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Paper-based microfluidic device was designed with wax-printing to combine potentiometric, fluorimetric and colorimetric detection zones. This newly developed trimodal paper chip has been used for on-site determination of ketamine hydrochloride (KET) as a date rape drug in beverages. The device employed polyaniline nano-dispersion as conducting polymer in ion sensing paper electrodes designed to fit USB plug connector. Carbon dots-gold nanoparticles and cobalt thiocyanate were used in fluorescence and color detection zones, respectively. Cellular phone's camera facilitated the on-site fluorimetric and color detection. The implemented trimodal detection system exhibited specificity for KET detection in the presence of several other beverage interferences i.e., biogenic amines. This innovative sensor brings together analytical figures of merit for effective KET detection in single aliquot of spiked beverages. The proposed paper-based chip also fulfils WHO criteria for point-of-care devices posing the proposed trimodal paper device as an active part for rapid, on-site drug diagnostics and to be applied further for other similar drugs.

Paper-based biosensor is one of the most commonly used platforms for point-of-care testing (POCT). Among these platforms, microfluidic paper-based analytical devices (μPADs) have the most versatile designs due to the different hydrophobic barrier patterns and layers of the devices. In addition, μPADs can also be used in combination with other biosensor platforms to improve the performance of the device. Simple and convenient methods for fabricating low-cost and design-adjustable hydrophobic barriers on paper are one of the most challenging aspects for creating μPADs. This work demonstrated a simple technique for using the common polylactic acid (PLA) filament and wax filament to create hydrophobic barriers on paper for μPADs using a commercialized 3D printer. As a proof of concept, the papers with 3D printed PLA barrier were used in combination with a fluidic chip in a prototype biosensor, in which the barrier paper housed four cell-free reactions and the fluidic chip achieved sample delivery to the reactions in the device. Our designed prototype was capable of discriminating dengue virus serotypes based on small nucleotide sequence differences. The proposed combination of 3D-printed barrier paper and fluidic chip provides a versatile platform for rapid prototyping of POCT with possible compatibility with various detection systems.

In this work, a facile kinetic matching approach for total polyphenol content (TPC) measurement was developed based on the adoption of microfluidic paper-based analytical devices with symmetric channel distribution. A set of Folin-Ciocalteu reactions performed on the same paper chip were activated all at the same time through synchronized filling of sodium carbonate solution among individual channels. Gallic acid was found valid as a standard compound for kinetic matching measurement of tea samples. TPC of tea infusions was successfully measured within ten minutes without any complexed time control procedure needed. Under the optimized conditions, the new developed method showed good linearity in the TPC range of 10–100 mg/L (r > 0.9955) and the inter-chip precision was 5.6% (n = 11). The results measured with the new developed approach were in good agreement with those with the conventional FC assay.

Protein corona coated onto the hydrophilic cellulose fiber turns into hydrophobic upon UV irradiation without hindering the porosity of the paper while simultaneously reducing nonspecific adsorption. Taking advantage of the biofouling-resistant, hydrophobic, and fluid transport through property, we demonstrated hanging drop three-dimensional (3D) spheroid culture and in-site analysis, including drug testing, time-dependent detection of secreted protein, and fluorescence staining without disturbing the spheroids. This single hanging drop system can also be extended to a networked hanging drop chip to mimic in vivo microphysiology by combining with wax-patterned microfluidic channels, where well-to-well interaction can be accurately controlled in a passive manner. As a proof of concept, the effects of a concentration gradient of nutrient and variable dosage of anticancer drugs were studied in the 3D spheroids cultured on paper. The experimental results suggested that a complex network device could be fabricated on a large scale on demand at a minimal cost for 3D spheroid culture. Our method demonstrates a future possibility for paper as a low cost, high-throughput 3D spheroid-based "body-on-a-chip" platform material.

