High Sensitivity Detection Research Articles

Pseudotyped Viruses: A Useful Platform for Pre-Clinical Studies Conducted in a BSL-2 Laboratory Setting

The study of pathogenic viruses has always posed significant biosafety challenges. In particular, the study of highly pathogenic viruses requires methods with low biological risk but relatively high sensitivity and convenience in detection. In recent years, pseudoviruses, which consist of a backbone of one virus and envelope proteins of another virus, have become one of the most widely used tools for exploring the mechanisms of viruses binding to cells, membrane fusion and viral entry, as well as for screening the libraries of antiviral substances, evaluating the potential of neutralizing monoclonal antibodies, developing neutralization tests, and therapeutic platforms. During the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), pseudotyped virus-based assays played a pivotal role in advancing our understanding of virus–cell interactions and the role of its proteins in disease pathogenesis. Such tools facilitated the search for potential therapeutic agents and accelerated epidemiological studies on post-infection and post-vaccination humoral immunity. This review focuses on the use of pseudoviruses as a model for large-scale applications to study enveloped viruses.

Fluorescence Detection of DNA/RNA G-Quadruplexes (G4s) by Twice-as-Smart Ligands.

Fluorescence detection of DNA and RNA G-quadruplexes (G4s) is a very efficient strategy to assess not only the existence and prevalence of cellular G4s but also their relevance as targets for therapeutic interventions. Among the fluorophores used to this end, turn-on probes are the most interesting since their fluorescence is triggered only upon interaction with their G4 targets, which ensures a high sensitivity and selectivity of detection. We reported on a series of twice-as-smart G4 probes, which are both smart G4 ligands (whose structure is reorganized upon interaction with G4s) and smart fluorescent probes (whose fluorescence is turned on upon interaction with G4s). The fine mechanistic details behind the excellent properties of the best prototype N-TASQ remain to be deciphered: to investigate this, we report here on the synthesis and studies of two analogues, TzN-TASQ and AlkN-TASQ, and on a careful analysis of their G4-interacting properties, investigated both in vitro and in silico. Our results show that fine-tuning their constitutive structural elements allows for increasing the efficiency of both their 'off' (i. e., a conformation with a low fluorescence) and 'on' states (i. e., a conformation with a high fluorescence), which opens interesting ways for the design of more efficient fluorogenic G4 probes.

Broadband photothermal spectroscopy with a mid-infrared quantum cascade laser frequency comb

We demonstrate a broadband photothermal spectroscopy in the mid-infrared region using a quantum cascade laser frequency comb operating between ∼7.7 and ∼8.2 µm covering a frequency range of ∼70 cm-1. The photothermal spectroscopy technique employs a Mach-Zehnder interferometer operating in a pump-probe configuration, where the mid-infrared pump beam is modulated by a Fourier transform spectrometer. A 76-m Herriott-type multipass cell is used for signal enhancement. As a proof-of-concept, we have measured the photothermal spectra of nitrous oxide that show good agreement with the HITRAN database. A minimum detection limit of 83 ppb of nitrous oxide in nitrogen is estimated from a broadband photothermal spectrum with 9.9 GHz spectral point spacing and acquired over 78 minutes. This detection scheme also provides over three orders of magnitude of photothermal signal linearity with gas concentration. This spectroscopic method combines the functionality of high sensitivity and background-free detection of photothermal spectroscopy as well as broadband mid-infrared operation of quantum cascade laser frequency comb, which could find applications in trace gas sensing systems that benefit from these features.

