Abstract
The development of a universal sensing mechanism for the rapid and quantitative detection of small molecules directly in whole blood would drastically impact global health by enabling disease diagnostics, monitoring, and treatment at home. We have previously shown that hybridization between a free DNA strand and its complementary surface-bound strand can be sterically hindered when the former is bound to large antibodies. Here, we exploit this effect to design a competitive antibody-based electrochemical assay, called CeSHHA, that enables the quantitative detection of small molecules directly in complex matrices, such as whole blood or soil. We discuss the importance of this inexpensive assay for point-of-care diagnosis and for treatment monitoring applications.
Highlights
The main challenges that have slowed down the commercialization of new quantitative home meters are that enzyme-based sensing mechanisms are hardly adaptable for the detection of most small molecules[19] while other assays based on electrocatalysis[20−24] or biorecognition[25−28] typically fail when performed directly in whole blood, or remain too cumbersome to be employed at home
CeSHHA relies on the ability of DNA strands to hybridize in a very specific and selective manner to a surface-bound complementary DNA strand directly in complex matrices, with a hybridization efficiency that can be modulated by steric hindrance
We have recently demonstrated that when a large macromolecule such as an antibody binds to a DNA strand, this reduces the number of DNA
Summary
Letter strands that can reach and hybridize to the complementary strand attached to a surface at high density (Figure 1, bottom). CeSHHA is capable of enabling multiplexed detection of numerous small target molecules, by taking advantage of the unique ability of DNA to create numerous specific capturingsignaling pairs.[29] CeSHHA displays significant advantages compared to other universal DNA-based sensors such as the EDNA scaffold platform.[39,40,42] In addition to being robust enough to enable detection directly in whole blood, CeSHHA provides a 20-fold enhancement in the electrochemical current due to its ability to work at high surface density.
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