| dc.description.abstract | Cancer is the second leading cause of death in the United States. The most effective way to improve survival rate is to diagnose cancer at the early stage. Cancer screening has been developed for early stage cancer diagnosis. However, conventional imaging-based cancer screening methods still have many limitations to achieve early stage cancer diagnosis. For example, high doses of radiation may be delivered by some imaging methods. The size of the tumor must be big enough to be detectable. Moreover, many imaging-based methods fail to differentiate cancer tumor from benign tumor, due to the lack of detailed information. These limitations abate the capability of imaging-based cancer screening methods for early stage cancer diagnosis. In addition, further tests such as tissue biopsy may be required as supplement. Nevertheless, the invasiveness, consumption of time, localized sampling, and failure in monitoring inhibit the applications of tissue biopsy. Therefore, cancer screening methods using liquid biopsy is appealing to early stage cancer diagnosis. Liquid biopsy analyzes biomarkers in body fluids, particularly blood, for cancer diagnosis. Compared with tissue biopsy, liquid biopsy is non-invasive, rapid, less painful and risky, and capable of longitudinal monitoring. These advantages make liquid biopsy ideal for early stage cancer diagnosis. Many types of cancer biomarkers have been investigated, including circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and extracellular vesicles (EVs). However, the rarity of CTCs in blood, and the incapability of providing proteomic information in ctDNA impede their applications for early stage cancer diagnosis. Contrarily, EVs, particularly exosomes, benefit from its abundance and comprehensive molecular profile. In the first and second projects, we have developed a microfluidic continuous-flow platform (ExoSearch chip) for rapid exosome isolation streamlined with in situ, multiplexed detection of exosomes. Three tumor markers on exosome surface (CA-125, EpCAM, and CD24) were detected simultaneously by a mixture of three distinct fluorophores labeled respective antibodies. In the third project, we have developed a pneumatically gated microfluidic communicating vessel (μCOVE) chip for rapid and sensitive immunomagnetic enzyme-linked immunosorbent assay (ELISA). In the last project, we have further developed the μCOVE chip for on-chip exosome capture, lysis, and digital detection of exosomal proteins. We conclude that these microfluidic platforms will contribute to liquid biopsy toward early stage cancer diagnosis. | |
