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1

Coltro, Wendell. "Paper-based microfluidics: What can we expect?" Brazilian Journal of Analytical Chemistry 9, no. 37 (October 5, 2022): 11–13. http://dx.doi.org/10.30744/brjac.2179-3425.point-of-view-wktcoltro.n37.

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In the last three decades, the scientific community has observed exponential growth in the development of microfluidic platforms and their use for applications in different fields. The noticeable advances are attributed to the advantages provided by miniaturization.1 In summary, the downscaling of analytical devices has offered attractive features, including reduced consumption of samples and reagents, short analysis time, and minimal waste generation. In addition, the possibility to perform multiplexed assays in portable devices without bulky instrumentation is another attractive feature that boosted the investigation of miniaturized devices with the capability to be tested directly in the point-of-care (POC). Due to the sample volume required to proceed with a chemical analysis on a microscale (typically in the µL range), a complete understanding of the fluid control and handle on channels defined in micrometric dimensions was necessary, giving rise to the science known as microfluidics.2 Many platforms including rigid and flexible materials can be explored for manufacturing microfluidic networks. Among all the substrates reported in the literature, the “paper” is by far the simplest and cheapest material currently employed for the development of microfluidic devices dedicated to analytical, bioanalytical, biomedical, environmental, food, and forensics applications.3 For many readers, the first question is why paper is used instead of other materials such as glass. Well, glass is a rigid material, and microchannel engraving requires cleanroom facilities, photolithographic patterning, developing steps, and thermal sealing. This standard protocol makes use of sophisticated instrumentation, and it is not readily available to most researchers. In this way, paper emerges as a simple and alternative material to be used for microfluidics. One of the major benefits of microfluidics refers to the sample-in-answer-out capability, which requires a fully automated fluid control to allow sample preparation, analytical separation, and detection stages. The fluid-controlled handling inside microchannels opens the possibility to integrate multiple analytical tasks in parallel into a high-throughput device. Considering these possibilities, it is worthwhile reflecting on how paper can be used to transport and handle a fluid. Paper is currently one of the most widely used raw materials in research laboratories. Its use has been explored for over a century. In 1949, a paper containing barriers made of paraffin was exploited to successfully demonstrate the elution of pigments within a channel based on the sample diffusion process.4 In 2007, paper was reinvented by the Whitesides group as a globally affordable substrate material for the development of miniaturized analytical platforms.5 Since this period, paper has become an increasingly popular platform for multipurpose applications. Probably, its broad use is associated with advantages over other conventional substrates, as well as the fabrication technologies and the concept of “do-it-yourself microfluidics”.6 In comparison with other conventional materials, like glass and silicon, paper is relatively inexpensive, globally affordable, lightweight, bioactive, and easy to transport and store. Furthermore, paper-based products can be easily found as kitchen towels, coffee filters, blood separation paper, filter paper, office paper, and others. How does one create an analytical device on paper? This question is a common inquiry of undergraduate and graduate students when starting to study microfluidics. Initially, it is important to emphasize that paper substrates have a porous structure, which facilitates the spontaneous transport of fluid by capillarity. The wicking speed of liquid on a microchannel defined on paper depends on pore size and paper thickness. Microfluidic networks can be created on paper using hydrophobic barriers or defined by cutting approaches, which make it possible to obtain single paper strips or more complex designs containing interconnected microchannels for multiplexed assays3. In this regard, lithography-based fabrication methods were first employed to demonstrate the potential of paper substrates for developing microfluidic structures. However, due to the contradictory view in terms of cost, many other alternative approaches were developed to make affordable and popular the concept and potential of paper-based microfluidics. Thanks to the researchers´ creativity and paper versatility, the fabrication of microfluidic paper-based analytical devices is feasible through direct printing using wax, inkjet, or laser printing processes or even by manual protocols (freehand drawing or spraying) involving pens, pencils, stamps, scissors, scholar’s glue, or lacquer resins. Paper-based microfluidic devices, including examples of simple spot test arrays, chemosensors, biosensors, electrochemical sensors, wearable devices, and lateral flow assays, have been found in the main scientific Journals associated with analytical and bioanalytical chemistry.7-10 In the academy, most of the advances seen in the recent literature have demonstrated improvements in terms of durability, shelf life, reproducibility, robustness, and analytical reliability, making paper-based microfluidic devices promising and emerging candidates to gain space in the market as alternatives to other materials. In this way, entrepreneurship and innovation deserve to be highlighted and emerge as the focus of many researchers interested in opening their businesses or company. The bridge between the academy and the productive sector depends on investment and engagement to overcome administrative and legal bureaucracies not only to open a company but also to maintain it in full operating mode. The commercialization of microfluidic devices has been constantly growing. In the last three years, for example, many companies located in different countries have shipped over five hundred million units/year, clearly demonstrating the potential of microfluidic devices for different application areas including drug delivery, flow chemistry, analytical devices, pharmaceutical and life science, point-of-care diagnostics and clinical and veterinary settings.11 Considering the advantages of paper-based materials, what can we expect in the coming years? Commercially available products with sample-in-answer-out capabilities are highly desirable to be found more and more in the market. Due to the global affordability of paper as well as its attractive features to create microfluidic and sensor prototypes, it is possible to see a real niche full of possibilities for success. In this view, it is time to try our best and make commercially available paper-based products like wearable sensors or lateral flow devices to monitor clinically relevant compounds in different biological fluids like blood, urine, serum, sweat, saliva, and tears. This may be accelerated by spin-offs or startups independently or in partnership with well-established companies. In other words, it is time to innovate and transform an idea into a commercial product with a societal impact. The interface between rapid tests and immediate responses directly by the end user are highly desirable features in the market and risk analysis. The SARS-CoV-2 worldwide outbreak is the most recent example that science can offer the possibility to obtain clinical diagnostics in a matter of minutes, allowing one to decide on the ideal treatment or, in this case, social isolation to prevent the virus transmission. Tens of self-diagnostics kits based on paper strips for SARS-CoV-2 are already commercially available for society in drug shops, hospitals, or healthcare clinics. Similar strategies may be seen shortly for Monkeypox or other global outbreaks.
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2

