CaltechTHESIS
  A Caltech Library Service

Biotechnologies for Cancer Diagnostics: Cell Sorting, Protein Analysis and Imaging of Cellular Metabolism

Citation

Hwang, Kiwook (2013) Biotechnologies for Cancer Diagnostics: Cell Sorting, Protein Analysis and Imaging of Cellular Metabolism. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/Z6DN-0483. https://resolver.caltech.edu/CaltechTHESIS:06072013-111912342

Abstract

This thesis presents the development of chip-based technology for informative in vitro cancer diagnostics. In the first part of this thesis, I will present my contribution in the development of a technology called “Nucleic Acid Cell Sorting (NACS)”, based on microarrays composed of nucleic acid encoded peptide major histocompatibility complexes (p/MHC), and the experimental and theoretical methods to detect and analyze secreted proteins from single or few cells.

Secondly, a novel portable platform for imaging of cellular metabolism with radio probes is presented. A microfluidic chip, so called “Radiopharmaceutical Imaging Chip” (RIMChip), combined with a beta-particle imaging camera, is developed to visualize the uptake of radio probes in a small number of cells. Due to its sophisticated design, RIMChip allows robust and user-friendly execution of sensitive and quantitative radio assays. The performance of this platform is validated with adherent and suspension cancer cell lines. This platform is then applied to study the metabolic response of cancer cells under the treatment of drugs. Both cases of mouse lymphoma and human glioblastoma cell lines, the metabolic responses to the drug exposures are observed within a short time (~ 1 hour), and are correlated with the arrest of cell-cycle, or with changes in receptor tyrosine kinase signaling.

The last parts of this thesis present summaries of ongoing projects: development of a new agent as an in vivo imaging probe for c-MET, and quantitative monitoring of glycolytic metabolism of primary glioblastoma cells. To develop a new agent for c-MET imaging, the one-bead-one-compound combinatorial library method is used, coupled with iterative screening. The performance of the agent is quantitatively validated with cell-based fluorescent assays. In the case of monitoring the metabolism of primary glioblastoma cell, by RIMChip, cells were sorting according to their expression levels of oncoprotein, or were treated with different kinds of drugs to study the metabolic heterogeneity of cancer cells or metabolic response of glioblastoma cells to drug treatments, respectively.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Bioengineering, Cancer Diagnostics
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemistry
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Heath, James R.
Thesis Committee:
  • Goddard, William A., III (chair)
  • Cai, Long
  • Shan, Shu-ou
  • Heath, James R.
Defense Date:30 May 2013
Additional Information:Chapter 0 includes abstract and acknowledgment Chapter 1 includes introduction From Chapter 2 to Chapter 3, I present my past projects which are already published or in press. Chapter 4 and 5 summarize the current works, which I hope to release a year later. Appendix A and B includes the papers which I contributed.
Funders:
Funding AgencyGrant Number
Samsung ScholarshipUNSPECIFIED
Record Number:CaltechTHESIS:06072013-111912342
Persistent URL:https://resolver.caltech.edu/CaltechTHESIS:06072013-111912342
DOI:10.7907/Z6DN-0483
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:7865
Collection:CaltechTHESIS
Deposited By: Kiwook Hwang
Deposited On:17 Jun 2013 21:55
Last Modified:04 Oct 2019 00:02

Thesis Files

[img]
Preview
PDF (full thesis) - Final Version
See Usage Policy.

24MB
[img]
Preview
PDF (Chapter 0) - Final Version
See Usage Policy.

164kB
[img]
Preview
PDF (Chapter 1) - Final Version
See Usage Policy.

737kB
[img]
Preview
PDF (Chapter 2) - Final Version
See Usage Policy.

3MB
[img]
Preview
PDF (Chapter 3) - Final Version
See Usage Policy.

5MB
[img]
Preview
PDF (Chapter 4) - Final Version
See Usage Policy.

2MB
[img]
Preview
PDF (Chapter 5) - Final Version
See Usage Policy.

428kB
[img]
Preview
PDF (Appendix A) - Final Version
See Usage Policy.

810kB
[img]
Preview
PDF (Appendix B) - Final Version
See Usage Policy.

2MB

Repository Staff Only: item control page