Biosensor Applications Research Articles

Self-Assembly of Microstructured Protein Coatings with Programmable Functionality for Fluorescent Biosensors.

Proteins, as genetically programmable functional macromolecules, hold immense potential as biocompatible self-assembling building blocks, owing to their versatility in building coating materials and programming their functionality genetically. In this study, we demonstrate a modular self-assembly of protein coatings that are genetically programmable for a biosensor application. We designed and produced recombinant fusion protein building blocks to form microstructured coatings on diverse substrates, such as glass or polymers, through thermally triggered liquid-liquid phase separation and an orthogonal high-affinity coiled-coil interaction. We incorporated fluorescence proteins into coatings and controlled the protein density to enable fluorescence imaging and quantification in a low-resource setting. Then, we created a coating for a calcium biosensor using a genetically engineered calcium indicator protein. This protein coating served as the foundation for our smartphone-based fluorescent biosensor, which successfully measured free calcium concentrations in the millimolar range at which extracellular calcium homeostasis is maintained. Using this fluorescent biosensor, we were able to detect abnormal physiological conditions, such as mild or moderate hypercalcemia. We envision that this modular and genetically programmable functional protein coating platform could be extended to the development of highly accessible, low-cost fluorescent biosensors for a variety of targets.

Diatoms: harnessing nature’s microscopic marvels for biosensing and multifaceted applications

AbstractThis article discusses the use of diatom in biosensing and various applications. A thorough understanding of the biosensing properties of diatoms is essential for the advancement of life sciences technologies. This review elucidates the emerging significance of diatoms in biosensing applications by highlighting the high surface area-to-volume ratio, biocompatibility, and facile functionalization of them. We examined the possible application of diatoms as flexible biosensing systems for the detection of various analytes, such as biological molecules, heavy metals, and poisons, by considering the findings of earlier research. Additionally, to show how diatoms can be used to create precise and sensitive biosensors, by integrating with several transduction modalities, including optical, electrochemical, and piezoelectric methods. We also delve into the potential applications of diatom-based biosensing in the future as well as pertinent topics such as repeatability, stability, and scalability. This provides an in-depth analysis of the quickly evolving field of diatom-based biosensing, which could affect several industries, such as environmental monitoring, food security and medical diagnostics.

Extraordinary terahertz transmission and field enhancement via hybrid surface plasmon coupling in rhombic and bow-tie composite aperture metasurface

Metasurface that achieves extraordinary terahertz transmission (ETT) and local electric field enhancement (FE) holds significant potential for terahertz studies involving extremely low concentrations of target materials. In this study, we explore a composite aperture metasurface capable of both ETT and local FE. By inserting bow-tie apertures in the “minimum-resonance” zone between four adjacent rhombic lattices, a local FE factor is achieved. Notably, adjusting the configuration of the bow-tie aperture enhances the coupling between surface plasmons, thereby expanding the transmission bandwidth. Through parameter optimization, the metasurface achieves a peak transmission exceeding 95% and a transmittance above 80% in the frequency range of 2.44–3.65 THz, while simultaneously exhibiting a maximum local FE factor of 1005 at 3.45 THz. This approach offers a promising avenue for the design of metasurfaces for spectroscopy and biosensor applications.

Cohesive Living Bacterial Films with Tunable Mechanical Properties from Cell Surface Protein Display.

Engineered living materials (ELMs) constitute a novel class of functional materials that contain living organisms. The mechanical properties of many such systems are dominated by the polymeric matrices used to encapsulate the cellular components of the material, making it hard to tune the mechanical behavior through genetic manipulation. To address this issue, we have developed living materials in which mechanical properties are controlled by the cell-surface display of engineered proteins. Here, we show that engineered Esherichia coli cells outfitted with surface-displayed elastin-like proteins (ELPs, designated E6) grow into soft, cohesive bacterial films with biaxial moduli around 14 kPa. When subjected to bulge-testing, such films yielded at strains of approximately 10%. Introduction of a single cysteine residue near the exposed N-terminus of the ELP (to afford a protein designated CE6) increases the film modulus 3-fold to 44 kPa and eliminates the yielding behavior. When subjected to oscillatory stress, films prepared from E. coli strains bearing CE6 exhibit modest hysteresis and full strain recovery; in E6 films much more significant hysteresis and substantial plastic deformation are observed. CE6 films heal autonomously after damage, with the biaxial modulus fully restored after a few hours. This work establishes an approach to living materials with genetically programmable mechanical properties and a capacity for self-healing. Such materials may find application in biomanufacturing, biosensing, and bioremediation.

