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Technologies for protein analysis and tissue engineering, with applications in cancer


Vermesh, Udi Benjamin (2011) Technologies for protein analysis and tissue engineering, with applications in cancer. Dissertation (Ph.D.), California Institute of Technology.


The first part of this thesis describes electrolyte transport through an array of 20 nm wide, 20 μm long SiO2 nanofluidic transistors. At sufficiently low ionic strength, the Debye screening length exceeds the channel width, and ion transport is limited by the negatively charged channel surfaces. At source-drain biases > 5 V, the current exhibits a sharp, nonlinear increase, with a 20 − 50-fold conductance enhancement. This behavior is attributed to a breakdown of the zero-slip condition. Implications for peptide sequencing as well as energy conversion devices are discussed. The next part describes a technology for the detection of the highly aggressive brain cancer glioblastoma multiforme (GBM). In this study, we used an antibody-based microarray to compare plasma samples from glioblastoma patients and healthy controls with respect to the plasma levels of 35 different proteins known to be generally associated with tumor growth, survival, invasion, migration, and immune regulation. Average-linkage hierarchical clustering of the patient data stratified the two groups effectively, permitting accurate assignment of test samples into either GBM or healthy control groups with a sensitivity and specificity as high as 90 % and 94 %, respectively. Using the same 35-protein panel, we then analyzed plasma samples from GBM patients who were treated with the chemotherapeutic drug Avastin (Bevacizumab) and were able to effectively stratify patients based on treatment-responsiveness. Finally, single-cell resolution patterning of tissue engineered structures is demonstrated. The proper functioning of engineered constructs for tissue and organ transplantation requires positioning different cell types in anatomically precise arrangements that mimic their configurations in native tissues. Toward this end, we have developed a technique that involves two microfluidic-patterning steps run perpendicularly to each other using “anchor” and “bridge” DNA oligomers to create dense arrays of DNA grids which can then be converted into cell arrays. As a proof-of-concept, both a neuron-astrocyte construct and a pancreatic islet construct containing 2 distinct islet cell types were patterned separately as a dense array of cell grids. Once fixed in a hydrogel matrix, layers of patterned cells were then stacked to form 3-D tissue engineered constructs.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:protein analysis; nanofluidics; tissue engineering; cancer; diagnostics; glioblastoma
Degree Grantor:California Institute of Technology
Division:Engineering and Applied Science
Major Option:Bioengineering
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Heath, James R.
Thesis Committee:
  • Heath, James R. (chair)
  • Tirrell, David A.
  • Gharib, Morteza
  • Grubbs, Robert H.
Defense Date:4 October 2010
Record Number:CaltechTHESIS:12182010-040540249
Persistent URL:
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:6218
Deposited By: Udi Vermesh
Deposited On:18 Feb 2011 00:18
Last Modified:22 Aug 2016 21:21

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