Two Potential Clinical Applications of Origami-Based Paper Devices

Abstract

Detecting small amounts of analyte in clinical practice is challenging because of deficiencies in specimen sample availability and unsuitable sampling environments that prevent reliable sampling. Paper-based analytical devices (PADs) have successfully been used to detect ultralow amounts of analyte, and origami-based PADs (O-PADs) offer advantages that may boost the overall potential of PADs in general. In this study, we investigated two potential clinical applications for O-PADs. The first O-PAD we investigated was an origami-based enzyme-linked immunosorbent assay (ELISA) system designed to detect different concentrations of rabbit IgG. This device was designed with four wing structures, each of which acted as a reagent loading zone for pre-loading ELISA reagents, and a central test sample loading zone. Because this device has a low limit of detection (LOD), it may be suitable for detecting IgG levels in tears from patients with a suspected viral infection (such as herpes simplex virus (HSV)). The second O-PAD we investigated was designed to detect paraquat levels to determine potential poisoning. To use this device, we sequentially folded each of two separate reagent zones, one preloaded with NaOH and one preloaded with ascorbic acid (AA), over the central test zone, and added 8 µL of sample that then flowed through each reagent zone and onto the central test zone. The device was then unfolded to read the results on the test zone. The three folded layers of paper provided a moist environment not achievable with conventional paper-based ELISA. Both O-PADs were convenient to use because reagents were preloaded, and results could be observed and analyzed with image analysis software. O-PADs expand the testing capacity of simpler PADs while leveraging their characteristic advantages of convenience, cost, and ease of use, particularly for point-of-care diagnosis.

Development of a New Lab-on-Paper Microfluidics Platform Using Bi-Material Cantilever Actuators for ELISA on Paper

“…Although the reported NC paper plate needs a small amount of sample (5 μL), their method is not an autonomous technique and an expert user should follow a multistep protocol to detect the concentration of antigen in the sample. Finally, Kuo et al [ 44 ] proposed a 3D folding ELISA device to detect different concentrations of rabbit IgG. They designed four wing-shaped zones for pre-loading reagents, and a center space was set aside as a testing zone for loading samples.…”

A Microfluidic Paper-Based Lateral Flow Device for Quantitative ELISA

“…This control is critical for reducing variability and potential errors [17]. Our use of autonomous sequential reagent loading ensures precise timing, significantly reducing the margin for error compared to manually intensive assays, such as those reported in studies that use manually controlled paper valves [20] and origami-based designs [30]. These features ensure that each assay component interacts correctly, thus enhancing the reliability of our results.…”

“…An LOD of 255 pM was achieved with a 250 µL sample using a desktop scanner, with an assay time of 55 min [20]. Another study reported an LOD of 201 pM with an 8 µL sample, detected by a low-cost desktop scanner in 46 min [30]. Yet, another study achieved an LOD of 5.5 ng/mL (36.6 pM) using a 130 µL sample with a semi-autonomous device, and signal detection via a low-cost desktop scanner in about 1 h [23].…”

“…The use of rabbit IgG as a model analyte is imperative in the development of paperbased assays, due to its well-characterized immune response, facilitating accurate and reliable evaluation of the system's capability for autonomous operation [17,20,23,29,30]. From these studies, the detection limit for rabbit IgG using the p-ELISA method is reported to range from 1.016 µg/mL to 2.27 ng/mL.…”

Paper-Based Electrochemical Biosensors for Food Safety Analysis

“…To date, only a few papers have reported the development of e-PADs for veterinary drug determination, all of which target antibiotic detection in milk samples [ 83 , 103 ]. Majority of reported e-PADs deployed optical detection methods such as colorimetry [ 104 , 105 , 106 , 107 ] and fluorescence [ 108 , 109 , 110 , 111 ].…”