Catalan-Carrio, Raquel, Tugce Akyazi, Lourdes Basabe-Desmonts, and Fernando Benito-Lopez. "Predicting Dimensions in Microfluidic Paper Based Analytical Devices." Sensors 21, no. 1 (December 26, 2020): 101. http://dx.doi.org/10.3390/s21010101.

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The main problem for the expansion of the use of microfluidic paper-based analytical devices and, thus, their mass production is their inherent lack of fluid flow control due to its uncontrolled fabrication protocols. To address this issue, the first step is the generation of uniform and reliable microfluidic channels. The most common paper microfluidic fabrication method is wax printing, which consists of two parts, printing and heating, where heating is a critical step for the fabrication of reproducible device dimensions. In order to bring paper-based devices to success, it is essential to optimize the fabrication process in order to always get a reproducible device. Therefore, the optimization of the heating process and the analysis of the parameters that could affect the final dimensions of the device, such as its shape, the width of the wax barrier and the internal area of the device, were performed. Moreover, we present a method to predict reproducible devices with controlled working areas in a simple manner.
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3

Meredith, Nathan A., Casey Quinn, David M. Cate, Thomas H. Reilly, John Volckens, and Charles S. Henry. "Paper-based analytical devices for environmental analysis." Analyst 141, no. 6 (2016): 1874–87. http://dx.doi.org/10.1039/c5an02572a.

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4

Juang, Yi-Je, and Shu-Kai Hsu. "Fabrication of Paper-Based Microfluidics by Spray on Printed Paper." Polymers 14, no. 3 (February 8, 2022): 639. http://dx.doi.org/10.3390/polym14030639.

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Since the monumental work conducted by Whitesides et al. in 2007, research and development of paper-based microfluidics has been widely carried out, with its applications ranging from chemical and biological detection and analysis, to environmental monitoring and food-safety inspection. Paper-based microfluidics possesses several competitive advantages over other substrate materials, such as being simple, inexpensive, power-free for fluid transport, lightweight, biodegradable, biocompatible, good for colorimetric tests, flammable for easy disposal of used paper-based diagnostic devices by incineration, and being chemically modifiable. Myriad methods have been demonstrated to fabricate paper-based microfluidics, such as solid wax printing, cutting, photolithography, microembossing, etc. In this study, fabrication of paper-based microfluidics was demonstrated by spray on the printed paper. Different from the normally used filter papers, printing paper, which is much more accessible and cheaper, was utilized as the substrate material. The toner was intended to serve as the mask and the patterned hydrophobic barrier was formed after spray and heating. The processing parameters such as toner coverage on the printing paper, properties of the hydrophobic spray, surface properties of the paper, and curing temperature and time were systematically investigated. It was found that, after repetitive printing four times, the toner was able to prevent the hydrophobic spray (the mixture of PDMS and ethyl acetate) from wicking through the printing paper. The overall processing time for fabrication of paper-based microfluidic chips was less than 10 min and the technique is potentially scalable. Glucose detection was conducted using the microfluidic paper-based analytical devices (µPADs) as fabricated and a linear relationship was obtained between 1 and 10 mM.
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5

Ozer, Tugba, Catherine McMahon, and Charles S. Henry. "Advances in Paper-Based Analytical Devices." Annual Review of Analytical Chemistry 13, no. 1 (June 12, 2020): 85–109. http://dx.doi.org/10.1146/annurev-anchem-061318-114845.

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Microfluidic paper-based analytical devices (μPADs) are the newest generation of lab-on-a-chip devices and have made significant strides in both our understanding of fundamental behavior and performance characteristics and expansion of their applications. μPADs have become useful analytical techniques for environmental analysis in addition to their more common application as medical point-of-care devices. Although the most common method for device fabrication is wax printing, numerous other techniques exist and have helped address factors ranging from solvent compatibility to improved device function. This review highlights recent reports of fabrication and design, modes of detection, and broad applications of μPADs. Such advances have enabled μPADs to be used in field and laboratory studies to address critical needs in fast, cheaper measurement technologies.
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6

Lim, Jafry, and Lee. "Fabrication, Flow Control, and Applications of Microfluidic Paper-Based Analytical Devices." Molecules 24, no. 16 (August 7, 2019): 2869. http://dx.doi.org/10.3390/molecules24162869.

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Paper-based microfluidic devices have advanced significantly in recent years as they are affordable, automated with capillary action, portable, and biodegradable diagnostic platforms for a variety of health, environmental, and food quality applications. In terms of commercialization, however, paper-based microfluidics still have to overcome significant challenges to become an authentic point-of-care testing format with the advanced capabilities of analyte purification, multiplex analysis, quantification, and detection with high sensitivity and selectivity. Moreover, fluid flow manipulation for multistep integration, which involves valving and flow velocity control, is also a critical parameter to achieve high-performance devices. Considering these limitations, the aim of this review is to (i) comprehensively analyze the fabrication techniques of microfluidic paper-based analytical devices, (ii) provide a theoretical background and various methods for fluid flow manipulation, and iii) highlight the recent detection techniques developed for various applications, including their advantages and disadvantages.
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7

Channon, Robert B., Michael P. Nguyen, Alexis G. Scorzelli, Elijah M. Henry, John Volckens, David S. Dandy, and Charles S. Henry. "Rapid flow in multilayer microfluidic paper-based analytical devices." Lab on a Chip 18, no. 5 (2018): 793–802. http://dx.doi.org/10.1039/c7lc01300k.

