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In this transformative study, machine learning (ML) and t‐distributed stochastic neighbor embedding (t‐SNE) are employed to interpret intricate patterns in colorimetric images of cold atmospheric plasma (CAP)‐treated water. The focus is on CAP's therapeutic potential, particularly its ability to generate reactive oxygen and nitrogen species (RONS) that play a crucial role in antimicrobial activity. RGB, HSV, LAB, YCrCb, and grayscale color spaces are extracted from the colorimetric expression of oxidative stress induced by RONS, and these features are used for unsupervised ML, employing density‐based spatial clustering of applications with noise (DBSCAN). The DBSCAN model's performance is evaluated using homogeneity, completeness, and adjusted rand index with a predictive data distribution graph. The best results are achieved with 3,3′,5,5′‐tetramethylbenzidine–potassium iodide colorimetric assay solution immediately after plasma treatment, with values of 0.894, 0.996, and 0.826. t‐SNE is further conducted for the best‐case scenario to evaluate the clustering efficacy and find the best combination of features to better present the results. Correspondingly, t‐SNE enhances clustering efficacy and adeptly handles challenging points. The approach pioneers dynamic and comprehensive solutions, showcasing ML's precision and t‐SNE's transformative visualization. Through this innovative fusion, complex relationships are unraveled, marking a paradigm shift in biomedical analytical methodologies. [ABSTRACT FROM AUTHOR]

In this transformative study, machine learning (ML) and t‐distributed stochastic neighbor embedding (t‐SNE) are employed to interpret intricate patterns in colorimetric images of cold atmospheric plasma (CAP)‐treated water. The focus is on CAP's therapeutic potential, particularly its ability to generate reactive oxygen and nitrogen species (RONS) that play a crucial role in antimicrobial activity. RGB, HSV, LAB, YCrCb, and grayscale color spaces are extracted from the colorimetric expression of oxidative stress induced by RONS, and these features are used for unsupervised ML, employing density‐based spatial clustering of applications with noise (DBSCAN). The DBSCAN model's performance is evaluated using homogeneity, completeness, and adjusted rand index with a predictive data distribution graph. The best results are achieved with 3,3′,5,5′‐tetramethylbenzidine–potassium iodide colorimetric assay solution immediately after plasma treatment, with values of 0.894, 0.996, and 0.826. t‐SNE is further conducted for the best‐case scenario to evaluate the clustering efficacy and find the best combination of features to better present the results. Correspondingly, t‐SNE enhances clustering efficacy and adeptly handles challenging points. The approach pioneers dynamic and comprehensive solutions, showcasing ML's precision and t‐SNE's transformative visualization. Through this innovative fusion, complex relationships are unraveled, marking a paradigm shift in biomedical analytical methodologies.

Soil nutrition is a key pillar in agricultural productivity. However, point-of-need testing for soil nutrition is not readily available in resource-limited settings such as Kenya. We set out to study the perceived need for soil testing among farmers in this country. A group of 547 farmers from Murang'a and Kiambu counties in central Kenya were recruited through multi-stage sampling to help assess the perceptions and willingness to pay (WTP) toward a prototype technology for surveillance of in-situ soil nutrition. The technology is based on a cafetière-style filter system for extraction and a microfluidic paper-based analytical device (μPAD) for nutrient readout. We employed the double bounded choice contingent valuation method (CVM) to analyze the willingness of farmers to accept and pay for the prototype if the technology was available on the market. It was found that currently, only 1.5 % of farmers carry out soil testing. The high costs of analysis at testing centers, which are often far from the farmers, are among the main reasons contributing to the majority of farmers not testing their soils. The farmers surveyed were generally willing to make their soil data publicly accessible, especially to extension officers. CVM showed that uncontrolled WTP had a 94.24 % premium above KSh1,000 ($6.60) incurred by using the existing rapid testing method. Factoring the control variables and disaggregating the model into gender categories, the findings showed that youth, women, and men had WTP values of KSh1,612.53 ($10.75), KSh1,558.68 ($10.39), and KSh1,504.83 ($10.03), respectively, indicating that farmers can indeed pay for the convenience to test their soils in situ. Through the democratization of soil nutrition data, extension agents can enhance the improvement of agricultural productivity, which implies that farmers can commercialize their agricultural activities.

Microfluidic paper-based analytical devices (µPADs) have been successfully developed using dual detection: electrochemical and colorimetric systems. The µPADs have the potential to be used as Pb(II), Cd(II), and Cu(II) sensors to test the quality of water. The fabrication process uses hot embossing and screen-printing methods. The working electrode in the electrochemical zone was enhanced by the bismuth metal deposition process, while in the colorimetric zone, the gold nanoparticles modified with thioctic acid and dansylhydrazine (TA-Au-DNS) were used as a colorimetric sensor to detect Cu. The basic material of µPADs was characterized using a Fourier-transform infrared (FTIR) and a contact angle meter (CAM). In the electrochemical zone, the signals of square wave anodic stripping voltammetry (SWASV) resulted in good detection of Pb(II) and Cd(II) (from 0 to 100 ppb) with a limit of detection of 1.588 and 1.42 ppb, respectively. In the colorimetric zone, the performance of TA-Au-DNS for detecting Cu metal was obtained from readings through the red-green-blue (RGB) sensor as a miniature of µPADs reader. The LOD, LOQ, and average Vx0 (linearity values) in the detection of Cu(II) (from 58 to 100 ppb) are 8.51 ppb, 28.36 ppb, and 0.41%, respectively.