Enzyme Activity Inhibition of α-Amylase Using Molecularly Imprinted Polymer (MIP) Hydrogel Microparticles.

Molecularly imprinted polymers (MIPs) are a class of synthetic recognition materials that offer a cost-effective and robust alternative to antibodies. While MIPs have found predominant use in biosensing and diagnostic applications, their potential for alternative uses, such as enzyme inhibition, remains unexplored. In this work, we synthesized a range of acrylamide-based hydrogel MIP microparticles (35 μm) specific for the recognition of α-amylase. These MIPs also showed good selectivity toward the target protein with over 96% binding of the target protein, compared with the control nonimprinted polymer (NIP) counterparts. Specificity of the MIPs was determined with the binding of nontarget proteins, trypsin, human serum albumin (HSA), and bovine serum albumin (BSA). The MIPs were further evaluated for their ability to inhibit α-amylase enzymatic activity, showing a significant decrease in activity. These findings highlight the potential of MIPs as enzyme inhibitors, suggesting an innovative application beyond their conventional use.

A label-free electrochemical detection of cadmium ions using aptamer-based biosensor

Abstract Cadmium is considered one of the most toxic pollutants that can be found in water as well as in soil, which might accumulate in living organisms causing severe effects such as skeletal, cardiovascular, and respiratory diseases. Hence, it is necessary to develop methods allowing for sensitive and fast detection as well as portability. One possibility is the application of biosensors containing aptamer strands as receptor layer selective towards cadmium ions. Here, we present studies on the utilization of DNA aptamer strand for fabrication of sensing layer toward cadmium ions on gold disk macroelectrodes. It is shown that proposed aptasensor enables Cd2+ ions detection in the range from 10 to 50 nM with LOD of 9.5 nM and exhibits high selectivity towards cadmium cations with a response at least two times higher than that for interfering ions. Moreover, studies on the stability revealed that sensing layer preserved its binding properties after storage and allowed for cadmium ions detection in the range from 10 to 50 nM and the aptamer sensing layer could be regenerated and applied for another set of analysis of cadmium ions.

Graphene electrochemical biosensors combining effervescent solid-phase extraction (ESPE) for rapid, ultrasensitive, and simultaneous determination of DA, AA, and UA

Simultaneous monitoring of key metabolites like dopamine, ascorbic acid, and uric acid is essential for early disease diagnosis and evaluating treatment. Electrochemical techniques are increasingly used for precise, point-of-care testing (POCT) of these metabolites. Herein, a sample pretreatment method called effervescent solid-phase extraction (ESPE) was proposed for efficient enrichment of trace analytes for electrochemical detection. In an ESPE process, effervescent tablets made of gold nanoparticle-decorated graphene oxide (Au/GO) were first self-dispersed in a test solution to promote the enrichment of analytes on the Au/GO adsorbents, followed by the addition of flocculant effervescent tablets to cause Au/GO sheets to form self-assembled aggregates, which then can be efficiently collected by the foam electrodes. The entire sample pretreatment process operates without external power and takes only 5 min. With the assistance of the ESPE method, our electrochemical sensors achieve an ultralow detection limit for dopamine, ascorbic acid, and uric acid of 80 pM, 1.8 nM, and 460 pM, respectively, which are two to three orders of magnitude lower than the results obtained by the drop casting technique. The enhancement mechanism of our approach is based on increasing the contact probability with analytes through dynamic dispersion of the Au/GO adsorbents, in contrast to the static diffusion mechanism relied on Brownian motion. We also show that combining the ESPE solution kit with a portable micro-electrochemical workstation can attain the same detection level as HPLC in real urine samples. The proposed ESPE approach holds great promise for POCT applications in 2D material-based biosensors.

