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Captopril (CP) is commonly used as an active enzyme inhibitor for the treatment of coronary heart disease, hypertension and angina pectoris. The development of sensitive and efficient method for CP analysis is of great importance in biomedical research. Herein, we fabricated a sensitive and robust hydrogel-assisted paper-based sensor based on fluorescence UiO-66-NH 2 @ZIF-8 and Co, N-doped carbon nanozymes with oxidase-mimicking activity for accurate monitoring of captopril. The hydrogel-assisted paper-based sensor appeared a visible pink signal due to the catalytic oxidation of colorless N,N-diethyl-p-phenylenediamine (DPD) to oxDPD by Co, N-doped carbon-based nanozymes, and resulted in the fluorescence quenching of UiO-66-NH 2 @ZIF-8. In the presence of captopril, the oxidation of chromogenic substrate DPD by Co, N-doped nanozymes in the hydrogel-assisted paper-based sensor was hindered and accompanied by a change in the visible color, leading to recovery of the fluorescence of UiO-66-NH 2 @ZIF-8, and the change in the fluorescence color could also be observed. Therefore, the quantitative detection of captopril is achieved by taking a smartphone photograph and converting the image parameters into data information using ImageJ software. The portable hydrogel-assisted paper sensor provided sensitive detection of captopril in two modes based on visible color change as well as fluorescence color change with limits of detection of 0.45 μM and 0.47 μM, respectively. This hydrogel-assisted paper-based sensor has been successfully applied to the accurate monitoring of captopril in human serum, providing a potential avenue for in situ detection of captopril., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

