Paper-based microfluidic platforms are widely utilized in point-of-care (POC) diagnostics, filtration, and fluid handling due to their cost-effectiveness and simplicity. However, uncontrolled capillary-driven transport often results in performance inconsistencies, compromising sensitivity, specificity, and reproducibility. Hydrogel-infused paper matrices present a promising strategy to regulate fluid flow by modifying the porous microstructure, though their impact on transport dynamics remains insufficiently explored. This study investigates the role of hydrogel concentration and fluid viscosity in controlling flow behavior in paper membranes, relevant to diagnostics applications. Hydrogel is pre-imbibed into paper assays to modulate capillary transport, and the effects of varying injected fluid viscosities (0.954–1.54 cP, corresponding to solute concentrations of 0.055–0.555 M) and hydrogel concentrations (4.83–8.06 mg/mL) are examined across three distinct porous substrates. Real-time, high-resolution imaging enables quantitative analysis of fluid front evolution, including angular deviations, length variations, and interface curvature. Hydrogel presence increases flow resistance by 3-33.5
Regulating fluid transport and efficiently controlling imbibition dynamics across the surface of paper assays may increase the detection sensitivity in medical diagnostic applications. The present paper deals with inert additives strategically implemented on various cellulose-based filter-paper membrane surfaces to control the flow dynamics. Studies have been carried out to investigate the effect of additive positioning, additive amount, and the cascading effect of the additive on time delay. Fluid-imbibed images have been processed via mean grayscale intensity variation to understand the saturation extent qualitatively. The tactical application of additives resulted in a flow time increment of up to 121.6 %. A flow time delay analysis was carried out to display the effect of the influencing parameters. Further, imbibition dynamics in the additive-laden paper membrane were captured using a modified Lucas-Washburn model. Finally, the extent of reusability of the paper membranes used was investigated using various drying procedures.
Paper membranes find applications in various fields, including Point-of-Care (POC) diagnostics, separation, filtration, and fluid transport. Still, they are frequently plagued by dispersion-related issues that lead to uneven flow, further affecting sensitivity and specificity, especially in detection assays. Hence, flow control in paper membranes becomes essential to achieving an effective paper-based platform. The present work develops a novel methodology based on adaptive flow regulation to optimize dispersion and flow control. This approach leverages real-time data to measure the controlled flow rates and prevent dispersion using hydrogel across paper-based membranes. Effects of three major parameters, namely mixing speed (100 rpm - 400 rpm), hydrogel concentration (6.45 mg/ml -12.9 mg/ml) for preparing hydrogel, and types of filter paper membranes are investigated in detail. Imaging techniques are applied to capture high-resolution images of fluid behavior on the paper strip surface at various time intervals, and the results are demonstrated in terms of mean intensity as a quantifiable indicator (0-255). It was found that the hydrogel prepared using 400 rpm mixing speed at a specific concentration exhibited significant resistance to the fluid flow with minimal dispersion. Furthermore, the Filter-paper 441 membrane is compared with other filter-paper membranes used in this experiment. Notably, a 43 %-79 % reduction in dispersion was observed for the hydrogel-laden paper membranes. Additionally, the dispersion was largely minimized even when lower concentrations of sodium hydroxide were detected on hydrogel-based paper assays, enhancing its sensitivity. Overall, this research offers a multifaceted solution to reduce dispersion and optimize flow control in paper-based membranes using hydrogel to improve the performance of the paper assays.
Paper-based diagnostics offer a promising alternative to traditional diagnostic methods for point-of-care use due to their low cost, ease of use, portability, rapid results, versatility, and low environmental impact. While paper-based serology tests in the form of lateral flow assays can provide rapid test results for past pathogen exposure, they currently lack the accuracy and sensitivity offered by molecular diagnostic tests such as the polymerase chain reaction (PCR). Loop-mediated isothermal amplification (LAMP)-an isothermal nucleic acid amplification test (NAAT)-provides PCR-like performance while simultaneously reducing the instrumentation and assay complexity associated with PCR. In this review, we discuss a newly emerging class of paper-based LAMP platforms that integrates the versatility of paper microfluidics with the accuracy of NAATs. Since its first adoption in 2015, we have discussed all paper-based LAMP platforms in terms of the paper substrates, reagent incorporation techniques, paper platform design, heating hardware, detection methods, and sensitivity and specificity of paper-based LAMP assays. We conclude by identifying the current challenges and future prospects of paper-based NAATs.
