Stimuli-Responsive Valving Mechanisms for Paper-Based Diagnostics

2020-03-10T16:17:52Z (GMT) by Elizabeth Anne Phillips
Rapid identification of disease-causing pathogens at the point-of-care enables immediate treatment and infection control. However, existing rapid diagnostic devices fail to detect the low concentrations of pathogens present in the early stages of infection, causing delayed and even incorrect treatment. A delay in antibiotic treatment of as few as 24 hours after infection onset will drastically decrease a patient’s chance of survival. The transport of a patient’s sample to a centralized testing laboratory can contribute hours to this delay. For instance, the most sensitive assay, nucleic acid detection, can only be performed at centralized laboratories. The multistep sample preparation and costly instrumentation required to analyze samples has prohibited nucleic acid detection assays from reaching the point-of-care. There remains a critical need to bring rapid and sensitive pathogen identification technologies out of the laboratory to ensure effective treatment.

Paper-based devices have emerged as a portable platform for nucleic acid detection but are limited by their imperfect control of reagent incubation and false positive results. Here, I have developed mechanisms to specifically and automatically detect the nucleic acids of pathogens on paper-based devices. First, I characterize wax-ink valves that enable controlled incubation and delivery of reagents through device stages. Next, I implement toe-hold mediated strand displacement reactions to increase the specificity of nucleic acid detection with paper-based devices. Lastly, I functionalize polymers with nucleic acid probes and explore their potential integration into paper-based devices as bio-responsive valves. I demonstrate how such novel valving mechanisms enable the automatic and multi-step analysis of bacteria and viruses on paper-based platforms, improving the detection of infectious diseases at patients’ point-of-care.