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Disposable diagnostics is ramping up the development of green practices for healthcare. Paper is an excellent natural substrate for emerging low-cost, ecologically acceptable analytical devices. Flexibility, three-dimensional fibre structure, mechanical characteristics, ease of manufacturing and customization are the key advantages of cellulose as preferable materials for green analytical devices. This article overviews the advances in paper-based optical and electroanalytical devices, including manufacturing, validation of functions, detection methodology, and applications. The renewable resources hold the potential to accomplish the biodegradable analytical techniques due to their climate neutral waste management. The paper-based electrodes have demonstrated excellent performance for diagnostics while being eco-friendly at the same time. Therefore, the forthcoming sustainable diagnostics approaches require integrating paper-based analytical devices (PADs) built out of disposable electrodes. The diverse green materials and methods facilitate climate neural point-of-care products for the net-zero market. Numerous researches have been conducted in recent years to develop innovative technologies capable of analysing clinical samples quickly, accurately, simply, and sensitively, with the primary objective of offering competent tools for illness diagnosis and treatment efficacy follow-up. The micro-PADs show excellent abilities for quick onsite diagnostics within μ-level detection range. The sensitivity, stability, and reliability of analytical devices are the essential factors enabling larger-scale production and commercialization. The projected fabrication and analytical methods in the direction of paper-based devices could be nicely and reliably utilized for understanding and adaptation of climate neutral diagnostic technologies in healthcare sector. This detailed article discusses the sustainable framework that integrates green bioelectronics and sensor technologies adhering to diverse functionality for health and the environment. The paper-based digital technology (PDigiT) could be employed as a simple, cost-effective, and efficient net-zero technology for real-time monitoring of outbreaks and bio-surveillance.

Urinary or serum uric acid concentration is an indicator of chronic kidney condition. An increase in uric acid concentration may indicate renal dysfunction. Reliable instantaneous detection of uric acid without requiring sophisticated laboratory and analytical instrumentation, such as: chromatographic and spectrophotometric methods, would be invaluable for patients with renal complication. This paper reports the early development of a simple, low-cost, instantaneous and user-friendly paper based diagnostic device (PAD) for the qualitative and quantitative detection of uric acid in urine. A colorimetric detection technique was developed based on the intensity of Prussian blue color formation on paper in presence of uric acid; the reaction rate of corresponding chemical reactions on paper surface was also studied. Based on the colorimetric signal produced on paper surface, a calibration curve was developed to detect unknown concentration of uric acid in urine. The effect of temperature on formation of color signal on paper surface was also analyzed. In this study, estimation of urinary uric acid using MATLAB coding on a windows platform was demonstrated as the use of software application and digital diagnostics. This paper-based technique is faster and less expensive compared to traditional detection techniques. The paper-based diagnostic can be integrated with a camera of smart phone, tablet computer or laptop and an image processing application (using windows/android/IOS platform) as a part of digital diagnostics. Therefore, with proper calibration, the paper-based technique can be compatible and economical to the sophisticated detection techniques used to detect urinary uric acid.

Abstract In this work, a paper-based optoelectronic sensor (paper-nose) is presented for sensing volatile gases in air. The proposed optoelectronic sensor is a combination of both colorimetric (optical) and chemiresistive (electronic) sensor arrays in order to improve the selectivity of the paper-nose in the complex air background. The optical sensors are based on chemoresponsive dyes, namely Reichardt's dye (2,6-diphenyl-4-(2,4,6-triphenyl-1-pyridinio)phenolate), bromocresol purple, methyl red, bromothymol blue, brilliant yellow and manganese tetraphenylporphyrin (Mn-TPP). The chemiresistive sensors are based on nanomaterials, such as carbon nanotubes (CNT), PEDOT:PSS, graphite, and an ionic liquid, 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (EMI TFSI). Sensor is fabricated through direct handwriting of sensing materials using a pen on paper without the need of expensive cleanroom facilities. The optoelectronic sensor is tested in ambient air with different volatile gases such as methanol, ammonia, toluene, acetone and ethanol and their mixtures of varying concentrations. The detected electrical and optical responses together form a unique signature for each volatile gas and its mixture. Support-vector machine (SVM) is applied for target classification and detection. From the SVM result, it is found that better discriminative power is achieved by combining optical and electrical responses. Graphical abstract Image 1 Highlights • Presents an array of colorimetric and chemiresistive sensors on paper (paper-nose). • Machine learning assists paper nose to detect volatile gases and their mixtures in air. • Combining colorimetric and chemiresistive sensing is key to improving accuracy. [ABSTRACT FROM AUTHOR]

