Fabrication for paper-based microfluidic analytical devices and saliva analysis application
TL;DR: There have been a lot of researches on μPADs, but the fabrication methods and applications need to be further studied to meet the commercial needs, and the research directions of saliva analysis are discussed.
Abstract: Paper-based microfluidic analytical devices (μPADs) have shown great potential in the field of analysis due to their advantages of rapid analysis, environmental friendliness and the ability to realize the flow of fluid without external power. Saliva is an emerging biofluid which is used in diseases diagnostic and screening for the easy collection and the reflection of the physiological state. This review focuses on the fabrication methods for two-dimensional (2D) and three-dimensional (3D) μPADs and their applications on the saliva analysis. In the first part, the flow mechanism in μPADs is discussed. The second part mainly introduces the fabrication methods for the μPADs and compares the different methods. The third part presents the application of μPADs in the detection of biomarkers such as nitrite, glucose, and thiocyanate in saliva. Finally, the research directions of saliva analysis are discussed in the conclusion. There have been a lot of researches on μPADs, but the fabrication methods and applications need to be further studied to meet the commercial needs.
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TL;DR: In this paper , a review summarizes the research progress in this field utilizing paper, understanding fundamental properties w.r.t application, performance enhancement w. r.t material advancements (i.e., paper modification), and technological trends, which is otherwise not yet reviewed earlier.
24 citations
TL;DR: In this paper , a paper-based microfluidic analytical devices (μPADs) were used for multi-analyte discrimination based on molecular imprinting technology, and its sensing behavior was studied by using three nitrophenol (NP) isomers (2-, 3-, and 4-NP) as the testing models.
8 citations
TL;DR: Cut and heat (CH-microPADs) as mentioned in this paper is a two-step process for the selective fabrication of hydrophilic channels and reservoirs on a wide variety of porous media such as tissue/printing/filter paper and cloth types, such as cotton and polyester, by a lamination process.
Abstract: Microfluidic paper-based analytical devices (microPADs) are emerging as simple-to-use, low-cost point-of-care testing platforms. Such devices are mostly fabricated at present by creating hydrophobic barriers using wax or photoresist patterning on porous paper sheets. Even though devices fabricated using these methods are used and tested with a wide variety of analytes, still they pose many serious practical limitations for low-cost automated mass fabrication for their widespread applicability. We present an affordable and simple two-step process - cut and heat (CH-microPADs) - for the selective fabrication of hydrophilic channels and reservoirs on a wide variety of porous media such as tissue/printing/filter paper and cloth types, such as cotton and polyester, by a lamination process. The technique presents many advantages as compared to existing commonly used methods. The devices possess excellent mechanical strength against bending, folding and twisting, making them virtually unbreakable. They are structurally flexible and show good chemical resistance to various solvents, acids and bases, presenting widespread applicability in areas such as clinical diagnostics, biological sensing applications, food processing, and the chemical industry. Fabricated paper media 96 well-plate CH-microPAD configurations were tested for cell culture applications using mice embryonic fibroblasts and detection of proteins and enzymes using ELISA. With a simple two-step process and minimal human intervention, the technique presents a promising step towards mass fabrication of inexpensive disposable diagnostic devices for both resource-limited and developed regions.
7 citations
TL;DR: In this article , the role of nanomaterials to boost the analytical performance and increase the reliability of the test in human saliva samples is discussed, and the critical factors for further modernization of the Nanomaterial-based electrochemical sensors, envisaging the development and implementation of next generation sample-in-answer-out systems.
Abstract: The focus on precise medicine enhances the need for timely diagnosis and frequent monitoring of chronic diseases. Moreover, the recent pandemic of severe acute respiratory syndrome coronavirus 2 poses a great demand for rapid detection and surveillance of viral infections. The detection of protein biomarkers and antigens in the saliva allows rapid identification of diseases or disease changes in scenarios where and when the test response at the point of care is mandated. While traditional methods of protein testing fail to provide the desired fast results, electrochemical biosensors based on nanomaterials hold perfect characteristics for the detection of biomarkers in point‐of‐care settings. The recent advances in electrochemical sensors for salivary protein detection are critically reviewed in this work, with emphasis on the role of nanomaterials to boost the biosensor analytical performance and increase the reliability of the test in human saliva samples. Furthermore, this work identifies the critical factors for further modernization of the nanomaterial‐based electrochemical sensors, envisaging the development and implementation of next‐generation sample‐in‐answer‐out systems.