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Chlorpyrifos (CHL), profenofos (PRO) and cypermethrin (CYP) are widely used in combination to increase crop yields. However, these three pesticides can cause serious harm to human health and do not easily degrade. In this study, a novel visible paper sensor has been prepared successfully and different colorimetric reactions were utilized to detect the three pesticides simultaneously. The sensor was constructed by grafting a zwitterionic polymer onto a cellulose filter (CF) and placing it on a glass surface modified with PDMS. The branch shape was designed to form multiple detection areas, which were modified with specific pesticides and corresponding chromogenic reagents. The as-prepared colorimetric platform exhibited high sensitivity, a short detection time, a good linear response and a low detection limit (LOD) for the three pesticides (chlorpyrifos: y = 46.801 − 1.939x, R2 = 0.983, LOD = 0.235 mg/L; profenofos: y = 40.068 + 42.5x, R2 = 0.988, LOD = 4.891 mg/L; cypermethrin: y = 51.993 + 1.474x, R2 = 0.993, LOD = 4.053 mg/L). The comparison of the results obtained by the proposed paper sensor and those obtained by spectrophotometry further revealed the stability and reliability of the paper sensor. In particular, the color intensity of the interaction between the pesticides and coloring agents could be directly observed by the human eye. The consistency of the colorimetric/optical assay was proven in real target pesticide samples. Thus, this sensing strategy provides a portable, cost-effective, accurate and visualized paper platform, which could be suitable for application in the fruit and vegetable industry for monitoring CHL, PRO and CYP in parallel. [ABSTRACT FROM AUTHOR]

Nowadays, food safety has become a major concern for the sustainability of global public health. Through the production and distribution steps, food can be contaminated by either chemical hazards or pathogens, and the determination of these plays a critical role in the processes of ensuring food safety. Therefore, the development of analytical tools that can provide rapid screening of these hazards is highly necessary. Microfluidic paper-based analytical devices (µPADs) have advanced significantly in recent years as they are rapid and low-cost analytical screening tools for testing contaminated food products. This review focuses on recent developments of µPADs for various applications in the food safety field. A description of the fabrication of selected papers is briefly discussed, and evaluation of the μPADs' performance with regard to their precision and accuracy as well as their limits of detection is critically assessed. The advantages and disadvantages of these devices are highlighted. [ABSTRACT FROM AUTHOR]

The aim of this study is to employ a response surface methodology (RSM) to optimize experimental parameters in microfluidic paper-based analytical devices (µ-PADs). The independent parameters include concentrations and volumes of acetylcholinesterase, acetylthiocholine iodide, and 5,5-dithiobis-(2-nitrobenzoic acid). Their effect on mean color intensity was tested and optimized. From the analysis of variance, high regression and fitting values were obtained between the experimental and RSM predicted mean color intensity. Under optimum conditions, satisfactory linearity (R2 > 0.9990) in the range of 0.25–16 mg/L was obtained for the studied pesticides. The limit of detection (LOD) varies from 0.13 to 0.27 mg/L; high precision (RSD of 3.8–8.0%), reproducibility (RSD of 7.2–11.0%), and recovery (78–97%) were achieved. The RSM approach has been demonstrated to be more efficient than the traditional approach. It resulted in a µ-PAD system with less amount of reagent usage and better LOD compared with a univariate approach. [ABSTRACT FROM AUTHOR]

Accurately predicting durian maturity is a critically unresolved worldwide issue. Farmers currently determine durian ripeness based on their own observation and experience leading to inconsistencies in harvest timing. This reliance on human judgment often results in premature or overripe harvests, impacting fruit quality, yield, and market value. Existing technological solutions, such as sensors are often complex and require specialized expertise, hindering their adoption by farmers and consumers. Developing sensors that can accurately measure durian ripeness without damaging the fruit, are easy to use, and affordable remains a challenge. We introduce a microfluidic paper-based analytical device (μPAD) for on-site, safe matching to meet the demands of durian maturity evaluation. The μPAD automatically collected peduncle fluid without destroying the durian fruit for dual detection of total sugar and amino acid. For determining total sugar including sucrose, glucose, and fructose, several enzymatic steps were reduced to a single step of invertase for sucrose hydrolysis before total reducing sugar was measured using gold nanoparticle (AuNP) generation. Kinetics study of invertase on the μPAD showed V max and K m values of 1.42 mM min−1 and 2.17 mM, respectively, that agreed with the direct study of sucrose conversion. To increase device reliability, amino acid was also simultaneously measured with sugar using the simple ninhydrin test with the addition of SnCl 2. The developed sensor provided LODs of 3.50, 3.10, 3.30 μM, and 0.02 mg mL−1 for glucose, fructose, sucrose, and amino acid respectively. The μPADs were able to nondestructively discriminate between the mature and immature durians, showing high linear correlation with the standard dry weight method. The development of this μPAD technology has the potential to revolutionize durian cultivation practices, reduce post-harvest losses, and enhance the overall sustainability and profitability of the durian value chain, and can be further developed for maturity tests of other fruits. [Display omitted] • A user-friendly microfluidic paper-based device (μPAD) was introduced for on-site durian maturity evaluation. • The μPAD analyzed durian peduncle fluid, eliminating the need to damage the fruit itself. • The μPAD offered a single-step enzyme process to measure sugars and amino acids, simplifying traditional methods. • Kinetic study of invertase on paper substrate corresponded to the direct conversion of sucrose. • The μPAD accurately distinguished mature and immature durians, providing a reliable and affordable tool. [ABSTRACT FROM AUTHOR]

In this work, we developed an alternative manufacturing paper-based microfluidics method through 3D printing and wax filament. Microfluidic paper-based analytical devices (µPADs) are low-cost and easy-to-manufacture tools used for various chemical and biological analyses and studies. Paper-based microfluidics with wax has been limited as the manufacturers have discontinued most wax printing equipment. We aim to develop a low-cost and accessible manufacturing method that can replace conventional wax-on paper-based microfluidic manufacturing methods. Using highly available commercial 3D printing technology and wax filament, we could create hydrophobic wax barriers on the surface of different paper types. The properties and limits of this manufacturing method were characterized. Moreover, using this paper-based microfluidic manufacturing method, we were able to measure dopamine electrochemically using µPAD as a passive flow-based method in concentrations as low as 1 nM using injections as small as 15 µL.

