Integrating optical techniques such as reflection, interferometry, scattering and fluorescence; bulk and surface acoustic waves; and microfluidics for measuring refractive index, viscosity, diffusion, surface tension, cell properties, and for sorting cell

The dream of all researchers working on microfluidic technology is the realization of fully automated and integrated systems for point-of-care diagnostics. Such systems are typically referred to as lab-on-a-chip (LoC) systems or micro-total-analysis-systems (μTAS). These systems hope to revolutionize medical diagnostics by decreasing both the size and cost of diagnostic systems.;In order to realize such a feat, radical new designs must be implemented in these systems. Furthermore, it is difficult to remain in one scientific discipline while working in this field. These integrated systems quickly become complicated with concerns in fluid dynamics, electronics, nanophotonics, acoustics, etc. Researchers must be versatile in this field and ready to learn new technologies as we push for smaller diagnostic systems with improved performance.;The title of this dissertation is a tribute to the multi-disciplinary atmosphere in the microfluidics field. The contributions in this dissertation involve design of complex fluid systems, optical detection techniques, and acoustic manipulation. This dissertation is organized into five chapters. Chapter 1 introduces microfluidic point-of-care systems, some basics of microfluidics, the integration of optics with microfluidics (optofluidics), and the integration of acoustics with microfluidics (acoustofluidics).;Chapter 2 describes several of the experimental methods which are common across all of the subsequent chapters. The microfabrication method (utilizing ultraviolet (UV) photolithograph, deep reactive ion etching (DRIE) of silicon, and mold replica production of polydimethylsiloxane (PDMS)) used to fabricate microfluidic channels is described in detail. The integration of optical fibers with microfludic channels is described, and the purpose for single-mode and multimode optical fibers is explained. The process of designing integrated microlenses in PDMS using a ray tracing simulation programed in MATLAB is described.;Chapter 3 introduces several systems based on optical reflection. A variable optical attenuator was developed using optofluidic integration of optical fibers with a reflection-based signal transduction method. An optical switch was designed using bulk acoustic waves to alter the reflectivity of an optical interface and tune the output of the switch. This project was an interesting combination of acoustic, optical and microfluidic systems. The final technology described in chapter 3 is the application of reflection-based sensing for monitoring diffusive mass transfer in a microfluidic channel. This system utilized simple fabrication processes and was able to detect refractive index, viscosity, and diffusion.;In chapter 4, interference based detection is utilized for three projects. The first project introduced a simple, but highly sensitive, optical interferometer that easily integrates with any typical microfluidic system. This interferometer could detect minute changes in refractive index, and to demonstrate a biosensing application, various concentrations of the protein bovine serum albumin (BSA) were detected using the interferometer. The second installment of chapter 4 describes a system which integrates droplet microfluidics with interferometry for high through-put analysis. This system was able to detect concentrations of calcium chloride, glucose and polyethylene glycol (PEG) 8000. In the third project, a bubble was trapped in the active region of the interferometer. The interferometer could detect acoustic oscillations of the bubble on the order of a few microns. This could have applications in characterizing acoustic oscillations of bubbles, measuring fluid parameters such as viscosity and surface tension, or possibly even detect material properties of artificial cell membranes. Extensive video processing was used to analyze videos captured with a high speed camera. Oscillations of the bubble at 135 kHz push the limit of the 500,000 frames per second camera and a program was written to use time-to-period correlation to reconstruct the oscillation at this high frequency. Interestingly, the interferometer could easily recored the oscillations of the bubble at this frequency.;Chapter 5 introduces a system integrating microfluidic flow focusing, optical detection and acoustic sorting to produce a highly integrated fluorescent activated cell sorting (FACS) system. In this system, the CD-45 receptor of human promyelocytic leukemia cells (HL-60) was tagged with a antibody-fluorescent complex. This is a good model for testing the FACS system, because this is a standard method for tagging cell for flow cytometry, as opposed to using fluorescent beads to test the system. An integrated optofludic system was designed to detect both fluorescent on non-fluorescent cells. A custom electrical feedback system was created to trigger sorting of the fluorescent cells. Surface acoustic waves (SAW), generated by on-chip, interdigitated transducers (IDTs), were used to sort the cells. Such a system could have a drastic impact on the miniaturization of flow cytometry systems.;This dissertation represents a strong multi-disciplinary contribution to the microfluidic and point-of-care diagnostic fields. It has been as serious undertaking that has provided the author with a wide range of skills in theoretical modeling, data analysis, project management, communication, and team work.