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Background: Human sweat can be collected non-invasively with low infectivity; however, its application as a determination method has been challenged due to the presence of trace amounts of chiral metabolites. Moreover, its application as a biological fluid for disease diagnosis has not been previously reported. In this study, the human dried sweat spot paper (DSSP) method was proposed for the derivatization of a novel mass spectrometric chiral probe, N-[1-Oxo-5-(triphenylphosphonium) pentyl]-(S)-3-aminopyrrolidine (OTPA), determination and resolution of DL-lactic acid (DL-LA) enantiomers in human elbow sweat., Results: The methodological validation revealed the resolution (Rs) as 1.78, the limit of detection (S/N = 3) as 20.83 fmol, good linearity (R 2  ≥ 0.9996), and the intra-day and intra-day stability with RSD ranging from 0.53 to 10.85 %, while the average recovery rate of D-LA and L-LA were 104.00 % ± 4.68 % and 107.41 % ± 8.34 %, respectively, with high accuracy. In addition, the method was applied for the determination of DL-LA in the sweat on elbow of 10 healthy volunteers and 30 diabetic patients. The results demonstrated that the D/L ratio and L/D ratio were significantly different (p < 0.0001). In addition, a moderate positive linear correlation between the D/L-LA ratio in human sweat and fasting blood glucose level (r = 0.7744, p < 0.0001) was observed, thereby suggesting that the D/L ratio of lactate in human sweat correlate the glucose level in human fasting blood., Significance and Novelty: The D/L lactate ratio in human sweat could be used as a potential biomarker for diabetes screening. The method can be used to screen for diabetes by providing a dry sweat paper to test equipment and has the potential to be a non-invasive early-warning diagnostic tool for diabetes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Okadaic acid (OA), as a diarrhetic shellfish poisoning, can increase the risk of acute carcinogenic or teratogenic effects for the ingestion of OA contaminated shellfish. At present, much effort has been made to graft immunoassay onto a paper substrate to make paper-based sensors for rapid and simple detection of shellfish toxin. However, the complicated washing steps and low protein fixation efficiency on the paper substrate need to be further addressed., Results: A novel paper-tip immunosensor for detecting OA was developed combined with smartphone and naked eye readout. The trapezoid paper tip was consisted of quantitative and qualitative detection zones. To improve the OA antigen immobilization efficiency on the paper substrate, graphene oxide (GO)-assisted protein immobilization method was introduced. Meanwhile, Au nanoparticles composite probe combined with the lateral flow washing was developed to simplify the washing step. The OA antigen-immobilized zone, as the detection zone Ⅰ, was used for quantitative assay by smartphone imaging. The paper-tip front, as the detection zone Ⅱ, which could qualitatively differentiate OA pollution level within 45 min using the naked eye. The competitive immunoassay on the paper tip exhibited a wide linear range for detecting OA (0.02-50 ng∙mL -1 ) with low detection limit of 0.02 ng∙mL -1 . The recovery of OA in spiked shellfish samples was in the range of 90.3 %-113.%., Significance: These results demonstrated that the proposed paper-tip immunosensor could provide a simple, low-cost and high-sensitivity test for OA detection without the need for additional large-scale equipment or expertise. We anticipate that this paper-tip immunosensor will be a flexible and versatile tool for on-site detecting the pollution of marine products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Hyperuricemia (HUA) has gradually become a public health burden as an independent risk factor for a variety of chronic diseases. Herein, a user-friendly point-of-care (POC) detection system (namely "Smart-HUA-Monitor") based on smartphone-assisted paper-based microfluidic is proposed for colorimetric quantification of HUA urinary markers, including uric acid (UA), creatinine (CR) and pH. The detection limits of UA and CR were 0.0178 and 0.5983 mM, respectively, and the sensitivity of pH were 0.1. The method was successfully validated in artificial urine samples and 100 clinical samples. Bland-Altman plots showed a high consistency between μPAD and the testing instruments (HITACHI 7600 Automatic Analyzer, URIT-500B Urine Analyzer and AU5800B automatic biochemical analyzer) in hospital. Smart-HUA-Monitor provides an accurate quantitative, rapid, low-cost and reliable tool for the monitoring and early diagnosis of HUA urine indicators., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The rapid emergence of microfluidic paper-based devices as point-of-care testing (POCT) tools for early disease diagnosis and health monitoring, particularly in resource-limited