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Bloodstream infection (BSI) is a major complication in patients with cancers due to therapy-induced neutropenia and underlying conditions, which increases hospitalization time and mortality rate. Targeted and timely antimicrobial management is crucial to save the patients’ lives and reduce the social and economic burdens. Blood culture is a routine clinical diagnostic method of BSI with a long turnaround time, and generally identifies monomicrobial BSI. Thus, polymicrobial BSI often goes undetected although it occurs more frequently in these patients and results in more severe outcomes compared to monomicrobial BSI. In this work, we apply glutaric anhydride, N-hydroxysuccinimide and N,N′-dicyclohexylcarbodiimide to fabricate a functional surface on cellulose filter paper. Targeting three pathogens (Escherichia coli, Saccharomyces cerevisiae, and human cytomegalovirus) commonly occurring in BSI in neutropenic patients, we demonstrate rapid and accurate triplex pathogen DNA detection using the functionalized paper. All three pathogen DNA was identified in 1–5 min with a detection limit of 0.1–0.5 ng/µL. The developed test tool has the potential to provide rapid polymicrobial BSI diagnosis in support of timely, accurate antimicrobial treatment, and could be integrated into an automatic sample-to-result portable equipment.

As a two-dimensional material, graphene has attracted increasing attention as heat dissipation material owing to its excellent thermal transport property. In this work, we fabricated sisal nanocrystalline cellulose/functionalized graphene papers (NPGs) with high thermal conductivity by vacuum-assisted self-assembly method. The papers exhibit in-plane thermal conductivity as high as 21.05 W m−1 K−1 with a thermal conductivity enhancement of 403% from the pure cellulose paper. The good thermal transport properties of NPGs are attributed to the strong hydrogen-bonding interaction between nanocrystalline cellulose and functionalized graphene and the well alignment structure of NPGs.

Microfluidic paper-based analytical devices (microPADs) are emerging as cost-effective and portable platforms for point-of-care assays. A fundamental limitation of microPAD fabrication is the imprecise nature of most methods for patterning paper. The present work demonstrates that paper patterned via wax printing can be miniaturized by treating it with periodate to produce higher-resolution, high-fidelity microPADs. The optimal miniaturization parameters were determined by immersing microPADs in various concentrations of aqueous sodium periodate (NaIO4) for varying lengths of time. This treatment miniaturized microPADs by up to 80% in surface area, depending on the concentration of periodate and length of the reaction time. By immersing microPADs in 0.5-M NaIO4 for 48 hours, devices were miniaturized by 78% in surface area, and this treatment allowed for the fabrication of functional channels with widths as small as 301 µm and hydrophobic barriers with widths as small as 387 µm. The miniaturized devices were shown to be compatible with redox-based colorimetric assays and enzymatic reactions. This miniaturization technique provides a new option for fabricating sub-millimeter-sized features in paper-based fluidic devices without requiring specialized equipment and could enable new capabilities and applications for microPADs.

Cellulose fibers are a major industrial input, but due to their irregular shape and anisotropic material response, accurate material characterization is difficult. Single fiber tensile testing is the most popular way to estimate the material properties of individual fibers. However, such tests can only be performed along the axis of the fiber and are associated with problems of enforcing restraints. Alternative indirect approaches, such as micro-mechanical modeling, can help but yield results that are not fully decoupled from the model assumptions. Here, we compare these methods with nanoindentation as a method to extract elastic material constants of the individual fibers. We show that both the longitudinal and the transverse elastic modulus can be determined, additionally enabling the measurement of fiber properties in-situ inside a sheet of paper such that the entire industrial process history is captured. The obtained longitudinal modulus is comparable to traditional methods for larger indents but with a strongly increased scatter as the size of the indentation is decreased further.

Polistes paper wasps are a widespread taxon inhabiting various climates. They build nests in the open without a protective outer layer, which makes them vulnerable to changing temperatures. To better understand the options they have to react to environmental variation and climate change, we here compare the thermoregulatory behavior of Polistes biglumis from cool Alpine climate with Polistes gallicus from warm Mediterranean climate. Behavioral plasticity helps both of them to withstand environmental variation. P. biglumis builds the nests oriented toward east-south-east to gain solar heat of the morning sun. This increases the brood temperature considerably above the ambience, which speeds up brood development. P. gallicus, by contrast, mostly avoids nesting sites with direct insolation, which protects their brood from heat stress on hot days. To keep the brood temperature below 40–42 °C on warm days, the adults of the two species show differential use of their common cooling behaviors. While P. biglumis prefers fanning of cool ambient air onto the nest heated by the sun and additionally cools with water drops, P. gallicus prefers cooling with water drops because fanning of warm ambient air onto a warm nest would not cool it, and restricts fanning to nests heated by the sun.

The high cost, complexity and reliance on electricity, specialized equipment and supplies associated with conventional diagnostic methods limit the scope and sustainability of newborn screening for sickle cell disease (SCD) in sub-Saharan Africa and other resource-limited areas worldwide. Here we describe the development of a simple, low-cost, rapid, equipment- and electricity-free paper-based test capable of detecting sickle hemoglobin (HbS) in newborn blood samples with a limit of detection of 2% HbS. We validated this newborn paper-based test in a cohort of 159 newborns at an obstetric hospital in Cabinda, Angola. Newborn screening results using the paper-based test were compared to conventional isoelectric focusing (IEF). The test detected the presence of HbS with 81.8% sensitivity and 83.3% specificity, and identified SCD newborns with 100.0% sensitivity and 70.7% specificity. The use of the paper-based test in a two-stage newborn screening process could have excluded about 70% of all newborns from expensive confirmatory testing by IEF, without missing any of the SCD newborns in the studied cohort. This study demonstrates the potential utility of the newborn paper-based test for reducing the overall cost of screening newborns for SCD and thus increasing the practicality of universal newborn SCD screening programs in resource-limited settings.

