Search

The appearance and quick spread of the new severe acute respiratory syndrome coronavirus disease, COVID-19, brought major societal challenges. Importantly, suitable medical diagnosis procedures and smooth clinical management of the disease are an emergent need, which must be anchored on novel diagnostic methods and devices. Novel molecular diagnostic tools relying on nucleic acid amplification testing have emerged globally and are the current gold standard in COVID-19 diagnosis. However, the need for widespread testing methodologies for fast, effective testing in multiple epidemiological scenarios remains a crucial step in the fight against the COVID-19 pandemic. Biosensors have previously shown the potential for cost-effective and accessible diagnostics, finding applications in settings where conventional, laboratorial techniques may not be readily employed. Paper- and cellulose-based biosensors can be particularly relevant in pandemic times, for the renewability, possibility of mass production with sustainable methodologies, and safe environmental disposal. In this review, paper-based devices and platforms targeting SARS-CoV-2 are showcased and discussed, as a means to achieve quick and low-cost PoC diagnosis, including detection methodologies for viral genomic material, viral antigen detection, and serological antibody testing. Devices targeting inflammatory markers relevant for COVID-19 are also discussed, as fast, reliable bedside diagnostic tools for patient treatment and follow-up., The authors acknowledge funding through projects Eco2Covid (POCI-01-02B7-FEDER-068174) and TecniCov (POCI-01-02B7-FEDER-069745), co-funded by FEDER through COMPETE2020 and Lisboa2020. T.P., A.R.C. and A.C.M. acknowledge funding to National Foundation for Science and Technology, I.P., FCT, through their PhD grants, references DFA/BD/8606/2020, SFRH/BD/130107/2017 and SFRH/BD/115173/2016, respectively, info:eu-repo/semantics/publishedVersion

Programmed cell death protein 1 (PD-1) is one of the coinhibitory checkpoints upon T cell activation, the abnormal expression of which severely threatens host immune modulatation for chronic infection. Thus, fast and sensitive monitoring of PD-1 is of vital importance for early diagnosis and cancer treatment. The current detection methods largely based on enzyme-linked immunosorbent assay (ELISA) require time-consuming incubation and complicated washing steps. Herein, we designed a simple and portable nanofiber paper (NFP)-based fluorescence "off-on" immunosensor for PD-1 rapid determination. Molybdenum disulfide (MoS2) nanosheets modified NFP (MoS2-NFP) was employed for adsorbing and immobilizing CdSe/ZnS quantum dots-antibody (QDs-Ab) complex to construct a ready-to-use fluorescent immunosensor. The fluorescent signal of QDs-Ab was initially quenched by MoS2 under the Forster resonance energy transfer (FRET) effect. When the PD-1 target was specifically captured onto NFP by immunization, the QDs-Ab-PD-1 complex was promptly desorbed from the MoS2-NFP surface, resulting in FRET impediment and fluorescence recovery. As an alternative quenching agent, graphene oxide (GO) served as a contrast to investigate NFP-based sensing performance. Owing to superior quenching and desorption efficiency, the MoS2-NFP-based fluorescence immunosensor exhibited nearly 2-fold lower detection limit (85.5 pg/mL) than GO-NFP-based sensor (151 pg/mL) for PD-1 monitoring. Excellent selectivity and satisfactory recovery in PD-1 mouse cell culture supernatant samples were confirmed as well. In addition, the comparable detectability of the MoS2-NFP-based immunosensor was accurately evaluated by a standard PD-1 mouse ELISA kit. This study displayed a simple, rapid, low-cost, and portable point-of-care PD-1 assay, indicating its broad application prospect toward clinical diagnoses.

A cellulosic fibre based well-being fragrance packet has been developed by Central Institute for Research on Cotton Technology (CIRCOT). Inside the packet, three layers of cotton nonwoven (gram per square meter 100) have been used as core material. Fragrance based natural essential oil (citronella oil) has been incorporated in the middle non-woven layer of the cotton. Volatile active species of the essential oil infused in the cotton non-woven slowly has been diffused through the upper and lower non-woven layers in the surrounding atmosphere through the pores of the paper based sheath material. As per feedback report, a fragrance released from the packet is satisfactory up to seven days in the 25–30 square feet area. Mosquito repellency of the well-being packet also has been examined by following the standard cone test method. It has been observed that the smell release from the pack is capable to repel mosquitoes (100%) up to five days after opening the pack. The intensity of the active ingredients of fragrance released from the packet with time has been measured by gas chromatography analysis. The engineered pack has lightweight, is biodegradable, delivers well-being fragrance and repels mosquitoes up to one week.

COVID-19 first appeared in December of 2019 in Wuhan, China. Since then it has become a global pandemic. A robust and scalable diagnostics strategy is crucial for containing and monitoring the pandemic. RT-PCR is a known, reliable method for COVID-19 diagnostics which can differentiate between SARS-CoV-2 and other viruses. However, PCR is location dependent, time consuming and relatively expensive. Thus, there is a need for a more flexible method which may be produced in an off-the-shelf format and distributed more widely. Paper-based immunoassays can fulfill this function. Here we present the first steps towards a paper-based test which can differentiate between different between the Spike protein of various coronaviruses, SARS-CoV-1, SARS-CoV-2 and CoV-HKU1 with negligible cross reactivity for HCoV-OC43 and HCoV-229E in a single assay which takes less than 30 minutes. Furthermore, our test can distinguish between fractions of the same Spike protein. This is done by an altered assay design with four test line locations where each antigen builds a unique, identifiable binding pattern. The effect of several factors, such as running media, immunoprobe concentration and antigen interference is considered. We find that running media has a significant effect on the final binding pattern where human saliva provides results while human serum leads to the lowest signal quality.