Aiming to overcome the obstacles of power supply requirement and chip usefulness in practice, a low-cost and convenient portable electrochemical sensing device is introduced for the first time, featuring bipolar electrode system, LED read-out, laminated paper-based devices, and low-voltage button cells. The electric circuits of this practical device are constructed on laminating films with copper and conductive carbon tapes, and the reservoirs facilitating chemical reactions are made with chromatography paper. The device is sensitive to electrochemical responses, validated by the demonstrative hydrogen peroxide and enzyme-assisted glucose detection. The business-card-size chip achieves sensitive analyte detection by naked eyes as well as further image processing in both laboratory samples and human serum samples testing, featuring detection limit as low as 1.79 μM and a dynamic range from 10 μM to 10 mM. This new practical design of point-of-care sensing chip entails the properties of facile fabrication, simple usage, high robustness, low power consumption, and accurate sensing showing the attainability of fabricating a useful and portable analytical device.

Although significant technological advancements have been made in the development of analytical biosensor chips for detecting bacterial strains (E. coli, S. Mutans and B. Subtilis), critical requirements i.e. limit of detection (LOD), fast time of response, ultra-sensitivity with high reproducibility and good shelf-life with robust sensing capability have yet to be met within a single sensor chip. In order to achieve these criteria, we present an electrically-receptive thermally-responsive (ER-TR) sensor chip comprised of simple filter paper used as substrate coated with composite of poly(N-isopropylacrylamide) polymer (PNIPAm) - graphene nanoplatelet (GR) followed by evaporation of Au electrodes for capturing both Gram-positive (S. mutans and B. subtilis) and Gram-negative (E. coli) bacterial cells in real-time. Autoclave water, tap water, lake water and milk samples were tested with ER-TR chip with and without bacterial strains at varying concentration range 101-105 cells/mL. The sensor was integrated with in-house built printed circuit board (PCB) to transmit/receive electrical signals. The interaction of E. coli, S. mutans and B. subtilis cells with fibers of PNIPAm-GR resulted in a change of electrical resistance and the readout was monitored wirelessly in real-time using MATLAB algorithm. Finally, prepared ER-TR chip exhibited the reproducibility of 85-97% with shelf-life of up to four weeks after testing with lake water sample.

Intelligent packaging is an emerging technology, aiming to improve the standard communication function of packaging. Radio frequency identification (RFID) assisted smart packaging is of high interest, but the uptake is limited as the market needs cost-efficient and sustainable applications. The integration of screen printed antennas and RFID chips as smart labels in reusable cardboard packaging could offer a solution. Although paper is an interesting and recyclable material, printing on this substrate is challenging as the ink conductivity is highly influenced by the paper properties. In this study, the best paper/functional silver ink combinations were first selected out of 76 paper substrates based on the paper surface roughness, air permeance, sheet resistance and SEM characterization. Next, a flexible high frequency RFID chip (13.56 MHz) was connected on top of screen printed antennas with a conductive adhesive. Functional RFID labels were integrated in cardboard packaging and its potential application as reusable smart box for third party logistics was tested. In parallel, a web-based software application mimicking its functional abilities in the logistic cycle was developed. This multidisciplinary approach to developing an easy-scalable screen printed antenna and RFID-assisted smart packaging application is a good example for future implementation of hybrid electronics in sustainable smart packaging. ispartof: MATERIALS vol:14 issue:19 ispartof: location:Switzerland status: published

The present study was aimed to develop an ultrasensitive technique for electroanalysis of ketamine; a date rape drug. It involved the fabrication of nano-hybrid based electrochemical micro fluidic paper-based analytical device (EμPADs) for electrochemical sensing of ketamine. A paper chip was developed using zeolites nanoflakes and graphene-oxide nanocrystals (Zeo–GO). EμPAD offers many advantages such as facile approach, economical and potential for commercialization. Nanocrystal modified EμPAD showed wide linear range 0.001–5 nM/mL and a very low detection limit of 0.001 nM/mL. The developed sensor was tested in real time samples like alcoholic and non-alcoholic drinks and found good correlation (99%). The hyphenation of EμPAD integrated with nanocrystalline Zeo–GO for detection of ketamine has immense prospective for field-testing platforms. An extensive development could be made for industrial translation of this fabricated device.