Distinguishing a specific biomarker from a biofluid sample containing a large variety of proteins often requires the selective preconcentration of that particular biomarker to a detectable level for analysis. Low-cost, paper-based device is an emerging opportunity in diagnostics. In the present study, we report a novel Zinc oxide nanorods functionalized paper platform for the preconcentration of Myoglobin, a cardiac biomarker. Zinc oxide nanorods were grown on a Whatman filter paper no. 1 via the standard hydrothermal route. The growth of Zinc oxide nanorods on paper was confirmed by a combination of techniques consisting of X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS,) scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDX) analysis. The Zinc oxide nanorods modified Whatman filter paper (ZnO-NRs/WFP) was further tested for use as a protein preconcentrator. Paper-based ELISA was performed for determination of pre-concentration of cardiac marker protein Myoglobin using the new ZnO-NRs/WFP platform. The ZnO-NRs/WFP could efficiently capture the biomarker even from a very dilute solution (Myoglobin

Ovarian cancer has a poor cure rate and rates of relapse are high. Current recurrence detection is limited by non-specific methods such as blood testing and ultrasound. Based on reports that human epididymis four (HE4) / creatinine (CRE) ratios found in urine are elevated in ovarian cancers, we have developed a paper-based device that combines lateral flow technology and cell phone analysis to quantitatively measure HE4/CRE. Surrogate samples were used to test the performance over clinically expected HE4/CRE ratios. For HE4/CRE ratios of 2 to 47, the percent error was found to be 16.0% on average whether measured by a flatbed scanner or cell phone. There was not a significant difference between the results from the cell phone or scanner. Based on published studies, error in this method was less than the difference required to detect recurrence. This promising new tool, with further development, could be used at home or in low-resource settings to provide timely detection of ovarian cancer recurrence.

Here, we discuss the development of a paper-based diagnostic device that is inexpensive, portable, easy-to-use, robust, and capable of running simultaneous tests to monitor a relevant inflammatory protein for clinical diagnoses i.e. C-reactive protein (CRP). In this study, we first attempted to make a paper-based diagnostic device via the wax printing method, a process that was used in previous studies. This device has two distinct advantages: 1) reduced manufacturing and assay costs and operation duration via using wax printing method to define hydrophobic boundaries (for fluidic devices or general POC devices); and, 2) the hydrophilicity of filter paper, which is used to purify and chromatographically correct interference caused by whole blood components with a tiny amount of blood sample (only 5 μL). Diagnosis was based on serum stain length retained inside the paper channels of our device. This is a balanced function between surface tension and chromatographic force following immune reactions (CRP assays) with a paper-embedded biomarker.

Throughout the last decade, the expansion of food testing has been gradually moving towards ordinary high throughput screening methods performed on-site. The demand for point-of-care testing, able to distinguish molecular signatures with high accuracy, sensitivity and specificity has been significantly increasing. This new requirement relies on the on-site detection and monitorization of molecular signatures suitable for the surveillance of food production and processing. The widespread use of antibiotics has contributed to disease control of livestock but has also created problems for the dairy industry and consumers. Its therapeutic and subtherapeutic use has increased the risk of contamination in milk in enough concentrations to cause economic losses to the dairy industry and have a health impact in highly sensitive individuals. This study focuses on the development of a simple Surface-Enhanced Raman Spectroscopy (SERS) method for fast high throughput screening of tetracycline (TET) in milk. For this, we integrate a paper-based low-cost, fully recyclable and highly stable SERS platform, with a minimal sample preparation protocol. A two-microliter sample of milk solutions spiked with TET (from 0.01 to 1000 ppm) is dried on a silver nanoparticle coated cardboard substrate and measured via a Raman spectrophotometer. The SERS substrate showed to be extremely stable with a shelf life of several months. A global spectrum principal component analysis approach was used to test all the detected vibrational modes and their correlation with TET concentration. Peak intensity ratios (455 cm−1/1280 cm−1 and 874 cm−1/1397 cm−1) were found to be correlated with TET concentrations in milk, achieving a sensitivity as low as 0.1 ppm. Results indicate that this SERS method combined with portable Raman spectrometer is a potential tool that can be used on-site for the monitoring of TET residues and other antibiotics.

This work presents a cost-effective, label-free in point-of-care (POC) biosensor for the sensitive detection of 8-hydroxy-2′-deoxyguanosine (8-OHdG), the most abundant oxidative product of DNA, that may allow a premature assessment of cancer disease, thereby improving diagnosis, prognostics and survival rates. The device targets the direct detection of 8-OHdG by using for the first time a carbon-ink 3-electrode on a paper substrate coupled to Differential Pulse Voltammetry readings. This design was optimized by adding nanostructured carbon materials to the ink and the conducting polymer PEDOT, enhancing the electrocatalytic properties of the sensor towards 8-OHdG detection. Meanwhile, the ability of this oxidative stress biomarker to undertake an oxidation reaction enabled the development of the sensing electrochemical device without the need of chemical probes and long incubation periods. This paper-modified sensor presented high electrochemical performance on the oxidation of 8-OHdG with a wide linear range (50–1000 ng/ml) and a low detection limit (14.4 ng/ml). Thus, our results showed the development of a direct and facile sensor with good reproducibility, stability, sensitivity and more importantly, selectivity. The proposed carbon-based electrochemical sensor is a potential candidate to be miniaturized to small portable size, which make it applicable for in-situ 8-OHdG sensing in real biological samples.

Paper-based microfluidic devices have many applications in biomedical and environmental analysis. However, the process of prototyping device designs can be tedious, error-prone, and time-consuming. Here, we present a cross-platform, open-source software tool—AutoPAD—developed to quickly create and modify device designs and provide a free alternative to commercial design software. The capabilities that we designed to be inherent to AutoPAD (e.g., automatic zone alignment and design refactoring) highlight its potential use in nearly any paper-based microfluidic device application and for creating nearly any desired design, which we demonstrate through the recreation of numerous device designs from the literature.

