Biosensor Applications Research Articles

Synthesis and nanoparticle formation of pyrazine, benzodithiophene (BDT) and fluorene containing conjugated polymer (P-PBF) and its biosensing performance toward catechol

The development of laccase-based biosensors, in particular, have attracted much interest due to their ability to detect highly toxic molecules in the environment. This article reports a novel biosensor for catechol detection that can be used to determine toxic molecules in the environment. For this purpose, a novel conjugated polymer (P-PBF) and conjugated polymer nanoparticles (P-PBFNPs) were synthesized and characterized, respectively. To our knowledge, research has yet to be done on conjugated polymer nanoparticle-based electrochemical biosensing platforms for catechol determination. The biosensor comprises a GE/P-PBF NPs/Lac electrode, constructed with P-PBF NPs deposited onto a bare graphite electrode followed by laccase (Lac) enzyme immobilization. While electrochemical characterization was performed by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), surface characterization was performed by field emission scanning electron microscopy (FE-SEM). The biosensor exhibited high sensitivity (1.229 μA/μM.cm2), a good linear range (0.5–25 μM) and a low limit of detection (LOD) (0.49 μM). Moreover, the developed biosensor exhibited high selectivity in the presence of interfering analytes without any memory effects. The potential of the GE/P-PBF NPs/Lac electrode in tap water, green tea, synthetic urine and serum samples indicates the inspiring biosensing applications for monitoring environmental pollution.

Towards understanding Trans-cleavage of natural and synthetic nucleic acids by Cas12a for sensitive CRISPR biosensing

CRISPR/Cas systems have been widely utilized for the development of biosensing platforms for precision molecular diagnostics. Their remarkable biosensing performance critically depends on the efficiency of sequence-independent trans-cleavage in type V and VI Cas effectors. Cas12a, a typical example of type V Cas effector exhibits varying trans-cleavage efficiency on different types of nucleic acids, and also in response to different nucleobase sequences. However, the underlying mechanism of Cas12a’s trans-cleavage characteristic remains unclear. To explore this mechanism, we introduced Xeno nucleic acids (XNA) as potential trans-cleavage substrates of Cas12a. XNAs are chemically modified nucleic acid analogues, which originate from chemical modifications of nucleobases, sugar moieties, and the backbone. We observed a progressive decrease in trans-cleavage rates by Cas12a across different types of XNAs, in the following sequence: nucleobase-modified XNA > sugar moiety-modified XNA > backbone-modified XNA. In addition, more complex chemical modifications on either of the three above locations led to the lowering of the trans-cleavage rate of Cas12a. These findings elucidate the mechanism behind Cas12a’ trans-cleavage characteristic, which is attributed to its higher affinity of Cas12a for substrates with simpler chemical structures, leading to increased trans-cleavage efficiency. Based on these findings, we also developed a colorimetric CRISPR/Cas12a biosensing system utilizing XNA for the detection of circulating tumor DNA (ctDNA), with a limit of detection of 10 pM and a 4 logs detection range from 10 pM to 100 nM. These results indicate that XNA can serve as a novel Cas12a trans-cleavage substrate for sensitive biosensing applications.

Acoustofluidic tweezers via ring resonance.

Ring resonator (RR) devices are closed-loop waveguides where waves circulate only at the resonant frequencies. They have been used in sensor technology and optical tweezers, but controlling micron-scale particles with optical RR tweezers is challenging due to insufficient force, short working distances, and photodamage. To overcome these obstacles, an acoustofluidic RR-based tweezing method is developed to manipulate micro-sized particles that can enhance particle trapping through the resonance interaction of acoustic waves with high Q factor (>3000), more than 20 times greater than traditional acoustic transducers. Particles can be precisely manipulated within the RR by adjusting the signal phase, with trapping amplified by enlarging the connected waveguide. Rapid particle mixing is achieved when particles are placed between the waveguide and RR. The signal path is strengthened by strategically positioning the RR in a two-dimensional plane. Acoustofluidic RR tweezers have immense potential for advancing applications in biosensing, mechanobiology, lab-on-a-chip, and cell-cell communication research.