Effective Surveillance of Water Quality in Recirculating Aquaculture Systems through the Application of Intelligent Biosensors

Water quality (WQ) is the paramount element influencing fish well-being and productivity in aquaculture farming systems. The survival of fish is mostly reliant on the aquatic environment that sustains them. Consequently, it is vital to possess a comprehensive awareness of the WQ prerequisites for the fish. Optimal WQ in Recirculating Aquaculture Systems (RAS) is essential for cultivating species' effective development and survival. Currently, no laws dictate the parameters to be monitored in RAS, leaving each farmer to choose which parameters to monitor. Historically, WQ measurements have been assessed at certain intervals using portable sensors and laboratory tests, which may be labor-intensive. This study proposes an Effective Surveillance of Water Quality (ESWQ) in RAS using Intelligent Biosensors (IBS). This study examines essential water characteristics (temperature, pH, calcium, magnesium, and Dissolved Oxygen (DO)) for RAS and evaluates the IBS for monitoring these factors. This research provides a potential solution for RAS using IBS, which would enhance ESWQ aspects, facilitate data-driven decision-making, and enable more rapid adaptation to evolving RAS situations.

CRISPR/Cas9-Mediated Genome Editing of T4 Bacteriophage for High-Throughput Antimicrobial Susceptibility Testing.

The accurate and effective determination of antimicrobial resistance is essential to limiting the spread of infectious diseases and ensuring human health. Herein, a simple, accurate, and high-throughput phage-based colorimetric sensing strategy was developed for antimicrobial susceptibility testing (AST). Taking advantage of the CRISPR/Cas9 system, the genome of the T4 phage was modularly engineered to carry lacZ-α (lacZa), a marker gene encoding the α-fragment of β-galactosidase (β-gal). T4lacZa phages were identified by blue-white selection and then used for a biosensing application. In this strategy, the bacterial solution is exposed to the T4lacZa phage, causing target bacteria to overexpress β-gal. Upon the addition of a colorimetric substrate, the β-gal initiates an enzymatic reaction, resulting in a solution color change from yellow to red. This sensing strategy offers a visual way to monitor bacterial growth in the presence of antibiotics, enabling the determination of bacterial antimicrobial susceptibility. As a proof of concept, our developed sensing strategy was successfully applied to identify 9 different multidrug-resistant Escherichia coli (E. coli) in urine samples with 100% specificity. Compared with conventional disk diffusion susceptibility tests, the engineered phage-based sensing strategy can shorten the detection time by at least half without losing detection sensitivity, providing an alternative high-throughput method for AST in clinical diagnosis.

Enhancing mycotoxins detection through quantum dots-based optical biosensors

Abstract Quantum dot-based optical biosensors represent a significant advancement for detection of mycotoxins that are toxic secondary metabolites produced by fungi and pose serious health risk effects. This review highlights the importance of detection of filamentous fungi such as Aspergillus, Penicillium, Fusarium, Claviceps, and Alternaria in mycotoxin production, leading to contamination of agricultural products and subsequent health issues. Conventional detection methods such as thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), gas chromatography (GC), and enzyme-linked immunosorbent assay (ELISA) are discussed with their respective advantages and limitations. Then the innovative use of quantum dots (QDs) in fabrication of biosensors is discussed in the present review, emphasizing their unique optical properties, such as size-tunable fluorescence and high photostability. These properties enable the development of highly sensitive and specific biosensors for mycotoxin detection. The application of QD-based biosensors, based on their applied bioreceptors including antibodies, molecularly imprinted polymers (MIPs) and aptamer, is explored through various detection strategies and recent advancements. The review concludes by underscoring the potential of QD-based biosensors in providing portable, cost-effective, and efficient solutions for real-time monitoring of mycotoxin for enhancing food safety and protecting public health.