A user-friendly, low-cost detector able to read the RGB indexes of microfluidic paper-based analytical devices (µPADs) was developed. The RGB-detector was built with 3D printing using PLA+ and reused Li-ion batteries. It is Arduino-based, which provides an easy interface between the sensor TCS3200, which reads the quadratic wave of the times corresponding to the RGB numbers, the Arduino itself, whose software translates the times into RGB values, and the touchscreen display, NX3224T028, which shows the results. This detector permits multi-sample analysis since it has a sample holder that can keep up to six µPADs simultaneously and rotate after the display's request. This work shows how the readings of the RGB indexes by the proposed RGB-detector implement the measurements' reproducibility. As a proof-of-concept, the RGB-detector application to a green array of µPADs for pH measurement coupled with chemometric analysis allowed us to achieve good results in terms of precision and agreement with the pH values measured by a classical pH-meter. [ABSTRACT FROM AUTHOR]

Tea (Camellia sinensis (L.) Kuntze—surname of German origin) is a popular beverage consumed worldwide due to its health benefits. Its quality depends on measuring features that may discriminate teas from distinct provenances. Protected designation of origin (PDO) is therefore a very useful label for tea quality evaluation. In the present work, antioxidant activity profiles obtained from microfluidic paper-based analytical devices (µPADs) were analyzed by chemometrics to determine the tea geographic origin. Based on the existing literature, we constructed a database containing chemical data from 26 samples and evaluated it by principal component analysis (PCA) coupled to linear discriminant analysis (LDA). Antioxidant activity was an effective LDA predictor for sample discrimination accomplishing accuracies from 75 to 82%. Modeling performance was favored by an external validation method. The best classification model was found using the first nine PCs as input variables. Training samples achieved a perfect success rate, while the test ones were predicted with 83% specificity, 100% sensitivity, and 90% overall accuracy. The modeling robustness was verified by integrating AUC (0.943) from ROC curve. The PCA-LDA approach taken here demonstrated that the teas coming from different countries can be correctly authenticated through µPADs, thus contributing to certificate samples PDO. [ABSTRACT FROM AUTHOR]

Soil nutrition is a key pillar in agricultural productivity. However, point-of-need testing for soil nutrition is not readily available in resource-limited settings such as Kenya. We set out to study the perceived need for soil testing among farmers in this country. A group of 547 farmers from Murang'a and Kiambu counties in central Kenya were recruited through multi-stage sampling to help assess the perceptions and willingness to pay (WTP) toward a prototype technology for surveillance of in-situ soil nutrition. The technology is based on a cafetière-style filter system for extraction and a microfluidic paper-based analytical device (μPAD) for nutrient readout. We employed the double bounded choice contingent valuation method (CVM) to analyze the willingness of farmers to accept and pay for the prototype if the technology was available on the market. It was found that currently, only 1.5 % of farmers carry out soil testing. The high costs of analysis at testing centers, which are often far from the farmers, are among the main reasons contributing to the majority of farmers not testing their soils. The farmers surveyed were generally willing to make their soil data publicly accessible, especially to extension officers. CVM showed that uncontrolled WTP had a 94.24 % premium above KSh1,000 ($6.60) incurred by using the existing rapid testing method. Factoring the control variables and disaggregating the model into gender categories, the findings showed that youth, women, and men had WTP values of KSh1,612.53 ($10.75), KSh1,558.68 ($10.39), and KSh1,504.83 ($10.03), respectively, indicating that farmers can indeed pay for the convenience to test their soils in situ . Through the democratization of soil nutrition data, extension agents can enhance the improvement of agricultural productivity, which implies that farmers can commercialize their agricultural activities., Competing Interests: 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., (© 2024 The Authors.)

For the first time, in-tube gel electro-membrane microextraction (IT-G-EME) system followed by microfluidic paper-based analytical devices (µPADs) as a low-cost reading platform was fabricated for the speciation of trivalent chromium (Cr(III)) and hexavalent chromium (Cr(VI)) as model cationic and anionic compounds. In this new miniaturized extraction mode, a transparent narrow-bore polymeric tube was used as housing of the aqueous acceptor phase (AP, 30 µL), while an agarose gel membrane was placed as a micro plug (2.5 mm) at the beginning of the tube. A circular shape vial (1.5 mL, pH 5.5) containing chromium species as donor phase (DP) was connected between two tubes which previously filled with gel membrane and aqueous AP. By applying electric potential, the positively charged Cr(III) and negatively charged Cr(VI) in the DP migrated selectively toward cathodic and anodic tubes, respectively. After extraction, each AP was analyzed by µPAD, which had already been modified with diphenylcarbazide (DPC). Under the optimized extraction conditions, a good limit of detection (LOD) equal to 7.0 µg L–1 was achieved for both analytes, while the extraction recoveries for Cr(VI) and Cr(III) were 72% and 84%. In addition, the developed approach was used for the quantification of chromium species in water samples.

The global prevalence of diabetes mellitus, a serious chronic disease with fatal consequences for millions annually, is of utmost concern. The development of efficient and simple devices for monitoring glucose levels is of utmost significance in managing diabetes. The advancement of nanotechnology has resulted in the indispensable utilization of advanced nanomaterials in high-performance glucose sensors. Modulating the morphology and intricate composition of transition metals represents a viable approach to exploit their structure/function correlation, thereby achieving optimal electrocatalytic performance of the synthesized catalysts. Herein, a sensitive and rapid Cu-encapsulated Cu 2 S@nitrogen-doped carbon (Cu@Cu 2 S@N–C) hollow nanocubes-functionalized microfluidic paper-based analytical device (μ-PAD) was fabricated. Through a delicate sacrificial template/interface technique and thermal decomposition, inter-connected hollow networks were formed to boost the active sites, and the carbon shell was coated to protect Cu from being oxidation. For application, the constructed μ-PAD is used for glucose sensing utilizing an origami automated sample pretreatment system enabled by a simple application of strong alkaline solution on wax paper. Under optimal circumstances, the Cu@Cu 2 S@N–C electrochemical biosensor exhibits broad detection range of 2–7500 μM (R2 = 0.996) with low detection limit of 0.16 μM (S/N = 3) and high sensitivity of 1996 μA mM−1 cm−2. Additionally, the constructed μ-PAD also exhibited excellent selectivity, stability, and reproducibility. By rationally designing the double-shell hollow nanostructure and introducing Cu-encapsulated inner layer, the synthesized Cu@Cu 2 S@N–C hollow nanocubes show large specific surface area, short diffusion channels, and high stability. The proposed origami μ-PAD has been successfully applied to serum samples without any additional sample preparation steps for glucose determination, offering a new perspective for early nonenzymatic glucose diagnosis. [Display omitted] • Cu@Cu 2 S@N–C hollow nanocubes-based origami μ-PAD sensor was fabricated. • Cu@Cu 2 S@N–C hollow nanocubes possessed large specific surface area and high stability. • Cu@Cu 2 S@N–C hollow nanocubes exhibited excellent electrocatalytic performance for glucose. • The proposed sensor was applied for glucose detection without any additional sample preparation steps. [ABSTRACT FROM AUTHOR]

