Fabrication Of Paper-based Microfluidic Devices Research Articles

Saturation Equation: An Analytical Expression for Partial Saturation during Wicking Flow in Paper Microfluidic Channels.

The design and fabrication of paper-based microfluidic devices is critically dependent on modeling fluid flow through porous paper membranes. A commonly observed phenomenon is partial saturation, i.e., regions of the paper membrane not being filled completely due to pores of different sizes. The most comprehensive model to date of partial saturation during wicking flow in paper is the Richards equation. However, the solution to the Richards equation requires numerical solvers like COMSOL, which makes it largely inaccessible to the paper microfluidics and lateral flow assay community. There is therefore a need for a simple and appropriate model of partial saturation in paper membranes, easily usable by the wider research community. In the current work, we present an approach to model paper membranes as a bundle of parallel capillaries whose radii follow a two-parameter log-normal distribution. Application of the Washburn equation to the bundle provides a distribution of fluid fronts, which can be used to calculate saturation. Using this approach, we developed the "saturation equation"─an explicit analytical expression to calculate saturation as a function of space and time in 1D wicking flow. Experimentally obtained data for spatiotemporal saturation for four different paper materials were fit to this analytical model to obtain parameters for each material. Results obtained from this analytical model match well with both experimental data and numerical results obtained from the Richards equation. The availability of an explicit analytical expression for partial saturation will enable incorporation of the critical phenomenon of partial saturation in the design of paper microfluidic devices.

Fabrication of paper-based microfluidic devices using a 3D printer and a commercially-available wax filament

In this work, we developed an alternative manufacturing paper-based microfluidics method through 3D printing and wax filament. Microfluidic paper-based analytical devices (µPADs) are low-cost and easy-to-manufacture tools used for various chemical and biological analyses and studies. Paper-based microfluidics with wax has been limited as the manufacturers have discontinued most wax printing equipment. We aim to develop a low-cost and accessible manufacturing method that can replace conventional wax-on paper-based microfluidic manufacturing methods. Using highly available commercial 3D printing technology and wax filament, we could create hydrophobic wax barriers on the surface of different paper types. The properties and limits of this manufacturing method were characterized. Moreover, using this paper-based microfluidic manufacturing method, we were able to measure dopamine electrochemically using µPAD as a passive flow-based method in concentrations as low as 1 nM using injections as small as 15 µL.

Low-cost and Rapid Fabrication of Paper-based Microfluidic Devices with Stencil Film

This study proposed a method for the rapid fabrication of paper-based microfluidic devices with a stencil film, which has wide application potential in analytical chemistry. Compared with the conventional approaches, the wax transfer and wax reflow was conducted simultaneously, resulting in a shorter fabrication duration (about 15 s per device) and ultra-low fabrication cost. For the demonstration of the proposed method, a quantitative analysis of amino acid content in tea was also conducted.

A novel method for fabrication of paper-based microfluidic devices using BSA-ink

This paper describes the fabrication of paper-based microfluidic devices using a novel, inexpensive ink composed of bovine serum albumin (BSA), utilizing BSA's thermal denaturation and aggregation to create a hydrophobic barrier on Whatman® Grade 4 filter paper. A 20% aqueous solution of BSA was inked onto the paper using a pen plotter at moderate speed (5 cm/s) with desired shape and size followed by heating at 80 °C to denature the BSA leading to hydrophobic barriers formation, whereas below 80 °C the barrier layer is prone to collapse. The minimum line gap and line width of ~1 mm and ~1.3 mm were achieved. Finally, a proof-of-concept glucose sensing was shown while addressing the issue of the coffee ring effect using the biopolymer NanoCheck-ATH® from ChitoLytic Inc. The glucose concentration limit of detection (LOD) as low as 0.2 mg/mL was estimated. The developed technique offers ease of fabrication, high reproducibility, cost-effectiveness, and is environmentally friendly.

Fabrication of Paper-based Microfluidic Devices Using a Laser Beam Scanning Technique.

