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Environmental toxic pollutants and pathogens that enter the ecosystem are major global issues. Detection of these toxic chemicals/pollutants and the diagnosis of a disease is a first step in efficiently controlling their contamination and spread, respectively. Various analytical techniques are available to detect and determine toxic chemicals/pathogens, including liquid chromatography, HPLC, mass spectroscopy, and enzyme-linked immunosorbent assays. However, these sensing strategies have some drawbacks such as tedious sample pretreatment and preparation, the requirement for skilled technicians, and dependence on large laboratory-based instruments. Alternatively, biosensors, especially paper-based sensors, could be used extensively and are a cost-effective alternative to conventional laboratory testing. They can improve accessibility to testing to identify chemicals and pollutants, especially in developing countries. Due to its low cost, abundance, easy disposal (by incineration, for example) and biocompatible nature, paper is considered a versatile material for the development of environmentally friendly electrochemical/optical (bio) sensor devices. This review presents an overview of sensing platforms constructed from paper, pointing out the main merits and demerits of paper-based sensing systems, their fabrication techniques, and the different optical/electrochemical detection techniques that they exploit.

This manuscript offers a concise overview of paper microfluidics, emphasizing its sustainable sensing applications in healthcare, environmental monitoring, and food safety. Researchers have developed innovative sensing platforms for detecting pathogens, pollutants, and contaminants by leveraging the paper's unique properties, such as biodegradability and affordability. These portable, low-cost sensors facilitate rapid diagnostics and on-site analysis, making them invaluable tools for resource-limited settings. This review discusses the fabrication techniques, principles, and applications of paper microfluidics, showcasing its potential to address pressing challenges and enhance human health and environmental sustainability. [ABSTRACT FROM AUTHOR]

This manuscript offers a concise overview of paper microfluidics, emphasizing its sustainable sensing applications in healthcare, environmental monitoring, and food safety. Researchers have developed innovative sensing platforms for detecting pathogens, pollutants, and contaminants by leveraging the paper’s unique properties, such as biodegradability and affordability. These portable, low-cost sensors facilitate rapid diagnostics and on-site analysis, making them invaluable tools for resource-limited settings. This review discusses the fabrication techniques, principles, and applications of paper microfluidics, showcasing its potential to address pressing challenges and enhance human health and environmental sustainability.

Abstract Urinary tract infections (UTIs) are the most common nosocomial infection in North America leading to over $12 billion in annual health care costs. UTIs can significantly reduce the quality of life and, in severe cases, result in sepsis and mortality. According to Public Health Ontario, over 80% of long‐term care home (LTCH) residents with asymptomatic bacteriuria are treated with antibiotics, however, less than 50% of the antibiotic treatments for UTIs show clinical benefit. Current confirmatory processes for UTIs are primarily dependent on the completion of urine cultures which can result in a delay of more than 24 h. Therefore, there is a need to develop new efficient diagnostic methods to provide timely test results and prevent multidrug resistance. Emerging nanomaterials with special physical and chemical properties have demonstrated great potential in rapid detection of UTI‐associated bacteria. This review paper provides a thorough analysis of current diagnostic tools for UTIs. Emerging nanostructured biosensors are reviewed to elucidate the most recent progress in the detection of uropathogens. It is believed that advanced biosensors integrated with nanotechnology will contribute to the timely diagnosis of UTIs and improve the accuracy of the results, which will lead to better treatment of this prevalent clinical condition.

In this study, a novel, cost-effective, and environmental-friendly acetylcholinesterase (AChE)-based electrochemical biosensor was developed and utilized for paraoxon-ethyl (PE) detection. In this biosensor, cerium oxide (CeO2) and poly(3,4 ethylenedioxythiophene):poly(styrenesulfonate) (PESOT:PSS) modified paper electrode was fabricated by a simple dip-coating method. The synergistic effect of CeO2 and PEDOT:PSS enhance the performance of AChE-based biosensor in terms of sensitivity and selectivity. The electrical conductivity and stability of the fabricated electrode are further improved with the treatment of ethylene glycol (EG). EG decreases the coulombic interactions between PEDOT and PSS molecules, causes polymer chain reorientation, and improves the non-covalent interaction between cellulose molecules and PEDOT, which further leads to higher conductivity. All electrochemical results validate that the biosensor shows good selectivity (Kselectivity < 1), high sensitivity of 52.10 µA/nM, and a low detection limit of 0.12 nM. The accuracy and applicability of the proposed biosensor were also checked with two real samples. All results validate that the fabricated paper electrode can be a promising alternative to other conventional electrodes. [ABSTRACT FROM AUTHOR]

The development and rapid progression of cancer are major social problems. Medical diagnostic techniques and smooth clinical care of cancer are new necessities that must be supported by innovative diagnostic methods and technologies. Current molecular diagnostic tools based on the detection of blood protein markers are the most common tools for cancer diagnosis. Biosensors have already proven to be a cost-effective and accessible diagnostic tool that can be used where conventional laboratory methods are not readily available. Paper-based biosensors offer a new look at the world of analytical techniques by overcoming limitations through the creation of a simple device with significant advantages such as adaptability, biocompatibility, biodegradability, ease of use, large surface-to-volume ratio, and cost-effectiveness. In this review, we covered the characteristics of exosomes and their role in tumor growth and clinical diagnosis, followed by a discussion of various paper-based biosensors for exosome detection, such as dipsticks, lateral flow assays (LFA), and microfluidic paper-based devices (µPADs). We also discussed the various clinical studies on paper-based biosensors for exosome detection.