Rewritable paper is meaningful to the recyclable and sustainable utilization of environmental resources and thus has been extensively investigated for several decades. In this work, we demonstrated an efficient and convenient strategy to fabricate rewritable paper based on reversible hydrochromism of donor-acceptor Stenhouse adducts (DASAs). The kinetics and efficiency of isomerization could be well-controlled by adjusting the surrounding temperature and humidity. Monocolored rewritable paper was prepared by coating cyclic DASA·xH2O on the paper surface. Writing, printing, stamping and patterning were realized on the rewritable paper. The information could be controllably erased by treatment in a humid atmosphere. More importantly, the rewritable paper was upgraded to multicolored by combination of two DASA materials. The color of chirography was switched by controlling the writing speed.

The salivary glands are closely associated with stress conditions and the neuroendocrine system. The concentrations of these salivary biomarkers fluctuate with a person’s disease status. Until now, salivary diagnostics have been promising; however, the analytical tools for detecting salivary biomarkers have remained burdensome due to the lack of user-friendly and cost-effective equipment. In this study, we used a microfluidic starch-coated paper-based chip to isolate ɑ-amylase from human saliva. The concentration of ɑ-amylase on the head and tail sections of the paper-based chip was compared in the presence or absence of starch. We found that ɑ-amylase was highly concentrated only in the head section of the starch-coated paper-based chip through Western blotting (WB) and enzyme-linked immunosorbent assay (ELISA). We expect our designed paper-based chip will aid in α-amylase detection technologies using saliva and small amounts of other biofluids including blood, tears, pancreatic juice, and urine.

We report a paper-based photodetector made from mixed cation organic perovskite halide MA1–xFAxPbI3 (MA = methylammonium (CH3NH3); FA = formamidium CH(NH2)2). The detector shows a substantial photo...

One of the most cited limitations of biochemical detection is its poor sensitivity, owing to the relatively high complexity of micro-samples. Moreover, some samples cannot be easily self-replicated and their abundance cannot be increased through traditional technologies. Therefore, the preconcentration of low-abundance samples is a key requirement for microfluidic biological analysis. In recent years, the ion-concentration polarization phenomenon has aroused widespread interest in the application of microfluidic technology. In addition, paper-based materials are readily available, easy to modify, and exhibit good hydrophilicity. The study of the ion-concentration polarization preconcentration of micro-samples in paper-based microfluidic chips is of considerable significance. In this review, we discuss the development and applications of ion-concentration polarization paper-based preconcentrator in the past 5 years, with emphasis on key progresses in chip fabrication and performance optimization under different conditions. The current needs and development prospects in this field have also been discussed.

Due to their unique properties, paper-based biosensors have attracted attention as inexpensive devices for on-site analysis. To achieve fast and sensitive detection of analytes, immobilization of enzymes with high apparent activities on paper is highly desirable; however, this is challenging. Herein, we report an improved approach to attach a malathion degrading enzyme, PoOPHM9, on paper via an interlocking network of Pluronic F127 (PF127)–poly(acrylic acid)–enzyme conjugates. The addition of PF127 improved retention of enzymatic activity as the apparent kinetic constant Vmax of the immobilized enzyme increased two-fold compared with the paper prepared without PF127. The PF127–poly(acrylic acid)–PoOPHM9 papers provided rapid colorimetric detection of malathion at 0.1–50 mM. The detection was completed within 5 min using a smartphone and image analysis software. As a proof-of-concept, malathion-contaminated water, plant, and apple samples were analyzed with the papers successfully. This material is promising for on-site rapid analysis of malathion-contaminated samples.

Microfluidic paper-based analytical devices (μPADs) have developed rapidly in recent years, because of their advantages, such as small sample volume, rapid detection rates, low cost, and portability. Due to these characteristics, they can be used for in vitro diagnostics in the laboratory, or in the field, for a variety of applications, including food evaluation, disease screening, environmental monitoring, and drug testing. This review will present various detection methods employed by μPADs and their respective applications for the detection of target analytes. These include colorimetry, electrochemistry, chemiluminescence (CL), electrochemiluminescence (ECL), and fluorescence-based methodologies. At the same time, the choice of labeling material and the design of microfluidic channels are also important for detection results. The construction of novel nanocomponents and different smart structures of paper-based devices have improved the performance of μPADs and we will also highlight some of these in this manuscript. Additionally, some key challenges and future prospects for the use of μPADs are briefly discussed.

Microfluidic paper-based analytical devices are emerging as promising options for on-the-spot detection of chemical contaminants in water. The coupling of these devices with digital imaging technol...

A newly developed research topic, fabricated paper-based microfluidic sensors, was discussed in the field of low-cost environmental detection. Distinguished with the traditional dipstick or lateral-flow setups, these paper-based microfluidic sensors can serve as a tool for onsite quantitative and semi-quantitative measurements, without risks to cause environmental pollution. They have attracted increasing interest since the first easy-fabricated paper-based setup reported by Whitesides group in 2007. Most of the publications utilized paper-based sensors in clinical detection. In recent years, some groups started to use these sensors in environmental measurement, leading to precise, easy operation, low-cost, and eco-friendly methods for onsite detection. In this review, paper-based microfluidic sensors were briefly introduced, followed by literatures review and discussion for future perspectives.

