Project 6

Assessing Ultrasound-Mediated Molecular Delivery In Microchamber Systems

(Prof. Jonathan Kopechek, BE)

(top) 3D-printed acoustofluidic device for rapid intracellular delivery of biomolecules. (bot) PDMS microwell chamber for single cell microscopy analysis.

Intracellular delivery of biomolecules is often required to transform cells for therapeutic effect. However, current molecular delivery techniques have safety concerns or are slow and inefficient. To address this problem, we have developed a unique 3D-printed acoustofluidic platform combining ultrasound technology in a flow system for rapid delivery of DNA or other biomolecules into cells (Figure 1) [1-4]. To further understand the key mechanisms involved in acoustofluidic molecular delivery, we are developing PDMS-based microchamber systems to analyze cellular behavior using single cell microscopy analysis. The goal of this project is to elucidate key factors that influence ultrasound-guided molecular delivery mechanisms of human cells. The results of these studies will enable optimization of acoustofluidic transfection methods for manufacturing of cellular therapies for improved human health, including development of novel dehydrated blood products for transfusion medicine and improved T cell immunotherapies for cancer treatment. The REU student will design and perform experiments to assess molecular delivery efficiency by delivering biomolecules into cells with microwell chambers for single-cell analysis. Students interested in BE, ME, ChE, Chem, or Bio would be excellent candidates.

References

1.           Centner, C.S., et al., Acoustofluidic-mediated molecular delivery to human T cells with a three-dimensional-printed flow chamber. J Acoust Soc Am, 2021. 150(6): p. 4534.

2.           Centner, C.S., et al., Comparison of Acoustofluidic and Static Systems for Ultrasound-Mediated Molecular Delivery to T Lymphocytes. Ultrasound Med Biol, 2023. 49(1): p. 90-105.

3.           Centner, C.S., et al., Ultrasound-induced molecular delivery to erythrocytes using a microfluidic system. Biomicrofluidics, 2020. 14(2): p. 024114.

4.           Centner, C.S., et al., Assembly and Operation of an Acoustofluidic Device for Enhanced Delivery of Molecular Compounds to Cells. J Vis Exp, 2021(167).