Sensitive Detection Research Articles

Optical Nanosensor Passivation Enables Highly Sensitive Detection of the Inflammatory Cytokine Interleukin-6.

Interleukin-6 (IL-6) is known to play a critical role in the progression of inflammatory diseases such as cardiovascular disease, cancer, sepsis, viral infection, neurological disease, and autoimmune diseases. Emerging diagnostic and prognostic tools, such as optical nanosensors, experience challenges in translation to the clinic in part due to protein corona formation, dampening their selectivity and sensitivity. To address this problem, we explored the rational screening of several classes of biomolecules to be employed as agents in noncovalent surface passivation as a strategy to screen interference from nonspecific proteins. Findings from this screening were applied to the detection of IL-6 by a fluorescent-antibody-conjugated single-walled carbon nanotube (SWCNT)-based nanosensor. The IL-6 nanosensor exhibited highly sensitive and specific detection after passivation with a polymer, poly-l-lysine, as demonstrated by IL-6 detection in human serum within a clinically relevant range of 25 to 25,000 pg/mL, exhibiting a limit of detection over 3 orders of magnitude lower than prior antibody-conjugated SWCNT sensors. This work holds potential for the rapid and highly sensitive detection of IL-6 in clinical settings with future application to other cytokines or disease-specific biomarkers.

A new three-dimensional (3D) molecularly imprinted polymer fluoroprobe based on green-red dual-emission signals of carbon quantum dots and self-polymerization of dopamine (CDs@PDA-MIPs) for sensitive detection of nifedipine.

Nifedipine (NIF), as one of the dihydropyridine calcium channel blockers, is widely used in the treatment of hypertension. However, misuse or ingestion of NIF can result in serious health issues such as myocardial infarction, arrhythmia, stroke, and even death. It is essential to design a reliable and sensitive detection method to monitor NIF. In this work, an innovative molecularly imprinted polymer dual-emission fluorescent sensor (CDs@PDA-MIPs) strategy was successfully designed for sensitive detection of NIF. The fluorescent intensity of the probe decreased with increasing NIF concentration, showing a satisfactory linear relationship within the range 1.0 × 10-6M ~ 5.0 × 10-3M. The LOD of NIF was 9.38 × 10-7M (S/N = 3) in fluorescence detection. Theapplication of the CDs@PDA-MIPs in actual samples such as urine and Qiangli Dingxuan tablets has been verified, with recovery ranging from 97.8 to 102.8% for NIF. Therefore, the fluorescent probe demonstrates great potential as a sensing system for detecting NIF.

Fluorescent and Colorimetric Dual-Readout Immunochromatographic Assay for the Detection of Phenamacril Residues in Agricultural Products.

The fungicide phenamacril has been employed to manage Fusarium and mycotoxins in crops, leading to persistent residues in the environment and plants. Detecting phenamacril is pivotal for ensuring environmental and food safety. In this study, haptens and artificial antigens were synthesized to produce antiphenamacril monoclonal antibodies (mAbs). Additionally, gold nanoparticles coated with a polydopamine shell were synthesized and conjugated with mAbs, inducing fluorescence quenching in quantum dots. Moreover, a dual-readout immunochromatographic assay that combines the positive signal from fluorescence with the negative signal from colorimetry was developed to enable sensitive and precise detection of phenamacril within 10 min, achieving detection limits of 5 ng/mL. The method's reliability was affirmed by using spiked wheat flour samples, achieving a limit of quantitation of 0.05 mg/kg. This analytical platform demonstrates high sensitivity, outstanding accuracy, and robust tolerance to matrix effects, making it suitable for the rapid, onsite, quantitative screening of phenamacril residues.

The Evaluation of a Lateral Flow Strip Based on the Covalently Fixed "End-On" Orientation of an Antibody for Listeria monocytogenes Detection.