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Multilayer paper devices are used to generate fast flow rates (1.56 cm s−1) which are 145-fold quicker than classical single-layer paper device designs. These self-pumping devices are demonstrated for the sequential injection stripping analysis of cadmium.
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8

Li, Qi, Xingchen Zhou, Qian Wang, Wenfang Liu, and Chuanpin Chen. "Microfluidics for COVID-19: From Current Work to Future Perspective." Biosensors 13, no. 2 (January 20, 2023): 163. http://dx.doi.org/10.3390/bios13020163.

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Spread of coronavirus disease 2019 (COVID-19) has significantly impacted the public health and economic sectors. It is urgently necessary to develop rapid, convenient, and cost-effective point-of-care testing (POCT) technologies for the early diagnosis and control of the plague’s transmission. Developing POCT methods and related devices is critical for achieving point-of-care diagnosis. With the advantages of miniaturization, high throughput, small sample requirements, and low actual consumption, microfluidics is an essential technology for the development of POCT devices. In this review, according to the different driving forces of the fluid, we introduce the common POCT devices based on microfluidic technology on the market, including paper-based microfluidic, centrifugal microfluidic, optical fluid, and digital microfluidic platforms. Furthermore, various microfluidic-based assays for diagnosing COVID-19 are summarized, including immunoassays, such as ELISA, and molecular assays, such as PCR. Finally, the challenges of and future perspectives on microfluidic device design and development are presented. The ultimate goals of this paper are to provide new insights and directions for the development of microfluidic diagnostics while expecting to contribute to the control of COVID-19.
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9

Mentele, Mallory M., Josephine Cunningham, Kirsten Koehler, John Volckens, and Charles S. Henry. "Microfluidic Paper-Based Analytical Device for Particulate Metals." Analytical Chemistry 84, no. 10 (April 26, 2012): 4474–80. http://dx.doi.org/10.1021/ac300309c.

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10

Kugimiya, Akimitsu, Akane Fujikawa, Xiao Jiang, Z. Hugh Fan, Toshikazu Nishida, Jiro Kohda, Yasuhisa Nakano, and Yu Takano. "Microfluidic Paper-Based Analytical Device for Histidine Determination." Applied Biochemistry and Biotechnology 192, no. 3 (June 27, 2020): 812–21. http://dx.doi.org/10.1007/s12010-020-03365-z.

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11

Amin, Reza, Fariba Ghaderinezhad, Caleb Bridge, Mikail Temirel, Scott Jones, Panteha Toloueinia, and Savas Tasoglu. "Pushing the Limits of Spatial Assay Resolution for Paper-Based Microfluidics Using Low-Cost and High-Throughput Pen Plotter Approach." Micromachines 11, no. 6 (June 24, 2020): 611. http://dx.doi.org/10.3390/mi11060611.

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To transform from reactive to proactive healthcare, there is an increasing need for low-cost and portable assays to continuously perform health measurements. The paper-based analytical devices could be a potential fit for this need. To miniaturize the multiplex paper-based microfluidic analytical devices and minimize reagent use, a fabrication method with high resolution along with low fabrication cost should be developed. Here, we present an approach that uses a desktop pen plotter and a high-resolution technical pen for plotting high-resolution patterns to fabricate miniaturized paper-based microfluidic devices with hundreds of detection zones to conduct different assays. In order to create a functional multiplex paper-based analytical device, the hydrophobic solution is patterned on the cellulose paper and the reagents are deposited in the patterned detection zones using the technical pens. We demonstrated the effect of paper substrate thickness on the resolution of patterns by investigating the resolution of patterns on a chromatography paper with altered effective thickness. As the characteristics of the cellulose paper substrate such as thickness, resolution, and homogeneity of pore structure affect the obtained patterning resolution, we used regenerated cellulose paper to fabricate detection zones with a diameter as small as 0.8 mm. Moreover, in order to fabricate a miniaturized multiplex paper-based device, we optimized packing of the detection zones. We also showed the capability of the presented method for fabrication of 3D paper-based microfluidic devices with hundreds of detection zones for conducting colorimetric assays.
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12

Lai, Xiaochen, Yanfei Sun, Mingpeng Yang, and Hao Wu. "Rubik’s Cube as Reconfigurable Microfluidic Platform for Rapid Setup and Switching of Analytical Devices." Micromachines 13, no. 12 (November 24, 2022): 2054. http://dx.doi.org/10.3390/mi13122054.

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Microfluidics technology plays an important role in modern analytical instruments, while the modular design of microfluidics facilitates the reconfiguration of analytical instrument functions, making it possible to deploy on-demand systems in the field. However, modular design also faces the challenges such as connection reliability and reconfiguration convenience. Inspired by the self-locking structure of the Rubik’s cube, a modular, reconfigurable microfluidic instrument architecture is proposed in this paper. The system has a self-locking structure of Rubik’s cube components and an O-ring-based alignment and sealing mechanism, which enables reliable interconnection and rapid rearrangement of microfluidic modules by simply rotating the faces of the microfluidic cube. In addition, the system is capable of integrating a variety of customized modules to perform analysis tasks. A proof-of-concept application of detecting multiple pollutants in water is demonstrated to show the reconfigurable characteristics of the system. The findings of this paper provide a new idea for the design of microfluidic analytical instrument architectures.
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13

Männel, Max J., Elif Baysak, and Julian Thiele. "Fabrication of Microfluidic Devices for Emulsion Formation by Microstereolithography." Molecules 26, no. 9 (May 10, 2021): 2817. http://dx.doi.org/10.3390/molecules26092817.