The ability to simultaneously heat and image samples using transmitted light is crucial for several biological applications. However, existing techniques such as heated stage microscopes, thermal cyclers equipped with imaging capabilities, or non-contact heating systems are often bulky, expensive, and complex. This work presents the development and characterization of a Miniaturized Optically-clear Thermal Enclosure (MOTE) system—an open-source, inexpensive, and low-powered modular system—capable of convectively heating samples while simultaneously imaging them with transmitted light. We develop and validate a computational fluid dynamics (CFD) model to design and optimize the heating chamber. The model simulates velocity and temperature profiles within the heating chamber for various chamber materials and sizes. The computational model yielded an optimal chamber dimension capable of achieving a stable temperature ranging from ambient to 95 °C with a spatial discrepancy of less than 1.5 °C, utilizing less than 8.5 W of power. The dual-functionality of the MOTE system, enabling synchronous heating and transmitted light imaging, was demonstrated through the successful execution of paper-based LAMP reactions to detect λ DNA samples in real-time down to 10 copies/µL of the target concentration. The MOTE system offers a promising and flexible platform for various applications, from molecular diagnostics to biochemical analyses, cell biology, genomics, and education.
Lateral flow assays and paper microfluidics have the potential to replace benchtop instrumented medical diagnostic systems with instrument-free systems that rely on passive transport of liquid through micro-porous paper substrates. Predicting the imbibition dynamics of liquid through dry paper substrates is mostly modeled through the Lucas-Washburn (LW) equations. However, the LW framework assumes that the fluid front exhibits a sharp boundary between the dry and wet phases across the liquid imbibition interface. Additionally, the relative humidity in the environment results in moisture trapped within the pores of the paper substrates as the paper attains an equilibrium with the ambient air. Here, we apply a two-phase transport framework based on Brooks and Corey's model to capture imbibition dynamics on partially saturated paper substrates. The model is experimentally validated and is then used to predict the liquid-paper imbibition dynamics in simulated environments with 1-70% relative humidity. The model was also used to determine the saturation gradient of liquid along the imbibition interface of the paper substrate. Insights from these studies enabled us to determine the mechanism of the liquid transport in partially saturated porous paper substrates. The model also enabled us to evaluate the optimal paper shapes and relative humidity of the environment that maximize imbibition rates and minimize imbibition front broadening. Finally, we evaluate the effect of moisture content of paper on the rate of paper-based biochemical reaction by amplifying a sequence of the SARS-CoV-2 RNA target via reverse transcriptase loop-mediated isothermal amplification. Taken together, this study provides some important guidelines to academic and applied researchers working in point-of-care diagnostics to develop paper-based testing platforms that are capable of functioning in a robust manner across multiple environmental conditions.
Paper-based point-of-care (POC) devices have attracted tremendous attention because of low-cost, sim-ple fabrication, and portability. LAMP-based POC platform comprises a paper substrate on which the DNA amplification reaction occurs. The quality of the paper substrate plays a critical role in performing an efficient LAMP reaction and for effective visualization of the amplification result. The major objective of the current work is to replace the frequently utilized nitrocellulose (NC) membrane by a cost-effective and high quality paper membrane viz. Whatman filter paper (WF) for rapid detection of E. coli via LAMP reaction. Isolated DNA is added on the paper membranes, which undergo LAMP reaction. The effect of initial DNA concentration and time on LAMP amplification reaction rate is analyzed on paper membranes via image analysis for the first time. Overall study inferred that WF is suitable for effective naked-eye detection and greater extent of LAMP reaction (generation of 19 968 DNA copies). (C) 2020 Elsevier Ltd. All rights reserved.
Loop-Mediated Isothermal Amplification reaction or LAMP has been identified as a feasible DNA amplification process. Paper-based LAMP diagnostic devices offer several advantages for point-of-care (POC) applications. LAMP occurs at a constant temperature of higher limits, which remains a major challenge on-site. This calls for an efficient thermal design which is beneficial in maintaining a constant high temperature at POC locations. The present study reports thermal design and energy consumption analysis of a paper-based LAMP POC device for the first time using CFD analysis. The POC design consists of a rectangular porous membrane embedded on a rectangular solid material, heated from the side walls. Isothermal and discrete heating with different horizontal and vertical clearance configurations are used as a design parameter. CFD analysis of different thermal configurations is carried out in COMSOL Multiphysics platform to solve the energy and convection-diffusion-reaction equation in porous media. The thermal analysis demonstrated that two discrete heating configurations with high horizontal clearance are effective in reducing energy consumption. It was inferred that two portable AA batteries are sufficient for the POC device operation. Overall, the current work successfully demonstrates the energy optimization and speed of operation of the POC medical device by detailed thermal analysis.