Functional Organic Electrochemical Transistor-Based Biosensors for Biomedical Applications

Organic electrochemical transistors (OECTs), as an emerging device for the development of novel biosensors, have attracted more and more attention in recent years, demonstrating their promising prospects and commercial potential. Functional OECTs have been widely applied in the field of biosensors due to their decisive advantages, such as high transconductance, easy functionalization, and high integration capability. Therefore, this review aims to provide a comprehensive summary of the most recent advances in the application of functional OECT-based biosensors in biomedicine, especially focusing on those biosensors for the detection of physiological and biochemical parameters that are critical for the health of human beings. First, the main components and basic working principles of OECTs will be briefly introduced. In the following, the strategies and key technologies for the preparation of functional OECT-based biosensors will be outlined and discussed with regard to the applications of the detection of various targets, including metabolites, ions, neurotransmitters, electrophysiological parameters, and immunological molecules. Finally, the current main issues and future development trends of functional OECT-based biosensors will be proposed and discussed. The breakthrough in functional OECT-based biosensors is believed to enable such devices to achieve higher performance, and thus, this technology could provide new insight into the future field of medical and life sciences.

Modeling Electrochemical Impedance Spectroscopy Using Time-Dependent Finite Element Method

A time-dependent electrochemical impedance spectroscopy (EIS) model is presented using the finite element method (FEM) to simulate a 2D interdigitated electrode in an aqueous NaCl electrolyte. Developed in COMSOL Multiphysics, the model incorporates ion transport, electric field distribution, Stern layer effects, and electrode sheet resistance, governed by the Poisson and Nernst–Planck equations. This model can predict the transient current response to an applied excitation voltage, which gives information about the dynamics of the electrochemical system. The simulation results are compared with the experimental data, reproducing key features of the measurements. The transient current response indicates the need for multiple excitation cycles to stabilize the impedance measurement. At low frequencies (<1 kHz), the voltage drop at the Stern layer is significant, while at higher frequencies (>100 kHz), the voltage drop due to sheet resistance dominates. Moreover, the amplitude of the excitation voltage influences the EIS measurement, higher amplitudes (above 0.1 V) lead to non-linear impedance behavior, particularly at low ion concentrations. Discrepancies at low frequencies suggest that Faradaic processes may need to be incorporated for improved accuracy. Overall, this model provides quantitative insights for optimizing EIS sensor design and highlights critical factors for high-frequency and low-concentration conditions, laying the foundation for future biosensing applications with functionalized electrodes.

Oriented triplex DNA as a synthetic receptor for transmembrane signal transduction.

Signal transduction across biological membranes enables cells to detect and respond to diverse chemical or physical signals, and replicating these complex biological processes through synthetic methods is of significant interest in synthetic biology. Here we present an artificial signal transduction system using oriented cholesterol-tagged triplex DNA (TD) as synthetic receptors to transmit and amplify signals across lipid bilayer membranes through H+-mediated TD conformational transitions from duplex to triplex. An auxiliary sequence, complementary to the third strand of the TD, ensures a controlled and preferred outward orientation of cholesterol-tagged TD on membranes. Upon external H+ stimuli, the conformational change triggers the translocation of the third strand from the outer to the inner membrane leaflet, resulting in effective transmembrane signal transduction. This mechanism enables fluorescence resonance energy transfer (FRET), selective photocleavage, catalytic signal amplification, and logic gate modulation within vesicles. Our findings demonstrate that these TD-based receptors mimic the functional dynamics of natural G protein-coupled receptors (GPCRs), providing a foundation for advanced applications in biosensing, cell signaling modulation, and targeted drug delivery systems.