In this study, the covalently fixed "end-on" orientation of a monoclonal Listeria monocytogenes antibody (mAb-Lis) to amino terminated oligo (ethylene glycol)-capped gold nanoparticles (NH2-TEG-AuNPs) was used to fabricate an in-house lateral flow strip (LFS), namely, the fixed "end-on" Lis-mAb-NH-TEG-AuNPs LFS. The aim was to evaluate the performance of the fixed "end-on" Lis-mAb-NH-TEG-AuNPs LFS in detecting L. monocytogenes. The proposed LFS enabled the sensitive detection of L. monocytogenes in 15 min with a visual limit of detection of 102 CFU/mL. Quantitative analysis indicated an LOD at 10 CFU/mL. The fixed "end-on" Lis-mAb-NH-TEG-AuNPs LFS showed no cross-reactivity with other pathogenic bacteria and practical performance across different food matrices, including human blood, milk, and mushroom samples. Furthermore, the clinical performance of the fixed "end-on" Lis-mAb-NH-TEG-AuNPs LFS for detecting L. monocytogenes was evaluated by using 12 clinical samples validated by the hemoculture method. It demonstrated excellent concordance with the reference methods, with no false-positive or false-negative results observed. Therefore, the fixed "end-on" Lis-mAb-NH-TEG-AuNPs LFS serves as a promising candidate for a point-of-care test (POCT), enabling the rapid, precise, and highly sensitive detection of L. monocytogenes in clinical samples and contaminated food.

Advancing MicroRNA Detection: Enhanced Biotin-Streptavidin Dual-Mode Phase Imaging Surface Plasmon Resonance Aptasensor.

MicroRNAs (miRNAs) are novel tumor biomarkers owing to their important physiological functions in cell communication and the progression of multiple diseases. Due to the small molecular weight, short sequence length, and low concentration levels of miRNA, miRNA detection presents substantial challenges, requiring the advancement of more refined and sensitive techniques. There is an urgent demand for the development of a rapid, user-friendly, and sensitive miRNA analysis method. Here, we developed an enhanced biotin-streptavidin dual-mode phase imaging surface plasmon resonance (PI-SPR) aptasensor for sensitive and rapid detection of miRNA. Initially, we evaluated the linear sensing range for miRNA detection across two distinct sensing modalities and investigated the physical factors that influence the sensing signal in the aptamer-miRNA interaction within the PI-SPR aptasensor. Then, an enhanced biotin-streptavidin amplification strategy was introduced in the PI-SPR aptasensor, which effectively reduced the nonspecific adsorption by 20% and improved the limit of detection by 548 times. Furthermore, we have produced three types of tumor marker chips, which utilize the rapid sensing mode (less than 2 min) of PI-SPR aptasensor to achieve simultaneous detection of multiple miRNA markers in the serum from clinical cancer patients. This work not only developed a new approach to detect miRNA in different application scenarios but also provided a new reference for the application of the biotin-streptavidin amplification system in the detection of other small biomolecules.

A Novel MXene@MOF@Pt NPs-Based Enzyme-Free Electrochemical Sensor for highly Sensitive Detection of Hydrogen Peroxide Released from Living Cells

A Novel MXene@MOF@Pt NPs-Based Enzyme-Free Electrochemical Sensor for highly Sensitive Detection of Hydrogen Peroxide Released from Living Cells

RFX6 haploinsufficiency predisposes to diabetes through impaired beta cell function.

Regulatory factor X 6 (RFX6) is crucial for pancreatic endocrine development and differentiation. The RFX6 variant p.His293LeufsTer7 is significantly enriched in the Finnish population, with almost 1:250 individuals as a carrier. Importantly, the FinnGen study indicates a high predisposition for heterozygous carriers to develop type 2 and gestational diabetes. However, the precise mechanism of this predisposition remains unknown. To understand the role of this variant in beta cell development and function, we used CRISPR technology to generate allelic series of pluripotent stem cells. We created two isogenic stem cell models: a human embryonic stem cell model; and a patient-derived stem cell model. Both were differentiated into pancreatic islet lineages (stem-cell-derived islets, SC-islets), followed by implantation in immunocompromised NOD-SCID-Gamma mice. Stem cell models of the homozygous variant RFX6-/- predictably failed to generate insulin-secreting pancreatic beta cells, mirroring the phenotype observed in Mitchell-Riley syndrome. Notably, at the pancreatic endocrine stage, there was an upregulation of precursor markers NEUROG3 and SOX9, accompanied by increased apoptosis. Intriguingly, heterozygous RFX6+/- SC-islets exhibited RFX6 haploinsufficiency (54.2% reduction in protein expression), associated with reduced beta cell maturation markers, altered calcium signalling and impaired insulin secretion (62% and 54% reduction in basal and high glucose conditions, respectively). However, RFX6 haploinsufficiency did not have an impact on beta cell number or insulin content. The reduced insulin secretion persisted after in vivo implantation in mice, aligning with the increased risk of variant carriers to develop diabetes. Our allelic series isogenic SC-islet models represent a powerful tool to elucidate specific aetiologies of diabetes in humans, enabling the sensitive detection of aberrations in both beta cell development and function. We highlight the critical role of RFX6 in augmenting and maintaining the pancreatic progenitor pool, with an endocrine roadblock and increased cell death upon its loss. We demonstrate that RFX6 haploinsufficiency does not affect beta cell number or insulin content but does impair function, predisposing heterozygous carriers of loss-of-function variants to diabetes. Ultra-deep bulk RNA-seq data for pancreatic differentiation stages 3, 5 and 7 of H1 RFX6 genotypes are deposited in the Gene Expression Omnibus database with accession code GSE234289. Original western blot images are deposited at Mendeley ( https://data.mendeley.com/datasets/g75drr3mgw/2 ).