On-site protein analysis is crucial for disease diagnosis in community and family medicine in which microfluidic paper-based analytical devices (μPADs) have attracted growing attention. However, the practical applications of μPADs in protein analysis for physiological samples with high complexity is still limited. Herein, we developed a three-dimensional (3D) paper-based isoelectric focusing (IEF) platform, which is composed of power supply, reservoirs, and separation channel and made by the origami and stacking method, to simultaneously separate and enrich proteins in both low-salt and high-salt samples. Under the optimized experimental conditions, standard proteins (bovine hemoglobin (BHb) and phycocyanin (Phy)) were separated within 18 min under a 36 V power supply and obtained a 10-fold enrichment using the 3D paper-based IEF platform. Then, the capability of the 3D paper-based IEF platform for direct pretreatment of high-salt samples using a 12 V battery as power supply was measured through separating three standard proteins in saline (0.9% NaCl) with separation resolution (SR) > 1.29. Through further coupling with colorimetric and lateral flow strip measurements, the 3D paper-based IEF platform was applied to directly pretreat and quantitatively analyze microalbuminuria and C-reactive proteins in clinical urine and serum samples with analytical results with relative deviations of

Competitive immunoassays comprise the standard means of detecting small molecules. However, conventional methods using microwells are difficult to apply during point-of-care tests (POCT) because they require complicated handling and are time consuming. Although paper-based analytical devices (PAD) have received considerable focus because of their rapid and straightforward operation, only a few devices have been proposed for competitive immunoassays. Herein, we describe a novel universal PAD format with a 3-dimensional configuration for competitive immunoassays that rapidly and sensitively detects small molecules. The proposed device comprised a layered structure with uniform color formation and high capture efficiency between antigen and antibody that results in rapid and reproducible results. The device rapidly (90 s) assayed biotin as a model target, with a limit of detection (LOD) of 5.08 ng mL−1, and detected progesterone with an LOD of 84 pg mL−1 within 5 min. Moreover, sample volumes and reagent consumption rates were minimized. Thus, our device could be applied to competitive immunoassays of various small molecules in POCT.

The development of industry and of the Internet of Things (IoTs) have brought energy issues and huge challenges to the environment. The emergence of triboelectric nanogenerators (TENGs) has attracted wide attention due to their advantages, such as self-powering, lightweight, and facile fabrication. Similarly to paper and other fiber-based materials, which are biocompatible, biodegradable, environmentally friendly, and are everywhere in daily life, paper-based TENGs (P-TENGs) have shown great potential for various energy harvesting and interactive applications. Here, a detailed summary of P-TENGs with two-dimensional patterns and three-dimensional structures is reported. P-TENGs have the potential to be used in many practical applications, including self-powered sensing devices, human–machine interaction, electrochemistry, and highly efficient energy harvesting devices. This leads to a simple yet effective way for the next generation of energy devices and paper electronics.

A novel platform for the phenolics in wastewater based on an electrochemical multiwalled carbon nanotube paper-based analytical device (MWCNT-ePAD) has been developed. Phenolics such as catechol ar...

Loop-mediated isothermal amplification (LAMP) has been widely used to detect many infectious diseases. However, minor inconveniences during the steps of adding reaction ingredients and lack of simple color results hinder point-of-care detection. We therefore invented a fluorometric paper-based LAMP by incorporating LAMP reagents, including a biotinylated primer, onto a cellulose membrane paper, with a simple DNA fluorescent dye incubation that demonstrated rapid and accurate results parallel to quantitative polymerase chain reaction (qPCR) methods. This technology allows for instant paper strip detection of methicillin-resistant Staphylococcus aureus (MRSA) in the laboratory and clinical samples. MRSA represents a major public health problem as it can cause infections in different parts of the human body and yet is resistant to commonly used antibiotics. In this study, we optimized LAMP reaction ingredients and incubation conditions following a central composite design (CCD) that yielded the shortest reaction time with high sensitivity. These CCD components and conditions were used to construct the paper-based LAMP reaction by immobilizing the biotinylated primer and the rest of the LAMP reagents to produce the ready-to-use MRSA diagnostic device. Our paper-based LAMP device could detect as low as 10 ag (equivalent to 1 copy) of the MRSA gene mecA within 36-43 min, was evaluated using both laboratory (individual cultures of MRSA and non-MRSA bacteria) and clinical blood samples to be 100% specific and sensitive compared to qPCR results, and had 35 day stability under 25 °C storage. Furthermore, the color readout allows for quantitation of MRSA copies. Hence, this device is applicable for point-of-care MRSA detection.

This feature article summarizes recent works in paper-based potentiometry and voltammetry in heavy metal determination. Interactions of paper substrates with heavy metals, influence on the sensing response, and modification methods applied to paper substrates to improve the performance of recently developed electrochemical sensors are discussed. Since the rekin-dling of interest in paper-based analytical devices, methodologies and electrode designs for heavy metal determinations are highlighted. Promising aspects of the use of these sensors for samples containing solids, and the increased versatility of the use of paper in analytics offers the possibility of increased acceptance of these low-cost platforms. Economic Development Board (EDB) Accepted version The authors thank NEWRI (Nanyang Environment and Water Research Institute) and Singapore’s Economic Development Board (EDB) for their financial support of this research.

Herein, combined with a pervasive smartphone installed with a color recognition app, dual-responsive CDs@Eu/GMP ICPs were designed as a red-to-blue paper-based colorimetric sensor for the point-of-use analysis of cerebral acetylcholinesterase (AChE) upon Cd2+ exposure. Blue-emitting CDs with multi-functional groups as guests were encapsulated into the network of Eu/GMP ICPs to obtain CDs@Eu/GMP ICPs with the sensitized red fluorescence of Eu3+. With the presence of thiocholine (TCh), derived from acetylthiocholine (ATCh) hydrolyzed by AChE, the coordination environment of the CDs@Eu/GMP ICPs was interrupted, leading to the collapse of the CDs@Eu/GMP ICP network and the corresponding release of guest CDs into the surrounding environment. Consequently, the sensitized red fluorescence of Eu3+ decreased and the blue fluorescence of the CDs increased. This obvious red-to-blue fluorescent color changes of CDs@Eu/GMP ICPs on test paper could then be integrated with the smartphone for point-of-use analysis of cerebral AChE upon Cd2+ exposure, which not only offers a new analytical platform for a better understanding of the environmental risk of Alzheimer's Dementia (AD), but also holds great potential in the early diagnosis of AD even at the asymptomatic stage with the decrease in CSF AChE as an early biomarker.

