Paper-based Analytical Devices Research Articles

Laser-ablated acoustofluidics-driven paper devices for controllable chemical engineering in color display applications

Paper-based analytical devices (PADs) have rapidly thrived in the last decade for their easy operation and rapid response. However, because of its low chemical reactivity, it’s still challenging to endow the paper substrate with more functions and expand its application field. Here, this work leverages lasers to do surface modifications of paper to raise its chemical reactivity. A gentle power of laser was utilized to ablate a part thickness of the paper. The effect of laser types was studied, including continuous-wave, nanosecond, and femtosecond lasers. Continuous-wave laser caused severe photothermal effects and produced more pyrolytic oil. The physical changes including mechanical strength and fluid wicking were studied. The chemical changes were analyzed by XPS and FTIR. Because of the produced aldehydes by laser ablation, the laser-modified papers were endowed with more functions and we experimented with aldehyde-related color reactions on them, which might promote the color printing industry. In addition, to fully exploit the produced aldehydes, our recently developed acoustofluidic PADs were employed for flow intensification and homogeneous mixing. This work demonstrates an economical and effective method for a new type of functional paper substrates which holds potential for various fields.

Tuning the Chemical and Electrochemical Properties of Paper-Based Carbon Electrodes by Pyrolysis of Polydopamine.

Electrochemical paper-based analytical devices represent an important platform for portable, low-cost, affordable, and decentralized diagnostics. For this kind of application, chemical functionalization plays a pivotal role to ensure high clinical performance by tuning surface properties and the area of electrodes. However, controlling different surface properties of electrodes by using a single functionalization route is still challenging. In this work, we attempted to tune the wettability, chemical composition, and electroactive area of carbon-paper-based devices by thermally treating polydopamine (PDA) at different temperatures. PDA films were deposited onto pyrolyzed paper (PP) electrodes and thermally treated in the range of 300-1000 °C. After deposition of PDA, the surface is rich in nitrogen and oxygen, it is superhydrophilic, and it has a high electroactive area. As the temperature increases, the surface becomes hydrophobic, and the electroactive area decreases. The surface modifications were followed by Raman, X-ray photoelectron microscopy (XPS), laser scanning confocal microscopy (LSCM), contact angle, scanning electron microscopy (SEM-EDS), electrical measurements, transmission electron microscopy (TEM), and electrochemical experiments. In addition, the chemical composition of nitrogen species can be tuned on the surface. As a proof of concept, we employed PDA-treated surfaces to anchor [AuCl4]- ions. After electrochemical reduction, we observed that it is possible to control the size of the nanoparticles on the surface. Our route opens a new avenue to add versatility to electrochemical interfaces in the field of paper-based electrochemical biosensors.

Electrochemical microfluidic paper-based analytical device for label-free detection of SARS-CoV-2 antigen by LDH redox probe

In the offered study, the proposed sensor combined the innovative disposable microfluidic paper-based immunosensor and cost-effective plant-based anti-SARS-CoV-2 monoclonal antibody CR3022, expressed in Nicotiana benthamiana. An electrochemical microfluidic paper-based analytical device (µPAD) was introduced for quantitative detection of the SARS-CoV-2 antigen employing electrocatalytic activity of the Ni Fe layered double hydroxide (NiFe LDH). Its electrocatalytic activity asthe platform of proposed the analytical device enhanced the signal output via redox-recycling of the species the ferri/ferrocyanide [Fe(CN)6]3-/4- in solution and is applied to µPAD response signal. Layered NiFe double hydroxide (LDH) nanosheets with a suitable redox potential were prepared by incorporating Fe into the Ni-based LDH. With the help of Fe, the charge-transfer kinetics for the reduction of Ni3+ to Ni2+ was improved and the formation of unwanted Ni components with higher oxidation state was suppressed. The incorporated Fe as the electron transfer mediator enhanced the process of Ni(OH)2/NiOOH redox cycle. Under the optimum conditions, the dependency of impedance signal and SARS-CoV-2 concentration showed a linear region from 10 fg/mL-5 ng/mL with a detection limit of 0.23 fg/mL. This Paper-based immunosensor device also showed long stability and good reproducibility, which can be used for the quantitative assay of the SARS-CoV-2. The results of nasal samples analysis revealed the applicability of the resulting biosensor.

