TY - JOUR
T1 - Biomolecular Steric Hindrance Effects Are Enhanced on Nanostructured Microelectrodes
AU - Mahshid, Sahar Sadat
AU - Vallée-Bélisle, Alexis
AU - Kelley, Shana O.
N1 - Funding Information:
This work was supported by Genome Canada and the Ontario Genomics Institute (Grant OGI-077), the Province of Ontario through the Ministry of Research and Innovation (ORF-GAPP), and the Natural Sciences and Engineering Research Council of Canada (Discovery Grants S.O.K. and A.V.-B.).
Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/9/19
Y1 - 2017/9/19
N2 - The availability of rapid approaches for quantitative detection of biomarkers would drastically impact global health by enabling decentralized disease diagnosis anywhere that patient care is administered. A promising new approach, the electrochemical steric hindrance hybridization assay (eSHHA) has been introduced for quantitative detection of large proteins (e.g., antibodies) with a low nanomolar detection limit within 10 min. Here, we report the use of a nanostructured microelectrode (NME) platform for eSHHA that improves the performance of this approach by increasing the efficiency and kinetics of DNA hybridization. We demonstrated that eSHHA on nanostructured microelectrodes leverages three effects: (1) steric hindrance effects at the nanoscale, (2) a size-dependent hybridization rate of DNA complexes, and (3) electrode morphology-dependent blocking effects. As a proof of concept, we showed that the sensitivity of eSHHA toward a model antibody is enhanced using NMEs as scaffolds for this reaction. We improved the detection limit of eSHHA, taking advantage of nanostructured surfaces to allow the use of longer capture strands for detection of proteins. Finally, we concluded that using the eSHHA approach in conjunction with nanostructured microelectrodes is an advantageous alternative to conventional macroelectrodes as the sensitivity and detection limits are enhanced.
AB - The availability of rapid approaches for quantitative detection of biomarkers would drastically impact global health by enabling decentralized disease diagnosis anywhere that patient care is administered. A promising new approach, the electrochemical steric hindrance hybridization assay (eSHHA) has been introduced for quantitative detection of large proteins (e.g., antibodies) with a low nanomolar detection limit within 10 min. Here, we report the use of a nanostructured microelectrode (NME) platform for eSHHA that improves the performance of this approach by increasing the efficiency and kinetics of DNA hybridization. We demonstrated that eSHHA on nanostructured microelectrodes leverages three effects: (1) steric hindrance effects at the nanoscale, (2) a size-dependent hybridization rate of DNA complexes, and (3) electrode morphology-dependent blocking effects. As a proof of concept, we showed that the sensitivity of eSHHA toward a model antibody is enhanced using NMEs as scaffolds for this reaction. We improved the detection limit of eSHHA, taking advantage of nanostructured surfaces to allow the use of longer capture strands for detection of proteins. Finally, we concluded that using the eSHHA approach in conjunction with nanostructured microelectrodes is an advantageous alternative to conventional macroelectrodes as the sensitivity and detection limits are enhanced.
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U2 - 10.1021/acs.analchem.7b01595
DO - 10.1021/acs.analchem.7b01595
M3 - Article
C2 - 28829912
AN - SCOPUS:85029583951
SN - 0003-2700
VL - 89
SP - 9751
EP - 9757
JO - Analytical Chemistry
JF - Analytical Chemistry
IS - 18
ER -