Advances in Paper-Based Microfluidics: From Fabrication to Applications

Introduction To Paper Microfluidics

Microfluidics is defined as the science of controlling fluid flow in extremely low quantities, that is within the range of few µL – nL, through chambers or channels having dimensions in the micron – sub micron scale. The behavior of fluids at these dimensions are governed by the principles which are markedly different from the macroscopic scenario. The liquid flow through microscale channels have been known to be Newtonian and incompressible (Kirby, 2010). In such approximated cases, the flow pattern can be modelled using the Navier-Stokes equation as shown in equations 1 and 2 (Lammertyn et al., 2006):

It is seen that the velocity gradient () and pressure gradient () are the key parameters which needs to be computed, and the optimization of which is vital for developing efficient microfluidic platforms/devices.

Paper-based microfluidics has drawn considerable attention in the scientific community over the past decade, and is defined as the use of paper substrates in microfluidic devices (Anushka et al., 2022). Research in the field of paper-based microfluidics was first initiated by Martinez and co-workers, demonstrating the simultaneous detection of glucose and protein on a patterned cellulose sheet which utilized sample volume as less as ~ 5 µL (Martinez et al., 2007). One of the key advantages of paper substrates, as compared to conventional ones namely glass, silicon and polymers, is its flexibility, light-weight, abundant availability and biocompatibility which allows for the development of cost-effective and portable as well as wireless healthcare and environment monitoring modules (Shen et al., 2020). These devices are then termed as Microfluidic Paper-based Analytical Devices (µPADs). Fluid flow in paper microfluidics occurs without the requirement of external perturbation, and is governed primarily by capillary action. The widely known Lateral Flow Immunoassays (LFAs) such as pregnancy test strips and the recently commercialized home-based COVID-19 monitoring electrodes, the latter developed by Mylab Discovery Solutions Pvt. Ltd. India, work on the principles of capillary-driven flow. There are normally two opposing forces which governs the interaction between paper substrates and the liquid which is in contact with the former. These are the cohesive and adhesive forces. When the liquid is brought in contact with paper, there exists an intermolecular force between the fluid molecules at liquid–air interface termed as cohesion as well as between the solid-liquid interface known as adhesion. The adhesive force is results in the spreading of the liquid over the porous surface, while the cohesive force (surface tension) leads to reduction in the liquid contact area. Therefore, the liquid flows only when the adhesive force is greater than the cohesive counterpart. Moreover, the wicking process depends on numerous geometrical properties of the paper such as paper structure, pore size, permeability as well as on the physical properties of the liquid. The liquid transport can generally be categorized into two groups. These are the wet-out and fully wetted flow processes. In the former, the liquid front simply remains in contact with the porous paper surface, which then can be modelled by the Lucas-Washburn equation as per equation-3 (Mathur & Roy, 2022).

where,

x(t) = distance traversed by liquid under capillary pressure.