The use of enzyme-based biosensors for the detection and quantification of analytes of interest such as contaminants of emerging concern, including over-the-counter medication, provides an attractive alternative compared to more established techniques. However, their direct application to real environmental matrices is still under investigation due to the various drawbacks in their implementation. Here, we report the development of bioelectrodes using laccase enzymes immobilized onto carbon paper electrodes modified with nanostructured molybdenum disulfide (MoS2). The laccase enzymes were two isoforms (LacI and LacII) produced and purified from the fungus Pycnoporus sanguineus CS43 that is native to Mexico. A commercial purified enzyme from the fungus Trametes versicolor (TvL) was also evaluated to compare their performance. The developed bioelectrodes were used in the biosensing of acetaminophen, a drug widely used to relieve fever and pain, and of which there is recent concern about its effect on the environment after its final disposal. The use of MoS2 as a transducer modifier was evaluated, and it was found that the best detection was achieved using a concentration of 1 mg/mL. Moreover, it was found that the laccase with the best biosensing efficiency was LacII, which achieved an LOD of 0.2 µM and a sensitivity of 0.108 µA/µM cm2 in the buffer matrix. Moreover, the performance of the bioelectrodes in a composite groundwater sample from Northeast Mexico was analyzed, achieving an LOD of 0.5 µM and a sensitivity of 0.015 µA/µM cm2. The LOD values found are among the lowest reported for biosensors based on the use of oxidoreductase enzymes, while the sensitivity is the highest currently reported. [ABSTRACT FROM AUTHOR]

Aptamers are short oligonucleotides designed to possess high binding affinity towards specific target compounds (ions, molecules, or cells). Due to their function and unique advantages, aptamers are considered viable alternatives to antibodies as biorecognition elements in bioassays and biosensors. On the other hand, paper-based devices (PADs) have emerged as a promising and powerful technology for the fabrication of low-cost analytical tools, mainly intended for on-site and point-of-care applications. The present work aims to provide a comprehensive overview of paper-based aptasensors. The review describes the fabrication methods and working principles of paper-based devices, the properties of aptamers as bioreceptors, the different modes of detection used in conjunction with aptasensing PADs, and representative applications for the detection of ions, small molecules, proteins, and cells. The future challenges and prospects of these devices are also discussed.

A portable paper-based enzyme-linked biosensor that integrates a multi-enzyme cascade reaction, natural enzyme, and nanozyme with filter paper, combined with smartphones, is proposed for the detection of xanthine (XA) and sarcosine (SA) in urine. The primary biological component of the sensor is horseradish peroxidase (HRP). By chemically modifying cellulose filter paper (CFP) the HRP in horseradish crude extract is specifically immobilized through boron affinity and metal chelation techniques. Furthermore, the incorporation of UiO-66 on CFP had a good synergistic effect on the electron transfer of HRP and the detection of H 2 O 2 , significantly increasing the sensor's sensitivity. Under optimized experimental conditions, the sensor demonstrated a dynamic response range of 8–400 μmol L−1 for SA with a minimum detection limit (LOD) of 5 μmol L−1, and a dynamic response range of 10–400 μmol L−1 with an LOD of 8 μmol L−1 for XA. Additionally, the well-designed detection area of the portable test strip simplifies the detection operation, reduces the detection time, and enables rapid on-site analysis. UV-Vis analysis further confirmed the sensor's accuracy in detecting disease markers in urine. The sensing platform has good reproducibility, specificity and stability, suitable for the detection of SA and XA in real human urine samples, and the sensor has the advantages of simple manufacturing, easy operation, strong portability, low reagent consumption, and low cost benefit. Therefore, the development of this paper-based enzyme-linked biosensor offers a novel approach to the detection of disease markers in urine and has potential applications in medical testing. [Display omitted] • Paper-based enzyme-linked biosensor was successfully prepared. • Smartphone-assisted test paper detected xanthine and sarcosine in urine. • The sensor immobilizes HRP from horseradish by modifying the filter paper. • The addition of UiO-66 had good synergistic effect on the HRP's electron transfer. • The portable test paper can realize the simultaneous detection of multiple copies. [ABSTRACT FROM AUTHOR]

Paper-based sensors have received increasing attention in the last decade, their use has spread to various application fields, such as clinical diagnostic, food safety, environmental monitoring, etc. Feature inherent to on-side detection is suitable to be used as point-of-care (POC) testing, including avoided sampling, sample preparation, and laborious procedure in the classical clinical lab, which is undoubtedly driving many developments of this lab-on-paper technology. The detection of biomarkers that are related to human health conditions has to play important role in the indication of the risk of diseases. In this review, the development of paper-based sensors for the detection of important biomarkers is presented. The also emphasis on recognition elements, such as chromophores/fluorophores, plasmonic nanoparticles, metal nanoclusters, etc., used to serve suitable selectivity and sensitivity. The performance of paper-based sensors using various techniques, including optical and electrochemical and other detection techniques are addressed. Furthermore, their limitations and prospects are discussed. The review also highlights cutting-edge technologies for further enhancement in the sensor performances for biomarkers detection.

Sunitinib malate (SM) is a chemical compound belonging to the class of kinase inhibitors and is mainly used in cancer treatment. However, despite its effectiveness, SM can cause multiple side effects, including fatigue, nausea, vomiting, and diarrhea, which can affect the patient's quality of life. Therefore, rapid and accurate diagnosis of SM is very important in many fields, especially for human health. Surface-enhanced Raman spectroscopy (SERS), an improved method for identifying biological and chemical substances with very low concentrations, is fast, reliable, and accurate. In order to identify the SM drug, filter paper substrates covered with silver nanoparticles (AgNPs) were used as SERS biosensors. First, AgNPs were prepared using a chemical reduction method. Then, the characteristics of the produced AgNPs were examined using FE-SEM, TEM, XRD, AFM, and UV–Vis analyses. The AgNPs were then coated on the substrates to create plasmonic active sites for identifying molecular vibrations of the SM drug. By coating the SM drug onto these substrates, the AgNPs reacted with the SM drug, successfully identifying trace amounts of the drug. The detection limit of the SERS plasmonic substrates for identifying the SM drug was 10−10 M. The average RSD for six repeated measurements was calculated at 5.39%. The enhancement factor for identifying molecular vibrations of the SM drug was experimentally calculated at 2.741 × 105 and numerically as 2.504 × 105. Therefore, the results indicate that these substrates are suitable for identifying low concentrations of this drug and can be used for drug monitoring purposes. [ABSTRACT FROM AUTHOR]