On-Chip Annealing Using Embedded Micro-Heater for Highly Sensitive and Selective Gas Detection.

The demand for gas sensing systems that enable fast and precise gas recognition is growing rapidly. However, substantial challenges arise from the complex fabrication process of sensor arrays, time-consuming data transmission to an external processor, and high energy consumption in multi-stage data processing. In this study, a gas sensing system using on-chip annealing for fast and power-efficient gas detection is proposed. By utilizing a micro-heater embedded in the gas sensor, the sensing material of adjacent sensors in the same substrate can be easily varied without further fabrication steps. The response to oxidizing gas is constrained in metal oxide (MOX) sensing material with small grain sizes, as the depletion width of grain cannot extend beyond the grain size during the gas reaction. On the other hand, the response to reducing gases and humidity, which decrease the depletion width, is less affected by grain sizes. A readout circuit integrating a differential amplifier and dual FET-type gas sensors effectively emphasizes the response to oxidizing gases by canceling the response to reducing gases and humidity. The selective on-chip annealing method is applicable to various MOX sensing materials, demonstrating its potential for application in commercial fields due to its simplicity and expandability.

Coumarin-Modified Starch Fluorescent Nanoparticles as Sensor of Fe3+ and Zn2+ ions Utilizing Dynamic Quenching and Chelation Mechanisms.

Zinc and iron are two essential trace minerals that play a pivotal role in maintaining optimal health and well-being in the human body. Despite being required in relatively small quantities, their significance can be understated as they participate in a wide array of critical physiological processes such as oxygen transport, DNA synthesis, controlling nutrient availability, etc. Understanding the distribution and behavior of these ions in natural water bodies is essential for assessing water quality, studying ecological processes, and managing environmental impacts. In this study, we have developed a dual fluorescence probe using starch which was functionalized with coumarin derivatives, for efficient detection of Fe3+ and Zn2+ ions. This structure led a self-assembled starch/coumarin (SC) fluorescent nanoparticles with strong fluorescence intensity under ultraviolet light (365nm). The quenching effect of Fe3+ on the SC fluorescent probe enabled efficient specific detection of Fe3+. Furthermore, Zn2+ ions increased fluorescence intensity of coumarin compounds (λemission = 459). This phenomenon occurs when the coumarin compound forms a complex or interacts with the zinc ion, resulting in enhanced fluorescence emission. In summary, the developed fluorescent probe offered a promising approach for sensitive and specific detection of iron and zinc ions in aqueous solutions.

Dielectrophoresis: Measurement technologies and auxiliary sensing applications.

Dielectrophoresis (DEP), which arises from the interaction between dielectric particles and an aqueous solution in a nonuniform electric field, contributes to the manipulation of nano and microparticles in many fields, including colloid physics, analytical chemistry, molecular biology, clinical medicine, and pharmaceutics. The measurement of the DEP force could provide a more complete solution for verifying current classical DEP theories. This review reports various imaging, fluidic, optical, and mechanical approaches for measuring the DEP forces at different amplitudes and frequencies. The integration of DEP technology into sensors enables fast response, high sensitivity, precise discrimination, and label-free detection of proteins, bacteria, colloidal particles, and cells. Therefore, this review provides an in-depth overview of DEP-based fabrication and measurements. Depending on the measurement requirements, DEP manipulation can be classified into assistance and integration approaches to improve sensor performance. To this end, an overview is dedicated to developing the concept of trapping-on-sensing, improving its structure and performance, and realizing fully DEP-assisted lab-on-a-chip systems.