We present a simple all-in-one paper-based sensor for E. coli detection using a composite ink made of a fluorogenic DNAzyme probe for bacterial recognition and signal generation, lysozyme that lyses whole bacterial cells, and pullulan/trehalose sugars that stabilize printed bioactive molecules. The paper sensor is capable of producing a fluorescence signal as a readout within 5 minutes upon contacting E. coli, can achieve a limit of detection of 100 cells/mL, in a variety of sample matrixes, without sample enrichment, and remains stable for at least 6 months when stored at ambient temperature. Therefore, this simple paper sensor provides rapid bacterial testing on site, and can be shipped and stored under ambient conditions to benefit users living in resource-limited regions.

For the first time, a paper-based fluorescence resonance energy transfer (FRET) determination with cyclic AMP (cAMP)-specific phosphodiesterase 4B (PDE4B) inhibitory assay using an inkjet-printing technique is proposed. Non-fabricated parchment paper is found to constitute a unique substrate to measure fluorescent energy transfer, due to its insignificant self-absorption, and enables efficient sample interaction. Here, we report the responsive FRET signals generated on paper, upon sequentially printing reaction components on parchment paper using a conventional inkjet printer equipped with four cartridges. After printing, the energy emitted by Eu chelate was transferred by FRET to ULight molecule on paper, detected at 665 nm. In the absence of free cAMP, a maximum FRET signal was achieved on paper, while a decrease in FRET signals was recorded when free cAMP produced by PDE4B inhibitors compete with Eu-cAMP, binding with ULight-mAb. The IM50 value was determined as 2.46 × 10−13 mole for roliparm and 1.86 × 10−13 mole for roflumilast, to effectively inhibit PDE4B activity. Inkjet printing-based FRET signal determination utilizes components that are less than the femtomole range, which was four-orders less than the standard assay method. The methodology reported here constitutes an innovative approach towards the determination of FRET signals generated on paper.

Paper-based micro analytical devices offer significant advantages compared to the conventional microfluidic chips including cost-effectiveness, ease of fabrication, and ease of use while preserving critical features including strong capillary action and biological compatibility. In this work, we demonstrate an inexpensive, rapid method for high-throughput fabrication of paper-based microfluidics by patterning hydrophobic barriers using a desktop pen plotter integrated with a custom-made, low-cost paper feeder. We tested various types of commercial permanent markers and compared their water-resistant capabilities for creating hydrophobic barriers. Additionally, we studied the performance of markers with different types of paper, plotting speeds, and pattern dimensions. To verify the effectiveness of the presented fabrication method, colorimetric analysis was performed on the results of a glucose assay.

Peaches are known for their palatable flavor and abundant nutrients. However, peaches are perishable, and the existing preservation techniques for peaches are still immature. To further extend the shelf life and prevent nutrient loss of perishable peaches under ambient temperature in summer (approximately 25–32 °C), we conducted experiments wrapping peaches (Prunus persica cv ‘Baihua’) in single- and composite-treated vegetal fibrous papers that contained calcium carbonate, phytic acid, Na-alginate and vitamin C. The pathogenic fungi that primarily caused peach decay during storage belonged to the genera of Penicillium, Botrytis, Aspergillus, Alternaria, and Rhizopus. After analyzing quality attributes, including weight loss, firmness, soluble sugar content, respiration rate, relative electric conductivity, malonaldehyde content, peroxidase activity and the decay index, we proved that vitamin C within the preservative paper greatly contributes to peach preservation. Combined with phytic acid and Na-alginate, the composite vitamin C preservative papers played significant roles in delaying fruit senescence, and 0.4% (w/v) vitamin C preservative paper with 1% Na-alginate could maintain quality and extend shelf life with the best effect. This preservation technique significantly postponed the respiration peak by 2–3 days and is a significant contribution to contemporary commercial production.

The most performing techniques enabling early diagnosis of infectious diseases rely on nucleic acid detection. Today, because of their high technicality and cost, nucleic acid amplification tests (NAAT) are of benefit only to a small fraction of developing countries population. By reducing costs, simplifying procedures and enabling multiplexing, paper microfluidics has the potential to considerably facilitate their accessibility. However, most of the studies performed in this area have not quit the lab. This letter brings NAAT on paper closer to the field, by using clinical samples and operating in a resource-limited setting. We first performed isothermal reverse transcription and Recombinase Polymerase Amplification (RT-RPA) of synthetic Ribonucleic Acid (RNA) of Ebola virus using paper microfluidics devices. We further applied this method in Guinea to detect the presence of Ebola virus in human sample RNA extracts, with minimal facilities (carry-on detection device and freeze-dried reagents on paper). RT-RPA results were available in few minutes and demonstrate a sensitivity of 90.0% compared to the gold-standard RT-PCR on a set of 43 patient samples. Furthermore, the realization of a nine-spot multilayered device achieving the parallel detection of three distinct RNA sequences opens a route toward the detection of multiple viral strains or pathogens.

Paper spray ionization (PSI) mass spectrometry (MS) is an emerging tool for ambient reaction monitoring via microdroplet reaction acceleration. PSI-MS was used to accelerate and monitor the time course of the reaction of dansyl chloride with aniline, in acetonitrile, to produce dansyl aniline. Three distinct PSI arrangements were explored in this study representing alternative approaches for sample loading and interaction; conventional single tip as well as two novel setups, a dual-tip and a co-axial arrangement were designed so as to limit any on-paper interaction between reagents. The effect on product abundance was investigated using these different paper configurations as it relates to the time course and distance of microdroplet travel. It was observed that product yield increases at a given distance and then decreases thereafter for all PSI configurations. The fluorescent property of the product (dansyl aniline) was used to visually inspect the reaction progress on the paper substrate during the spraying process. Amongst the variety of sample loading methods the novel dual-tip arrangement showed an increased product yield and microdroplet density, whilst avoiding any on-paper interaction between the reagents.

