding an installed metallocofactor. Herein, we report a combined structural, spectroscopic, and computational approach to enhance the conformation-dependent changes in H-bond interactions surrounding the metallocofactor site of a swArM. Structure-informed molecular dynamics simulations were employed to predict point mutations that could enhance active site H-bond interactions preferentially in the Gln-bound holo-conformation of the swArM. Testing our predictions via the unique infrared spectral signals associated with the metallocofactor site, we have identified three key residues capable of imparting conformational control over the metallocofactor microenvironment. The resultant swArMs not only model biologically relevant structural regulation but also provide an enhanced Gln-responsive biological probe to be leveraged in future biosensing applications.

A novel and effective oxidation-resistant approach in plasmonic MIM biosensors for real-time detection of urea and glucose in urine for monitoring diabetic and kidney disease severity

In this research article, we introduce a novel oxidation-resistant approach in a Metal–Insulator–Metal (MIM) plasmonic biosensor, specifically designed for the detection and diagnosis of diabetes and kidney disease severity using urea and glucose biomarkers in urine. The proposed biosensor features a four-hand-shaped fan resonator with integrated nanodots and stubs within its waveguide. We optimized its performance through Finite Element Method (FEM) simulations, achieving a maximum sensitivity of 2470.48 nm/RIU and a Figure of Merit (FOM) of 50.15. To ensure chemical stability, we utilized an oxidation-resistant plasmonic material (Au) in our sensor, a critical factor for reliable biosensing applications. Additionally, we focus on Diabetic Kidney Disease (DKD), a significant global health challenge, emphasizing the need for early detection and point-of-care treatment. By exploiting minute changes in resonant wavelength resulting from light–matter interactions through the properties of Surface Plasmon Polaritons (SPPs) and MIM structures, our biosensor demonstrates promising capabilities for real-time and quantitative analysis of biomarkers critical for monitoring the stages of DKD.

Implantable Triboelectric Nanogenerators in the Biomedical Field

Implantable Triboelectric Nanogenerators (TENGs) have revolutionized the biomedical field by providing innovative power solutions for medical devices and enhancing diagnostic and therapeutic applications. Internally implanted TENG transforms kinetic energy from the body into electrical power, providing a constant energy supply for Implantable Medical Devices (IMD). Their ability to generate high voltage and low current makes them particularly effective for applications in biosensing, patient monitoring, and therapeutic interventions. Therapeutically, TENGs power cardiac pacemakers, promote wound healing, enhance bone regeneration, and support muscle and nerve stimulation. They also enable controlled drug release, particularly in targeted cancer treatments.

A bivariate fluorescence biosensor based on Janus DNA nanoarchitecture-loaded dual-emissive Ag nanoclusters as bi-responsive signaling reporters

Constructing label-free bivariate fluorescence biosensor would be intriguing and desired for the recognizable and accurate detection of two specific DNA segments, yet the design of functional DNA structures with low overlapped interference might be challenging. Herein in this work, a double-faced Janus DNA nanoarchitecture (JDNA) with bi-responsive recognition regions on opposite sides was assembled, which consisted of two substrate strands and two template strands for loading green-/red-emissive Ag nanoclusters (gAgNC and rAgNC) as bivariate signaling reporters. Of note, the hybridized double helix in the middle rationally oriented two flank faces and stabilized the rigid conformation of JDNA, while the template sequences of bicolor clusters were blocked to minimize non-specific background leakage. Upon inputting two targets, the discernible hairpins lost their hairpin structures due to forming two dsDNA complexes. They were executed to simultaneously invade JDNA for activating two individual target-recycled strand displacement (TRSD) events, guiding signal transduction and efficient amplification. Consequently, the clustering templates were unlocked via the tailored conformation switch of JDNA, in which gAgNC and rAgNC were in situ synthesized in two diagonal positions, thereby significantly emitting bi-responsive signal without cross interference. Benefited from the logic integration of double-faced JDNA and TRSD, a label-free, sensitive and specific bivariate fluorescence approach was developed, which would open a new avenue for the potential application in biosensing and bioanalysis.