This work reports the development of low-cost and rapid multiplexed colorimetric assay of antioxidants (total phenolics, antioxidant capacity, flavonoids and anthocyanins) in wines at daisy-shaped fluidic paper-based analytical devices (PADs). The desired fluidic patterns were formed on paper by pen drawing and colorimetric reagents were immobilized at the 6 peripheral test zones. The sample was added at the central sample zone, migrated to the test zones and reacted with the immobilized reagents producing characteristic colors that were captured and analyzed. The paper-based approach was applied to the analysis of several wine samples and the results were statistically correlated to standard solution-based colorimetric assays, indicating that it could be reliably used for ranking wines according to their antioxidants content. In addition, the paper-based analytical methodology is simple, instrument-free, portable, cost-effective, rapid and environment friendly., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The detections of H 2 O 2 and catalase play an important role in daily life. This study introduces a paper-based flow sensor that is specifically designed to detect H 2 O 2 and catalase. The sensor utilizes a hydrogel composed of cross-linked 4-carboxyphenylboronic acid and polyvinyl alcohol. When H 2 O 2 is in contact with the hydrogel, the B-C bonds of the hydrogel undergo a reactive process, causing decomposition of the hydrogel. The pH indicator strip enables the visual monitoring of the viscosity change that occurs during the gel-sol transition. The quantification of H 2 O 2 is accomplished by assessing the proportion of water coverage on the pH indicator strip. The sensor shows a detection limit of 0.077 wt% and is applicable for the quantitative measurement of H 2 O 2 in routinely used disinfectants. Furthermore, the presence of catalase is effectively identified and the detection of catalase in milk is successfully fulfilled. In summary, this work proposes a simple, user-friendly, label-free, and cost-effective method for constructing a paper-based flow sensor using borate cross-linked polyvinyl alcohol hydrogel, showing great potential for detecting H 2 O 2 and catalase in various practical scenarios., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Due to the common contamination of multiple mycotoxins in food, which results in stronger toxicity, it is particularly important to simultaneously test for various mycotoxins for the protection of human health. In this study, a disposable immunosensor array with low-cost was designed and fabricated using cellulose paper, polydimethylsiloxane (PDMS), and semiconducting single-walled carbon nanotubes (s-SWCNTs), which was modified with specific antibodies for mycotoxins AFB1 and FB1 detection. The strategy for fabricating the immunosensor array with two individual channels involved a two-step protocol starting with the form of two kinds of carbon films by depositing single-wall carbon nanotubes (SWCNTs) and s-SWCNTs on the cellulose paper as the conductive wire and sensing element, followed by the assembly of chemiresistive biosensor with SWCNTs strip as the wire and s-SWCNTs as the sensing element. After immobilizing AFB1-bovine serum albumin (AFB1-BSA) and FB1-bovine serum albumin (FB1-BSA) separately on the different sensing regions, the formation of mycotoxin-BSA-antibody immunocomplexes transfers to electrochemical signal, which would change with the different concentrations of free mycotoxins. Under optimal conditions, the immunosensor array achieved a limit of detection (LOD) of 0.46 pg/mL for AFB1 and 0.34 pg/mL for FB1 within a wide dynamic range from 1 pg/mL to 20 ng/mL. Furthermore, the AFB1 and FB1 spiked in the ground corn and wheat extracts were detected with satisfactory recoveries, demonstrating the excellent practicality of this established method for simultaneous detection of mycotoxins., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Di(2-ethylhexyl)phthalate (DEHP) is commonly released from plastics in aqueous environment, which can disrupt endocrine system and cause adverse effects on public health. There is a pressing need to highly sensitive detect DEHP. Herein, a near-infrared (NIR) light-driven lab-on-paper cathodic photoelectrochemical aptasensing platform integrated with AgInS 2 /Cu 2 O/FeOOH photocathode and "Y"-like ternary conjugated DNA nanostructure-mediated "ON-OFF" catalytic switching of hemin monomer-to-dimer was established for ultrasensitive DEHP detection. Profiting from the collaborative roles of the effective photosensitization of NIR-response AgInS 2 and the fast hole extraction of FeOOH, the NIR light-activated AgInS 2 /Cu 2 O/FeOOH photocathode generated a markedly enhanced photocathodic signal. The dual hemin-labelled "Y"-like ternary conjugated DNA nanostructures made the hemin monomers separated in space and they maintained highly active to catalyze in situ generation of electron acceptors (O 2 ). The hemin monomers were relocated in close proximity with the help of target-induced allosteric change of DNA nanostructures, which could spontaneously dimerize into catalytically inactive hemin dimers and fail to mediate electron acceptors generation, resulting in a decreased photocathodic signal. Therefore, the ultrasensitive DEHP detection was realized with a linear response range of 1 pM-500 nM and a detection limit of 0.39 pM. This work rendered a promising prototype to construct powerful paper-based photocathodic aptasensing system for sensitive and accurate screening of DEHP in aqueous environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study presents a potent paper-based analytical device (PAD) for quantifying various sugars using an innovative bi-nanozyme made from a 2-dimensional Fe/Ce metal-organic framework (FeCe-BTC). The MOF showed excellent bifunctional peroxidase-oxidase activities, efficiently catalyzing luminol's chemiluminescence (CL) reaction. As a peroxidase-like nanozyme, FeCe-BTC could facilitate the dissociation of hydrogen peroxide (H 2 O 2 ) into hydroxyl radicals, which then oxidize luminol. Additionally, it was also discovered that when reacting with H 2 O 2 , the MOF turns into a mixed-valence MOF, and acts as an oxidase nanozyme. This activity is caused by the generated Ce 4+ ions in the structure of MOF that can directly oxidize luminol. The MOF was directly synthesized on the PAD and cascaded with specific natural enzymes to establish simple, rapid, and selective CL sensors for the measurement of different sugars. A cell phone was also used to record light intensities, which were then correlated to the analyte concentration. The designed PAD showed a wide linear range of 0.1-10 mM for glucose, fructose, and sucrose, with detection limits of 0.03, 0.04, and 0.04 mM, respectively. It showed satisfactory results in food and biological samples with recovery values ranging from 95.8 to 102.4 %, which makes it a promising candidate for point-of-care (POC) testing for food control and medicinal purposes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Timely and rapid detection of antibiotic residues in the environment is conducive to safeguarding human health and promoting an ecological virtuous cycle. A foldable paper-based photoelectrochemical (PEC) sensor was successfully developed for the detection of ampicillin (AMP) based on glutathione/zirconium dioxide hollow nanorods/aptamer (GSH@ZrO 2 HS@apt) modified cellulose paper as a reactive zone with laser direct-writing lead sulfide/cadmium sulfide/graphene (PbS/CdS/LIG) as photoelectrode and cobalt hydroxide (CoOOH) as a photoresist material. Initially, AMP was introduced into the paper-based reaction zone as a biogate aptamer, which specifically recognized the target and then left the ZrO 2 HS surface, releasing glutathione (GSH) encapsulated inside. Subsequently, the introduction of GSH into the reaction region and etching of CoOOH nanosheets to expose the PbS/CdS/LIG photosensitive material increased photocurrent. Under optimal conditions, the paper-based PEC biosensor showed a linear response to AMP in the range of 5.0 - 2 × 10 4 pM with a detection limit of 1.36 pM (S/N = 3). In addition, the constructed PEC sensing platform has excellent selectivity, high stability and favorable reproducibility, and can be used to assess AMP residue levels in various real water samples (milk, tap water, river water), indicating its promising application in environmental antibiotic detection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Developing portable and sensitive biosensors for bacteria detection is highly demanded due to their association with environmental and food safety. Paper-based microfluidic chip is the suitable candidate for constructing pump-free biosensor since paper is hydrophilic, low-cost and easy to use. However, the contradiction between sensitivity and small sample volume seriously affects the application of paper-based chip for bacteria detection. Here, a new microfluidic biosensor, combining large PDMS reservoir for sample storage, hydrophilic paper substrate for pump-free water transport, coated microspheres for bacteria capture and super absorbent resin for water absorption, is designed for the detection of bacteria in aqueous samples. Once the sample solution is introduced in the reservoir, water will automatically flow through the gaps between microspheres and the target bacteria will be captured by the aptamer coated on the surface. To facilitate PDMS reservoir bonding and ensure water transport, the upper side of paper substrate is coated with Polyethylenimine modified PDMS and the bottom side is kept unchanged. After all the solution is filtrated, fluorescent dye strained bacteria are enriched on the microspheres. The fluorescent intensity representing the number of bacteria captured is then measured using a portable instrument. Through the designed microfluidic biosensor, the bacteria detection can be achieved with 2 mL sample solution in less than 15 min for water or 20 min for diluted milk. A linear range from 10 CFU/mL to 1000 CFU/mL is obtained. The paper-based 3D biosensor has the merits of low-cost, simple operation, pump-free and high sensitivity and it can be applied to the simultaneous detection of multiple bacteria via integrating different aptamers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A paper electrochemical immunosensor for the combined binding and quantification of the heart failure (HF) biomarker Galectin-3 has been developed. The simple design of the new sensor is comprised of paper material that is decorated with gold nanostructures, to maximize its electroactive surface area, and functionalized with target-specific recognition molecules to selectively bind the protein from aqueous solutions. The binding of the protein caused the blockage of the electron flow to the sensor electroactive surface, thus causing its oxidation potential to shift and the corresponding current to reduce quantitatively with the increase in the protein concentration within the working range of 0.5ng/mL-8ng/mL (LOQ-0.5 ng/mL). This novel sensor was able to quantify Galectin-3 concentration in saliva samples from HF patients and healthy controls within 20 min with good reproducibility (RSD = 3.64%), without the need for complex sample processing steps. The electrochemical measurements of the patient samples were cross validated by ELISA where the percent agreement between the two methods was found to be 92.7% (RSD = 7.20%). Therefore, the new paper immunosensor sensor has a strong potential for rapid and cost-effective screening of the Galectin 3 biomarker at points of care, thus supporting the timely diagnosis of heart failure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Borax is strictly regulated in the food processing and pharmaceutical industry due to its physiological toxicity, and the development of a direct analytical method is essential for effectively monitoring the borax abuse. In this work, the fluorescence properties of flavonoids, including flavones, isoflavones and flavonols, were systematically investigated from aqueous to borax solutions, and it was found that the weak intrinsic fluorescence of flavonols could be