title: Detection of the antiepileptic drug phenytoin using a single free-standing piezoresistive microcantilever for therapeutic drug monitoring.
abstract: Phenytoin, one of the most widely used antiepileptic drugs, suppresses the abnormal brain activity often seen in seizures. In this study, we report the electrical detection of phenytoin as an antiepileptic medication with a narrow therapeutic dosage range to which therapeutic drug monitoring (TDM) is applied. The measurement technique used an electrical detection of a piezoresistive microcantilever biosensor. This label-free, electrically measured microcantilever can be miniaturized in order to be portable for point-of-care, personal diagnosis or for personalized therapeutic drug monitoring. The miniaturized piezoresistive microcantilever was fabricated by micro-electro-mechanical system processes, and was integrated into a microfluidic channel with a system for label-free detection. The microcantilever biosensor was approved for the detection of phenytoin in solutions of deionized water and 100% fetal bovine serum. A linear profile in a drug-concentration range of 10-80 μg/mL was detected, with the signal resolution being about 0.005 Ω. The concentration sensitivity was 2.94×10(-6) (μg/mL)(-1). The binding affinity (KD) was calculated to be 58 μg/mL. The results of the present piezoresistive microcantilever biosensors showed a solid correlation of phenytoin drug detection with that in the clinically used fluorescence polarization immunoassay (FPIA).
authors.affiliation: Institute of Applied Mechanics, National Taiwan University, Taipei 106, Taiwan. Electronic address: Lshuang@ntu.edu.tw.
authors.forename: Long-Sun
authors.initials: LS
authors.lastname: Huang
authors.affiliation: Institute of Applied Mechanics, National Taiwan University, Taipei 106, Taiwan.
authors.forename: Yotsapoom
authors.initials: Y
authors.lastname: Pheanpanitporn
authors.affiliation: Institute of Applied Mechanics, National Taiwan University, Taipei 106, Taiwan.
authors.forename: Yi-Kuang
authors.initials: YK
authors.lastname: Yen
authors.affiliation: Institute of Applied Mechanics, National Taiwan University, Taipei 106, Taiwan.
authors.forename: Kai-Fung
authors.initials: KF
authors.lastname: Chang
authors.affiliation: Institute of Applied Mechanics, National Taiwan University, Taipei 106, Taiwan.
authors.forename: Lung-Yi
authors.initials: LY
authors.lastname: Lin
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei 106, Taiwan.
authors.forename: Dar-Ming
authors.initials: DM
authors.lastname: Lai
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000032:analysis / Q000097:blood*; D015374:Biosensing Techniques / Q000295:instrumentation; D002417:Cattle; D016903:Drug Monitoring / Q000295:instrumentation*; D004867:Equipment Design; D057230:Limit of Detection; D055617:Micro-Electrical-Mechanical Systems / Q000295:instrumentation*; D010672:Phenytoin / Q000032:analysis / Q000097:blood*; D014867:Water / Q000032:analysis
chemical_list: D000927:Anticonvulsants; D014867:Water; D010672:Phenytoin
keywords: Antiepileptic drug; Phenytoin; Piezoresistive microcantilever; Serum; Therapeutic drug monitoring