Narrow Dynamic Range Research Articles

Simplified shielded MEG-MRI multimodal system with scalar-mode optically pumped magnetometers as MEG sensors

Magnetoencephalography (MEG) conventionally operates within high-performance magnetic shields due to the extremely weak magnetic field signals from the measured objects and the narrow dynamic range of the magnetic sensors employed for detection. This limitation results in elevated equipment costs and restricted usage. Additionally, the information obtained from MEG is functional images, and to analyze from which part of the brain the signals are coming, it is necessary to capture morphological images separately. When MEG and morphological imaging devices are separate, despite their individual high measurement accuracies, discrepancies in positional information may arise. In response, we have developed a low-field magnetic resonance imaging system that incorporates scalar-mode optically pumped magnetometers with a wide dynamic range and exceptionally high measurement sensitivity as sensors for MEG. Operating at low magnetic fields eliminates the need for superconducting coils in magnetic resonance imaging and the high-performance magnetic shields essential for MEG, promising a substantial cost reduction compared to traditional approaches. We achieved a noise level of about 16.7pT/Hz1/2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${16.7}\\,\\hbox {pT/Hz}^{1/2}$$\\end{document} with a single channel magnetometer, and reached a noise level of 367fT/cm/Hz1/2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${367}\\,\\hbox {fT/cm/Hz}^{1/2}$$\\end{document} with a baseline of 1 cm through differential measurements. We employed this system to conduct sequential OPM-based magnetic field measurements and MRI imaging, successfully demonstrating the compatibility of high OPM sensitivity with clear MRI acquisition.

Quantification of autoantibodies using a luminescent profiling method in autoimmune interstitial lung disease

Autoantibodies are important for the diagnosis of autoimmune interstitial lung disease (ILD). Standard immunoassays have limitations, including their qualitative nature and/or a narrow dynamic range of detection, hindering the usefulness of autoantibodies as biomarkers of disease activity. Here, the luciferase immunoprecipitation system (LIPS) was evaluated for measuring myositis-specific and other lung-related autoantibodies in 25 subjects with idiopathic inflammatory myopathies (IIM), 26 with Sjögren’s disease (SjD), and 10 healthy volunteers. LIPS detected a broad dynamic range of autoantibodies, to MDA5, Jo-1, PL12, KS, U1-70K, and Ro52, and matched seropositivity status with established immunoassays. Robust anti-MDA5 autoantibodies in four IIM-ILD patients had a median value of 1,134,000 LU (IQR 473,000-2,317,000), which was 500 times higher than in 21 seronegative IIM patients. Markedly elevated anti-Jo-1 autoantibodies in five IIM-ILD patients demonstrated a median value of 1,177,000 LU (IQR: 604,000-2,520,000), which was 1000-fold higher than in seronegative patients. Robust anti-Ro52 and other anti-tRNA-synthetase autoantibodies were detected in a subset of IIM-ILD subjects. In SjD, only anti-U1-70K and KS autoantibodies were identified in ILD patients with a prevalence of 30% and 20%, respectively. In longitudinal samples of five IIM-ILD patients, anti-Jo-1 autoantibody levels paralleled clinical improvement of lung function. LIPS can accurately quantify autoantibody levels as biomarkers for treatment response in patients with autoimmune ILD.

Application Evaluation and Performance-Directed Improvement of the Native and Engineered Biosensors.

Transcription factor (TF)-based biosensors (TFBs) have received considerable attention in various fields due to their capability of converting biosignals, such as molecule concentrations, into analyzable signals, thereby bypassing the dependence on time-consuming and laborious detection techniques. Natural TFs are evolutionarily optimized to maintain microbial survival and metabolic balance rather than for laboratory scenarios. As a result, native TFBs often exhibit poor performance, such as low specificity, narrow dynamic range, and limited sensitivity, hindering their application in laboratory and industrial settings. This work analyzes four types of regulatory mechanisms underlying TFBs and outlines strategies for constructing efficient sensing systems. Recent advances in TFBs across various usage scenarios are reviewed with a particular focus on the challenges of commercialization. The systematic improvement of TFB performance by modifying the constituent elements is thoroughly discussed. Additionally, we propose future directions of TFBs for developing rapid-responsive biosensors and addressing the challenge of application isolation. Furthermore, we look to the potential of artificial intelligence (AI) technologies and various models for programming TFB genetic circuits. This review sheds light on technical suggestions and fundamental instructions for constructing and engineering TFBs to promote their broader applications in Industry 4.0, including smart biomanufacturing, environmental and food contaminants detection, and medical science.