Progress and Prospect of Liquid Crystal Droplets

Liquid crystal (LC) droplets are highly attractive for applications in privacy windows, optical switches, optical vortices, optical microresonators, microlenses, and biosensors due to their ease of fabrication and easy alignment at surfaces. This review presents the latest advancements in LC droplets, which have nematic, chiral nematic, and twist–bend nematic and ferroelectric nematic phases, or blue phases. Finally, it discusses the challenges and opportunities for applications based on LC droplets. The main challenges encompass the precise control of internal structures and defects to meet diverse application requirements, enhancing stability and durability across various environments, reducing large-scale production costs to improve commercial feasibility, increasing response speeds to external stimuli to adapt to rapidly changing scenarios, and developing tunable LC droplets to achieve broader functionalities.

Evaluation of sensitivity in a vertically misaligned double-gate electrolyte-insulator-semiconductor extended source tunnel FET as pH sensor

In this research, the primary objective is to investigate the impact of vertical gate misalignment on the source and drain regions of 30 nm. The double-gate Electrolyte-Insulated-Semiconductor extended-source Tunnel Field-Effect Transistor (ES-VTFET) is proposed for its potential application as a pH sensor. The gate electrode cannot be perfectly aligned with the channel due to fabrication tolerances, particularly in very short-channel structures. This study aims to introduce a vertical electrolyte Bio-TFET-based pH sensor capable of detecting pH changes in aqueous (electrolyte) solutions. The effect of variation in pH values on the electrical characteristics of the device such as drain current (IDS), transconductance (gm), voltage sensitivity (SV) and current sensitivity (SI) have been examined. It has been assumed that the electrolyte section is an intrinsic semiconductor material where electrons and holes signify mobile ions in aqueous solutions. The electrolyte region has an electrolyte dielectric constant of 78, an energy bandgap of 1.12 eV, and an electron affinity of 1.32 eV. Finally, the gate misalignment aspect of the proposed bio TFET-based pH sensor is emphasized by comparing sensitivity parameters. Hence, the proposed pH sensor can be used as a potential candidate for the futuristic application of biosensors.

Design and optimization of photonic crystal fibre THz bio‐sensor for extremely impressible identification of dengue

AbstractThe detection of human diseases is a major application for biosensors. During this work, a 2D photonic crystal fibre (PCF) biosensor design for dengue virus detection has been suggested. This work presents the decagonal hollow core PCF‐based dengue virus bio‐sensor and quantitatively investigates it over the terahertz regime. The suggested biosensor's performance is assessed using COMSOL Multiphysics, a professional tool that uses the Finite Element Method. The simulation's outcomes show that the suggested sensor performed better than earlier research, with a high sensitivity of 98.79%, 97.96%, 97.71%, 98.58%, 96.99% and 97.47% with more less confinement loss 1.2766 × 10−12 dB/m, 1.6385 × 10−12 dB/m, 2.8015 × 10−13 dB/m, 1.1798 × 10−13 dB/m, 7.0336 × 10−12 dB/m and 0.00 dB/m respectively for infected Haemoglobin (Hgb), Normal Haemoglobin (Hgb), Infected Platelets (Plt), Normal Platelets (Plt), Infected Plasma (Psm) and Normal Plasma (Psm) at 3.0 THz using the ideal geometric configuration. Very soon, its remarkable sensitivity and guiding capabilities will be crucial to dengue virus detection technology.

Design of a PIT biosensor based on plasmonic-graphene-black phosphorous hybrid for hypercholesterolemia detection