Mycotoxin contamination causes over $5 billion of economic loss per year in the North American food and feed industry. A rapid, low-cost, portable, and reliable method for on-site detection of deoxynivalenol (DON), a representative mycotoxin predominantly occurring in grains, would be helpful to control mycotoxin contamination. In this study, a paper-based microfluidic chip capable of measuring DON (DON-Chip) in food, feed, and feed ingredients was developed. The DON-Chip incorporated a colorimetric competitive immunoassay into a paper microfluidic device and used gold nanoparticles as a signal indicator. Furthermore, a novel ratiometric analysis method was proposed to improve detection resolvability. Detection of DON in the aqueous extracts from solid food, feed, or feed ingredients was successfully validated with a detection range of 0.01-20 ppm (using dilution factors from 10 to 104). Compared with conventional methods, the DON-Chip method could greatly reduce the cost and time of mycotoxin detection in the food and feed industry.

Washing is a standard step for enzyme-linked immunosorbent assays (ELISA) performed on a paper-based chip, in which nonspecific-binding antibodies and antigens should be removed completely from the paper surface. In this study, a novel three-dimensional (3D) washing strategy using a heating ring-oven was carried out on a paper-based chip. Compared with a plane washing mode by a ring-oven, this 3D washing strategy obtained a lower background, as gravity played an important role in the washing step. The paper-based chip was placed on a 3D plastic holder and the waste area was connected to a heating ring. Use of a heating waste area meant that the nonspecific-binding protein was continuously carried to the waste area through gravity and capillary action. The angle between the plastic holder and the ring plane was carefully selected. The effect of washing on different parts of the detection area was investigated by upconversion fluorescence and chemiluminescence (CL). This novel 3D washing strategy was performed for carcinoembryonic antigen detection through CL and a lower detection limit of 2 pg ml-1 was obtained. This approach provides an effective washing strategy to remove nonspecific-binding antibody from a paper-based immunodevice.

Paper-based fluorescence resonance energy transfer assay (FRET) is gaining great interest in detecting macro-biological molecule. It is difficult to achieve conveniently and fast detection for macro-biological molecule. Herein, a graphene oxide (GO)-based paper chip (glass fiber) integrated with fluorescence labeled single-stranded DNA (ssDNA) for fast, inexpensive and direct detection of biological macromolecules (proteins and nucleic acids) has been developed. In this paper, we employed the Cy3/FAM-labeled ssDNA as the reporter and the GO as quencher and the original glass fiber paper as data acquisition substrates. The chip which was designed and fabricated by a cutting machine is a miniature biosensor that monitors fluorescence recovery from resonance energy transfer. The hybridization assays and fluorescence detection were all simplified, and the surface of the chip did not require immobilization or washing. A Nikon Eclipse was employed as excited resource and a commercial digital camera was employed for capturing digital images. This paper-based microfluidics chip has been applied in the detection of proteins and nucleic acids. The biosensing capability meets many potential requirements for disease diagnosis and biological analysis.

Paper diagnostics have successfully been employed to detect the presence of antigens or small molecules in clinical samples through immunoassays; however, the detection of many disease targets relies on the much higher sensitivity and specificity achieved via nucleic acid amplification tests (NAAT). The steps involved in NAAT have recently begun to be explored in paper matrices, and our group, among others, has reported on paper-based extraction, amplification, and detection of DNA and RNA targets. Here, we integrate these paper-based NAAT steps into a single paperfluidic chip in a modular, foldable system that allows for fully integrated fluidic handling from sample to result. We showcase the functionality of the chip by combining nucleic acid isolation, isothermal amplification, and lateral flow detection of human papillomavirus (HPV) 16 DNA directly from crude cervical specimens in less than 1 hour for rapid, early detection of cervical cancer. The chip is made entirely of paper and adhesive sheets, making it low-cost, portable, and disposable, and offering the potential for a point-of-care molecular diagnostic platform even in remote and resource-limited settings.

