This proposal puts forth a series of synthetic and physical-organic studies aimed at developing three classes of thermally-stable signal amplification reagents for use in point-of-care diagnostics. The reagents will enable trace-level detection of markers of disease and pollution in assays that are inexpensive and straightforward to conduct in resource-limited environments (such as the developing world, in homes for home healthcare, and in emergency situations). The reagents are based on the hypothesis that autocatalytic and auto inductive reactions will be particularly effective at amplifying signal for detection event. The focus of the proposal is on the design, synthesis, and physical organic studies of these reagents in an effort to optimize their performance for diagnostic assays. This optimization effort includes enabling 5000? signal amplification within a 1 h assay, providing unambiguous colorimetric readouts, and ensuring that background signal that could lead to false positive results is eliminated. The performance of the reagents will be tested in the context of assays for water quality (fluoride will be the analyte), the purity of drugs (palladium will be the analyte), and for detecting influenza neuraminidase at levels that correspond to the first 24-48 h of an infection.
Currently, the ability to detect markers of disease or pollution of food and water is restricted primarily to laboratories that contain expensive equipment and trained personnel to perform the tests. The proposed studies seek to create reagents that will allow untrained personnel to conduct tests in nearly any setting (i.e., not in laboratories). The advance that will make this possible is a set of reagents that will amplify a colorimetric signal fr a detection event to enable assays that are simple to perform, yet that are nearly as sensitive as laboratory assays.
|Sun, Xiaolong; Shabat, Doron; Phillips, Scott T et al. (2018) Self-Propagating Amplification Reactions for Molecular Detection and Signal Amplification: Advantages, Pitfalls, and Challenges. J Phys Org Chem 31:|
|Kim, Hyungwoo; Baker, Matthew S; Phillips, Scott T (2015) Polymeric materials that convert local fleeting signals into global macroscopic responses. Chem Sci 6:3388-3392|
|Mohapatra, Hemakesh; Kim, Hyungwoo; Phillips, Scott T (2015) Stimuli-Responsive Polymer Film that Autonomously Translates a Molecular Detection Event into a Macroscopic Change in Its Optical Properties via a Continuous, Thiol-Mediated Self-Propagating Reaction. J Am Chem Soc 137:12498-501|
|Brooks, Adam D; Yeung, Kimy; Lewis, Gregory G et al. (2015) A Strategy for Minimizing Background Signal in Autoinductive Signal Amplification Reactions for Point-of-Need Assays. Anal Methods 7:7186-7192|
|Brooks, Adam D; Mohapatra, Hemakesh; Phillips, Scott T (2015) Design, Synthesis, and Characterization of Small-Molecule Reagents That Cooperatively Provide Dual Readouts for Triaging and, When Necessary, Quantifying Point-of-Need Enzyme Assays. J Org Chem 80:10437-45|
|Thom, Nicole K; Lewis, Gregory G; Yeung, Kimy et al. (2014) Quantitative Fluorescence Assays Using a Self-Powered Paper-Based Microfluidic Device and a Camera-Equipped Cellular Phone. RSC Adv 4:1334-1340|