Evaluation of paper substrates for microfluidic application in medical diagnostic kits.

Abstract

Recent studies in the biomedical field have shown the use of paper in microfluidic analytical devices. However, no studies have been undertaken to ascertain what type(s) of paper substrates are ideal for such microfluidic applications. Hence, this study was conducted to determine the feasibility of using different paper substrates for implementation in microfluidic analytical devices, specifically in the South African context, compared to currently used materials such as glass and silicone. In addition, fibres in paper substrates were substituted with nanofibrillated cellulose (NFC) fibres to ascertain the impact of NFC on the microfluidics of the paper substrates. The wicking rate of the substrates was the focus of the study, with high -resolution field emission gun-scanning electron microscopy and contact angle tests being used to support the results obtained. Solid wax printing was also conducted to determine whether the paper substrates were suited to fabrication for microfluidic applications. High-resolution morphological studies of the paper substrates showed that pore sizes of the pulp fibres were in the order sulphite> bleached kraft > unbleached kraft > Whatman No. 1 Chromatography Filter Paper > Whatman 3MM Chromatography Filter Paper > thermo-mechanical > recycled. It was concluded that the larger pore size of fibres correlated with faster wicking rates of the relevant paper substrates. The substitution of pulp fibres with NFC led to reduced pore size of the fibres thus leading to reduced wicking rates due to the presence of the small NFC particles. Contact angle is directly linked to the hydrophobicity of the substrate and is indicative of the resistance to absorption of a liquid. The results revealed that all the paper substrates were hydrophilic. However, the hydrophilicity of two of the substrates (sheets substituted with 100% NFC unbleached kraft pulp and 100% NFC recycled pulp) were higher than those of the other substrates indicating that, although these substrates were still hydrophilic in nature, their absorption of aqueous liquid would take longer periods of time. The results showed that Whatman glass microfiber GF/D filter paper was the fastest wicking substrate, using both dye and blood simulant as wicking liquids. Similarly, paper substrates made with recycled fibres exhibited the slowest wicking rates when using both wicking liquids. These results can be used when determining which of the substrates to use for paper-based microfluidic device (μPAD) application, whereby the desired detection time would be the factor used to establish which of the substrates to use. Comparison of vertical and horizontal tests showed varying results. In theory, the horizontal wicking test should result in a faster wicking rate than the vertical test, taking hydrostatic pressure into consideration. The majority of the substrates showed that the horizontal wicking rate was faster when using the dye solution, whereas vertical wicking was faster when using the blood simulant. Discrepancies between the results obtained from the dye and blood simulant experiments could be attributed to the additional viscosity drag when using the higher viscosity liquid (blood simulant), as well as possible capillarity differences of the samples. The results were used in conjunction with the morphological studies, whereby the pore size was correlated with the wicking rate. The solid wax printing test revealed that, in general, the substrates were not well suited to the fabrication method. The results showed that the wax was not able to penetrate through the depth of the sheet, hence allowing for the possibility of leakage of liquid from the channels. Two of the substrates (Whatman No. 1 Chromatography filter paper and paper made from sulphite pulp fibres containing 20% nanofibrillated cellulose) exhibited 100% wax penetration and could be considered for μPAD application. However, for paper substrates that do not meet requirements for μPAD applications, their pulp fibres could be chemically modified to induce hydrophobicity thus altering the microfluidic characteristics of the paper substrates.