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Oxazolidine is a new category of stimuli-chromic organic compounds with unique characteristics in response to polarity, pH changes, water, light, and metal ions that were well-known as solvatochromism, acidochromism, hydrochromism, photochromism, and ionochromism, respectively. Therefore, oxazolidine derivatives have been developed for their potential applications in chemosensors, anticounterfeiting, and rewritable hydrochromic papers. In this study, various oxazolidine derivatives containing hydroxyl and naphthalene substituted groups were synthesized by using two different indolenine compounds. The synthesized oxazolidine derivatives were used for investigation of solvatochromism in different solvents, and also acidochromism in various pHs by using UV–Vis and fluorescence spectroscopies. In addition, the oxazolidine derivatives were coated on cellulosic papers using a layer-by-layer strategy to develop rewritable acidochromic papers for printing of security tags on cellulosic papers by using acidic and alkaline solutions as water-based inks. Therefore, the developed rewritable acidochromic papers could be used as security papers.

The increasing prevalence of antibiotic resistance threatens to make currently treatable bacterial diseases deadly again. As drug resistance rises, antibiotic susceptibility testing needs to adapt to allow for widespread, individualized testing. Paper-based diagnostics offer low-cost, disposable alternatives to traditional time consuming and costly in-house methods. Here, we describe a paper-based microfluidic device, called the Bac-PAC, capable of categorizing the antibiotic susceptibly of individual strains of Carbapenem-resistant Enterobacterales. Each chip provides a colored readout with actionable susceptibility classification of three antibiotics, thus maximizing the chances of identifying a viable therapy. We verified the technology on thirty bacterial strains with two dyes using six clinically relevant antibiotics. We demonstrated that the dried tests are stable for one month and can be incubated in a rechargeable coffee mug that reduces the need for external infrastructure.

Hydrogen peroxide (H2O2) has attracted considerable attention for use as a disinfectant ingredient for various applications over the decades. The use of H2O2 within the safety regulations can avoid its toxicity to human health and the environment. In this study, a paper-based sensor containing green-synthesized silver nanoparticles (P-AgNPs) was developed for use in a smartphone in the determination of the H2O2 concentration. In the synthesis process, an extract of spent coffee grounds was used as a bioreducing agent. The effects of reaction time and silver nitrate (AgNO3) concentration on the green synthesis of silver nanoparticles (AgNPs) were investigated. The optimum conditions for the preparation of P-AgNPs were determined to be 100 mM AgNO3 (P-AgNPs-100) and 15 h synthesis time. The P-AgNPs-100 sensor exhibited high sensitivity with a detection limit of 1.26 mM H2O2, which might be suitable for the detection of H2O2-based household and beverage sanitizers. The H2O2 detection capability of P-AgNPs-100 was comparable to that of a commercial strip sensor. Furthermore, P-AgNPs-100 had a detection efficiency of more than 95% after long-term storage for 100 days.

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.

Infectious diseases are among the leading causes of mortality worldwide. A new coronavirus named severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) was identified in Wuhan, China in 2019, and the World Health Organization (WHO) declared its outbreak, coronavirus disease 2019 (COVID-19), as a global pandemic in 2020. COVID-19 can spread quickly from person to person. One of the most challenging issues is to identify the infected individuals and prevent potential spread of SARS-CoV-2. Recently, anti-SARS-CoV-2 immunoglobulin M (IgM) and immunoglobulin G (IgG) antibody tests using immunochromatographic methods have been used as a complement to current detection methods and have provided information of the approximate course of COVID-19 infection. However, blood sampling causes pain and poses risks of infection at the needle puncture site. In this study, a novel patch sensor integrating porous microneedles and an immunochromatographic assay (PMNIA) was developed for the rapid detection of anti-SARS-CoV-2 IgM/IgG in dermal interstitial fluid (ISF), which is a rich source of protein biomarkers, such as antibodies. Biodegradable porous microneedles (MNs) made of polylactic acid were fabricated to extract ISF from human skin by capillary effect. The extracted ISF was vertically transported and flowed into the affixed immunoassay biosensor, where specific antibodies could be detected colorimetrically on-site. Anti-SARS-CoV-2 IgM/IgG antibodies were simultaneously detected within 3 min in vitro. Moreover, the limit of detection of anti-SARS-CoV-2 IgM and IgG concentrations was as low as 3 and 7 ng/mL, respectively. The developed device integrating porous MNs and immunochromatographic biosensors is expected to enable minimally invasive, simple, and rapid anti-SARS-CoV-2 IgM/IgG antibody testing. Furthermore, the compact size of the MN and biosensor-integrated device is advantageous for its widespread use. The proposed device has great potential for rapid screening of various infectious diseases in addition to COVID-19 as an effective complementary method with other diagnostic tests.

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.

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.

There has been growing interest in the development of paper-based biosensors because their simplicity and low cost are attractive for point-of-care diagnosis, especially in low-resource areas. However, only a limited range of paper materials – primarily chromatography papers – have been incorporated into diagnostics thus far. Here, we investigate the performance of different types of paper in order to develop an aptamer- and MoS2 nanosheet-based sensor relying on fluorescence resonance energy transfer (FRET) to signal the presence of a target protein. An aptamer which binds to a malarial biomarker, Plasmodium lactate dehydrogenase (pLDH), is chosen for this study, as point-of-care diagnostics would be especially advantageous in low-resource areas, such as those where malaria is prevalent. We observe that of all papers tested, a measurable and specific fluorescence recovery can only be produced on the sensor created with printer paper, while no significant fluorescence recovery is generated on sensors made from other types of paper, including chromatography, lens, and filter papers. Therefore, our findings demonstrate the importance of careful material selection for the development of a paper-based diagnostic test, and suggest that commercially-available products such as printer paper may serve as viable materials to develop cost-effective and simple diagnostics.

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.

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.

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.

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.

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.

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.

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.

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.

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.