Prostate cancer diagnosed and staged using UV-irradiated urine samples and a paper-based analytical device

The early detection of prostate cancer (CaP), one of the most common cancers in males, improves treatment efficacy. However, current methods to detect CaP are limited by specificity and sensitivity or require an invasive and unpleasant procedure. Therefore, there is a need for a novel, fast, and noninvasive CaP detection method. This proof-of-concept study aimed to diagnose CaP from urine samples by detecting the UV-induced fluorescent clusters formed in situ that reflect a urine composition specific to CaP patients using fluorescence spectroscopy. The UV-induced clusters formed upon irradiation by UV light with a wavelength of 254 nm were detected at excitation and emission wavelengths of 400 nm and 460 nm. Fifteen patients with CaP were correctly distinguished from 5 controls. The different stages of CaP could be further determined using molecular imprinting technology. Additionally, a paper-based analytical device was developed that enabled the correct identification of stage I cancer patients by fluorescent spectroscopy detection and the naked eye. In conclusion, this novel, easy-to-operate, point-of-care assay can enable early diagnosis of CaP with high accuracy and judgement of the disease stage. The simplicity, as well as versatility of the proposed method, will enable its application also to other diseases and disorders.

A dual-mode assay kit using a portable potentiostat connected to a smartphone via Bluetooth communication and a potential-power angle-based paper device susceptible for low-cost point-of-care testing of iodide and dopamine

BackgroundConsidering that the brain controls most of the body's activities, it is very important to measure the factors affecting its function, such as dopamine and iodide. Due to the growing population in the world, it is necessary to provide fast, cheap and accurate methods with the capability of on-site analysis and without the need for invasive sampling and operator skill. As a result, there is a strong desire to replace laboratory instruments with small sensors for point-of-care testing. Paper-based analytical devices (PADs) are one of the popular zero-cost approaches to achieve this goal. ResultsWe developed a simple and disposable diagnostic paper system based on electroanalytical and potential-power angle-based methods. First, we prepared an angle-based analytical system capable of performing semi-quantitative iodide analysis simply by reading the colored angle traveled. This system design is based on a channel containing complex reagents and two pencil-drawn electrodes to apply a constant voltage accelerating the anions migration. Meanwhile, a three-electrode system based on conductive pencil graphite is developed to measure dopamine concentration based on linear sweep voltammetry. For the quantitative analysis, the voltammetric data was wirelessly transmitted to a mobile device via Bluetooth communication. In this context, a power supply providing the required voltage for the migration of iodide ions, a portable potentiostat system, and a mobile application for measuring dopamine were developed. The calibration curves for I− and dopamine range from 3.5 × 10−4-47.0 × 10−4 and 10.0 × 10−6-1000.0 × 10−6 mol L−1 with LODs of 2.3 × 10−4 and 5.0 × 10−6 mol L−1, respectively. Significance and noveltyA new portable dual-mode voltage-assisted integrated PAD platform was designed for iodide and dopamine analysis. The characteristics of this device allow non-experts to carry out in-field analysis using sub-100 μL saliva sample with a time-to-result of <10 min along with reducing the overall cost and operational complexity.

Improving pesticide residue detection: Immobilized enzyme microreactor embedded in microfluidic paper-based analytical devices

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.

Development of Microfluidic Paper-Based Analytical Devices (µPADs) for Determination of Cd2+, Pb2+, and Cu2+ Ions in Mineral Water

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.

Smart dual imprinted Origami 3D-ePAD for selective and simultaneous analysis of vanillylmandelic acid and 5-hydroxyindole-3-acetic acid carcinoid cancer biomarkers using graphene quantum dots coated with dual molecularly imprinted polymers

