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A Highly Selective Electrochemical DNA-Based Sensor That Employs Steric Hindrance Effects to Detect Proteins Directly in Whole Blood

Mahshid, Sahar Sadat, Camiré, Sébastien, Ricci, Francesco, Vallée-Bélisle, Alexis
Journal of the American Chemical Society 2015 v.137 no.50 pp. 15596-15599
DNA, blood, electrochemistry, hybridization, point-of-care systems, proteins
Here we describe a highly selective DNA-based electrochemical sensor that utilizes steric hindrance effects to signal the presence of large macromolecules in a single-step procedure. We first show that a large macromolecule, such as a protein, when bound to a signaling DNA strand generates steric hindrance effects, which limits the ability of this DNA to hybridize to a surface-attached complementary strand. We demonstrate that the efficiency of hybridization of this signaling DNA is inversely correlated with the size of the molecule attached to it, following a semilogarithmic relationship. Using this steric hindrance hybridization assay in an electrochemical format (eSHHA), we demonstrate the multiplexed, quantitative, one-step detection of various macromolecules in the low nanomolar range, in <10 min directly in whole blood. We discuss the potential applications of this novel signaling mechanism in the field of point-of-care diagnostic sensors.