Fluid control on a paper channel is necessary for analysis with multiple reagents, such as enzyme-linked immunosorbent assay (ELISA) in microfluidic paper-based analytical devices (µPADs). In this study, a thermo-responsive valve was fabricated by polymerizing N-isopropylacrylamide on a PVDF porous membrane by plasma-induced graft polymerization. The polymerized membrane was observed by scanning electron microscopy (SEM), and it was confirmed that more pores were closed at temperatures below 32 °C and more pores were opened at temperatures above 32 °C. Valve permeability tests confirmed that the proposed polymerized membrane was impermeable to water and proteins at temperatures below 32 °C and permeable to water at temperatures above 32 °C. The valve could also be reversibly and repeatedly opened and closed by changing the temperature near 32 °C. These results suggest that plasma-induced graft polymerization may be used to produce thermo-responsive valves that can be opened and closed without subsequent loss of performance. These results indicate that the thermo-responsive valve fabricated by plasma-induced graft polymerization could potentially be applied to ELISA with µPADs. [ABSTRACT FROM AUTHOR]

Microfluidic paper-based analytical devices (µPADs) represent one of the promising green analytical strategies for low-cost and simple determination of various analytes. The actual task is the development of such devices for quantitation of antioxidants, e.g., flavonoids. In this paper, possibilities of a novel three-reagent µPAD including silver nitrate, 4-nitrophenyldiazonium tetrafluoroborate, and iron(III) chloride as reagents are assessed with respect to the determination of dihydroquercetin. It is shown that all the three reagents produce different colorimetric responses that can be detected by a mini-spectrophotometer–monitor calibrator or by a smartphone. The method is applicable to direct measuring high contents of dihydroquercetin (the linearity range is 0.026–1 mg mL−1, and the limit of detection is 7.7 µg mL−1), which is favorable for many dietary supplements. The analysis of a food supplement was possible with the relative standard deviations of 9–26%, which is satisfactory for quantitative and semiquantitative determinations. It was found that plotting a calibration graph in 3D space of the three reagents' responses allows us to distinguish dihydroquercetin from its close structural analogue, quercetin. [ABSTRACT FROM AUTHOR]

Microfluidic paper‐based analytical devices (μPADs) are commonly used in point‐of‐care testing (POCT) due to their advantages of low cost and easy operation. However, the fabrication and potential environmental pollution of μPADs are the universal and pendent concerns. In this respect, a simple and novel method is developed for preparing photo‐adjustable μPADs using the photocatalytic properties of TiO2. A superhydrophobic TiO2‐paper substrate with unique photoactivity is fabricated. The flow channels on the superhydrophobic TiO2‐paper substrate can be quickly generated and on‐demand edited by a simple UV irradiation process, to fabricate various 2D and 3D μPADs for specific applications. After usage, the residual organics and biological specimens on μPADs can be easily bleached via TiO2‐assited degradation under UV or sunlight, avoiding the risk of potential environment pollution and disease transmission. The successful application of such novel substrate in the fabrication of smart and safe μPADs for sweat analysis and motion monitoring is shown. [ABSTRACT FROM AUTHOR]

Chlorpyrifos (CHL), profenofos (PRO) and cypermethrin (CYP) are widely used in combination to increase crop yields. However, these three pesticides can cause serious harm to human health and do not easily degrade. In this study, a novel visible paper sensor has been prepared successfully and different colorimetric reactions were utilized to detect the three pesticides simultaneously. The sensor was constructed by grafting a zwitterionic polymer onto a cellulose filter (CF) and placing it on a glass surface modified with PDMS. The branch shape was designed to form multiple detection areas, which were modified with specific pesticides and corresponding chromogenic reagents. The as-prepared colorimetric platform exhibited high sensitivity, a short detection time, a good linear response and a low detection limit (LOD) for the three pesticides (chlorpyrifos: y = 46.801 − 1.939x, R2 = 0.983, LOD = 0.235 mg/L; profenofos: y = 40.068 + 42.5x, R2 = 0.988, LOD = 4.891 mg/L; cypermethrin: y = 51.993 + 1.474x, R2 = 0.993, LOD = 4.053 mg/L). The comparison of the results obtained by the proposed paper sensor and those obtained by spectrophotometry further revealed the stability and reliability of the paper sensor. In particular, the color intensity of the interaction between the pesticides and coloring agents could be directly observed by the human eye. The consistency of the colorimetric/optical assay was proven in real target pesticide samples. Thus, this sensing strategy provides a portable, cost-effective, accurate and visualized paper platform, which could be suitable for application in the fruit and vegetable industry for monitoring CHL, PRO and CYP in parallel.

Herein, we describe the development of a paper-based device to detect nucleic acids of pathogens of interest in complex samples using loop-mediated isothermal amplification (LAMP) by producing a colorimetric response visible to the human eye. To demonstrate the utility of this device in emerging public health emergencies, we developed and optimized our device to detect SARS-CoV-2 in human saliva without preprocessing. The resulting device was capable of detecting the virus within 60 min and had an analytical sensitivity of 97% and a specificity of 100% with a limit of detection of 200 genomic copies/μL of patient saliva using image analysis. The device consists of a configurable number of reaction zones constructed of Grade 222 chromatography paper separated by 20 mil polystyrene spacers attached to a Melinex® backing via an ARclean® double-sided adhesive. The resulting device is easily configurable to detect multiple targets and has the potential to detect a variety of pathogens simply by changing the LAMP primer sets.

Microfluidic paper-based analytical devices (µPADs) are leading the field of low-cost, quantitative in-situ assays. However, understanding the flow behavior in cellulose-based membranes to achieve an accurate and rapid response has remained a challenge. Previous studies focused on commercial filter papers, and one of their problems was the time required to perform the test. This work studies the effect of different cellulose substrates on diffusion-based sensor performance. A diffusion-based sensor was laser cut on different cellulose fibers (Whatman and lab-made Sisal papers) with different structure characteristics, such as basis weight, density, pore size, fiber diameter, and length. Better sensitivity and faster response are found in papers with bigger pore sizes and lower basis weights. The designed sensor has been successfully used to quantify the ionic concentration of commercial wines with a 13.6 mM limit of detection in 30 s. The developed µPAD can be used in quantitative assays for agri-food applications without the need for any external equipment or trained personnel.

