A Love-mode Surface Acoustic Wave Based Sensor
For Gravimetric Detection of Extracellular Vesicles in Liquid Samples
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Abstract
Prostate cancer is the most prevalent form of cancer among men, increasing in annual prevalence. Often, the disease progression is less intrusive then treatment. Sensitive and low-intrusive diagnosis methods exist but these are not specific. Causing the need for biopsy, an intrusive and high risk for complication procedure.
This thesis sets out to design, fabricate and test a low cost, maximum sensitivity for surface mass loading Love-mode surface acoustic wave (SAW) based sensor. The thesis goal and requirements build up to answer the research question: Can the biomarker CD9 in a liquid sample be detected by means of a Love-mode surface acoustic wave device?
SAW based sensors utilise the modulation of acoustic vibrations to detect an analyte. In this thesis, the change is caused by the immobilisation of a biomarker on a delay line between an input and output transducer. The method, more often referred to as gravimetric sensing, is based on the shift of the passband frequency by a change in surface mass density due to selective immobilisation of the biomarker. The change in passband frequency is detected by the change in phase at the fixed frequency. In this work, the fixed frequency within the passband is around 620MHz.
The Love-mode SAW is transceived by 8$\mu$m wavelength spaced interdigitated transducers on piezoelectric crystalline ST-cut quartz utilising Y propagating waves. The wave mode becomes Love-mode by capturing the wave energy using a slower shear horizontal wave speed 900nm polyimide waveguide layer.
The biomarker is the transmembrane protein CD9, present on extra cellular vesicles. These CD9 positive extracellular vesicles are well accessible as they are present in body fluids including urine. In this work, in vitro cell culture derived CD9 positive extracellular vesicles are used.
After an extensive study to the design of a Love-mode SAW based sensor and micro fabrication, using the high frequency probe station device characterisation method, it can be concluded Love-mode SAWs were excited. The devices show sensitivity for different liquids and are proven to be able to immobilise CD9 utilising covalent immobilised streptavidin and biotinylated monoclonal anti-CD9. The devices show a response to CD9 containing samples but are not proven to be sufficiently sensitive for CD9 in liquid sample detection.
It is recommended the sensor achieved sensitivity is first more systematically determined. Then a more robust measurement setup must be designed, less prone to cross sensitivity to environmental changes and experimental variations. Then a next generation sensor for better sensitivity to surface mass loading in liquid samples can be designed.