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Droplet microfluidics—the art and science of forming droplets—has been revolutionary for high-throughput screening, directed evolution, single-cell sequencing, and material design. However, traditional fabrication techniques for microfluidic devices suffer from several disadvantages, including multistep processing, expensive facilities, and limited three-dimensional (3D) design flexibility. High-resolution additive manufacturing—and in particular, projection micro-stereolithography (PµSL)—provides a promising path for overcoming these drawbacks. Similar to polydimethylsiloxane-based microfluidics 20 years ago, 3D printing methods, such as PµSL, have provided a path toward a new era of microfluidic device design. PµSL greatly simplifies the device fabrication process, especially the access to truly 3D geometries, is cost-effective, and it enables multimaterial processing. In this review, we discuss both the basics and recent innovations in PµSL; the material basis with emphasis on custom-made photopolymer formulations; multimaterial 3D printing; and, 3D-printed microfluidic devices for emulsion formation as our focus application. Our goal is to support researchers in setting up their own PµSL system to fabricate tailor-made microfluidics.
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14

Mabbott, Samuel, Syrena C. Fernandes, Monika Schechinger, Gerard L. Cote, Karen Faulds, Charles R. Mace, and Duncan Graham. "Detection of cardiovascular disease associated miR-29a using paper-based microfluidics and surface enhanced Raman scattering." Analyst 145, no. 3 (2020): 983–91. http://dx.doi.org/10.1039/c9an01748h.

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15

Meredith, Nathan A., John Volckens, and Charles S. Henry. "Paper-based microfluidics for experimental design: screening masking agents for simultaneous determination of Mn(ii) and Co(ii)." Analytical Methods 9, no. 3 (2017): 534–40. http://dx.doi.org/10.1039/c6ay02798a.

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16

Prasad, Alisha, Tiffany Tran, and Manas Gartia. "Multiplexed Paper Microfluidics for Titration and Detection of Ingredients in Beverages." Sensors 19, no. 6 (March 14, 2019): 1286. http://dx.doi.org/10.3390/s19061286.

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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.
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17

Sameenoi, Yupaporn, Pantila Panymeesamer, Natcha Supalakorn, Kirsten Koehler, Orawon Chailapakul, Charles S. Henry, and John Volckens. "Microfluidic Paper-Based Analytical Device for Aerosol Oxidative Activity." Environmental Science & Technology 47, no. 2 (December 21, 2012): 932–40. http://dx.doi.org/10.1021/es304662w.

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18

Jiang, Qingyun, Tingting Han, Haijun Ren, Aziz Ur Rehman Aziz, Na Li, Hangyu Zhang, Zhengyao Zhang, and Bo Liu. "Bladder cancer hunting: A microfluidic paper‐based analytical device." ELECTROPHORESIS 41, no. 16-17 (June 26, 2020): 1509–16. http://dx.doi.org/10.1002/elps.202000080.

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19

Zhang, Yuxin, Tim Cole, Guolin Yun, Yuxing Li, Qianbin Zhao, Hongda Lu, Jiahao Zheng, Weihua Li, and Shi-Yang Tang. "Modular and Self-Contained Microfluidic Analytical Platforms Enabled by Magnetorheological Elastomer Microactuators." Micromachines 12, no. 6 (May 23, 2021): 604. http://dx.doi.org/10.3390/mi12060604.

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Portability and low-cost analytic ability are desirable for point-of-care (POC) diagnostics; however, current POC testing platforms often require time-consuming multiple microfabrication steps and rely on bulky and costly equipment. This hinders the capability of microfluidics to prove its power outside of laboratories and narrows the range of applications. This paper details a self-contained microfluidic device, which does not require any external connection or tubing to deliver insert-and-use image-based analysis. Without any microfabrication, magnetorheological elastomer (MRE) microactuators including pumps, mixers and valves are integrated into one modular microfluidic chip based on novel manipulation principles. By inserting the chip into the driving and controlling platform, the system demonstrates sample preparation and sequential pumping processes. Furthermore, due to the straightforward fabrication process, chips can be rapidly reconfigured at a low cost, which validates the robustness and versatility of an MRE-enabled microfluidic platform as an option for developing an integrated lab-on-a-chip system.
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20

He, Mengyuan, and Zhihong Liu. "Paper-Based Microfluidic Device with Upconversion Fluorescence Assay." Analytical Chemistry 85, no. 24 (December 5, 2013): 11691–94. http://dx.doi.org/10.1021/ac403693g.

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21

Bleul, Regina, Marion Ritzi-Lehnert, Julian Höth, Nico Scharpfenecker, Ines Frese, Dominik Düchs, Sabine Brunklaus, Thomas E. Hansen-Hagge, Franz-Josef Meyer-Almes, and Klaus S. Drese. "Compact, cost-efficient microfluidics-based stopped-flow device." Analytical and Bioanalytical Chemistry 399, no. 3 (November 30, 2010): 1117–25. http://dx.doi.org/10.1007/s00216-010-4446-5.

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22

Hassan, Sammer-ul, and Xunli Zhang. "Microfluidics as an Emerging Platform for Tackling Antimicrobial Resistance (AMR): A Review." Current Analytical Chemistry 16, no. 1 (January 8, 2020): 41–51. http://dx.doi.org/10.2174/1573411015666181224145845.