SERS Detection of Hydrophobic Molecules: Thio-β-Cyclodextrin-Driven Rapid Self-Assembly of Uniform Silver Nanoparticle Monolayers and Analyte Trapping

High-sensitivity and repeatable detection of hydrophobic molecules through the surface-enhanced Raman scattering (SERS) technique is a tough challenge because of their weak adsorption and non-uniform distribution on SERS substrates. In this research, we present a simple self-assembly protocol for monolayer SERS mediated by 6-deoxy-6-thio-β-cyclodextrin (β-CD-SH). This protocol allows for the rapid assembly of a compact silver nanoparticle (Ag NP) monolayer at the oil/water interface within 40 s, while entrapping analyte molecules within hotspots. The proposed method shows general applicability for detecting hydrophobic molecules, exemplified as Nile blue, Nile red, fluconazole, carbendazim, benz[a]anthracene, and bisphenol A. The detection limits range from 10−6to 10−9 M, and the relative standard deviations (RSDs) of signal intensity are less than 10%. Moreover, this method was used to investigate the release behaviors of a hydrophobic pollutant (Nile blue) adsorbed on the nanoplastic surface in the water environment. The results suggest that elevated temperatures, increased salinities, and the coexistence of fulvic acid promote the release of Nile blue. This simple and fast protocol overcomes the difficulties related to hotspot accessibility and detection repeatability for hydrophobic analytes, holding out extensive application prospects in environmental monitoring and chemical analysis.

High-Sensitivity Hydrogen Detection Based on Thermo-Optical Effect of Liquid Sealed in a Hollow-Core Fiber Interferometer

High-Sensitivity Hydrogen Detection Based on Thermo-Optical Effect of Liquid Sealed in a Hollow-Core Fiber Interferometer

Green Synthesis of Eosin-Y Coated Silver Nanoparticles for Sensitive and Selective Fluorometric Detection of L-Dopa.

This study is to produce biogenic silver nanoparticles (AgNPs) by utilizing aqueous extracts derived from Turnera Sublata (TS) leaves under visible light. Subsequently, these nanoparticles are coated with eosin-yellow (EY) to enhance sensitivity and selectivity in L-3,4-dihydroxyphenylalanine (L-dopa) detection. This method encompasses the deposition of metal onto the Ag NPs, resulting in the formation of EY-AgNPs. The crystalline, spherical nanoparticles, prepared as described, exhibit a particle size of 20nm. Different instruments were used to characterize them, including UV-Vis spectroscopy, fluorescence spectroscopy, FTIR spectroscopy, selected area electron diffraction (SAED), transmission electron microscopy (TEM), and X-ray diffraction (XRD) analysis. The spherical structured morphology and size of the EY-AgNPs has been confirmed through SAED and TEM studies. This study pioneered the integration of characteristic hydroxyl-Ag chemistry and specialized steric interference of organic pigment in luminescent AgNPs to develop a simple method for detecting dopa. The sensor's dynamic range and limit of detection were assessed. Experimental results revealed that green-emitting AgNPs shielded by interference from biogenic AgNPs and the strong affinity of hydroxyl-silver provided a high-sensitivity detection limit of 1.84 nM. Furthermore, a new green approach for sensor development using human serum albumin (HSA) assay demonstrated that organic dye on the surface of nanomaterials further enhances sensing properties.

Characterization of adrenal glands on computed tomography with a 3D V-Net-based model

ObjectivesTo evaluate the performance of a 3D V-Net-based segmentation model of adrenal lesions in characterizing adrenal glands as normal or abnormal.MethodsA total of 1086 CT image series with focal adrenal lesions were retrospectively collected, annotated, and used for the training of the adrenal lesion segmentation model. The dice similarity coefficient (DSC) of the test set was used to evaluate the segmentation performance. The other cohort, consisting of 959 patients with pathologically confirmed adrenal lesions (external validation dataset 1), was included for validation of the classification performance of this model. Then, another consecutive cohort of patients with a history of malignancy (N = 479) was used for validation in the screening population (external validation dataset 2). Parameters of sensitivity, accuracy, etc., were used, and the performance of the model was compared to the radiology report in these validation scenes.ResultsThe DSC of the test set of the segmentation model was 0.900 (0.810–0.965) (median (interquartile range)). The model showed sensitivities and accuracies of 99.7%, 98.3% and 87.2%, 62.2% in external validation datasets 1 and 2, respectively. It showed no significant difference comparing to radiology reports in external validation datasets 1 and lesion-containing groups of external validation datasets 2 (p = 1.000 and p > 0.05, respectively).ConclusionThe 3D V-Net-based segmentation model of adrenal lesions can be used for the binary classification of adrenal glands.Critical relevance statementA 3D V-Net-based segmentation model of adrenal lesions can be used for the detection of abnormalities of adrenal glands, with a high accuracy in the pre-surgical scene as well as a high sensitivity in the screening scene.Key PointsAdrenal lesions may be prone to inter-observer variability in routine diagnostic workflow.The study developed a 3D V-Net-based segmentation model of adrenal lesions with DSC 0.900 in the test set.The model showed high sensitivity and accuracy of abnormalities detection in different scenes.Graphical