pervasively sensitized by borax. A natural flavonol, morin, was subsequently chosen as a representative probe to develop a turn-on fluorescence sensing method for borax analysis, which achieved a linear response spanning four orders of magnitude with a detection limit of 1.07 μM (0.22 μg mL -1 in terms of Na 2 B 4 O 7 content). Furthermore, a smartphone-assisted paper-based test device was designed and constructed by 3D printing technology. Using morin-impregnated test strips as the carrier, the borax could be visually detected by the RGB signals of the captured images, with a detection limit of 0.13 mM (27.05 μg mL -1 for Na 2 B 4 O 7 ). Combining ion exchange treatment for food samples and sodium periodate oxidation for drug samples, the developed methods were successfully applied for the direct analysis of borax in various products with the recoveries of 86.9-106.3% for traditional fluorescence analysis and 82.7-108.8% for smartphone-assisted fluorescence sensing. The fluorescence property of the morin-borax system was studied using time-dependent density functional theory, and the sensing mechanism was discussed in conjunction with experimental research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The discovery of pancreatic lipase (PL) inhibitors is an essential route to develop new anti-obesity drugs. In this experiment, chitosan was used to add amino groups to cellulose filter paper (CFP) and then glutaraldehyde was used to covalently combine PL with amino-modified CFP through the Schiff base reaction. Under optimal immobilization conditions, CFP immobilized PL has a wide range of pH and temperature tolerance, as well as excellent reproducibility, reusability and storage stability. Subsequently, 26 natural products (NPs) were screened by immobilized PL with black tea extract having the highest inhibition rate. Three compounds with binding effects on PL (epigallocatechin gallate, theaflavin-3-gallate and theaflavin-3,3'-digallate) were captured. Molecular docking proved that these three compounds have a strong binding affinity for PL. Fluorescence spectra further revealed that theaflavin-3,3'-digallate could statically quench the intrinsic fluorescence of pancreatic lipase. The molecular docking and thermodynamic parameters indicated that electrostatic interaction was considered as the main interaction force between PL and theaflavin-3,3'-digallate. Finally, the potential anti-obesity targets and pathways of the three compounds were discussed through network pharmacology. This study not only proposes a simple and efficient method for screening PL inhibitors, but also sheds light on the anti-obesity mechanism of active compounds in black tea., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Monitoring various biomarkers in saliva samples emerges as a dynamic and non-invasive method. However, the high viscosity of saliva presents a distinct challenge when integrating paper-based platforms for on-site analysis. In addressing this challenge, we introduced the capillary-driven microfluidic paper-based analytical devices (μCD-PAD) designed for user-friendly and simultaneous detection of ethanol and tetrahydrocannabinol (THC) in saliva without a sample preparation step. Employing a colorimetric approach, we quantified both analytes. Synthetic salivas of varying viscosity flowed seamlessly to the detection zone without needing a sample preparation step, and no impact on colorimetric detection due to viscosity was observed (RSD <5 %). Within 10 min after the solution reached the detection zone, the device produced a homogeneous color signal, easily analyzed by a smartphone camera. To extend the application for determination to cover a legal limit concentration of ethanol and concentration of salivary THC even 24 h after marijuana consumption, the detection time of 30 min was optimized. Moreover, a saliva sample containing both analytes was used to demonstrate the capability of the developed device to detect ethanol and THC simultaneously. No cross-talk between ethanol and THC occurred and showed recovery in the 98-102 % for ethanol and 95-105 % for THC with acceptable accuracy. This developed device exhibits excellent potential for forensic applications, providing a user-friendly, cost-effective, and real-time screening tool for detecting ethanol and THC in saliva., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Herein, oxidized 3,3',5,5'-tetramethylbenzidine (oxTMB) nanobelts were developed to enhance the colorimetric and paper-based sensing of H 2 O 2 . It was found that the minor component of Fe 2+ in Na 2 SO 4 reagent could catalyze the oxidization of TMB by H 2 O 2 into positively charged oxTMB, which was further assembled into dark blue oxTMB nanobelts via electrostatic interaction with SO 4 2- . The extinction originating from the absorption and scattering of oxTMB nanobelts was utilized to quantitatively detect H 2 with a wide linear detection range (1.0-300 μM) and a low limit of detection (0.48 μM). In addition, no coffee-ring effect was observed in the test zone of the paper-based colorimetric array, which was beneficial to judge the color by naked eye. Finally, the colorimetric method was applied to detect H 2 with a wide linear detection range (1.0-300 μM) and a low limit of detection (0.48 μM). In addition, no coffee-ring effect was observed in the test zone of the paper-based colorimetric array, which was beneficial to judge the color by naked eye. Finally, the colorimetric method was applied to detect H 2 O 2 in contact lens care solution. This work not only proposed a new colorimetric sensing platform for H 2 O 2 , but also highlighted the minor component in the reagent might influence the experimental result., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The similar transmission patterns and early symptoms of respiratory viral infections, particularly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza (H1N1), and respiratory syncytial virus (RSV), pose substantial challenges in the diagnosis, therapeutic management, and handling of these infectious diseases. Multiplexed point-of-care testing for detection is urgently needed for prompt and efficient disease management. Here, we introduce an electrochemical paper-based analytical device (ePAD) platform for multiplexed and label-free detection of SARS-CoV-2, H1N1, and RSV infection using immobilized pyrrolidinyl peptide nucleic acid probes. Hybridization between the probes and viral nucleic acid targets causes changes in the electrochemical response. The resulting sensor offers high sensitivity and low detection limits of 0.12, 0.35, and 0.36 pM for SARS-CoV-2 (N gene), H1N1, and RSV, respectively, without showing any cross-reactivities. The amplification-free detection of extracted RNA from 42 nasopharyngeal swab samples was successfully demonstrated and validated against reverse-transcription polymerase chain reaction (range of cycle threshold values: 17.43-25.89). The proposed platform showed excellent clinical sensitivity (100 %) and specificity (≥97 %) to achieve excellent agreement (κ ≥ 0.914) with the standard assay, thereby demonstrating its applicability for the screening and diagnosis of these respiratory diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A state-of-the-art, ultrasensitive, paper-based SERS sensor has been developed using silver nanostars (AgNSs) in combination with synthetic and natural antibodies. A key component of this innovative sensor is the plastic antibody, which was synthesized using molecularly imprinted polymer (MIP) technology. This ground-breaking combination of paper substrates/MIPs with AgNSs, which is similar to a sandwich immunoassay, is used for the first time with the aim of SERS detection and specifically targets nucleolin (NCL), a cancer biomarker. The sensor device was carefully fabricated by synthesizing a polyacrylamide-based MIP on cellulose paper (Whatman Grade 1 filter) by photopolymerization. The binding of NCL to the MIP was then confirmed by natural antibody binding using a sandwich assay for quantitative SERS analysis. To facilitate the detection of NCL, antibodies were pre-bound to AgNSs with a Raman tag so that the SERS signal could indicate the presence of NCL. The composition of the sensory layers/materials was meticulously optimized. The intensity of the Raman signal at ∼1078 cm -1 showed a linear trend that correlated with increasing concentrations of NCL, ranging from 0.1 to 1000 nmol L -1 , with a limit of detection down to 0.068 nmol L -1 in human serum. The selectivity of the sensor was confirmed by testing its analytical response in the presence of cystatin C and lysozyme. The paper-based SERS detection system for NCL is characterized by its simplicity, sustainability, high sensitivity and stability and thus embodies essential properties for point-of-care applications. This approach is promising for expansion to other biomarkers in various fields, depending on the availability of synthetic and natural antibodies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The development of point-of-care testing (POCT) for circulating tumor DNA (ctDNA) is meaningful for the non-invasive cancers screening and diagnosis, particularly in resource-limited settings. The microfluidic paper-based analytical device (μPAD) provides an ideal platform, its application in ctDNA assays remains underexplored. In this work, a multifunctional μPAD was manufactured, which can enhance the efficiency and reduce the cost of ctDNA sensing. Additionally, a smartphone-based application analysis was fabricated for convenient, portable detection and colorimetric signal readout. Moreover, the novel oxidase-like MnB 2 nanozyme was introduced in the sandwiches sensing strategy, utilizing its catalytic properties to effectively generate a colorimetric signal. The use of MnB 2 nanozyme in sensing application is relatively novel, and its catalytic performance and mechanism was thoroughly evaluated via experiment and density functional theory (DFT) calculations. After optimizing the detection conditions, the proposed biosensor exhibited satisfactory results. Furthermore, the method was successfully used to detect ctDNA in tumor cell lysates and peripheral blood samples from tumor-bearing mice. The results were consistent with standard qPCR method, affirming the reliability of our POCT analysis device in ctDNA detection. Thus, this work not only provides a paper-based POCT device and intelligent analysis tool for portable cancers diagnosis, but it also paves a new application path for MnB 2 nanozyme in the sensing filed., Competing Interests: Declaration of Competing interest The author(s) declared no potential conflicts of interest with respect to the research, author-ship, and/or publication of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Sensitive and accurate analysis of pyrophosphate (PPi) is of great importance for preventing health hazard in environment. Nevertheless, most of sensors focus on sensitivity and selectivity, but practicality is also a significant quota. How to reconciling sensitivity, selectivity and practicability in one single sensor is desirable but remains challenging. Here, we created a novel metal-carbon nanozyme V 2 O 5 @C with two-dimensional (2D) morphology and high yet exclusive peroxidase (POD)-like activity via a glucose and NH 4 NO 4 -co-directed avenue, and further showed its application in constructing a portable and disposable paper-based analytical chip (PA-chip) for rapid, visual and onsite analysis of PPi. PPi etched V 2 O 5 to prevent the decomposition of H 2 O 2 into ·OH, resulting in weakened POD-like activity. In comparison with PPi deficiency, colorless TMB couldn't be oxidized into oxidized TMB with a dropped absorption at 652 nm. Therefore, obviously shallowed blue color on PA-chip surface was recorded, and demonstrated a negative relationship with PPi dosage, enabling rapid and visual detection of PPi with a limit of detection of 2.6 nM. This study demonstrated the burgeoning applications of nanozymes with POD-like activity in construction of PA-chips for PPi and will quicken the advancement of practical sensors, guaranteeing environmental safety., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