A user-friendly, low-cost detector able to read the RGB indexes of microfluidic paper-based analytical devices (µPADs) was developed. The RGB-detector was built with 3D printing using PLA+ and reused Li-ion batteries. It is Arduino-based, which provides an easy interface between the sensor TCS3200, which reads the quadratic wave of the times corresponding to the RGB numbers, the Arduino itself, whose software translates the times into RGB values, and the touchscreen display, NX3224T028, which shows the results. This detector permits multi-sample analysis since it has a sample holder that can keep up to six µPADs simultaneously and rotate after the display’s request. This work shows how the readings of the RGB indexes by the proposed RGB-detector implement the measurements’ reproducibility. As a proof-of-concept, the RGB-detector application to a green array of µPADs for pH measurement coupled with chemometric analysis allowed us to achieve good results in terms of precision and agreement with the pH values measured by a classical pH-meter.

[Display omitted] • An enrichment method of glycoproteins using microfluidic paper-based analytical devices (μPADs) was developed. • The μPADs consist of two separate parts: the enrichment part (Chip I) and the detection part (Chip II). • The 3-aminophenylboronic acid immobilized on Chip I can capture glycoproteins at pH 8.0 and release them at pH 3.0. • The method can effectively enrich an ovalbumin solution with concentrations as low as 1.0 × 10−11 mol/L. • Glycoproteins was enriched from 1 × 106-fold diluted real egg white samples. We introduce a facile method for glycoprotein enrichment, separation, and detection using microfluidic paper-based analytical devices (μPADs). The μPADs comprise two distinct components: the enrichment region (Chip I) and the detection section (Chip II). The reusable Chip I is fabricated by immobilizing 3-aminophenylboronic acid (APBA) onto a circular paper substrate, demonstrating exceptional glycoprotein affinity. In disposable Chip II, glycoproteins react with periodic acid, generating carbonyl compounds that produce a purple-colored product upon reacting with the Schiff reagent. Alterations in color intensity are captured using an ordinary cell phone and are subsequently analyzed using Photoshop software. Observations note a linear increase in average color intensities from 1.0 × 10−3 to 5.0 × 10−3 mol/L, with an R2 value of 0.9927. The relative standard deviations (RSDs) of inter-day (n = 5) and intra-day (n = 5) assessments stand at 1.5 % and 1.4 %, respectively. Our proposed approach can effectively enrich an ovalbumin (OVA) solution with concentrations as low as 1.0 × 10−11 mol/L, resulting in enrichment rates of 107 to 108 times. The interference deviations of five substances relative to OVA lie within the range of − 2.0 % to + 2.0 %. The methodology successfully enriches glycoproteins from egg white samples diluted by a factor of 1 × 106, demonstrating that the proposed method is remarkably suitable for enriching glycoproteins from authentic samples. [ABSTRACT FROM AUTHOR]

[Display omitted] • Orientationally immobilized enzyme microreactor (OIMER) was developed. • OIMER embedded microfluidic paper-based analytical devices was prepared. • The method is simple, accurate, low cost, rapid and effective in pesticide detection. • The method avoids the need for sophisticated instruments. • The system was applied to detect pesticide residues in vegetable samples. Orientationally immobilized enzyme microreactors (OIMERs), embedded in microfluidic paper-based analytical devices (μPADs) were developed for improved detection of pesticide residues in food. Acetylcholinesterase (AChE) was orientationally immobilized on the reusable Part I of the μPADs, using the specific affinity binding of concanavalin A (Con A) to a glycosyl group on AChE. Using the disposable Part II, facile colorimetric quantification was performed with a smartphone and software, or qualitative detection by a naked-eye visual test. The AChE immobilized in OIMERs not only had improved activity and stability, but also high sensitivity, with a limit of detection as low as (0.007 ± 0.003) μg/mL. The method was used to detect pesticides residues in real vegetable samples; the recovery (88.6–102.7%) showed high reliability for pesticide residues detection in foods. A molecular docking study and an enzyme kinetic analysis were conducted to characterize the mechanism of action of the OIMERs. [ABSTRACT FROM AUTHOR]

Fluid control on a paper channel is necessary for analysis with multiple reagents, such as enzyme-linked immunosorbent assay (ELISA) in microfluidic paper-based analytical devices (µPADs). In this study, a thermo-responsive valve was fabricated by polymerizing N-isopropylacrylamide on a PVDF porous membrane by plasma-induced graft polymerization. The polymerized membrane was observed by scanning electron microscopy (SEM), and it was confirmed that more pores were closed at temperatures below 32 °C and more pores were opened at temperatures above 32 °C. Valve permeability tests confirmed that the proposed polymerized membrane was impermeable to water and proteins at temperatures below 32 °C and permeable to water at temperatures above 32 °C. The valve could also be reversibly and repeatedly opened and closed by changing the temperature near 32 °C. These results suggest that plasma-induced graft polymerization may be used to produce thermo-responsive valves that can be opened and closed without subsequent loss of performance. These results indicate that the thermo-responsive valve fabricated by plasma-induced graft polymerization could potentially be applied to ELISA with µPADs.

Microfluidic paper-based analytical devices (µPADs) represent one of the promising green analytical strategies for low-cost and simple determination of various analytes. The actual task is the development of such devices for quantitation of antioxidants, e.g., flavonoids. In this paper, possibilities of a novel three-reagent µPAD including silver nitrate, 4-nitrophenyldiazonium tetrafluoroborate, and iron(III) chloride as reagents are assessed with respect to the determination of dihydroquercetin. It is shown that all the three reagents produce different colorimetric responses that can be detected by a mini-spectrophotometer–monitor calibrator or by a smartphone. The method is applicable to direct measuring high contents of dihydroquercetin (the linearity range is 0.026–1 mg mL−1, and the limit of detection is 7.7 µg mL−1), which is favorable for many dietary supplements. The analysis of a food supplement was possible with the relative standard deviations of 9–26%, which is satisfactory for quantitative and semiquantitative determinations. It was found that plotting a calibration graph in 3D space of the three reagents’ responses allows us to distinguish dihydroquercetin from its close structural analogue, quercetin.