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Background: Antimicrobial resistance (AMR) occurs when microbes become resistant to antibiotics causing complications and limited treatment options. AMR is more significant where antibiotics use is excessive or abusive and the strains of bacteria become resistant to antibiotic treatments. Current technologies for bacteria and its resistant strains identification and antimicrobial susceptibility testing (AST) are mostly central-lab based in hospitals, which normally take days to weeks to get results. These tools and procedures are expensive, laborious and skills based. There is an ever-increasing demand for developing point-of-care (POC) diagnostics tools for rapid and near patient AMR testing. Microfluidics, an important and fundamental technique to develop POC devices, has been utilized to tackle AMR in healthcare. This review mainly focuses on the current development in the field of microfluidics for rapid AMR testing. Method: Due to the limitations of conventional AMR techniques, microfluidic-based platforms have been developed for better understandings of bacterial resistance, smart AST and minimum inhibitory concentration (MIC) testing tools and development of new drugs. This review aims to summarize the recent development of AST and MIC testing tools in different formats of microfluidics technology. Results: Various microfluidics devices have been developed to combat AMR. Miniaturization and integration of different tools has been attempted to produce handheld or standalone devices for rapid AMR testing using different formats of microfluidics technology such as active microfluidics, droplet microfluidics, paper microfluidics and capillary-driven microfluidics. Conclusion: Current conventional AMR detection technologies provide time-consuming, costly, labor-intensive and central lab-based solutions, limiting their applications. Microfluidics has been developed for decades and the technology has emerged as a powerful tool for POC diagnostics of antimicrobial resistance in healthcare providing, simple, robust, cost-effective and portable diagnostics. The success has been reported in research articles; however, the potential of microfluidics technology in tackling AMR has not been fully achieved in clinical settings.
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23

Zhou, Cai Bin, Yun Zhang, Shang Wang Le, Jin Fang Nie, Ting Zhang, Fang Liu, and Jian Ping Li. "Fabrication of Paper-Based Microfluidics by Single-Step Wax Printing for Portable Multianalyte Bioassays." Advanced Materials Research 881-883 (January 2014): 503–8. http://dx.doi.org/10.4028/www.scientific.net/amr.881-883.503.

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In this paper, we initially report a new type of wax printing method for rapid fabrication of microfluidic devices in paper using a commercially available, cheap, minitype (home-use) CO2laser engraving machine. This method combines the two core operations commonly involved in all previous wax printing methods, namely the printing and heating (melting) of wax patterns into one operation of engraving home-made wax slice (put in contact with the surface of paper) by laser. The heat produced by the laser makes the wax being engraved melt and then spread into paper to form complete hydrophobic barriers which are used to define the hydrophilic flow channels or separate test microzones. Under the optimized experimental conditions, a typical device on a 3 cm × 3 cm piece of paper could be fabricated separately within ~320 sec and is ready for use once the engraving process is completed. The fabrication resolution and multiplexed analytical capability of the wax-patterned paper were additionally characterized.
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24

Atabakhsh, Saeed, Zahra Latifi Namin, and Shahin Jafarabadi Ashtiani. "Paper-based resistive heater with accurate closed-loop temperature control for microfluidics paper-based analytical devices." Microsystem Technologies 24, no. 9 (April 7, 2018): 3915–24. http://dx.doi.org/10.1007/s00542-018-3891-5.

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25

Ramana, Lakshmi Narashimhan, Santosh S. Mathapati, Nitin Salvi, M. V. Khadilkar, Anita Malhotra, Vishal Santra, and Tarun Kumar Sharma. "A paper microfluidic device based colorimetric sensor for the detection and discrimination of elapid versus viper envenomation." Analyst 147, no. 4 (2022): 685–94. http://dx.doi.org/10.1039/d1an01698a.

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26

Evard, Hanno, Hans Priks, Indrek Saar, Heili Aavola, Tarmo Tamm, and Ivo Leito. "A New Direction in Microfluidics: Printed Porous Materials." Micromachines 12, no. 6 (June 8, 2021): 671. http://dx.doi.org/10.3390/mi12060671.

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In this work, the feasibility of a novel direction for microfluidics is studied by demonstrating a set of new methods to fabricate microfluidic systems. Similarly to microfluidic paper-based analytical devices, porous materials are being used. However, alternative porous materials and different printing methods are used here to give the material the necessary pattern to act as a microfluidic system. In this work, microfluidic systems were produced by the following three separate methods: (1) by curing a porous monolithic polymer sheet into a necessary pattern with photolithography, (2) by screen printing silica gel particles with gypsum, and (3) by dispensing silica gel particles with polyvinyl acetate binder using a modified 3D printer. Different parameters of the printed chips were determined (strength of the printed material, printing accuracy, printed material height, wetting characteristics, repeatability) to evaluate whether the printed chips were suitable for use in microfluidics. All three approaches were found to be suitable, and therefore the novel approach to microfluidics was successfully demonstrated.
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27

Buser, Joshua R., Samantha A. Byrnes, Caitlin E. Anderson, Arielle J. Howell, Peter C. Kauffman, Joshua D. Bishop, Maxwell H. Wheeler, Sujatha Kumar, and Paul Yager. "Understanding partial saturation in paper microfluidics enables alternative device architectures." Analytical Methods 11, no. 3 (2019): 336–45. http://dx.doi.org/10.1039/c8ay01977k.

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Zhang, Lina, Yanhu Wang, Chao Ma, Panpan Wang, and Mei Yan. "Self-powered sensor for Hg2+detection based on hollow-channel paper analytical devices." RSC Advances 5, no. 31 (2015): 24479–85. http://dx.doi.org/10.1039/c4ra14154g.