Graphene-Based, Flexible, Wearable Piezoresistive Sensors with High Sensitivity for Tiny Pressure Detection

Flexible, wearable, piezoresistive sensors have significant potential for applications in wearable electronics and electronic skin fields due to their simple structure and durability. Highly sensitive, flexible, piezoresistive sensors with the ability to monitor laryngeal articulatory vibration supply a new, more comfortable and versatile way to aid communication for people with speech disorders. Here, we present a piezoresistive sensor with a novel microstructure that combines insulating and conductive properties. The microstructure has insulating polystyrene (PS) microspheres sandwiched between a graphene oxide (GO) film and a metallic nanocopper-graphene oxide (n-Cu/GO) film. The piezoresistive performance of the sensor can be modulated by controlling the size of the PS microspheres and doping degree of the copper nanoparticles. The sensor demonstrates a high sensitivity of 232.5 kPa−1 in a low-pressure range of 0 to 0.2 kPa, with a fast response of 45 ms and a recovery time of 36 ms, while also exhibiting excellent stability. The piezoresistive performance converts subtle laryngeal articulatory vibration into a stable, regular electrical signal; in addition, there is excellent real-time monitoring capability of human joint movements. This work provides a new idea for the development of wearable electronic devices, healthcare, and other fields.

Advances of immunosensors based on noble metal composite materials for detecting procalcitonin.

Procalcitonin (PCT) is a reliable biomarker for diagnosing and monitoring bacterial infections and sepsis. PCT exhibits good stability both in vivo and in vitro, and its levels drastically increase in response to bacterial infection or inflammatory reactions in the human body, making it a dependable indicator for sepsis diagnosis and monitoring with significant implications for clinical diagnosis and treatment guidance. Currently, immunosensors are widely utilized in PCT detection due to their high sensitivity and low detection limits. Noble metals, because of their excellent electronic conductivity, biocompatibility, and superior physicochemical properties, are extensively combined with other materials to play a pivotal role in the construction of PCT immunosensors. This review summarizes the research progress on PCT antigen immunosensors based on noble metal composite materials, encompassing the classification and principles of immunosensors. Starting from noble metals, which are widely used as electrode materials in sensors, the review categorizes and discusses the carbon materials, metal oxides, metal sulfides, and other composites with noble metals. The reviewalso elaborates on the influence of sensitive materials on the performance of immunosensors. Finally, the review discusses and anticipates the challenges and future opportunities for the research on PCT antigen immunosensors using noble metal-composite nanomaterials, providing new insights and directions for their application in the treatment and clinical management of sepsis and other diseases.

Open-set deep learning-enabled single-cell Raman spectroscopy for rapid identification of airborne pathogens in real-world environments.

Pathogenic bioaerosols are critical for outbreaks of airborne disease; however, rapidly and accurately identifying pathogens directly from complex air environments remains highly challenging. We present an advanced method that combines open-set deep learning (OSDL) with single-cell Raman spectroscopy to identify pathogens in real-world air containing diverse unknown indigenous bacteria that cannot be fully included in training sets. To test and further enhance identification, we constructed the Raman datasets of aerosolized bacteria. Through optimizing OSDL algorithms and training strategies, Raman-OSDL achieves 93% accuracy for five target airborne pathogens, 84% accuracy for untrained air bacteria, and 36% reduction in false positive rates compared to conventional close-set algorithms. It offers a high detection sensitivity down to 1:1000. When applied to real air containing >4600 bacterial species, our method accurately identifies single or multiple pathogens simultaneously within an hour. This single-cell tool advances rapidly surveilling pathogens in complex environments to prevent infection transmission.

