PhD. Thesis Defense: İsmail Bütün
New Generation Microfluidic Chips for Micromixing and Early Cancer Diagnosis
İsmail Bütün
Mechatronics Engineering, PhD Dissertation, 2025
Thesis Jury
Prof. Dr. Ali Koşar (Thesis Advisor),
Assoc. Prof. Dr. Hüseyin Üvet,
Asst. Prof. Dr. Özlem Kutlu,
Prof. Dr. Burç Mısırlıoğlu,
Assoc. Prof. Dr. Yegan Erdem,
Date & Time: 17th July, 2025 – 2:00 PM
Place: FENS - 2019
Online Link (Zoom): https://sabanciuniv.zoom.us/j/
Keywords : Microfluidics, Micromixers, Diagnosis, Surface Acoustic Wave Resonators, Biosensors, Early Cancer Diagnosis.
Abstract
Driven by the growing demand for rapid, label-free, and ultra-sensitive diagnostic technologies, this thesis presents advanced microfluidic platforms, namely serpentine and three-dimensional nonlinear helical micromixers (3D NHMs), which were designed and developed for high-performance micromixing and diagnostic applications, along with shear-horizontal surface acoustic wave (SH-SAW) resonators developed for ultra-sensitive biomolecular detection. Together, these platforms offer compact, real-time, and clinically relevant solutions for early-stage disease diagnostics, with a particular focus on cancer diagnostics. 3D NHMs achieve near-complete mixing (mixing index >99.8%) within microseconds, across a broad range of Reynolds numbers. Unlike conventional passive micromixers, this platform delivers rapid and efficient homogenization without relying on internal surface roughness, as confirmed by numerical approaches and experimental validation. To evaluate the diagnostic capability, the micromixers were tested using functionalized superparamagnetic iron oxide nanoparticles (SPIONs) by monitoring the change in the hydrodynamic size during biomarker coalescence. Shifts in the nanoparticle hydrodynamic size revealed highly specific biomolecular interactions, which were characterized by linear increase, exponential association kinetics and saturation behavior, demonstrating the platform’s sensitivity and precision for molecular detection. The second platform, microfluidic integrated SAW resonators with ST-cut quartz substrate, features interdigitated transducers (IDTs) fabricated using optical and electron beam lithography, along with a gold sensing surface functionalized through self-assembled monolayers and EDC/NHS chemistry. Upon target molecule binding, the sensor exhibited substantial acoustic responses, including resonance frequency shifts of up to 1.2 MHz and insertion loss changes of up to 3.5 dB. The device achieved a detection limit as low as 1 pg/mL, with excellent linearity (R² > 0.98), confirming its ultra-sensitive performance. Both platforms were developed as modular, standalone units with low-cost, scalable designs that are readily adaptable to portable, point-of-care diagnostic devices. By integrating microfluidics, nanotechnology, and acoustics, this thesis, an outcome of TUBITAK (Turkish Scientific and Technological Council) Center of Excellence SUNUM 1004 NANOSIS Programme, presents a significant advancement in miniaturized, label-free sensing platforms, offering high-resolution, real-time biomarker analysis with strong potential for future clinical and personalized medicine applications.