Measuring the levels of the biomarkers vanillylmandelic acid (VMA) and 5-Hydroxyindole-3-acetic acid (5-HIAA) is a valuable tool for clinical diagnosis not only of neuroblastoma or carcinoid syndrome, but also of essential hypertension, depression, migraine, and Tourette's syndrome. Herein, we explore using graphene quantum dots (GQDs) coated with molecularly imprinted polymer (MIP) as novel dual-imprinted sensors for selective and simultaneous determination of VMA and 5-HIAA in urine and plasma samples. The dual-MIP was successfully coated on the GQDs core via co-polymerization of (3-aminopropyl) triethoxysilane (APTES) and tetraethyl orthosilicate (TEOS), acting as functional and cross-linking monomers, respectively. In addition, we successfully created the dual imprinted VMA and 5-HIAA shell on the GQDs' core via a one-pot synthesis. We fabricated a facile and ready-to-use Origami three-dimensional electrochemical paper-based analytical device (Origami 3D-ePAD) for simultaneous determination of VMA and 5-HIAA using a GQDs@dual-MIP modified graphene electrode (GQDs@dual-MIP/SPGE). The Origami 3D-ePAD was designed to form a voltammetric cell on a three-layer foldable sheet with several advantages. For example, they were quickly assembled and enhanced the device's physical durability with the hydrophobic backup sheet. The developed dual imprinted Origami 3D-ePAD leads to substantially enhanced sensitivity and selectivity to electrochemical signal amplification generated from increasing the electrode-specific surface area, electrocatalytic activity, and the large numbers of dual imprinted sites for VMA and 5-HIAA detection. The synthetic recognition sites are highly selective for 5-HIAA and VMA molecules with an imprinting factor of 8.46 and 7.10, respectively. Quantitative analysis relying on square wave voltammetry reveals excellent linear dynamic ranges of around 0.001–25 μM, with detection limits of 0.023 nM for 5-HIAA and 0.047 nM for VMA (3Sb, n = 3). The Origami 3D-ePAD provides high accuracy and precision (i.e., recovery values of 5-HIAA ranged from 82.98 to 98.40 %, and VMA ranged from 83.28 to 104.39 %), and RSD less than 4.37 %) in urine and plasma samples without any evidence of interference. Hence, it is well suited as a facile and ready-to-use disposable device for point-of-care testing. It is straightforward, cost-effective, reproducible, and stable. Furthermore, it allows for rapid analysis (analysis time ∼20s) useful in medical diagnosis and other relevant fields.

Fast and sensitive smartphone colorimetric detection of whole blood samples on a paper-based analytical device

BackgroundMethods based on paper-based analytical devices (PAD) and smartphone photographic colorimetric detection have become representative instrument-independent point-of-care testing (POCT) platforms due to their low cost and simplicity. However, the detection of target components from whole blood sample still presents challenges in terms of field preparation of small amounts of blood sample and detection sensitivity. This paper presents a rapid online processing method for whole blood samples on PAD based on plasma separation membrane (PSM), and combined with electrokinetic stacking and selective chromatic reaction. Real-time smartphone-based colorimetric detection of free hemoglobin (FHb) and human serum albumin (HSA) was successfully demonstrated. ResultsWith the proposed method, both detections for low and high concentration analytes could be implemented. The limits of detection of 16.6 mg L-1 for FHb and 0.67 g L-1 for HSA were obtained, respectively, with RSD below 8 %. The reliability of the method was verified by the recovery test and desktop spectrophotometric method. The detection results for real blood samples were in agreement with that by clinical methods. Significance and noveltyThe PAD method is inexpensive, simple and fast, and detection of a whole blood sample of 5 μL can be finished in 5 min. This work shows that POCT of biomarkers from whole blood with PAD is possible without using any desktop facilities.

µPAD-based colorimetric nanogold aptasensor for CRP and IL-6 detection as sepsis biomarkers

Point-of-care testing is defined as medical diagnostic testing at or near the time and place of a patient. The integration of microfluidics with functionalized nanomaterials provides a rapid and sensitive detection method for biomarkers. Due to their optical characteristics, gold nanoparticles (GNPs) and aptamers can be used in a colorimetric technique. In this research, accurate and quick aptasensors were created using aptamers for two sepsis biomarkers, interleukin-6 (IL-6) and C-reactive protein (CRP). Aptamers were combined with GNPs to create aptasensors, which were then used to analyze various biomarker concentrations after aptamer-protein docking on the online HDOCK server to verify aptamer-protein interactions. To improve the results' stability and ease of use during the reaction time, microfluidic paper-based analytical devices (µPAD) was employed. The linear diagnostic ranges in this method were 50–1000 mg L−1 and 1–25 ng/L, and limit of detection values were 1.9 mg L−1 and 0.07 ng/L for CRP and IL-6, respectively; These values decreased when µPADs were used and became more suitable to diagnosis of sepsis. Two aptasensors were highly stable, reproducible, accurate, and recoverable. Our result suggests that colorimetric GNPs can be used to detect a specific analyte through color changes visible to the naked eye for monitoring purposes or as simple optical detectors for quantitative measurements.

Smartphone-integrated colorimetric and microfluidic paper-based analytical devices for the trace-level detection of permethrin.

