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Point-of-care testing (POCT) technology is urgently required owing to the prevalence of the Internet of Things and portable electronics. In light of the attractive properties of low background and high sensitivity caused by the complete separation of excitation source and detection signal, the paper-based photoelectrochemical (PEC) sensors, featured with fast in analysis, disposable and environmental-friendly have become one of the most promising strategies in POCT. Therefore, in this review, the latest advances and principal issues in the design and fabrication of portable paper-based PEC sensors for POCT are systematically discussed. Primarily, the flexible electronic devices that can be constructed by paper and the reasons why they can be used in PEC sensors are expounded. Afterwards, the photosensitive materials involved in paper-based PEC sensor and the signal amplification strategies are emphatically introduced. Subsequently, the application of paper-based PEC sensors in medical diagnosis, environmental monitoring and food safety are further discussed. Finally, the main opportunities and challenges of paper-based PEC sensing platforms for POCT are briefly summarized. It provides a distinct perspective for researchers to construct paper-based PEC sensors with portable and cost-effective, hoping to enlighten the fast development of POCT soon after, as well as benefit human society. • The merits of functionalized paper for PEC sensor are introduced. • Photosensitive material and signal amplification strategy of paper-based PEC sensor are discussed. • The application of paper-based PEC sensor in the field of POCT is highlighted. • The limitations and challenges of paper-based PEC sensor are summarized. [ABSTRACT FROM AUTHOR]

In the past few years, point-of-care testing (POCT) technology has crossed the boundaries of laboratory determination and entered the stage of practical applications. Herein, the latest advances and principal issues in the design and fabrication of paper-based bipolar electrode electrochemiluminescence (BPE-ECL) sensors, which are widely used in the POCT field, are highlighted. After introducing the attractive physical and chemical properties of cellulose paper, various approaches aimed at enhancing the functions of the paper, and their underlying principles are described. The materials typically employed for fabricating paper-based BPE are also discussed in detail. Subsequently, the universal method of enhancing BPE-ECL signal and improving detection accuracy is put forward, and the ECL detector widely used is introduced. Furthermore, the application of paper-based BPE-ECL sensors in biomedical, food, environmental and other fields are displayed. Finally, future opportunities and the remaining challenges are analyzed. It is expected that more design concepts and working principles for paper-based BPE-ECL sensors will be developed in the near future, paving the way for the development and application of paper-based BPE-ECL sensors in the POCT field and providing certain guarantee for the development of human health. • Preparation and application prospect of paper-based BPE-ECL sensor are discussed. • Approaches to boost functionalization of paper and existing limitations are described. • Fabricating BPE from classical electrode materials are introduced exhaustively. • Strategies of enhancing ECL signal to improve device sensitivity are displayed. [ABSTRACT FROM AUTHOR]

Abstract Developing low-cost, portable and simple analysis tools is of vital importance for food safety point-of-care testing. Therefore, herein, a new low-cost, simple to fabricate, disposable, electrochemical mast cell-based paper sensor is proposed and developed to sensitively determine the major milk allergen casein. Then, a graphene (GN)/carbon nanofiber (CN)/ Gelatin methacryloyl (GelMA) composite material with high conductivity and good biocompatibility was modified on the cell-based paper sensor to improve the electrical conductivity and provide a sensing recognition interface for the immobilization of rat basophilic leukemia (RBL-2H3) mast cells. The cyclic voltammetry and differential pulse voltammetry measurement of the mast cells in the paper sensor revealed an irreversible anodic peak, whose peak current is proportional to the number of cells in the range from 1 × 102 to 1 × 108 cells/mL. For the milk allergen detection tests, mast cells exposed to the casein caused a significant reduction in the current signal, displaying an inverse dose-dependent relationship. The developed cell sensor exhibited a range of linearity between 1 × 10−7 and 1 × 10−6 g/mL of casein with a detection limit of 3.2 × 10−8 g/mL and a great reproducibility and selectivity. The electrochemical responses obtained using the cell-based paper sensor were well consistent with the conventional detection assay, with good stability and reproducibility. Therefore, a simple and novel electrochemical method for food allergens detection was developed, demonstrating its potential application in the food safety determination and evaluation. Highlights • An electrochemical cell sensor was first reported based on paper platform. • Carbon nanofiber/graphene/GelMA composite was prepared to fabricate the sensor. • Low detection limit (3.2 × 10−8 g/mL) for casein was achieved using the present sensor. [ABSTRACT FROM AUTHOR]