Foodborne pathogen is the primary cause of foodborne disease outbreak. Given its great damage, a sensitive, simple and rapid detection method is demanded. Herein, we described a self-priming polydimethylsiloxane (PDMS)/paper hybrid microfluidic chip, termed SPH chip, with mixed-dye-loaded loop-mediated isothermal amplification (LAMP) for multiplex foodborne pathogens detection. Staphylococcus aureus (SA) and Vibrio parahaemolyticus (VP) were chosen to verify the novel method. Compared to other similar detection devices, the SPH chip required easier fabrication process, less operation steps and lower cost. Additionally, the reaction result, especially for the weak-positive reaction, could be judged more accurately and conveniently due to the use of mixed-dye. Without pre-enrichment of bacteria in the food contaminated sample, the limit of detection (LOD) reached down to 1000 CFU mL −1 with high specific. Additionally, for fully exploiting the potential of SPH chip, a conceptual eight-channel detection chip was also developed. Overall, the reliable and excellent result demonstrated that the novel method had great potential to be applied in the wider range of pathogens detection or disease diagnose, especially in some resource-limited area.

Controlled integration of features that enhance the analytical performance of a sensor chip is a challenging task in the development of paper sensors. A critical issue in the fabrication of low-cost biosensor chips is the activation of the device surface in a reliable and controllable manner compatible with large-scale production. Here, we report stable, well-adherent, and repeatable site-selective deposition of bioreactive amine functionalities and biorepellant polyethylene glycol-like (PEG) functionalities on paper sensors by aerosol-assisted, atmospheric-pressure, plasma-enhanced chemical vapor deposition. This approach requires only 20 s of deposition time, compared to previous reports on cellulose functionalization, which takes hours. A detailed analysis of the near-edge X-ray absorption fine structure (NEXAFS) and its sensitivity to the local electronic structure of the carbon and nitrogen functionalities. σ*, π*, and Rydberg transitions in C and N K-edges are presented. Application of the plasma-processed paper sensors in DNA detection is also demonstrated.

We describe herein the fabrication of an electrochemical microfluidic paper based device (EμPAD) for the detection of diazepam, a sedative, anxiety-relieving and muscle-relaxing drug. To achieve it, silica coated gold nanorods (Si@GNRs) were synthesized and drop casted on an electrochemical microfluidic paper based device (EμPAD) for the detection of diazepam. The synthesized composites were characterized by recording its images in scanning electron microscope (SEM) and transmission electron microscope (TEM). The experimental results confirmed that Si@GNRs had good electrocatalytic activity towards diazepam. The modified paper based electrode showed a stable electrochemical response for diazepam in the concentration range of 3.5 nM to 3.5 mM. EμPAD offers many advantageous features such as facile approach, economical and have potential for commercialization. Si@GNRs modified EμPAD was also employed for determination of diazepam in spiked human urine samples. Reported facile lab paper approach integrated with Si@GNRs could be well applied for the determination of serum metabolites.

Cortisol has been identified as a biomarker in saliva to monitor psychological stress. In this work, we report a label-free paper-based electrical biosensor chip to quantify salivary cortisol at a point-of-care (POC) level. A high specificity of the sensor chip to detect cortisol with a detection limit of 3 pg/mL was achieved by conjugating anticortisol antibody (anti-CAB) on top of gold (Au) microelectrodes using 3,3′-dithiodipropionic acid di(N-hydroxysuccinimide ester (DTSP) as a self-assembled monolayer (SAM) agent. The electrode design utilized poly(styrene)-block-poly(acrylic acid) (PS67-b-PAA27) polymer and graphene nanoplatelets (GP) suspension coated on filter paper to increase the sensitivity of the immune response. A biosensor chip was then integrated with a lab-built low-cost miniaturized printed circuit board (PCB) to provide an electrical connection and to wirelessly transmit/receive electrical signals using MATLAB. This fully integrated proposed hand-held device successfully exhibited a wid...

