Two-Dimensional Paper Network Format That Enables Simple Multistep Assays for Use in Low-Resource Settings in the Context of Malaria Antigen Detection

Abstract

The lateral flow test has become the standard bioassay format in low-resource settings because it is rapid, easy to use, low in cost, uses reagents stored in dry form, and is equipment-free. However, lateral flow tests are often limited to a single chemical delivery step and not capable of the multi-step processing characteristic of high performance laboratory-based assays. To address this limitation, we are developing a paper network platform that extends the conventional lateral flow test to two dimensions; this allows incorporation of multi-step chemical processing, while still retaining the advantages of conventional lateral flow tests. Here we demonstrate this format for an easy-to-use, signal-amplified sandwich format immunoassay for the malaria protein PfHRP2. The card contains reagents stored in dry form such that the user need only add sample and water. The multiple flows in the device are activated in a single user step of folding the card closed; the configuration of the paper network automatically delivers the appropriate volumes of i) sample plus antibody conjugated to a gold particle label, ii) a rinse buffer, and iii) a signal amplification reagent to the capture region. These results highlight the potential of the paper network platform to enhance access to high-quality diagnostic capabilities in low-resource settings in the developed and developing worlds.

The role of nanogold in human tropical diseases: research, detection and therapy

“…AuNPs/Al 2 O 3 sol-gel/SPE was three times more sensitive compared to unmodified/bare SPE for the same concentration of analyte. Recently, Fu et al [59] developed a device consisting on a two-dimensional paper network signal-amplified immunoassay for malaria protein PfHRP2 detection. The paper card contains reagents stored in dry form, including an antibody conjugated to a gold particle label, and the user only needs to add water and the sample.…”

Automatic sequential fluid handling with multilayer microfluidic sample isolated pumping

“…The existing sequential flow devices either introduce valving mechanisms into pumping systems, such as paper-based microfluidic circuits, 39,40 or build integrated micropumps based on the flow control structures, such as the Quake systems. 33 In our work, pneumatic diaphragm microvalves are integrated into an mlSIP device since both of the fluidic actuation and the diaphragm microvalves are built with multi-layer structures and driven by the vacuum pressure, 49 which is described as unified pumping and control.…”

“…Microfluidic sequential flow devices have been developed for bioassays, such as pneumatic microvalve-based systems, [30][31][32][33] capillary-based systems, [34][35][36][37][38][39][40] the SlipChip systems, [41][42][43] and manual valving systems. 44 For most of these systems, liquid pumping process and flow control functions are separately driven by different accessory equipment, which ultimately increases the system complexity and the overall cost.…”

Paper-like Surface Microstructure Fabricated on a Polymer Surface by Femtosecond Laser Machining

“…12 The flow rate of a fluid through the paper channel is proportional to the channel's cross-sectional area, length, and permeability and to the fluid's viscosity. Several researchers have attempted to change the permeability 8,[13][14][15][16] of paper to control the fluid flow. In particular, Chu et al 8 and Lutz et al 14 demonstrated lateral flow control by changing the permeability via infiltration of sugars into paper strips.…”