Low energy surface coatings have found wide range of applications for generating hydrophobic and superhydrophobic surfaces. Most of the studies have been related to use of a single coating material over a single substrate or using a single technique. The degree of hydrophobicity is highly dependent on fabrication processes as well as materials being coated and as such warrants a high-level study using experimental optimization leading to the evaluation of the parametric behavior of coatings and their application techniques. Also, a single platform or system which can predict the required set of parameters for generating hydrophobic surface of required nature for given substrate is of requirement. This work applies the powerful machine learning algorithms (Levenberg Marquardt using Gauss Newton and Gradient methods) to evaluate the various processes affecting the anti-wetting behavior of coated printable paper substrates with the capability to predict the most optimized method of coating and materials that may lead to a desirable surface contact angle. The major application techniques used for this study pertain to dip coating, spray coating, spin coating and inkjet printing and silane and sol–gel base coating materials.

3D printed and paper-based microfluidics are promising formats for applications that require portable miniaturized fluid handling such as point-of-care testing. These two formats deployed in isolation, however, have inherent limitations that hamper their capabilities and versatility. Here, we present the convergence of 3D printed and paper formats into hybrid devices that overcome many of these limitations, while capitalizing on their respective strengths. Hybrid channels were fabricated with no specialized equipment except a commercial 3D printer. Finger-operated reservoirs and valves capable of fully-reversible dispensation and actuation were designed for intuitive operation without equipment or training. Components were then integrated into a versatile multicomponent device capable of dynamic fluid pathing. These results are an early demonstration of how 3D printed and paper microfluidics can be hybridized into versatile lab-on-chip devices.

Graphite pencil stroked electrodes for paper-based Microfluidic devices are gaining immense attention due to their electrochemical properties, cost efficiency, and ease-of-use. However, their widespread use has been hindered by the challenges associated with their manual fabrication such as non-uniformity in graphite deposition, applied pressure, etc. This work presents the design and development of an automated graphite pencil stroking device for graphite electrode fabrication with high efficiency through a compact, inexpensive and automatic process, with reduced fabrication time and human intervention leading to more uniformity. The motion platform of Graphtec plotter was used to create multiple strokes with the help of the proposed device. Such inexpensive graphite electrodes (less than the US $1) have been observed to be porous in nature, acting as diffusion agents. The automated graphite electrodes were used to study the performance of microfluidic paper fuel cells (MPFCs) with formic acid, oxygen, and sulphuric acid acting as fuel, oxidising agent and electrolyte respectively. From this configuration, the maximum current density and power density were measured to be 1,305.5 µA cm−2 and 135.5 µW cm−2, respectively at 0.3 V stable OCP at 100 strokes. Overall, the study enumerates the development of an automated pencil stroke device for fabricating graphite electrodes, which can potentially be harnessed in numerous miniaturized paper based applications.

Triboelectric nanogenerators (TENGs) offer an emerging market of self-sufficient power sources, converting the mechanical energy of the environment to electricity. Recently reported high power densities for the TENGs provide new applications opportunities, such as self-powered sensors. Here in this research, a flexible graphene oxide (GO) paper was fabricated through a straightforward method and utilized as the electrode of TENGs. Outstanding power density as high as 1.3 W.m−2, an open-circuit voltage up to 870 V, and a current density of 1.4 µA.cm−2 has been extracted in vertical contact-separation mode. The all-flexible TENG has been employed as a self-powered humidity sensor to investigate the effect of raising humidity on the output voltage and current by applying mechanical agitation in two forms of using a tapping device and finger tapping. Due to the presence of superficial functional groups on the GO paper, water molecules are inclined to be adsorbed, resulting in a considerable reduction in both generated voltage (from 144 V to 14 V) and current (from 23 µA to 3.7 µA) within the range of relative humidity of 20% to 99%. These results provide a promising applicability of the first suggested sensitive self-powered GO TENG humidity sensor in portable/wearable electronics.

In offset printing process, poor mechanical properties and printability of paper substrate usually result in printing problems, low quality of print and waste of paper materials. Therefore, many researches focus on the quality improvement of paper substrates using suitable additives. In this work, N-methylated chitosan, including N, N-dimethyl chitosan (DMC) and N, N, N-trimethyl chitosan (TMC), were prepared and employed as coating agents to ameliorate the mechanical properties and printability of paper sheets. Analysis results showed that the mechanical strength of coated papers with DMC and TMC were largely improved, because the fibers with negative charges were prone to form electrostatic bonding with the positively charged N-methylated chitosan, thus enhancing paper strength. Particularly, compared with chitosan and DMC, the TMC-coated paper exhibited better mechanical properties, printability and surface properties due to the high cationic charge density of TMC. Therefore, surface coating with TMC is of great benefit to decrease the printing problem of paper sheets and enhance the operation speed in offset printing. This work provides a valuable reference for the amelioration of the printability and physical properties of high-quality paper products for many promising applications.

Paper has been pursued as an interesting substrate material for sensors in applications such as microfluidics, bio-sensing of analytes and printed microelectronics. It offers advantages of being inexpensive, lightweight, environmentally friendly and easy to use. However, currently available paper-based mechanical sensors suffer from inadequate range and accuracy. Here, using the principle of supercapacitive sensing, we fabricate force sensors from paper with ultra-high sensitivity and unprecedented configurability. The high sensitivity comes from the sensitive dependence of a supercapacitor’s response on the contact area between a deformable electrolyte and a pair of electrodes. As a key component, we develop highly deformable electrolytes by coating ionic gel on paper substrates which can be cut and shaped into complex three-dimensional geometries. Paper dissolves in the ionic gel after determining the shape of the electrolytes, leaving behind transparent electrolytes with micro-structured fissures responsible for their high deformability. Exploiting this simple paper-based fabrication process, we construct diverse sensors of different configurations that can measure not just force but also its normal and shear components. The new sensors have range and sensitivity several orders of magnitude higher than traditional MEMS capacitive sensors, in spite of their being easily fabricated from paper with no cleanroom facilities.