Cardiovascular diseases are the primary and fundamental reasons of people death around the world. Precise, fast responding, compact and integrable biosensors are considered as the most important prevention or treatment devices. In this work, remarkable absorbers based on graphene-plasmonic-black phosphorous hybrid structures are proposed. These devices are utilized for bio-sensing applications. The presented device is consisted of different quarter-cylindrical and plate shaped layers of graphene, black phosphorous, Ag, Au and Al2O3. In order to improve functionality of the presented absorber (improving the absorption’s peak value), effects of structural parameters and chemical potential (Ef) on the absorption spectrum are being considered. The proposed structure will be considered as a biosensor for detection of cholesterol concentrations in blood samples (this would help physicians in diagnosis of hypercholesterolemia and prevention of cardiovascular diseases), after improving its characteristics. Finally, it is expected for this biosensor the following remarkable sensitivity, figure of merit, quality factor and detection limit of 6045.6 nm/RIU, 237.61 RIU− 1, (80.3–90.1) and (2.1e-4–2.26e-5) RIU, respectively. Therefore, the proposed device can be an appropriate candidate for bio-sensing applications in optical integrated circuits.

Analysis on density of states and ION/IOFF ratio of GaN/GaN-graphene nanoribbon tunnel FET for enhanced bio-sensing applications

Abstract This research introduces a new analytical model that studies the effect of ferro-dielectric on the operational performance of TFETs doped with halogens. The effect of source and drain depletions, voltage-drain & gate, thickness and capacitance of gate insulator are all investigated in this study. Accurate measurements of the surface potential are required to ascertain the transconductance, gate-to-drain capacitance, and lateral electric field of the device. Our model, which employs Ferroelectric Halo-Doped double gate (FHDD)-gated device designs, has been demonstrated to produce results that nearly match those produced from TCAD simulations. This was accomplished by doing a comparative analysis of the outcomes derived from both sets of simulations. Furthermore, the performance of the suggested structure of TFET, which integrates a dielectric of Fe and GaN heterostructure, surpasses that of other similar devices (fT) in terms of ON current, ON/OFF ratio, transconductance, and cut-off frequency. A ferroelectric dielectric was used to create a ferroelectric heterostructure. This study also centers on the creation and application of a graphene nanoribbon field effect transistor (GNR-TFET) to detect sugar molecules, specifically fructose, xylose, and glucose. The detecting signal is generated by utilizing the fluctuation in the electrical current of the GNR-TFET caused by the presence of individual sugar molecules. The GNR-TFET exhibits noticeable variations in the density of states, transmission spectrum, and current when exposed to individual sugar molecules. The sensor under investigation is being developed and examined using a combination of semi-empirical modeling and non-equilibrium Green's functional theory (SE + NEGF). According to the research, the modified GNR TFET has the ability to quickly and accurately detect individual sugar molecules in real-time.

Advanced functional polymer materials for biomedical applications

AbstractPolymer structures are essential in biomedical applications due to their biocompatibility, biodegradability, and ability to form intricate structures on micro‐ to nanometer scales. This review, emphasizing electrospinning and phase inversion techniques, examines the fabrication strategies and chemical design of polymer structures for biomedical use. Electrospinning, particularly needleless electrospinning, produces nanofibres with high porosity and flexibility and is widely applied in tissue engineering and drug delivery. Phase inversion, including thermal, nonsolvent‐, vapor‐ and evaporation‐induced phase separation, allows precise control over polymer properties but faces challenges in terms of cooling rates and solvent characteristics. Chemical design through doping, functionalization, cross‐linking and copolymerization enhances the biocompatibility, biodegradability and mechanical properties of polymers, facilitating advanced applications in drug delivery, tissue scaffolding and biosensors. Advanced functional polymers are revolutionizing biomedical fields, offering innovative solutions for therapeutic medicine delivery, disease detection, diagnostics, and regenerative medicine. Despite remarkable progress, challenges, such as scalability, cost‐effectiveness, and environmental impact, persist. This review underscores the transformative potential of advanced polymer materials in medical treatments and advocates for continuous research and interdisciplinary collaboration to overcome existing challenges and fully exploit the capabilities of these materials in improving patient care and medical outcomes. Future perspectives highlight enhancing precision control mechanisms, integrating phase inversion with other techniques and developing large‐scale production methods to advance the field further.

Deep-Learning Empowered Customized Chiral Metasurface for Calibration-Free Biosensing.

