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Design Principles for Enhancing Sensitivity in Paper-Based Diagnostics via Large-Volume Processing.

Eric A Miller1, Yara Jabbour Al Maalouf1, Hadley D Sikes1

  • 1Department of Chemical Engineering , Massachusetts Institute of Technology , Cambridge , Massachusetts 02142 , United States.

Analytical Chemistry
|June 21, 2018
PubMed
Summary
This summary is machine-generated.

Processing larger sample volumes in paper-based immunoassays significantly enhances analytical sensitivity. This is achieved by increasing the local concentration of analyte-binding species, improving target capture kinetics for dilute analytes.

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Area of Science:

  • Biomedical Engineering
  • Analytical Chemistry
  • Assay Development

Background:

  • Flow-through paper-based immunoassays are susceptible to limitations in analytical sensitivity, particularly with dilute analytes.
  • Processing larger sample volumes offers potential for increased analyte capture but requires optimized assay design.

Purpose of the Study:

  • To investigate the impact of large-volume sample processing on the analytical sensitivity of paper-based immunoassays.
  • To define principles for designing assays that effectively capture dilute analytes from large sample volumes.

Main Methods:

  • Development of a finite-element model to simulate pressure-driven convective flow and analyte binding.
  • Experimental validation using a novel bifunctional binding protein (rcSso7d-cellulose-binding domain fusion construct).

Main Results:

  • High local concentration of analyte-binding species within the porous substrate is crucial for enhanced binding signal.
  • Optimized binding kinetics, matching target capture to effective residence time, improves sensitivity.
  • Experimental validation confirmed that high surface density binding proteins enable sensitivity enhancement via large-volume processing.

Conclusions:

  • Large-volume processing can significantly improve the sensitivity of paper-based immunoassays.
  • Achieving high local concentrations of binding species is key to maximizing sensitivity.
  • Guidance is provided for optimizing large-volume sample processing in assay design.