Antibody-functionalized nanoporous surfaces enable high throughput specific cell capture

Thesis (Ph. D. in Medical and Electrical Engineering)--Harvard-MIT Program in Health Sciences and Technology, 2012.

Bibliographic Details
Main Author: Mittal, Sukant
Other Authors: Mehmet Toner.
Format: Thesis
Language:eng
Published: Massachusetts Institute of Technology 2012
Subjects:
Online Access:http://hdl.handle.net/1721.1/72913
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author Mittal, Sukant
author2 Mehmet Toner.
author_facet Mehmet Toner.
Mittal, Sukant
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description Thesis (Ph. D. in Medical and Electrical Engineering)--Harvard-MIT Program in Health Sciences and Technology, 2012.
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spelling mit-1721.1/729132019-04-10T17:07:31Z Antibody-functionalized nanoporous surfaces enable high throughput specific cell capture Nanoporous surfaces enable high throughput specific cell capture Mittal, Sukant Mehmet Toner. Harvard--MIT Program in Health Sciences and Technology. Harvard--MIT Program in Health Sciences and Technology. Harvard--MIT Program in Health Sciences and Technology. 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 2012-09-13T19:01:44Z 2012-09-13T19:01:44Z 2012 2012 Thesis http://hdl.handle.net/1721.1/72913 809078294 eng 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 114 p. application/pdf Massachusetts Institute of Technology
spellingShingle Harvard--MIT Program in Health Sciences and Technology.
Mittal, Sukant
Antibody-functionalized nanoporous surfaces enable high throughput specific cell capture
title Antibody-functionalized nanoporous surfaces enable high throughput specific cell capture
title_full Antibody-functionalized nanoporous surfaces enable high throughput specific cell capture
title_fullStr Antibody-functionalized nanoporous surfaces enable high throughput specific cell capture
title_full_unstemmed Antibody-functionalized nanoporous surfaces enable high throughput specific cell capture
title_short Antibody-functionalized nanoporous surfaces enable high throughput specific cell capture
title_sort antibody functionalized nanoporous surfaces enable high throughput specific cell capture
topic Harvard--MIT Program in Health Sciences and Technology.
url http://hdl.handle.net/1721.1/72913
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