As a 2D metamaterial, metasurfaces offer an unprecedented avenue to facilitate light-matter interactions. The current "one-by-one design" method is hindered by time-consuming, repeated testing within a confined space. However, intelligent design strategies for metasurfaces, limited by data-driven properties, have rarely been explored. To address this gap, a data iterative strategy based on deep learning, coupled with a global optimization network is proposed, to achieve the customized design of chiral metasurfaces. This methodology is applied to precisely identify different chiral molecules in a label-free manner. Fundamentally different from the traditional approach of collecting data purely through simulation, the proposed data generation strategy encompasses the entire design space, which is inaccessible by conventional methods. The dataset quality is significantly improved, with a 21-fold increase in the number of chiral structures exhibiting the desired circular dichroism (CD) response (>0.6). The method's efficacy is validated by a monolayer structure that is easily prepared, demonstrating advanced sensing abilities for enantiomer-specific analysis of bio-samples. These results demonstrate the superior capability of data-driven schemes in photonic design and the potential of chiral metasurface-based platforms for calibration-free biosensing applications. The proposed approach will accelerate the development of complex systems for rapid molecular detection, spectroscopic imaging, and other applications.

Cohesion Regulation of Polyphenol Cross‐Linked Hydrogel Adhesives: From Intrinsic Cross‐Link to Designs of Temporal Responsiveness

AbstractPolyphenol hydrogels have found widespread application in wound healing, bone repair, drug delivery, and biosensors due to their robust wet adhesion, high ductility, and excellent self‐healing ability. However, these hydrogels often exhibit low intrinsic cohesion, which limits their overall adhesive strength. Enhancing cohesion is critical for improving both the adhesion and mechanical properties of the hydrogels, thereby expanding their utility in biomedical fields. This review begins by exploring strategies to enhance the cohesion of polyphenol hydrogel adhesives, detailing modifications that act individually or synergistically. The importance of temporally regulating cohesion is emphasized to accommodate various applications and environmental conditions. Finally, this paper discusses remaining challenges in cohesion regulation and outlines prospects for future research. It is hoped that this comprehensive review will provide new insights into the development of advanced polyphenolic hydrogel adhesives and contribute to the design of “smart adhesives” for increasingly complex needs in biomedical applications.

Regulation of transmembrane current through modulation of biomimetic lipid membrane composition.

Ion transport through biological channels is influenced not only by the structural properties of the channels themselves but also by the composition of the phospholipid membrane, which acts as a scaffold for these nanochannels. Drawing inspiration from how lipid membrane composition modulates ion currents, as seen in the activation of the K+ channel in Streptomyces A (KcsA) by anionic lipids, we propose a biomimetic nanochannel system that integrates DNA nanotechnology with two-dimensional graphene oxide (GO) nanosheets. By modifying the length of the multibranched DNA nanowires generated through the hybridization chain reaction (HCR) and varying the concentration of the linker strands that integrate these DNA nanowire structures with the GO membrane, the composition of the membrane can be effectively adjusted, consequently impacting ion transport. This method provides a strategy for developing devices with highly efficient and tunable ion transport, suitable for applications in mass transport, environmental protection, biomimetic channels, and biosensors.

Electroosmotic Flow-Driven DNA-CNT Nanomotor via Tunable Surface-Charged Nanopore Array.

Nanomotors are usually designed to work in liquid media and carry cargo; they exhibit excellent potential for biosensing and disease treatment applications due to their small size. Graphene and carbon nanotubes (CNTs) are crucial components of rotary nanomotors because of excellent mechanical properties and adaptability to the human body. Herein, we introduce a DNA-CNT-based nanomotor that achieves its rotational control through an array of nanopores with tunable surface charges. The findings demonstrate that by adjusting the surface charge density of the nanopores and the direction of electric field, a DNA strand can be sequentially captured by the nanopores, thereby rotating the connected CNT. The transition from a four-nanopore array to a six-nanopore array reveals that reducing the step angle to 60° significantly enhances the rotational stability of the nanomotor and reduces random fluctuations caused by Brownian motion. This method improves the control stability of the nanomotor, providing robust support for future applications in nanoscale manipulation.