Fusarium mycotoxins: The major food contaminants

AbstractMycotoxins, which are secondary metabolites produced by toxicogenic fungi, are natural food toxins that cause acute and chronic adverse reactions in humans and animals. The genus Fusarium is one of three major genera of mycotoxin‐producing fungi. Trichothecenes, fumonisins, and zearalenone are the major Fusarium mycotoxins that occur worldwide. Fusarium mycotoxins have the potential to infiltrate the human food chain via contamination during crop production and food processing, eventually threatening human health. The occurrence and development of Fusarium mycotoxin contamination will change with climate change, especially with variations in temperature, precipitation, and carbon dioxide concentration. To address these challenges, researchers have built a series of effective models to forecast the occurrence of Fusarium mycotoxins and provide guidance for crop production. Fusarium mycotoxins frequently exist in food products at extremely low levels, thus necessitating the development of highly sensitive and reliable detection techniques. Numerous successful detection methods have been developed to meet the requirements of various situations, and an increasing number of methods are moving toward high‐throughput features. Although Fusarium mycotoxins cannot be completely eliminated, numerous agronomic, chemical, physical, and biological methods can lower Fusarium mycotoxin contamination to safe levels during the preharvest and postharvest stages. These theoretical innovations and technological advances have the potential to facilitate the development of comprehensive strategies for effectively managing Fusarium mycotoxin contamination in the future.

Metal-ligand cross-link strategy engineered iron-doped dopamine-based superstructure as peroxidase-like nanozymes for detection of glucose.

Nanozymes are nanomaterials with mimetic enzyme properties and the related research has attracted much attention. It is of great value to develop methods to construct nanozymes and to study their application in bioanalysis. Herein, the metal-ligand cross-linking strategy was developed to fabricate superstructure nanozymes. This strategy takes advantage of beingeasy to operate, adjustable, cheap, and universal. The fabricated superstructure nanozymes possess efficient peroxidase-like catalytic activity. The enzyme reaction kinetic tests demonstrated that for TMB and H2O2, the Km is 0.229 and 1.308mM, respectively. Furthermore, these superstructure nanozymes are applied to highly efficient and sensitive detection of glucose. The linear range for detecting glucose is 20-2000μM, and the limit of detection is 17.5μM. Furthermore, mechanistic research illustrated that this integrated system oxidizes glucose to produce hydrogen peroxide and further catalyzes the production of ·OH and O2·-, which results in a chromogenic reaction of oxidized TMB for the detection of glucose. This work could not only contribute to the development of efficient nanozymes but also inspire research in the highly sensitive detection of other biomarkers.

Hexagonal Boron Nitride Quantum Dots Embedded on Layer-by-Layer Films for Peroxidase-Assisted Colorimetric Detection of β-Galactosidase Producing Pathogens.

Pathogen detection has become a major research area all over the world for water quality surveillance and microbial risk assessment. Therefore, designing simple and sensitive detection kits plays a key role in envisaging and evaluating the risk of disease outbreaks and providing quality healthcare settings. Herein, we have designed a facile and low-cost colorimetric sensing strategy for the selective and sensitive determination of β-galactosidase producing pathogens. The hexagonal boron nitride quantum dots (h-BN QDs) were established as a nanozyme that showed prominent peroxidase-like activity, which catalyzes 3,3',5,5'-tetramethylbenzidine (TMB) oxidation by H2O2. The h-BN QDs were embedded on a layer-by-layer assembled agarose biopolymer. The β-galactosidase enzyme partially degrades β-1,4 glycosidic bonds of agarose polymer, resulting in accessibility of h-BN QDs on the solid surface. This assay can be conveniently conducted and analyzed by monitoring the blue color formation due to TMB oxidation within 30 min. The nanocomposite was stable for more than 90 days and was showing TMB oxidation after incubating it with Escherichia coli (E. coli). The limit of detection was calculated to be 1.8 × 106 and 1.5 × 106 CFU/mL for E. coli and Klebsiella pneumonia (K. pneumonia), respectively. Furthermore, this novel sensing approach is an attractive platform that was successfully applied to detect E. coli in spiked water samples and other food products with good accuracy, indicating its practical applicability for the detection of pathogens in real samples.

