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Measuring the effects of drugs on single cancer cell growth

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dc.contributor.advisor Scott R. Manalis. en_US Weng, Yaochung en_US
dc.contributor.other Massachusetts Institute of Technology. Computational and Systems Biology Program. en_US 2012-09-11T17:28:42Z 2012-09-11T17:28:42Z 2012 en_US 2012 en_US
dc.description Thesis (Ph. D.)--Massachusetts Institute of Technology, Computational and Systems Biology Program, 2012. en_US
dc.description This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections. en_US
dc.description Cataloged from student submitted PDF version of thesis. en_US
dc.description Includes bibliographical references. en_US
dc.description.abstract Understanding the effectiveness of a drug therapy on halting disease progression is an essential aspect of cancer biology. Conventional assays that study cell behavior after a drug intervention report the average response of a cell population which can mask the heterogeneity and dynamics of seemingly identical cells. Recently, many single-cell techniques have been developed, but there are currently no methods that can fully characterize the long-term effects of drug treatment on cancer cell growth. To accomplish such, we developed an instrument to measure single-cell growth before and after drug treatment. In order to achieve femtogram-level mass resolution, we employed the suspended microchannel resonator (SMR), a vacuum-packaged cantilever with an embedded channel. Here, we describe three implementations that involve different technologies (optical trap, mechanical trap, and dynamic ow trapping) to capture a cell for repeated measurements and to perform drug delivery. Applying the technique we developed based on the dynamic ow trapping, we were able to monitor one or more generations of a cancer cell before and after drug treatment. We investigated the growth of mouse leukemia cells in response to drugs that inhibit the mammalian target of rapamycin (mTOR) pathway, induce apoptosis, or prevent translational activity directly at the ribosome. Our method was able to discern a particular growth signature for each drug investigated and to discover a new phenotype in cells following mTOR inhibition. Furthermore, our data demonstrates that the instantaneous growth rate changes following a drug treatment could potentially predict the long-term inhibitory effect on cellular biogenesis and mass accumulation. en_US
dc.description.statementofresponsibility by Yaochung Weng. en_US
dc.format.extent 122 p. en_US
dc.language.iso eng en_US
dc.publisher Massachusetts Institute of Technology en_US
dc.rights 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. en_US
dc.rights.uri en_US
dc.subject Computational and Systems Biology Program. en_US
dc.title Measuring the effects of drugs on single cancer cell growth en_US
dc.type Thesis en_US Ph.D. en_US
dc.contributor.department Massachusetts Institute of Technology. Computational and Systems Biology Program. en_US
dc.identifier.oclc 806957124 en_US

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