Search

The use of paper microfluidics to perform chemical measurements for various analytical applications has gained interest over the last decade. One of the growing applications of these platforms is for the qualitative and quantitative determination of drugs. The low cost and self-pumping ability of paper microfluidics are attractive for developing analytical tools capable of on-site drug screening. This review aims to present the unique features of microfluidic paper-based analytical devices (μPADs) that offer advantages to pharmaceutical analysis and evaluate the state-of-the-art technologies and applications of the platform for drug analysis in research and real-world settings. The current challenges and potential future directions of the field are also highlighted., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Pathogen detection is crucial for human, animal, and environmental health; crop protection; and biosafety. Current culture-based methods have long turnaround times and lack sensitivity. Nucleic acid amplification tests offer high specificity and sensitivity. However, their cost and complexity remain a significant hurdle to their applications in resource-limited settings. Thus, point-of-need molecular diagnostic platforms that can be used by minimally trained personnel are needed. The nuclease protection assay (NPA) is a nucleic acid hybridization-based technique that does not rely on amplification, can be paired with other methods to improve specificity, and has the potential to be developed into a point-of-need device. In traditional NPAs, hybridization of an anti-sense probe to the target sequence is followed by single-strand nuclease digestion. The double-stranded target-probe hybrids are protected from nuclease digestion, precipitated, and visualized using autoradiography or other methods. We have developed a paper-based nuclease protection assay (PB-NPA) that can be implemented in field settings as the detection approach requires limited equipment and technical expertise. The PB-NPA uses a lateral flow format to capture the labeled target-probe hybrids onto a nitrocellulose membrane modified with an anti-label antibody. A colorimetric enzyme-substrate pair is used for signal visualization, producing a test line. The nuclease digestion of non-target and mismatched DNA provides high specificity while signal amplification with the reporter enzyme-substrate provides high sensitivity. We have also developed an on-chip sample pretreatment step utilizing chitosan-modified paper to eliminate possible interferents from the reaction and preconcentrate nucleic acids, thereby significantly reducing the need for auxiliary equipment. Graphical abstract.

Paper-based sensors offer an affordable yet powerful platform for field and point-of-care (POC) testing due to their self-pumping ability and utility for many different analytical measurements. When combined with electrochemical detection using small and portable electronics, sensitivity and selectivity of the paper devices can be improved over naked eye detection without sacrificing portability. Herein, we review how the field of electrochemical paper-based analytical devices (ePADs) has grown since it was introduced a decade ago. We start by reviewing fabrication methods relevant to ePADs with more focus given to the electrode fabrication, which is fundamental for electrochemical sensing. Multiple sensing approaches applicable to ePADs are then discussed and evaluated to present applicability, advantages and challenges associated with each approach. Recent applications of ePADs in the fields of clinical diagnostics, environmental testing, and food analysis are also presented. Finally, we discuss how the current ePAD technologies have progressed to meet the analytical and practical specifications required for field and/or POC applications, as well as challenges and outlook.

An electrochemical paper-based analytical device (ePAD) was developed for quasi-steady flow detection at microwire electrodes, for the first time. The device implements a fan shaped geometry connected to an analysis channel whereby solution is pulled from an inlet, through a channel, and into the steadily increasing capillary network of the fan. The network counteracts the decrease in solution flow rate associated with increasing viscosity within the channel, generating quasi-steady flow within the analysis channel. Microwire electrodes were embedded between two paper layers within the analysis channel, such that solution flow occurred on both sides of the wire electrodes. The quasi-steady flow ePAD increased the current by 2.5 times and 0.7 times from a saturated channel with no flow and from a single-layer paper device with flow, respectively. Amperometric detection was used for flow injection analysis (FIA) of multiple analytes at both Au and Pt microwire working electrodes, both of which provided similar sensitivity (ca. 0.2 mM -1 ) when normalized to the same standard. The two-layer paper devices provided a detection limit of 31 μM for p-aminophenol (PAP) using Pt electrodes and was also used to detect enzyme activity for the reaction of β-galactosidase with p-aminophenyl-galactopyranoside (PAPG). Measured enzyme kinetics provided similar V max (0.079 mM/min) and K m (0.36 mM) values as those found in the literature. This device shows great promise toward use in enzyme-linked immunosorbent assays or other analytical techniques where flow or washing steps are necessary. The developed sensor provides a simple and inexpensive device capable of performing multiple injection analysis with steady-flow and online detection that would normally require an external pump to perform.