Impact of Air-Cathodes on Operational Stability of Single-Chamber Microbial Fuel Cell Biosensors for Wastewater Monitoring

The increasing global water pollution leads to the need for urgent development of rapid and accurate water quality monitoring methods. Microbial fuel cells (MFCs) have emerged as real-time biosensors for biochemical oxygen demand (BOD), but they grapple with several challenges, including issues related to reproducibility, operational stability, and cost-effectiveness. These challenges are substantially shaped by the selection of an appropriate air-breathing cathode. Previous studies indicated a critical influence of the cathode on both the enduring electrochemical performance of MFCs and the taxonomic diversity at the electroactive anode. However, the effect of different gas diffusion electrodes (GDE) on 3D-printed single-chamber MFCs for BOD biosensing application and its effect on the bioelectroactive anode was not investigated before. Our study focuses on comparing GDE cathode materials to enhance MFC performance for precise and rapid BOD analysis in wastewater. We examined for over 120 days two Pt-coated air-breathing cathodes with distinct carbonaceous gas diffusion layers (GDLs) and catalyst layers (CLs): cost-effective carbon paper (CP) with hand-coated CL and more expensive woven carbon cloth (CC) with CL pre-applied by the supplier. The results show significant differences in electrochemical characteristics and anodic biofilm composition between MFCs with CP and CC GDE cathodes. CP-MFCs exhibited lower sensitivity (16.6 C L mg−1 m−2) and a narrower dynamic range (25 to 600 mg L−1), attributed to biofouling-related degradation of the GDE. In contrast, CC-MFCs demonstrated superior performance with higher sensitivity (37.6 C L mg−1 m−2) and a broader dynamic range (25 to 800 mg L−1). In conclusion, our study underscores the pivotal role of cathode selection in 3D-printed MFC biosensors, influencing anodic biofilm enrichment time and overall BOD assessment performance. We recommend the use of cost-effective CP GDL with hand-coated CL for short-term MFC biosensor applications, while advocating for CC GDL supplied with CL as the preferred choice for long-term sensing implementations with enduring reliability.

Instrument recognition in unprocessed musical audio through transformer-based modeling

This study focuses on identifying primary instruments in musical audio using an adapted Wav2Vec 2.0 model, initially intended for extracting speech features from raw audio. Modifications to the model's convolutional layers and transformer element were made to facilitate the recognition of instruments in complex audio mixes. The task of instrument recognition is approached as a multi-labelled classification problem. The effectiveness of the model is measured through accuracy, precision, recall, F1-score, and analysis via a confusion matrix. Key findings reveal the model's differential efficiency in recognising various instruments, with notable success in detecting violins, pianos, saxophones, and human voices. However, the model encounters difficulties in recognising instruments with a narrower dynamic range or lower volume, like the organ that may provide harmonic support, and those with scarce representation, such as the cello and clarinet. The research also indicates that while pre-separation of certain instruments like guitars may enhance recognition, it may not be necessary for others.

1β-Hydroxydeoxycholic Acid as an Endogenous Biomarker in Human Plasma for Assessment of CYP3A Clinical Drug-Drug Interaction Potential.