Introduction We developed low-cost, portable paper-based diagnostic devices for detection of human immunoglobulin M (IgM) and immunoglobulin G (IgG) in serum without any sample preparation. These devices can be used to help identify presence of diseases, used to provide rapid results ( Materials and Methods We successfully accomplished colorimetric detection of human IgG and human IgM using a sandwich-style assay within the microfluidic paper device via vertical flow immunoassay configuration. The reaction zone in the wax printed paper layer is a small circular pattern. Gold nanoparticles conjugated with anti-human IgG and IgM antibodies have been used for colorimetric detection of IgG or IgM by naked eye. Colorimetric signal can be precisely quantified through implementation of image analysis software which can be developed as an app for a smartphone. The size of the device is 2 cm × 2 cm × 1 mm. Results Colorimetric detection of human IgG was accomplished at 100 fg/mL concentration using a gold nanoparticle–conjugated anti-human IgG antibody. The developed platform has a dynamic range of IgM and IgG concentrations between 0.1 pg/mL and 100 μg/mL. These devices provided a color readout in Conclusions Because of the inherent simplicity of the device operation and their ease of use, there is no variation between samples and users of the device. This low-cost approach enables multiplexing with >1 measurement performed in parallel at the same time. We anticipate that because of the sensitivity, specificity, ease of use, and overall reliability, this approach will become a standard for diagnosis of diseases and health conditions.

Paper-based diagnostics are leading the field of low-cost, point of care analytical techniques. However, large scale testing facilities such as hospitals are still primarily using the gel column agglutination technique. This is because paper-based systems are single use tests that are generally more time consuming and less automatable than traditional methods. Here, we present a novel, rapid and scalable, paper-based blood typing method that can produce test results in under ten seconds. We believe this is the fastest blood typing test that is appropriate for large scale automation. The test consists of placing a drop of antibody solution on paper, followed by a drop of blood on the same locus, and measuring the evolution of blood stain area as a function of time. Positive reactions for both forward and reverse tests have significantly slower growth rates and smaller final stain sizes when compared to negatives. We analyse the effect paper type, red blood cell concentration, antibody specificity (A, B and D) and antibody dilution have on the sensitivity and reproducibility of the technique. A high sensitivity is found in papers with a low density and thickness. The optimum red blood cell concentration is determined from a balance between wicking rate, strength of reaction and optical contrast. A and B antibodies give more sensitive results than D; however, the D antigen can still be successfully identified. This technique has the potential to significantly cut down the time and cost of blood typing tests and enable design of a new high throughput and fully automatable system.

Sophora tonkinensis Gagnep. (ST) (Fabaceae) is distributed chiefly in south-central and southeast China and Vietnam. In traditional Chinese medicine theory, the root and rhizome of ST are toxic and mainly used in the treatment of pharyngeal and laryngeal diseases. Modern studies provide new insights into the pharmacological and toxicological aspects of ST. The pharmacological and toxicological properties of ST were reviewed in this paper based on the literature from Google Scholar and CNKI, and the bioinformatics platforms were applied to explore the pharmacological and toxicological potentials of ST. The results of the literature analysis showed that ST has hepatoprotective, immunomodulatory, and anticancer effects and produces obvious toxicity to the liver and nervous and cardiovascular system. The results of bioinformatics showed that the compounds from ST may be applied to the treatment of cancer and digestive and nervous system diseases and show the possibility to cause hematotoxicity, neurotoxicity, and immunotoxicity. The present review demonstrates that attention should be paid to the potential toxicity of ST in the treatment of diseases and provides the reference for the subsequent pharmacological toxicological studies on the mechanism and chemical basis of ST.

Leukocyte esterase (LE) is a useful marker that can be used in establishing a diagnosis of urinary tract infections (UTIs). The development of a UTI diagnostic method with quantitative determinations of biomarkers across all age groups is becoming more important. In this report, microfluidic resistance sensors based on silver ink (Ag ink) and silver ink mixed with ZnO nanoparticles (Ag-ZnO ink) were synthesized and coated on cellulose paper, namely LE-Ag-μPADs and LE-Ag-ZnO-μPADs, respectively, for the sensitive detection of LE. The microfluidic design increases the precision of data and further allows for quantitative determination and early detection of LE in human urine. The quantification of LE relies on the change in the resistance readout coating with Ag ink as well as Ag-ZnO ink in the detection zone. A mixture of 3-(N-tosyl-l-alaninyloxy)-5-phenylpyrrole (PE) and 1-diazo-2-naphthol-4-sulfonic acid (DAS) was deposited in the sample zone to selectively recognize LE, and the resulting nonconductive products, i.e., azo compounds, further reacted with the Ag ink and Ag-ZnO ink to increase resistance. The quantitative detectable LE concentrations between 2 to 32 (×5.2 U mL-1), i.e. ≈12 to 108 μg L-1, cover the commercial dipstick range of trace, +1 and +2. The minimum detectable concentration of LE in urine was 1 (×5.2 U mL-1). The lower concentrations of LE detectable by LE-Ag-μPADs (1-8 × 5.2 U mL-1) are below the value achieved with the ELISA LE kit. Urine samples from inpatients with indwelling urinary catheters were used, and the LE levels measured by the present device were highly correlated with those determined by a commercial urine analyser.

