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• Onen, O
• Sisman, A
• Gallant, N
• Kruk, P
• Guldiken, R
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• Onen, O
• Sisman, A
• Gallant, N
• Kruk, P
• Guldiken, R
• [+] on PubMed
• Onen, O
• Sisman, A
• Gallant, N
• Kruk, P
• Guldiken, R

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Sensors 2012, 12(6), 7423-7437; doi:10.3390/s120607423

Article

A Urinary Bcl-2 Surface Acoustic Wave Biosensor for Early Ovarian Cancer Detection

Onursal Onen ¹ , Alper Sisman ^1,2 , Nathan D. Gallant ¹ , Patricia Kruk ³  and Rasim Guldiken ^1,*

¹ Department of Mechanical Engineering, University of South Florida, 4202 E. Fowler Avenue, ENB 118, Tampa, FL 33620, USA ² Department of Electrical and Electronics Engineering, Marmara University, Goztepe 34722, Istanbul, Turkey ³ Department of Pathology and Cell Biology, University of South Florida Health, 12901 Bruce B. Downs Blvd., MDC 11, Tampa, FL 33612, USA

* Author to whom correspondence should be addressed.

Received: 31 March 2012; in revised form: 22 May 2012 / Accepted: 28 May 2012 / Published: 31 May 2012

(This article belongs to the Special Issue BioMEMS and Advanced Analytical Sensors for Biological Applications)

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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.

Keywords: ovarian cancer; MEMS; piezoelectric; sensor; early detection; Bcl-2; SH; SAW; SAM; ultrasound

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