4β-Hydroxycholesterol (4β-HC) in plasma has been used as a biomarker to assess CYP3A drug-drug interaction (DDI) potential during drug development. However, due to the long half-life and narrow dynamic range of 4β-HC, its use has been limited to the identification of CYP3A inducers, but not CYP3A inhibitors. The formation of 1β-hydroxydeoxycholic acid (1β-OH DCA) from deoxycholic acid (DCA) is mediated by CYP3A, thus 1β-OH DCA can potentially serve as an alternative to 4β-HC for assessment of CYP3A DDI potential. To study this feasibility, we developed a sensitive liquid chromatography-tandem mass spectrometry method for the simultaneous quantitation of 1β-OH DCA and its glycine and taurine conjugates in human plasma with the lower limit of quantitation of 50 pg/ml, which enabled the quantitation of basal levels and further reduction. The method was applied to a DDI study to assess how 1β-OH DCA and its glycine and taurine conjugates would respond to CYP3A induction or inhibition. Rifampin induction resulted in an increase of 1β-OH DCA and its conjugates in plasma, with 6.8-, 7.8-, 8.3-, and 10.3-fold increases of area under the curve from the time of dosing to the last measurable concentration (AUCLST), area under the curve from the time of dosing to 24 hours (AUC24h), C max, and mean concentrations for total 1β-OH DCA (total of all three forms), respectively. Importantly, inhibition with itraconazole resulted in notable reduction of these biomarkers, with 84%, 85%, 82%, and 81% reductions of AUCLST, AUC24h, C max, and mean concentrations for total 1β-OH DCA, respectively. These preliminary data demonstrate for the first time that total 1β-OH DCA in plasma has the potential to serve as a biomarker for CYP3A DDI assessment in early clinical development and may provide key advantages over 4β-HC. SIGNIFICANCE STATEMENT: The authors have reported the use of total 1β-hydroxydeoxycholic acid (1β-OH DCA) (sum of 1β-OH DCA and its glycine and taurine conjugates) plasma exposure as a biomarker for CYP3A activity. Itraconazole inhibition led to an 81%-85% decrease of total 1β-OH DCA plasma exposures, whereas rifampin induction led to a 6.8- to 10.3-fold increase of total 1β-OH DCA plasma exposures. Using 1β-OH DCA exposures in plasma also provides the benefit of allowing pharmacokinetic and biomarker assessment using the same matrix.

NeMeHg, genetically encoded indicator for mercury ions based on mNeonGreen green fluorescent protein and merP protein from Shigella flexneri.

The detection of mercury ions is an important task in both environmental monitoring and cell biology research. However, existing genetically encoded sensors for mercury ions have certain limitations, such as negative fluorescence response, narrow dynamic range, or the need for cofactor supplementation. To address these limitations, we have developed novel sensors by fusing a circularly permutated version of the mNeonGreen green fluorescent protein with the merP mercury-binding protein from Gram-negative bacteria Shigella flexneri. The developed NeMeHg and iNeMeHg sensors responded to mercury ions with positive and negative fluorescence changes, respectively. We characterized their properties in vitro. Using the developed biosensors, we were able to successfully visualize changes in mercury ion concentration in mammalian cultured cells.

Retinex Jointed Multiscale CLAHE Model for HDR Image Tone Compression

Tone-mapping algorithms aim to compress a wide dynamic range image into a narrower dynamic range image suitable for display on imaging devices. A representative tone-mapping algorithm, Retinex theory, reflects color constancy based on the human visual system and performs dynamic range compression. However, it may induce halo artifacts in some areas or degrade chroma and detail. Thus, this paper proposes a Retinex jointed multiscale contrast limited adaptive histogram equalization method. The proposed algorithm reduces localized halo artifacts and detail loss while maintaining the tone-compression effect via high-scale Retinex processing. A performance comparison of the experimental results between the proposed and existing methods confirms that the proposed method effectively reduces the existing problems and displays better image quality.

Cervical and Ocular Vestibular Evoked Myogenic Potentials in Fibromyalgia Syndrome Patients.

Fibromyalgia syndrome (FMS) is a chronic pain condition that may be associated with dysfunction in the central nervous system. The aim of this study was to assess the vestibulo-spinal reflex (VSR) and vestibulo-ocular reflex (VOR) in FMS using the cervical vestibular evoked myogenic potential (cVEMP) and ocular vestibular evoked myogenic potential (oVEMP) tests, respectively, and to evaluate their relation to disease severity. This study included 30 female FMS patients and 30 well-matched healthy controls. They underwent full history taking and assessment of the severity of dizziness/vertigo using the Dizziness Handicap Inventory; assessment of the severity of FMS symptoms using the Revised Fibromyalgia Impact Questionnaire; bedside examination of the dizzy patient; videonystagmography, cVEMP, and oVEMP tests; basic audiologic evaluation; and uncomfortable loudness level (UCL) testing. Dizziness was reported in 46.6% and vertigo in 11.1% of patients. Abnormalities in cVEMP (50%) and oVEMP (63.3%) were mostly unilateral, irrespective of FMS severity. Disease duration affected only the oVEMP amplitude. Fibromyalgia syndrome patients had a statistically significant lower UCL and narrower dynamic range compared to controls. The VSR and VOR are commonly affected in FMS patients, and findings suggest central sensitization involving the brain stem. We recommend routine cVEMP and oVEMP testing to assess brainstem function in FMS patients.

Diarylethene-Type Photochromic Electron Traps Extending Narrow Linear Dynamic Range of Organic Photodetectors. Design Principles and Fate After Electron Transfer. Self-Destructive or Self-Protective?