Permethrin is a pyrethroid pesticide and insect repellent that prevents mosquito-borne infections like dengue and malaria in tropical areas. This work describes a new colorimetric sensor based on metronidazole-stabilized silver nanoparticles (MTZ-AgNPs) for the first rapid, sensitive, and selective permethrin detection. The MTZ-AgNPs-based colorimetric sensor has a limit of detection (LOD) of 0.0104µM and a limit of quantification (LOQ) of 0.0348µM, respectively. The sensor is further integrated with smartphone and microfluidic fabrication of paper-based analytical devices (µPADs) for real-time and on-site detection of permethrin. Under optimal settings, no potential environmental contaminants interfere with permethrin detection, confirming its high selectivity. Finally, the practical applicability of sensors is confirmed in real tomato and apple extract samples. The US environmental protection agency's recommended UPLC method validated the detection efficiency of the proposed colorimetric sensor. The % recoveries from UPLC and MTZ-AgNPs suggest that the present sensor can quantitatively analyze permethrin in real samples.

Construction of fluorescent sensor array and three-dimensional microfluidic paper based analytical device for specific identification and visual determination of antibiotics in food.

For antibiotics misuse since the global outbreak of COVID 19, a novel strategy for discriminating and detecting antibiotics is proposed based on the graphene quantum dots with multi-doped heteroatoms including F, N and P (M-GQDs), which exhibit blue emission (419.0nm) under the excitation of 336.0nm. Specifically, the fluorescence of M-GQDs is quenched by tetracyclines (TCs) owing to inner filter effect (IFE) and enhanced by alkane-modified fluoroquinolones (AFQs), which is attributed to restricted conformational rotation based on π-π stacking, hydrogen-bonding and electrostatic interactions. Meanwhile, the electron-accepting property of oxazine ring in oxazine-modified fluoroquinolones (OFQs) increases emission peak at 498.0nm and decreases emission peak at 419.0nm as the color changes from blue to cyan. Moreover, a cascade system integrated with 3D microfluidic paper-based analytical device (3D-μPAD) is applied successfully for visually distinguishing three antibiotics, which shows great potential and versatility of M-GQDs for food safety monitoring.

The use of Clitoria ternatea as sustainable detection tool for Ni (II) and Cu (II) ions in simple paper-based analytical device

Clitoria ternatea plants was growth widely in Indonesia. It was used as natural coloring in food or supplements. In this study, the C. ternatea flower was extracted using ethanol 70% and used for detection of metal ions (Ni, Cu) in aqueous medium. The ability of anthocyanins in C. ternatea extract to react with metal ions was studied using UV-Visible spectroscopy. It was found that the complex of metal ions with C. ternatea flower extract making the hypsocromic effect to the spectra of C. ternatea pure extract. Furthermore, simple paper based analytical device attached with C. ternatea extract was used as test spot to detect the metal ions. It reveals that the color of C. ternatea extract was changed and the calibration curve was obtained. The limit of detection (LOD) in the optimum pH for Ni (II) and Cu (II) was 8.89 ppm, and 4.49 ppm, respectively. Thus, this study showed that C. ternatea flower extract provides sustainable color detection for metal ions with economic and environmental benefits.

A simple and low-cost paper-based device for simultaneous determination of hematocrit and hemoglobin levels in point-of-care settings

Hematocrit and hemoglobin levels are common blood tests used to assess the overall health status of patients as well as the oxygen-carrying capacity of the blood. The gold-standard technologies to determine the hematocrit and hemoglobin levels are precise and fast, but they are not pragmatic in extreme point-of-care settings due to the prohibitive cost, process complexity, and sophisticated facilities. Therefore, here, we report the development of a microfluidic paper-based analytical device to determine hematocrit and hemoglobin levels simultaneously. This device exploits the area of the stain formed by a spreading drop of 20 μl of whole blood on Whatman filter paper immobilized with sodium chloride and ethylenediaminetetraacetic acid for hematocrit level, whereas for hemoglobin concentration, it utilizes the gray color intensity of a 20 μl droplet of a mixture of blood and de-ionized water. The performance of the device is verified by comparing with gold-standard results of the automated hematology analyzer, showing a high degree of correlation (R2) of 0.9651 and 0.9701 for hematocrit and hemoglobin levels, respectively. The bias and standard deviation of the differences between the two measurements for hematocrit determination are 0.002 and 1.005, respectively, while the bias and standard deviation of differences between the two methods for hemoglobin determination are 0.065 and 0.398, respectively. This device is likely to provide a simple, fast, disposable, and inexpensive tool to determine the hematocrit and hemoglobin levels in resource-constraint settings.

