Haun’s Tumor Tissue Processing Technology Wins NIH Funding
July 16, 2021 – UC Irvine biomedical engineering researchers have been awarded $1.1 million from the NIH National Cancer Institute’s Innovative Molecular Analysis Technologies program to further their work on an integrated microfluidic platform that could help dramatically change the way tumor tissue is clinically evaluated. With three years of funding support, the team, led by Jered Haun, associate professor, will be able to test the technology on human tissue samples. The results could help scientists make progress in disease diagnosis and drug development.
Solid tumors are complex mixtures of different cell types, and these differences are key factors driving disease progression, metastasis and drug resistance. “Assessing cellular heterogeneity and identifying key driver cells are critical for understanding tumor biology, and for creating the most powerful clinical diagnostics,” said Haun. “Targeted therapies must be directed toward the most important cell types if effective cures are to be achieved. With this technology applied in clinical settings, we hope to help usher in an era of precision molecular medicine.”
Currently, single cell analysis studies are hindered, as tissues must first be dissociated into single cell suspensions using methods that are often inefficient, labor-intensive and highly variable. Importantly, certain cell types can be released more easily than others, which will bias the single cell analysis assay and lead to incorrect conclusions.
The new platform will combine four separate microfluidic device technologies that Haun has pioneered. The devices were designed to work sequentially, starting from tissue specimen digestion, through dissociation and filtration to finally extracting single cells. Any remaining cell clusters would be recirculated back into the front end of the device to maximize cell recovery. Single cells will be continuously extracted from the system as soon as they are ready, within minutes after dissociation, to prevent overtreatment and maintain viability.
“This multifaceted approach will enable us to tailor flow properties and shear forces to the appropriate magnitude and size scale, resulting in gradual and ultimately complete breakdown of tissue in a fast, efficient and gentle manner,” said Haun.
The researchers will test each device separately using human breast, pancreatic and prostate tumor tissue specimens. They will then integrate all the devices into a versatile system that will operate one, multiple or all devices, as well as establish continuous processing. Finally, they will evaluate suspensions using single cell RNA sequencing, which assesses each cell’s gene expression profile, to determine whether cell subtypes are biased by any device component and/or released at different time points during the process.
Collaborators on the project include UCI’s Abraham Lee, professor of biomedical engineering, and Kai Kessenbrock, assistant professor of biological chemistry, as well as Denmark Technical University’s Henrik Bruus, professor of theoretical physics.
– Lori Brandt