In this study, we developed a new type of paper-based analytical device (PAD), the three-dimensional (3D) slip-PAD, to detect infectious human norovirus for global healthcare. The 3D configuration of the papers combined with a slip design provides unique features and versatility that overcome the limitations of fluidic manipulation and sensitivity in point-of-care (POC) tests. The assay can be carried out in a single step based on a moveable slip design, making it suitable for unskilled users. The 3D fluidic network developed by layered construction of wax-patterned papers provides different fluidic paths for the sequential delivery of multiple fluids without the need for peripheral equipment. The release and mixing of enhancement reagents on the device improved the sensitivity and detection limit. The assay results could be visualized by naked eye within 10 min, with subsequent amplification of the signal over time (4 copies ml−1 for human norovirus. These results demonstrate that the 3D slip-PAD is a sensitive diagnostic assay for detecting human norovirus infection that is particularly suitable for POC testing in regions where resources are scarce.

A paper-based upconversion fluorescence resonance energy transfer assay device is proposed for sensitive detection of CEA. The device is fabricated on a normal filter paper with simple nano-printing method. Upconversion nanoparticles tagged with specific antibodies are printed to the test zones on the test paper, followed by the introduction of assay antigen. Upconversion fluorescence measurements are directly conducted on the test zones after the antigen-to-antibody reactions. Furthermore, a multi-channel test paper for simultaneous detection of multiple cancer biomarkers was established by the same method and obtained positive results. The device showed high anti-interfere, stability, reproducible and low detection limit (0.89 ng/mL), moreover it is very easy to fabricate and operate, which is a promising prospect for a clinical point-of-care test.

Scientific Reports 6: Article number: 38171; published online: 02 December 2016; updated: 16 March 2017 The original version of this Article contained errors in the spelling of the authors Chung-Yuh Tzeng and Hsueh-Yao Chu, which were incorrectly given as Chung-Yuh Tseng and Shueh-Yao Chu respectively.

Spatially uniform reconstitution of dried reagents is critical to the function of paper microfluidic devices. Advancing fluid fronts in paper microfluidic devices drive (convect) and concentrate rehydrated reagents to the edges, causing steep chemical gradients and imperfect mixing. This largely unsolved problem in paper microfluidics is exacerbated by increasing device dimensions. In this article, we demonstrate that mixing of dried reagents with a rehydrating fluid in paper microfluidics may be significantly enhanced by stacking paper layers having different wicking rates. Compared to single-layer paper membranes, stacking reduced the “non-reactive area”, i.e. area in which the reconstituted reagents did not interact with the rehydrating fluid, by as much as 97% in large (8 cm × 2 cm) paper membranes. A paper stack was designed to collect ~0.9 ml liquid sample and uniformly mix it with dried reagents. Applications of this technology are demonstrated in two areas: (i) collection and dry storage of sputum samples for tuberculosis testing, and (ii) salivary glucose detection using an enzymatic assay and colorimetric readout. Maximizing the interaction of liquids with dried reagents is central to enhancing the performance of all paper microfluidic devices; this technique is therefore likely to find important applications in paper microfluidics.

Analyzing electrolytes in urine, such as sodium, potassium, calcium, chloride, and nitrite, has significant diagnostic value in detecting various conditions, such as kidney disorder, urinary stone disease, urinary tract infection, and cystic fibrosis. Ideally, by regularly monitoring these ions with the convenience of dipsticks and portable tools, such as cellphones, informed decision making is possible to control the consumption of these ions. Here, we report a paper-based sensor for measuring the concentration of sodium, potassium, calcium, chloride, and nitrite in urine, accurately quantified using a smartphone-enabled platform. By testing the device with both Tris buffer and artificial urine containing a wide range of electrolyte concentrations, we demonstrate that the proposed device can be used for detecting potassium, calcium, chloride, and nitrite within the whole physiological range of concentrations, and for binary quantification of sodium concentration.

A novel strategy for the direct analysis of non-conjugated steroids in water using paper spray mass spectrometry (PS-MS) has been developed. PS-MS was used in the identification and quantification of non-conjugated (free) steroids in fish tank water samples. Data shown herein indicates that individual amounts of free steroids can be detected in aqua as low as; 0.17 ng/µL, 0.039 ng/µL, 0.43 ng/µL, 0.0076 ng/µL for aldosterone, corticosterone, cortisol, and β-estrone, respectively, and with an average relative standard deviation of ca. in aqua.

Contamination of the environment by mercury(II) ions (Hg2+) poses a serious threat to human health and ecosystems. Up to now, many reported Hg2+ sensors require complex procedures, long measurement times and sophisticated instrumentation. We have developed a simple, rapid, low cost and naked-eye quantitative method for Hg2+ environmental analysis using a paper-based colorimetric device (PCD). The sample solution to which platinum nanoparticles (PtNPs) have been added is dispensed to the detection zone on the PCD, where the 3,3,5,5-tetramethylbenzidine (TMB) substrate has been pre-loaded. The PtNPs effect a rapid oxidization of TMB, inducing blue colorization on the PCD. However, Hg2+ in the solution rapidly interact with the PtNPs, suppressing the oxidation capacity and hence causing a decrease in blue intensity, which can be observed directly by the naked eye. Moreover, Hg2+ at concentrations as low as 0.01 uM, can be successfully monitored using a fiber optic device, which gives a digital readout proportional to the intensity of the blue color change. This paper-based colorimetric device (PCD) shows great potential for field measurement of Hg2+.