Enhanced long-lasting luminescence nanorods for ultrasensitive detection of SARS-CoV-2 N protein

AbstractPersistent luminescence nanomaterials can remain luminescence when the light source is turned off, which exhibits promise in biosensor and bioimaging fields since they have the ability to completely eradicate tissue autofluorescence. Although significant progress has been made in the persistent luminescence biosensing, there is still a dearth of long-afterglow detection platform with low limit of detection (LOD) and high sensitivity. Herein, Zn2GeO4:Mn, Cr persistently luminescent nanorods (PLNRs) with superior persistent luminescence and long afterglow time were developed. The addition of Cr3+ manifestly improves persistent luminescence intensity and afterglow duration through creating a deep defect trap. Then the biosensors were constructed by combining the Zn2GeO4:Mn,Cr PLNRs-antibody and Fe3O4 magnetic nanoparticles (MNPs)-antibody for nucleocapsid protein detection based on electrostatic attraction. The LOD value for nucleocapsid protein realizes as low as 39.82 ag/mL, which is much lower than the previously reported persistent luminescent-based biosensors. Accordingly, the low detection sensitivity is attributed to fluorescence resonance energy transfer. In addition, high specificity is also achieved. Therefore, the as-prepared Zn2GeO4:Mn,Cr persistently luminescent materials can act as the promising candidate in biosensors applications. This strategy provides effective guidance for the development of biosensing platforms with high sensitivity and specificity.

Programmable orientation of blue phase soft photonic crystal

Understanding the structure formation and its underlying physical mechanism is a fundamental topic in condensed matter systems, with both academic and practical implications. Soft matter is playing a remarkable role in current era of information explosion, demonstrating enormous potential in integrated functional photonics. As unique soft photonic crystals with cubic symmetries, not only liquid crystalline blue phases (BPs) have circularly polarized selective reflection and ultra-fast electro-optical response, but also their three-dimensional photonic structures increase degrees-of-freedom for multiplexed optical modulation. In the thriving field of soft-matter-based photonics, precise and programmable engineering of BP crystal orientation is of vital importance for planar optical elements, which remains a challenging task due to the complexity of the nucleation process as well as the interaction between the BP building blocks and the boundary conditions. Aiming to gain a comprehensive understanding of how to tailor the orientation of BP crystals for the photonic applications of next generation, here we discuss the solutions for uniformity improvement and orientation control of BP crystals, about which a few of examples in combination with the underlying mechanisms are explained. In addition, the remaining challenges and the efforts that are expected are also reviewed. We expect this work provides a deeper understanding of phase transitions and resulting structures in soft crystals, which may open encouraging perspectives for their applications in photonics, biosensing, interfacial, and chemical engineering.

Solvent-Free Approaches for the Synthesis of Lophine Derivatives

AbstractSolvent-free synthesis comes with many advantages such as cost reduction, waste reduction, ease of operation, sustainability, environmentally benign operations, etc. These benefits have prompted many chemists to develop new protocols for solvent-free synthesis of various interesting chemical compounds. One such class of compounds is 2,4,5-triarylimidazoles, commonly known as lophines due to their applications in materials science, chemo- and bio-sensors, and pharmacology. This article focuses on solvent-free synthesis of lophine derivatives via different protocols, including the use of inorganic-, organic-, and biocatalysts; solid-supported catalysts; microwave-mediated heating; and grinding.

β-Cyclodextrin Functionalized Au@Ag Core-Shell Nanoparticles: Plasmonic Sensors for Cysteamine and Efficient Nanocatalysts for Nitrobenzene-to-Aniline Conversion