We report a simple and cost-effective paper-based and colorimetric dual-mode detection of As(iii) and Pb(ii) based on glucose-functionalized gold nanoparticles under optimized conditions. The paper-based detection of As(iii) and Pb(ii) is based on the change in the signal intensity of AuNPs/Glu fabricated on a paper substrate after the deposition of the analyte using a smartphone, followed by processing with the ImageJ software. The colorimetric method is based on the change in the color and the red shift of the localized surface plasmon resonance (LSPR) absorption band of AuNPs/Glu in the region of 200-800 nm. The red shift (Δ

Infectious diseases cause millions of deaths annually in the developing world. Recently, microfluidic paper-based analytical devices (μPADs) have been developed to diagnose such diseases, as these tests are low cost, biocompatible, and simple to fabricate. However, current μPADs are difficult to use in resource-limited areas due to their reliance on external instrumentation to measure and analyze the test results. In this work, we propose an electricity and external instrumentation-free μPAD sensor based on the colorimetric enzyme-linked immunosorbent assay (ELISA) for the diagnosis of infectious disease (3D-tPADs). Designed based on the principle of origami, the proposed μPAD enables the sequential steps of the colorimetric ELISA test to be completed in just ∼10 min. In addition, in order to obtain an accurate ELISA result without using any instrument, we have integrated an electricity-free "timer" within the μPAD that can be controlled by the buffer viscosity and fluid path volume to indicate the appropriate times for washing and color development steps, which can avoid false positive or false negative results caused by an extended or shortened amount of washing and development times. Due to the low background noise and high positive signal intensity of the μPAD, positive and negative detection results can be distinguished by just the naked eye. Furthermore, the ELISA result can be semi-quantified by comparing the results shown on the μPAD with a color chart diagram with a detection limit of HIV type 1(HIV-1) p24 antigen as low as 0.03 ng mL-1. These results demonstrate the proposed sensor can perform infectious disease diagnosis without external instrumentation or electricity, extending the application of the μPAD test for on-site detection and use in resource-limited settings.

Human papillomavirus (HPV) is one of the most common sexually transmitted infections which causes cervical cancer in women. In order to avoid the development of cancer and the onset of the disease, a reliable and on-site diagnosis for early screening of HPV is still required. To achieve this goal, a smartphone-assisted paper-based colorimetric assay using pyrrolidinyl peptide nucleic acid (acpcPNA) as a probe for the detection of HPV DNA was developed. Dextrin-stabilized gold nanoparticles (d-AuNPs) were used as the colorimetric reagent. The aggregation of the d-AuNPs can be induced by the outstanding properties of the positively charged acpcPNA, generating a distinctive color change. After the duplex formation between the acpcPNA probe and the HPV DNA target, the acpcPNA probe was depleted and the residual probe can cause different degrees of d-AuNPs aggregation, resulting in a detectable color change. The different color change before and after the introduction of the DNA target as a function of the DNA concentration was quantified by analyzing the color intensity through a smartphone application. Under the optimal conditions, the linearity in the range from 1 to 1000 nM with a correlation coefficient of 0.9996 and an experimental limit of detection of 1 nM was obtained. In addition, the acpcPNA probe exhibited high selectivity for the DNA target over single-base-mismatch, two-base-mismatch, and non-complementary DNA. Moreover, this DNA sensor was successfully applied for the detection of HPV DNA from cell line samples. The proposed smartphone-based colorimetric DNA sensor offers a simple, sensitive, and selective way of detecting HPV DNA. Therefore, this DNA sensing device can be utilized as an alternative tool for the point-of-care (POC) screening of HPV.

Food safety is always one of the most important issues for human being. With the variety of food, it is required to develop rapid, low-cost and convenient detection techniques for food safety. As a representative, paper-based detection techniques have developed rapidly from simple test papers to various microfluidic paper-based devices. The paper-based analytical devices combining paper platform with a variety of advanced analytical methods have shown great application prospects for rapid testing of food safety. In this review, the surface functionalization and modification of paper are introduced. Then, the construction and development of various detection techniques are discussed, including colorimetric analysis, fluorescent analysis, electrochemical analysis, surface enhanced Raman spectroscopic analysis, and multimethods on paper-based platforms for the application in rapid detection for food safety. Finally, the prospects and future challenges of rapid detection techniques in food safety are also discussed.

This work describes a terbium luminescence-based protocol to selectively detect gallate-derived green tea polyphenols on a supramolecular gel immobilised paper platform for the first time. This user-friendly, inexpensive (� 0.0015) approach requires very low sample volumes for the analysis. The developed strategy enables simultaneous detection of gallate polyphenols in multiple tea samples with the potential for practical applications. © 2020 Wiley-VCH GmbH

Paper-based colorimetric sensor array has attracted extensive attention due to its low-cost, easy-operation, powerful discrimination, good selectivity, rapid response and versatility. It combines the advantages of paper-based analytical devices and colorimetric sensor array, and extends its application fields in analytical chemistry. This review described the recent progress in paper-based colorimetric sensor array and summarized its applications in biomedicine, environmental and food safety. Moreover, the sensing materials, characteristics and performances of different paper-based colorimetric sensor arrays were investigated. The prospects of future research for the paper-based colorimetric sensor array were discussed.

Microfluidic paper-based analytical devices (μ-PADs) fabricated in Japan were employed for the determination of total chromium (Cr) in water, soil, and lettuce irrigated with wastewater in Ethiopia. The μ-PADs, which were printed by wax printing in Japan, were transported to Ethiopia and prepared for the determination of total Cr by adding appropriate reagents to the pretreatment and detection zones. Soil and lettuce samples were determined by the μ-PADs and a UV-Vis spectrophotometer in Ethiopia. A paired t-test showed that the mean total Cr concentrations determined in the soil and lettuce samples were not significantly different between μ-PADs and UV-Vis spectrophotometric analysis at the 5% level of significance. This implies that the μ-PADs have good accuracy and reliability, and could be employed to monitor Cr in environmental samples. We found that the total Cr concentrations in all soil and lettuce samples were above the permissible limit. Moreover, evaluating Cr contamination level using the geo-accumulation index indicated that the soils were contaminated with Cr moderately to heavily. Thus, the present work successfully demonstrated the potential of remote investigations of pollution in a less-equipped laboratory by transporting the μ-PADs fabricated in another laboratory.

