Fabrication of bimetallic microfluidic surface-enhanced Raman scattering sensors on paper by screen printing

Au–Ag bimetallic microfluidic, dumbbell-shaped, surface enhanced Raman scattering (SERS) sensors were fabricated on cellulose paper by screen printing. These printed sensors rely on a sample droplet injection zone, and a SERS detection zone at either end of the dumbbell motif, fabricated by printing silver nanoparticles (Ag NPs) and gold nanoparticles (Au NPs) successively with microscale precision. The microfluidic channel was patterned using an insulating ink to connect these two zones and form a hydrophobic circuit. Owing to capillary action of paper in the millimeter-sized channels, the sensor could enable self-filtering of fluids to remove suspended particles within wastewater without pumping. This sensor also allows sensitive SERS detection, due to advantageous combination of the strong surface enhancement of Ag NPs and excellent chemical stability of Au NPs. The SERS performance of the sensors was investigated by employing the probe rhodamine 6G, a limit of detection (LOD) of 1.1 × 10⁻¹³ M and an enhancement factor of 8.6 × 10⁶ could be achieved. Moreover, the dumbbell-shaped bimetallic sensors exhibited good stability with SERS performance being maintained over 14 weeks in air, and high reproducibility with less than 15% variation in spot-to-spot SERS intensity. Using these dumbbell-shaped bimetallic sensors, substituted aromatic pollutants in wastewater samples could be quantitatively analyzed, which demonstrated their excellent capability for rapid trace pollutant detection in wastewater samples in the field without pre-separation.     

Progress in patterned paper sizing for fabrication of paper-based microfluidic sensors

In this paper, we report the progress in using paper sizing chemistry to fabricate patterned paper for chemical and biological sensing applications. Patterned paper sizing uses paper sizing agents to selectively hydrophobize certain area of a sheet. The hydrophilic-hydrophobic contrast of the pattern so created has an excellent ability to control capillary penetration of aqueous liquids in channels of the pattern. Incorporating this idea with digital ink jet printing technique, a new fabrication method of paper-based microfluidic devices is established. Ink jet printing can deliver biomolecules and chemicals with precision into the microfluidic patterns to form biological/chemical sensing sites within the patterns, forming the complete sensing devices. This study shows the potential of combining paper sizing chemistry and ink jet printing to produce paper-based sensors at low cost and at commercial volume.     

Use of a mobile phone for potentiostatic control with low cost paper-based microfluidic sensors

By exploiting its ability to play sounds, a mobile phone with suitable software installed can serve the basic functions of a potentiostat in controlling an applied potential to oxidise ECL-active molecules, while the resultant photonic signal is monitored using the camera in video mode. In combination with paper microfluidic sensors this opens significant new possibilities for low-cost, instrument-free sensing.     

USB powered microfluidic paper-based analytical devices

Microfluidic paper-based analytical devices (μPADs) allow user-friendly and portable chemical determinations, although they provide limited applicability due to insufficient sensitivity. Several approaches have been proposed to address poor sensitivity in μPADs, but they frequently require bulky equipment for power and/or read-outs. Universal serial buses (USB) are an attractive alternative to less portable power sources and are currently available in many common electronic devices. Here, USB-powered μPADs (USB μPADs) are proposed as a fusion of both technologies to improve performance without adding instrumental complexity. Two ITP USB μPADs were developed, both powered by a 5 V potential provided through standard USB ports. The first device was fabricated using the origami approach. Its operation was analyzed experimentally and numerically, yielding a two-order-of-magnitude sample focusing in 15 min. The second ITP USB μPAD is a novel design, which was numerically prototyped with the aim of handling larger sample volumes. The reservoirs were moved away from the ITP channel and capillary action was used to drive the sample and electrolytes to the separation zone, predicting 25-fold sample focusing in 10 min. USB μPADs are expected to be adopted by minimally-trained personnel in sensitive areas like resource-limited settings, the point-of-care and in emergencies.     

Reprint of: Use of a mobile phone for potentiostatic control with low cost paper-based microfluidic sensors

By exploiting its ability to play sounds, a mobile phone with suitable software installed can serve the basic functions of a potentiostat in controlling an applied potential to oxidise ECL-active molecules, while the resultant photonic signal is monitored using the camera in video mode. In combination with paper microfluidic sensors this opens significant new possibilities for low-cost, instrument-free sensing.     