4 citations
TL;DR: In this paper , the authors reviewed the literature to date describing the development of ICSTs for the detection of different types of mycotoxins using different nanomaterials, nanoparticle size, and replicates in an attempt to identify the most important determinants of the limit of detection (LOD).
Abstract: Mycotoxins are secondary metabolic products of fungi. They are poisonous, carcinogenic, and mutagenic in nature and pose a serious health threat to both humans and animals, causing severe illnesses and even death. Rapid, simple and low-cost methods of detection of mycotoxins are of immense importance and in great demand in the food and beverage industry, as well as in agriculture and environmental monitoring, and, for this purpose, lateral flow immunochromatographic strips (ICSTs) have been widely used in food safety and environmental monitoring. The literature to date describing the development of ICSTs for the detection of different types of mycotoxins using different nanomaterials, nanoparticle size, and replicates was reviewed in an attempt to identify the most important determinants of the limit of detection (LOD). It is found that the particle size and type of materials contribute significantly to determining the LOD. The nanoparticle sizes used in most studies have been in the range 15–45 nm and gold nanoparticle-based ICSTs have been shown to exhibit the lowest LOD. Perspectives for potential future development to reduce the LODs of ICSTs are also discussed.
3 citations
References
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TL;DR: In this article, the rate of penetration into a small cylindrical capillary of radius $r$ was shown to be: ρ(r}^{2}+4\ensuremath{\epsilon}r)
Abstract: Penetration of Liquids into Cylindrical Capillaries.---The rate of penetration into a small capillary of radius $r$ is shown to be: $\frac{\mathrm{dl}}{\mathrm{dt}}=\frac{P({r}^{2}+4\ensuremath{\epsilon}r)}{8\ensuremath{\eta}l}$, where $P$ is the driving pressure, $\ensuremath{\epsilon}$ the coefficient of slip and $\ensuremath{\eta}$ the viscosity. By integrating this expression, the distance penetrated by a liquid flowing under capillary pressure alone into a horizontal capillary or one with small internal surface is found to be the square root of ($\frac{\ensuremath{\gamma}\mathrm{rt}\ifmmode\cdot\else\textperiodcentered\fi{}cos\ensuremath{\theta}}{2\ensuremath{\eta}}$), where $\ensuremath{\gamma}$ is the surface tension and $\ensuremath{\theta}$ the angle of contact. The quantity ($\frac{\ensuremath{\gamma}cos\ensuremath{\theta}}{2\ensuremath{\eta}}$) is called the coefficient of penetrance or the penetrativity of the liquid.Penetration of Liquids into a Porous Body.---(1) Theory. If a porous body behaves as an assemblage of very small cylindrical capillaries, the volume which penetrates in a time $t$ would be proportional to the square root of ($\frac{\ensuremath{\gamma}t}{\ensuremath{\eta}}$). (2) Experiments with mercury, water and other liquids completely verify the theoretical deductions.Dynamic capillary method of measuring surface tension is described. It possesses certain advantages on the static method of capillary rise.
5,658 citations
TL;DR: A procedure that makes it possible to design and fabricate microfluidic systems in an elastomeric material poly(dimethylsiloxane) (PDMS) in less than 24 h by fabricating a miniaturized capillary electrophoresis system is described.
Abstract: This paper describes a procedure that makes it possible to design and fabricate (including sealing) microfluidic systems in an elastomeric materialpoly(dimethylsiloxane) (PDMS)in less than 24 h. A network of microfluidic channels (with width >20 μm) is designed in a CAD program. This design is converted into a transparency by a high-resolution printer; this transparency is used as a mask in photolithography to create a master in positive relief photoresist. PDMS cast against the master yields a polymeric replica containing a network of channels. The surface of this replica, and that of a flat slab of PDMS, are oxidized in an oxygen plasma. These oxidized surfaces seal tightly and irreversibly when brought into conformal contact. Oxidized PDMS also seals irreversibly to other materials used in microfluidic systems, such as glass, silicon, silicon oxide, and oxidized polystyrene; a number of substrates for devices are, therefore, practical options. Oxidation of the PDMS has the additional advantage that it ...
