Intracellular delivery of functional macromolecules is essential for biological research and medical application. For example, DNA and RNA delivery has been studied for gene therapy and CRISPR-based biosensing; enzymes and other proteins delivery has been investigated for manipulating cell metabolism; delivery of functional nanoparticles, such as gold nanoparticles and carbon nanotubes, has been explored for cancer therapy and intracellular single-molecule studies. Advancements in microfabrication have paved the way to control physical phenomena more accurately and efficiently. This makes the method of physical disruption of the membrane more promising than the others. However, the internal loading of the macromolecules can lead to some unexpected scenarios, such as disruption of the cell membrane, cytoplasmic content loss, and protein denaturation; leading to cell damage. This poses a dilemma that high payload usually leads to more cell damage and reduced cell viability. Yet, there is no in-depth study on the mechanism of pore opening due to the microscale and transient nature of the pores. A better understanding of the mechanism of pore formation on the cell surface and better methods for drug loading is needed to allow high loading efficiency while balancing the cells’ integrity. The aim of the project is to develop an integrated computational modeling and microfluidic system to study intracellular delivery of macromolecules for mammalian cells via shear-induced membrane pore formation. The computational model will be developed to help understand the mechanism of deformation-induced pore opening and cargo loading. The optimal flow rate and channel geometry will be explored to maximize the payload while maintaining cell integrity.
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