There is an ongoing effort in the US illicit drug market to make new psychoactive compounds more potent and addictive. Due to continuous chemical modifications, many fentanyl analogs are developed and mixed with more traditional illicit drugs, such as cocaine and heroin. Detecting fentanyl and fentanyl analogs in these illicit drug mixtures has become more crucial because of the increased potency and associated health risks. Most confirmatory procedures require time-consuming and expensive, highly sophisticated laboratory equipment and experimental procedures, which can delay critical information that might save a victim or find a suspect. In this study, we propose miniaturizing and accelerating this process by combining surface-enhanced Raman spectroscopy (SERS) analysis and paper spray mass spectrometry (PS-MS). For this aim, dual-purposed paper substrates were developed through soaking in Au/Ag nanostars suspensions. These novel, in-house prepared paper SERS substrates showed stability for up to four weeks with and without the presence of drug compounds. Fentanyl analogs with similar SERS spectra were differentiated by coupling with PS-MS. The limit of detection (LOD) for fentanyl on the paper substrates is 34 μg/mL and 0.32 μg/mL for SERS and PS-MS, respectively. Fentanyl and fentanyl analogs show selective SERS enhancement that helped to detect trace amounts of these opioids in heroin and cocaine street samples. In short, we propose the combination of SERS/PS-MS by using modified paper substrates to develop cost-effective, sensitive, rapid, portable, reliable, and reproducible methods to detect illicit drugs, especially trace amounts of fentanyl and fentanyl analogs in illicit drug mixtures. The combination of these two category A techniques allows for the identification of illicit drugs according to the SWGDRUG guidelines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

