The Many Roads to an Ideal Paper-based Device

Abstract

The recent Zika and Ebola virus outbreaks highlight the need for low-cost diagnostics that can be rapidly deployed and used outside of established clinical infrastructure. This demand for robust point-of-care (POC) diagnostics is further driven by the increasing burden of drug-resistant diseases, concern for food and water safety, and bioterrorism, among many other necessities. As has been discussed in previous chapters, paper-based tests provide a simple and compelling solution to such needs. Paper-based tests and devices are themselves not new and in fact were first developed in the 1930s [1], but have only emerged recently as broadly capable tools for rapid diagnostics outside of laboratory settings.The most widely recognized paper-based diagnostic is the home pregnancy test that came on the market in 1988 [2]. This one-step assay to assess urine for the pregnancy hormone human chorionic gonadotropin uses the chromatographic effect of paper to drive flow for the onboard immunoassay that underpins detection. While the pregnancy test has been a tremendous success, many other clinical needs require portable diagnostics that are similarly complex and sensitive and, in turn, this has given birth to a whole field dedicated to the development of paper-based, POC diagnostics [3]. Accordingly, the lateral flow assay concept has been extended to a wide range of infectious disease antigens, nucleic acid sequences, and illicit drugs from diverse sample types (e.g., sputum, blood, fecal, food).In 2004, the Whitesides group developed the "POCKET immunoassay" [4], a microfluidic compatible immunoassay to bring enzyme-linked immunosorbent assays (ELISAs) to the field and resource-limited environments where such analytical techniques are not usually available. Three years later this was followed by another report, from the same group, that used patterned paper to create paperbased microfluidics for the simultaneous analysis of glucose and protein in urine [5].

Promise and perils of paper-based point-of-care nucleic acid detection for endemic and pandemic pathogens

“…8 To conduct diagnostics by NAAT, multiple processes are involved as follows; (I) collection of clinical samples, (II) sample preparation incorporating concentration or dilution of pathogens, cell lysis to release genetic contents, purification or isolation of NA by separating them from a complex sample or removing inhibitors from sample, (III) amplification of NA to obtain more amplified products or amplicons, (IV) signal transduction, and (V) detection of the amplified product. 14 It is important to note that price of these commercial products is beyond the affordable range in most resource-limited settings (RLS) and therefore, and are not applicable to resource-limited point-of-care (POC) settings. 10 The major differences between isothermal methods are the mechanism of primer annealing and enzymes used in the polymerization step.…”

A sample-to-answer, quantitative real-time PCR system with low-cost, gravity-driven microfluidic cartridge for rapid detection of SARS-CoV-2, influenza A/B, and human papillomavirus 16/18

“…7 In contrast, passive pumping techniques (e.g., surface tension, capillary force, hydrostatic, or hydrodynamic pressure) do not require any external power sources/pumps or actuators to drive fluid flow, thus facilitating a higher degree of miniaturization and consequently cost reduction. [33][34][35] Such methods have emerged as a simple and highly efficient means for fluid flow control in POC hematological and immunological test cartridges. In most commercialized cartridges for NA testing, nucleic acid preparation typically involves two separate steps: (1) NA release via lysis and (2) extraction (i.e., separation and purification) of the NA from complex samples containing inhibitors of qPCR via solid-phase extraction techniques, which rely on precise control of the liquid transfer into the specific cartridge chambers.…”

“…, surface tension, capillary force, hydrostatic, or hydrodynamic pressure) do not require any external power sources/pumps or actuators to drive fluid flow, thus facilitating a higher degree of miniaturization and consequently cost reduction. 33–35 Such methods have emerged as a simple and highly efficient means for fluid flow control in POC hematological and immunological test cartridges. In most commercialized cartridges for NA testing, nucleic acid preparation typically involves two separate steps: (1) NA release via lysis and (2) extraction ( i.e.…”