Diarylethene-Type Photochromic Electron Traps Extending Narrow Linear Dynamic Range of Organic Photodetectors. Design Principles and Fate After Electron Transfer. Self-Destructive or Self-Protective?

Comparing endpoint and real-time PCR for forensic body fluid identification

ABSTRACT Identifying the body fluid source of stains can give an indication of activities, prioritize samples for DNA profiling, and provide probative evidence when the presence of DNA alone does not. Messenger RNA profiling assays using endpoint reverse-transcription polymerase-chain reaction (RT-PCR), were developed to address the issues with conventional body fluid identification and have since been used in forensic casework. However, endpoint RT-PCR has a narrow linear dynamic range (LDR), and there is currently no specific method for mRNA quantification to direct case strategy and optimize input template. Real-time reverse-transcription quantitative PCR (RT-qPCR) collects data during the amplification phase which reflects the starting quantity. The application of RT-qPCR assays as a quantification precursor to endpoint RT-PCR was investigated using previously described assays for circulatory blood, saliva, menstrual fluid, spermatozoa, seminal fluid, and vaginal material. While blood marker SLC4A1 and vaginal marker CYP2B7P showed a strong relationship, the remaining body fluid markers lacked a robust predictive relationship, likely due to differences in LDR. CYP2B7P and SLC4A1 showed high sensitivity when compared with other markers – resulting in a greater number of data points for estimation of the linear relationship. Compared with endpoint, the RT-qPCR assays had higher precision, LDR, and sensitivity.

Methods comparison of two-dimensional gel electrophoresis for host cell protein characterization.

Two-dimensional electrophoresis (2DE) is a gel-based protein separation method based on size and charge which is commonly used for the characterization of host cell proteins (HCPs) during drug development in biotech and pharmaceutical companies. HCPs are a heterogenous mixture of proteins produced by host cells during a biologics drug manufacturing process. Different gel electrophoresis methods including traditional 2D SDS-PAGE with silver and SYPRO Ruby fluorescent dye staining as well as two-dimensional difference gel electrophoresis (2D-DIGE) were compared for their relative abilities to characterize HCPs. SYPRO Ruby was shown to be more sensitive than silver stain in the traditional 2D gels both with and without product protein present. Silver stain also displayed a significant preference for staining acidic proteins over basic ones while SYPRO Ruby was more consistent in imaging proteins across different isoelectric points. The non-traditional method of 2D-DIGE provides high resolution and reproducibility when comparing samples with similar protein profiles but was limited in imaging HCP spots due to its narrow dynamic range. Overall, 2DE is a powerful tool to separate and characterize HCPs and is optimized by choosing the best stain or method for each specific application. Using a combination of two or more different 2DE staining methods, when possible, provides the most comprehensive coverage to support the characterization of a complex mixture like HCPs. However, in instances where only one staining method can be used, SYPRO Ruby is shown to be the more reliable, more sensitive, and easier to use traditional staining method for most HCP-based applications.

Early assessment of fungal and oomycete pathogens in greenhouse irrigation water using Oxford nanopore amplicon sequencing.

Water-borne plant pathogenic fungi and oomycetes are a major threat in greenhouse production systems. Early detection and quantification of these pathogens would enable us to ascertain both economic and biological thresholds required for a timely treatment, thus improving effective disease management. Here, we used Oxford nanopore MinION amplicon sequencing to analyze microbial communities in irrigation water collected from greenhouses used for growing tomato, cucumber and Aeschynanthus sp. Fungal and oomycete communities were characterized using primers that amplify the full internal transcribed spacer (ITS) region. To assess the sensitivity of the MinION sequencing, we spiked serially diluted mock DNA into the DNA isolated from greenhouse water samples prior to library preparation. Relative abundances of fungal and oomycete reads were distinct in the greenhouse irrigation water samples and in water samples from setups with tomato that was inoculated with Fusarium oxysporum. Sequence reads derived from fungal and oomycete mock communities were proportionate in the respective serial dilution samples, thus confirming the suitability of MinION amplicon sequencing for environmental monitoring. By using spike-ins as standards to test the reliability of quantification using the MinION, we found that the detection of spike-ins was highly affected by the background quantities of fungal or oomycete DNA in the sample. We observed that spike-ins having shorter length (538bp) produced reads across most of our dilutions compared to the longer spikes (>790bp). Moreover, the sequence reads were uneven with respect to dilution series and were least retrievable in the background samples having the highest DNA concentration, suggesting a narrow dynamic range of performance. We suggest continuous benchmarking of the MinION sequencing to improve quantitative metabarcoding efforts for rapid plant disease diagnostic and monitoring in the future.