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In this work, a novel and effective self-powered device was introduced in a microfluidic paper-based analytical device (μ-PAD) with hollow channels to transport fluids for mercury ion (Hg2+) detection.
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29

Kim, Uihwan, Byeolnim Oh, Jiyeon Ahn, Sangwook Lee, and Younghak Cho. "Inertia–Acoustophoresis Hybrid Microfluidic Device for Rapid and Efficient Cell Separation." Sensors 22, no. 13 (June 22, 2022): 4709. http://dx.doi.org/10.3390/s22134709.

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In this paper, we proposed an integrated microfluidic device that could demonstrate the non-contact, label-free separation of particles and cells through the combination of inertial microfluidics and acoustophoresis. The proposed device integrated two microfluidic chips which were a PDMS channel chip on top of the silicon-based acoustofluidic chip. The PDMS chip worked by prefocusing the particles/cells through inducing the inertial force of the channel structure. The connected acoustofluidic chips separated particles based on their size through an acoustic radiation force. In the serpentine-shaped PDMS chip, particles formed two lines focusing in the channel, and a trifugal-shaped acoustofluidic chip displaced and separated particles, in which larger particles focused on the central channel and smaller ones moved to the side channels. The simultaneous fluidic works allowed high-efficiency particle separation. Using this novel acoustofluidic device with an inertial microchannel, the separation of particles and cells based on their size was presented and analyzed, and the efficiency of the device was shown. The device demonstrated excellent separation performance with a high recovery ratio (up to 96.3%), separation efficiency (up to 99%), and high volume rate (>100 µL/min). Our results showed that integrated devices could be a viable alternative to current cell separation based on their low cost, reduced sample consumption and high throughput capability.
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Temirel, Mikail, Sajjad Rahmani Dabbagh, and Savas Tasoglu. "Hemp-Based Microfluidics." Micromachines 12, no. 2 (February 12, 2021): 182. http://dx.doi.org/10.3390/mi12020182.

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Hemp is a sustainable, recyclable, and high-yield annual crop that can be used to produce textiles, plastics, composites, concrete, fibers, biofuels, bionutrients, and paper. The integration of microfluidic paper-based analytical devices (µPADs) with hemp paper can improve the environmental friendliness and high-throughputness of µPADs. However, there is a lack of sufficient scientific studies exploring the functionality, pros, and cons of hemp as a substrate for µPADs. Herein, we used a desktop pen plotter and commercial markers to pattern hydrophobic barriers on hemp paper, in a single step, in order to characterize the ability of markers to form water-resistant patterns on hemp. In addition, since a higher resolution results in densely packed, cost-effective devices with a minimized need for costly reagents, we examined the smallest and thinnest water-resistant patterns plottable on hemp-based papers. Furthermore, the wicking speed and distance of fluids with different viscosities on Whatman No. 1 and hemp papers were compared. Additionally, the wettability of hemp and Whatman grade 1 paper was compared by measuring their contact angles. Besides, the effects of various channel sizes, as well as the number of branches, on the wicking distance of the channeled hemp paper was studied. The governing equations for the wicking distance on channels with laser-cut and hydrophobic side boundaries are presented and were evaluated with our experimental data, elucidating the applicability of the modified Washburn equation for modeling the wicking distance of fluids on hemp paper-based microfluidic devices. Finally, we validated hemp paper as a substrate for the detection and analysis of the potassium concentration in artificial urine.
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Davic, Andrew, and Michael Cascio. "Development of a Microfluidic Platform for Trace Lipid Analysis." Metabolites 11, no. 3 (February 24, 2021): 130. http://dx.doi.org/10.3390/metabo11030130.

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The inherent trace quantity of primary fatty acid amides found in biological systems presents challenges for analytical analysis and quantitation, requiring a highly sensitive detection system. The use of microfluidics provides a green sample preparation and analysis technique through small-volume fluidic flow through micron-sized channels embedded in a polydimethylsiloxane (PDMS) device. Microfluidics provides the potential of having a micro total analysis system where chromatographic separation, fluorescent tagging reactions, and detection are accomplished with no added sample handling. This study describes the development and the optimization of a microfluidic-laser induced fluorescence (LIF) analysis and detection system that can be used for the detection of ultra-trace levels of fluorescently tagged primary fatty acid amines. A PDMS microfluidic device was designed and fabricated to incorporate droplet-based flow. Droplet microfluidics have enabled on-chip fluorescent tagging reactions to be performed quickly and efficiently, with no additional sample handling. An optimized LIF optical detection system provided fluorescently tagged primary fatty acid amine detection at sub-fmol levels (436 amol). The use of this LIF detection provides unparalleled sensitivity, with detection limits several orders of magnitude lower than currently employed LC-MS techniques, and might be easily adapted for use as a complementary quantification platform for parallel MS-based omics studies.
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Jiang, Yan, Zhenxia Hao, Qiaohong He, and Hengwu Chen. "A simple method for fabrication of microfluidic paper-based analytical devices and on-device fluid control with a portable corona generator." RSC Advances 6, no. 4 (2016): 2888–94. http://dx.doi.org/10.1039/c5ra23470k.

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Cate, David M., Scott D. Noblitt, John Volckens, and Charles S. Henry. "Multiplexed paper analytical device for quantification of metals using distance-based detection." Lab on a Chip 15, no. 13 (2015): 2808–18. http://dx.doi.org/10.1039/c5lc00364d.

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Multiplexed detection of Ni, Cu, and Fe from particulate air pollution with paper-based microfluidic devices is described. Analysis is simple, inexpensive, and does not require any external instrumentation.
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Raj, Nikhil, Victor Breedveld, and Dennis W. Hess. "Flow control in fully enclosed microfluidics paper based analytical devices using plasma processes." Sensors and Actuators B: Chemical 320 (October 2020): 128606. http://dx.doi.org/10.1016/j.snb.2020.128606.