Abstract: We report a paper‐based aptasensor platform that uses two reaction zones and a connecting bridge along with printed multifunctional bio/nano materials to achieve molecular recognition and signal amplification. Upon addition of analyte to the first zone, a fluorescently labelled DNA or RNA aptamer is desorbed from printed graphene oxide, rapidly producing an initial fluorescence signal. The released aptamer then flows to the second zone where it reacts with printed reagents to initiate rolling circle amplification, generating DNA amplicons containing a peroxidase‐mimicking DNAzyme, which produces a colorimetric readout that can be read in an equipment‐free manner or with a smartphone. The sensor was demonstrated using an RNA aptamer for adenosine triphosphate (a bacterial marker) and a DNA aptamer for glutamate dehydrogenase (Clostridium difficile marker) with excellent sensitivity and specificity. These targets could be detected in spiked serum or feacal samples, demonstrating the potential for testing clinical samples. [ABSTRACT FROM AUTHOR]

There is a need for an accurate end-of-life indicator for packaged food (meat, seafood, dairy food etc.) beyond a simple “best use by” date on the food package. In this work, we propose a low cost solution by repurposing the food’s barcode as a colorimetric sensor array to monitor food condition. A smart phone camera is used to read color information from the sensor barcode for quantitative estimate of the food aging and quality. The sensor is based on cross-reactive vapor sensitive dyes encapsulated in resin microbeads, which are impregnated onto a low cost paper substrate in a barcode pattern. The entire sensor platform is validated by accurately monitoring chicken aging and eventual spoilage under different temperature conditions. The proposed food diagnostics platform has the potential to reduce food waste and eliminate food-borne illness. [ABSTRACT FROM AUTHOR]

Paper diagnostics are devices made of paper and cellulosic materials to recognize and quantify biomolecules and chemical agents affecting health. There has been a rapid increase in interest for paper-based diagnostic methods in recent years. This is because paper is cheap, widely available, easily engineered, biodegradable, combustible, biocompatible, sterilizable, hydrophilic, and easy to functionalize and process into diagnostic devices. Paper is a very attractive substrate to develop as a low-cost diagnostic platform. Paper can serve four functions in a diagnostic: 1) transport and measurement of sample and analytes, 2) reaction support, 3) separation of reactants from products, and 4) communication of results. When an aqueous analyte, such as blood, saliva, urine or feces is tested using a paper diagnostics analytical device (PAD), the fluid is driven by capillary flow induced by the porous and hydrophilic structure of the cellulose fibers, causing wicking through the paper inter-fiber space. Should hydrophobic barriers be formed onto or within paper, microfluidic systems can be created, allowing for the passive transport of the analyte. This article has four sections. The first presents paper as a composite and highlights its properties and attributes with respect to modern paper diagnostics needs. Functional printing is presented as a technology to manufacture paper diagnostics. The second section analyzes paper diagnostic design. PADs based on one dimension (1D), 2D and 3D flow, the methods of reporting, and the principles of detection are reviewed. The third section investigates applications in health and medicine for paper diagnostics in terms of clinical diagnostics, physiological disorders, and pathogenic diseases. The last section presents an analytical perspective of some of the critical issues. It is the objective of this article to analyze paper as a viable technology for producing low-cost medical analysis and to delimit the range of applications and potential best suited to paper diagnostics.