We reported the gold/silver core-shell nanoparticles (Aucore@Agshell NPs) functionalized with β-cyclodextrin (β-CD) as versatile nano-agents demonstrated for human urine-based biosensing of cysteamine and catalytic conversion from nitrobenzene (NB) to aniline. First, the hybrid bimetallic nanoparticles, i.e., β-CD-Aucore@Agshell NPs, constituted a colorimetric sensing platform based on localized surface plasmons, enabling cysteamine (Cyst) to be detected in a remarkably rapid manner, i.e., within 2 min, which was greatly shortened in comparison with that of our previous report. This was due largely to use of β-CD being effectively replaceable by Cyst. The detection of Cyst was demonstrated using human urine specimens in the linear range of 25–750 nM with a limit of detection of 1.83 nM. Excellent specificity in detecting Cyst was also demonstrated against potential interfering molecules. Meanwhile, the β-CD-Aucore@Agshell NPs were demonstrated as nanocatalysts for converting NB to aniline with efficiency enhanced by more than three-fold over the pure gold nanoparticles previously reported, due to the dual functions of the structural core-shell. The demonstrated versatile features of the hybrid nanoparticles can find applications in human urine-based biosensors for Cyst detection, and in the screening of Cyst-containing drugs, while detoxicating NB for ecological protection in aqueous media.

An Enzyme-Free Impedimetric Sensor Based on Flower-like NiO/Carbon Microspheres for L-Glutamic Acid Assay

This research introduces a non-enzymatic electrochemical sensor utilizing flower-like nickel oxide/carbon (fl-NiO/C) microspheres for the precise detection of L-glutamic acid (LGA), a crucial neurotransmitter in the field of healthcare and a frequently utilized food additive and flavor enhancer. The fl-NiO/C were synthesized with controllable microstructures using metal–organic frameworks (MOFs) as precursors followed by a simple calcination process. The uniformly synthesized fl-NiO/C microspheres were further characterized using Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), energy-dispersive X-ray spectroscopy (EDX), and field emission scanning electron microscopy (FE-SEM). The fl-NiO/C was utilized as a modifier on the surface of a glassy carbon electrode, and an impedimetric sensor based on electrochemical impedance spectroscopy (EIS) was developed for the detection of LGA. The proposed sensor demonstrated excellent catalytic activity and selectivity towards LGA across a broad concentration range of 10–800 μM with a sensitivity of 486.9 µA.mM−1.cm−2 and a detection limit of 1.28 µM (S/N = 3). The sensor was also employed to identify LGA in blood plasma samples, yielding results that align with those obtained through HPLC. This achievement highlights the potential of fl-NiO/C microspheres in advancing cutting-edge biosensing applications.

DNA Nanomaterial-Based Electrochemical Biosensors for Clinical Diagnosis.

Sensitive and quantitative detection of chemical and biological molecules for screening, diagnosis and monitoring diseases is essential to treatment planning and response monitoring. Electrochemical biosensors are fast, sensitive, and easy to miniaturize, which has led to rapid development in clinical diagnosis. Benefiting from their excellent molecular recognition ability and high programmability, DNA nanomaterials could overcome the Debye length of electrochemical biosensors by simple molecular design and are well suited as recognition elements for electrochemical biosensors. Therefore, to enhance the sensitivity and specificity of electrochemical biosensors, significant progress has been made in recent years by optimizing the DNA nanomaterials design. Here, the establishment of electrochemical sensing strategies based on DNA nanomaterials is reviewed in detail. First, the structural design of DNA nanomaterial is examined to enhance the sensitivity of electrochemical biosensors by improving recognition and overcoming Debye length. In addition, the strategies of electrical signal transduction and signal amplification based on DNA nanomaterials are reviewed, and the applications of DNA nanomaterial-based electrochemical biosensors and integrated devices in clinical diagnosis are further summarized. Finally, the main opportunities and challenges of DNA nanomaterial-based electrochemical biosensors in detecting disease biomarkers are presented in an aim to guide the design of DNA nanomaterial-based electrochemical devices with high sensitivity and specificity.

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.