Unpacking the packaged optical fiber bio-sensors: understanding the obstacle for biomedical application.

A biosensor is a promising alternative tool for the detection of clinically relevant analytes. Optical fiber as a transducer element in biosensors offers low cost, biocompatibility, and lack of electromagnetic interference. Moreover, due to the miniature size of optical fibers, they have the potential to be used in microfluidic chips and in vivo applications. The number of optical fiber biosensors are extensively growing: they have been developed to detect different analytes ranging from small molecules to whole cells. Yet the widespread applications of optical fiber biosensor have been hindered; one of the reasons is the lack of suitable packaging for their real-life application. In order to translate optical fiber biosensors into clinical practice, a proper embedding of biosensors into medical devices or portable chips is often required. A proper packaging approach is frequently as challenging as the sensor architecture itself. Therefore, this review aims to give an unpack different aspects of the integration of optical fiber biosensors into packaging platforms to bring them closer to actual clinical use. Particularly, the paper discusses how optical fiber sensors are integrated into flow cells, organized into microfluidic chips, inserted into catheters, or otherwise encased in medical devices to meet requirements of the prospective applications.

Adsorption-controlled electrochemical reaction with reversible dimerization, coupled to a preceding chemical reaction on porous graphenic surface: Modelling and application in label-free capacitive biosensing

Electrokinetic modelling and experimental studies are conducted on an adsorption system, with a model redox-active adsorbate 3,3′,5,5′-tetramethylbenzidine (TMB), strongly adsorbed to a platinum nanoparticle (PtNP)-modified porous laser induced graphene (LIG) surface. The adsorption-assisted system defined here involves an electrochemical reaction coupled to a preceding, surface-bound, chemical oxidation of the adsorbate. TMB is also known to undergo intermediate reversible dimerization during oxidation. A shift in the general expressions governing the voltammetric trends due to this reversible dimerization step, and the associated impact on the electrokinetic parameters is presented here for the first time. Impedance analysis reveals a modified Randles circuit, with the faradaic contribution of the adsorbate represented by a CPE circuit component. The adsorption-associated phasance, Qads, is expressed as a function of the surface concentrations, ΓO and ΓR, of the oxidised and reduced forms. Changes in the total surface concentration of the adsorbate, Γm, as a result of the presence of localised non-conductive entities, such as proteins, can be correlated to Qads, and subsequently, this capacitive change can be utilised for affinity sensing of an antigen on a specific immunosurface. Proof of concept is carried out with the immunosensing of a model protein, rheumatoid factor, on a PtNP-modified LIG surface biofunctionalised with the specific capture probe, the Fc fragment of IgG. The relationship between the antigenic concentration CRF, Qads and Γm is established. This label-free, adsorption-assisted, capacitive biosensing mechanism has not be reported previously, to the best of our knowledge, with a linear range of 0–300 U mL−1 and an LOD of 0.515 U mL−1 in spiked serum samples, comparable to the gold standard, ELISA.

A review on development of enzymatic biosensors for industrial applications

Enzymatic biosensors are vital tools across various industries due to their high specificity, sensitivity, and rapid response times. They are extensively used in medical diagnostics for monitoring biomarkers like glucose and lactate, environmental monitoring to detect pollutants, food safety and quality assurance, bioprocess control in industrial fermentation, pharmaceutical drug development and quality control, soil health and agrochemical detection in agriculture, and for identifying biological warfare agents. However, several challenges limit their broader adoption and effectiveness in industrial settings. Key challenges include enzyme stability, as enzymes can denature under extreme environmental conditions, reducing sensor lifespan and performance. Variability in enzyme activity and immobilization techniques also leads to inconsistencies, affecting sensor reproducibility and reliability. Complex sample matrices, such as those in environmental and food samples, introduce interference that can affect sensor accuracy. Integrating biosensors into existing industrial processes is another significant challenge, requiring compatibility with automated systems and real-time data processing capabilities. Additionally, high production costs and scalability issues hinder widespread adoption. Regulatory and standardization barriers further complicate the development and deployment of enzymatic biosensors. Despite these limitations, advancements in materials science, nanotechnology, and bioengineering are paving the way for more robust and reliable biosensors. Innovations such as nanomaterial-based enzyme immobilization, synthetic biology for enzyme engineering, and advanced data analytics integration hold promise for overcoming current limitations. Collaborative efforts among researchers, industry stakeholders, and regulatory bodies are essential to accelerate the development and application of enzymatic biosensors in industrial settings. While enzymatic biosensors offer significant potential, addressing these challenges through ongoing research and technological advancements is crucial for their widespread implementation and optimization.