Enzyme linked immunosorbent assay (ELISA) is one of the most widely used laboratory disease diagnosis methods. However, performing ELISA in low-resource settings is limited by long incubation time, large volumes of precious reagents and well-equipped laboratories. Herein, we developed a simple, miniaturized paper/PMMA (poly(methyl methacrylate)) hybrid microfluidic microplate for low-cost, high throughput and point-of-care (POC) infectious disease diagnosis. The novel use of porous paper in flow-through microwells facilitates rapid antibody/antigen immobilization and efficient washing, avoiding complicated surface modifications. The top reagent delivery channels can simply transfer reagents to multiple microwells thus avoiding repeated manual pipetting and costly robots. Results of colorimetric ELISA can be observed within an hour by the naked eye. Quantitative analysis was achieved by calculating the brightness of images scanned by an office scanner. Immunoglobulin G (IgG) and Hepatitis B surface Antigen (HBsAg) were quantitatively analyzed with good reliability in human serum samples. Without using any specialized equipment, the limits of detection of 1.6 ng/mL for IgG and 1.3 ng/mL for HBsAg were achieved, which were comparable to commercial ELISA kits using specialized equipment. We envisage that this simple POC hybrid microplate can have broad applications in various bioassays, especially in resource-limited settings.

Transparent paper is an alternative substrate for electronic devices due to its unique properties. However, energy-intensive and/or time-consuming procedures currently limit the scalable production of transparent paper. In this report, we demonstrate a rapid process to fabricate optically transparent paper with regenerative cellulose fibers (RCFs) by employing a dissolving-debonding strategy. The RCFs have an average width of 19.3 μm and length of several hundred microns and are prepared into transparent paper by vacuum filtration. This new dissolving-debonding approach enables high production efficiency while creating transparent paper with excellent optical and mechanical properties.

Herein we present a novel approach for the quantification of active pharmaceutical ingredients (APIs) using mass spectrometry imaging. This strategy uses a filter paper previously “eluted” with a MALDI matrix solution as a support for analyte application. Samples are submitted to mass spectrometry imaging (MSI) and quantification through characteristic fingerprints is ultimately performed. Results for the content of rosuvastatin from a known formulation are comparable to those obtained with a validated HPLC method.

Constructing methods for cleaning stains on paper artworks that meet the requirements of preservation of cultural relics are still challenging. In response to this problem, a novel electrochemical cleaning method and the preparation of corresponding electrodes were proposed. For this purpose, the conductive graphene (rGO)/polyacryamide (PAM)/montmorillonite (MMT) composite hydrogel as cathode and PbO2-based material as anode were prepared and characterized. The electrochemical cleaning efficiencies of real sample and mimicking paper artifacts were evaluated, and the effects of the electrochemical cleaning on paper itself were detected. Based on the above experiments, the following results were obtained. The composite hydrogel with attractive mechanical properties is mainly based on the hydrogen bond interactions between PAM chains and MMT. The results of cleaning efficiency revealed that the black mildew stains together with the yellowish foxing stains were almost completely eliminated within 6 min at 8 mA/cm2, and various stains formed by tideline, foxing, organic dyes and drinks could be thoroughly removed at 4 mA/cm2 within 5 min. In addition, the proposed cleaning method has advantages in local selectivity, easy control of cleaning course, and reusability, which represents a potential utility of this approach.

Here we report the vertical paper analytical devices (vPADs) fabricated using the principles of quilling and kirigami. What differentiates the vPADs from conventional paper microfluidic devices is that the paper substrate used to fabricate the device is placed vertically to the device plane. The fabrication of vPADs with high precision is instrument-free, requiring no photolithography, printing or heating. Two- and three-dimensional vPADs are fabricated for multiplex colorimetric assays of four biochemical indicators and automated enzyme-linked immunosorbent assay of human myoglobin, respectively.

For analytical applications in portable sensors to be used in the point-of-need, low-cost SERS substrates using paper as a base, are an alternative. In this work, SERS substrates were produced on two different types of paper: a high porosity paper (Whatman no. 1); and a low porosity paper (commercially available office paper, Portucel Soporcel). Solutions containing spherical silver nanoparticles (AgNPs) and silver nanostars (AgNSs) were separately drop-casted on hydrophilic wells patterned on the papers. The porosity of the paper was found to play a determinant role on the AgNP and AgNS distribution along the paper fibres, with most of the nanoparticles being retained at the illuminated surface of the office paper substrate. The highest SERS enhancements were obtained for the office paper substrate, with deposited AgNSs. A limit of detection for rhodamine-6G as low as 11.4 ± 0.2 pg could be achieved, with an analytical enhancement factor of ≈107 for this specific analyte. The well patterning technique allowed good signal uniformity (RSD of 1.7%). Besides, these SERS substrates remained stable after 5 weeks of storage (RSD of 7.3%). Paper-induced aggregation of AgNPs was found to be a viable alternative to the classical salt-induced aggregation, to obtain a highly sensitive SERS substrates.

We reported a scalable and modular method to prepare a new type of sandwich-structured graphene-based nanohybrid paper and explore its practical application as high-performance electrode in flexible supercapacitor. The freestanding and flexible graphene paper was firstly fabricated by highly reproducible printing technique and bubbling delamination method, by which the area and thickness of the graphene paper can be freely adjusted in a wide range. The as-prepared graphene paper possesses a collection of unique properties of highly electrical conductivity (340 S cm−1), light weight (1 mg cm−2) and excellent mechanical properties. In order to improve its supercapacitive properties, we have prepared a unique sandwich-structured graphene/polyaniline/graphene paper by in situ electropolymerization of porous polyaniline nanomaterials on graphene paper, followed by wrapping an ultrathin graphene layer on its surface. This unique design strategy not only circumvents the low energy storage capacity resulting from the double-layer capacitor of graphene paper, but also enhances the rate performance and cycling stability of porous polyaniline. The as-obtained all-solid-state symmetric supercapacitor exhibits high energy density, high power density, excellent cycling stability and exceptional mechanical flexibility, demonstrative of its extensive potential applications for flexible energy-related devices and wearable electronics.