Polymer-integrated acoustic graphene plasmon resonator for sensitive detection of CO2 gas

Abstract Acoustic graphene plasmons exhibit an exceptional density of electromagnetic states within the mid-infrared and terahertz frequency ranges, leading to a pronounced near-field amplification and localization at the nanometer scale. This characteristic renders them highly promising for the development of ultra-sensitive plasmon-enhanced mid-infrared sensing and spectroscopic applications. However, the tight spatial confinement inherent to acoustic graphene plasmons results in a significant momentum mismatch, which in turn leads to poor coupling efficiency with light in free space. To overcome this limitation, we leverage numerical simulations to show that graphene plasmons can act as an intermediary to facilitate efficient excitation of acoustic graphene plasmons by incident mid-infrared radiation, achieving an extinction spectrum peak value of approximately 0.9. The proposed gas sensor based on the acoustic graphene plasmon resonator is composed of pristine, large-area graphene, an array of periodic metal nanocubes, and a slender polyethylenimine layer that adsorbs CO2, situated between the nanocubes and the graphene sheet. The sensing performance of the proposed sensor is numerically investigated. It is demonstrated that by incorporating a CO2-absorbing material into the acoustic graphene plasmons, we can perform highly sensitive assessments of the absorption bands within the polyethylenimine layer upon CO2 adsorption. The observed behavior of the acoustic graphene plasmons indicates a weakening and broadening with increasing CO2 concentrations, a phenomenon attributed to the alteration in the permittivity of the polyethylenimine in the interstitial layer due to CO2 adsorption. Numerical simulation results indicate that the sensitivity of the proposed hybrid gas sensor can reach up to 0.0183‰ ppm-1, which offers a remarkable 95-fold enhancement over the gas sensor based on graphene nanoribbons. Our findings underscore the potential of acoustic graphene plasmon nanoresonators as a transformative platform for ultrasensitive plasmon-enhanced sensing applications, particularly when integrated with various gas adsorption layers or molecular agents.

A portable transistor immunosensor for fast identification of porcine epidemic diarrhea virus

Widespread distribution of porcine epidemic diarrhea virus (PEDV) has led to catastrophic losses to the global pig farming industry. As a result, there is an urgent need for rapid, sensitive and accurate tests for PEDV to enable timely and effective interventions. In the present study, we develop and validate a floating gate carbon nanotubes field-effect transistor (FG CNT-FET)-based portable immunosensor for rapid identification of PEDV in a sensitive and accurate manner. To improve the affinity, a unique PEDV spike protein-specific monoclonal antibody is prepared by purification, and subsequently modified on FG CNT-FET sensor to recognize PEDV. The developed FET biosensor enables highly sensitive detection (LoD: 8.1 fg/mL and 100.14 TCID50/mL for recombinant spike proteins and PEDV, respectively), as well as satisfactory specificity. Notably, an integrated portable platform consisting of a pluggable FG CNT-FET chip and a portable device can discriminate PEDV positive from negative samples and even identify PEDV and porcine deltacoronavirus within 1 min with 100% accuracy. The portable sensing platform offers the capability to quickly, sensitively and accurately identify PEDV, which further points to a possibility of point of care (POC) applications of large-scale surveillance in pig breeding facilities.

Near-infrared fluorescent probe for selective and sensitive detection of glutathione based on thioctic acid-functionalized Ag/Au NCs-assisted by ferric ion