We report a pseudo-paper microfluidic chip based on patterned photonic nitrocellulose. The photonic nitrocellulose is fabricated using self-assembled monodisperse SiO2 nanoparticles as template. The SiO2 nanoparticles form a photonic crystal having a close-packed hexagonal structure in the microchannels, so the resulting nitrocellulose has a complementary inverse-opal structure. After lamination, a hollow channel is obtained that is partially filled with the photonic nitrocellulose. Owing to the highly ordered photonic structure of the pseudo-paper chip, the flow profile of aqueous solution wicking through the channel is more uniform than conventional paper microfluidic chip. It is also found that the wicking rate of aqueous solution can be easily manipulated by changing the diameter of the self-assembled monodisperse SiO2 nanoparticles, which determines the pore size of the photonic nitrocellulose. The fluorescent enhancement property of the photonic nitrocellulose is used to increase the fluorescent intensity for multiplex detection of two cancer biomarkers. Label-free detection of human immunoglobin G based on the structure color of the photonic nitrocellulose is also demonstrated.

There is increasing interest in the development of cost-effective, practical, portable, and disposable diagnostic devices suited to on-site detection and analysis applications, which hold great promise for global health care,[1,2] environmental monitoring,[3] water and food safety,[4] as well as medical and threat reductions.[5] Lab-on-a-chip (LOC) devices, which scale single or multiple lab processes down to chip format (millimeters to a few square centimeters in size), facilitated by micro- and nanoscale technologies have attracted significant attention because of their small sample volume requirements and excellent portability.[6] Various LOC devices have been designed and fabricated in the past two decades, most of which involve a lithography-based patterning process on a solid or elastomeric substrate, such as glass or plastic, for a variety of functionalities that include sample preparation,[7] microfluidic mixing,[8] biochemical reactions,[9] and analysis.[10]

Reliable, autonomous, internally self-powered microfluidic pumps are in critical demand for rapid point-of-care (POC) devices, integrated molecular-diagnostic platforms, and drug delivery systems. Here we report on a Self-powered Imbibing Microfluidic Pump by Liquid Encapsulation (SIMPLE), which is disposable, autonomous, easy to use and fabricate, robust, and cost efficient, as a solution for self-powered microfluidic POC devices. The imbibition pump introduces the working liquid which is sucked into a porous material (paper) upon activation. The suction of the working liquid creates a reduced pressure in the analytical channel and induces the sequential sample flow into the microfluidic circuits. It requires no external power or control and can be simply activated by a fingertip press. The flow rate can be programmed by defining the shape of utilized porous material: by using three different paper shapes with circular section angles 20°, 40° and 60°, three different volume flow rates of 0.07 μL s(-1), 0.12 μL s(-1) and 0.17 μL s(-1) are demonstrated at 200 μm × 600 μm channel cross-section. We established the SIMPLE pumping of 17 μL of sample; however, the sample volume can be increased to several hundreds of μL. To demonstrate the design, fabrication, and characterization of SIMPLE, we used a simple, robust and cheap foil-laminating fabrication technique. The SIMPLE can be integrated into hydrophilic or hydrophobic materials-based microfluidic POC devices. Since it is also applicable to large-scale manufacturing processes, we anticipate that a new chapter of a cost effective, disposable, autonomous POC diagnostic chip is addressed with this technical innovation.

This work presents a paper spray mass spectrometry-based method, to analyze microdroplets produced in a gravity-driven microchip. Droplets at ambient pressure were passively transferred from the chip to a paper substrate by the capillary wicking effect. Paper spray ionization was then performed for mass spectrometry (MS) analysis of droplet contents. The qualitative and quantitative analytical performances of this technique for single droplets were demonstrated. This manually controlled interface is straightforward, low-cost and simple to implement. Moreover, paper spray ionization MS holds promise in the direct analysis of real biological/chemical microreaction samples because of its tolerance with complex matrices. As a proof-of-concept example, the droplet-based acetylcholine hydrolysis was carried out to demonstrate the validation of our method for the direct analysis of micro-chemical/biological reactions. We also introduced a flow injection analysis (FIA) system combined with our droplet system to generate a concentration gradient. As a result, the microreaction can be performed at different concentrations and kinetic information can be obtained in one sample injection. In conclusion, the combination of a microdroplet chip with paper spray ionization and the introduction of the FIA system and make our droplet-MS scheme a useful platform for monitoring and analyzing organic-phase chemical/biological reactions.

