UC San Diego

This dissertation demonstrates the development of a portable and low cost lab-on-a-chip flow cytometer, in which various methods are applied to achieve label-free detections for rapid, accurate and high performance point- of-care applications. This work is based on the measurement of scattering light from cells or beads in the microfluidic channel to either collect scattering signals or image scattering light. An optical-coding technique is proposed to enhance the cell classification and minimize the cost with the compact form. The encoded scattering signals are collected by off-the-shelf PIN photoreceivers. The spatial distribution of cells or beads in the microfluidic channel can be readily extracted with the specific waveform. Although the theory of the inertial effect can explain the spatial distribution of objects with different sizes, the stiffness of cells is found to play a role on the distribution. The stiffness of cells can be used as an effective biomarker for cell classification. Moreover, with the aid of machine learning algorithms, the optical-coding technique can be expanded to proceed a multi-dimensional analysis, which further enhances the performance of the microfluidic flow cytometer. Recently, the study of sub-cellular structure has drawn more attention because the size and shape of cellular nucleus carry important information about biological activities such as apoptosis, cell cycle, cancerous metastasis, etc. However, current technologies have only used labeling technique to image cell nuclei for further observation. Another part of this work is to build up a label-free technique to unambiguously retrieve the information of cell nucleus, more importantly, by using widely available CMOS imagers. The scattering-imaging- based cytometer is demonstrated to record the scattering images from cancer or human white blood cells. The signature of cells can be graphically established to represent the size, shape and orientation of cell nucleus. Such a low-cost, compact, portable lab-on-a-chip cytometer platform can be easily afforded by individual clinics and research labs, satisfying point-of-care diagnosis and telemedicine applications. The development executed in this dissertation is aiming to improve the global health and lead a better life for human beings