Accurate determination of glutathione (GSH) levels in biological fluids and food supplements is paramount. To address this need, we developed a near-infrared (NIR) fluorescent probe with high sensitivity and selectivity for GSH detection. This probe comprises thioctic acid-functionalized silver and gold nanoclusters (ThA@Ag/Au NCs), emitting red light at 720 nm upon excitation at 310 nm. In the presence of Fe3+ ions, which form complexes with ThA, the fluorescence of ThA@Ag/Au NCs is quenched due to aggregation. However, upon addition of GSH, a potent chelator for Fe3+, the fluorescence of the probe is restored, leading to enhanced emission. Under optimized conditions, the fluorescence response (F/F°) exhibits a linear relationship with increasing GSH concentration within the range of 0.03–95 µM, achieving a limit of detection (LOD) of 9.0 nM. This designed scheme demonstrates excellent selectivity, sensitivity, and accuracy for GSH detection. Furthermore, the NIR fluorescent probe effectively estimated GSH levels in various matrices, including capsules, serum, urine, and saliva samples, yielding recoveries % ranging from 97.2 % to 103.2 %, with RSD % below 4.34 %. Due to its NIR properties, this fluorescent probe holds promise for diagnosing various diseases and potential in vivo applications.

Synthesis of polyvinylpyrrolidone-protected silver nanoclusters with strong fluorescence for highly sensitive and selective hexavalent chromium ion detection

Synthesis of polyvinylpyrrolidone-protected silver nanoclusters with strong fluorescence for highly sensitive and selective hexavalent chromium ion detection

A multifunctional fluorescent Eu‐MOF probe: Its synthesis, structure, and sensing properties

Based on 3‐(2,4‐dicarboxylphenyl)‐6‐carboxylpyridine ligand (H3dpcp), a lanthanide metal–organic framework with the porous three‐dimensional structure was successfully synthesized, namely, [Eu (dpcp)(H2O)]n (1). The experimental results indicated that complex 1 exhibited stable luminescence in the range of pH = 2–11 in aqueous solution. It is noteworthy that complex 1 could recognize tryptophan (Trp) and trans, trans‐muconic acid (tt‐MA) molecules through the fluorescence quenching effect, and showed high sensitivity, selectivity, recoverability, anti‐interference, and low detection limits for the identification of Trp and tt‐MA in aqueous solution. In addition, the fluorescence mechanisms of complex 1 for sensing of tt‐MA and Trp were elucidated in detail.

A novel nanosheets assembled porous fusiform Co2P2O7 for sensitive electrochemical detection of ultratrace As(III) ions

A facile and low-cost method was used to synthesize a novel nanosheets assembled porous fusiform Co2P2O7 for ultrasensitive electrochemical sensing detection of As(III) in water. The porous fusiform Co2P2O7 formed by small nanosheets exhibits a three-dimensional porous structure with a rough surface and good dispersion, facilitating a well-connected electron transfer path and providing numerous electroactive sites to bind with As(III). The proposed electrochemical sensor exhibited a high sensitivity of 91.04 µA µg/L cm−2 and a low detection limit of 0.087 µg/L towards As(III) in 0.1 M HAc-NaAc buffer (pH 5.0). Furthermore, it exhibited great potential for the electrochemical detection of As(III) in tap water.

Photocatalytic colorimetry and fluorescence dual-signal biosensor for instant determination of terminal deoxynucleotidyl transferase

Terminal deoxynucleotidyl transferase (TdT) is a crucial biomarker for diseases such as lymphoblastic leukemia. Herein, a photocatalytic colorimetry and fluorescence dual-signal biosensor (PhoCoF-sensor) for simple, low-cost and sensitive detection of TdT was developed, which integrated with the TdT-triggered polymerization reaction and the fluorescence-photocatalytic dual performance of double-strand DNA/SYBR Green-I (dsDNA/SG-I) complex. The target TdT catalyzed the elongation of single-stranded DNA in the dTTP substrate pool, and then hybridized with complementary DNA to form dsDNA/SG-I complex that exhibited obvious fluorescent and excellent photocatalytic activity. Reactive oxygen species were generated from photosensitization of the dsDNA/SG-I complex acted as the visual colorimetric readout. The PhoCoF-sensor was successfully used to detect TdT activity with a series of color and fluorescence changes in the concentration range from 0.5 U/mL to 20.0 U/mL. The PhoCoF-sensor further improves the assay simplicity and accuracy and reduces the time and cost, which overcomes the limitations of traditional detection TdT methods and single-signal sensors. Additionally, this PhoCoF-sensor can readily be integrated with centrifugal microfluidic device for one-step test and achieve quantitative determination without sophisticated instruments. Moreover, the PhoCoF-sensor has good sensitivity and good practical reliability and is suitable for instant determination in early disease diagnosis and drug discovery.