/In-flow Cell Electroporation with Impedance Assessment for Improving Cell Therapy Development.

In-flow Cell Electroporation with Impedance Assessment for Improving Cell Therapy Development.

Leuven | More than two weeks ago

Explore the impedance fingerprint of electroporated cells.

Cell therapies have acquired increasing interest in recent years due to their growing effectiveness in treating diseases ranging from cancer to autoimmune disorders. A prime example is chimeric antigen receptor (CAR) T cell therapy, in which a patient’s own immune cells are reprogrammed to act as a living drug specifically against the patient’s cancer cells. A crucial step in the development and manufacturing of cell therapies is the intracellular delivery of exogeneous cargo (e.g. mRNA, nanoparticles, proteins, ...) into living cells to modify its innate function. However, current viral delivery methods suffer from safety and scaling issues, making researchers look for other alternatives.

 

One popular alternative method is electroporation: a technique where cells are exposed to a pulsed electric field which induces the formation of nanometer sized holes (pores) in the cell membrane. Molecules in the extracellular medium enter the cell through the pores, whereafter the membrane reseals, and the cell recovers. The characteristics of the applied electric pulse determine the size, amount, and lifetime of the induced pores, and therefore the size and amount of cargo delivered to the cell; while excessive pore formation can lead to cell death. Consequently, choosing the appropriate pulse parameters is of critical importance for delivery efficiency and cell viability.

 

With standard optical techniques like fluorescence microscopy or flow cytometry, the optimization of the electric pulse parameters is a long and tedious process. To allow for a more dynamic process, real-time analysis techniques are needed. Here, we integrate impedance cytometry modalities inside a microfluidic electroporation setup, to study the electroporation process in real-time, opening the possibility of developing “smart” in-flow electroporation devices.

 

The goal of this topic is to perform impedance analysis of electroporated cells to understand the relationship between electroporation parameters and the resulting impedance cytometry signal.


 

A summary of the work split is as follows:

  • Literature review (10%)
  • Experiments (40%)
    • Perform experiments on microfluidic platforms with integrated electroporation and impedance modalities.
    • Optimization of measurement setup and protocols
  • Data analysis (40%)
    • Analyze generated impedance and fluorescence data to understand the relationship between electroporation parameters and resulting impedance signal.
  • Documentation and Reporting (10%)


Type of project: Thesis, Internship

Required degree: Master of Science, Master of Engineering Science, Master of Bioengineering

Required background: Nanoscience & Nanotechnology, Physics, Biomedical engineering, Bioscience Engineering

Supervising scientist(s): For further information or for application, please contact: Mathijs Meert (Mathijs.Meert@imec.be) and Koen de Wijs (Koen.deWijs@imec.be)

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