TY - JOUR
T1 - An electrochemical biosensor exploiting binding-induced changes in electron transfer of electrode-attached DNA origami to detect hundred nanometer-scale targets
AU - Arroyo-Currás, Netzahualcóyotl
AU - Sadeia, Muaz
AU - Ng, Alexander K.
AU - Fyodorova, Yekaterina
AU - Williams, Natalie
AU - Afif, Tammy
AU - Huang, Chao Min
AU - Ogden, Nathan
AU - Andresen Eguiluz, Roberto C.
AU - Su, Hai Jun
AU - Castro, Carlos E.
AU - Plaxco, Kevin W.
AU - Lukeman, Philip S.
N1 - Funding Information:
PSL is grateful for support from Army Research Office (awards W911NF-16-1-0178 and W911NF-19-1-0326). PSL thanks Paul Rothemund and Gabriel Ortega for insightful discussions. PSL also thanks LukemanLab members for their hard work; particularly Christopher Chen and Ekaterina Selivanovitch for preliminary study of the triangle.
Publisher Copyright:
© 2020 The Royal Society of Chemistry.
PY - 2020/7/14
Y1 - 2020/7/14
N2 - The specific detection in clinical samples of analytes with dimensions in the tens to hundreds of nanometers, such as viruses and large proteins, would improve disease diagnosis. Detection of these "mesoscale"analytes (as opposed to their nanoscale components), however, is challenging as it requires the simultaneous binding of multiple recognition sites often spaced over tens of nanometers. In response, we have adapted DNA origami, with its unparalleled customizability to precisely display multiple target-binding sites over the relevant length scale, to an electrochemical biosensor platform. Our proof-of-concept employs triangular origami covalently attached to a gold electrode and functionalized with redox reporters. Electrochemical interrogation of this platform successfully monitors mesoscale, target-binding-induced changes in electron transfer in a manner consistent with coarse-grained molecular dynamics simulations. Our approach enables the specific detection of analytes displaying recognition sites that are separated by ~40 nm, a spacing significantly greater than that achieved in similar sensor architectures employing either antibodies or aptamers.
AB - The specific detection in clinical samples of analytes with dimensions in the tens to hundreds of nanometers, such as viruses and large proteins, would improve disease diagnosis. Detection of these "mesoscale"analytes (as opposed to their nanoscale components), however, is challenging as it requires the simultaneous binding of multiple recognition sites often spaced over tens of nanometers. In response, we have adapted DNA origami, with its unparalleled customizability to precisely display multiple target-binding sites over the relevant length scale, to an electrochemical biosensor platform. Our proof-of-concept employs triangular origami covalently attached to a gold electrode and functionalized with redox reporters. Electrochemical interrogation of this platform successfully monitors mesoscale, target-binding-induced changes in electron transfer in a manner consistent with coarse-grained molecular dynamics simulations. Our approach enables the specific detection of analytes displaying recognition sites that are separated by ~40 nm, a spacing significantly greater than that achieved in similar sensor architectures employing either antibodies or aptamers.
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U2 - 10.1039/d0nr00952k
DO - 10.1039/d0nr00952k
M3 - Article
C2 - 32578652
AN - SCOPUS:85088485474
SN - 2040-3364
VL - 12
SP - 13907
EP - 13911
JO - Nanoscale
JF - Nanoscale
IS - 26
ER -