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Micromachined Devices For In Vitro Biomedical Applications
Tata, Uday Shankar
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Cell migration is a central process in the development and maintenance of tissues. Any deviation in the process can have serious consequences, such as atherosclerosis and cancer metastasis. During cancer metastasis, chemokines produced at secondary sites form chemical gradients and attract the cancer cells from primary sites. One of the primary limitations for the study of cancer cell migration has been the lack of a suitable cost-effective assay for cell migration with easy translatability to clinical situations. To address these issues, a microfluidic device was designed for assaying of cancer cell migration towards different chemoattractants. The device was created with polydimethylsiloxane (PDMS). The device featured two chambers each with diameter of 5 mm and height of 6 mm. The chambers were designated as cell chamber and attractant chamber and were connected by ten microchannels. Each channel had a width of 20 μm, a length of 1 mm and a height of 10 μm. Using these devices, we obtained cell number, location, migration rate and time taken for cells to migrate in response to chemoattractants. Prostate cancer cells (PC-3), lung metastasized prostate cancer (PC-3 ML), normal prostate cells (PNT1A, PZ-HPV-7) and breast cancer cells (MDA-MB-231) response to different concentrations of Transforming Growth Factor-beta (TGF-β), Vascular Endothelial Growth Factor (VEGF), Epidermal Growth Factor (EGF), and basic Fibroblast Growth Factor (bFGF) was investigated. The effect of chemotherapy drugs like Docetaxel, Doxorubicin, Epirubicin and Gemzar on cell migration was also investigated. The device was also used to test the blood serum of patients with prostate cancer. Prostate and breast cancer preferentially metastasize to a particular set of organs. In order to investigate the preferential organ based metastasis, the effect of different organ extracts from a male rat on lung metastasized prostate cancer cells (PC-3 ML) was studied. To study synergistic effects of chemical and physical gradient on cell migration behavior during cancer metastasis, a tapered microchannels based microfluidic device was designed and fabricated. Width of the channel tapers from 20 µm to 5 µm over transition length of 50 µm. Three phenotype driven migratory behaviors namely, permeation, retreat and repolarization of PC-3, PNT1A, PC-3 ML and MDA-MB-231 to Epidermal Growth Factor (EGF), was observed. In order to investigate the proliferation driven migration of smooth muscles cells during atherosclerosis, A PDMS based compact 6-well device was developed. This device was used to study the combined effect of cyclic strain and various growth factors on cultured VSMCs. Cell adhesion, alignment, and proliferation under 10% or 20% cyclic strain at 1 Hz were studied using this surface-enhanced PDMS device. The combined effect of cyclic strain and growth factors on VSMC proliferation was also examined. The results demonstrate the utility of these micromachined microfluidic devices as a high throughput, cost effective and real time monitoring platform to study cell migration due to chemical and mechanical factors which is major process involved in diseases like cancer metastasis and atherosclerosis.