title: A urinary Bcl-2 surface acoustic wave biosensor for early ovarian cancer detection.
abstract: In this study, the design, fabrication, surface functionalization and experimental characterization of an ultrasonic MEMS biosensor for urinary anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) detection with sub ng/mL sensitivity is presented. It was previously shown that urinary Bcl-2 levels are reliably elevated during early and late stages of ovarian cancer. Our biosensor uses shear horizontal (SH) surface acoustic waves (SAWs) on surface functionalized ST-cut Quartz to quantify the mass loading change by protein adhesion to the delay path. SH-SAWs were generated and received by a pair of micro-fabricated interdigital transducers (IDTs) separated by a judiciously designed delay path. The delay path was surface-functionalized with monoclonal antibodies, ODMS, Protein A/G and Pluronic F127 for optimal Bcl-2 capture with minimal non-specific adsorption. Bcl-2 concentrations were quantified by the resulting resonance frequency shift detected by a custom designed resonator circuit. The target sensitivity for diagnosis and identifying the stage of ovarian cancer was successfully achieved with demonstrated Bcl-2 detection capability of 500 pg/mL. It was also shown that resonance frequency shift increases linearly with increasing Bcl-2 concentration.
authors.affiliation: Department of Mechanical Engineering, University of South Florida, Tampa, FL 33620, USA. onursalonen@mail.usf.edu
authors.forename: Onursal
authors.initials: O
authors.lastname: Onen
authors.forename: Alper
authors.initials: A
authors.lastname: Sisman
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Gallant
authors.forename: Patricia
authors.initials: P
authors.lastname: Kruk
authors.forename: Rasim
authors.initials: R
authors.lastname: Guldiken
mesh_terms: D000162:Acoustics; D015374:Biosensing Techniques / Q000295:instrumentation*; D016022:Case-Control Studies; D055088:Early Detection of Cancer / Q000295:instrumentation* / Q000379:methods*; D004581:Electronics; D005260:Female; D006801:Humans; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000652:urine*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000652:urine*; D013499:Surface Properties
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2