areas, holds immense potential for enhancing healthcare accessibility. Leveraging the numerous advantages of paper, such as capillary-driven flow, porous structure, hydrophilic functional groups, biodegradability, cost-effectiveness, and flexibility, it has become a pivotal choice for microfluidic substrates. The repertoire of microfluidic paper-based devices includes one-dimensional lateral flow assays (1D LFAs), two-dimensional microfluidic paper-based analytical devices (2D μPADs), and three-dimensional (3D) μPADs. In this comprehensive review, we provide and examine crucial information related to paper substrates, design strategies, and detection methods in multi-dimensional microfluidic paper-based devices. We also investigate potential applications of microfluidic paper-based devices for detecting viruses, metabolites and hormones in non-invasive samples such as human saliva, sweat and urine. Additionally, we delve into capillary-driven flow alternative theoretical models of fluids within the paper to provide guidance. Finally, we critically examine the potential for future developments and address challenges for multi-dimensional microfluidic paper-based devices in advancing noninvasive early diagnosis and health monitoring. This article showcases their transformative impact on healthcare, paving the way for enhanced medical services worldwide., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Fluoroquinolones (FQs) are widely used for their excellent antimicrobial properties, yet their release into aquatic environments pose risks to ecosystems and public health. The accurate monitoring and analysis of FQs present challenges due to their low concentrations and the complex matrices found in actual environmental samples. To address the need for auto-pretreatment and on-line instrumental analysis, developing new microextraction materials and protocols is crucial. Such advancements will provide better analytical assurance for the effective extraction and determination of FQs at trace levels, which is of great significance to environmental protection and human health., Results: In this work, we presented a Co 2+ mediated paper-based molecularly imprinted polymer chip (CMC@Co-MIP), combined with UPLC analysis, to develop an effective analytical method for identifying and quantifying trace amounts of ciprofloxacin (CIP) and enrofloxacin (ENR) in water samples. Notably, the addition of Co 2+ in CMC@Co-MIP helped to capture the template molecule CIP through coordination before imprinting, which significantly improved the ordering of the imprinted cavities. CMC@Co-MIP exhibited a maximum adsorption capacity up to 500.20 mg g -1 with an imprinting factor of 4.12, surpassing previous reports by a significant margin. Furthermore, the enrichment mechanism was extensively analyzed by various characterization techniques. The developed method showed excellent repeatability and reproducibility (RSD < 13.0 %) with detection limits ranging from 0.15 to 0.21 μg L -1 and recoveries ranging from 64.9 % to 102.3 % in real spiked water samples., Significance: We developed a novel microextraction paper-based chip based on Co 2+ mediation, which effectively improved the selectivity and convenience of extracting FQs. This breakthrough allowed the chip to have a high enrichment efficiency as well as provide a robust on-line instrumental program. It also confirms that the imprinting scheme based on metal ion coordination is a high-performance strategy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The rapid development of micro-solid phase extraction (μ-SPE) procedures with new sorption materials, in particular, based on using natural materials, is currently reported. The production of these sorbents and the entire extraction procedure should support the implementation of Green Analytical Chemistry (GAC) principles. Promising materials are sorbents based on paper, which can be relatively easily modified, among others: by covering it with a polymer membrane. In this work, the practical application of paper-supported polystyrene used in the analysis of urine samples containing selected date-rape drugs (DRD) substances, and evaluation of the entire procedure using GAC metrics is presented., Results: The paper-supported polystyrene membranes were successfully fabricated and characterized. The successful polystyrene coating on the paper was confirmed through ATR-FTIR measurements, ensuring even coverage. The μ-SPE procedure using this material facilitated extraction with a throughput of approximately 120 samples per hour in just a few steps. Throughout the research, a mixture of 100 mM acetic acid:methanol:acetonitrile (70:15:15, v/v/v) was selected as an optimal background electrolyte for capillary electrophoresis - mass spectrometry analysis. Validation results of this method demonstrated its suitability, exhibiting good linearity (R 2  > 0.95), low limits of detection (3.1-15 ng mL -1 ), acceptable precision (<15 %), and recovery for all tested analytes. Furthermore, the greenness evaluation conducted with six different metrics: AGREEprep, AGREE, ComplexGAPI, SPMS, hexagonal metric, and WAC indicated the overall eco-friendliness and sustainability of the method, with minor concerns regarding energy consumption., Significance: The use of cellulose paper with polystyrene membranes for μ-SPE provides a versatile and eco-friendly extraction method for detecting DRDs in urine samples. The presented work is an example of the use of GAC metrics in the evaluation of the analytical procedure. The optimized PT-μ-SPE/CE-MS method allows for minimized reagent usage and waste production. Moreover, the method proves to be sustainable and efficient for forensic toxicology analysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Calcium and magnesium ions are highly abundant and important cations in human body. At the same time, both dyscalcemia and dysmagnesemia are frequently encountered in the clinical practice. As deficiency or excess of Ca(II) or Mg(II) can cause severe symptoms, determining these ions in serum is of great importance. Concentration of these ions in biological samples is typically assayed in clinical laboratories with the use of expensive and specialized equipment. Since those methods cannot be easily adapted for self-diagnosis purposes, there is a great need to develop a convenient tool for reliable determination of calcium and magnesium in serum at the point-of-care., Results: The colorimetric methods employed for calcium and magnesium analysis were o-cresophtalein complexone assay and xylidyl blue assay, respectively. Analytical signal acquisition was accomplished using an ordinary flatbed scanner or smartphone and free software. For increased user-friendliness the device was optimized to perform simultaneous determination of calcium and magnesium ions in only 10 min. In the optimized conditions, the limit of detection for calcium ions was 0.09 mmol L -1 , while for magnesium it was 0.04 mmol L -1 . Determination of both ions requires only 4 μL of serum sample. The developed paper-based sensors were validated with control human serum samples and the obtained relative errors for majority of samples were below 20 %., Significance: In this paper, a microfluidic paper-based analytical device for simultaneous determination of calcium and magnesium ions in human serum is reported for the first time. Additionally, this is also the first report on colorimetric determination in serum of any of these ions in paper-based format. Simultaneous detection of both ions allows for fast and user-friendly screening of disturbance in calcium and magnesium homeostasis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Alzheimer's disease (AD) is a prevalent neurodegenerative disease with no effective treatment. Efficient and rapid detection plays a crucial role in mitigating and managing AD progression. Deep learning-assisted smartphone-based microfluidic paper analysis devices (μPADs) offer the advantages of low cost, good sensitivity, and rapid detection, providing a strategic pathway to address large-scale disease screening in resource-limited areas. However, existing smartphone-based detection platforms usually rely on large devices or cloud servers for data transfer and processing. Additionally, the implementation of automated colorimetric enzyme-linked immunoassay (c-ELISA) on μPADs can further facilitate the realization of smartphone μPADs platforms for efficient disease detection., Results: This paper introduces a new deep learning-assisted offline smartphone platform for early AD screening, offering rapid disease detection in low-resource areas. The proposed platform features a simple mechanical rotating structure controlled by a smartphone, enabling fully automated c-ELISA on μPADs. Our platform successfully applied sandwich c-ELISA for detecting the β-amyloid peptide 1-42 (Aβ 1-42, a crucial AD biomarker) and demonstrated its efficacy in 38 artificial plasma samples (healthy: 19, unhealthy: 19, N = 6). Moreover, we employed the YOLOv5 deep learning model and achieved an impressive 97 % accuracy on a dataset of 1824 images, which is 10.16 % higher than the traditional method of curve-fitting results. The trained YOLOv5 model was seamlessly integrated into the smartphone using the NCNN (Tencent's Neural Network Inference Framework), enabling deep learning-assisted offline detection. A user-friendly smartphone application was developed to control the entire process, realizing a streamlined "samples in, answers out" approach., Significance: This deep learning-assisted, low-cost, user-friendly, highly stable, and rapid-response automated offline smartphone-based detection platform represents a good advancement in point-of-care testing (POCT). Moreover, our platform provides a feasible approach for efficient AD detection