Loop-mediated isothermal amplification or LAMP has been identified to be an efficient technology for point-of-care diagnostics. Paper-based LAMP technique has tremendous potential in replacing the existing tube–based technology as the manufacturing cost of a paper-based device is comparatively lower and easy-to-use. LAMP-based paper diagnostic device for Mycobacterium tuberculosis (MTB) detection is of extreme importance as it will help in early and rapid diagnosis of the affected patients. The fabrication of these devices requires assessment of design parameters on the extent of LAMP amplification reaction. Hence, CFD studies would be extremely beneficial from the design perspective. The current work presents an insight into the CFD simulations for LAMP amplification reaction on a porous paper membrane (nitrocellulose membrane). The convection–diffusion–reaction model is solved on a COMSOL Multiphysics 5.0 platform. Studies on effect of pore size, aspect ratio and initial DNA concentration on the extent of DNA amplification reaction have been carried out. The current paper-based technique is effective in detecting a minimum of 5 copies of DNA contrasting the previous semi-quantitative technique which demonstrated the detection of minimum 98 copies. Overall, the simulation results displayed almost 96% enhancement in the DNA amplification rate on paper membrane.
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.
Purpose The purpose of the paper is to study natural convection within porous square and triangular geometries (design 1: regular isosceles triangle, design 2: inverted isosceles triangle) subjected to discrete heating with various locations of double heaters along the vertical (square) or inclined (triangular) arms. Design/methodology/approach Galerkin finite element method is used to solve the governing equations for a wide range of modified Darcy number, Da m = 10 −5 –10 −2 with various fluid saturated porous media, Pr m = 0.015 and 7.2 at a modified Rayleigh number, Ra m = 10 6 involving the strategic placement of double heaters along the vertical or inclined arms (types 1-3). Adaptive mesh refinement is implemented based on the lengths of discrete heaters. Finite element based heat flow visualization via heatlines has been adopted to study heat distribution at various portions. Findings The strategic positioning of the double heaters (types 1-3) and the convective heatline vortices depict significant overall temperature elevation at both Da m = 10 −4 and 10 −2 compared to type 0 (single heater at each vertical or inclined arm). Types 2 and 3 are found to promote higher temperature uniformity and greater overall temperature elevation at Da m = 10 −2 . Overall, the triangular design 2 geometry is also found to be optimal in achieving greater temperature elevation for the porous media saturated with various fluids ( Pr m ). Practical implications Multiple heaters (at each side [left or right] wall) result in enhanced temperature elevation compared to the single heater (at each side [left or right] wall). The results of the current work may be useful for the material processing, thermal storage and solar heating applications. Originality/value The heatline approach is used to visualize the heat flow involving double heaters along the side (left or right) arms (square and triangular geometries) during natural convection involving porous media. The heatlines depict the trajectories of heat flow that are essential for thermal management involving larger thermal elevation. The mixing cup or bulk average temperature values are obtained for all types of heating (types 0-3) involving all geometries, and overall temperature elevation is examined based on higher mixing cup temperature values.
The present work involves the entropy generation studies within the porous square and triangular (models 1 and 2) cavities subjected to various discrete heating strategies at side walls (cases 1-4: symmetric heater locations, case 5: asymmetric heater locations) during natural convection over the wide range of Darcy number, , for various fluids (Pr-m=0.015 and 7.2) at . Galerkin finite-element method has been used to solve the governing equations. The symmetric and asymmetric distributions of heaters have similar effects at lower Da(m). However, the symmetric distribution of heaters corresponds to lower entropy generation rates at higher Da(m). The triangular (model 1 and model 2) cavities are found to be optimal over the entire range of Da(m) based on the higher heat transfer rate and optimal entropy generation rates.
The discrete heating strategy has been identified as an energy efficient method. The current work is aimed at achieving a thermally efficient triangular-design 1 (regular isosceles triangle), triangular-design 2 (inverted isosceles triangle) and square enclosures based on the entropy generation studies involving strategic positioning of the double heaters along each side wall (case 1: larger heater in lower half and smaller heater in central half, case 2: larger heater in central half and smaller heater in lower half, case 3: two heaters of identical lengths located at central and lower halves) for Pr = 0.015 and 7.2 involving Ra = 10(3)-10(5). The numerical results of the cases 1-3 have been further compared with the case involving single heater along each side wall (case 0). Galerkin finite element method is implemented for the accurate evaluation of the entropy generation terms based on elemental basis set. Cases 1-3 exhibit lower entropy generation and higher heat transfer rates in the convection dominant regime (Ra = 10(5)) compared to the case O. Overall, case 3 is concluded to be optimal based on higher rate of heat transfer and lower entropy generation. (C) 2018 Elsevier Ltd. All rights reserved.