This research explores the dynamics of a fluidically loaded Bi-Material cantilever (B-MaC), a critical component of μPADs (microfluidic paper-based analytical devices) used in point-of-care diagnostics. Constructed from Scotch Tape and Whatman Grade 41 filter paper strips, the B-MaC's behavior under fluid imbibition is examined. A capillary fluid flow model is formulated for the B-MaC, adhering to the Lucas–Washburn (LW) equation, and supported by empirical data. This paper further investigates the stress–strain relationship to estimate the modulus of the B-MaC at various saturation levels and to predict the behavior of the fluidically loaded cantilever. The study shows that the Young's modulus of Whatman Grade 41 filter paper drastically decreases to approximately 20 MPa (about 7% of its dry-state value) upon full saturation. This significant decrease in flexural rigidity, in conjunction with the hygroexpansive strain and coefficient of hygroexpansion (empirically deduced to be 0.008), is essential in determining the B-MaC's deflection. The proposed moderate deflection formulation effectively predicts the B-MaC's behavior under fluidic loading, emphasizing the measurement of maximum (tip) deflection using interfacial boundary conditions for the B-MaC's wet and dry regions. This knowledge of tip deflection will prove instrumental in optimizing the design parameters of B-MaCs. [ABSTRACT FROM AUTHOR]

Safe, accurate, and reliable analysis of urinary biomarkers is clinically important for early detection and monitoring of the progression of chronic kidney disease (CKD), as it has become one of the world's most prevalent non-communicable diseases. However, current technologies for measuring urinary biomarkers are either time-consuming and limited to well-equipped hospitals or lack the necessary sensitivity for quantitative analysis and post a health risk to frontline practitioners. Here we report a robust paper-based dual functional biosensor, which is integrated with the clinical urine sampling vial, for the simultaneous and quantitative analysis of pH and glucose in urine. The pH sensor was fabricated by electrochemically depositing IrOx onto a paper substrate using optimised parameters, which enabled an ultrahigh sensitivity of 71.58 mV pH-1. Glucose oxidase (GOx) was used in combination with an electrochemically deposited Prussian blue layer for the detection of glucose, and its performance was enhanced by gold nanoparticles (AuNPs), chitosan, and graphite composites, achieving a sensitivity of 1.5 μA mM-1. This dual function biosensor was validated using clinical urine samples, where a correlation coefficient of 0.96 for pH and 0.98 for glucose detection was achieved with commercial methods as references. More importantly, the urine sampling vial was kept sealed throughout the sample-to-result process, which minimised the health risk to frontline practitioners and simplified the diagnostic procedures. This diagnostic platform, therefore, holds high promise as a rapid, accurate, safe, and user-friendly point-of-care (POC) technology for the analysis of urinary biomarkers in frontline clinical settings. [ABSTRACT FROM AUTHOR]

Gas, ion, and biological sensors have been widely utilized to detect analytes of great significance to the environment, food, and health. Paper-based sensors, which can be constructed on a low-cost paper substrate through a simple and cost-effective fabrication process, have attracted much interests for development. Moreover, many materials can be employed in designing sensors, such as metal oxides and/or inorganic materials, carbon-based nanomaterials, conductive polymers, and composite materials. Most of these provide a large surface area and pitted structure, along with extraordinary electrical and thermal conductivities, which are capable of improving sensor performance regarding sensitivity and limit of detection. In this review, we surveyed recent advances in different types of paper-based gas, ion, and biological sensors, focusing on how these materials' physical and chemical properties influence the sensor's response. Challenges and future perspectives for paper-based sensors are also discussed below. [ABSTRACT FROM AUTHOR]

The development of fluorometric paper-based analytical devices (fPADs) integrated with smartphone for fluorometric quantification of ethanol in an instrument-free and portable setup is described. The NAD+-dependent alcohol dehydrogenase immobilized within chitosan modified paper substate was utilized as a bio-recognition element and enzymatically generated NADH was used as a fluorescent probe. 3D-printed imaging setup which houses a paper chip holder and UV-light emitting device (LED) was developed for rapid, accurate capture of the fluorescent images. The biocompatible chitosan layer covering the paper provides a feasible environment for enzyme immobilization and enhances the fluorescence signal. The developed fPADs exhibited high sensitivity for ethanol detection and has a linear range for ethanol detection from 17 µM to 8.75 mM (R2 =0.99). Additionally, the fPADs were applied to quantify ethanol in four different wine samples including red, white, rose, and sparkling wines successfully. Moreover, the fPADs produce reproducible signals without loss of enzyme activity for at least 14 days and ~80% activity remained till 28 days. Thus, the proposed approach can provide a facile, affordable, portable, and instrument-free tool for the onsite quantification of ethanol in real samples and is applicable for food quality controls. [ABSTRACT FROM AUTHOR]

