Recent Advances of Fluid Manipulation Technologies in Microfluidic Paper-Based Analytical Devices (μPADs) toward Multi-Step Assays

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.

Point-of-care diagnostics for infectious diseases: From methods to devices

“…μ PADs are attractive POC devices that are very potential toward commercialization due to their low cost, easy fabrication and operation, no need of external pumps or power sources, and well compatibility. However, they are currently limited by their inherent shortcomings such as lack of flow control, difficulty of multiplexing and multi-step assays, limited sensitivity, inability of instant response and repeatable use [386] , [496] , [497] . Lateral flow devices have been widely deployed POC diagnostics due to their superiorities of user-friendly, low cost, easy miniaturization and development, and independent on equipment, they have limited capability to achieve quantitative detection, and the multiplexing capability and throughput need to be further improved [421] , [498] , [499] .…”

“… Devices Pros Cons Refs. LOC devices High-throughput, multiplex and faster analysis, small sample volume, less power consumption and more efficient control and manipulation Difficulty of fabricating, packaging and interfacing, and difficulty of multiplexing [56] , [490] , [491] , [492] LOAD devices Low cost and easy control by centrifugal force, simple and independent liquid handling, large-scale parallelization and multiplexing Short shelf life, difficult on-board reagent storage, and hard to work with very small volumes [492] , [493] , [494] , [495] μ PADs devices Low cost, easy fabrication and operation, no need of external pumps or power sources, and well compatibility Lack of flow control, difficulty of multiplexing and multi-step assays, limited sensitivity, inability of instant response and repeatable use [386] , [496] , [497] Lateral flow devices Low cost, user-friendly, independent on equipment easy miniaturization and development Difficulty of achieving quantitative detection, limited multiplexing capability and throughput [421] , [498] , [499] Miniaturized PCR devices Accurate quantification, small sample and high sensitivity High production cost, expensive complex device [294] , [441] , [500] INAA devices Fast, simple device, and high sensitivity High requirements for the primers and expensive reagents [501] , [502] , [503] …”

Paper-Based Biosensors: Frontiers in Point-of-Care Detection of COVID-19 Disease

“…Paper-based microfluidics, also referred to as microfluidic paper-based analytical devices (µPADs), are diagnostic systems made of patterned paper, on which a small volume of fluid will move by capillarity, through multi-channel designs within the paper substrate [89][90][91][92]. An example is shown in Figure 7.…”

Recent Advances in Microfluidic Paper-Based Analytical Devices toward High-Throughput Screening

“…Depending on the shapes and width of the patterns modified in the channel, the fluid transportation can be controlled quantitatively ( Figure 3 ) [ 99 ]. Recent review papers have summarized progress in the development of flow control tools and the integration of those tools for paper microfluidics [ 30 , 31 , 107 , 108 ].…”