With the public heightened emphasis on mitigating the occurrence risks of health-related ailment and optimizing personal physical performance, portable chemical sensing devices emerged as an indispensable component of pervasive health monitoring. Chemical sensing enabled the immediate and on-site identification of biomarkers in biological fluids by integrating colorimetry, fluorescence, electrochemical, and other methods into portable sensor devices. These sensor devices incorporated microneedles, hydrogels, microfluidic modules, and papers, facilitating conformal human-device contact and providing several visual sensing options for disease prevention and healthcare management. This review systematically overviewed recent advancements in chemical sensors for marker detection, categorizing them based on monitoring device types. Furthermore, we also offered recommendations and opportunities for developing portable chemical sensing devices by summarizing sensor integration methods and tracking sites on the human body., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

In this paper, paper microfluidic channel fabricated by directly screen-printing of polydimethylsiloxane (PDMS) is proposed for paper spray mass spectrometry analysis of therapeutic drugs in the blood samples. Compared with traditional paper spray, PDMS-printed paper spray (PP-PS) allows fluid to flow to the tip of paper with less sample loss which significantly improved the signal intensity of target compounds in blood samples. As paper can reduce the matrix effect, PP-PS also has a greater advantage than electro-spray Ionization (ESI) when directly analyzing complex biological sample in terms of the detection efficiency. Linearity and limits of detection (LOD) were evaluated for five psychotropic drugs: olanzapine, quetiapine, 9-hydroxyrisperidone, clozapine, risperidone. As a result, PP-PS improved the signal intensity of the psychotropic drugs at a concentration of 250 ng/ml in blood samples by a factor of 2-5 times and lowered the relative standard deviation (RSD) by a factor of 2-5.6 times compared with traditional paper spray. And PP-PS also improved signal intensity by a factor of 9-33 times compared with ESI. Quantitative experiments of PP-PS mass spectrometry indicated that the linear range was 5-500 ng/ml and the LOD were improved by a factor of 5-71 times for all these drugs compared with traditional paper spray. In addition, PP-PS was applied to the home-made miniaturized mass spectrometer and the precursor ions of all five psychotropic drugs (250 ng/ml) in the mass spectrometry results were obtained as well. These could prove that PP-PS has the potential to analyze complex biological samples in application on the miniaturized mass spectrometer which can be used outside the laboratory., Competing Interests: Declaration of competing interest The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Deoxyribonuclease I (DNase I) is a biomarker which has important applications in various biological processes. Thus, it is highly important to develop a user-friendly method for the detection of DNase I. Here, we present a paper-based distance sensor for the rapid detection of DNase I based on changes in the viscosity of DNA mucus. The viscosity of DNA mucus varies with different concentrations of DNase I, showing different water flow lengths on the pH test papers, this makes the quantification of DNase I possible. This method has a wide linear range (0.01–10 U/mL), excellent sensitivity, remarkable specificity and excellent reproducibility. The detection limit reaches 0.003 U/mL. Additionally, it can be well applied to detection of DNase I inhibitors, assay of DNase I in human serum and quality evaluation of nucleic acid scavengers. In general, this study offers a brief, convenient, label-free, and economical method to construct paper-based distance sensors using DNA mucus, which is very promising in the detection of DNase I in various applications. [Display omitted] • The paper-based sensor detects DNase I by distance signal. • The new method for detecting DNase I based on viscosity changes. • The detection limit for DNase I is 0.003 U/mL. • The sensor shows excellent specificity, remarkable practicality and portability. [ABSTRACT FROM AUTHOR]

