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Enabling Multi-Zone Impedance Measurements for Higher Resolution Trans-Endothelial Electrical Resistance (TEER), and Single-Cell Viscoelastic Analysis.

Abstract

The spatial and temporal resolution improvements of current and future biological assays are crucial elements in our advance toward single-cell assays, by which we dissect population-level averages to better understand disease progression and treatment. In this dissertation, spatial and temporal resolution improvements are demonstrated for two platforms by implementing a multi-zone measurement approach. For the first platform, we implement a multi-zone trans-endothelial electrical resistance (mz-TEER) continuous measurement within a microfluidic platform. This has enabled us to measure four distinct TEER zones within a single sample versus measuring one bulk TEER value. This work opens the door to questions of hetero- and homogeneity, and crosstalk between the cells on each of the respective zones. I will discuss how our results, using MCF-7GFP cell monolayers, showed that we are capable of monitoring these zones independently, and provide important future objectives for biologically relevant experiments, and improvements to the platform. Secondly, using the knowledge gained from developing mz-TEER, I then aimed to improve another impedance-based microfluidic platform developed in our lab previously, visco node-pore-sensing (viscoNPS) which is capable of measuring the viscoelastic properties of single cells at a single user-defined frequency. With an improvement similar to mz-TEER, we enhanced this platform by adding multi-zone measurement capabilities supported through the development of custom hardware and software, enabling each cell to be tested at up to four user defined frequencies.

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