The role of multiple discrete solar heaters have been studied for energy efficiency in the heating of fluids. Current work involves natural convection studies with the various locations of the double heat sources along each side wall of the triangular-design 1 (regular isosceles triangle), triangular-design 2 (inverted isosceles triangle) and square enclosures for various cases (case 1: larger heater in lower half and smaller heater in central half, case 2: larger heater in central half and smaller heater in lower half, case 3: two heaters of identical lengths are located at the central and lower halves) involving various fluids (Pr=0.015 and 7.2) for various Rayleigh numbers, 103≤Ra≤105. The thermal mixing and energy flow in the cavities are visualized using the mathematical tool of heatlines. Also, the overall rate of heat transfer in conduction and convection dominant regimes is evaluated using Nusselt numbers (average and local). The case 2 discrete heating configuration is inferred as the optimal heating configuration based on the larger zone of uniform temperature and thermal mixing. Also, the thermal management is significantly improved in triangular-design 2 and square cavities.
Since Andreas Manz first introduced the microchip technology for chemical applications back in the 1990s, the field of 'microfluidics' has expanded widely and microfluidic tools have become ubiquitous in life sciences research. However, pumps and controllers associated with most current microfluidic chips continue to be bulky and costly. A new class of microfluidic devices in which flow channels are composed of multidimensional (2D or 3D) shapes of porous materials is becoming increasingly popular. The ability of porous materials to wick fluids obviates the need for pumps, making such devices portable, low-cost, and ideal for use in low-resource settings. Such devices are broadly referred to as "paper microfluidic devices". The ability to manipulate fluids in paper microfluidics has progressively increased over the past decade and such devices are currently being used to develop highly sensitive and multiplexed low-cost diagnostic/sensing devices. In this article, we review the area of paper microfluidics covering the basic fluid physics, methods of fabrication, flow control tools, applications in diagnostics/sensing, and applications in other emerging areas like tissue engineering and power storage. This review is targeted to a broad audience that does not have prior exposure to the field of paper-based microfluidics. Through this article, we wish to invite researchers from multiple backgrounds to contribute to further development in this new and exciting area of research.
The bulk motion of fluid and diffusive transport within fluid are two processes during natural or forced convection. The complexity of the convective heat flow is realized since last few decades and the analysis of the heat flow as well as thermal characteristics gradually becomes cumbersome. Although earlier researchers studied convective heat flow via velocity profiles, streamlines and isotherms, these tools were not enough for the efficient visualization of the unique features of convection heat flow. An efficient tool, termed as ‘heatline’ (mathematically represented as heatfunction) was first proposed by Kimura and Bejan in 1983 for the heat flow visualization during convective heat flow. The aim of this article is to review existing works on ‘heatline’ involving various physical systems. The mathematical implications of heatfunctions based on derivations of governing equations and boundary conditions for heatfunctions are presented in detail. The non-homogeneous boundary conditions for heatfunctions arise due to hot or cold or adiabatic walls as well as the junction between the walls and these conditions vary with the location of the reference or datum of the heatfunction. The physics on the heat flow via ‘heatlines’ are found to be invariant with the locations of the reference value of the heatfunction. The heat flow visualization is analyzed for various test cases from simple one dimensional boundary layer problem to convection in two dimensional complex cavities. The detailed explanations of earlier works on ‘heatlines’ during one dimensional flow involving forced or natural convection with various applications are discussed. Further, applications of ‘heatlines’ during convective heat flow within enclosed cavities involving uniform or non uniform heating of walls, discrete heating or cooling, conjugate convection and mixed convection are discussed and ‘heatlines’ are found to be successful to demonstrate various complex heat flow paths and multiple heat flow circulation cells. Overall, the analysis of convective heat flow from simple to complicated geometries via ‘heatline’ is crucial for the visualization of the thermal transport, mixing and efficient thermal management.