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35

Kudo, Hiroko, Kento Maejima, Yuki Hiruta, and Daniel Citterio. "Microfluidic Paper-Based Analytical Devices for Colorimetric Detection of Lactoferrin." SLAS TECHNOLOGY: Translating Life Sciences Innovation 25, no. 1 (October 28, 2019): 47–57. http://dx.doi.org/10.1177/2472630319884031.

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Lactoferrin is an abundant glycoprotein in human body fluids and is known as a biomarker for various diseases. Therefore, point-of-care testing (POCT) for lactoferrin is of interest. Microfluidic paper-based analytical devices (µPADs) have gained a lot of attention as next-generation POCT device candidates, due to their inexpensiveness, operational simplicity, and being safely disposable. This work presents a colorimetric sensing approach for quantitative lactoferrin analysis. The detection mechanism takes advantage of the high affinity of lactoferrin to ferric ions (Fe3+). Lactoferrin is able to displace an indicator from a colorimetric 2-(5-bromo-2-pyridylazo)-5-diethylaminophenol (5-Br-PADAP)-Fe3+ complex, resulting in a color change. A 5-Br-PADAP-Fe3+ complex was encapsulated into water-dispersible poly(styrene- block-vinylpyrrolidone) particles, whose physical entrapment in the cellulosic fiber network results in the immobilization of the complex to the paper matrix. The complex-encapsulating particles showed a color change response in accordance with lactoferrin concentration. Both color intensity-based paper well plates and distance readout-based µPADs are demonstrated. Color intensity-based devices allowed quantitative analysis of lactoferrin concentrations with a limit of detection of 110 µg/mL, using a smartphone and a color readout app. On the other hand, distance readout-based µPADs showed changes of the length of colored sections in accordance with lactoferrin concentration. In summary, we successfully developed both colorimetric intensity-based paper wells and distance-based µPADs for lactoferrin detection. This work demonstrates a user-friendly colorimetric analysis platform for lactoferrin without requiring lab equipment and expensive antibodies.
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Rosenfeld, Tally, and Moran Bercovici. "1000-fold sample focusing on paper-based microfluidic devices." Lab Chip 14, no. 23 (2014): 4465–74. http://dx.doi.org/10.1039/c4lc00734d.

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37

Weng, Xuan, and Suresh Neethirajan. "Aptamer-based fluorometric determination of norovirus using a paper-based microfluidic device." Microchimica Acta 184, no. 11 (September 11, 2017): 4545–52. http://dx.doi.org/10.1007/s00604-017-2467-x.

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38

Young, Katherine M., Peter G. Shankles, Theresa Chen, Kelly Ahkee, Sydney Bules, and Todd Sulchek. "Scaling microfluidic throughput with flow-balanced manifolds to simply control devices with multiple inlets and outlets." Biomicrofluidics 16, no. 3 (May 2022): 034104. http://dx.doi.org/10.1063/5.0080510.

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Microfluidics can bring unique functionalities to cell processing, but the small channel dimensions often limit the throughput for cell processing that prevents scaling necessary for key applications. While processing throughput can be improved by increasing cell concentration or flow rate, an excessive number or velocity of cells can result in device failure. Designing parallel channels can linearly increase the throughput by channel number, but for microfluidic devices with multiple inlets and outlets, the design of the channel architecture with parallel channels can result in intractable numbers of inlets and outlets. We demonstrate an approach to use multiple parallel channels for complex microfluidic designs that uses a second manifold layer to connect three inlets and five outlets per channel in a manner that balances flow properties through each channel. The flow balancing in the individual microfluidic channels was accomplished through a combination of analytical and finite element analysis modeling. Volumetric flow and cell flow velocity were measured in each multiplexed channel to validate these models. We demonstrate eight-channel operation of a label-free mechanical separation device that retains the accuracy of a single channel separation. Using the parallelized device and a model biomechanical cell system for sorting of cells based on their viability, we processed over 16 × 106 cells total over three replicates at a rate of 5.3 × 106 cells per hour. Thus, parallelization of complex microfluidics with a flow-balanced manifold system can enable higher throughput processing with the same number of inlet and outlet channels to control.
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39

Pesaran, Shiva, Elmira Rafatmah, and Bahram Hemmateenejad. "An All-in-One Solid State Thin-Layer Potentiometric Sensor and Biosensor Based on Three-Dimensional Origami Paper Microfluidics." Biosensors 11, no. 2 (February 10, 2021): 44. http://dx.doi.org/10.3390/bios11020044.

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An origami three-dimensional design of a paper-based potentiometric sensor is described. In its simplest form, this electrochemical paper-based analytical device (ePAD) is made from three small parts of the paper. Paper layers are folded on each other for the integration of a solid contact ion selective electrode (here a carbon-paste composite electrode) and a solid-state pseudo-reference electrode (here writing pencil 6B on the paper), which are in contact with a hydrophilic channel fabricated on the middle part (third part) of the paper. In this case, the pseudo-reference and working electrodes are connected to the two sides of the hydrophilic channel and hence the distance between them is as low as the width of paper. The unmodified carbon paste electrode (UCPE) and modification with the crown ether benzo15-crown-5 (B15C5) represented a very high sensitivity to Cu (II) and Cd2+ ions, respectively. The sensor responded to H2O2 using MnO2-doped carbon paste electrode (CPE). Furthermore, a biosensor was achieved by the addition of glucose oxidase to the MnO2-doped CPE and hence made it selective to glucose with ultra-sensitivity. In addition to very high sensitivity, our device benefits from consuming a very low volume of sample (10.0 µL) and automatic sampling without need for sampling devices.
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40

Yamada, Kentaro, Hiroyuki Shibata, Koji Suzuki, and Daniel Citterio. "Toward practical application of paper-based microfluidics for medical diagnostics: state-of-the-art and challenges." Lab on a Chip 17, no. 7 (2017): 1206–49. http://dx.doi.org/10.1039/c6lc01577h.