In this study, a microfluidic paper-based analytical device (mu PAD) was integrated with a smartphone app capable of offline (without internet access) image processing and analysis for the rapid colorimetric detection of glucose. A self-inking stamp was used to form hydrophobic channels on a piece of paper-towel due to its superior water absorption efficiency. As demonstrated, the developed sensor was employed for the colorimetric detection of glucose in artificial saliva in the linear scope of 0 - 1 mM with a calculated detection limit of 29.65 mu M. The experimental results show that the quantitative analysis of glucose with the proposed smartphone platform could be completed in less than one minute. The app developed for the smartphone platform is capable of extracting the color-changing area with an embedded image processing tool which could address the problem of color uniformity in the detection zones of mu PAD. The integrated platform has great potential to be used for non-invasive measurements of glucose in body fluids, like tears, sweat and saliva.

The growing need for reliable analytical tools to perform measurements at the point-of-need has prompted the development of novel sensors that are low cost, portable, sensitive, easy to use, and capable of multiplexed analysis. Miniaturization of the sensors into microfluidic platforms has become a promising approach to achieve these self-contained sensors. However, traditional microfluidics often require relatively expensive and complicated pumping mechanisms that increase the cost and limit the portability of the sensors. From a material perspective, paper is an attractive substrate for constructing point-of-need sensors because of its affordability, vast availability, and self-pumping ability, particularly when combined with electrochemical detection. In this mini-review, we discuss various strategies to achieve multiplexing or simultaneous detection of multiple analytes in electrochemical paper-based devices and provide a brief guide on selecting the detection strategy based on the electrochemical property of the analytes.

We describe a paper-based microfluidic device for iron(III) assay in an applied instrumental analysis laboratory. Simple and convenient devices were fabricated by the students using patterning of f...

In recent years, the need for portable, low-cost, and eco-friendly devices for testing and monitoring has arisen. Paper-based devices have emerged as a response to these needs due to the properties induced by capillarity, flexibility, disposability, and biodegradability. In this work, the authors explored the possibility of tuning the hygro-mechanical response of paper-based cantilever beams using glycerol. A lumped-parameter model with non-linear stiffness is used to describe the dynamic response of the beams using three parameters. An experimental method based on resonance frequency tests is used to study the influence of glycerol on the dynamic response of four different beam configurations. The obtained results demonstrate that the resonance frequency of paper-based mechanical systems can be easily tuned by the imbibition of a glycerol–water solution. This study could lead to the development of tunable paper-based mechanical systems for specific applications such as energy harvesters and hygro-mechanical-based sensors.

Microfluidic paper-based analytical devices (μPADs) as a potentially powerful analytical platform have recently gained significant attention for on-site monitoring of heavy metal ions, which are one of the most significant environmental concern because of non-degradability and high toxicity. The commonly applied μPADs suffers from some defects, such as heterogeneous deposition of reagent, resulting in poor detection limits and low sensitivity. So, in this work, a three-dimensional origami μPAD combined with PVC Membrane was developed, which can manage problems of movement of colored products or leaching out the dye and leading to color heterogeneity in the detection zones. Furthermore, a waste layer was added to μPAD for loading of more amounts of the analyte, which results in improvement of detection limit. As a proof of concept, the μPAD was used for the analysis of Cu2+ ion. For this purpose, pyrocatechol violet and chrome azurol S as colorimetric reagents were doped into PVC membrane and injected in the detection zone. The proposed μPAD was presented good linearity in the ranges of 5.0–1400.0 and 5.0–200.0 mg L−1, and the limits of detections of 1.7 and 1.9 mg L−1 in presence of chrome azurol S and pyrocatechol violet, respectively.

A novel paper-based capacitance mast cell sensor has been designed and developed for real-time monitoring of the major peanut allergen Ara h 2. In this study, we created the 3D paper chip printed with carbon electrodes as a non-contact capacitance sensing platform. To improve the conductivity and biocompatibility of the cellulose paper, a polyvinyl alcohol (PVA)-gelatin methacryloyl (GelMA)-nano-hydroxyapatite (nHAP) composite hydrogel (PGHAP gel) was employed to fabricate the prepared paper chip. When rat basophilic leukemia mast cells (RBL-2H3) are immobilized and cultured in the 3D culture system consisting of PGHAP gel and paper fibers, identification signals of Ara h 2 could be specifically monitored non-contact and real-time by capacitance change measurement. This 3D structure combined with time-lapse monitoring completes the capacitance cell sensor. Results indicate that Ara h 2 has given a remarkable decrease to the capacitance in dose-dependent range from 0.1 to 100 ng/mL. Therefore, the real-time cell allergic response could be accurately monitored by this low-cost, disposable cell sensor, which supplies a novel and effective pathway for the rapid and accurate evaluation for food allergens.

Development of paper-based microfluidic devices that perform colorimetric measurements requires quantitative image analysis. Because the design geometries of paper-based microfluidic devices are not standardized, conventional methods for performing batch measurements of regularly spaced areas of signal intensity, such as those for well plates, cannot be used to quantify signal from most of these devices. To streamline the device development process, we have developed an open-source program called ColorScan that can automatically recognize and measure signal-containing zones from images of devices, regardless of output zone geometry or spatial arrangement. This program, which measures color intensity with the same accuracy as standard manual approaches, can rapidly process scanned device images, simultaneously measure identified output zones, and effectively manage measurement results to eliminate requirements for time-consuming and user-dependent image processing procedures.

