Development and validation of an optical biosensor for rapid monitoring of adalimumab in serum of patients with Crohn's disease

Abstract

Therapeutic drug monitoring of adalimumab is recommended to improve therapeutic outcome in patients with Crohn's disease. Performing an ELISA requires a rather long time-to-result and the necessity of collecting multiple samples to decrease the cost per adalimumab determination. In this study, we aim to develop and validate a rapid assay suitable for measuring a single adalimumab serum sample using a fiber-optic surface plasmon resonance (FO-SPR) based sensor. Therefore, we have immobilized MA-ADM28B8 as capture antibody on an FO-probe and conjugated MA-ADM40D8 as detecting antibody to gold nanoparticles. A dose-response curve ranging from 2.5 to 40 ng/mL adalimumab was obtained in 1/400 diluted serum. Serum samples of patients with adalimumab concentrations between 1 and 16 μg/mL were measured whereas the negative control, a sample spiked with infliximab at a concentration of 16 μg/mL, showed no significant signal. Using a pre-functionalized FO-probe, the technology requires less than 45 minutes for measuring a single sample. Comparison of measurements between the biosensor and the ELISA revealed an excellent agreement with a Pearson r coefficient of 0.99 and an intra-class coefficient of 0.99. The reduced assay time and the possibility of measuring a single sample are major advantages compared to the ELISA. The developed and validated optical adalimumab biosensor could be a valuable point-of-care diagnostic tool for adalimumab quantification in patients with Crohn's disease.

Label-Free Quantification of Anti-TNF-α in Patients Treated with Adalimumab Using an Optical Biosensor

“…Bian et al, have reported a study evaluating adalimumab in Crohn’s disease patients’ serum by fibre optic SPR (FO-SPR). Anti-TNF-α mAb was immobilised using self-assembling monolayer (SAM) having high detection sensitivity [ 72 , 73 ]. However, (comparing our study to that reported by Bian) we used direct immobilisation which has been widely used in studies involving proteins [ 17 , 74 ], thereby avoiding the SAM formation step and taking advantage of the chip for functionalising it and directly evaluating anti-TNF-α antibodies.…”

Label-Free LSPR-Vertical Microcavity Biosensor for On-Site SARS-CoV-2 Detection

“…For functionalization, we adopted the method we proposed before with minor modifications [22]. Biofunctionalization was performed through a four-step process: carboxylic group functionalization with 11-mercaptoundecanoic acid; carboxylic group activation using a 0.4 M EDC/0.1 M NHS mixture solution; antibody immobilization; blocking.…”

Rapid biosensing SARS-CoV-2 antibodies in vaccinated healthy donors

“…Sufficient signal amplification is required when developing BLI into a biosensor. Gold nanoparticles proved to be an effective enhancer in surface plasmon resonance-based optical biosensors ( Bian et al, 2018 ; Lu et al, 2016 ), but their enhancing effect in BLI-based optical biosensors seems limited, as reflected by a recent study wherein maximal signals of approximately 3 nm were obtained for semi-quantitative detection of SARS-CoV-2 BAbs ( Dzimianski et al, 2020 ). Meanwhile, 3,3′-diaminobenzidine tetrahydrochloride (DAB), a metal precipitating substrate, combined with secondary antibody-conjugated horseradish peroxidase (HRP), is a more effective strategy for improving BLI signals ( Auer et al, 2015 ; Gandolfini et al, 2017 ; Gao et al, 2017 ).…”