Paper-based analysis has captivated scientists' attention in the field of analytical chemistry and related areas for the last two decades. Arguably no other area of modern chemical analysis is so broad and diverse in its approaches spanning from simple 'low-tech' low-cost paper-based analytical devices (PADs) requiring no or simple instrumentation, to sophisticated PADs and microfluidic paper-based analytical devices (μPADs) featuring elements of modern material science and nanomaterials affording high selectivity and sensitivity. Correspondingly diverse is the applicability, covering resource-limited scenarios on the one hand and most advanced approaches on the other. Herein we offer a view reflecting this diversity in the approaches and types of devices. The core idea of this article rests in dividing μPADs according to their type into two groups: A) instrumentation-free μPADs for resource-limited scenarios or developing countries and B) instrumentation-based μPADs as futuristic POC devices for e-diagnostics mainly aimed at developed countries. Each of those two groups is presented and discussed with the view of the main requirements in the given area, the most common targets, sample types and suitable detection approaches either implementing high-tech elements or low-tech low-cost approaches. Finally, a socioeconomic perspective is offered in discussing the fabrication and operational costs of μPADs, and, future perspectives are offered., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Paper spray mass spectrometry (PSMS) is currently used in different analytical fields, but less effort has been made so far to use PSMS for highly polar compounds. Such analytes usually show poor performance in PSMS due to their high affinity for common paper substrates in addition to high matrix effects. In this study, strategies for hydrophobic modifications of commercially available paper substrates using ten different organosilanes were developed. The modified substrates were generated, characterized, and applied for PSMS analysis of polar toxins. By using the modified paper, PSMS performance of some of the toxins could be considerably increased, especially for orellanine, showing a more than 80-fold signal enhancement when substrates modified with chlorotrimethylsilane were used. For other toxins like ricinine, only small beneficial effects could be shown on PSMS performance when using modified substrates. Statistical equivalence tests showed sufficient ruggedness of the developed procedures also compared to conventional substrates. Thus, further systematic development of paper substrates modified with organosilane derivatives based on the presented study for application in PSMS should be encouraged. Image 1 • Comprehensive study using 10 different mono-/trichlorosilanes for paper modification. • Optimization of modification methods and characterization of modified substrates. • Improvements for paper spray MS performance were achieved for many polar toxins. • Equivalence tests proved robustness of paper spray MS performance using modified substrates. [ABSTRACT FROM AUTHOR]

Abstract Patterned paper sensors such as letter- and barcode-shaped sensors have become a subject of growing interest due to the potential in information embedding and data interpretation, which brings a requirement on easily fabricating these paper-based analytical devices. The answer, in part, may lie in the influence of paper structure on the performance of paper-based analytical devices. After investigating the effect of physical properties of paper on precipitation and non-precipitation assays for detecting Fe(II), here we propose a simple and promising approach for barrier-free paper patterning. Without building hydrophobic boundaries, the precipitates of sensing reactions on low-bulk and medium-thick paper substrates allow patterned signal readout directly. As a proof of concept, barrier-free patterned paper sensors for detecting heavy metals were fabricated, with detection limits of 0.25 ppm for Fe(II), 0.4 ppm for Ni(II), and 0.5 ppm for Cu(II). Our work provides a valuable perspective on fabrication of patterned paper sensors. Graphical abstract fx1 Highlights • Skipping the hydrophobic treatment in fabrication of patterned paper sensors. • Providing a versatile platform for facile preparation of patterned paper sensors. • Low-bulk and medium-thick paper substrate holds the key to barrier-free fabrication. [ABSTRACT FROM AUTHOR]

In this study, nanomaterials capable of enzyme-free glucose quantification and colorimetric readout are integrated into a microfluidic paper-based analytical devices (μPADs). Gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) were utilized as a peroxidase-like nanozyme and a colorimetric probe to achieve glucose monitoring. In this developed device, glucose is oxidized by AuNPs to generate hydrogen peroxide (H 2 O 2 ), which flows in the paper microchannels toward detection zones. H 2 O 2 then etches the immobilized AgNPs to induce a color change. The intensity of color change is easily monitored using a smartphone application. Following method optimization, we obtained a linear range from 0.50 to 10.0 mmol L -1  (R 2  = 0.9921) and a detection limit (LOD) of 340.0 μmol L -1 . This falls in the clinically relevant range for glucose monitoring and diabetes diagnosis in humans. In addition, the total analysis time is just 20 min, which is significantly less than the same experiment performed in the solution phase. Also, our method is markedly selective; other substrates do not interfere. The recovery test in human control samples was in the range of 98.47-102.34% and the highest relative standard deviation (RSD) was 3.58%. The enzyme-free approach for glucose sensing is highly desirable for diabetes diagnosis as it replaces the more expensive enzyme with cheaper nanomaterials. Furthermore, since nanomaterials are more environmentally stable compared to enzymes, it has the potential for widespread deployment as point-of-care diagnostics (POC) in resource-limited settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Widening the methodology of chromophore analysis in pulp and paper science, a sensitive gas-chromatographic approach with electron-capture detection is presented and applied to model samples and real-world historic paper material. Trifluoroacetic anhydride was used for derivatization of the chromophore target compounds. The derivative formation was confirmed by NMR and accurate mass analysis. The method successfully detects and quantifies hydroxyquinones which are key chromophores in cellulosic matrices. The analytical figures of merit appeared to be in an acceptable range with an LOD down to approx. 60 ng/g for each key chromophore, which allows for their successful detection in historic sample material. [ABSTRACT FROM AUTHOR]