A rapid and simple paper-based elution assay for red blood cell antigen typing by the indirect antiglobulin test (IAT) was established. This allows to type blood using IgG antibodies for the important blood groups in which IgM antibodies do not exist. Red blood cells incubated with IgG anti-D were washed with saline and spotted onto the paper assay pre-treated with anti-IgG. The blood spot was eluted with an elution buffer solution in a chromatography tank. Positive samples were identified by the agglutinated and fixed red blood cells on the original spotting area, while red blood cells from negative samples completely eluted away from the spot of origin. Optimum concentrations for both anti-IgG and anti-D were identified to eliminate the washing step after the incubation phase. Based on the no-washing procedure, the critical variables were investigated to establish the optimal conditions for the paper-based assay. Two hundred ten donor blood samples were tested in optimal conditions for the paper test with anti-D and anti-Kell. Positive and negative samples were clearly distinguished. This assay opens up new applications of the IAT on paper including antibody detection and blood donor-recipient crossmatching and extends its uses into non-blood typing applications with IgG antibody-based diagnostics. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Viruses cause many infectious diseases and consequently epidemic health threats. Paper based diagnostics and filters can offer attractive options for detecting and deactivating pathogens. However, due to their infectious characteristics, virus detection using paper diagnostics is more challenging compared to the detection of bacteria, enzymes, DNA or antigens. The major objective of this study was to prepare reliable, degradable and low cost paper diagnostics to detect viruses, without using sophisticated optical or microfluidic analytical instruments. T7 bacteriophage was used as a model virus. A paper based sandwich ELISA technique was developed to detect and quantify the T7 phages in solution. The paper based sandwich ELISA detected T7 phage concentrations as low as 100 pfu/mL to as high as 10 9 pfu/mL. The compatibility of paper based sandwich ELISA with the conventional titre count was tested using T7 phage solutions of unknown concentrations. The paper based sandwich ELISA technique is faster and economical compared to the traditional detection techniques. Therefore, with proper calibration and right reagents, and by following the biosafety regulations, the paper based technique can be said to be compatible and economical to the sophisticated laboratory diagnostic techniques applied to detect pathogenic viruses and other microorganisms. [ABSTRACT FROM AUTHOR]

Background and Objectives Paper biodiagnostics for blood typing are novel, cheap, fast and easy to use. Agglutinated red blood cells cannot travel through the porous structure of paper, indicating a positive antibody-antigen interaction has occurred. Conversely, non-agglutinated blood can disperse and wick through the paper structure with the ease to indicate a negative result. This principle has been demonstrated to detect blood group phenotypes: ABO and RhD. However, typing for red blood cell antigens such as Rh, Kell, Duffy and Kidd has not yet been explored on paper. Materials and Methods Two paper testing methods - an elution and a direct flow-through method - were investigated to detect red blood cell antigens excluding the ABO system and RhD. Antigens explored include the following: C, c, E, e, K, k, Fya, Fyb, Jka, Jkb, M, N, S and s, P1, Lea and Leb. The variables tested include the following: reaction time and reagent concentration. The importance of antibody type/structure for successful agglutination on paper was confirmed. Results Some blood group phenotypes showed less agglutination due to weaker antibody-antigen interactions. Most blood groups with antibodies available as IgM, such as C, c, E, e, K and k, and Jka and Jkb, and P1, were successful using both methods. However, other blood groups, especially those with antibodies only available as polyclonal antibodies, were unsuccessful and require further scrutiny. Conclusion Paper can be used as an alternative blood grouping diagnostic tool for selected blood group phenotypes. [ABSTRACT FROM AUTHOR]

The challenge of changing the healthcare outcomes of many in low- and middle-income countries (LMICs) looms as a major potential cost to all of humankind. A majority of global health initiatives have focused upon increasing access and innovation in treatment options. However, the reliable and appropriate use of candidate treatments must be preceded by diagnoses that ensure the correct clinical path. Foremost in addressing this challenge is the need to develop and distribute appropriate, low cost, accessible diagnostic technologies to engender quality care. Such a need is pressing, for both communicable and non-communicable diseases, which continue to present a growing burden to LMICs. The emergence of paper diagnostics, microfluidic-based total analytical systems (μTAS), BioMEMS, and nano-inspired bioanalytical biosensors; which by their very sophistication promise to render diagnostic tests simple and potentially widely affordable, present exciting options to addressing this need. This paper discusses complementary policy issues in regulation and procurement that must be considered to make low cost, point of care diagnostic technology an accepted step in patient care within LMICs and presents a number of emerging technologies that are poised to address this need. [ABSTRACT FROM AUTHOR]

This editorial discusses the expanding role of paper as a platform on which to build new point-of-care assays, particularly those intended for use in resource-limited settings. Successful diagnostics for use in these environments require a low-cost platform (possibly paper) as well as new assay strategies, reagents and materials for achieving selectivity and sensitivity. Paper provides a common platform for bringing these components together and serves as a low-cost medium for prototyping new point-of-care assays. [ABSTRACT FROM AUTHOR]

Whatman No. 1 chromatography paper is widely used as a substrate for cellulose-based immunoassays. The immobilized proteins are used to capture target biomarkers for detection. However, alternative paper substrates may facilitate mass production of immunoassays as diagnostic tests. Here, we assessed the physical characteristics and protein immobilization capabilities of different commercial papers. Some substrates fulfilled our design criteria, including adequate flow rate and sufficient protein immobilization for efficient target capture. This study demonstrates that a variety of paper substrates can be bioactivated and used to capture target biomarkers, enabling development of affordable diagnostic tests from a range of starting materials.

