Nanoplasmonic biosensor device for the monitoring of acenocoumarol therapeutic drug in plasma

Abstract

Acenocoumarol (Sintrom®) is an oral anticoagulant prescribed for the treatment of a variety of thromboembolic disorders such as atrial fibrillation and thrombosis or embolism. It inhibits fibrin production preventing clot formation. Acenocoumarol has a narrow therapeutic range, and its effects depend on several factors, such as body weight, age, metabolism, diet, certain medical conditions or the intake of additional drugs, among others. A higher dose may result in the risk of bleeding, while if it is too low, the risk of blood clot can increase. Complementary tools that allow the therapeutic drug monitoring (TDM) of acenocoumarol plasmatic levels from the starting of the treatment would be of paramount importance to personalize the treatment. Point-of-care (POC) devices can offer an added value in facilitating on-site monitoring (i.e. hospitals, primary care doctor or even by the patient itself) and can aid in dosage management. With this aim, we have developed a compact and simple nanoplasmonic sensing device based on gold nanodisks for the rapid monitoring of acenocoumarol, using highly specific polyclonal antibodies produced against this drug. A specific and reproducible label free indirect competitive assay has been developed and the viability of performing the evaluation directly in plasma diluted 1:1 has been demonstrated. A limit of detection (LOD) of only 0.77 ± 0.69 nM, an IC of 48.2 ± 5.12 nM and a dynamic range between 3.38 ± 1.33 nM and 1154 ± 437 nM were achieved, which easily fit within the drug plasma levels of acenocoumarol, making this approach a highly attractive option for its decentralized monitoring in human plasma.

Optical biosensors - Illuminating the path to personalized drug dosing

“…Further, the detection of acenocoumarol using gold nanodisks and an indirect competitive antibody immunoassay was demonstrated in diluted plasma (Fig. 6B), with recoveries of 90.5-103.5% (Peláez et al, 2018). Another study quantified lidocaine using homocysteine coated AuNPs with a recovery of 94.75% in spiked urine, with an RSD of 4.1% (Dou et al, 2013).…”

Label-Free Plasmonic Biosensor for Rapid, Quantitative, and Highly Sensitive COVID-19 Serology: Implementation and Clinical Validation

“…1:1)) to carboxyl groups on the gold sensor chip through EDC/s-NHS chemistry [33][34][35] . For all the immobilized surfaces, a final blocking step was included to avoid non-specific adsorptions employing PLL-g-PEG 36,37 .…”

“…For this reason, we decided to employ a combination of blocking agents including poly-L-Lysine grafted Poly(ethylene glycol) (PLL-g-PEG), detergent Tween 20 and sodium sulfate dextran salt, all of which have successfully reduced non-specific interactions in previous works. 36,37 The performance of the assays in serum was directly evaluated with serum diluted at 10%, as the detectability range of the assay might certainly tolerate this dilution (i.e., LOD in the ng mL -1 range and presumably expected Ig concentrations in the μg mL -1 level) and still ensure a reliable semi-and quantitative detection. This dilution factor is considerably lower than the one commonly employed in ELISA or CLIA tests, which is around 40-200 times.…”

Label-Free Plasmonic Biosensor for Rapid, Quantitative, and Highly Sensitive COVID-19 Serology: Implementation and Clinical Validation

“…1:1)) to carboxyl groups on the gold sensor chip through EDC/s-NHS chemistry [33][34][35] . For all the immobilized surfaces, a final blocking step was included to avoid non-specific adsorptions employing PLL-g-PEG 36,37 . Finally, the sensor chips were kept under a continuous flow of PBST+DS (PBS 10 mM + 0.5% Tween 20 + 2 mg mL −1 DS) at 15 µL min −1 .…”