by examining the level of Aβ 1-42, particularly in areas with low resources and limited communication infrastructure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Alpha-fetoprotein (AFP) is a fetal protein that can indicate congenital anomalies such as Down syndrome and spinal canal blockage when detected at abnormal levels in pregnant women. Current AFP detection methods rely on invasive blood or serum samples, which require sophisticated equipment. From the many solutions proposed, colorimetric paper-based assays excel in point-of-care settings. The concept of paper-based ELISA (p-ELISA) enhances traditional methods, aligning with the ASSURED criteria for diagnostics in resource-limited regions. Despite success in microfluidic paper-based assay devices, laser printing remains underexplored for p-ELISA. Additionally, modifying the paper surface provides an additional layer of sensitivity enhancement., Results: In this study, we developed a novel laser-printed paper-based ELISA (LP-pELISA) for rapid, sensitive, and noninvasive detection of AFP in saliva samples. The LP-pELISA platform was fabricated by printing hydrophobic barriers on filter paper using a laser printer, followed by depositing hydroxyapatite (HAp) as an immobilization material for the antibodies. The colorimetric detection was achieved using AuNPs functionalized with anti-AFP antibodies and silver nitrate enhancement. The LP-pELISA exhibited a linear response for AFP detection in both buffer and saliva samples over a range of 1.0-800 ng mL -1 , with a limit of detection (LOD) reaching 1.0 ng mL -1 . The assay also demonstrated good selectivity, repeatability, reproducibility, and stability. The LP-pELISA was further validated by testing spiked human saliva samples, showing its potential for point-of-care diagnosis of congenital disabilities., Significance: The LP-pELISA is a noninvasive platform showcasing simplicity, cost-effectiveness, and user-friendliness, utilizing laser printing, hydroxyapatite modification, and saliva samples to efficiently detect AFP. Beyond its application for AFP, this method's versatility extends to other biomarkers, positioning it as a catalyst for the evolution of paper-based biosensors. The LP-pELISA holds promise as a transformative tool for point-of-care diagnostics, fostering advancements in healthcare with its innovative technology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Cyanide anion can be found in foodstuffs, tobacco smoke and a variety of types of waters, mainly originating from anthropogenic activities. Due to its highly toxic nature, several agencies have established limits for cyanide levels in water. Additionally, monitoring cyanide levels in biological samples, such as blood and urine, is crucial for obtaining clinical information about the health condition of patients. Therefore, there is a pressing need for the development of simple, cost-effective, and reliable analytical methods capable of quantifying cyanide at low concentrations., Results: This study presents a novel analytical method for the selective and sensitive determination of cyanide based on analyte volatilization, pre-concentration via single-drop microextraction (SDME) using a selective reagent, and colorimetric quantification using a paper-based analytical device. For this, 10 mL of a liquid sample was acidified with phosphoric acid and the generated HCN was collected using a single drop of 3 μL of a palladium dimethylglyoximate solution (Pd (DMG) 2 2- ) positioned in the flask headspace using a syringe. The reaction of Pd (DMG) 2 and the demasking of the organic ligand. After 15 min of extraction time, the reagent drop was added to a paper-based analytical device that has been previously impregnated with 3 μL of nickel chloride, resulting in the formation of a red precipitate of nickel (II) dimethylglyoximate. Digital images of the paper-based device were captured and the red channel (R) was used for quantification purposes. Under optimized conditions, the method demonstrates a suitable linear relation (r 2- leads to the formation of Pd(CN) 4 2- and the demasking of the organic ligand. After 15 min of extraction time, the reagent drop was added to a paper-based analytical device that has been previously impregnated with 3 μL of nickel chloride, resulting in the formation of a red precipitate of nickel (II) dimethylglyoximate. Digital images of the paper-based device were captured and the red channel (R) was used for quantification purposes. Under optimized conditions, the method demonstrates a suitable linear relation (r 2  > 0.99) ranging from 26 to 286 μg L -1 and a limit of detection of 5 μg L -1 ., Significance: As a proof of concept, cyanide levels were quantified in water and urine samples using this method. The proposed approach offers high sensitivity and selectivity while requiring only a small volume of reagents. Furthermore, it exhibits a high degree