PhD Thesis Proposal: Mimi Lan

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"Tracking cell proliferation in 3D cell culture using electrical impedance"

Abstract:

Electrical impedance presents a non-invasive alternative for real-time monitoring of cell cultures. Bioimpedance, which measures the electrical properties of biological tissues, can be conducted using various electrode configurations and methods such as electrical impedance spectroscopy (EIS) and electrical impedance tomography (EIT). These techniques provide valuable data on tissue and cell characteristics, with EIT offering spatial imaging through impedance reconstruction.

Advances in tissue engineering holds great promise for new regenerative therapies and improved in-vitro drug testing systems. Regenerative therapies aim to repair or replace damaged tissues with functional tissues grown in laboratories, while advanced drug testing systems using 3D cultures can better recapitulate in-vivo conditions and accelerate drug development. Opportunities to access low Earth orbit are increasing, and the microgravity environment is being explored for its potential to develop higher-quality and more complex tissue cultures than those grown on the ground. However, these efforts are limited by current monitoring techniques. Light microscopy, confocal microscopy, biochemical assays, and histological sectioning are the primary methods used to evaluate the proliferation, viability, and differentiation status of 3D tissue cultures. These methods are often destructive, labor-intensive, and provide limited or single time-point data. Therefore, the ability to non-invasively and continuously monitor cell culture quality with spatial resolution using EIT is highly appealing.

This proposal aims to develop a tissue growth chamber integrated with EIT monitoring to facilitate real-time, non-invasive analysis of cell proliferation on 3D scaffolds. The project will design a biocompatible and stable system capable of detecting subtle changes in impedance over time. Initial experiments will characterize the detection and reconstruction capabilities of a 32-channel transimpedance EIT system. A new bioreactor integrating the 32-channel system will be designed and fabricated. A culminating experiment will use the system to cultivate and monitor a 3D tissue culture using EIT.

By leveraging these bioimpedance techniques, the proposed research seeks to improve the monitoring and analysis of 3D cell cultures, contributing to the advancement of tissue engineering. Successful outcomes will demonstrate the feasibility of EIT for real-time monitoring and provide a robust platform for future studies in tissue growth and drug testing under various conditions, including microgravity.

Thesis Committee

• Professor Ryan Halter (Chair)
• Professor Ethan Murphy
• Professor Katie Hixon
• Sarindr Bhumiratana, PhD (EpiBone)
  

Contact

For more information, contact Thayer Registrar at thayer.registrar@dartmouth.edu.