Over the past decades, paper-based lateral flow immunoassays (LFIAs) have been extensively developed for rapid, facile, and low-cost detection of a wide array of target analytes in a point-of-care manner. Conventional home pregnancy tests are the most significant example of LFAs, which detect elevated concentrations of human chorionic gonadotrophin (hCG) in body fluids to identify early pregnancy. In this work, we have upgraded these platforms to a higher version by developing a customized microfluidic paper-based analytical device (μPAD), as the new generation of paper-based point-of-care platforms, for colorimetric immunosensing. This will offer a cost-efficient and environmentally friendly alternative platform for paper-based immunosensing, eliminating the need for nitrocellulose (NC) membrane as the substrate material. The performance of the developed platform is demonstrated by detection of hCG (as a model case) in urine samples and subsequently indicating positive or negative pregnancy. A dual-functional silane-based composite was used to treat filter paper in order to enhance the colorimetric signal intensity in the detection zones of μPADs. In addition, microfluidic pathways were designed in a manner to provide the desired regulated fluid flow, generating sufficient incubation time (delays) at the designated detection zones, and consequently enhancing the obtained signal intensity. The presented approaches allow to overcome the existing limitations of μPADs in immunosensing and will broaden their applicability to a wider range of assays. Although, the application of the developed hCG μPAD assay is mainly in qualitative (i.e., positive or negative) detection of pregnancy, the semi-quantitative measurement of hCG was also investigated, indicating the viability of this assay for sensitive detection of the target hCG analyte within the related physiological range (i.e., 10–500 ng/mL) with a LOD value down to 10 ng/mL.

A fully integrated device for salivary detection with a sample-in-answer-out fashion is critical for noninvasive point-of-care testing (POCT), especially for the screening of contagious disease infection. Microfluidic paper-based analytical devices (μPADs) have demonstrated their huge potential in POCT due to their low cost and easy adaptation with other components. This study developed a generic POCT platform by integrating a centrifugal microfluidic disc with μPADs to realize sample-to-answer salivary diagnostics. Specifically, a custom centrifugal microfluidic disc integrated with μPADs is fabricated, which demonstrated a high efficiency in saliva treatment. To demonstrate the capability of the integrated device for salivary analysis, the SARS-CoV-2 Nucleocapsid (N) protein, a reliable biomarker for SARS-CoV-2 acute infection, is used as the model analyte. By the chemical treatment of the μPAD surface, and by optimizing the protein immobilization conditions, the on-disc μPADs were able to detect the SARS-CoV-2 N protein down to 10 pg mL -1 with a dynamic range of 10-1000 pg mL -1 and an assay time of 8 min. The integrated device was successfully used for the quantification of the N protein of pseudovirus in saliva with high specificity and demonstrated a comparable performance to the commercial paper lateral flow assay test strips.

Microfluidic paper-based analytical devices modified with molecularly imprinted polymers (μPADs@MIPs) were developed for fluorescent detection of targeted thiols via in situ UV-induced formation of quantum dots (μPADs@MIPs@QDs). The selectivity enhancement by the MIP layer formed on the filter paper surface was demonstrated for the isolation of L-homocysteine from wine. Followed by the addition of metal precursors solution (Zn/Cd/Cu) and UV irradiation, fluorescent quantum dots were formed thus enabling quantitative detection of the thiol (serving as a QD capping agent). The effect of different semiconductors was investigated to achieve a lower band gap and higher fluorescence intensity. Increasing fluorescence intensity in the presence of thiol groups was obtained for the following precursors mixture composition: ZnCdCu/S > ZnCd/S > ZnCu/S > ZnS. The proposed method has a good relationship between the fluorescence intensity of ZnCdCu/S QDs and L-homocysteine in a linear range from 0.74 to 7.40 μM with a limit of detection (LOD) and quantification (LOQ) of 0.51 and 1.71 μM respectively. This method was applied for the determination of L-homocysteine in white wine with RSD under 6.37%. [Display omitted] • Microfluidic paper-based analytical devices modified with MIPs (μPADs@MIPs). • Selective isolation of L-homocysteine from wine. • UV- induced in situ formation of fluorescent clusters. [ABSTRACT FROM AUTHOR]

Smartphone has long been considered as one excellent platform for disease screening and diagnosis, especially when combined with microfluidic paper-based analytical devices (μPADs) that feature low cost, ease of use, and pump-free operations. In this paper, we report a deep learning-assisted smartphone platform for ultra-accurate testing of paper-based microfluidic colorimetric enzyme-linked immunosorbent assay (c-ELISA). Different from existing smartphone-based μPAD platforms, whose sensing reliability is suffered from uncontrolled ambient lighting conditions, our platform is able to eliminate those random lighting influences for enhanced sensing accuracy. We first constructed a dataset that contains c-ELISA results (n = 2048) of rabbit IgG as the model target on μPADs under eight controlled lighting conditions. Those images are then used to train four different mainstream deep learning algorithms. By training with these images, the deep learning algorithms can well eliminate the influences of lighting conditions. Among them, the GoogLeNet algorithm gives the highest accuracy (>97%) in quantitative rabbit IgG concentration classification/prediction, which also provides 4% higher area under curve (AUC) value than that of the traditional curve fitting results analysis method. In addition, we fully automate the whole sensing process and achieve the "image in, answer out" to maximize the convenience of the smartphone. A simple and user-friendly smartphone application has been developed that controls the whole process. This newly developed platform further enhances the sensing performance of μPADs for use by laypersons in low-resource areas and can be facilely adapted to the real disease protein biomarkers detection by c-ELISA on μPADs. [Display omitted] • This deep learning-assisted smartphone platform is unaffected by ambient lighting. • A fully automated "image in, answer out" operation fashion. • A 2048 custom image dataset is used to test 4 mainstream deep learning algorithms. • GoogLeNet provides >97% accuracy in quantitative rabbit IgG testing. • The area under the curve (AUC) is 4% higher than that of conventional methods. [ABSTRACT FROM AUTHOR]

