Microfluidic paper-based analytical devices (µPADs) for fast and ultrasensitive sensing of biomarkers and monitoring of diseases.
ABSTRACT: Through the development of analytical techniques, microscaled devices have displayed attractive advantages, including ultrasensitive detection and analysis, cost-effectiveness, portability, process integrity, multi-process functionality, and in-situ analysis. In the last decade, a new generation of analytical devices has emerged based on the cellulose materials - so-called microfluidic paper-based analytical devices (µPADs) - a field that will change the face of the diagnosis of different diseases and sensing of a wide range of biological/chemical/biochemical phenomena. The main aim of the current editorial is to highlight the importance of the µPADs in the research and development of diagnostic devices and pharmaceuticals.
Project description:Microfluidic paper-based analytical devices (µPADs) have provided a breakthrough in portable and low-cost point-of-care diagnostics. Despite their significant scope, the complexity of fabrication and reliance on expensive and sophisticated tools, have limited their outreach and possibility of commercialization. Herein, we report for the first time, a facile method to fabricate µPADs using a commonly available laser printer which drastically reduces the cost and complexity of fabrication. Toner ink is used to pattern the µPADs by printing, without modifying any factory configuration of the laser printer. Hydrophobic barriers are created by heating the patterned paper which melts the toner ink, facilitating its wicking into the cross-section of the substrate. Further, we demonstrate the utilization of the fabricated device by performing two assays. The proposed technique provides a versatile platform for rapid prototyping of µPADs with significant prospect in both developed and resource constrained region.
Project description:This work demonstrates the fabrication of microfluidic paper-based analytical devices (µPADs) suitable for the analysis of sub-microliter sample volumes. The wax-printing approach widely used for the patterning of paper substrates has been adapted to obtain high-resolution microfluidic structures patterned in filter paper. This has been achieved by replacing the hot plate heating method conventionally used to melt printed wax features into paper by simple hot lamination. This patterning technique, in combination with the consideration of device geometry and the influence of cellulose fiber direction in filter paper, led to a model µPAD design with four microfluidic channels that can be filled with as low as 0.5 µL of liquid. Finally, the application to a colorimetric model assay targeting total protein concentrations is shown. Calibration curves for human serum albumin (HSA) were recorded from sub-microliter samples (0.8 µL), with tolerance against ±0.1 µL variations in the applied liquid volume.
Project description:Metals in particulate matter (PM) are considered a driving factor for many pathologies. Despite the hazards associated with particulate metals, personal exposures for at-risk workers are rarely assessed due to the cost and effort associated with monitoring. As a result, routine exposure assessments are performed for only a small fraction of the exposed workforce. The objective of this research was to evaluate a relatively new technology, microfluidic paper-based analytical devices (µPADs), for measuring the metals content in welding fumes. Fumes from three common welding techniques (shielded metal arc, metal inert gas, and tungsten inert gas welding) were sampled in two welding shops. Concentrations of acid-extractable Fe, Cu, Ni, and Cr were measured and independently verified using inductively coupled plasma-optical emission spectroscopy (ICP-OES). Results from the µPAD sensors agreed well with ICP-OES analysis; the two methods gave statistically similar results in >80% of the samples analyzed. Analytical costs for the µPAD technique were ~50 times lower than market-rate costs with ICP-OES. Further, the µPAD method was capable of providing same-day results (as opposed several weeks for ICP laboratory analysis). Results of this work suggest that µPAD sensors are a viable, yet inexpensive alternative to traditional analytic methods for transition metals in welding fume PM. These sensors have potential to enable substantially higher levels of hazard surveillance for a given resource cost, especially in resource-limited environments.
Project description:Fluid flow behaviour in paper is of increasing interest due to the advantages and expanding use of microfluidic paper-based analytical devices (known as µPADs). Applications are expanding from those which often have low sample fluid volumes, such as diagnostic testing, to those with an abundance of sample fluid, such as water quality testing. The rapid development of enhanced features in ?PADs, along with a need for increased sensitivity and specificity in the embedded chemistry requires understanding the passively-driven fluid motion in paper to enable precise control and consistency of the devices. It is particularly important to understand the influence of parameters associated with larger fluid volumes and to quantify their impact. Here, we experimentally investigate the impacts of several properties during imbibition in paper, including geometry (larger width and length) and the surrounding conditions (humidity and temperature) using abundant fluid reservoirs. Fluid flow velocity in paper was found to vary with temperature and width, but not with length of the paper strip and humidity for the conditions we tested. We observed substantial post-wetting flow for paper strips in contact with a large fluid reservoir.
Project description:Microfluidic paper-based analytical devices (?PADs) are a versatile and inexpensive point-of-care (POC) technology, but their widespread adoption has been limited by slow flow rates and the inability to carry out complex in field analytical measurements. In the present work, we investigate multilayer ?PADs as a means to generate enhanced flow rates within self-pumping paper devices. Through optical and electrochemical measurements, the fluid dynamics are investigated and compared to established flow theories within ?PADs. We demonstrate a ?145-fold increase in flow rate (velocity = 1.56 cm s-1, volumetric flow rate = 1.65 mL min-1, over 5.5 cm) through precise control of the channel height in a 2 layer paper device, as compared to archetypical 1 layer ?PAD designs. These design considerations are then applied to a self-pumping sequential injection device format, known as a three-dimensional paper network (3DPN). These 3DPN devices are characterized through flow injection analysis of a ferrocene complex and anodic stripping detection of cadmium, exhibiting a 5× enhancement in signal compared to stationary measurements.