Biosensing and Biotechnological Applications of Nanofillers: Current Status and Perspectives

Biosensing and Biotechnological Applications of Nanofillers: Current Status and Perspectives

Surface plasmon resonance sensors: Temperature effects

In this paper, we present a detailed study of the temperature effect (0−100°C), on the plasmonic resonance and sensitivity of a surface plasmon resonance (SPR) to the medium detection refraction index change. We examine this SPR based on the Kretschmann multilayer configuration constituted by a BK7 prism, an Ag/Au bimetallic layer deposited on TiO2/SiO2 and a BlueP/MoS2 heterostructure monolayer. First, a simple numerical calculation is provided to analyze the temperature effect on the plasmonic resonance. The model take into account the dependence on temperature of the refractive index of different materials composing the investigated structures. The main idea is to show how the sensitivity of the SPR based sensor is influenced according to operating temperature which is critical parameter when considering bio-sensing applications.

Redesigned Guide DNA Enhanced Clostridium butyricum Argonaute Activity for Amplification-Free and Multiplexed Detection of Pathogens.

Clostridium butyricum (CbAgo)-based bioassays are popular due to their programmability and directional cleavage capabilities. However, the relatively compact protein structure of CbAgo limits its cleavage activity (even at the optimal temperature), thus restricting its wider application. Here, we observed that guide DNA (gDNA) with specific structural features significantly enhanced CbAgo cleavage efficiency. Then, we invented a novel gDNA containing DNAzyme segments (gDNAzyme) that substantially enhanced the CbAgo cleavage efficency (by 100%). Using a molecular dynamics simulation system, we found that the augmented cleavage efficiency might be attributed to the large-scale global movement of the PIWI domain of CbAgo and an increased number of cleavage sites. Moreover, this gDNAzyme feature allowed us to create a biosensor that simultaneously and sensitively detected three pathogenic bacteria without DNA extraction and amplification. Our work not only dramatically expands applications of the CbAgo-based biosensor but also provides unique insight into the protein-DNA interactions.

Biosynthesis of Indigo Dyes and Their Application in Green Chemical and Visual Biosensing for Heavy Metals.

Fermentative production of natural colorants using microbial strains has emerged as a cost-effective and sustainable alternative to chemical synthesis. Visual pigments are used as signal outputs in colorimetric bacterial biosensors, a promising method for monitoring environmental pollutants. In this study, we engineered four self-sufficient indigo-forming enzymes, including HbpAv, bFMO, cFMO, and rFPMO, in a model bacterium E. coli. TrxA-bFMO was chosen for its strong ability to produce indigo under T7 lac and mer promoters' regulation. The choice of bacterial hosts, the supplementation of substrate l-tryptophan, and ventilation were crucial factors affecting indigo production. The indigo reporter validated the biosensors for Hg(II), Pb(II), As(III), and Cd(II). The biosensors reported Hg(II) as low as 14.1 nM, Pb(II) as low as 1.5 nM, and As(III) as low as 4.5 nM but increased to 25 μM for Cd(II). The detection ranges for Hg(II), Pb(II), As(III), and Cd(II) were quantified from 14.1 to 225 nM, 1.5 to 24.4 nM, 4.5 to 73.2 nM, and 25 to 200 μM, respectively. The sensitivity, responsive concentration range, and selectivity are comparable to β-galactosidase and luciferase reporter enzymes. This study suggests that engineered enzymes for indigo production have great potential for green chemical synthesis. Additionally, heterologous biosynthesis of indigo production can lead to the development of novel, low-cost, and mini-equipment bacterial biosensors with zero background noise for visual monitoring of pollutant heavy metals.