This work was partially supported by the Portuguese Science Foundation (FCT-MEC) through the projects EXCL/CTM-NAN/0201/2012, Pest-C/CTM/LA0025/2013-14, Pest-C/EQB/LA0006/2013-14, PTDC/BBB-BEP/0753/2012 and the ERC Advanced Grant (INVISIBLE, contract number 228144). Geobacter sulfurreducens cells were kindly provided by Prof. Derek Lovley from University of Massachusetts (USA). We would like to thank to Dr. Daniela Nunes for the SEM images. Electrochemically active bacteria (EAB) have the capability to transfer electrons to cell exterior, a feature that is currently explored for important applications in bioremediation and biotechnology fields. However, the number of isolated and characterized EAB species is still very limited regarding their abundance in nature. Colorimetric detection has emerged recently as an attractive mean for fast identification and characterization of analytes based on the use of electrochromic materials. In this work, WO 3 nanoparticles were synthesized by microwave assisted hydrothermal synthesis and used to impregnate non-treated regular office paper substrates. This allowed the production of a paper-based colorimetric sensor able to detect EAB in a simple, rapid, reliable, inexpensive and eco-friendly method. The developed platform was then tested with Geobacter sulfurreducens, as a proof of concept. G. sulfurreducens cells were detected at latent phase with an RGB ratio of 1.10 ± 0.04, and a response time of two hours. publishersversion published

We present a prototype for conducting rapid, inexpensive and point-of-care-compatible nucleic acid amplification tests (NAATs) for tuberculosis (TB). The fluorescent isothermal paper-and-plastic NAAT (FLIPP-NAAT) uses paper-based loop mediated isothermal amplification (LAMP) for DNA detection. The cost of materials required to build a 12-test-zone device is $0.88 and the cost of reagents per reaction is $0.43. An inexpensive imaging platform enables filter-free fluorescence detection of amplified DNA using a cell-phone camera. FLIPP-NAAT can be operated by an untrained user and only requires a regular laboratory incubator as ancillary equipment. All reagents can be dry-stored in the device, facilitating storage and transportation without cold chains. The device design is modular and the assay demonstrated high specificity to Mycobacterium tuberculosis (Mtb), analytical sensitivity of the order of 10 copies of Mtb gDNA, and tolerance to complex samples. The clinical sensitivity and specificity of sputum-based FLIPP NAAT tests were 100% (zero false negatives) and 68.75% (five false positives), respectively (N = 30), using Xpert MTB/RIF assay as the reference standard. FLIPP-NAAT has the potential to provide affordable and accessible molecular diagnostics for TB in low- and middle-income countries, when used in conjunction with an appropriate sample preparation technique. Although demonstrated for the detection of TB, FLIPP-NAAT is a platform technology for amplification of any nucleic acid sequence.

Microfluidic paper-based analytical devices (µPADs) have provided a breakthrough in portable and low-cost point-of-care diagnostics. Despite their significant scope, the complexity of fabrication and reliance on expensive and sophisticated tools, have limited their outreach and possibility of commercialization. Herein, we report for the first time, a facile method to fabricate µPADs using a commonly available laser printer which drastically reduces the cost and complexity of fabrication. Toner ink is used to pattern the µPADs by printing, without modifying any factory configuration of the laser printer. Hydrophobic barriers are created by heating the patterned paper which melts the toner ink, facilitating its wicking into the cross-section of the substrate. Further, we demonstrate the utilization of the fabricated device by performing two assays. The proposed technique provides a versatile platform for rapid prototyping of µPADs with significant prospect in both developed and resource constrained region.

In this paper we report a cheap, paper electronics based solid state gas sensor to detect NH3 gas selectively with a detection capability of better than 1 ppm. The sensor uses perovskite halide CH3NH3PbI3 (MAPI) as the active sensor material grown on a paper. This paper based sensor works at room temperature. The current through the paper sensor increases by one order on exposure to only 10 ppm NH3 gas. The calibrated sensitivity is ~55% for 1 ppm of NH3 gas in Nitrogen or Air. The current noise limited resolution estimated to be ~10 ppb. This work establishes perovskite halide as a new solid state gas sensing material that can reach sub ppm sensitivity using simple paper electronics. Use of paper and also solution method used to grow the active material makes the sensor cost effective and easy to manufacture. This type of disposable high sensitive paper sensor can be used for detection of NH3 as a marker in exhaled breathes for non-invasive diagnosis. The sensor formed on the paper, since it supports unheated operation, needs less than few nanowatt power for its operation.

The sensitivity of localized surface plasmon resonance (LSPR) of metal nanostructures to adsorbates lends itself to a powerful class of label-free biosensors. Optical properties of plasmonic nanostructures are dependent on the geometrical features and the local dielectric environment. The exponential decay of the sensitivity from the surface of the plasmonic nanotransducer calls for the careful consideration in its design with particular attention to the size of the recognition and analyte layers. In this study, we demonstrate that short peptides as biorecognition elements (BRE) compared to larger antibodies as target capture agents offer several advantages. Using a bioplasmonic paper device (BPD), we demonstrate the selective and sensitive detection of the cardiac biomarker troponin I (cTnI). The smaller sized peptide provides higher sensitivity and a lower detection limit using a BPD. Furthermore, the excellent shelf-life and thermal stability of peptide-based LSPR sensors, which precludes the need for special storage conditions, makes it ideal for use in resource-limited settings.