Abstract The research progress in the centrifugal microfluidic platform provides great opportunities for simple and effective analytical measurements in a variety of areas including biomedical engineering. In this study, we propose an optical reader that can measure the transmittance in a very sensitive and rapid manner on a hybrid paper-polymer centrifugal disc platform. This device enables real-time monitoring of multiple samples by measuring the absorbance of the light transmitted through the paper integrated on the disc between the light emitting diode (LED) and the photodiode (PD) regardless of the ambient light condition. To confirm its efficiency, we analyzed one of the blood's important indicators, glucose in a successful manner within 10 s without any additional complex image analysis. In addition, we discussed the results by comparing with the reflectance-based methods and with those of the previously reported studies by introducing a figure of merit to evaluate the performance of the assay. Highlights • Optical reader was developed for hybrid paper-polymer centrifugal disc platform. • This device enables real-time detection by measuring light transmission through the paper integrated on the disc between LED and photodiode. • As proof of concept, enzymatic colorimetric glucose detection was successfully performed. • Micromolar detection was achieved using the present technique within 10 s without any additional complex image analysis. [ABSTRACT FROM AUTHOR]

This study is an investigation for an inexpensive, simple and sensitive biosensor to detect prostate cancer using bioactivated-multi wall carbon nanotubes (MWCNTs, diameter of 20 nm, length of 5 µm) and a micro-pore filter paper (pore size of 0.45 µm). For the immunoassay of prostate specific antigen (PSA), which is a biomarker of prostate cancer, MWCNTs were activated with PSA antibody (monoclonal antibody of the prostate specific antigen) by using N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysulfosuccinimide sodium salt (NHSS). The activated MWCNTs were deposited on the micro-pore filter paper to use as a biosensor. The prepared biosensor can assay from 0 to 500 ng/mL of PSA level within 2 h with the detection limit of 1.18 ng/mL by the measurement of resistance change. The resistance change was caused by site selective interaction between PSA and PSA-antigen with an inexpensive bench top digital multimeter (5 1/2 digits). The detection range and sensitivity of the prepared sensor are good enough to diagnose the early stage of prostate cancer (> 4 ng/mL of PSA). This paper-based biosensor is about 20 times cheaper (fabricated biosensor price: 2.4 $) and over 10 times faster than enzyme-linked immunosorbent assay (ELISA), which is a general method for the detection of a specific protein in the modernized hospitals. Furthermore, the maximum detection limit is about 50 times higher than ELISA. [ABSTRACT FROM AUTHOR]

A multi-amplified paper-based electrochemical strategy using Pb 2+ dependent DNAzyme as the recognition unit for Pb 2+ detection was developed. In this work, flower-like reduced graphene (FrGO) was prepared utilizing flower-like ZnO as template, which was first one step grown on the gold nanoparticles modified paper working electrode (Au-PWE). After being treated with acid and then modified with Au, a novel sensor platform named Au/FrGO/Au-PWE with large specific surface area and good electrical conductivity was fabricated. The Mn 2 O 3 nanoparticle-assembled hierarchical hollow spheres (H-Mn 2 O 3 ) was served as nanocarrier to immobilize GOx, HRP and signal strand (S3), resulting to the formation of S3/H-Mn 2 O 3 /HRP/GOx bioconjugations. In the presence of Pb 2+ , the DNAzyme (S1) was activated and the substrate strand (S2) was cleaved. After the incubation with S3/H-Mn 2 O 3 /HRP/GOx in 0.1 M HAc–NaAc solution (pH 4.3) containing 30 mM aniline and 15 mM glucose, a readily measurable “turn-on” electrochemical signal could be measured. On the basis of the signal amplification strategy of Au/FrGO/Au-PWE sensing platform and S3/H-Mn 2 O 3 /HRP/GOx bioconjugations, the developed biosensor exhibited a good linear response toward over a wide range of concentration from 0.005 to 2000 nM. [ABSTRACT FROM AUTHOR]