Detecting sputum pyocyanin (PYO) with a competitive immunoassay is a promising approach for diagnosing Pseudomonas aeruginosa respiratory infections. However, it is not possible to perform a negative control to evaluate matrix-effects in competitive immunoassays, and the highly complex sputum matrix often interferes with target detection. Here, we show that these issues are alleviated by performing competitive immunoassays with a paper biosensor. The biosensing platform consists of a paper reservoir, which contains antibody-coated gold nanoparticles, and a substrate containing a competing recognition element, which is a piece of paper modified with an albumin-antigen conjugate. Detection of PYO with a limit of detection of 4.7·10−3 µM and a dynamic range between 4.7·10−1 µM and 47.6 µM is accomplished by adding the sample to the substrate with the competing element and pressing the reservoir against it for 5 min. When tested with patient samples, the biosensor was able to qualitatively differentiate spiked from non-spiked samples, whereas ELISA did not show a clear cut-off between them. Furthermore, the relative standard deviation was lower when determining sputum with the paper-based biosensor. These features, along with a mild liquefaction step that circumvents the use of harsh chemicals or instruments, make our biosensor a good candidate for diagnosing Pseudomonas infections at the bedside through the detection of sputum PYO. [ABSTRACT FROM AUTHOR]

Specialized cancer treatments have the potential to exploit glutamine dependence to increase patient survival rates. Glutamine diagnostics capable of tracking a patient's response to treatment would enable a personalized treatment dosage to optimize the tradeoff between treatment success and dangerous side effects. Current clinical glutamine testing requires sophisticated and expensive lab-based tests, which are not broadly available on a frequent, individualized basis. To address the need for a low-cost, portable glutamine diagnostic, this work engineers a cell-free glutamine biosensor to overcome assay background and signal-to-noise limitations evident in previously reported studies. The findings from this work culminate in the development of a shelf-stable, paper-based, colorimetric glutamine test with a high signal strength and a high signal-to-background ratio for dramatically improved signal resolution. While the engineered glutamine test is important progress towards improving the management of cancer and other health conditions, this work also expands the assay development field of the promising cell-free biosensing platform, which can facilitate the low-cost detection of a broad variety of target molecules with high clinical value. [ABSTRACT FROM AUTHOR]

Environmental toxic pollutants and pathogens that enter the ecosystem are major global issues. Detection of these toxic chemicals/pollutants and the diagnosis of a disease is a first step in efficiently controlling their contamination and spread, respectively. Various analytical techniques are available to detect and determine toxic chemicals/pathogens, including liquid chromatography, HPLC, mass spectroscopy, and enzyme-linked immunosorbent assays. However, these sensing strategies have some drawbacks such as tedious sample pretreatment and preparation, the requirement for skilled technicians, and dependence on large laboratory-based instruments. Alternatively, biosensors, especially paper-based sensors, could be used extensively and are a cost-effective alternative to conventional laboratory testing. They can improve accessibility to testing to identify chemicals and pollutants, especially in developing countries. Due to its low cost, abundance, easy disposal (by incineration, for example) and biocompatible nature, paper is considered a versatile material for the development of environmentally friendly electrochemical/optical (bio) sensor devices. This review presents an overview of sensing platforms constructed from paper, pointing out the main merits and demerits of paper-based sensing systems, their fabrication techniques, and the different optical/electrochemical detection techniques that they exploit.

We have achieved a successful synthesis of a label-free, flexible, portable, and colour-indicating biosensor using cholesteric nanostructure liquid crystals (LCs), commonly referred to as cholesteric LCs (CLCs), on paper fibres. This innovative approach holds significant promise for rapid screening in precision medicine and other applications. We incorporated optically active nematic LCs in various configurations within CLCs, allowing them to rotate along different axes. When exposed to light, these LCs reflected light at specific wavelengths. By employing polarised optical microscopy and a charged couple device (CCD), we conducted titration experiments with bovine serum albumin (BSA) on the paper substrate and quantified protein concentrations based on the observed colour shifts. Utilising internal Python pixel analysis software, we evaluated the red, green, and blue colour components, which served as biomarkers for different BSA concentrations. Our results demonstrated a linear correlation between BSA concentration and colour variations. This CLC-based paper-substrate biosensor exhibits the potential to efficiently screen a large number of samples, thereby enhancing the diagnostic accuracy in clinical settings. Combining the colour-indicating and quantifiable attributes of CLCs with the affordability and portability of paper substrates, we have developed a versatile biosensor. Its ease of use, rapid response, and high sensitivity make it a promising tool for future disease detection endeavours. [ABSTRACT FROM AUTHOR]

In this research, we design and implement a small, convenient, and noninvasive paper-based microfluidic sweat sensor that can simultaneously detect multiple key biomarkers in human sweat. The origami structure of the chip includes colorimetric and electrochemical sensing regions. Different colorimetric sensing regions are modified with specific chromogenic reagents to selectively identify glucose, lactate, uric acid, and magnesium ions in sweat, as well as the pH value. The regions of electrochemical sensing detect cortisol in sweat by molecular imprinting. The entire chip is composed of hydrophilically and hydrophobically treated filter paper, and 3D microfluidic channels are constructed by using folding paper. The thread-based channels formed after the hydrophilic and hydrophobic modifications are used to control the rate of sweat flow, which in turn can be used to control the sequence of reactions in the differently developing colored regions to ensure that signals of the best color can be captured simultaneously by the colorimetric sensing regions. Finally, the results of on-body experiments verify the reliability of the proposed sweat sensor and its potential for the noninvasive identification of a variety of sweat biomarkers. [ABSTRACT FROM AUTHOR]