Dual-spot ratiometric microfluidic paper-based analytical device for accuracy and precision improvement

Instrumental and environmental fluctuations are common sources of error in smartphone-based optical detection, significantly affecting the accuracy of analytical measurements. In this regard, spotting the sample and reference simultaneously and in close proximity compensates for the fluctuations. This “dual-spot” design is similar to the double-beam technique used in spectrophotometry, which reduces fluctuations in the results. The underlying hypothesis is that any instrumental and/or environmental factors influencing the color intensity in the detection zones will similarly impact the color intensity in the control zone under the same conditions. To test our design, a ratiometric microfluidic paper-based analytical device (μPAD), functionalized with a mixture of green-emissive carbon dots (CDs) and red-emissive ethidium bromide, was developed for the selective detection of ascorbic acid (AA). The green emission of the CDs is quenched by both AA and Fe3+; NaF was thus loaded onto the 3D connector as a masking agent to remove the interference effect of the Fe3+ ions. The color variations were monitored under a UV lamp, using a smartphone to capture the images, and the RGB intensities were processed using the Color Grab application. The proposed double-spot method greatly enhanced the analytical precision and accuracy of the device. A linear working range from 0 to 125 μM was obtained, and the limit of detection was 2.71 μM. The μPAD was successfully used for the detection of AA in human serum, with recoveries from 87.27 to 98.52 %.

Self-cleaning paper-based microfluidic biosensor employing DNAzyme and semiconducting single-walled carbon nanotube for copper ion detection

Microfluidic paper-based analytical device (μPAD) offers a simple and efficient platform for point-of-care monitoring, which can be beneficial for copper determination in livestock feed and manure. However, common cellulose paper has excellent hydrophilicity, causing μPAD is accompanied by poor mechanical properties, short service life, and low sensitivity. Here, a self-cleaning paper-based microfluidic biosensor for Cu2+ determination was proposed to overcome the mentioned shortages in the application. Polymeric octadecyl trichlorosilane was synthesized and decorated on cellulose paper to form hydrophobic paper, which can improve the hydrophobicity, self-cleaning, and pollution ability. In addition, hydrophobic paper, semiconducting single-walled carbon nanotube, and DNAzyme through the chemical bond were employed to fabricate a self-cleaning paper-based microfluidic biosensor. The properties were investigated using scanning electron microscopy, Raman, and electrochemical methods. The detecting parameters were also optimized. It could measure the Cu2+ concentration from 1 nM to 100 μM, and the detection limit was 0.65 nM. The self-cleaning paper-based microfluidic biosensor was applied to detect Cu2+ concentration in livestock feed and manure that can meet the requirements for fast screening and detection.

A Microfluidic Paper-based Analytical Device for Simultaneous Measurement of Albumin, Creatinine and Uric Acid in Urine based on Standard Addition Method

This work describes a simple method for the simultaneous measurement of urinary albumin, creatinine and uric acid using a standard addition approach on a microfluidic paper-based analytical device (µPAD). Hydrophobic barrier of the µPAD was created by stamping indelible ink onto a filter paper. The µPAD was designed with a flower-liked configuration. After aliquoting urine to a central sample zone, the sample flowed to ten surrounding channels, namely “the inner channels”, where the blank (water) or standard solutions had been added. The inner channels were connected to circular reagent zones where reagents had been immobilized. Tetrabromophenolphthalein ethyl ester, alkaline picrate, and a mixed solution of ferric chloride and ferric cyanide were used as the chromogenic reagents for the colorimetric detections of albumin, creatinine, and uric acid, respectively. Each reagent zone was linked with a circular detection zone through a second channel, namely “the outer channels”. The blue-, orange- and greenish-blue colored products were observed in the detection zones for the measurement of albumin, creatinine, and uric acid, correspondingly. A digital image of the µPAD was captured with a mobile phone. The color intensities were evaluated by ImageJTM and were employed for the quantitative analyses. The standard addition calibrations were found to be linear (r2 &gt; 0.99) for the spiked analyte concentrations up to 100 mg L-1 albumin, 1000 mg L-1 creatinine, and 50 mg dL-1 uric acid. The paper platform provided high precision (RSD &lt; 5 %) and good analytical recovery (91.8-109.7 %). Under paired t-test, the results obtained by the developed µPAD and the validating methods were not significantly different at 95 % confidence (albumin: tstat = -0.130, tcri = 3.182, creatinine: tstat = -0.133, tcri = 3.182, and uric acid: tstat = 1.119, tcri = 3.182).

Paper-Based Analytical Device Based on Potentiometric Transduction for Sensitive Determination of Phenobarbital.