Ultrasensitive "On-Off" Ratiometric Fluorescence Biosensor Based on RPA-CRISPR/Cas12a for Detection of Staphylococcus aureus.

Staphylococcus aureus (S. aureus) is a major pathogenic bacterium responsible for bacterial foodborne diseases, making its rapid, specific, and accurate detection crucial. In this study, we develop a ratiometric biosensor based on the recombinase polymerase amplification-clustered regularly interspaced short palindromic repeats/CRISPR associated protein 12a (RPA-CRISPR/Cas12a) system and Eu-metal-organic framework (Eu-MOF) fluorescent nanomaterials for the high-sensitivity detection of S. aureus, combining with RPA for efficient isothermal amplification, this sensor enhances specificity and sensitivity by utilizing the target activation of CRISPR/Cas12a. The Eu-MOF serves a dual function, providing stable red fluorescence as a reference signal and adsorbing FAM-labeled probes for fluorescence quenching, forming a dual-signal system that significantly reduces background interference. This ratiometric design enables accurate and quantitative detection over a wide range (7.9 × 100 to 7.9 × 108 CFU/mL) with a low detection limit of 3 CFU/mL. Overall, with these merits of simplicity, rapid response, high sensitivity, and specificity, this dual-signal biosensor offers a promising method for accurately evaluating S. aureus contamination in food under complex substrate conditions.

Polarity Sensor Based on Multivariate Lanthanide Metal-Organic Framework for Constructing Biosensing Platform.

It is significant but challenging to develop polarity sensors that can measure multiscenario polarity in a modular, customized, sensitive, and accurate manner. In this work, we proposed a polarity sensor based on multivariate lanthanide metal-organic framework (Ln-MOF) nanoclusters through the modular programming design of ligands. This multivariate Ln-MOF combines the advantages of modularity, ease of design, high flexibility and low cost, and can be precisely customized for different polarity systems. The MOF Eu0.1Tb0.9-isophthalic acid (IPA) and Eu0.3Tb0.7-o-phthalic acid (OPA) are suitable for the detection of trace water in dimethylsulfoxide (DMSO) and hyaluronidase activity, respectively. Especially, Eu0.3Tb0.7-OPA can achieve high-sensitivity detection of hyaluronidase activity within 8 min, with the limit of detection as low as 0.016 U/L. The results enable us to break through our previous understanding of polarity parameter, allowing us to develop more polarity-related biosensing platforms. Ln-MOFs are believed to utilize their adjustable polar intermolecular interactions to achieve the optimal compatibility and high sensitivity in polarity sensing systems, which is supported by experiments and density functional theory calculations. These polarity sensors based on multivariate Ln-MOF nanoclusters offer significant potential in biosensing and medical diagnostics, overcoming traditional biosensor limitations in synthesis and customization.

A Copper Sulfide Doped 2D‐MXene‐Based Ultrasensitive Label‐Free Electrochemical Immunosensor for EpCAM Antigen Detection

ABSTRACTHerein, a novel CuS‐anchored 2D‐Ti3C2Tx composite material was synthesized by a one‐pot hydrothermal method. This CuS/Ti3C2Tx hybrid was used to prepare a novel label‐free electrochemical immunosensor for EpCAM antigen detection. The immunosensor has been fabricated by electrophoretic deposition of CuS/Ti3C2Tx hybrid onto the ITO electrode followed by the immobilization of anti‐EpCAM. The electrochemical biosensing studies of this fabricated immunosensor, BSA/anti‐EpCAM/CuS/Ti3C2Tx@ITO demonstrated a wide linear range (0.01 fg/mL to 100 ng/mL) and low LOD (0.0057 fg/mL), together with high sensitivity (461.85 μA fg−1 mL cm−2) for EpCAM antigen detection. The clinical validation of the proposed immunosensor was conducted with serum samples. Moreover, the immunosensor was found to be reproducible, specific, selective, and stable over a long period of 42 days.