of portability for in-situ applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Total joint arthroplasty (TJA) has significantly improved the quality of life for millions suffering from end-stage arthritis. However, periprosthetic joint infections (PJI) remain a serious complication, necessitating extensive interventions and prolonged antimicrobial treatments. The aging population is expected to lead to a rise in TJA cases, subsequently increasing the incidence of PJI, particularly in the elderly who face higher mortality rates. Current diagnostic methods for suspected PJI, such as radiographs and biochemical markers like CRP and ESR, exhibit limited sensitivity. Therefore, there is a critical need for a specific synovial fluid biomarker assay to enhance PJI diagnosis using specific SF-based assay., Results: This study introduces a novel microfluidic chip with a paper-based aptamer-sandwich assay for the quantitative detection of HNP 1, a crucial PJI biomarker, in synovial fluid. The assay leverages the advantages of aptamers over antibodies, demonstrating high selectivity and affinity for target molecules. The integration of a nitrocellulose (NC) membrane onto the microfluidic platform represents a significant advancement, reducing background signals and simplifying the assay procedure without intricate procedure and pre-treatment. The NC membrane-based microfluidic device offers rapid, cost-effective, and highly sensitive detection of HNP 1, with a limit of detection of 0.5 mg L -1 . The microfluidic device demonstrates exceptional performance, detecting up to four clinical samples in approximately 42 min on a single chip with 100 % accuracy, as confirmed by analysis of 12 clinical samples and comparison with "gold-standard". Moreover, the assay exhibits a wide dynamic range of 0.5-100 mg L-1, underscoring its potential as a powerful tool for PJI diagnosis in clinical settings., Significance: This work introduces a paper-based microfluidic system tailored for rapid HNP 1 detection using synovial fluid near joint region (and not serum via blood) for better diagnosis. The innovative paper-based aptamer-sandwich assay yields results within 42-min. Significantly, it boasts a wide dynamic range, detecting levels from an impressive 0.5 mg L-1, crucial in the 2.6 mg L-1 threshold region. This heightened sensitivity and expansive detection capability establish our assay as a leader in PJI diagnostics, promising unmatched precision and efficiency in clinical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Many diseases are detected through blood tests. Currently, most blood tests are done on plasma instead of whole blood because of the interference of blood cells on detection results. Here, we developed a laminated microfluidic paper-based analytical device (L-μPAD) for the separation of plasma from whole blood without using plasma separation membrane (PSM). A lateral flow design consisting of a circular sampling zone and rectangular detection zone was patterned on the paper substrate using laser printing technology. The μPAD was then laminated after impregnation with KCl solution. Lamination and electrolyte addition represented synergistic effects on the separation by controlling the pore size of the paper. In addition, by preventing evaporation on one hand and squeezing paper pores on the other hand, lamination caused longer movement of the separated plasma, the longest plasma path reported so far. The separation process was monitored using colorimetric reagent bromocresol green and scanning electron microscopy. The process of separation was completed in less than 90s without significant hemolysis and the separated plasma was far from the interfering effect of red blood cells. We used the device for the determination of serum albumin. However, it represents the potential for point-of-care testing in multi-assay experiments too., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Herein, the applicability of electromembrane extraction (EME), as an efficient and paper-compatible separation technique, was envisaged over customized microfluidic paper-based analytical devices (μPADs). The utility of EME was assessed on 2D planar and 3D origami structures using different types of electrodes including stainless steel and paper-based electrodes. The overall separation procedure was integrated to colorimetric detection demonstrated for copper ions as the model analyte. According to the obtained results, EME based on 3D design of μPADs could effectively be performed under low applied voltage. Using 3D architecture, the analyte could be quantified within the range of 40.0-1500.0 μg L -1 with limit of detection down to 20.0 μg L -1 using smart phone camera as signal read-out. The proposed platform showed remarkable compatibility with direct analysis from untreated real samples of human blood and spring water., (Copyright © 2022 Elsevier B.V. All rights reserved.)