Microfluidic Devices for Isolation of Circulating Tumor Cells

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Material Information

Title:
Microfluidic Devices for Isolation of Circulating Tumor Cells
Physical Description:
1 online resource (151 p.)
Language:
english
Creator:
Sheng, Weian
Publisher:
University of Florida
Place of Publication:
Gainesville, Fla.
Publication Date:

Thesis/Dissertation Information

Degree:
Doctorate ( Ph.D.)
Degree Grantor:
University of Florida
Degree Disciplines:
Mechanical Engineering, Mechanical and Aerospace Engineering
Committee Chair:
FAN,ZHONGHUI HUGH
Committee Co-Chair:
HAHN,DAVID WORTHINGTON
Committee Members:
ANGELINI,THOMAS ETTOR
TAN,WEIHONG

Subjects

Subjects / Keywords:
aptamers -- ctcs -- mems -- microfluidics
Mechanical and Aerospace Engineering -- Dissertations, Academic -- UF
Genre:
Mechanical Engineering thesis, Ph.D.
bibliography   ( marcgt )
theses   ( marcgt )
government publication (state, provincial, terriorial, dependent)   ( marcgt )
born-digital   ( sobekcm )
Electronic Thesis or Dissertation

Notes

Abstract:
Cancer induces high death rate because of the high probability of metastasis. During the progression of metastasis, cancer cells detach from primary tumors or metastatic sites and enter the bloodstream, becoming circulating tumor cells (CTCs). CTCs are thus responsible for the spreads of cancer to distant organs, which lead to cancer-induced death. The level of CTCs can provide valuable information for monitoring cancer status and predicting survival rate of cancer patients. However, CTCs are extraordinarily rare (only a few CTCs in 1 mL blood with billions of blood cells), making their isolation and characterization a formidable technological challenge. Therefore, the objective of this research is to develop microfluidic system-based approaches for efficient isolation of CTCs from blood. Firstly, we developed an aptamer-mediated micropillar-based microfluidic device, for efficiently capturing and enriching rare cancer cells. High-affinity DNA aptamers were used as an alternative capturing agent to antibodies for targeting cancer cells. The device consisted of >59,000 micropillars, which greatly enhanced the interactions between cells and the aptamer-coated surface. With optimized device geometry and flow rate, rare tumor cells were captured from whole blood with high efficiency, purity, throughput, and cell viability. Secondly, we incorporated nanoparticles in microfluidic devices for the enhanced capture of cancer cells. Simultaneous attachment of ~95 DNA aptamers onto each gold nanoparticle surface (forming DNA nanospheres) created an assembly of multivalent binding ligands, with significant enhancement of cell capture efficiency and throughput. The enhanced cell capture also accrues from the increased surface roughness, surface area and ligand density. A high-throughput flat channel device and micromixing device were developed for cancer cell isolation from lysed blood and whole blood, respectively. Finally, we developed a microfluidic geometrically enhanced mixing device for isolation of CTCs from pancreatic cancer patients. We demonstrated the potential utility of the device in monitoring the response to anti-cancer drug treatment in cancer patients. In summary, the microfluidic devices developed in this dissertation provide new means for efficient CTC isolation and accurate CTC enumeration. Since the methods are minimally invasive, the microfluidic devices show great potential for cancer diagnosis, monitoring disease progression and treatment response.
General Note:
In the series University of Florida Digital Collections.
General Note:
Includes vita.
Bibliography:
Includes bibliographical references.
Source of Description:
Description based on online resource; title from PDF title page.
Source of Description:
This bibliographic record is available under the Creative Commons CC0 public domain dedication. The University of Florida Libraries, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.
Statement of Responsibility:
by Weian Sheng.
Thesis:
Thesis (Ph.D.)--University of Florida, 2013.
Local:
Adviser: FAN,ZHONGHUI HUGH.
Local:
Co-adviser: HAHN,DAVID WORTHINGTON.
Electronic Access:
RESTRICTED TO UF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE UNTIL 2015-12-31

Record Information

Source Institution:
UFRGP
Rights Management:
Applicable rights reserved.
Classification:
lcc - LD1780 2013
System ID:
UFE0046115:00001