At present, most countries or regions use commercial centrifuges for centrifugation, but this is out of reaching for limited-resource areas. To overcome this problem, a portable electric yo-yo as centrifuge was firstly proposed to obtain serum, and this device can be combined with paper-based analytical devices for enzyme-linked immunosorbent assay (ELISA) analysis from human whole blood. In this study, inflammatory biomarkers C-reactive protein (CRP) and serum amyloid A (SAA) were used as target biomarker to verify the performance of the proposed method. The results shows good performance and their detection limits were determined to be 580 pg/mL for CRP and 800 pg/mL for SAA, respectively. We believe this method provides a new platform of low cost and fast detection for inflammatory biomarkers in the limited-resource settings. Using electric yo-yo device to implement inflammatory biomarkers detection in whole blood paper-based microfluidic immunoassay chip. [Display omitted] • A low-cost, portable and effective electric yo-yo centrifugal device is firstly proposed for blood centrifugation. • Paper-based microfluidic immunoassay chip used for inflammatory biomarkers analysis in whole blood. • The method shows good potential to on-site/limited-resource testing. [ABSTRACT FROM AUTHOR]

In this work, we developed an alternative manufacturing paper-based microfluidics method through 3D printing and wax filament. Microfluidic paper-based analytical devices (μPADs) are low-cost and easy-to-manufacture tools used for various chemical and biological analyses and studies. Paper-based microfluidics with wax has been limited as the manufacturers have discontinued most wax printing equipment. We aim to develop a low-cost and accessible manufacturing method that can replace conventional wax-on paper-based microfluidic manufacturing methods. Using highly available commercial 3D printing technology and wax filament, we could create hydrophobic wax barriers on the surface of different paper types. The properties and limits of this manufacturing method were characterized. Moreover, using this paper-based microfluidic manufacturing method, we were able to measure dopamine electrochemically using μPAD as a passive flow-based method in concentrations as low as 1 nM using injections as small as 15 μL., 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.

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. [Display omitted] • Electromembrane extraction was performed on microfluidic paper analytical device. • The utility of EME was assessed on 2D planar and 3D origami structures. • To demonstrate the device applicability copper ions were extracted and analyzed. • Effective parameters on the extraction efficiency of the analyte were optimized. • The method can extract efficiently the copper ions from complicated matrices. [ABSTRACT FROM AUTHOR]

Microfluidic paper-based analytical devices (µPADs) are leading the field of low-cost, quantitative in-situ assays. However, understanding the flow behavior in cellulose-based membranes to achieve an accurate and rapid response has remained a challenge. Previous studies focused on commercial filter papers, and one of their problems was the time required to perform the test. This work studies the effect of different cellulose substrates on diffusion-based sensor performance. A diffusion-based sensor was laser cut on different cellulose fibers (Whatman and lab-made Sisal papers) with different structure characteristics, such as basis weight, density, pore size, fiber diameter, and length. Better sensitivity and faster response are found in papers with bigger pore sizes and lower basis weights. The designed sensor has been successfully used to quantify the ionic concentration of commercial wines with a 13.6 mM limit of detection in 30 s. The developed µPAD can be used in quantitative assays for agri-food applications without the need for any external equipment or trained personnel.

Integration and storage of bioactive reagents is an important and challenging task in microfluidic paper-based analytical devices (μPADs). Here, we developed a convenient and universal method to store proteins and preserve their activities in μPADs by using aqueous two-phase systems (ATPs) evolved film. A polyethylene glycol (PEG)–dextran (DEX) double-layer film was formed through dehydration of ATPs. Functional biomolecules were stored in the bottom DEX layer on the basis of the biased partitioning and rehydrated conveniently by simple addition of buffer solution at usage. As a demonstration, enzyme immunoassay (EIA) of carcinoembryonic antigen was performed successfully on μPAD integrated with antibodies. Even after 104 days of storage at 4 °C and ambient conditions, the EIA signal just lost less than 10% and 30%, which meet the storage requirements of invitro diagnosis reagents. The ATPs evolved double-layer film has double functions of stabilization and insulation, and provide a high efficiency of biomolecule preservation, thereby promoting the applications of μPADs in POC diagnostic assay. We present a universal and high efficient biomolecules preservation technique using the PEG-DEX ATPs evolved double-layer film for paper based microdevice. [Display omitted] • Antibodies and enzyme were integrated on the paper based microdevice using the ATPs evolved double-layer film. • Signals of μPADs with integrated immuno-reagents were maintained more than 90% after 104 days of storage at 4 °C conditions. • This protein storing method possessed simple operation, high compatibility, and high efficiency in preserving biomolecules. [ABSTRACT FROM AUTHOR]

Paper-based biosensor is one of the most commonly used platforms for point-of-care testing (POCT). Among these platforms, microfluidic paper-based analytical devices (μPADs) have the most versatile designs due to the different hydrophobic barrier patterns and layers of the devices. In addition, μPADs can also be used in combination with other biosensor platforms to improve the performance of the device. Simple and convenient methods for fabricating low-cost and design-adjustable hydrophobic barriers on paper are one of the most challenging aspects for creating μPADs. This work demonstrated a simple technique for using the common polylactic acid (PLA) filament and wax filament to create hydrophobic barriers on paper for μPADs using a commercialized 3D printer. As a proof of concept, the papers with 3D printed PLA barrier were used in combination with a fluidic chip in a prototype biosensor, in which the barrier paper housed four cell-free reactions and the fluidic chip achieved sample delivery to the reactions in the device. Our designed prototype was capable of discriminating dengue virus serotypes based on small nucleotide sequence differences. The proposed combination of 3D-printed barrier paper and fluidic chip provides a versatile platform for rapid prototyping of POCT with possible compatibility with various detection systems. [Display omitted] • 3D printing PLA and wax filaments for creating hydrophobic barriers on paper. • New design for non-immobilized reactions into a prototype biosensor platform. • Prototype biosensor for POCT and discriminating DENV serotypes. [ABSTRACT FROM AUTHOR]