In medicine, barbiturates are a class of depressive medications used as hypnotics, anticonvulsants, and anxiolytics. For the treatment of specific forms of epilepsy and seizures in young children in underdeveloped countries, the World Health Organization recommends phenobarbital (PBAR), a barbiturate drug. This review describes the fabrication and characterization of a paper-based analytical apparatus for phenobarbital detection that is straightforward, affordable, portable, and disposable. All of the solid-state ion-selective electrodes (ISEs) for PBAR as well as a Ag/AgCl reference electrode were constructed and optimized on a nonconductive paper substrate. Using carbon nanotube ink, the sensors were made to function as an ion-to-electron transducer and to make the paper conductive. A suitable polymeric membrane is drop-cast onto the surface of the carbon ink orifice. The pyrido-tetrapeptide and pyrido-hexapeptide derivatives, which were recently synthesized, functioned as distinct ionophores in the PBAR-membrane sensor, enabling its detection. With a detection limit of 5.0 × 10-7 M, the manufactured analytical device demonstrated a Nernstian response to PBAR anions in 50 mM phosphate buffer, pH 8.5, over a linear range of 1.0 × 10-6 to 1.0 × 10-3 M. The PBAR-based sensors showed quick (less than 5 s) response times for PBAR ion detection. The modified separate solution method was utilized to evaluate the selectivity pattern of these novel ionophores with respect to PBAR ions in comparison to other common anions. The analytical instrument that was exhibited on paper had good precision both within and between days. The suggested technology assisted in the detection of trace amounts of PBAR in real pharmaceutical samples. A comparison was made between the data acquired using the HPLC reference method and the information obtained by the recommended potentiometric approach. The described paper-based analytical device may be a good choice for point-of-care PBAR determination because it is cheap and easy to find and can self-pump (especially when combined with potentiometric detection).

Miniaturized paper-based analytical device for the portable analysis of phyto-cannabinoids in plant and oral fluids

In this work, a low-cost and eco-friendly paper-based analytical device (PAD) method is described for the determination of phyto-cannabinoids in cannabis and oral fluids based on a simple colorimetric reaction. The PAD was able to distinguish tetrahydrocannabinol (THC)- and cannabidiol (CBD)-rich plant samples by using 4-aminophenol (4-AP) and later on to quantify total phyto-cannabinoid content (THC + CBD + CBN) in plant and oral fluids by using the Fast Corinth V reagent. The chemical and physical properties regarding paper type and reagent concentration in the PAD were optimized to achieve the best analytical performance. After that, analytical features were obtained, including a linear range of 0.01–0.1 mg mL−1, a limit of detection (LOD) of 0.003 mg mL−1, and a suitable precision, expressed as relative standard deviation (RSD) lower than 10%. Furthermore, no significant interferences were observed in colorimetric reactions when tea, herbs, and drug samples were analyzed. Additionally, the PAD proved color stability up to 1 month after the sampling at 25 °C. The developed PAD was suitable for determining total phyto-cannabinoid content in plants and oral fluids, obtaining good results compared to GC–MS. Overall, this method showed good reliability resulting in an operational on-site device for drug monitoring.Graphical

Colorimetric detection of glucose with smartphone-coupled µPADs: harnessing machine learning algorithms in variable lighting environments

Recent advances in microfluidic paper-based analytical devices (µPADs) have shown immense potential for point-of-care testing (POCT) in resource-constrained settings, especially for monitoring glucose levels in patients with diabetes. However, the practical adoption of smartphone-coupled µPADs has been limited due to the variability in ambient lighting conditions, which affects the colorimetric detection. In this study, we have developed a machine learning-based algorithm together with a flash/no-flash technic, adaptable to various µPADs and capable of accurately monitoring plasma glucose levels across a wide range (25 µM to 30 mM), addressing issues related to environmental illumination variations, and shooting angles.The algorithm is implemented in an Android application, Gluco estimator. It utilizes images captured by smartphones and incorporates intelligent feature engineering. The XYZ color space is adopted for device-independent analysis. KI and TMB color indicators are used to enhance resolution for low and high glucose concentrations, respectively. The EBC classifier, combined with a handcrafted feature set, exhibits outstanding performance, achieving an accuracy of 95% and 91% for TMB and KI, respectively. Additionally, multiple linear regression (MLR) yields high reliability among regression models, with R2 values of 0.95 at 0.25 µM to 3 mM and 0.97 at 3–30 mM. This work represents a significant stride toward realizing a portable, high-resolution, and reliable smartphone-coupled µPAD in uncontrolled environments.