High Dynamic Range Image Processing for Retinal Color Fundus Photography.

Color fundus photography is an important imaging modality that is currently limited by a narrow dynamic range. We describe a post-image processing technique to generate high dynamic range (HDR) retinal images with enhanced detail. This was a retrospective, observational case series evaluating fundus photographs of patients with macular pathology. Photographs were acquired with three or more exposure values using a commercially available camera (Topcon 50-DX). Images were aligned and imported into HDR processing software (Photomatix Pro). Fundus detail was compared between HDR and raw photographs. Sixteen eyes from 10 patients (5 male, 5 female; mean age 59.4 years) were analyzed. Clinician graders preferred the HDR image 91.7% of the time (44/48 image comparisons), with good grader agreement (81.3%, 13/16 eyes). HDR fundus imaging is feasible using images from existing fundus cameras and may be useful for enhanced visualization of retinal detail in a variety of pathologic states. [Ophthalmic Surg Lasers Imaging Retina 2024;55:263-269.].

Global optimization radiometric calibration method for an infrared system with a wide dynamic range.

Considering the conventional calibration restriction of the complicated calibration procedures, narrow dynamic range, and less correlation in the calibration data, a global optimization radiometric calibration method is proposed in this paper. First, a unified database is generated by integrating different gray-level images, neutral density attenuators, integration times, and target radiations under the deduced infrared physical model. Then, the calibration coefficients are automatically learned through the relative error backward propagation network. Finally, experiments are conducted on a large-aperture ground-based infrared system to evaluate the effectiveness of the proposed method. The results indicate the proposed method can solve the problem of learning imbalance with large fluctuations of infrared radiation, ensure global measurement precision with a simpler calibration procedure, and accurately measure the internal stray radiation of the optical system.

Engineering of a Substrate Affinity Reduced S-Adenosyl-methionine Synthetase as a Novel Biosensor for Growth-Coupling Selection of L-Methionine Overproducers.

Biosensors are powerful tools for monitoring specific metabolites or controlling metabolic flux towards the products in a single cell, which play important roles in microbial cell factory construction. Despite their potential role in metabolic flux monitoring, the development of biosensors for small molecules is still limited. Reported biosensors often exhibit bottlenecks of poor specificity and a narrow dynamic range. Moreover, fine-tuning the substrate binding affinity of a crucial enzyme can decrease its catalytic activity, which ultimately results in the repression of the corresponding essential metabolite biosynthesis and impairs cell growth. However, increasing intracellular substrate concentration can elevate the availability of the essential metabolite and may lead to restore cellular growth. Herein, a new strategy was proposed for constructing whole-cell biosensors based on enzyme encoded by essential gene that offer inherent specificity and universality. Specifically, S-adenosyl-methionine synthetase (MetK) in E. coli was chosen as the crucial enzyme, and a series of MetK variants were identified that were sensitive to L-methionine concentration. This occurrence enabled the engineered cell to sense L-methionine and exhibit L-methionine dose-dependent cell growth. To improve the biosensor's dynamic range, an S-adenosyl-methionine catabolic enzyme was overexpressed to reduce the intracellular availability of S-adenosyl-methionine. The resulting whole-cell biosensor effectively coupled the intracellular concentration of L-methionine with growth and was successfully applied to select strains with enhanced L-methionine biosynthesis from random mutagenesis libraries. Overall, our study presents a universal strategy for designing and constructing growth-coupled biosensors based on crucial enzyme, which can be applied to select strains overproducing high value-added metabolites in cellular metabolism.

Highly accurate slope-assisted distributed fiber strain and temperature sensor based on pseudo-Voigt profile and quartic function