We report the fabrication of a paper-sensor for quantitative detection of α -amylase activity in human blood serum. Pieces of filter papers were coated with starch–iodine solution leading to an intense blue coloration on the surface. Dispensing α- amylase solution on the starch–iodine coated paper reduced the intensity of the color because of starch-hydrolysis catalyzed by amylase. The variation in the intensity of the color with the concentration of amylase was estimated in three stages: (i) initially, the paper-surface was illuminated with a light emitting diode, (ii) then, the transmitted (reflected) rays emitted through (from) the paper were collected on a photoresistor, and (iii) the variations in the electrical resistance of the photoresistor were correlated with the amylase concentration in analyte. The resistance of photoresistor decreased monotonically with an increase in amylase concentration because the intensity of the reflected (transmitted) rays collected from (through) the paper increased with reduction in the color intensity on the paper surface. Since a specific bio-reaction was employed to detect the activity of amylase, the sensor was found to be equally efficient in detecting unknown quantities of amylase in human blood serum. The reported sensor has shown the potential to graduate into a point-of-care detection tool for α- amylase. [ABSTRACT FROM AUTHOR]

Paper is increasingly recognized as a user-friendly and ubiquitous substrate for construction of microfluidic devices. Microfluidic paper-based analytical devices (μPADs) provide an alternative technology for development of affordable, portable, disposable and low-cost diagnostic tools for improving point of care testing (POCT) and disease screening in the developing world, especially in those countries with no- or low-infrastructure and limited trained medical and health professionals. We in this review present fabrication techniques for microfluidic devices and their respective applications for biological detection as reported to date. These include: (i) fabrication techniques: examples of devices fabricated by using two-dimensional (2D) and three-dimensional (3D) methods; (ii) detection application: biochemical, immunological and molecular detection by incorporating efficient detection methods such as, colorimetric detection, electrochemical detection, fluorescence detection, chemiluminescence (CL) detection, electrochemiluninescence (ECL) detection, photoelectrochemi (PEC) detection and so on. In addition, main advantages, disadvantages and future trends for the devices are also discussed in this review. [ABSTRACT FROM AUTHOR]

Paper, a cheap and ubiquitous material, has great potential to be used as low-cost, portable and biodegradable platform for chemical and biological sensing application. In this paper, we are exploring a low-cost, flexible and reliable method to effectively pattern paper for capturing optical dyes and for flow-based delivery of target samples for colorimetric chemical sensing. In this paper, we target the detection of ammonia (NH 3 ) and carbon dioxide (CO 2 ), two of the important environmental and health biomarkers. By functionalizing the paper platform with diverse cross-reactive dyes sensitive to NH 3 and CO 2 , their selective sensing within a certain pH range, as well as their detection at different concentrations can be achieved. The images of paper based device were captured by a flatbed scanner and processed in MATLAB ® using a RGB model and PCA for quantitative analysis. Paper based devices with readout using ubiquitous consumer electronic devices (e.g. smartphones, flatbed scanner) are considered promising approaches for disease screening in developing countries with limited resources. [ABSTRACT FROM AUTHOR]

