The Akay Lab biomedical research team at the University of Houston reports an improvement in a microfluidic brain cancer chip previously developed in their laboratory. The new chip allows simultaneous administration of multiple medications and a massive parallel test of the drug response to patients with glioblastoma (GBM), the most common malignant brain tumor, which accounts for 50% of all cases. Patients with GBM have a five-year survival rate of only 5.6%.
The new chip generates tumor spheroids, or groups, and provides large-scale assessments of the response of these GBM tumor cells to various concentrations and combinations of drugs. This platform could optimize the use of rare tumor samples derived from patients with GBM to provide valuable information about tumor growth and responses to drug therapies. “
Metin Akay, John S. Dunn Endowed President Professor of Biomedical Engineering and Head of Department
The article is published in the inaugural edition of IEEE Engineering in Medicine and Biology Open magazine of the society of engineering in medicine and biology.
The ability to quickly assess the effectiveness of a cancer drug would be a marked improvement over typical cancer protocols in which chemotherapy drugs are administered, then tested for several months, and a patient changes to another medication if The first is not effective. The new device can determine the optimal combination of medications in just two weeks. “When we can tell the doctor that the patient needs a combination of medications and the exact proportion of each, this is precision medicine.”
Akay’s team takes a tumor biopsy, cultivates it and places it on the chip. Then they add chemotherapy drugs to the chip’s microvalves to determine the best combination of medications and the specific proportion that kills most tumor cells.
The team cultured spheroids or tumor groups in 3D, from GBM cell lines, as well as GBM cells derived from the patient. in vitro and investigated the effect of the combination of temozolomide and a κB nuclear factor inhibitor on tumor growth.
“Our study revealed that these drugs have synergistic effects in inhibiting the formation of spheroids when used in combination, and suggests that this brain cancer chip allows large-scale, low-cost drug detection with effective samples for 3D cancer tumors in vitro. In addition, this platform could be applied to drug detection studies related to tissue engineering, “said assistant professor Yasmine Akay. She joins the team for assistant research professor Naze Gul Avci and postdoctoral fellow Hui Xia. Samples of tissue were provided by collaborating project Jay-Jiguang Zhu, MD, director, Neuro Oncology, McGovern School of Medicine at UT Health.
To minimize any sample loss in vitro, the team improved its existing brain cancer chip system by adding an additional layer of laminar flow distribution, which reduces sample loss during cell seeding and prevents spheroids from escaping. This allows spheroids to form uniformly throughout the chip for consistent drug testing between each spheroid.
Xia, H., et al. (2019) Temozolomide in combination with the NF-κB inhibitor significantly disrupts the formation of glioblastoma spheroid multiforme. IEEE Open Journal of Engineering in Medicine and Biology. doi.org/10.1109/OJEMB.2019.2962801.