Paper-based electrochemical sensors have the characteristics of flexibility, biocompatibility, environmental protection, low cost, wide availability, and hydropathy, which make them very suitable for the development and application of biological detection. This work proposes electrospun cellulose acetate nanofiber (CA NF)-decorated paper-based screen-printed (PBSP) electrode electrochemical sensors. The CA NFs were directly collected on the PBSP electrode through an electrospinning technique at an optimized voltage of 16 kV for 10 min. The sensor was functionalized with different bio-sensitive materials for detecting different targets, and its sensing capability was evaluated by CV, DPV, and chronoamperometry methods. The test results demonstrated that the CA NFs enhanced the detection sensitivity of the PBSP electrode, and the sensor showed good stability, repeatability, and specificity (p < 0.01, N = 3). The electrochemical sensing of the CA NF-decorated PBSP electrode exhibited a short detection duration of ∼5–7 min and detection ranges of 1 nmol mL−1–100 μmol mL−1, 100 fg mL−1–10 μg mL−1, and 1.5 × 102–106 CFU mL−1 and limits of detection of 0.71 nmol mL−1, 89.1 fg mL−1, and 30 CFU mL−1 for glucose, Ag85B protein, and E. coli O157:H7, respectively. These CA NF-decorated PBSP sensors can be used as a general electrochemical tool to detect, for example, organic substances, proteins, and bacteria, which are expected to achieve point-of-care testing of pathogenic microorganisms and have wide application prospects in biomedicine, clinical diagnosis, environmental monitoring, and food safety. [ABSTRACT FROM AUTHOR]

Despite progress in the prevention and diagnosis of cancer, current technologies for tumor detection present several limitations including invasiveness, toxicity, inaccuracy, lengthy testing duration and high cost. Therefore, innovative diagnostic techniques that integrate knowledge from biology, oncology, medicinal and analytical chemistry are now quickly emerging in the attempt to address these issues. Following this approach, here we developed a paper-based electrochemical device for detecting cancer-derived Small Extracellular Vesicles (S-EVs) in fluids. S-EVs were obtained from cancer cell lines known to express, at a different level, the αvβ6 integrin receptor, a well-established hallmark of numerous epithelial cancer types. The resulting biosensor turned out to recognize αvβ6-containing S-EVs down to a limit of 0.7*103 S-EVs/mL with a linear range up to 105 S-EVs /mL, and a relative standard deviation of 11%, thus it may represent a novel opportunity for αvβ6 expressing cancers detection. The detection of cancer in its early stages can greatly prevent disease development, however, current technologies for tumor detection present several limitations. Here, the authors develop a paper-based electrochemical device for detecting cancer-derived small extracellular vesicles (S-EVs) in fluids, recognizing αvβ6-containing S-EVs down to a limit of 0.7*103 S-EVs/mL with a linear range up to 105 S-EVs/mL. [ABSTRACT FROM AUTHOR]

Over the past ten years, microfluidic paper-based analytical devices (micro-PADs) have attracted a lot of attention as a viable analytical platform. It is expanding as a result of advances in manufacturing processes and device integration. Conventional microfluidics approaches have some drawbacks, including high costs, lengthy evaluation times, complicated fabrication, and the necessity of experienced employees. Hence, it is extremely important to construct a detection system that is quick, affordable, portable, and efficient. Nowadays, micro-PADs are frequently employed, particularly in electrochemical analyses, to replicate the classic standard laboratory experiments on a miniature paper chip. It has benefits like rapid assessment, small sample consumption, quick reaction, accuracy, and multiplex function. The goal of this review is to examine modern paper microfluidics-based electrochemical sensing devices for the detection of macromolecules, small molecules, and cells in a variety of real samples. The design and fabrication of micro-PADs using conventional and the latest techniques have also been discussed in detail. Lastly, the limitations and potential of these analytical platforms are examined in order to shed light on future research. [ABSTRACT FROM AUTHOR]

The utilization of electrochemical detection techniques in paper-based analytical devices (PADs) has revolutionized point-of-care (POC) testing, enabling the precise and discerning measurement of a diverse array of (bio)chemical analytes. The application of electrochemical sensing and paper as a suitable substrate for point-of-care testing platforms has led to the emergence of electrochemical paper-based analytical devices (ePADs). The inherent advantages of these modified paper-based analytical devices have gained significant recognition in the POC field. In response, electrochemical biosensors assembled from paper-based materials have shown great promise for enhancing sensitivity and improving their range of use. In addition, paper-based platforms have numerous advantageous characteristics, including the self-sufficient conveyance of liquids, reduced resistance, minimal fabrication cost, and environmental friendliness. This study seeks to provide a concise summary of the present state and uses of ePADs with insightful commentary on their practicality in the field. Future developments in ePADs biosensors include developing novel paper-based systems, improving system performance with a novel biocatalyst, and combining the biosensor system with other cutting-edge tools such as machine learning and 3D printing. [ABSTRACT FROM AUTHOR]

The spread and resurgence of the SARS-CoV-2 virus (COVID-19 disease) threatens human health and social relations. Prevention of COVID-19 disease partly relies on fabricating low-cost, point-of-care (POC) sensing technology that can rapidly and selectively detect the SARS-CoV-2 virus. We report a colorimetric, paper-based polydiacetylene (PDA) biosensor, designed to detect SARS-CoV-2 spike protein in artificial saliva. Analytical characterizations of the PDA sensor using NMR and FT-IR spectroscopy showed the correct structural elucidation of PCDA-NHS conjugation. The PDA sensor platform containing the N-Hydroxysuccinimide ester of 10, 12-pentacosadiynoic acid (PCDA-NHS) was divided into three experimental PCDA-NHS concentration groups of 10%, 20%, and 30% to optimize the performance of the sensor. The optimal PCDA-NHS molar concentration was determined to be 10%. The PDA sensor works by a color change from blue to red as its colorimetric output when the immobilized antibody binds to the SARS-CoV-2 spike protein in saliva samples. Our results showed that the PDA sensing platform was able to rapidly and qualitatively detect the SARS-CoV-2 spike protein within the concentration range of 1 to 100 ng/mL after four hours of incubation. Further investigation of pH and temperature showed minimal influence on the PDA sensor for the detection of COVID-19 disease. After exposure to the SARS-CoV-2 spike protein, smartphone images of the PDA sensor were used to assess the sensor output by using the red chromatic shift (RCS) of the signal response. These results indicate the potential and practical use of this PDA sensor design for the rapid, colorimetric detection of COVID-19 disease in developing countries with limited access to medical testing.