Blood separation on microfluidic paper-based analytical devices

A microfluidic paper-based analytical device (μPAD) for the separation of blood plasma from whole blood is described. The device can separate plasma from whole blood and quantify plasma proteins in a single step. The μPAD was fabricated using the wax dipping method, and the final device was composed of a blood separation membrane combined with patterned Whatman No.1 paper. Blood separation membranes, LF1, MF1, VF1 and VF2 were tested for blood separation on the μPAD. The LF1 membrane was found to be the most suitable for blood separations when fabricating the μPAD by wax dipping. For blood separation, the blood cells (both red and white) were trapped on blood separation membrane allowing pure plasma to flow to the detection zone by capillary force. The LF1-μPAD was shown to be functional with human whole blood of 24-55% hematocrit without dilution, and effectively separated blood cells from plasma within 2 min when blood volumes of between 15-22 μL were added to the device. Microscopy was used to confirm that the device isolated plasma with high purity with no blood cells or cell hemolysis in the detection zone. The efficiency of blood separation on the μPAD was studied by plasma protein detection using the bromocresol green (BCG) colorimetric assay. The results revealed that protein detection on the μPAD was not significantly different from the conventional method (p > 0.05, pair t-test). The colorimetric measurement reproducibility on the μPAD was 2.62% (n = 10) and 5.84% (n = 30) for within-day and between day precision, respectively. Our proposed blood separation on μPAD has the potential for reducing turnaround time, sample volume, sample preparation and detection processes for clinical diagnosis and point-of care testing.     

Quantitative biomarker assay with microfluidic paper-based analytical devices

This article describes the use of microfluidic paper-based analytical devices (μPADs) to perform quantitative chemical assays with internal standards. MicroPADs are well-suited for colorimetric biochemical assays; however, errors can be introduced from the background color of the paper due to batch difference and age, and from color measurement devices. To reduce errors from these sources, a series of standard analyte solutions and the sample solution are assayed on a single device with multiple detection zones simultaneously; an analyte concentration calibration curve can thus be established from the standards. Since the μPAD design allows the colorimetric measurements of the standards and the sample to be conducted simultaneously and under the same condition, errors from the above sources can be minimized. The analytical approach reported in this work shows that μPADs can perform quantitative chemical analysis at very low cost.      

Integration of paper-based microfluidic devices with commercial electrochemical readers

The combination of simple Electrochemical Micro-Paper-based Analytical Devices (EμPADs) with commercially available glucometers allows rapid, quantitative electrochemical analysis of a number of compounds relevant to human health (e.g., glucose, cholesterol, lactate, and alcohol) in blood or urine.     

Use of multiple colorimetric indicators for paper-based microfluidic devices

We report here the use of multiple indicators for a single analyte for paper-based microfluidic devices (μPAD) in an effort to improve the ability to visually discriminate between analyte concentrations. In existing μPADs, a single dye system is used for the measurement of a single analyte. In our approach, devices are designed to simultaneously quantify analytes using multiple indicators for each analyte improving the accuracy of the assay. The use of multiple indicators for a single analyte allows for different indicator colors to be generated at different analyte concentration ranges as well as increasing the ability to better visually discriminate colors. The principle of our devices is based on the oxidation of indicators by hydrogen peroxide produced by oxidase enzymes specific for each analyte. Each indicator reacts at different peroxide concentrations and therefore analyte concentrations, giving an extended range of operation. To demonstrate the utility of our approach, the mixture of 4-aminoantipyrine and 3,5-dichloro-2-hydroxy-benzenesulfonic acid, o-dianisidine dihydrochloride, potassium iodide, acid black, and acid yellow were chosen as the indicators for simultaneous semi-quantitative measurement of glucose, lactate, and uric acid on a μPAD. Our approach was successfully applied to quantify glucose (0.5-20 mM), lactate (1-25 mM), and uric acid (0.1-7 mM) in clinically relevant ranges. The determination of glucose, lactate, and uric acid in control serum and urine samples was also performed to demonstrate the applicability of this device for biological sample analysis. Finally results for the multi-indicator and single indicator system were compared using untrained readers to demonstrate the improvements in accuracy achieved with the new system.     

Bladder cancer hunting: A microfluidic paper-based analytical device

Bladder cancer is the fourth most common cancer in men, and it is becoming a prevalent malignancy. Most of the regular clinical examinations are prompt evaluations with cystoscopy, renal function testing, which require high-precision instrument, well-trained operators, and high cost. In this study, a microfluidic paper-based analytical device (μPAD) was fabricated to detect nuclear matrix protein 22 (NMP22) and bladder cancer antigen (BTA) from the urine samples. Urine samples were collected from 11 bladder cancer patients and 10 well-beings as experiment and control groups, respectively, to verify the working efficiency of μPAD. A remarkable checkout efficiency of up to 90.91% was found from the results. Meanwhile, this method is feasible for home-based self-detection from urine samples within 10 min for the total process, which provides a new way for quick, economical, and convenient tumor diagnosis, prognosis evaluation, and drug response.     

