Phase-Switching Depolymerizable Poly(carbamate) Oligomers for Signal Amplification in Quantitative Time-Based Assays

Abstract

This article describes the use of poly(carbamate) oligomers that depolymerize from head-to-tail as phase-switching reagents for increasing the sensitivity of quantitative point-of-care assays that are based on measurements of time. The poly(carbamate) oligomers selectively react with hydrogen peroxide (a model analyte) and provide sensitivity by depolymerizing in the presence of the analyte to convert from water-insoluble oligomers to water-soluble products. This switching reaction enables a sample to wick through a three-dimensional paper-based microfluidic device, where the flow-through time reflects the quantity of the analyte in the sample. Oligomers as short as octamers enable quantitative detection to low nanomolar concentrations of the analyte.

Paper and Fiber-Based Bio-Diagnostic Platforms: Current Challenges and Future Needs

“…These bridges wick fluids until complete dissolution disconnects the flow [82,84,85]. Other techniques, such as phase-switching [86] and razor-crafting channels [87] have also introduced innovative strategies to address this challenge. These techniques have successfully offered higher sensitivity of the assay, enhanced accommodation of small sample volumes within the channels, and the increased retention of the analyte of interest in the network of the paper [87,88].…”

“…Combined with a self-calibrating system, this time-based detection strategy changes the incubation time to minimize the influence of external parameters and to elicit a reliable readout signal. Further advances in the time-based measurement involved a phase-switching design of the platform in which specific types of oligomers depolymerize themselves in the presence of target analyte [86]. Oligomers are hydrophobic in their nature; however, they tend to become hydrophilic after depolymerization, thereby allowing the flow to travel through the channel and reach the detection zone.…”

Progress in The Development of Paper-Based Diagnostics for Low-Resource Point-Of-Care Settings

“…In this case, a commercially available gold-enhancement reagent was used; further gains in sensitivity should be possible using alternate signal-amplification methods such as enzyme-based systems. Lewis et al have developed a novel signal amplification method in a time measurement-based paper assay [79]. Their method for the detection of hydrogen peroxide uses the reaction between hydrogen peroxide and an initially water insoluble oligomer to produce a water-soluble oligomer and allows the flow of sample through the device [79].…”

“…Lewis et al have developed a novel signal amplification method in a time measurement-based paper assay [79]. Their method for the detection of hydrogen peroxide uses the reaction between hydrogen peroxide and an initially water insoluble oligomer to produce a water-soluble oligomer and allows the flow of sample through the device [79]. The transport time for the sample decreases with increasing concentration of analyte [79].…”

Design, Synthesis, and Characterization of Small-Molecule Reagents That Cooperatively Provide Dual Readouts for Triaging and, When Necessary, Quantifying Point-of-Need Enzyme Assays

“…While no current assay satisfies all of the requirements for an effective high-throughput, low-cost, quantitative point-of-need assay, new approaches are being developed to address this deficiency. These strategies include assays based on cell phones, 5–17 repurposing glucose meters to detect analytes other than glucose, 18–25 using a voltage meter to measure the results of an electrochemical assay, 26–35 assays based on relative measurements of time, 36–41 detection based on the release of odorous compounds, 42–45 as well as assays based on the distance that a sample travels on an assay platform. 46–48 …”