SPR Biosensor for Quantification of Fetuin-A as a Promising Multibiomarker

Abstract

Early diagnosis of ongoing malignant disease is crucial to improve survival rate and life quality of the patients and requires sensitive detection of specific biomarkers e.g. prostate-specific antigen (PSA), carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), etc. In spite of current technological advances, malignant diseases are still identified in rather late stages, which have detrimental effect on the prognosis and treatment of the disease. Here, we present a biosensor able to detect fetuin-A, a potential multibiomarker. The biosensing platform is based on polymer brush combining antifouling monomer units of N-(2-hydroxypropyl)methacrylamide (HPMA) and carboxybetaine methacrylamide (CBMAA), statistically copolymerized by surface-initiated atom transfer radical polymerization. The copolymer poly(HPMA-co-CBMAA) exhibits excellent non-fouling properties in the most relevant biological media (i.e. blood plasma) as well as antithrombogenic surface properties by preventing the adhesion of blood components (i.e. leukocytes; platelets; and erythrocytes). Moreover, the polymer brush can be easily functionalized with biorecognition elements maintaining high resistance to blood fouling and the binding capacity can be regulated by tuning the ratio between CBMAA and HPMA units. The superior antifouling properties of the copolymer even after biofunctionalization were exploited to fabricate a new plasmonic biosensor for the analysis of fetuin-A in real clinical blood plasma samples. The assay used in this work can be explored as label-free affinity biosensor for diagnostics of different biomarkers in real clinical plasma samples and to shift the early biomarker detection toward novel biosensor technologies allowing point of care analysis.

Compact Grating-Coupled Biosensor for the Analysis of Thrombin

“…The surface mass density of the irreversibly deposited constituents Γ was determined from the change in the SPR signal baseline before and after the exposure to HBP as summarized in Figure 3b. In agreement with the previous studies, 46 there was no measurable change in Γ for pristine brushes demonstrating that the antifouling properties are not affected by the grating topology (Γ < 0.02 ng/mm 2 ). These characteristics are superior to those measured for bare gold (Γ = 0.66 ng/mm 2 ) and conventional gold modified with PEG-thiol SAM (Γ = 0.59 ng/mm 2 ).…”

“…Notably, the SPR analysis of complex biological media can be simplified by the implementation of an antifouling biointerface architecture that will resist the biological matrix effect and thus enable the specific detection of the target analyte without the need of sample dilution or signal amplification. The poly­[( N -(2-hydroxypropyl)­methacrylamide)- co -(carboxybetaine methacrylamide)] (poly­(HPMA- co -CBMAA)) brushes have become among the most successful strategies for eliminating protein adsorption on the sensor surface from blood serum and plasma − and saliva . Most importantly, the immobilization of the receptor molecules to these poly­(HPMA- co -CBMAA) brushes induces only minute changes in their structure, and thus, it minimally impairs their antifouling properties.…”

Affinity-Based Nanoarchitectured Biotransducer for Sensitivity Enhancement of Surface Plasmon Resonance Sensors for In Vitro Diagnosis: A Review

“…In a recent study, fetuin A detection using SPR biosensor has been divulged by Riedelová et al Herein, chicken polyclonal antifetuin-A IgY (affinity antibodies) was immobilized by EDC/NHS chemistry through the construction of amide bonds among carboxylic groups of the polymer and primary amines of the selected antibodies. Moreover, this detection protocol can be utilized for the fabrication of ultramodern SPR biosensors for early and accurate detection of various disease biomarkers . The excellent potential of COOH-GO decorated affinity-based SPR biosensors for protein (BSA) detection has been accomplished in recent years by another research group.…”

“…Moreover, this detection protocol can be utilized for the fabrication of ultramodern SPR biosensors for early and accurate detection of various disease biomarkers. 142 The excellent potential of COOH-GO decorated affinity-based SPR biosensors for protein (BSA) detection has been accomplished in recent years by another research group. In that, surface carboxyl groups of pristine GO were activated via EDC-NHS chemistry.…”