Project description:Food safety and access to systematic approaches for ensuring detection of food hazards is an important issue in most developing countries. With the arrival of paper-based analytical devices (µPADs) as a promising, rapid, easy-to-use, and low-cost analytical tool, we demonstrated a simple microfluidic-based titration study for the analysis of packaged fruit juices. Similar, to the titration experiments using traditional glassware in chemistry laboratories, in this study the titration experiments were developed using paper microfluidics for the analysis of several analytes such as pH, vitamin C, sugars, and preservatives present in the packaged fruit juices. The allergen found commonly in dairy based mixtures and the non-pathogenic biochemical component responsible for food spoilage in cider based fruit juices were also determined. The results obtained using paper microfluidics were compared with those obtained using a conventional spectrophotometric technique. Finally, a paper microfluidics based multiplexed sensor was developed for the analysis of common nutritional ingredients, an allergen, and a non-pathogenic byproduct present in packaged fruit juices on a single platform. Overall, the results presented in this study reveal that the proposed paper microfluidic assisted colorimetric multiplexed sensor offers a quick and reliable tool for on-spot routine analysis for food safety applications.
Project description:A chemically patterned microfluidic paper-based analytical device (C-µPAD) is developed to create fluidic networks by forming hydrophobic barriers using chemical vapor deposition (CVD) of trichlorosilane (TCS) on a chromatography paper. By controlling temperature, pattern size, and CVD duration, optimal conditions were determined by characterizing hydrophobicity, spreading patterns, and flow behavior on various sized fluidic patterns. With these optimal conditions, we demonstrated glucose assay, immunoassay, and heavy metal detection on well-spot C-µPAD and lateral flow C-µPAD. For these assays, standard curves showing correlation between target concentration and gray intensity were obtained to determine a limit of detection (LOD) of each assay. For the glucose assays on both well-spot C-µPAD and lateral flow C-µPAD, we achieved LOD of 13?mg/dL, which is equivalent to that of a commercial glucose sensor. Similar results were obtained from tumor necrosis factor alpha (TNF?) detection with 3?ng/mL of LOD. For Ni detection, a colorimetric agent was immobilized to obtain a stationary and uniform reaction by using thermal condensation coupling method. During the immobilization, we successfully functionalized amine for coupling the colorimetric agent on the C-µPAD and detected as low as 150 ?g/L of Ni. These C-µPADs enable simple, rapid, and cost-effective bioassays and environmental monitoring, which provide practically relevant LODs with high expandability and adaptability.
Project description:Point-of-care platforms can provide fast responses, decrease the overall cost of the treatment, allow for in-home determinations with or without a trained specialist, and improve the success of the treatment. This is especially true for microfluidic paper-based analytical devices (?PAD), which can enable the development of highly efficient and versatile analytical tools with applications in a variety of biomedical fields. The objective of this work was the development of ?PADs to identify and quantify levels of nitrite in saliva, which has been proposed as a potential marker of periodontitis. The devices were fabricated by wax printing and allowed the detection of nitrite by a colorimetric reaction based on a modified version of the Griess reaction. The presented modifications, along with the implementation of a paper-based platform, address many of the common drawbacks (color development, stability, etc.) associated with the Griess reaction and are supported by results related to the design, characterization, and application of the proposed devices. Under the optimized conditions, the proposed devices enable the determination of nitrite in the 10-1000 ?mol L(-1) range with a limit of detection of 10 ?mol L(-1) and a sensitivity of 47.5 AU [log (?mol L(-1))](-1). In order to demonstrate the potential impact of this technology in the healthcare industry, the devices were applied to the analysis of a series of real samples, covering the relevant clinical range.
Project description:In this paper, we determine the smallest feature size that enables fluid flow in microfluidic paper-based analytical devices (µPADs) fabricated by laser cutting. The smallest feature sizes fabricated from five commercially available paper types: Whatman filter paper grade 50 (FP-50), Whatman 3MM Chr chromatography paper (3MM Chr), Whatman 1 Chr chromatography paper (1 Chr), Whatman regenerated cellulose membrane 55 (RC-55) and Amershan Protran 0.45 nitrocellulose membrane (NC), were 139 ± 8 µm, 130 ± 11 µm, 103 ± 12 µm, 45 ± 6 µm, and 24 ± 3 µm, respectively, as determined experimentally by successful fluid flow. We found that the fiber width of the paper correlates with the smallest feature size that has the capacity for fluid flow. We also investigated the flow speed of Allura red dye solution through small-scale channels fabricated from different paper types. We found that the flow speed is significantly slower through microscale features and confirmed the similar trends that were reported previously for millimeter-scale channels, namely that wider channels enable quicker flow speed.
Project description:Here we report the vertical paper analytical devices (vPADs) fabricated using the principles of quilling and kirigami. What differentiates the vPADs from conventional paper microfluidic devices is that the paper substrate used to fabricate the device is placed vertically to the device plane. The fabrication of vPADs with high precision is instrument-free, requiring no photolithography, printing or heating. Two- and three-dimensional vPADs are fabricated for multiplex colorimetric assays of four biochemical indicators and automated enzyme-linked immunosorbent assay of human myoglobin, respectively.