The need for agile and proper identification of drugs of abuse has encouraged the scientific community to improve and todevelop new methodologies. The drug lysergic acid diethylamide (LSD) is still widely used due to its hallucinogenic effects. The use ofvoltammetric methods to analyze narcotics has increased in recent years, and the possibility of miniaturizing the electrochemical equipmentallows these methods to be applied outside the laboratory; for example, in crime scenes. In addition to portability, the search for affordable andsustainable materials for use in electroanalytical research has grown in recent decades. In this context, employing paper substrate, graphite pen-cil, and silver paint to construct paper-based electrodes is a great alternative. Here, a paper-based device comprising three electrodes was drawnon 300 g/m2watercolor paper with 8B pencils, and its efficiency was compared to the efficiency of a commercially available screen-printedcarbon electrode. Square wave voltammetry was used for LSD analysis in aqueous medium containing 0.05 mol/L LiClO4. The limits of detec-tion and quantification were 0.38 and 1.27 mol/L, respectively. Both electrodes exhibited a similar voltammetric response, which was alsoconfirmed during analysis of a seized LSD sample, with recovery of less than 10%. The seized samples were previously analyzed by GCMStechnique, employing the full scan spectra against the software spectral library. The electrode selectivity was also tested against 3,4-methylene-dioxymethamphetamine (MDMA) and methamphetamine. It was possible to differentiate these compounds from LSD, indicating that the devel-oped paper-based device has potential application in forensic chemistry analyses., Financial support provided by the Polícia Científica do Estado de São Paulo for the partnership, and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP - Process 2016/23825-3), Fundação para a Ciência e Tecnologia, FCT, Portugal, (UID/QUI/00686/2016 and UID/QUI/00686/2019), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Process Capes Pro Forenses 25/2014).

A laminated paper-based analytical device (LPAD) for histidine detection was fabricated from a chromatography filtration paper and laminate films. Histidine recognition was effected by histidyl-tRNA synthetase (HisRS), and its detection was signaled colorimetrically based on the molybdenum blue reaction. The analytical conditions and detectable concentration range of histidine were examined. The method provided selective quantification from 1 to 100 μM histidine. LPAD fabrication is considerably simple, involving only the craft-cutting of the chromatography filtration paper and laminate film, and is cost-effective.

Bladder cancer is the fourth most common cancer in men, and it is becoming a prevalent malignancy. Most of the regular clinical examinations are prompt evaluations with cystoscopy, renal function testing, which require high-precision instrument, well-trained operators, and high cost. In this study, a microfluidic paper-based analytical device (μPAD) was fabricated to detect nuclear matrix protein 22 (NMP22) and bladder cancer antigen (BTA) from the urine samples. Urine samples were collected from 11 bladder cancer patients and 10 well-beings as experiment and control groups, respectively, to verify the working efficiency of μPAD. A remarkable checkout efficiency of up to 90.91% was found from the results. Meanwhile, this method is feasible for home-based self-detection from urine samples within 10 min for the total process, which provides a new way for quick, economical, and convenient tumor diagnosis, prognosis evaluation, and drug response.

Paper-based products are similar to paper wasps’ “nests” built by “biofiber separation” and “biofiber reassembly”, where they add “saliva” for structural reinforcement and waterproofing. Rice leave...

Background Surface enhanced Raman scattering (SERS) based on highly sensitive, flexible, solid-state sensors can provide molecular vibrational fingerprints of targeted substances in point-of-care (POC) analysis. Cellulose paper offers many advantages for the build-up of silver and gold nanostructures on a three-dimensional scaffold. Such composites can be made to contain SERS hot spots required for sensitive SERS detection in an active solid-state sensor. Scope and approach In this review, we discuss the key technical issues involved in the fabrication of SERS sensors combining a metallic SERS substrate and a cellulose paper support. We then survey recent literature for methods designed to address these issues with applications to support food safety where POC analysis serves as a valuable tool. Key findings and conclusions Sensitivity of detection is a primal challenge in the development of a paper-based SERS substrate. The fibril structures of paper materials, a suitable modification for improved bonding at the paper-metal interface, and the surface conditions of metal nanostructures all contribute to sensitive SERS performance on paper. Continuing expansion of spectrum collection in a database format, diverse methods for the statistical analyses of Raman spectra, and advanced integration of portable Raman instruments with the mobile tele-networks are critical in the further development of flexible SERS sensor in POC testing of food-borne substances.

Paper is emerging as a versatile platform for automated fluid handling with a broad range of applications in medical diagnostics and analytical chemistry. However, selectively controlling analyte transport in paper to achieve concentration or selection has been a challenge for functional analysis. Here, by combining paper-based microfluidics with acoustics, we present a rapid and powerful method to size dependently control movement of microparticles and cells in paper using surface acoustic waves (SAW). We demonstrate the unique capability of the paper-based SAW approach to trap and concentrate microparticles in paper and release them when required, achieving collection efficiency of over 98%. Given the correlation between collection efficiency, size, and applied power, the paper-based SAW approach is applied to isolate a mixture of microparticles (1.1, 3.2, and 5 μm in diameter) into different regions and also to trap and concentrate human prostate cancer PC3 cells at a predetermined site. This paper-based SAW approach provides opportunities to develop powerful and low-cost selection and analysis tools, capable of processing complex multicomponent samples, with potential applications in medical diagnostics.

A simple and effective ratiometric fluorescence sensor of CdTe QDs/GCNNs for on-site and rapid analysis of Cu2+ has been established by mixing physically CdTe QDs and graphite carbon nitride (GCNNs). Two emissions peaks of CdTe QDs at 572 nm and GCNNs at 436 nm are both excitated at 340 nm. Under a UV lamp, fluorescent of traffic yellow CdTe QDs is linearly quenched by Cu2+ (as the detection signal), while blue GCNNs remains unchanged (as the reference), resulting in a distinguishable color change gradually from pink yellow to blue. The limit of detection (LOD) of this new sensor for Cu2+ is as low as 0.47 ng mL-1 with 1.4 % RSD. The established method has been successfully applied to detection of Cu2+ in various drinks with satisfactory results. Moreover, a paper-based sensor, which has been prepared by soaking cellulose acetate membrane in CdTe QDs/GCNNs sensor solution, has a wide semiquantitative detection range for Cu2+ (0.01 ~ 5.0 μg mL-1 ). It has realized successfully on-site and rapid determination of Cu2+ in red wine without any pretreatment procedure and is of great promotion and application value in determination of Cu2+ in liquid samples.