The illegal use of β-adrenergic agonists during livestock growth poses a threat to public health; the long-term intake of this medication can cause serious physiological side effects and even death. Therefore, rapid detection methods for β-adrenergic agonist residues on-site are required. Traditional detection methods such as liquid chromatography have limitations in terms of expensive instruments and complex operations. In contrast, paper methods are low cost, ubiquitous, and portable, which has led to them becoming the preferred detection method in recent years. Various paper-based fluidic devices have been developed to detect β-adrenergic agonist residues, including lateral flow immunoassays (LFAs) and microfluidic paper-based analytical devices (μPADs). In this review, the application of LFAs for the detection of β-agonists is summarized comprehensively, focusing on the latest advances in novel labeling and detection strategies. The use of μPADs as an analytical platform has attracted interest over the past decade due to their unique advantages and application for detecting β-adrenergic agonists, which are introduced here. Vertical flow immunoassays are also discussed for their shorter assay time and stronger multiplexing capabilities compared with LFAs. Furthermore, the development direction and prospects for the commercialization of paper-based devices are considered, shedding light on the development of point-of-care testing devices for β-adrenergic agonist residue detection.

Aptamers are short oligonucleotides designed to possess high binding affinity towards specific target compounds (ions, molecules, or cells). Due to their function and unique advantages, aptamers are considered viable alternatives to antibodies as biorecognition elements in bioassays and biosensors. On the other hand, paper-based devices (PADs) have emerged as a promising and powerful technology for the fabrication of low-cost analytical tools, mainly intended for on-site and point-of-care applications. The present work aims to provide a comprehensive overview of paper-based aptasensors. The review describes the fabrication methods and working principles of paper-based devices, the properties of aptamers as bioreceptors, the different modes of detection used in conjunction with aptasensing PADs, and representative applications for the detection of ions, small molecules, proteins, and cells. The future challenges and prospects of these devices are also discussed. [ABSTRACT FROM AUTHOR]

Paper-based electrochemical analytical devices (ePADs) have gained significant interest as promising analytical units in recent years because they can be fabricated in simple ways, are low-cost, portable, and disposable platforms that can be applied in various fields. In this sense, paper-based electrochemical biosensors are attractive analytical devices since they can promote diagnose several diseases and potentially allow decentralized analysis. Electrochemical biosensors are versatile, as the measured signal can be improved by using mainly molecular technologies and nanomaterials to attach biomolecules, resulting in an increase in their sensitivity and selectivity. Additionally, they can be implemented in microfluidic devices that drive and control the flow without external pumping and store reagents, and improve the mass transport of analytes, increasing sensor sensitivity. In this review, we focus on the recent developments in electrochemical paper-based devices for viruses' detection, including COVID-19, Dengue, Zika, Hepatitis, Ebola, AIDS, and Influenza, among others, which have caused impacts on people's health, especially in places with scarce resources. Also, we discuss the advantages and disadvantages of the main electrode's fabrication methods, device designs, and biomolecule immobilization strategies. Finally, the perspectives and challenges that need to be overcome to further advance paper-based electrochemical biosensors' applications are critically presented. [ABSTRACT FROM AUTHOR]

A highly sensitive, flexible, cheap, and biodegradable biosensor has been fabricated to detect paraoxon-ethyl (PE) more effectively. In this work, copper oxide (CuO) and poly(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate) (PEDOT:PSS)-modified Whatman paper (WP)-based electrode are fabricated and then characterized by using different techniques. For the fabrication of CuO@PEDOT:PSS/WP electrode, firstly, the PEDOT:PSS/WP was optimized by various solvents such as ethylene glycol (EG), 1-methyl-2-pyrrolidone (NMP), dimethylformamide (DMF), N,N-dimethyl acetamide (NMA), and glycerol to enhance the conductivity. The EG-treated PEDOT:PSS/WP electrode shows maximum conductivity (1.4 × 10− 2 S cm− 1) among all solvents. Further, the incorporation of CuO enhances the electrochemical performance of proposed biosensor. All electrochemical results validate that the proposed biosensor (AChE/CuO@PEDOT:PSS/WP) shows high sensitivity and low detection limit of 9.1279 µA/nM and 0.42 nM, respectively. The proposed paper electrode can be a highly promising alternative to conventional electrodes that are known to have limited applications due to their high cost and limited flexibility. The accuracy of the proposed biosensor was successfully checked in two real samples, which makes it more applicable for PE detection in real-world scenarios. [ABSTRACT FROM AUTHOR]

Printable biosensors have gained numerous exciting advancements towards downstream applications in fundamental biomedical research, healthcare, food safety, environmental monitoring and governance, and to name a few. Particularly, paper-based printable biosensors have gained rising popularity in providing affordable platforms due to their merits, such as cost-effective, accurate, simple, and efficient detection of diseases for clinical diagnosis. In addition to advantages and opportunities in point-of-care detection, printable biosensors are also facing challenges. Herein, this review aims to provide a systematic summary of the development of printable biosensors, with a special focus on paper-based printable biosensors. Different types of substrates for printable biosensors are highlighted with a focus on paper substrates which have superior properties like low-cost, simple, flexible, lightweight, recyclable, etc. In addition, current printing technologies to fabricate paper-based sensors, including wax printing, photolithography, screen printing, inkjet printing, and laser printing summarize, are discussed, together with strategies for biomolecular fabrication on substrates and transducers. Finally, we also discuss the challenges and possible future perspectives, hoping to provide researchers and clinicians with informative insights into paper-based printable biosensors for smart and effective point-of-care detection. [ABSTRACT FROM AUTHOR]

