Abstract
Direct, small-molecule determination of the antiepileptic drug, valproic acid, was investigated by a label-free, nanomechanical biosensor. Valproic acid has long been used as an antiepileptic medication, which is administered through therapeutic drug monitoring and has a narrow therapeutic dosage range of 50–100 μg·mL−1 in blood or serum. Unlike labeled and clinically-used measurement techniques, the label-free, electrical detection microcantilever biosensor can be miniaturized and simplified for use in portable or hand-held point-of-care platforms or personal diagnostic tools. A micromachined microcantilever sensor was packaged into the micro-channel of a fluidic system. The measurement of the antiepileptic drug, valproic acid, in phosphate-buffered saline and serum used a single free-standing, piezoresistive microcantilever biosensor in a thermally-controlled system. The measured surface stresses showed a profile over a concentration range of 50–500 μg·mL−1, which covered the clinically therapeutic range of 50–100 μg·mL−1. The estimated limit of detection (LOD) was calculated to be 45 μg·mL−1, and the binding affinity between the drug and the antibody was measured at around 90 ± 21 μg·mL−1. Lastly, the results of the proposed device showed a similar profile in valproic acid drug detection with those of the clinically-used fluorescence polarization immunoassay.
Highlights
Microcantilever biosensors have shown great promise for application in chemical and biological analyses [1]
While the capture immunoglobin G (IgG) antibody has a molecular weight of around 150 kDa, this target drug of small molecules cannot be detected by the direct binding of the antigen-antibody interaction in label-free affinity optical surface plasmon resonance (SPR) biosensors
Direct determination of small molecular valproic acid was first investigated by a single, free-standing, label-free piezoresistive microcantilever biosensor
Summary
Microcantilever biosensors have shown great promise for application in chemical and biological analyses [1]. The microcantilever biosensing technique demonstrated label-free, direct determination in DNA hybridization [2,3], antibody-antigen binding [4,5], enzyme reactions [6], drug screening [7] and drug detection [8]. The specific bindings of molecular interactions induce a biomolecular conformation change, resulting in a nanomechanical response or the deflection of a microcantilever. In addition to not requiring fluorescence labeling, this biosensing technique provides high sensitivity and miniaturization for potential application in portable or disposable point-of-care platforms and personalized diagnostics. Several label-free techniques have been developed for biosensor detection. In label-free quartz crystal microbalance (QCM) immunosensors based on frequency change, the technique mainly focuses on measurements in the dry state in air. For dip-and-dry procedures, the measurement involves processes that are relatively cumbersome, time consuming and prone to error, due to hydration and humidity [9,10]
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