Label-Free Microfluidic Devices for Single-Cell Analysis and Liquid Biopsies

Mortality due to cancer is a global health issue that can be improved through further development of diagnostic and prognostic tools. Recent advancements in technologies aiding cancer research have made significant strides, however a demand for a non-invasive clinically relevant point-of-care tools exists. To accomplish this feat, the desired instrument needs to be low-cost, easy-to-operate, efficient, and have rapid processing and analysis. Microfluidic platforms in cancer research have proven to be advantageous due to its operation at the microscale, which has low costs, favorable physics, high precision, short experimentation time, and requires minimal reagent and sample sizes. Label-free technologies rely on cell biophysical characteristics to identify, evaluate, and study biological samples. Biomechanical probing of cells through deformability assays provides a label-free method of identifying cell health and monitoring response to physical and chemical stimuli. Bioimpedance analysis is an alternative versatile label-free method of evaluating cell characteristics by measuring cell response to electrical signals. Microfluidic technologies can facilitate biomechanical and bioelectrical analysis through deformability assays and impedance spectroscopy. This dissertation demonstrates scientific contributions towards single-cell analysis and liquid biopsy devices focusing on cancer research. First, cell deformability assays were improved through the introduction of multi-constriction channels, which revealed that cells have a non-linear response to deformation. Combining impedance analysis with microfluidic deformability assays provided a large dataset of mechano-electrical information, which improved cell characterization and greatly decreased post-processing times. Next, two unique biosensors demonstrated improved throughput while maintaining sensitivity of single-cell analysis assays through parallelization and incorporating machine learning for data processing. Liquid biopsies involve studying cancer cells in patient vascular systems, called circulating tumor cells (CTCs), through blood samples. CTC tests reveal valuable information on patient prognosis, diagnosis and can aide therapy selection in a minimally invasive manner. This body of work presents two liquid biopsy devices that enrich murine and human blood samples and isolate CTCs to ease detection and analysis. Additionally, a microfluidic CTC detection biosensor is introduced to reliably count and identify cancer cells in murine blood, where an extremely low-cost version of the assay is also validated. Thus, the assays presented in this dissertation show promise of microfluidic technologies towards point-of-care systems for cancer research.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Electrical Engineering

Department dc:contributor.department

Electrical Engineering

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

2023

Author dc:creator

• Ghassemi, Parham

Chair dc:contributor.committeechair

• Agah, Masoud

Committee members dc:contributor.committeemember

• Baumann, William T.
• Jia, Xiaoting
• Yi, Yang
• Li, Liwu

• Microfluidics
• impedance
• deformability
• liquid biopsy
• label-free

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Language dc:language.iso

en

Dc Identifier Other

vt_gsexam:33828

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/113064