Urinary or serum uric acid concentration is an indicator of chronic kidney condition. An increase in uric acid concentration may indicate renal dysfunction. Reliable instantaneous detection of uric acid without requiring sophisticated laboratory and analytical instrumentation, such as: chromatographic and spectrophotometric methods, would be invaluable for patients with renal complication. This paper reports the early development of a simple, low-cost, instantaneous and user-friendly paper based diagnostic device (PAD) for the qualitative and quantitative detection of uric acid in urine. A colorimetric detection technique was developed based on the intensity of Prussian blue color formation on paper in presence of uric acid; the reaction rate of corresponding chemical reactions on paper surface was also studied. Based on the colorimetric signal produced on paper surface, a calibration curve was developed to detect unknown concentration of uric acid in urine. The effect of temperature on formation of color signal on paper surface was also analyzed. In this study, estimation of urinary uric acid using MATLAB coding on a windows platform was demonstrated as the use of software application and digital diagnostics. This paper-based technique is faster and less expensive compared to traditional detection techniques. The paper-based diagnostic can be integrated with a camera of smart phone, tablet computer or laptop and an image processing application (using windows/android/IOS platform) as a part of digital diagnostics. Therefore, with proper calibration, the paper-based technique can be compatible and economical to the sophisticated detection techniques used to detect urinary uric acid.

The design of appropriate diagnostic assays for the point of care requires development of suitable biosensors, detection methods, and diagnostic platforms for sensitive, quantitative detection of biological analytes. Protein targets in particular are especially challenging to detect quantitatively and sensitively due to the lack of amplification strategies akin to nucleic acid amplification. However, recent advances in transducer and biosensor design, new detection labels, and paper-based microfluidics may realize the goal of sensitive, fast, portable, and low-cost protein detection. In this review, we discuss the biochemistry, optics, and engineering advances that may be leveraged to design such a sensitive protein diagnostic assay. The binding kinetics, mechanisms of binding in porous networks, and potential transducers are explained in detail. We discuss the relative merits of various optical detection strategies, potential detection labels, optical readout approaches, and image-processing techniques that are amenable to point-of-care use. To conclude, we present a systematic analysis of potential approaches to enhance the sensitivity of paper-based assays. The assay development framework presented here provides bioassay developers a strategy to methodically enhance the sensitivity and point-of-care suitability of protein diagnostics., (© 2017 Elsevier Inc. All rights reserved.)

This paper describes the design and fabrication of a “pop-up” electrochemical paper-based analytical device (pop-up-EPAD) to measure beta-hydroxybutyrate (BHB)—a key biomarker for diabetic ketoacidosis—using a commercial glucometer. Pop-up-EPADs are inspired by pop-up greeting cards and children's books. They are made from a single sheet of paper folded into a three-dimensional (3D) device that changes shape, and fluidic and electrical connectivity, by simply folding and unfolding the structure. The reconfigurable 3D structure makes it possible to change the fluidic path and to control timing; it also provides mechanical support for the folded and unfolded structures that enables good registration and repeatability on folding. A pop-up-EPAD designed to detect BHB shows performance comparable to commercially available plastic test strips over the clinically relevant range of BHB in blood when used with a commercial glucometer that integrates the ability to measure glucose and BHB (combination BHB/glucometer). With simple modifications of the electrode and fluid path design, the pop-up-EPAD also detects BHB using a simple glucometer—a device that is much more available than combination BHB/glucometers. Strategies that use a “3D pop-up”—that is, large-scale changes a 3D structure and fluidic paths—by folding/unfolding add functionality (e.g., controlled timing, fluidic handling and path programming, control over complex sequences of steps, and alterations in electrical connectivity) to EPADs, and should enable the development of new classes of paper-based diagnostic de-vices., Chemistry and Chemical Biology