UC San Diego

This dissertation details the development of a portable, low cost lab-on-a-chip flow cytometer and/or fluorescence- activated cell sorter [Mu]FACS), in which microfluidics, micro-acoustics, on-chip optics and electronics are integrated into one tiny polydimethylsiloxane (PDMS) chip creating novel functionalities. This work demonstrates a compact, high-speed sorter, integrated optofluidic waveguides, and a novel color-space-time coding technique for low-cost fluorescence detection. The microfluidic fluorescence-activated cell sorter employs fast-response piezoelectric actuators in conjunction with a high-speed, low timing jitter closed loop control system ensures high purity sorting of targeted biological samples with single- cell manipulation capabilities. By deflecting the entire sub-nanoliter volume of fluid, the [Mu]FACS can sort various biological samples regardless of their physical or chemical properties. A high enrichment factor (>230 fold) is demonstrated at a sorting throughput of greater than 1, 000 cells/sec. By integrating the entire sorting system onto the chip, this technology holds great promise to rapidly become competitive with commercial benchtop sorters. Teflon AF coated optofluidic waveguides demonstrated in this work enhance the coupling efficiency of photons to fluorescent samples, thus increasing sensitivity and permitting multi-spot illumination. The waveguides also enable the space-time coding technology, which works in conjunction with a specially designed spatial filter and the finite-impulse-response (FIR) match filter algorithm in order to further enhance detection sensitivity. The multi-color fluorescence detection technology with an on-chip color filter waveguide array, known as Color-Space-Time (COST) coding, enables the discrimination of up to 11 fluorescent wavelengths using a single photodetector. This novel technology holds great promise for compactness by fundamentally altering the scaling rule; that is the number of bulky optical components required for detection will no longer scale linearly with the number of detection parameters. In this way, the technique can significantly lower the cost and the volume of the whole system in addition to miniaturization of the device. Such a low-cost, compact, portable flow cytometer and [Mu]FACS system can be readily afforded by individual clinics and research labs, providing point-of-care diagnosis and analysis. The development of the microfluidic flow cytometer/[Mu]FACS can improve global quality of life; and while the technology is not fully ready today, great strides have been made towards achieving this goal, as demonstrated in this dissertation