Highly multiplexed label-free imaging sensor for accurate quantification of small-molecule binding kinetics

Date
2020-10-06
Authors
Chiodi, Elisa
Marn, Allison M.
Geib, Matthew T.
Ekiz Kanik, Fulya
Rejman, John
AnKrapp, David
Ünlü, M. Selim
Version
Published version
OA Version
Citation
E. Chiodi, A.M. Marn, M.T. Geib, F. Ekiz Kanik, J. Rejman, D. AnKrapp, M.S. Ünlü. 2020. "Highly Multiplexed Label-Free Imaging Sensor for Accurate Quantification of Small-Molecule Binding Kinetics.." ACS Omega, Volume 5, Issue 39, pp. 25358 - 25364. https://doi.org/10.1021/acsomega.0c03708
Abstract
Investigating the binding interaction of small molecules to large ligands is a compelling task for the field of drug development, as well as agro-biotechnology, since a common trait of drugs and toxins is often a low molecular weight (MW). Here, we improve the limit of detection of the Interferometric Reflectance Imaging Sensor (IRIS), a label-free, highly multiplexed biosensor, to perform small-molecule screening. In this work, characterization of small molecules binding to immobilized probes in a microarray format is demonstrated, with a limit of detection of 1 pg/mm2 in mass density. First, as a proof of concept to show the impact of spatial and temporal averaging on the system noise, detection of biotin (MW = 244.3 Da) binding to a streptavidin-functionalized chip is performed and the parameters are tuned to achieve maximum signal-to-noise ratio (SNR ≈ 34). The optimized system is then applied to the screening of a 20-multiplexed antibody chip against fumonisin B1 (MW = 721.8 Da), a mycotoxin found in cereal grains. The simultaneously recorded binding curves yield an SNR ≈ 8. Five out of twenty antibodies are also screened against the toxin in a lateral flow assay, obtaining consistent results. With the demonstrated noise characteristics, further sensitivity improvements are expected with the advancement of camera sensor technology.
Description
License
© 2020 American Chemical Society. This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.