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41

Ferreira, Francisca T. S. M., Karina A. Catalão, Raquel B. R. Mesquita, and António O. S. S. Rangel. "New microfluidic paper-based analytical device for iron determination in urine samples." Analytical and Bioanalytical Chemistry 413, no. 30 (October 15, 2021): 7463–72. http://dx.doi.org/10.1007/s00216-021-03706-9.

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42

Jayawardane, B. Manori, Shen Wei, Ian D. McKelvie, and Spas D. Kolev. "Microfluidic Paper-Based Analytical Device for the Determination of Nitrite and Nitrate." Analytical Chemistry 86, no. 15 (July 7, 2014): 7274–79. http://dx.doi.org/10.1021/ac5013249.

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43

Wang, Yanhu, Shoumei Wang, Shenguang Ge, Shaowei Wang, Mei Yan, Dejin Zang, and Jinghua Yu. "Ultrasensitive chemiluminescence detection of DNA on a microfluidic paper-based analytical device." Monatshefte für Chemie - Chemical Monthly 145, no. 1 (May 14, 2013): 129–35. http://dx.doi.org/10.1007/s00706-013-0971-1.

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44

Rattanarat, Poomrat, Wijitar Dungchai, David M. Cate, Weena Siangproh, John Volckens, Orawon Chailapakul, and Charles S. Henry. "A microfluidic paper-based analytical device for rapid quantification of particulate chromium." Analytica Chimica Acta 800 (October 2013): 50–55. http://dx.doi.org/10.1016/j.aca.2013.09.008.

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45

Taghizadeh-Behbahani, Maryam, Bahram Hemmateenejad, and Mojtaba Shamsipur. "Colorimetric determination of acidity constant using a paper-based microfluidic analytical device." Chemical Papers 72, no. 5 (December 12, 2017): 1239–47. http://dx.doi.org/10.1007/s11696-017-0357-7.

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46

Kim, Dami, SeJin Kim, and Sanghyo Kim. "An innovative blood plasma separation method for a paper-based analytical device using chitosan functionalization." Analyst 145, no. 16 (2020): 5491–99. http://dx.doi.org/10.1039/d0an00500b.

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47

Rosenfeld, Tally, and Moran Bercovici. "Amplification-free detection of DNA in a paper-based microfluidic device using electroosmotically balanced isotachophoresis." Lab on a Chip 18, no. 6 (2018): 861–68. http://dx.doi.org/10.1039/c7lc01250k.

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48

Liu, Yu-Ci, Chia-Hui Hsu, Bing-Jyun Lu, Peng-Yi Lin, and Mei-Lin Ho. "Determination of nitrite ions in environment analysis with a paper-based microfluidic device." Dalton Transactions 47, no. 41 (2018): 14799–807. http://dx.doi.org/10.1039/c8dt02960a.

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A new microfluidic paper-based analytical device, a (Ag-μPAD)-based chemiresistor composed of silver ink, has been developed for the selective, sensitive, and quantitative determination of nitrite ions in environmental analysis.
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49

Morbioli, Giorgio Gianini, Thiago Mazzu-Nascimento, Luis Aparecido Milan, Amanda M. Stockton, and Emanuel Carrilho. "Improving Sample Distribution Homogeneity in Three-Dimensional Microfluidic Paper-Based Analytical Devices by Rational Device Design." Analytical Chemistry 89, no. 9 (April 19, 2017): 4786–92. http://dx.doi.org/10.1021/acs.analchem.6b04953.

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50

Farasat, Malihe, Ehsan Aalaei, Saeed Kheirati Ronizi, Atin Bakhshi, Shaghayegh Mirhosseini, Jun Zhang, Nam-Trung Nguyen, and Navid Kashaninejad. "Signal-Based Methods in Dielectrophoresis for Cell and Particle Separation." Biosensors 12, no. 7 (July 11, 2022): 510. http://dx.doi.org/10.3390/bios12070510.

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Separation and detection of cells and particles in a suspension are essential for various applications, including biomedical investigations and clinical diagnostics. Microfluidics realizes the miniaturization of analytical devices by controlling the motion of a small volume of fluids in microchannels and microchambers. Accordingly, microfluidic devices have been widely used in particle/cell manipulation processes. Different microfluidic methods for particle separation include dielectrophoretic, magnetic, optical, acoustic, hydrodynamic, and chemical techniques. Dielectrophoresis (DEP) is a method for manipulating polarizable particles’ trajectories in non-uniform electric fields using unique dielectric characteristics. It provides several advantages for dealing with neutral bioparticles owing to its sensitivity, selectivity, and noninvasive nature. This review provides a detailed study on the signal-based DEP methods that use the applied signal parameters, including frequency, amplitude, phase, and shape for cell/particle separation and manipulation. Rather than employing complex channels or time-consuming fabrication procedures, these methods realize sorting and detecting the cells/particles by modifying the signal parameters while using a relatively simple device. In addition, these methods can significantly impact clinical diagnostics by making low-cost and rapid separation possible. We conclude the review by discussing the technical and biological challenges of DEP techniques and providing future perspectives in this field.
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