Stealth surface modification of surface-enhanced Raman scattering substrates for sensitive and accurate detection in protein solutions.
Reliable surface-enhanced Raman scattering (SERS) based biosensing in complex media is impeded by nonspecific protein adsorptions. Because of the near-field effect of SERS, it is challenging to modify SERS-active substrates using conventional nonfouling materials without introducing interference from their SERS signals. Herein, we report a stealth surface modification strategy for sensitive, specific and accurate detection of fructose in protein solutions using SERS by forming a mixed self-assembled monolayer (SAM). The SAM consists of a short zwitterionic thiol, N,N-dimethyl-cysteamine-carboxybetaine (CBT), and a fructose probe 4-mercaptophenylboronic acid (4-MPBA). The specifically designed and synthesized CBT not only resists protein fouling effectively, but also has very weak Raman activity compared to 4-MPBA. Thus, the CBT SAM provides a stealth surface modification to SERS-active substrates. The surface compositions of mixed SAMs were investigated using X-ray photoelectron spectroscopy (XPS) and SERS, and their nonfouling properties were studied with a surface plasmon resonance (SPR) biosensor. The mixed SAM with a surface composition of 94% CBT demonstrated a very low bovine serum albumin (BSA) adsorption (∼3 ng/cm(2)), and moreover, only the 4-MPBA signal appeared in the SERS spectrum. With the use of this surface-modified SERS-active substrate, quantification of fructose over clinically relevant concentrations (0.01-1 mM) was achieved. Partial least-squares regression (PLS) analysis showed that the detection sensitivity and accuracy were maintained for the measurements in 1 mg/mL BSA solutions. This stealth surface modification strategy provides a novel route to introduce nonfouling property to SERS-active substrates for SERS biosensing in complex media.
Department of Chemical Engineering, University of Washington, Seattle, Washington 98195, United States.
Fang
F
Sun
Department of Chemical Engineering, University of Washington, Seattle, Washington 98195, United States.
Jean-Rene
JR
Ella-Menye
Department of Chemical Engineering, University of Washington, Seattle, Washington 98195, United States.
Daniel David
DD
Galvan
Department of Chemical Engineering, University of Washington, Seattle, Washington 98195, United States.
Tao
T
Bai
Department of Chemical Engineering, University of Washington, Seattle, Washington 98195, United States.
Hsiang-Chieh
HC
Hung
Department of Chemical Engineering, University of Washington, Seattle, Washington 98195, United States.
Ying-Nien
YN
Chou
Department of Chemical Engineering, University of Washington, Seattle, Washington 98195, United States.
Peng
P
Zhang
Department of Chemical Engineering, University of Washington, Seattle, Washington 98195, United States.
Shaoyi
S
Jiang
Department of Chemical Engineering, University of Washington, Seattle, Washington 98195, United States.
Qiuming
Q
Yu
D000818:Animals; D001622:Betaine / Q000737:chemistry; D015374:Biosensing Techniques / Q000379:methods*; D001897:Boronic Acids / Q000737:chemistry; D002417:Cattle; D005632:Fructose / Q000032:analysis; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D012996:Solutions; D013059:Spectrum Analysis, Raman / Q000379:methods*; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013499:Surface Properties
C510906:4-mercaptophenylboronic acid; D001897:Boronic Acids; D012996:Solutions; D013438:Sulfhydryl Compounds; D012710:Serum Albumin, Bovine; D005632:Fructose; D001622:Betaine
complex media; nonfouling; surface modification; surface-enhanced Raman scattering; zwitterionic thiol