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Title: Biomechanical Microdevices to Study Circulating Cancer Cells In Hematogenous Metastasis
Keywords: Biomechanics, Cancer, Circulating Tumor Cells, Microfluidics, Metastasis
Issue Date: 6-Aug-2010
Citation: TAN SWEE JIN (2010-08-06). Biomechanical Microdevices to Study Circulating Cancer Cells In Hematogenous Metastasis. ScholarBank@NUS Repository.
Abstract: The morbidity and mortality of cancer typically arises from metastasis of the primary tumor and it is generally accepted that secondary prevention through early detection yields the opportunity for early intervention. Spreading of cancer to distant sites is usually established through the body circulatory system and thus the number of circulating tumor cells (CTCs) in peripheral blood of cancer patients is strongly associated to the disease development. The technical challenge lies in the rarity of these cells in peripheral blood of cancer patients which makes them hard to be distinguished. Recent advances in microdevice technology have allowed highly sensitive techniques, and the current investigation seeks to demonstrate a system for the effective isolation and study of CTCs. The study presents a label-free microdevice that is capable of isolating cancer cells from whole blood via cancer cells¿ distinctively different physical properties such as size and deformability. The isolation of CTCs using microfluidics is attractive as the flow conditions can be accurately manipulated to achieve an efficient separation. Using physical structures placed in the path of blood specimens in a microchannel, CTCs which are generally larger and stiffer are retained while most blood constituents are removed. The operations for processing blood are straightforward and permit multiplexing of the microdevices to concurrently work with different samples. The microfluidic device is optically transparent which makes it simple to be integrated to existing laboratory microscopes and immunofluorescence staining can be done in situ to distinguish cancer cells from hematopoietic cells. This also minimizes the use of expensive staining reagents, given the small size of the microdevice. In the development of this microfluidic device, computational studies of the proposed microfluidic design along with results from feasibility studies are first performed. A full characterization of the microdevice with numerous cancer cell lines from different origins is then conducted. Finally, its direct use with clinical blood specimens is investigated. With the microfluidic system, it was demonstrated that an effective isolation could be attained and the microdevice is versatile to address the heterogeneities associated with different cancer types. The microsystem was verified with studies using cancer cell lines from breast, colorectal, gastric, liver, tongue and throat cancer. Using clinical blood specimens, isolation of CTCs was achieved with high sensitivity and attained close to 100% detection rate. Due to the unique separation technique, it also enabled the capture of a more diverse group of CTCs without the use of antibodies during enrichment. With this system, real-time visualization of CTC isolation can be achieved during blood processing. The microdevice shows promise in the isolation and investigation of CTCs on patients with metastatic cancer.
Appears in Collections:Ph.D Theses (Open)

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