Constructing a Self-Referenced NIR-II Thermometer with Energy Tuning of Coordinating Water Molecules by a Minimalist Method.

Fluorescence thermometry based on metal halide perovskites is increasingly becoming a hotspot due to its advantages of high detection sensitivity, noninvasiveness, and fast response time. However, it still presents certain technical challenges in practical applications, such as complex synthesis methods, the use of toxic solvents, and being currently mainly based on the visible/first near-infrared light with poor penetration and severe autofluorescence. In this study, we synthesize the second near-infrared (NIR-II) luminescent crystals based on Yb3+/Nd3+-doped zero-dimensional Cs2ScCl5·H2O by a simple "dissolve-dry" method. The whole synthesized process does not involve high temperatures or high pressures. Cs2ScCl5·H2O/Yb3+,Nd3+ has an optimum fluorescence performance when the Yb3+/Nd3+ doping amount is 15%/20%. The emission intensity ratio attributed to Yb3+ and Nd3+ varies with temperature, and this variation is exacerbated due to the fact that the 2F5/2 energy level of Yb3+ can be effectively aligned with the O-H bond stretching vibration energy of coordinating water molecules to facilitate energy transfer. Ultimately, the crystals can act as self-referenced ratiometric NIR-II luminescent thermometers with a maximum relative sensitivity of 1.66% K-1 at 323 K. This work highlights the advantages of NIR-II luminescent materials for temperature sensing, which is significant for advancement in the field of noncontact thermometers.

A versatile gold leaf immunosensor with a novel surface functionalization strategy based on protein L and trastuzumab for HER2 detection

Although various sensors specifically developed for target analytes are available, affordable biosensing solutions with broad applicability are limited. In this study, a cost-effective biosensor for detecting human epidermal growth factor receptor 2 (HER2) was developed using custom-made gold leaf electrodes (GLEs). A novel strategy for antibody immobilization on a gold surface, for the first time mediated by protein L and HER2-specific antibody trastuzumab, was examined using commercial screen-printed gold electrodes and GLEs. A self-assembled monolayer of 11-mercaptoundecanoic acid (MUA) was formed on the gold surface, which was used to covalently immobilize protein L. Further binding of trastuzumab to the protein L was employed and HER2 detection was achieved through electrochemical impedance spectroscopy (EIS). The HER2 detection was examined in phosphate-buffered saline (PBS) and supplemented cell culture medium. The modified GLEs showed good specificity and high sensitivity of HER2 detection without any enrichment steps, achieving a limit of detection (LOD) of 1 ng mL− 1 in PBS and 2.7 ng mL− 1 in cell culture medium, making the proposed immunosensor a cost-effective and sensitive solution for detection in complex biological matrices.

Environmental DNA to track endangered Gobiobotia naktongensis: Assessment of distribution and habitat requirements.

Because of their noninvasive nature and high detection sensitivity, eDNA-based aquatic ecosystem surveys are useful for monitoring rare, elusive indicator species. Advancements in statistical techniques have expanded their use beyond simple population tracking to predict potential habitats based on the environmental conditions of sites detected eDNA. This study used species-specific molecular marker and targeted qPCR techniques to assess the distribution and habitat requirements of the endangered Gobiobotia naktongensis, a flagship fish species in Korean sandy river systems with increased public interest related to habitat restoration evaluations associated with dam construction. As a small and sand-burrowing species, G. naktongensis is difficult to identify using traditional sampling methods as its population size has declined because of the construction and operation of dams. However, eDNA investigations have detected genes from the species throughout the year, enabling the identification of stable population sites by comparing with those of historical sampling records. Logistic regression analysis of G. naktongensis eDNA absence/presence and environmental factors revealed that its habitat preferences are closely associated with streambed substrate structure, water quality, and food source diversity. eDNA analytical techniques are being actively used for species that are globally endangered and whose rarity makes population monitoring challenging. eDNA-based surveys are promising for species with small population sizes and species-specific ecological traits (e.g., benthic or sand-burrowing species), which have been limited in quantitative research approaches because of the low occurrence of eDNA in the water, because these methods can yield meaningful results with qualitative data alone.

