Electrochemical DNA-Based Immunoassay That Employs Steric Hindrance To Detect Small Molecules Directly in Whole Blood

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.