The detection of trypsin and its inhibitor is significantly important for both clinical diagnosis and disease treatment. Herein, we demonstrate a hydrogel-assisted paper-based lateral flow sensor for the detection of trypsin and its inhibitor for the first time. The gelatin hydrogel is hydrolyzed based on the gel-to-sol transition in the presence of trypsin, which results in the release of the trapped water molecules in the gelatin hydrogel. By placing one end of a pH indicator strip onto the hydrolyzed gelatin hydrogel, water is flowing along the pH indicator strip. However, in the absence of trypsin, water cannot flow along the pH indicator strip as the water molecules are trapped in the gelatin hydrogel. The detection limit of the system reaches as low as 1.0 × 10−6 mg/mL, and it is also applied to the quantitative detection of trypsin in human serum. In addition, the detection of a clinical drug aprotinin that is an inhibitor of trypsin is also successfully achieved. Noteworthy, only the gelatin hydrogel, pH indicator strip, and PS substrate are needed to fulfill the detection of trypsin without the need of other chemicals or reagents. Overall, we develop a particularly simple, elegant, robust, competitive, high-throughput, and low-cost approach for the rapid and label-free detection of trypsin and its inhibitor, which is very promising in the development of commercial products for sensing, diagnostic, and pharmaceutical applications. Besides, the hydrogel-assisted paper-based lateral flow sensor can also be employed to detect other analytes of interest by use of different stimuli-responsive hydrogel systems. • A hydrogel-assisted paper-based lateral flow sensor is developed for the detection of trypsin and its inhibitor. • The hydrolysis of the gelatin hydrogel by trypsin triggers release of the water trapped in the hydrogel. • The released water flows along a pH indicator strip, and the coverage ratio of the water mark is used to quantify trypsin. • This simple, convenient, and cost-effective method has high portability, remarkable sensitivity, and fast response time. • It shows excellent performance in label-free and high-throughput detection of trypsin in human serum. [ABSTRACT FROM AUTHOR]

Several tropical fever viruses transmitted by mosquitoes including zika, dengue, and chikungunya , are becoming a serious problem in global public health. Simple diagnostic tools in early stages are strongly required to monitor and prevent these diseases. Paper diagnostic platforms can provide a solution for these needs, with integration of fluidic control techniques and isothermal amplification methods. Here, we demonstrate a Lab-on-paper for all-in-one molecular diagnostics of zika, dengue, and chikungunya virus from human serum. The entire process of nucleic acid testing that involves sampling, extraction, amplification, and detection is simply operated on a single paper chip. Based on the engineered structure of paper materials and dried chemicals on the all-in-one chip, serum samples containing the target virus RNA were simply added by automatic flow from distilled water injection. Target RNA molecules were concentrated on the binding pad with chitosan and then transported to reaction pads following a pH increase for specific reverse transcription loop-mediated isothermal amplification with fluorescence signal generation. Three targets, zika virus, dengue virus, and chikungunya virus, in human serum were simultaneously detected on the all-in-one paper chip within 60 min at 65 °C. The all-in-one paper chip can be used as a real-time quantitative assay for 5–5000 copies of zika virus RNA. This all-in-one device was successfully used with 5 clinical specimens of zika and dengue virus from real patients. We believe that the proposed all-in-one paper chip can provide a portable, low-cost, user-friendly, sensitive, and specific NAT platform with great potential in point-of-care diagnostics. Image 1 • All-in-one nucleic acid testing paper chip from sample to result was demonstrated. • The entire nucleic acid testing process, sampling, extraction, amplification, and detection were conducted on single device by simple injection of sample. • Zika, dengue, and chikungunya spiked in serum samples were simultaneously detected and quantified within 60 min by RT-LAMP. • Small volumes, 5 clinical samples, and 5–5000 RNA copies were analyzed in real-time. • A fully-integrated, portable, low-cost, ready-to-use, easy-to-fabricate, sensitive, and specific paper-based nucleic acid testing system was developed. [ABSTRACT FROM AUTHOR]