Amino acid-based, sustainable organic nanozyme and integrated sensing platform for histamine detection.

Inorganic nanozymes hold promise for biomolecule sensing but face challenges like complex fabrication, toxicity, and low sustainability, limiting their use. To overcome these, a sustainable organic nanozyme (OA nanozyme) was created using amino acids and a biocompatible polymer for effective histamine detection. The OA nanozyme exhibits peroxidase-like activity and was fabricated through a single chelation/polymer entanglement method, enabling rapid production (within 3h) with uniform morphology (≤100nm diameter) and a negative surface charge at neutral pH. It shows decent kinetic performance (Km=0.009mM for H2O2) and biocompatibility, making it suitable for biological applications. The OA nanozyme achieved high sensitivity for histamine detection (LOD: 21.37 pgmL-1) with excellent selectivity and specificity against related molecules. The system's ability to detect histamine in real food samples (e.g., spinach) was also confirmed. These findings indicate that the OA nanozyme holds significant potential for broader applications in food safety and quality assurance.

Ag nanoparticles modified WO3 nanospheres structurally designed by NaBH4 have high sensitivity and selectivity for H2S detection at room temperature

Ag nanoparticles modified WO3 nanospheres structurally designed by NaBH4 have high sensitivity and selectivity for H2S detection at room temperature

Advances in detecting non-steroidal anti-inflammatory drugs (NSAIDs) using molecular receptors and nanostructured assemblies.

The detection and quantification of non-steroidal anti-inflammatory drugs (NSAIDs) are crucial due to their widespread use and potential impact on human health and the environment. This review provides a comprehensive survey of the recent advancements in sensing technologies for NSAIDs, focusing on molecular receptors and nanostructured assemblies. Molecular receptors based on different fluorescent molecules such as anthracene, naphthalimide, squaraine, quinoline, BINOL, etc. offer high selectivity and sensitivity for NSAID detection. In parallel, nanostructured assemblies including CdSe/ZnS, Cd/S quantum dots (QDs), carbon dot-containing imprinted polymers, Ag and Au nanoparticles (NPs), hydrogel-embedded chemosensors, etc. were utilized for NSAID detection. This review highlights the different binding pathways with the change of various photophysical properties combining molecular recognition elements with nanomaterials to develop innovative sensors that achieve rapid, sensitive, and selective detection of NSAIDs. The review also discusses current challenges and future prospects in the field and based on reported designed receptors and nanostructured assemblies. To the best of our knowledge, no reviews have been reported on this topic so far. Thus, this review will fruitfully guide researchers to design various new molecular receptors and nanostructured materials to detect NSAIDs.

Terahertz thickness measurement based on atomic superheterodyne detection

Terahertz thickness measurement is of great important in materials research and industrial test. And it’s can be applied in materials measurement including wood, paper, ceramics, plastics, and composite materials. Atomic superheterodyne terahertz detector has extremely high sensitivity. The sensitivity of terahertz electric field strength measurement can reach 5.76 μV cm<sup>-1</sup> Hz<sup>-1/2</sup>. Simultaneously, the linear dynamic range is better than 60 dB. So, it can be applied to realize precise thickness measurement of materials through the terahertz transmission efficiency. The experiments in this paper demonstrated the thickness measurement of sapphire crystal and organic materials PTFE. The terahertz signal is shown in Figure A1(a,b). The thickness can be calculated from the transmittance, which is consistent with the result measured directly with a vernier caliper. Furthermore, single-layer graphene and few-layer graphene can be clearly distinguished from terahertz transmission signals, as shown in Figure A1(c). Even for niobium meta thin films with thickness 1 μm, very weak terahertz signal can be well distinguished due to the high sensitivity of atomic superheterodyne terahertz detector. In summary, the technology developed for terahertz thickness measurement based on atomic superheterodyne detection is very important for defect detection, coating check, and parameter measurement of materials.