To improve accuracy in temperature and strain measured by the slope-assisted distributed optical fiber sensor based on Brillouin scattering, the Lorentzian, Gaussian, pseudo-Voigt and Voigt models are used to approximate the measured Brillouin spectra. The results reveal that the pseudo-Voigt and Voigt profiles can give the better approximation than the other two profiles. In view of computational burden, a slope-assisted Brillouin frequency shift (BFS) estimation method based on the pseudo-Voigt model is proposed. To simplify BFS estimation in the slope-assisted method, by fitting the quartic function to the pseudo-Voigt profiles, a slope-assisted method based on the quartic function is proposed and a closed-form analytical solution for BFS is obtained in the method. The computer programs for the slope-assisted methods based on the line, Lorentzian, Gaussian, pseudo-Voigt models and quartic function are written and are used to estimate BFS for the measured Brillouin spectra with different pulse widths and average times along an optical fiber. The results reveal that the line model-based slope-assisted method has a narrow dynamic range. The Lorentzian, Gaussian models-based methods cannot always ensure its accuracy for Brillouin spectra measured in different situations. The method based on the pseudo-Voigt model possesses higher accuracy and wider dynamic range than the line, Lorentzian, Gaussian models-based ones. The quartic function-based slope-assisted method has almost the same accuracy as the pseudo-Voigt model-based one.

Proteomic comparison between non-purified cerebrospinal fluid and cerebrospinal fluid-derived extracellular vesicles from patients with Alzheimer's, Parkinson's and Lewy body dementia.

Dementia is a leading cause of death worldwide, with increasing prevalence as global life expectancy increases. The most common neurodegenerative disorders are Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). With this study, we took an in-depth look at the proteome of the (non-purified) cerebrospinal fluid (CSF) and the CSF-derived extracellular vesicles (EVs) of AD, PD, PD-MCI (Parkinson's disease with mild cognitive impairment), PDD and DLB patients analysed by label-free mass spectrometry. This has led to the discovery of differentially expressed proteins that may be helpful for differential diagnosis. We observed a greater number of differentially expressed proteins in CSF-derived EV samples (N=276) compared to non-purified CSF (N=169), with minimal overlap between both datasets. This finding suggests that CSF-derived EV samples may be more suitable for the discovery phase of a biomarker study, due to the removal of more abundant proteins, resulting in a narrower dynamic range. As disease-specific markers, we selected a total of 39 biomarker candidates identified in non-purified CSF, and 37 biomarker candidates across the different diseases under investigation in the CSF-derived EV data. After further exploration and validation of these proteins, they can be used to further differentiate between the included dementias and may offer new avenues for research into more disease-specific pharmacological therapeutics.

RREGULARITIES OF OPTICAL DENSITY OF RADIOGRAPHIC IMAGES OF WELDED TUBULAR ELEMENTS OF HEAT EXCHANGERS. COMPENSATION METHOD IN THE MODE OF PANORAMIC DYNAMIC SLIT RADIOGRAPHY

With regard to the technological problem of leveling irregularities in the optical density of the image, due to differences in the radiation thicknesses of the profile of the welded joint and a narrow dynamic range of film detectors in the radiography of axisymmetric annular welded joints of tubular elements of heat exchangers in one exposure from the axial point of the internal cavity of the welded tubular element, a method of dynamic fanshaped slit radiography, which adaptively compensates for the imbalance in the levels of penetrating γ-radiation fluxes recorded by the detector, taking into account changes in the parameters of radiation thicknesses based on formalized analytical patterns for various zones of the welded joint.

Affinity-Switchable Interaction of Biotin and Streptavidin for the Signal-ON Detection of Small Molecules.

Lateral flow assay (LFA) based on gold nanoparticles (AuNPs) is a widely used analytical device for the rapid analysis of environmental hazards and biomarkers. Typically, a sandwich-type format is used for macromolecule detection, in which the appearance of a red test line indicates a positive result (Signal-ON). In contrast, small molecule detection usually relies on a competitive assay, where the absence of a test line indicates positive testing (Signal-OFF). However, such a "Signal-OFF" reading is usually detected within a narrower dynamic range and tends to generate false-negative signals at a low concentration. Moreover, inconsistent readings between macromolecule and small molecule testing might lead to misinterpretation when used by nonskilled individuals. Herein, we report a "Signal-ON" small molecule competitive assay based on the sterically modulated affinity-switchable interaction of biotin and streptavidin. In the absence of a small molecule target, a large steric hindrance can be imposed on the biotin to prevent interaction with streptavidin. However, in the presence of the small molecule target, this steric effect is removed, allowing the biotin to bind to streptavidin and generate the desired test line. In this article, we demonstrate the selective detection of two small molecule drugs, sulfonamides and trimethoprim, using this simple and modular affinity-switchable lateral flow assay (ASLFA). We believe that this affinity-switchable approach can also be adapted in drug discovery and clinical diagnosis, where the competitive assay format is always used for the rapid analysis of small molecules.