Solvent colorimetric paper-based polydiacetylene sensors from diacetylene lipids

A well known unique property of polydiacetylenes (PDAs) is the colorimetric response to external stimuli making it one of the most studied conjugated polymers for sensing applications. Here we report the synthesis of a novel series of diacetylene acids from the condensation of pentacosa-10,12-diynylamine (PCDAmine) and dicarboxylic acid or its anhydrides. One of these diacetylene lipids, 4-(pentacosa-10,12-diynylamino)-4-oxobutanoic acid (PCDAS), is used in combination with pentacosa-10,12-diynoic acid (PCDA) for dropcasting on pieces of filter paper which are consequently irradiated by UV light to generate a paper based sensor array for solvent detection and identification. Upon the exposure to various types of organic solvents, the blue colored sensors colorimetrically respond to give different shades of colors between blue to red. The color patterns of the sensor array are recorded as RedGreenBlue (RGB) values and statistically analyzed by principal component analysis (PCA). The PCA score plot reveals that the array is capable of identifying eleven common organic solvents.     

Electrochemical immunoassay on a 3D microfluidic paper-based device

A high-throughput, simple, fast, low-cost and sensitive paper-based electrochemical immunodevice has been demonstrated based on a functionalized 3D paper-based device for point-of-care diagnosis.     

微流控纸芯片在环境分析检测中的应用

近年来,微流控纸芯片由于低成本、便携化、检测快等优点,在需要快速检测的环境分析领域中展现出了巨大的应用前景.该综述从微流控纸芯片在环境分析中的应用角度,总结归纳了微流控纸芯片在环境分析中的最新研究进展,并展望了其在未来的发展趋势与挑战.论文内容引用150余篇源于科学引文索引(SCI)与中文核心期刊中的相关论文.该综述包...     

Aptamer-based fluorometric determination of norovirus using a paper-based microfluidic device

Microchimica Acta - The authors describe a rapid and highly sensitive point-of-care device for rapid determination of noroviruses, a leading cause of acute gastroenteritis. The assay is based on...     

Determination of nitrite in saliva using microfluidic paper-based analytical devices

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 (μPAD), 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 μPADs 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 μmol L⁻¹ range with a limit of detection of 10 μmol L⁻¹ and a sensitivity of 47.5 AU [log (μmol 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.     

Uniform mixing in paper-based microfluidic systems using surface acoustic waves

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.     

Fabrication of dipolar colloid particles by microcontact printing

A novel technique for preparation of dipolar colloid particles has been developed which is based on microcontact printing of films of water-insoluble ionic surfactants onto monolayers of colloid particles of opposite surface charge.     

High throughput method for prototyping three-dimensional, paper-based microfluidic devices

This paper describes an efficient and high throughput method for fabricating three-dimensional (3D) paper-based microfluidic devices. The method avoids tedious alignment and assembly steps and eliminates a major bottleneck that has hindered the development of these types of devices. A single researcher now can prepare hundreds of devices within 1 h.     

Colorimetric determination of acidity constant using a paper-based microfluidic analytical device

Acid dissociation constant is an important chemical characteristic of organic and inorganic compounds and it affects both chemical properties and biological activities of the molecules. Herein, a very simple, fast and cost-effective method based on microfluidic technology has been reported for colorimetric determination of acidity constants. The designed device works based on pH-metric titration of colorful indicators followed by colorimetric measurements by a smart phone mobile device or a flatbed scanner. So, it does not need sophisticated instrumentation and is accomplished in a very short time (about 1 min). All titration steps are transferred on a star-like designed µPAD device: (1) spotting 0.3 µL buffers of different pHs at the end of the channels (reaction zones), (2) spotting a 30 µL portion of the indicator on the center of µPAD followed by movement of indicator solution toward the reaction zone by capillary action of the paper. The measured color change of the indicators at the reaction zone is fitted to the Henderson–Hasselbalch equation, through which acidity constants are calculated. The performance of the device was evaluated by measuring acidity constant of 4 indicators including bromothymol blue, bromocresol green, bromocresol purple and phenolphthalein. A very close agreement was achieved between those measured by the suggested device here and the previously reported values. The reproducibility of this method was lower than 5% for relative standard deviation of three replicate measurements.     

A microfluidic paper-based analytical device for rapid quantification of particulate chromium

Occupational exposure to Cr is concerning because of its myriad of health effects. Assessing chromium exposure is also cost and resource intensive because the analysis typically uses sophisticated instrumental techniques like inductively coupled plasma-mass spectrometry (ICP-MS). Here, we report a novel, simple, inexpensive microfluidic paper-based analytical device (μPAD) for measuring total Cr in airborne particulate matter. In the μPAD, tetravalent cerium (Ce(IV)) was used in a pretreatment zone to oxidize all soluble Cr to Cr(VI). After elution to the detection zone, Cr(VI) reacts with 1,5-diphenylcarbazide (1,5-DPC) forming 1,5-diphenylcarbazone (DPCO) and Cr(III). The resulting Cr(III) forms a distinct purple colored complex with the DPCO. As proof-of-principle, particulate matter (PM) collected on a sample filter was analyzed with the μPAD to quantify the mass of total Cr. A log-linear working range (0.23–3.75 μg; r² = 0.998) between Cr and color intensity was obtained with a detection limit of 0.12 μg. For validation, a certified reference containing multiple competing metals was analyzed. Quantitative agreement was obtained between known Cr levels in the sample and the Cr measured using the μPAD.