The utility of strikingly simple and cheap optoelectronic detectors operating according to a Paired-Emitter-Detector-Diode (PEDD) principle for microfluidic paper-based analytical devices (μPAD) has been experimentally confirmed. The prototypes of these compact detectors have been made of only two customary light emitting diodes without any additional optical parts like lens, filters, fibers etc. Moreover, for their operation economic and portable equipment is required (low-power circuit and ordinary voltmeter). Photometric and fluorometric PEDDs for paper devices are developed. In both cases the possibility of their applicability in transmittance and reflectance modes of measurements are presented. In these investigations as model analytes some coloured and fluorescence substances have been handled, but the utility of several developed systems for real chemical analysis has also been demonstrated. The results of photometric determination of hemoglobin in human blood, as well as fluorometric determination of quinine in tonics and calcium ions in mineral waters using various PEDD-μPAD systems have been shown. [ABSTRACT FROM AUTHOR]

A cost-effective assay for antioxidant using simple cotton thread combining paper based device with mobile phone detection has been investigated. Standard and sample solutions flow along a bunch of cotton thread treated with sodium hydroxide via microfluidic behaviors without external pumping. The analyte solution reacts with the reagents that have been immobilized on the paper strip fixed at the end of the cotton bunch. The developed platforms were used for the assays of total phenolic content and antioxidant capacity by employing Folin-Ciocalteu and 2, 2-diphenyl-1-picryhydrazyl (DPPH) respectively. Simple detection can be made by employing a mobile phone camera (iPhone 4S) with Image J or Photoshop for image processing and evaluation. Gallic acid was used as a reference standard in this work, as its polyphenol structures can be found in many plants. The total phenolic content is expressed as gallic acid equivalents (GAE) (mg/g material). Inhibition capacity is calculated by the equation: % I = [(I o – I s )/ I o ] × 100, where I s is the relative magenta intensity (CMYK mode) of sample, and I o the relative magenta intensity of DPPH•. IC 50 inhibition can be estimated from the graph and can be used for the antioxidant capacity consideration. Applications to the assay green tea samples were demonstrated. The total phenolic contents in the green tea samples were found to be 48–105 mg/g, with %RSD of less than 10 for that of higher 50 GAE mg/g and IC 50 values of the samples studied were 25–50 mg/L. The results obtained by the developed methods agree with that of the standard methods. [ABSTRACT FROM AUTHOR]

Due to the serious risks of lead pollution to human health, it plays a great role in constructing a simple, inexpensive, portable, and user-friendly strategy for Pb2+ detection in environmental samples. Herein, a paper-based distance sensor is developed to detect Pb2+ assisted with the target-responsive DNA hydrogel. Pb2+ can activate DNAzyme to cleave its substrate strand, which results in the hydrolysis of the DNA hydrogel. The released water molecules trapped in the hydrogel can flow along the patterned pH paper due to the capillary force. The water flow distance (WFD) is significantly influenced by the amount of water released from the collapsed DNA hydrogel triggered by the addition of various Pb2+ concentrations. In this way, Pb2+ can be quantitatively detected without using specialized instruments and labeled molecules, and the limit of detection (LOD) of Pb2+ is 3.0 nM. Additionally, the Pb2+ sensor works well in lake water and tap water. Overall, this simple, inexpensive, portable, and user-friendly method is very promising for quantitative and in-field detection of Pb2+ with excellent sensitivity and selectivity. [Display omitted] • A novel paper-based distance sensor assisted with DNA hydrogel is developed. • The hydrolysis of the DNA hydrogel by Pb2+ triggers release of the water. • The water flow distance is used to assess the level of Pb2+. • The detection of Pb2+ is successfully demonstrated in lake water and tap water. [ABSTRACT FROM AUTHOR]

The possibility of using pyrolyzed paper as disposable working electrodes for trace metals determination is reported for the first time. A small piece of pyrolyzed paper (0.7×0.7 cm) was positioned at the bottom side of the electrochemical cell using a rubber O-ring, which defined the electrode area (0.48 cm; 0.18 cm 2 ). A large number of electrodes can be obtained from a single piece of standard dimensions (2.5 cm×7.5 cm) of paper, therefore minimizing the cost per unit. The electrochemical performance of the pyrolyzed paper was demonstrated by cyclic voltammetry, electrochemical impedance spectroscopy and by the determination of Zn, Cd, and Pb by square-wave anodic stripping voltammetry. The unmodified pyrolyzed paper showed excellent performance for Pb and Cd detection (LOD =0.19 and 0.16 ppb, respectively). In the presence of Bi 3+ (in-situ film formation), the simultaneous determination of Zn, Cd and Pb was also possible (LOD=0.26, 0.25, and 0.39 ppb, respectively). [ABSTRACT FROM AUTHOR]

