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.
Highlights
Ovarian cancer is the fifth leading cause of cancer death among women in United States and it has a1.4% (1 in 71) lifetime risk [1]
8 μL dropleets of Bcl-22 solutions to t ensure that thhe shape annd coverage of the dropplets on the delay path were w same in i each test
shear horizontal (SH)-surface acoustic waves (SAWs) were employed with microfabricated interdigital transducers (IDTs) on ST-cut Quartz to quantify the B-cell lymphoma 2 (Bcl-2) concentration
Summary
1.4% (1 in 71) lifetime risk [1]. Diagnosis of ovarian cancer in the early stages currently accounts for only 30% of all cases, and in most late stages the cancer is lethal. Pelvic examination, ultrasound and blood levels of serum biomarker CA125 are the standard screening methods for ovarian cancer [2,3,4]. The average urinary level of Bcl-2 was found to be 0.59 ng/mL in healthy controls, 1.12 ng/mL in benign disorders, 2.60 ng/mL in early-stage ovarian cancer and 3.58 ng/mL in late-stage ovarian cancer. The efficacy of Bcl-2 as a biomarker for ovarian cancer was further validated by comparison to CA125 serum levels using ELISA tests on 35 samples from the same cohort [18]. The studied biosensor employs shear horizontal (SH) surface acoustic waves (SAWs) to identify mass loading changes caused by Bcl-2 binding to antibodies on the sensor surface It is composed of a pair of interdigital transducers (IDTs) microfabricated on ST-cut Quartz wafers in the direction 90° off x-axis and delay path functionalized to capture Bcl-2 proteins while minimizing non-specific adsorption (Figure 1). The final section covers the discussions and conclusion along with the future work
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