This paper describes a novel method for fabricating paper-based microfluidic devices using a laser beam scanning technique. Cellulose chromatography papers were treated with octadecyltrichlorosilane (OTS) to make them entirely hydrophobic. A photoacid generator (CPI-410S) was soaked into the paper, and irradiated with a 405-nm laser beam to induce acid generating reactions. Since the silyl ether bond between cellulose and OTS was cleaved by the hydrolysis reaction, the photo-irradiated area changed to hydrophilic. By scanning the laser beam using a Galvo mirror system, arbitrary shaped hydrophilic patterns were successfully created on the paper in 50 μm resolution. To the best of our knowledge, this is the first report on the fabrication of hydrophilic channels on the OTS-treated paper using photo-induced acid generation processes coupled with the laser beam scanning technique. Quantification of nitrite was demonstrated with the paper device made by this method.

Roll-to-roll wax transfer for rapid and batch fabrication of paper-based microfluidics

This study proposed a novel method for the rapid fabrication of paper-based microfluidic devices using a roll-to-roll wax transfer method. In this approach, a custom-made device was designed and fabricated for the direct roll-to-roll wax transfer from commercially available wax ribbon to the surface of paper substrate. After wax transfer, a thermal reflow process was conducted to enable the melt wax penetration through the whole thickness of the hydrophilic paper substrate to form hydrophobic wax barriers. Compared with the conventional approaches for paper-based microfluidics (wax printing, photolithography, and inkjet printing), the proposed fabrication technique for paper-based microfluidic devices is suitable for the batch fabrication of paper-based microfluidic chips at high production speed. Additional advantages including simple fabrication process, low material and fabrication cost, low-energy consumption, and without the requirement of cleanroom environment or facilities. The paper-based microfluidics fabricated with the proposed roll-to-roll wax transfer method is widely adaptable for microfluidic applications in biological and chemical fields.

Parametric analysis of wax printing technique for fabricating microfluidic paper-based analytic devices (µPAD) for milk adulteration analysis

Accurate prediction of hydrophobic–hydrophilic channel barriers is essential in the fabrication of paper-based microfluidic devices. This research presents a detailed parametric analysis of wax printing technique for fabricating µPADs. Utilizing commonly used Grade 1 filter paper, experimental results show that the wax spreading in the paper porous structure depends on the initially deposited wax line thickness, a threshold melting temperature and melting time. Initial width of the printed line has a linear relationship with the final width of the barrier; however, a less pronounced effect of temperature was observed. Based on the spreading behavior of the molten wax at different parameters, a generalized regression model has been developed and validated experimentally. The developed model accurately predicts wax spreading in Whatman filter paper: a non-uniform distribution of pores and fibers. Finally, tests were carried out for calorimetric detection of commonly used adulterants present in milk samples.

Laser-induced selective wax reflow for paper-based microfluidics.

This study proposes a novel method for the fabrication of paper-based microfluidic devices using laser-induced selective thermal reflow for wax penetration. A layer of wax was evenly deposited on the front side of a filter paper; then a low-cost diode laser was used to scan the designed area from the back side of the filter paper. At the laser irradiated spot, the wax was heated, melted down and penetrated through the whole thickness of the filter paper, and formed hydrophobic barriers on the hydrophilic cellulose fibers. The patterned hydrophobic wax barriers on the filter paper defined the flow path of the fluid for the paper-based microfluidic device. Compared with conventional two-step (deposit and reflow) approaches for paper-based microfluidics using wax barriers, e.g. wax printing, stamping or photolithography, the proposed fabrication protocol achieved wax patterning and reflow simultaneously, conducted during the laser scan process, and without the requirement for any sophisticated instruments or a cleanroom environment. A series of tests were also conducted for the characterization of the proposed paper-based microfluidic device fabrication technique. The fabrication technique used in this approach could have broad application potential in point-of-care diagnosis and testing, especially for applications in the developing world.

Direct spraying method for fabrication of paper-based microfluidic devices

Direct spraying of hydrophobic materials is an affordable, easy-to-use and equipment-free method for fabrication of flexible microsensors, albeit not yet widely adopted. To explore its application potential, in this paper, we propose and demonstrate two novel hybrid methods to fabricate paper-based components. Firstly, through combing direct spraying with Parafilm embedding, a leak-free paper-based sample preconcentrator for fluorescence sensing was fabricated. The leak-free device worked on the principle of ion concentration polarization (ICP) effect, and achieved enhancement of fluorescent tracer by 220 folds on a paper substrate. Secondly, by using the sprayed hydrophobic patterns, paper-based microsized supercapacitors (mSCs) were fabricated. Vacuum filtration was used to deposit multi-wall carbon nanotubes (MWCNT)-dispersed solution on a porous substrate to form electrodes. A volumetric capacitance of 42.5 mF cm−3 at a current density of 2 mA cm−3 was obtained on the paper-based mSC. Our demonstrations have shown the versatility of direct spraying for the fabrication of integrative paper-based microfluidic devices.

