Development of a surface acoustic wave microfluidic system modified with an antibody specific to ceramide, a potential biomarker for lung cancer diagnosis, and a boronic acid derivative

In this thesis, detection of C24 ceramide levels, which are known to be associated with lung cancer, was investigated using a surface acoustic wave (SAW) microfluidic system, and its potential as a biomarker for lung cancer diagnosis was investigated. For this purpose, a microfluidic system based on SAW metamaterials was designed using finite element method (FEM) simulations. The metamaterial, which consists of periodic rectangular grooves oriented perpendicular to the Rayleigh SAW, exhibited a sharp Fabry-Perot (FP) absorption band around 200 MHz for specific groove lengths. The resonance frequency shifted linearly due to the mass-loading effect. (E)-(2-(((2-mercaptoethyl)imino)methyl)thiophen-3-yl)boronic acid and (E)-(2-(((2-mercaptoethyl)imino)methyl)phenyl)boronic acid were synthesized along with numerical calculations, and the following molecular assemblies were prepared: 3-thiopheneboronic acid-cysteamine, 4-mercaptophenylboronic acid-cysteamine, and methylboronic acid-cysteamine. Among the synthesized boronic acids, (E)-(2-(((2-mercaptoethyl)imino)methyl)phenyl)boronic acid, being soluble in phosphate-buffered saline (PBS), was selected for C24 detection experiments with the SAW metamaterial. Transmission spectra of the fabricated SAW metamaterial were consistent with the numerical calculations. When anti-ceramide monoclonal antibody (MID 15B4) or boronic acid was introduced into the microchannel in PBS solution, both were observed to adhere to the gold surfaces of the metamaterial, as indicated by shifts in the resonance frequency. When solutions containing C24 were introduced, distinct shifts in the FP resonance frequency were observed. These findings demonstrate that the metamaterial, decorated with MID 15B4 and/or boronic acid derivatives, can detect low C24 levels.