The detection of chemical pollution in an ecosystem requires rapid and accurate analysis in the field. The method presented here can help minimize preparation time and simple detection of the metal ions. Silver nanoparticles are known for their surface plasmon resonance characteristics that visibly display distinctive colors; this makes it possible to develop as colorimetric indicators. In this study, silver nanoparticles were synthesized on paper using velvet apple (Diospyros discolor Willd.) leaf extract as the Ag+ reducing agent. The paper was immersed in the water extract for 1 hour and for 24 hours. The formation of silver nanoparticles was indicated by the change in the paper’s color from white to light brown and dark brown. Furthermore, the paper was tested using several types of metal ions, namely, Cu2+, Mn2+, Pb2+, Zn2+, Mg2+, Ni2+ and Co2+. For all types of metal ions, the paper’s color changed selectively while detecting Cu2+ ions. The paper-based silver nanoparticles were sensitive enough to detect Cu2+ ions starting at concentrations of 100 mg/L. The Transmission Electron Microscope (TEM) revealed that the silver nanoparticles tended to aggregate after the addition of Cu2+ ions, which caused changes in the size and LSPR of the nanoparticles. This potential method needs further refinement and development to enhance the sensitivity of the paper-based colorimetric indicator, so that it can detect Cu2+ at lower concentrations.

Hydrocarbon gases, especially toxic ones like benzene and xylene, pose threats to human health and the environment. But existing detection techniques, like bulky GC-MS or portable PID, cannot fulfill people's requirement of affordable and reliable hydrocarbons monitoring for the purpose of personal exposure assessment. Here, a simple, low cost, and light hydrocarbon gases sensor using a smartphone camera as a readout was developed based on the paper based milli-cantilever bending induced by polymer swelling. Its sensing cantilever was composed of three layers: functional layer of polyethylene film, adhesive layer of double-side tape, and a substrate of weighing paper. And the dimensions of the milli-fabricated sensing cantilever are 8 mm long, 0.5 mm wide, and 50 μm thick. The sensor response was the displacement of milli-cantilever free end. As proof of concept, its performance to typical hydrocarbons of xylene, hexane, and BTEX was carefully examined. For all of them, the sensor showed good performance of linear response to hydrocarbon concentrations, wide detection range, low detection, and fast response. Taking xylene for example, the sensor showed wide detection range of 15-140 ppm, low detection limit of 15 ppm, and fast response of 30 s. The sensor cross-sensitivity to other hydrocarbons was consistent with polymer swelling theory that the more carbons the hydrocarbon has, the higher the sensor sensitivity. Taking advantage of the rough materials chosen and simple fabrication procedure, the developed sensors also had high stability with time, low cost, and good uniformity. The developed sensor is affordable both physically and financially, has good performance, could meet hydrocarbons monitoring requirements for occupational safety or air pollution in petroleum industry, and would benefit people's health.

Microfluidic paper-based analytical devices (µPADs) take the paper as a base material and integrate nanoscale microchannel on it for multiple detections. Its unique properties like low cost, portability, simple operation, and easy to save make it better than the traditional microfluidic chips. While designed originally for point-of-care medical diagnostics, µPADs have attracted the attention of many researchers in the fields of environmental monitoring, water quality, and food safety. The novelty of this paper is to present a detailed overview of µPADs for clinical applications. Firstly, a brief introduction to production methods, characteristics, and applications of these methods have been given. Secondly, the basic implementation, working principles, and corresponding performance of detection methods of clinical devices have been discussed, which enable the µPADs to detect biomarkers, human cells, bacteria, and viruses in a short time. Lastly, the factors that limit µPADs commercial applications, and their future research directions have also been briefly summarized.

We demonstrate a versatile and easily fabricated paper-based CO2 sensor. The sensor consists of a specially designed fluorescent color-shift chromophore infused into standard filter paper. The emission color of the resulting fluorescent paper changes upon exposure to CO2 due to the formation of carbonic acid, which underlies the sensing mechanism. By using a ratiometric method, the undesirable effects of photobleaching can be eliminated, leading to a stable and repeatable sensor performance. These multiuse sensors have a response time on the order of 1 min and feature low detection limits for a paper-based CO2 gas sensor, suggesting possible low-cost applications in smart buildings or other facilities in which CO2 levels are required to be continuously monitored.

Microfluidic paper-based analytical devices (μPADs) allow user-friendly and portable chemical determinations, although they provide limited applicability due to insufficient sensitivity. Several approaches have been proposed to address poor sensitivity in μPADs, but they frequently require bulky equipment for power and/or read-outs. Universal serial buses (USB) are an attractive alternative to less portable power sources and are currently available in many common electronic devices. Here, USB-powered μPADs (USB μPADs) are proposed as a fusion of both technologies to improve performance without adding instrumental complexity. Two ITP USB μPADs were developed, both powered by a 5 V potential provided through standard USB ports. The first device was fabricated using the origami approach. Its operation was analyzed experimentally and numerically, yielding a two-order-of-magnitude sample focusing in 15 min. The second ITP USB μPAD is a novel design, which was numerically prototyped with the aim of handling larger sample volumes. The reservoirs were moved away from the ITP channel and capillary action was used to drive the sample and electrolytes to the separation zone, predicting 25-fold sample focusing in 10 min. USB μPADs are expected to be adopted by minimally-trained personnel in sensitive areas like resource-limited settings, the point-of-care and in emergencies. Fil: Schaumburg, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina Fil: Kler, Pablo Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Centro de Investigaciones en Métodos Computacionales. Universidad Nacional del Litoral. Centro de Investigaciones en Métodos Computacionales; Argentina Fil: Carrell, Cody S.. State University of Colorado - Fort Collins; Estados Unidos Fil: Berli, Claudio Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina Fil: Henry, Charles S.. State University of Colorado - Fort Collins; Estados Unidos

A green analytical paper based assay of Cu (II) has been developed using egg white protein as a natural reagent. Either crayon and pencil graphite, or laser engraver may be used to effectively crea...