Dissolvable fluidic time delays for programming multi-step assays in instrument-free paper diagnostics

Abstract

Lateral flow tests (LFTs) are an ingenious format for rapid and easy-to-use diagnostics, but they are fundamentally limited to assay chemistries that can be reduced to a single chemical step. In contrast, most laboratory diagnostic assays rely on multiple timed steps carried out by a human or a machine. Here, we use dissolvable sugar applied to paper to create programmable flow delays and present a paper network topology that uses these time delays to program automated multi-step fluidic protocols. Solutions of sucrose at different concentrations (10-70% of saturation) were added to paper strips and dried to create fluidic time delays spanning minutes to nearly an hour. A simple folding card format employing sugar delays was shown to automate a four-step fluidic process initiated by a single user activation step (folding the card); this device was used to perform a signal-amplified sandwich immunoassay for a diagnostic biomarker for malaria. The cards are capable of automating multi-step assay protocols normally used in laboratories, but in a rapid, low-cost, and easy-to-use format.

Programmed sample delivery on a pressurized paper

“…For example, paperbased device's channel widths and fluid path lengths were configured to program delivery sequence; 7,8 multiple pads were arranged in specific orientation; 6,9,10 electromagnet and fluidic diodes were used for timed valving; 11,12 paper channel was sandwiched between two films to increase the velocity in the channel; 13 and dissolvable barriers were applied for fluidic delays. 14,15 However, increasing the width or fluidic path length to decrease flow velocity can result in increased sample consumption and may not be appropriate when dealing with small volume samples such as blood. Moreover, adding multiple pads, installing fluidic valves, covering films over channels, and applying dissolvable barriers resulted in complicated manufacturing processes of paper fluidic devices.…”

Controlling Capillary-Driven Fluid Transport in Paper-Based Microfluidic Devices Using a Movable Valve

“…The behavior of paper wicking in multidimensional channels clamped by paper pins also complied with the Washburn equation. 20,23 A separate experiment revealed that reproducibility was minimally affected by the pins. An orange dye solution was distributed on 16 test zones, and the signal intensity was measured by the homemade paper-based colorimetric readout device 8 (displayed in Figure S4).…”

Towards autonomous lab-on-a-chip devices for cell phone biosensing

“…In recent years the subject has been re-visited and expanded (Martinez et al, 2008b(Martinez et al, , 2010Noh et al, 2010;Lutz et al, 2013;Byrnes et al, 2013). Autonomous capillary systems can also be implemented using micro fabrication techniques rather than paper, which offer the benefits of compatibility with classical LOC architectures and the use of detection principles beyond colorimetry (Zimmermann et al, 2007;Gervais and Delamarche, 2009;Safavieha and Juncker, 2013).…”