A new sensitive non-invasive gold nanoparticle-based sensor that enables to detect thiols in the human skin has been developed. The detection procedure implied the assessment of the color change of a paper sensor resulting from aggregation of gold nanoparticles caused by thiols. The ratio of the intensity of the photo image blue channel vs the red one (in units of RGB coloration) served as analytical response. The main thiol in the skin is glutathione, therefore, it was used as model biothiol and spiking substance. The range of linearity for glutathione was 8–75 µM, the detection limit was 6.9 µM. RSD≤7% is for inter-day determination of 10 μM glutathione and RSD≤12% is the intra-day value. The recovery of 5 µM and 10 µM of glutathione was evaluated by applying solution, containing thiol-spikes, on skin. The results varied in the range 77–138%. A hundred-fold excess of serine, alanine, histidine, threonine, creatinine, urea, and ammonia; a ten-fold excess of glycine, proline, leucine, isoleucine, phenylalanine, asparagine; and a five-fold excess of valine, tryptophan, tyrosine, and uric acid, which can be extracted from the skin and is contained in the test matrix, have no significant effect on 10 µM glutathione signal. Thiols level in the skin of volunteers (21–65 years old, men and women) detected with the use of a proposed non-invasive sensor was 11.6–47.5 µM. [ABSTRACT FROM AUTHOR]

Microfluidic paper-based analytical devices (μPADs) offer a unique possibility for a cost-effective portable and rapid detection of a wide range of small molecules and macromolecules and even microorganisms. In this line, electrochemical detection methods are key techniques for the qualitative analysis of different types of ligands. The electrochemical sensing μPADs have been devised for the rapid, accurate, and quantitative detection of oncomarkers through two-/three-dimensional (2D/3D) approaches. The 2D μPADs were first developed and then transformed into 3D systems via folding and/or twisting of paper. The microfluidic channels and connections were created within the layers of paper. Based on the fabrication methods, 3D μPADs can be classified into origami and stacking devices. Various fabrication methods and materials have been used to create hydrophilic channels in μPADs, among which the wax printing technique is the most common method in fabricating μPADs. In this review, we discuss the fabrication and design strategies of μPADs, elaborate on their detection modes, and highlight their applications in affinity-based electrochemical μPADs methods for the detection of oncomarkers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Herein, we have developed a simple, sensitive and paper-based colorimetric sensor for the selective detection of Chromium (Ⅵ) ions (Cr (VI)). Silanization-titanium dioxide modified filter paper (STCP) was used to trap bovine serum albumin capped gold nanoparticles (BSA-Au NPs), leading to the fabrication of BSA-Au NPs decorated membrane (BSA-Au NPs/STCP). The BSA-Au NPs/STCP operated on the principle that BSA-Au NPs anchored on the STCP were gradually etched by Cr (VI) as the leaching process of gold in the presence of hydrobromic acid (HBr) and hence induced a visible color change. Under optimum conditions, the paper-based colorimetric sensor showed clear color change after reaction with Cr (VI) as well as with favorable selectivity to a variety of possible interfering counterparts. The amount-dependent colorimetric response was linearly correlated with the Cr (VI) concentrations ranging from 0.5 µM to 50.0 µM with a detection limit down to 280 nM. Moreover, the developed cost-effective colorimetric sensor has been successfully applied to real environmental samples which demonstrated the potential for field applications. [ABSTRACT FROM AUTHOR]

A microfluidic biosensor paper-based analytical device, or μPAD, was developed as a point-of-care assay platform for the simultaneous determination of three clinically important markers: uric acid, urea, and triglycerides. To achieve a simultaneous determination, thermosensitive valves based on N-isopropylacrylamide polymers controlled the flow of fluid in the μPAD. The evaluation of the analytical characteristics of the μPAD was done using a photographic camera at room temperature. The detection limits were 4.5·10 -5 , 2.5·10 -3 , and 1.5·10 -3  mg mL -1 , for uric acid, urea, and triglycerides, respectively, and the precision expressed as relative standard deviation (% RSD) 3.2, 1.2, and 1.6%. The obtained μPAD devices were validated with real human plasma samples, demonstrating high accuracy and precision. Multiple analyte point-of-care tests such as those developed here have excellent characteristics, being easy to manufacture, cost-effective, easy to use, and highly sensitive., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that would influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This manuscript describes the development and clinical testing of a paper-based, metabolic assay designed for rapid, semi-quantitative measurement of organophosphate poisoning. Paper-based platforms, including point-of-care devices and 96-well plates, provided semi-quantitative information regarding the concentration of AchE (a biomarker for organophosphate poisoning). The paper-based 96-well-plate developed and implemented in this study was used to measure the level of organophosphate poisoning in three different clinical patients. Results were comparable to those obtained using conventional hospital methods currently considered the “gold standard”. This diagnostic device offers several advantages over conventional methods, including short operating time (twice as fast as conventional methods), procedure simplicity, and reduced fabrication cost. With further commercialization efforts, the methods described in this manuscript could be applied to a wide range of potential diagnostic applications in the field. [ABSTRACT FROM AUTHOR]

Here we present a new and rapid immunofiltration assay for simultaneous detection of HIV p24 and hepatitis B virus antigens. The assay platform is composed of a 13 mm nitrocellulose filter spotted with capturing bioprobes and inserted in a Swinnex ® syringe filter holder. Samples and reagents are flown through the nitrocellulose filter by manual pressure on the syringe. A colorimetric detection allows for naked eye results interpretation. The assay provides sensitivity in the picomolar range in just 5 min, even using low volumes of sample in complex matrix. Probe deposition by spotting allows for flexible combinations of different capturing agents and multiple diagnoses; furthermore, the very simple and inexpensive set-up makes the syringe-based immunoassay on paper microarray a suitable diagnostic system for resource-limited settings. [ABSTRACT FROM AUTHOR]