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Mehmet Toner. Mittal, Sukant Harvard--MIT Program in Health Sciences and Technology. Harvard University--MIT Division of Health Sciences and Technology 2012-09-13T19:01:44Z 2012-09-13T19:01:44Z 2012 2012 http://hdl.handle.net/1721.1/72913 809078294 Thesis (Ph. D. in Medical and Electrical Engineering)--Harvard-MIT Program in Health Sciences and Technology, 2012. Cataloged from PDF version of thesis. Includes bibliographical references (p. 108-114). Adhesion-based cell capture on surfaces in microfluidic devices forms the basis of numerous biomedical diagnostics and in vitro assays. Solid surface microfluidic platforms have been widely explored for biomedical diagnostics since samples can be precisely and reproducibly manipulated under well-defined physicochemical conditions. However, at these small length scales, the fluid dynamics are dominated by the high surface-to-volume ratio and interfacial phenomena limiting device performance at high flow rates. In contrast, cell homing to porous vasculature is highly effective in vivo during inflammation; stem cell trafficking and cancer metastasis. In this work, we demonstrate that fluid-permeable surface functionalized with cell-specific antibodies can promote efficient and selective cell capture in vitro. This architecture might be advantageous due to enhanced transport due to fluid field modification leading to diverted streamlines towards the surface. Moreover, specific cell-surface interactions can be promoted due to reduced shear, allowing gentle cell rolling and arrest. Together, these synergistic effects enable highly effective target cell capture at flow rates over an order of magnitude larger than existing devices with solid surfaces. Additionally, in this study, we overcome a major limitation relevant to porous surfaces due to formation of stagnant layers of cells from non-target background population. These stagnant layers are detrimental to device performance as they act to reduce interaction of the cells with the reactive surface thereby reducing capture efficiency. We theoretically and experimentally understand the mechanisms for formation of the stagnant bioparticle layer in microfluidic devices and define a parameter space for optimal operation of the device over long periods of time. Key insights from these studies, collectively allow us to design a spatially modified microfluidic devices that allow us to isolate cancer lines as low as 5 cells/mL spiked into buffy coat. by Sukant Mittal. Ph.D. in Medical and Electrical Engineering 114 p. eng Massachusetts Institute of Technology M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 Harvard--MIT Program in Health Sciences and Technology. Antibody-functionalized nanoporous surfaces enable high throughput specific cell capture Nanoporous surfaces enable high throughput specific cell capture Thesis application/pdf false Publication unknown unknown <Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="4dc7c297-d8e3-4f2a-a051-13309b849e51"> <Type xmlns="https://www.openaire.eu/cerif-profile/vocab/COAR_Publication_Types">http://purl.org/coar/resource_type/c_1843</Type> <Language>eng</Language> <Title>Antibody-functionalized nanoporous surfaces enable high throughput specific cell capture</Title> <Subtitle>Nanoporous surfaces enable high throughput specific cell capture</Subtitle> <PublishedIn> <Publication> </Publication> </PublishedIn> <PublicationDate>2012</PublicationDate> <Authors> <Author> <DisplayName>Mittal, Sukant</DisplayName> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> </Authors> <Editors> </Editors> <Publishers> <Publisher> <DisplayName>Massachusetts Institute of Technology</DisplayName> <OrgUnit /> </Publisher> </Publishers> <License>http://dspace.mit.edu/handle/1721.1/7582</License> <Keyword>Harvard--MIT Program in Health Sciences and Technology.</Keyword> <Abstract>Adhesion-based cell capture on surfaces in microfluidic devices forms the basis of numerous biomedical diagnostics and in vitro assays. Solid surface microfluidic platforms have been widely explored for biomedical diagnostics since samples can be precisely and reproducibly manipulated under well-defined physicochemical conditions. However, at these small length scales, the fluid dynamics are dominated by the high surface-to-volume ratio and interfacial phenomena limiting device performance at high flow rates. In contrast, cell homing to porous vasculature is highly effective in vivo during inflammation; stem cell trafficking and cancer metastasis. In this work, we demonstrate that fluid-permeable surface functionalized with cell-specific antibodies can promote efficient and selective cell capture in vitro. This architecture might be advantageous due to enhanced transport due to fluid field modification leading to diverted streamlines towards the surface. Moreover, specific cell-surface interactions can be promoted due to reduced shear, allowing gentle cell rolling and arrest. Together, these synergistic effects enable highly effective target cell capture at flow rates over an order of magnitude larger than existing devices with solid surfaces. Additionally, in this study, we overcome a major limitation relevant to porous surfaces due to formation of stagnant layers of cells from non-target background population. These stagnant layers are detrimental to device performance as they act to reduce interaction of the cells with the reactive surface thereby reducing capture efficiency. We theoretically and experimentally understand the mechanisms for formation of the stagnant bioparticle layer in microfluidic devices and define a parameter space for optimal operation of the device over long periods of time. Key insights from these studies, collectively allow us to design a spatially modified microfluidic devices that allow us to isolate cancer lines as low as 5 cells/mL spiked into buffy coat.</Abstract> <Access xmlns="http://purl.org/coar/access_right" > </Access> </Publication>