Versatile fabrication of paper-based microfluidic devices with high chemical resistance using scholar glue and magnetic masks

Simple methods have been developed for fabricating microfluidic paper-based analytical devices (μPADs) but few of these devices can be used with organic solvents and/or aqueous solutions containing surfactants. This study describes a simple fabrication strategy for μPADs that uses readily available scholar glue to create the hydrophobic flow barriers that are resistant to surfactants and organic solvents. Microfluidic structures were defined by magnetic masks designed with either neodymium magnets or magnetic sheets to define the patter, and structures were created by spraying an aqueous solution of glue on the paper surface. The glue-coated paper was then exposed to UV/Vis light for cross-linking to maximize chemical resistance. Examples of microzone arrays and microfluidic devices are demonstrated. μPADs fabricated with scholar glue retained their barriers when used with surfactants, organic solvents, and strong/weak acids and bases unlike common wax-printed barriers. Paper microzones and microfluidic devices were successfully used for colorimetric assays of clinically relevant analytes commonly detected in urinalysis to demonstrate the low background of the barrier material and generally applicability to sensing. The proposed fabrication method is attractive for both its ability to be used with diverse chemistries and the low cost and simplicity of the materials and process.

Laser-induced photo-polymerisation for creation of paper-based fluidic devices.

Paper-based microfluidics is a rapidly progressing inter-disciplinary technology driven by the need for low-cost alternatives to conventional point-of-care diagnostic tools. For transport of reagents/analytes, such devices often consist of interconnected hydrophilic fluid-flow channels that are demarcated by hydrophobic barrier walls that extend through the thickness of the paper. Here, we present a laser-based fabrication procedure that uses polymerisation of a photopolymer to produce the required fluidic channels in paper. Experimental results showed that the structures successfully guide the flow of fluids and allow containment of fluids in wells, and hence the technique is suitable for fabrication of paper-based microfluidic devices. The minimum width for the hydrophobic barriers that successfully prevented fluid leakage was ~120 μm and the minimum width for the fluidic channels that can be formed was ~80 μm, the smallest reported so far for paper-based fluidic patterns.

One-step rapid fabrication of paper-based microfluidic devices using fluorocarbon plasma polymerization

In this work, we demonstrated an all-dry, top-down, and one-step rapid process to fabricate paper-based microfluidic devices using fluorocarbon plasma polymerization. This process is able to create fluorocarbon-coated hydrophobic patterns on filter paper substrates while maintaining the trench and detection regions intact and free of contamination after the fabrication process, as confirmed by attenuated total reflectance–Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. We have shown that the processing time is one critical factor that influences the device performance. For the device fabricated with a sufficiently long processing time (180 s), the sample fluid flow can be well confined in the patterned trenches. By testing the device with an 800 μm channel width, a sample solution amount as small as 4.5 μL is sufficient to perform the test. NO2 − assay is also performed and shows that such a device is capable for biochemical analysis.

Fabrication of Paper-based Microfluidic Devices by Plasma Treatment and Its Application in Glucose Determination

Fabrication of Paper-based Microfluidic Devices by Plasma Treatment and Its Application in Glucose Determination

Method for Fabrication of Paper-Based Microfluidic Devices by Alkylsilane Self-Assembling and UV/O3-Patterning

This work presents a novel and facile method for fabricating paper-based microfluidic devices by means of coupling of hydrophobic silane to paper fibers followed by deep UV-lithography. After filter paper being simply immersed in an octadecyltrichlorosilane (OTS) solution in n-hexane for 5 min, the hydrophilic paper became highly hydrophobic (water contact angle of about 125°) due to the hydrophobic OTS molecules were coupled to paper's cellulose fibers. The hydrophobized paper was then exposed to deep UV-lights through a quartz mask that had the pattern of the to-be-prepared channel network. Thus, the UV-exposed regions turned highly hydrophilic whereas the masked regions remained highly hydrophobic, generating hydrophilic channels, reservoirs and reaction zones that were well-defined by the hydrophobic regions. The resolution for hydrophilic channels was 233 ± 30 μm and that for between-channel hydrophobic barrier was 137 ± 21 μm. Contact angle measurement, X-ray photoelectron spectroscopy (XPS) and attenuated total reflectance Fourier transform-infrared (ATR-FT-IR) spectroscopy were employed to characterize the surface chemistry of the OTS-coated and UV/O(3)-treated paper, and the related mechanism was discussed. Colorimetric assays of nitrite are demonstrated with the developed paper-based microfluidic devices.

