Graduation Year

2013

Document Type

Dissertation

Degree

Ph.D.

Degree Granting Department

Mechanical Engineering

Major Professor

Rasim Guldiken

Keywords

Biomarker, Immunosensor, Love Wave, Perturbation, SAW, Surface Functionalization

Abstract

In this dissertation, guided surface acoustic wave sensors were investigated theoretically and experimentally in detail for immunosensing applications. Shear horizontal polarized guided surface acoustic wave propagation for mass loading sensing applications was modeled using analytical modeling and characterized by perturbation analysis. The model verification was performed experimentally and a surface acoustic wave immunosensor case study was presented. The results of the immunosensing were also investigated using the perturbation analysis.

Guided surface acoustic wave propagation problem was investigated in detail for gravimetric (or mass loading) guided wave sensors, more specifically for immunosensors. The analytical model was developed for multilayer systems taking viscoelasticity into account. The closed form algebraic solutions were obtained by applying appropriate boundary conditions. A numerical approach was used to solve dispersion equation. Detailed parametric investigation of dispersion curves was conducted using typical substrate materials and guiding layers. Substrate types of ST-cut quartz, 41° YX lithium Niobate and 36° YX lithium tantalate with guiding layers of silicon dioxide, metals (chromium and gold), and polymers (Parylene-C and SU-8) were investigated. The effects of frequency and degree of viscoelasticity were also studied. The results showed that frequency only has effect on thickness with same shaped dispersion curves. Dispersion curves were found to be unaffected by the degree of viscoelasticity. It was also observed that when there was a large shear velocity difference between substrate and guiding layer, a transition region with a gradual decrease in phase velocity was obtained. However, when shear velocities were close, a smooth transition was observed. Furthermore, it was observed that, large density differences between substrate and guiding layer resulted in sharp and with nearly constant slope transition. Smooth transition was observed for the cases of minimal density differences. Experimental verification of the model was done using multi-layer photoresists. It was shown that with modifications, the model was able to represent the cases studied.

Perturbation equations were developed with first order approximations by relating the slope of the dispersion curves with sensitivity. The equations were used to investigate the sensitivity for material selection (substrate, guiding layer, and mass perturbing layer) and degree of viscoelasticity. The investigations showed that the sensitivity was increased by using guiding layers with lower shear velocities and densities. Among the guiding layers investigated, Parylene C showed the highest sensitivity followed by gold and chrome. The perturbation investigations were also extended to viscoelasticity and to protein layers for immunosensing applications. It was observed that, viscous behavior resulted in slightly higher sensitivity; and sensitivity to protein layers was very close to sensitivity for polymers. The optimum case is found to be ST-cut quartz with Parylene-C guiding layer for protein layer sensing.

Finally, an immunosensing case study was presented for selective capture of protein B-cell lymphoma 2 (Bcl-2), which is elevated in many cancer types including ovarian cancer. The immunosensor was designed, fabricated, and experimentally characterized. An application-specific surface functionalization scheme with monoclonal antibodies, ODMS, Protein A/G and Pluronic F127 was developed and applied. Characterization was done using the oscillation frequency shift of with sensor used as the feedback element of an oscillator circuit. Detection of Bcl-2 with target sensitivity of 0.5 ng/ml from buffer solutions was presented. A linear relation between frequency shift and Bcl-2 concentration was observed. The selectivity was shown with experiments by introducing another protein, in addition to Bcl-2, to the buffer. It was seen that similar detection performance of Bcl-2 was obtained even with presence of control protein in very high concentrations. The results were also analyzed with perturbation equations.

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