5,491 citations
TL;DR: In this paper, a modular construction of a miniaturized "total chemical analysis system" is proposed, and theoretical performances of such systems based on flow injection analysis, chromatography and electrophoresis are compared with those of existing chemical sensors and analysis systems.
Abstract: Following the trend towards smaller channel inner diameter for better separation performance and shorter channel length for shorter transport time, a modular construction of a miniaturized 'total chemical analysis system' is proposed. The theoretical performances of such systems based on flow injection analysis, chromatography and electrophoresis, are compared with those of existing chemical sensors and analysis systems.
3,017 citations
TL;DR: This communication describes a simple method for patterning paper to create well-defined, millimeter-sized channels, comprising hydrophilic paper bounded by hydrophobic polymer, that will become the basis for low-cost, portable, and technically simple multiplexed bioassays.
Abstract: This communication describes a simple method for patterning paper to create well-defined, millimeter-sized channels, comprising hydrophilic paper bounded by hydrophobic polymer. We believe that this type of patterned paper will become the basis for low-cost, portable, and technically simple multiplexed bioassays. We demonstrate this capability by the simultaneous detection of glucose and protein in 5 μL of urine. The assay system is small, disposable, easy to use (and carry), and requires no external equipment, reagents, or power sources. We believe this kind of system is attractive for uses in less-industrialized countries, in the field, or as an inexpensive alternative to more advanced technologies already used in clinical settings.[1-4]
The analysis of biological fluids is necessary for monitoring the health of populations,[2] but these measurements are difficult to implement in remote regions such as those found in less-industrialized countries, in emergency situations, or in home health-care settings.[3] Conventional laboratory instruments provide quantitative measurements of biological samples, but they are unsuitable for these situations since they are large, expensive, and require trained personnel and considerable volumes of biological samples.[2] Other bioassay platforms provide alternatives to more expensive instruments,[5-7] but the need remains for a platform that uses small volumes of sample and that is sufficiently inexpensive to be used widely for measuring samples from large populations.
We believe that paper may serve as a particularly convenient platform for running bioassays in the remote situations locations. As a prototype for a mthod we believe to be particularly promosing, we patterned photoresist onto chromatography paper to form defined areas of hydrophilic paper separated by hydrophobic lines or “walls”; these patterns provide spatial control of biological fluids and enable fluid transport, without pumping, due to capillary action in the millimeter-sized channels produced. This method for patterning paper makes it possible to run multiple diagnostic assays on one strip of paper, while still using only small volumes of a single sample. In a fully developed technology, patterned photoresist would be replaced by an appropriate printing technology, but patterning paper with photoresist is: i) convenient for prototyping these devices, and ii) a useful new micropatterning technology in its own right.
We patterned chromatography paper with SU-8 2010 photoresist as shown in Figure 1a and as described below: we soaked a 7.5-cm diameter piece of chromatography paper in 2 mL of SU-8 2010 for 30 s, spun it at 2000 rpm for 30 s, and then baked it at 95 °C for 5 min to remove the cyclopentanone in the SU-8 formula. We then exposed the photoresist and paper to 405 nm UV light (50 mW/cm2) for 10 s through a photo-mask (CAD/Art Services, Inc.) that was aligned using a mask aligner (OL-2 Mask Aligner, AB-M, Inc). After exposure, we baked the paper a second time at 95 °C for 5 min to cross-link the exposed portions of the resist. The unpolymerized photoresist was removed by soaking the paper in propylene glycol monomethyl ether acetate (PGMEA) (5 min), and by washing the pattern with propan-2-ol (3 × 10 mL). The paper was more hydrophobic after it was patterned, presumably due to residual resist bound to the paper, so we exposed the entire surface to an oxygen plasma for 10 s at 600 millitorr (SPI Plasma-Prep II, Structure Probe, Inc) to increase the hydrophilicity of the paper (Figures 2a and 2b).
Figure 1
Chromatography paper patterned with photoresist. The darker lines are cured photoresist; the lighter areas are unexposed paper. (a) Patterned paper after absorbing 5 μL of Waterman red ink by capillary action. The central channel absorbs the sample ...
Figure 2
Assays contaminated with (a) dirt, (b) plant pollen, and (c) graphite powder. The pictures were taken before and after running an artificial urine solution that contained 550 mM glucose and 75 μM BSA. The particulates do not move up the channels ...