Paper-based biosensors are a potential paradigm of sensitivity achieved via microporous spreading/microfluidics, simplicity, and affordability. In this paper, we develop decorated paper with graphene and conductive polymer (herein referred to as graphene conductive polymer paper-based sensor or GCPPS) for sensitive detection of biomolecules. Planetary mixing resulted in uniformly dispersed graphene and conductive polymer ink, which was applied to laser-cut Whatman filter paper substrates. Scanning electron microscopy and Raman spectroscopy showed strong attachment of conductive polymer-functionalized graphene to cellulose fibers. The GCPPS detected dopamine and cytokines, such as tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) in the ranges of 12.5–400 µM, 0.005–50 ng/mL, and 2 pg/mL–2 µg/mL, respectively, using a minute sample volume of 2 µL. The electrodes showed lower detection limits (LODs) of 3.4 µM, 5.97 pg/mL, and 9.55 pg/mL for dopamine, TNF-α, and IL-6 respectively, which are promising for rapid and easy analysis for biomarkers detection. Additionally, these paper-based biosensors were highly selective (no serpin A1 detection with IL-6 antibody) and were able to detect IL-6 antigen in human serum with high sensitivity and hence, the portable, adaptable, point-of-care, quick, minute sample requirement offered by our fabricated biosensor is advantageous to healthcare applications. [ABSTRACT FROM AUTHOR]

A filter paper sputtered with a layer of Pt and subsequently coated with a Nafion® membrane is used as working electrode. The mixed potential of the Pt electrode allows the detection of H2O2 generated by the oxidation of galactose in the presence of the galactose oxidase enzyme. This provides a simple and mediator‐free approach method. The system shows sensitivity values of −62.8±9.4 mV/decade of galactose in the range from 0.3 to 31.6 mM, well within the clinical relevant range. MnO2 nanoparticles were added to decrease the interference from ascorbic acid so that validation of the sensor in whole blood samples was performed with good recovery. [ABSTRACT FROM AUTHOR]

The general objective of Analytical Chemistry, nowadays, is to obtain best-quality information in the shortest time to contribute to the resolution of real problems. In this regard, electrochemical biosensors are interesting alternatives to conventional methods thanks to their great characteristics, both those intrinsically analytical (precision, sensitivity, selectivity, etc.) and those more related to productivity (simplicity, low costs, and fast response, among others). For many years, the scientific community has made continuous progress in improving glucose biosensors, being this analyte the most important in the biosensor market, due to the large amount of people who suffer from diabetes mellitus. The sensitivity of the electrochemical techniques combined with the selectivity of the enzymatic methodologies have positioned electrochemical enzymatic sensors as the first option. This review, focusing on the electrochemical determination of glucose using paper-based analytical devices, shows recent approaches in the use of paper as a substrate for low-cost biosensing. General considerations on the principles of enzymatic detection and the design of paper-based analytical devices are given. Finally, the use of paper in enzymatic electrochemical biosensors for glucose detection, including analytical characteristics of the methodologies reported in relevant articles over the last years, is also covered. [ABSTRACT FROM AUTHOR]

Nowadays, foodborne pathogens and other food contaminants are among the major contributors to human illnesses and even deaths worldwide. There is a growing need for improvements in food safety globally. However, it is a challenge to detect and identify these harmful analytes in a rapid, sensitive, portable, and user-friendly manner. Recently, researchers have paid attention to the development of paper-based electrochemical biosensors due to their features and promising potential for food safety analysis. The use of paper in electrochemical biosensors offers several advantages such as device miniaturization, low sample consumption, inexpensive mass production, capillary force-driven fluid flow, and capability to store reagents within the pores of the paper substrate. Various paper-based electrochemical biosensors have been developed to enable the detection of foodborne pathogens and other contaminants that pose health hazards to humans. In this review, we discussed several aspects of the biosensors including different device designs (e.g., 2D and 3D devices), fabrication techniques, and electrode modification approaches that are often optimized to generate measurable signals for sensitive detection of analytes. The utilization of different nanomaterials for the modification of electrode surface to improve the detection of analytes via enzyme-, antigen/antibody-, DNA-, aptamer-, and cell-based bioassays is also described. Next, we discussed the current applications of the sensors to detect food contaminants such as foodborne pathogens, pesticides, veterinary drug residues, allergens, and heavy metals. Most of the electrochemical paper analytical devices (e-PADs) reviewed are small and portable, and therefore are suitable for field applications. Lastly, e-PADs are an excellent platform for food safety analysis owing to their user-friendliness, low cost, sensitivity, and a high potential for customization to meet certain analytical needs [ABSTRACT FROM AUTHOR]

Pancreatic cancer remains one of the most challenging malignancies to diagnose and treat effectively, resulting in poor patient outcomes due to late-stage detection and limited therapeutic options. The emergence of biosensors has revolutionized cancer diagnosis and therapy, providing new avenues for early detection and personalized treatment. This paper explores the development and integration of biosensors within a unique expert system for pancreatic cancer diagnosis and drug delivery automation. It discusses the principles, types, and applications of biosensors in pancreatic cancer diagnosis, their role in automating drug delivery, and the design of an expert system that leverages these technologies to enhance patient outcomes. [ABSTRACT FROM AUTHOR]

