Hierarchical zwitterionic modification of a SERS substrate enables real-time drug monitoring in blood plasma.
Surface-enhanced Raman spectroscopy (SERS) is an ultrasensitive analytical technique with molecular specificity, making it an ideal candidate for therapeutic drug monitoring (TDM). However, in critical diagnostic media including blood, nonspecific protein adsorption coupled with weak surface affinities and small Raman activities of many analytes hinder the TDM application of SERS. Here we report a hierarchical surface modification strategy, first by coating a gold surface with a self-assembled monolayer (SAM) designed to attract or probe for analytes and then by grafting a non-fouling zwitterionic polymer brush layer to effectively repel protein fouling. We demonstrate how this modification can enable TDM applications by quantitatively and dynamically measuring the concentrations of several analytes-including an anticancer drug (doxorubicin), several TDM-requiring antidepressant and anti-seizure drugs, fructose and blood pH-in undiluted plasma. This hierarchical surface chemistry is widely applicable to many analytes and provides a generalized platform for SERS-based biosensing in complex real-world media.
Department of Chemical Engineering, University of Washington, Box 351750, Seattle, Washington 98195, USA.
Fang
0000-0001-7193-9486
F
Sun
Department of Chemical Engineering, University of Washington, Box 351750, Seattle, Washington 98195, USA.
Hsiang-Chieh
HC
Hung
Department of Chemical Engineering, University of Washington, Box 351750, Seattle, Washington 98195, USA.
Andrew
0000-0002-2628-1686
A
Sinclair
Department of Chemical Engineering, University of Washington, Box 351750, Seattle, Washington 98195, USA.
Peng
P
Zhang
Department of Chemical Engineering, University of Washington, Box 351750, Seattle, Washington 98195, USA.
Tao
T
Bai
Department of Chemical Engineering, University of Washington, Box 351750, Seattle, Washington 98195, USA.
Daniel David
DD
Galvan
Department of Chemical Engineering, University of Washington, Box 351750, Seattle, Washington 98195, USA.
Priyesh
P
Jain
Department of Bioengineering, University of Washington, Seattle, Washington 98195, USA.
Bowen
B
Li
Department of Chemical Engineering, University of Washington, Box 351750, Seattle, Washington 98195, USA.|Department of Bioengineering, University of Washington, Seattle, Washington 98195, USA.
Shaoyi
S
Jiang
Department of Chemical Engineering, University of Washington, Box 351750, Seattle, Washington 98195, USA.
Qiuming
Q
Yu
D015374:Biosensing Techniques / Q000379:methods; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D004364:Pharmaceutical Preparations / Q000097:blood*; D013059:Spectrum Analysis, Raman / Q000379:methods*
D004364:Pharmaceutical Preparations