Direct determination of a small-molecule drug, valproic acid, by an electrically-detected microcantilever biosensor for personalized diagnostics

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.