The process of papermaking requires substantial amounts of energy and wood consumption, which contributes to larger environmental costs. In order to optimize the production of papermaking to suit its many applications in material science and engineering, a quantitative understanding of bonding forces between the individual pulp fibers is of importance. Here we show the first approach to quantify the bonding energies contributed by the individual bonding mechanisms. We calculated the impact of the following mechanisms necessary for paper formation: mechanical interlocking, interdiffusion, capillary bridges, hydrogen bonding, Van der Waals forces and Coulomb forces on the bonding energy. Experimental results quantify the area in molecular contact necessary for bonding. Atomic force microscopy experiments derive the impact of mechanical interlocking. Capillary bridges also contribute to the bond. A model based on the crystal structure of cellulose leads to values for the chemical bonds. In contrast to general believe which favors hydrogen bonding Van der Waals bonds play the most important role according to our model. Comparison with experimentally derived bond energies support the presented model. This study characterizes bond formation between pulp fibers leading to insight that could be potentially used to optimize the papermaking process, while reducing energy and wood consumption.

Carbon fiber papers supported Ag catalysts (Ag/CFP) with different coverage of electro-active site are prepared by electrochemical deposition and used as binder free cathodes in primary aluminum-air (Al-air) battery. Scanning Electron Microscopy and X-ray Diffraction studies are carried out to characterize the as-prepared Ag/CFP air cathodes. Oxygen reduction reaction (ORR) activities on these air cathodes in alkaline solutions are systematic studied. A newly designed aluminum-air cell is used to further determine the cathodes performance under real operation condition and during the test, the Ag/CFP electrodes show outstanding catalytic activity for ORR in concentrated alkaline electrolyte, and no obvious activity degradation is observed after long-time discharge. The electrochemical test results display the dependence of coverage of the electro-active Ag on the catalytic performance of the air cathodes. The resulting primary Al-air battery made from the best-performing cathode shows an impressive discharge peak power density, outperforming that of using commercial nano-manganese catalyst air electrodes.

Paper, a man-made material that has been used for hundreds of years, is a network of natural cellulosic fibres. To a large extent, it is the strength of bonding between these individual fibres that controls the strength of paper. Using atomic force microscopy, we explore here the mechanical properties of individual fibre-fibre bonds on the nanometre scale. A single fibre-fibre bond is loaded with a calibrated cantilever statically and dynamically until the bond breaks. Besides the calculation of the total energy input, time dependent processes such as creep and relaxation are studied. Through the nanometre scale investigation of the formerly bonded area, we show that fibrils or fibril bundles play a crucial role in fibre-fibre bonding because they act as bridging elements. With this knowledge, new fabrication routes can be deduced to increase the strength of an ancient product that is in fact an overlooked high-tech material.

A pulsed laser engineering approach is developed to prepare novel functional graphene paper with graphitic nanospheres homogeneously decorated on the surface and the superior performance of engineered paper is revealed in matrix-free mass spectrometry (MS) detection and imaging. We demonstrate that the stability of graphene paper under intense irradiation can be dramatically increased through a designed laser engineering process by forming densely packed graphitic nanospheres on the paper surface. Moreover, the surface hydrophobicity is enhanced and electric conductivity is improved. The engineered graphene paper can image the invisible micro-patterns of trace amount molecules and increases the detection limit towards diverse molecules by over two orders of magnitude compared to the pristine graphene paper and commercial products in MS analysis.

The recent Zika virus (ZIKV) outbreak has prompted the need for field-ready diagnostics that are rapid, easy-to-use, handheld, and disposable while providing extreme sensitivity and specificity. To meet this demand, we developed a wax-printed paper microfluidic chip utilizing reverse transcription loop-mediated isothermal amplification (RT-LAMP). The developed simple and sensitive ZIKV assay was demonstrated using undiluted tap water, human urine, and diluted (10%) human blood plasma. Paper type, pore size, and channel dimension of various paper microfluidic chips were investigated and optimized to ensure proper filtration of direct-use biological samples (tap water, urine, and plasma) during capillary action-driven flow. Once ZIKV RNA has flowed and reached to a detection area of the paper microfluidic chip, it was excised for the addition of an RT-LAMP mixture with a pH indicator, then placed on a hot plate at 68 °C. Visible color changes from successful amplification were observed in 15 minutes and quantified by smartphone imaging. The limit of detection was as low as 1 copy/μL. The developed platform can also be used for identifying other flaviviruses, such as Chikungunya virus (CHIKV) and Dengue virus (DENV), and potentially other quickly transmitted virus pathogens, towards field-based diagnostics.

When a fire strikes libraries or archives, physical deterioration of the paper is so severe that its chemical properties are often regarded as less important. However, knowledge of the chemical changes of the papers upon nearly burning is necessary to design a subsequent conservation treatment. In the present study, we have examined a rag paper object, which partially survived a fire, and analysed its chemical properties by various methods. The polymeric state of cellulose, as well as its low-molar mass degradation products, were assessed. Comparison to an identical, unharmed duplicate provided a more profound understanding of the changes caused by the fire. Light scattering analysis revealed conformational changes of the cellulose molecule after high-temperature impact, and a chemical cross-linking was observed. In our study, we found the integrity of cellulose to depend on the temperature profile induced by the fire. The low thermal conductivity of cellulose protects the material even in close proximity to the burned edges.

Development of cost-effective and environmentally friendly manufacturing methods will enable important advances for the production of large-scale flexible electronics. Laser processing has shown to be a promising candidate that offers a fast and non-destructive way to produce highly conductive patterns on flexible substrates such as plastics. However, an emerging option with a lower environmental impact is instead the use of cellulose-based flexible substrates, such as paper. In this work we investigate the use of laser sintering of silver nanoparticle inks, which were inkjet-printed on three different types of paper. Patterns with a high conductivity could be manufactured where a special care was taken to prevent the substrates from damage by the intense laser light. We found that the best results was obtained for a photopaper, with a conductivity of 1.63 ∗ 107 S/m corresponding to nearly 26% of the bulk silver conductivity. In addition, we demonstrate laser sintering to fabricate a fully functional near field communication tag printed on a photopaper. Our results can have an important bearing for the development of cost-effective and environmentally friendly production methods for flexible electronics on a large scale.