We present a novel, low-resource fabrication and assembly method for creating disposable amperometric detectors in hybrid paper-polymer devices. Currently, mere paper-based microfluidics is far from being able to achieve the same level of process control and integration as state-of-the-art microfluidic devices made of polymers. To overcome this limitation, in this work both substrate types are synergistically combined through a hybrid, multi-component/multi-material system assembly. Using established inkjet wax printing, we transform the paper into a profoundly hydrophobic substrate in order to create carbon electrodes which are simply patterned from carbon inks via custom made adhesive stencils. By virtue of the compressibility of the paper substrate, the resulting electrode-on-paper hybrids can be directly embedded in conventional, 3D polymeric devices by bonding through an adhesive layer. This manufacturing scheme can be easily recreated with readily available off-the-shelf equipment, and is extremely cost-efficient and rapid with turn-around times of only a few hours.

Paper-based microfluidics has recently received considerable interest due to their ease and low cost, making them extremely attractive as point-of-care diagnostic devices. The incorporation of basic fluid actuation and manipulation schemes on paper substrates, however, afford the possibility to extend the functionality of this simple technology to a much wider range of typical lab-on-a-chip operations, given its considerable advantages in terms of cost, size and integrability over conventional microfluidic substrates. We present a convective actuation mechanism in a simple paper-based microfluidic device using surface acoustic waves to drive mixing. Employing a Y-channel structure patterned onto paper, the mixing induced by the 30 MHz acoustic waves is shown to be consistent and rapid, overcoming several limitations associated with its capillary-driven passive mixing counterpart wherein irreproducibilities and nonuniformities are often encountered in the mixing along the channel--capillary-driven passive mixing offers only poor control, is strongly dependent on the paper's texture and fibre alignment, and permits backflow, all due to the scale of the fibres being significant in comparison to the length scales of the features in a microfluidic system. Using a novel hue-based colourimetric technique, the mixing speed and efficiency is compared between the two methods, and used to assess the effects of changing the input power, channel tortuousity and fibre/flow alignment for the acoustically-driven mixing. The hue-based technique offers several advantages over grayscale pixel intensity analysis techniques in facilitating quantification without limitations on the colour contrast of the samples, and can be used, for example, for quantification in on-chip immunochromatographic assays.

We report a simple, low-cost and detachable microfluidic chip incorporating easily accessible paper, glass slides or other polymer films as the chip materials along with adhesive wax as the recycling bonding material. We use a laser to cut through the paper or film to form patterns and then sandwich the paper and film between glass sheets or polymer membranes. The hot-melt adhesive wax can realize bridge bonding between various materials, for example, paper, polymethylmethacrylate (PMMA) film, glass sheets, or metal plate. The bonding process is reversible and the wax is reusable through a melting and cooling process. With this process, a three-dimensional (3D) microfluidic chip is achievable by vacuating and venting the chip in a hot-water bath. To study the biocompatibility and applicability of the wax-based microfluidic chip, we tested the PCR compatibility with the chip materials first. Then we applied the wax-paper based microfluidic chip to HeLa cell electroporation (EP). Subsequently, a prototype of a 5-layer 3D chip was fabricated by multilayer wax bonding. To check the sealing ability and the durability of the chip, green fluorescence protein (GFP) recombinant Escherichia coli (E. coli) bacteria were cultured, with which the chemotaxis of E. coli was studied in order to determine the influence of antibiotic ciprofloxacin concentration on the E. coli migration.

This paper presents a hybrid wearable bio-sensing system, which combines traditional small-area low-power and high-performance System-on-Chip (SoC), flexible paper substrate and cost-effective Printed Electronics. Differential bio-signals are measured, digitized, stored and transmitted by the SoC. The total area of the chip is 1.5 × 3.0 mm(2). This enables the miniaturization of the wearable system. The electrodes and interconnects are inkjet printed on paper substrate and the performance is verified in in-vivo tests. The quality of electrocardiogram signal sensed by printed electrodes is comparable with commercial electrodes, with noise level slightly increased. The paper-based inkjet printed system is flexible, light and thin, which makes the final system comfortable for end-users. The hybrid bio-sensing system offers a potential solution to the next generation wearable healthcare technology.