High-Q terahertz chirality enhancement using elliptical hole metasurface

Circular dichroism (CD) technology has garnered significant attention due to its extensive applications in ultra-sensitive biosensing and spin-selective optical frequency conversion. However, existing terahertz chiral structures are constrained by linewidth, which limits their effectiveness in narrowband signal processing. In this study, we propose the notion of quasi-bound states in the continuum (quasi-BIC) within a planar elliptical hole all-silicon terahertz metasurface that exhibits broken mirror symmetry. This approach achieves a CD value as high as 0.97, with a linewidth below 0.5 GHz and a Quality (Q)-factor reaching up to 107 in the 1.3 THz to 1.55 THz band, thereby enabling ultra-narrowband terahertz chirality. This method significantly enhances the Q-factor of optical resonant systems, reduces linewidth, and achieves strong CD while addressing the trade-off between high Q-factor and high CD observed in existing structures. The theoretical foundations for achieving ultra-narrow linewidth are established through band structure calculations and far-field polarization analysis. Additionally, the Q-factor of quasi-BIC can be flexibly optimized through parameter tuning, rendering it more practical than perfect BIC in real-world applications. This study presents a novel solution for terahertz narrowband chirality and optical filters, potentially advancing technologies in related fields.© 2024 Optica Publishing Group under the terms of the Optica Publishing Group Open Access Publishing Agreement.

Tunable Multi-Enzyme Activities of Platinum Nanoclusters for Enhanced Specificity and Sensitivity in Biosensing

Nanozymes have gained prominence for their utility in biosensing and disease diagnostics. However, challenges arise from complex sample matrices and nonspecific enzyme activities that contribute to false signals. This study introduces multifunctional platinum nanoclusters (Pt NCs) exhibiting peroxidase-like (POD-like), oxidase-like (OXD-like), and laccase-like activities tailored for enhanced biosensing capabilities. By adjusting pH, we optimized the conditions to achieve distinct POD-like and OXD-like responses, thereby reducing background signals and improving detection accuracy. The addition of ATP further amplified the POD-like activity while minimizing interference from OXD-like activity. This combined strategy substantially enhanced biomarker detection selectivity, demonstrated through glucose detection in human serum samples. Moreover, thiol inhibition of laccase-like activity in Pt NCs was leveraged for thiol-based antioxidant assessment, revealing their application in quantifying total antioxidant capacity (TAC) in human liver cancer cells, accounting for 44% of TAC. The Pt NCs demonstrated robust sensitivity and reusability, offering a novel multi-enzyme nanomaterial with potential for precise and interference-free biosensing applications. These findings contribute to the development of advanced nanozyme-based biosensors, addressing specificity regulation challenges and expanding their practical application in biosensing and disease diagnostics.

A Label-Free Electrochemical Detection of Cadmium Ions Using Aptamer-Based Biosensor

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.

Non-Destructive Integration of Spark-Discharge Produced Gold Nanoparticles onto Laser-Scribed Graphene Electrodes for Advanced Electrochemical Sensing Applications

Gold nanoparticles (AuNPs) decorated graphene materials are preferable materials in a wide range of electrochemical applications, however, the current methods for preparing them have several limitations. Herein, we have developed a green, solution-free, and non-destructive method for the in-situ generation of AuNPs on laser-scribed graphene electrodes (LSGEs), addressing the limitations of traditional preparation methods. This novel technique, contrasting with the conventional solution-based electrochemical deposition, utilizes spark discharge to modify LSGEs, demonstrating superior performance in sensors and biosensors applications. Through comprehensive characterizations (scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), Raman spectra, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and Kelvin probe force microscopy (KPFM)), we observed significant distinctions in particle size, metal loading, stability, surface-to-volume ratio, and graphene quality between spark-discharge produced AuNPs (SP-AuNPs) and electrodeposition produced AuNPs (EC-AuNPs). The average particle sizes of the SP-AuNPs and EC-AuNPs are 10 nm and 38 nm, respectively. The SP-AuNPs modified LSGEs demonstrate exceptional electroanalytical performance in dopamine detection, with a broad detection range (0.6–90 µM) and low LOD (0.40 µM), further validated in human neuroblastoma cells SH-SY5Y. Our findings suggest that the spark discharge method represents a significant advancement in the synthesis of metal nanoparticle enhanced LSG electrodes, with broad implications for electrochemical sensing, biosensing, and biomedical 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.