We firstly constructed a kind of self-powered rotating paper-based microfluidic chip and used it to detect thrombin. The integrated movable valve has the ability to control the fluid user-friendly on microfluidic paper-based analytical devices (µPADs), and this advantage let it convenient to implement the complex multistep operations. In addition, this technique is compatible and versatile to the self-powered µPADs at differing levels of complexity. To obtain the supercapacitor signal, the DNA sequence (DNA1) and a glucose oxidase (GOx) modified DNA sequence (GOx-DNA2) were linked with aptamer to form the sandwich structure. Then thrombin will combine with its specific aptamer by strong binding ability, and the GOx-DNA2 could be released and to catalyze the oxidation of glucose. Because of GOx-triggered reaction, the voltage can be generated to charge the paper supercapacitor and its signal could be monitored by digital multimeter. The assay shows good performance with wide linear range (3–1350 nM) and the limit of detection for the thrombin assay was down to 0.9 nM. The proposed rotating paper-based aptamer device can integrate the complex self-powered multistep operations, and show good potential to be applied for on-site assay in the field of diagnosis. • The novel self-powered rotating paper-based microfluidic chip (SPR-µPADs) was proposed and used for thrombin detection. • The integrated paper-based rotational valves is compatible and versatile to the SPR-µPADs. • The device provides a rapid, user-friendly and low-cost way for thrombin detection. [ABSTRACT FROM AUTHOR]

Microfluidic paper-based analytical devices (μPADs) have attracted much attention over the past decade. They embody many advantages, such as abundance, portability, cost-effectiveness, and ease of fabrication, making them superior for clinical diagnostics, environmental monitoring, and food safety assurance. Despite these advantages, μPADs lack the high sensitivity to detect many analytes at trace levels than other commercial analytical instruments such as mass spectrometry. Therefore, a preconcentration step is required to enhance their sensitivity. This review focuses on the techniques used to separate and preconcentrate the analytes onto the μPADs, such as ion concentration polarization, isotachophoresis, and field amplification sample stacking. Other separations and preconcentration techniques, including liquid-solid and liquid-liquid extractions coupled with μPADs, are also reviewed and discussed. In addition, the fabrication methods, advantages, disadvantages, and the performance evaluation of the μPADs concerning their precision and accuracy were highlighted and critically assessed. Finally, the challenges and future perspectives have been discussed. • A critical review of the preconcentration techniques for μPADs is presented. • Both online and offline preconcentration techniques are included. • The approaches for effective separation and preconcentration of chemical and biochemical analytes are highlighted. • A comparison between the preconcentration techniques is discussed. • Challenges and future outlooks of preconcentration techniques for μPADs are presented. [ABSTRACT FROM AUTHOR]

Over the past decades, paper-based lateral flow immunoassays (LFIAs) have been extensively developed for rapid, facile, and low-cost detection of a wide array of target analytes in a point-of-care manner. Conventional home pregnancy tests are the most significant example of LFAs, which detect elevated concentrations of human chorionic gonadotrophin (hCG) in body fluids to identify early pregnancy. In this work, we have upgraded these platforms to a higher version by developing a customized microfluidic paper-based analytical device (μPAD), as the new generation of paper-based point-of-care platforms, for colorimetric immunosensing. This will offer a cost-efficient and environmentally friendly alternative platform for paper-based immunosensing, eliminating the need for nitrocellulose (NC) membrane as the substrate material. The performance of the developed platform is demonstrated by detection of hCG (as a model case) in urine samples and subsequently indicating positive or negative pregnancy. A dual-functional silane-based composite was used to treat filter paper in order to enhance the colorimetric signal intensity in the detection zones of μPADs. In addition, microfluidic pathways were designed in a manner to provide the desired regulated fluid flow, generating sufficient incubation time (delays) at the designated detection zones, and consequently enhancing the obtained signal intensity. The presented approaches allow to overcome the existing limitations of μPADs in immunosensing and will broaden their applicability to a wider range of assays. Although, the application of the developed hCG μPAD assay is mainly in qualitative (i.e., positive or negative) detection of pregnancy, the semi-quantitative measurement of hCG was also investigated, indicating the viability of this assay for sensitive detection of the target hCG analyte within the related physiological range (i.e., 10–500 ng/mL) with a LOD value down to 10 ng/mL. [ABSTRACT FROM AUTHOR]

[Display omitted] • The detection of chromium species using µPADs is critically reviewed. • Paper selection, fabrication and detection methods are discussed. • Mechanisms for the determination of chromium species are compared and discussed. • Colorimetric detection is the most used method to due to its low cost and speed. Chromium pollution in the environment is a serious problem as it is harmful to humans and the environment. The current methods for the detection of chromium species require expensive instrumentation and need to be operated in centralized laboratories. Recently, microfluidic paper-based analytical devices (µPADs) have been developed as simple, cost-effective, and portable tools for on-site detection. In this review, we highlight the recent developments of µPADs for the screening and detection of chromium species in environmental samples. We first summarize the chemistry and toxicity of chromium, the selection of paper substrates, and the device fabrication methods. We then categorize the recent reports on the basis of chromium species into trivalent chromium, hexavalent chromium, speciation, and total chromium detection groups. The evaluation of the performance of µPADs with regard to their accuracy and detection limits is critically assessed. Finally, we discuss the future development and trends in the field of µPADs. [ABSTRACT FROM AUTHOR]

Herein, we describe the development of a paper-based device to detect nucleic acids of pathogens of interest in complex samples using loop-mediated isothermal amplification (LAMP) by producing a colorimetric response visible to the human eye. To demonstrate the utility of this device in emerging public health emergencies, we developed and optimized our device to detect SARS-CoV-2 in human saliva without preprocessing. The resulting device was capable of detecting the virus within 60 min and had an analytical sensitivity of 97% and a specificity of 100% with a limit of detection of 200 genomic copies/μL of patient saliva using image analysis. The device consists of a configurable number of reaction zones constructed of Grade 222 chromatography paper separated by 20 mil polystyrene spacers attached to a Melinex® backing via an ARclean® double-sided adhesive. The resulting device is easily configurable to detect multiple targets and has the potential to detect a variety of pathogens simply by changing the LAMP primer sets., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M.S.V. has interests in Krishi LLC, a company interested in licensing the technology developed here. The work performed here was not funded by Krishi LLC. Employees of Raytheon BBN (sponsor) were involved in the conceptualization and analysis of the data presented here. The contents of this manuscript have been filed for provisional patent protection by Purdue University and Raytheon BBN., (© 2021 The Authors.)