A new N,O-rich covalent organic framework (COFDHNDA-BTH) was synthesized by an amine-aldehyde condensation reaction between 2,6-dialdehyde-1,5-dihydroxynaphthalene (DHNDA) and 1,3,5-phenyltriformylhydrazine (BTH) for carbaryl detection. The free NH, OH, and C=O groups of COFDHNDA-BTH not only covalently couples with acetylcholinesterase (AChE) into the pores of COFDHNDA-BTH, but also greatly improves the catalytic activity of AChE in the constrained environment of COFDHNDA-BTH's pore. Under the catalysis of AChE, the acetylthiocholine (ATCl) was decomposed into positively charged thiocholine (TCl), which was captured on the COFDHNDA-BTH modified electrode. The positive charges of TCl can attract anionic probe [Fe(CN)6]3−/4− on the COFDHNDA-BTH-modified electrode to show a good oxidation peak at 0.25 V (versus a saturated calomel electrode). The carbaryl detection can inhibit the activity of AChE, resulting in the decrease in the oxidation peak. Therefore, a turn-off electrochemical carbaryl biosensor based on a flexible carbon paper electrode loaded with COFDHNDA-BTH and AChE was constructed using the oxidation peak of an anionic probe [Fe(CN)6]3−/4− as the detection signal. The detection limit was 0.16 μM (S/N = 3), and the linear range was 0.48~35.0 μM. The sensor has good selectivity, repeatability, and stability, and has a good application prospect in pesticide detection. [ABSTRACT FROM AUTHOR]

Hypocalcemia is caused by a sharp decline in blood calcium concentration after dairy cow calving, which can lead to various diseases or even death. It is necessary to develop an inexpensive, easy-to-operate, reliable sensor to diagnose hypocalcemia. The cellulose-paper-based microfluidic field-effect biosensor is promising for point-of-care, but it has poor mechanical strength and a short service life after exposure to an aqueous solution. Octadecyltrichlorosilane (OTS), as a popular organosilane derivative, can improve the hydrophobicity of cellulose paper to overcome the shortage of cellulose paper. In this work, OTS was used to produce the superhydrophobic cellulose paper that enhances the mechanical strength and short service life of MFB, and a microfluidic field-effect biosensor (MFB) with semiconducting single-walled carbon nanotubes (SWNTs) and DNAzyme was then developed for the Ca2+ determination. Pyrene carboxylic acid (PCA) attached to SWNTs through a non-covalent π-π stacking interaction provided a carboxyl group that can bond with an amino group of DNAzyme. Two DNAzymes with different sensitivities were designed by changing the sequence length and cleavage site, which were functionalized with SPFET/SWNTs-PCA to form Dual-MFB, decreasing the interference of impurities in cow blood. After optimizing the detecting parameters, Dual-MFB could determine the Ca2+ concentration in the range of 25 μM to 5 mM, with a detection limit of 10.7 μM. The proposed Dual-MFB was applied to measure Ca2+ concentration in cow blood, which provided a new method to diagnose hypocalcemia after dairy cow calving. [ABSTRACT FROM AUTHOR]

The present study reports the fabrication of reduced graphene oxide (rGO)/gold nanoparticles (AuNP) nanocomposites modified cellulose fiber paper‐based electrochemical biosensor for procalcitonin (PCT) biomarker detection. PCT is a biomarker specific for bacterial infection (BI) detection and has gained much attention as a potential solution to the problems associated with determining appropriate antibiotic use. In sepsis and other severe infections, serum PCT levels increase to values above 100 ng mL−1 in response to pro‐inflammatory stimulation. The structural and morphological characterization of the rGO‐AuNP composite are investigated using UV‐Vis spectroscopy, FTIR spectroscopy, X‐ray diffraction, and scanning electron microscopy. Monoclonal antibodies specific to PCT were covalently immobilized onto the rGO‐AuNP nanocomposite modified paper to fabricate an electrochemical biosensor. The fabricated biosensor exhibits linearity in the PCT concentration range 10 −15×103 pg mL−1, with a low detection limit 10 pg mL−1. Furthermore, the proposed biosensor also exhibited good selectivity and could detect PCT biomarkers even in the presence of other interfering electroactive species such as glucose, oxalic acid, and urea. The proposed CF‐based biosensor has been proven as an accelerated simple point‐of‐care (POC) exploratory approach for early PCT diagnosis in inadequate areas with limited production facilities, computational techniques, and highly skilled experts. [ABSTRACT FROM AUTHOR]

In this study, a novel paper biosensor based on Fe3O4@SiO2–NH2 magnetic polymer microspheres and multi walled carbon nanotubes (MWCNTs) for rapid detection of pseudorabies virus (PRV) was first developed. Fe3O4@SiO2–NH2 were functionalized with PRV antibody and doped in cellulose nitrate paper to fabricate the magnetic paper biosensor with good magnetic response and biocompatibility. Using MWCNTs to build conductive network of sensors, PRV antigen binds specifically to the immunomagnetic microspheres on the sensor, and the resulting immune complex changes the magnetic domain structure of the sensor and the structural gap of MWCNTs, causing the magnetic property and impedance change. TEM and EDS characterization proved that the biosensor was successfully doped with Fe3O4@SiO2–NH2 and effectively recognized PRV. Under optimized conditions, the impedance variation was found to be linearly related to the logarithm value of PRV concentrations in the range of 10–1 mg ml−1, with the detection limit of 10 ng ml−1. This paper biosensor demonstrated advantages of portability, high sensitivity and specificity, providing a valuable method for early control of PRV. [ABSTRACT FROM AUTHOR]

In this work, we present the development of a paper-based, low-cost, sensitive, quantitative and stable platform proper for smartphone-assisted colorimetric detection of the fresh fish product to eliminate people's concerns while consuming seafood. Biocompatible zones were prepared onto the paper filter material by chitosan modification an d mu lt i-enzyme immobilization in the developed biosensor system. The visual detected result was connected with the hypoxanthine (Hx) amount by using a smartphone app that can perform image processing to evaluate the quantitative detection. Selectivity, specificity, stability, and direct real sample tests indicated the potential usability of the developed paper-based biosensor system for Hx detection in meat samples with an easy-to-use method. An application for examination of Hx concentration in real fish meat was a chieved by placing t he p aper-based biosensor in contact with fish skin. As a future perspective, the developed method can be practical in developing portable biosensors to assess the fish freshness grade. [ABSTRACT FROM AUTHOR]