Abstract

Microfluidic paper-based analytical devices (μPADs) have been suggested as alternatives for developing countries with suboptimal medical conditions because of their low diagnostic cost, high portability, and disposable characteristics. Recently, paper-based diagnostic devices enabling multi-step assays have been drawing attention, as they allow complicated tests, such as enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR), which were previously only conducted in the laboratory, to be performed on-site. In addition, user convenience and price of paper-based diagnostic devices are other competitive points over other point-of-care testing (POCT) devices, which are more critical in developing countries. Fluid manipulation technologies in paper play a key role in realizing multi-step assays via μPADs, and the expansion of biochemical applications will provide developing countries with more medical benefits. Therefore, we herein aimed to investigate recent fluid manipulation technologies utilized in paper-based devices and to introduce various approaches adopting several principles to control fluids on papers. Fluid manipulation technologies are classified into passive and active methods. While passive valves are structurally simple and easy to fabricate, they are difficult to control in terms of flow at a specific spatiotemporal condition. On the contrary, active valves are more complicated and mostly require external systems, but they provide much freedom of fluid manipulation and programmable operation. Both technologies have been revolutionized in the way to compensate for their limitations, and their advances will lead to improved performance of μPADs, increasing the level of healthcare around the world.

Highlights

  • Paper-based diagnostic devices have been widely used for the past decades because of their capability to enable cost-effective point-of-care testing (POCT)

  • Many diagnostic products, such as the dipstick test and lateral flow assay (LFA), have already been commercialized, which are of single-test type and do not require the injection of additional reagents

  • The realization of multi-step assays with paper-based diagnostic devices is very important to enhance the quality of medical welfare around the world

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Summary

Introduction

Paper-based diagnostic devices have been widely used for the past decades because of their capability to enable cost-effective point-of-care testing (POCT). A fluid manipulation technology, which can control the flow of reagents and samples, is the most important element in paper-based diagnostic devices with multi-step assays. This is because it allows the required reagents to flow selectively as needed, and fluid control is essential for multi-step tests using various reagents, such as antibody solutions, washing buffers, and substrate solutions. Such a valve is structurally simple, which is advantageous for mass production and cost-effectiveness; it presents difficulties in response speed control of the fluid because the fluid movement is controlled by the structure of a predetermined paper strip Another passive valve technology is chemical-based fluid manipulation that works on the principle of fluid diodes using surfactants (Figure 1A, right). The following sections examine in detail the functions and applications of passive and active fluid manipulation technologies

Passive Fluid Manipulation
Chemical-Based Fluid Manipulation
Method
Method Cut switch
Mechanical Actuation-based Active Valves
Method Pressure valve
Colorimetric Enzymatic Assay
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