The study of natural convection in rhombic enclosure has been a subject of interest in the recent past. In the current work, the effect of various shapes of the rhombic enclosure (phi=45 degrees, 60 degrees, and 75 degrees) is investigated for fixed areas (A=0.5, 1, and 1.5) over an extensive range of parameters (Pr-m=0.015-1000, Da(m)=10(-5)-10(-2), and Ra-m=10(6)) for an optimal thermal configuration. The rhombic enclosure is subjected to the isothermal heating of the bottom wall along with the cold side and top walls. The results are shown in the form of entropy generation maps (S and S) along with the heatlines (), streamlines (), and isotherms (). It is observed that S decreases near the left wall whereas S near the top and right walls increases with phi, irrespective of A. A large regime near the bottom portion of the left wall and right portion of the bottom wall corresponds to the higher magnitude of S and that extends over a wider region for the higher phi. The results in terms of total entropy generation (S-total), average Bejan number (Be-av), and average Nusselt number (Nub) are compared with those within the square cavity (phi=90 degrees). Overall, it may be concluded that the rhombic enclosure with phi=45 degrees at A=0.5 is the optimal configuration for the thermal processing of the fluids based on the moderate
•Natural convection plays a vital role in energy related applications.•A review of natural convection studies within non-square enclosures is presented.•Mathematical models for fluid flow and heat transfer are elucidated for fluid and porous media.•Results on thermal and flow characteristics within various complex geometries are discussed.•Enhancement of heat transfer characteristics are highlighted on various applications.
Nusselt number is an important non-dimensional parameter which quantifies the heat transfer rate. Local Nusselt number is useful in predicting the heat transfer rate along the various hot and cold sections of the side walls in a discretely heated enclosed cavity. In addition, the overall heat balance in an enclosed cavity (total heat delivered by the hot isothermal walls should be equal to the total heat gained by the cold isothermal walls) can be validated via the average Nusselt numbers. Current finite element based simulations and post-processing have been carried out in order to analyze the influence of the multiple heaters on the Nusselt number along various sections (hot and cold) of the side walls in discretely heated square and triangular (design 1 and design 2) cavities. The working fluid is considered to be air (Pr = 0.7) and the numerical studies have been carried out for a large range of Rayleigh number (Ra = 103–105) for four different biquadratic elements (24 × 24, 28 × 28, 32 × 32 and 34 × 34). The current work also estimates the fractional error in the heat balance (ϵ) and it is clearly inferred that ϵ is comparatively lower for 34 × 34 biquadratic elements. Current work also reveals that the fractional error (ϵ) is mainly induced due to the sharp variations in the Nusselt number at the cold-hot junctions along the side walls. The present study also involves the detailed evaluation of the heatfunction (Π) expressions along the cold-hot junctions of the side walls. The computations of the heatfunctions are intrinsically related to the Nusselt numbers of the hot-cold junctions.
The conventional method of differential heating within an enclosure may result in the inadequate thermal mixing and that may further lead to the poor thermal management. In order to enhance the overall thermal mixing, the discrete heating strategy may be considered as an effective alternative. In the current work, natural convection studies have been carried out within discretely heated porous square and triangular (type 1 and type 2) enclosures during natural convection. Overall, five different discrete heating strategies (cases 1-4: symmetric heating, case 5: asymmetric heating) have been considered for the present work. The heatline method has been implemented to visualize the heat flow pattern within the cavities for a wide range of parameters (Pr-m = 0.015-7.2, Da(m) = 10(-6)-10(-2), Ram = 106). In order to solve the governing equations and Poisson equations for streamfunction and heatfunction, the Galerkin finite element method has been used. At Darn = 10(-4), computational results clearly indicate the onset of convection whereas enhanced convection is found to occur at Da(m) = 10(-2) based on the presence of intense fluid and heatline cells. The intensity of heat flow is observed to be higher for the asymmetric distributed heating strategy compared to the symmetric distributed heating configurations. Heatlines depict the role of hot regime along the side walls and they are also useful in explaining the variations of the local and average Nusselt numbers for the various cases. Common to all the cases, the average heat transfer rate within the triangular-type 1 enclosure is higher compared to the square and triangular-type 2 enclosures irrespective of Dam and Prm. The extent of the thermal mixing in each case has been quantified using the cup-mixing temperature which has been evaluated at higher and lower Dam in order to establish the effect of porosity. It is concluded that the thermal mixing is more effective within the square and triangular-type 2 enclosures at both Da(m) = 10(-4) and 10(-2). The cases 2 and 5 were inferred to be the optimal discrete heating strategies. (C) 2017 Elsevier Ltd. All rights reserved.