The patterned paper can be derivatized for biological assays by adding appropriate reagents to the test areas (Figures 1b and and2b).2b). In this communication, we demonstrate the method by detecting glucose and protein,[8] but the surface should be suitable for measuring many other analytes as well.[7] The glucose assay is based on the enzymatic oxidation of iodide to iodine,[9] where a color change from clear to brown is associated with the presence of glucose.[10] The protein assay is based on the color change of tetrabromophenol blue (TBPB) when it ionizes and binds to proteins;[11] a positive result in this case is indicated by a color change from yellow to blue.
For the glucose assay, we spotted 0.3 μL of a 0.6 M solution of potassium iodide, followed by 0.3 μL of a 1:5 horseradish peroxidase/glucose oxidase solution (15 units of protein per mL of solution). For the protein assay, we spotted 0.3 μL of a 250-mM citrate buffer (pH 1.8) in a well separate from the glucose assay, and then layered 0.3 μL of a 3.3 mM solution of tetrabromophenol blue (TBPB) in 95% ethanol over the citrate buffer. The spotted reagents were allowed to air dry at room temperature. This pre-loaded paper gave consistent results for the protein assay regardless of storage temperature and time (when stored for 15 d both at 0 °C and at 23 °C, wrapped in aluminum foil). The glucose assay was sensitive to storage conditions, and showed decreased signal for assays run 24 h after spotting the reagents (when stored at 23 °C); when stored at 0 °C, however, the glucose assay was as sensitive after day 15 as it was on day 1.
We measured artificial samples of glucose and protein in clinically relevant ranges (2.5-50 mM for glucose and 0.38-7.5 μM for bovine serum albumin (BSA))[12, 13] by dipping the bottom of each test strip in 5 μL of a pre-made test solution (Figure 2d). The fluid filled the entire pattern within ca. one minute, but the assays required 10-11 min for the paper to dry and for the color to fully develop.[14] In all cases, we observed color changes corresponding roughly in intensity to the amount of glucose and protein in the test samples, where the lowest concentrations define the lower limits to which these assays can be used (Figure 2e). For comparison, commercially-available dipsticks detect glucose at concentrations as low as 5 mM[7, 9] and protein as low as 0.75 μM;[6, 15] these limits indicate that these paper-based assays are comparable in sensitivity to commercial dipstick assays. Our assay format also allows for the measurement of multiple analytes.
This paper-based assay is suitable for measuring multiple samples in parallel and in a relatively short period of time. For example, in one trial, one researcher was able to run 20 different samples (all with 550 mM glucose and 75 μM BSA) within 7.5 min (followed by another 10.5 min for the color to fully develop). An 18-min assay of this type—one capable of measuring two analytes in 20 different sample—may be efficient enough to use in high-throughput screens of larger sample pools.
In the field, samples will not be measured under sterile conditions, and dust and dirt may contaminate the assays. The combination of paper and capillary action provides a mechanism for separating particulates from a biological fluid. As a demonstration, we purposely contaminated the artificial urine samples with quantities of dirt, plant pollen, and graphite powder at levels higher than we might expect to see in the samples in the field. These particulates do not move up the channels under the action of capillary wicking, and do not interfere with the assay (Figure 3).
Paper strips have been used in biomedical assays for decades because they offer an inexpensive platform for colorimetric chemical testing.[1] Patterned paper has characteristics that lead to miniaturized assays that run by capillary action (e.g., without external pumping), with small volumes of fluids. These methods suggest a path for the development of simple, inexpensive, and portable diagnostic assays that may be useful in remote settings, and in particular, in less-industrialized countries where simple assays are becoming increasingly important for detecting disease and monitoring health,[16, 17], for environmental monitoring, in veterinary and agricultural practice and for other applications.
2,580 citations
TL;DR: The progress made by lab-on-a-chip microtechnologies in recent years is analyzed, and the clinical and research areas in which they have made the greatest impact are discussed.
Abstract: Microfluidics, a technology characterized by the engineered manipulation of fluids at the submillimetre scale, has shown considerable promise for improving diagnostics and biology research. Certain properties of microfluidic technologies, such as rapid sample processing and the precise control of fluids in an assay, have made them attractive candidates to replace traditional experimental approaches. Here we analyse the progress made by lab-on-a-chip microtechnologies in recent years, and discuss the clinical and research areas in which they have made the greatest impact. We also suggest directions that biologists, engineers and clinicians can take to help this technology live up to its potential.
2,276 citations