Paper-based microfluidic point-of-care diagnostic devices

Dipstick and lateral-flow formats have dominated rapid diagnostics over the last three decades. These formats gained popularity in the consumer markets due to their compactness, portability and facile interpretation without external instrumentation. However, lack of quantitation in measurements has challenged the demand of existing assay formats in consumer markets. Recently, paper-based microfluidics has emerged as a multiplexable point-of-care platform which might transcend the capabilities of existing assays in resource-limited settings. However, paper-based microfluidics can enable fluid handling and quantitative analysis for potential applications in healthcare, veterinary medicine, environmental monitoring and food safety. Currently, in its early development stages, paper-based microfluidics is considered a low-cost, lightweight, and disposable technology. The aim of this review is to discuss: (1) fabrication of paper-based microfluidic devices, (2) functionalisation of microfluidic components to increase the capabilities and the performance, (3) introduction of existing detection techniques to the paper platform and (4) exploration of extracting quantitative readouts via handheld devices and camera phones. Additionally, this review includes challenges to scaling up, commercialisation and regulatory issues. The factors which limit paper-based microfluidic devices to become real world products and future directions are also identified.

Low-Cost Fabrication of Paper-Based Microfluidic Devices by One-Step Plotting

In this technical note, we describe a facile method for one-step fabrication of paper-based microfluidic devices, by simply using commercially available permanent markers and metal templates with specific patterns. The fabrication process involves only a single step of plotting pattern in paper; it can be typically finished within 1 min. The ink marks formed in the patterned paper will act as the hydrophobic barriers to define the hydrophilic flow paths or separate test zones. Various paper devices can be created by using different templates with corresponding patterns. Transparent adhesive tape-sandwiched devices could protect their assay surfaces from potential contamination. In the proof-of-concept experiments, circular paper test zones (~3 mm diameter) were fabricated for colorimetric and quantification detection of prostate-specific antigen (PSA) as a model target, based on dot-immunogold staining assays coupled with gold enhancement amplification. Several serum specimens were additionally evaluated with this new approach and the results were compared with the commercial chemiluminescence immunoassay, validating its feasibility of practical applications. Such a one-step plotting method for paper patterning does not require any specialized equipments and skills, is quite inexpensive and rapid, and thus holds great potential to find wide applications especially in remote regions and resource-limited environments such as small laboratories and private clinics.

Investigation of wax and paper materials for the fabrication of paper-based microfluidic devices

Paper-based microfluidic devices hold great potential in today’s microfluidic applications. They offer low costs, simple and quick fabrication processes, ease of uses, etc. In this work, several wax and paper materials are investigated for the fabrication of paper-based microfluidic devices. A novel method of using wax as a suitable backing to a paper-based analytical device has been demonstrated. Governing equations for the mechanics of the fluid flow in paper-based channels with constant widths have been experimentally validated. Experimental results showing deviations from the governing equations have been verified using fluidic channels with varying widths. There lies the possibility of manipulation of the fluid flow in paper-based microfluidic devices solely using geometric factors. This opens up many potential applications that may require sequential delivery of reagents or samples. Lastly, properties of paper such as the average pore diameter and permeability can be deduced from experimental results.

Fabrication and Characterization of Paper-Based Microfluidics Prepared in Nitrocellulose Membrane By Wax Printing

Paper-based microfluidics is a promising technology to develop a simple, low-cost, portable, and disposable diagnostic platform for resource-limited settings. Here we report the fabrication of paper-based microfluidic devices in nitrocellulose membrane by wax printing for protein immobilization related applications. The fabrication process, which can be finished within 10 min, includes mainly printing and baking steps. Wax patterning will form hydrophobic regions in the membrane, which can be used to direct the flow path or separate reaction zones. The fabrication parameters like printing mode and baking time were optimized, and performances of the wax-patterned nitrocellulose membrane such as printing resolution, protein immobilization, and sample purification capabilities were also characterized in this report. We believe the wax-patterned nitrocellulose membrane will enhance the capabilities of paper microfluidic devices and bring new applications in this field.