A research team from the University of Houston has recently reported improvements made on their microfluidic brain cancer chip, allowing for the administration of multiple drugs at the same time. This biomedical group, the Akay Lab, has also enabled their device to conduct parallel testing of drug responses for glioblastoma patients. The potential impact of this feature could be profound, with the glioblastoma being the most common cancerous brain tumor. Accounting for half of all malignant brain tumor cases, glioblastomas render an average ﬁve-year survival rate of less than 6%. These findings were recently published in the IEEE Open Journal of Engineering in Medicine and Biology.
“The new chip generates tumor spheroids, or clusters, and provides large-scale assessments on the response of these GBM tumor cells to various concentrations and combinations of drugs,” explained Metin Akay, the John S. Dunn Endowed Chair Professor of Biomedical Engineering and department chair at the University of Houston. “This platform could optimize the use of rare tumor samples derived from GBM patients to provide valuable insight on the tumor growth and responses to drug therapies.”
This ability to rapidly analyze how effective a cancer drug is would be a drastic improvement in comparison to the traditional way of doing so. Currently, cancer therapeutics are administered, tested for a few months and if ineffective, the patient is then switched to a new drug regimen. This trial and error approach is not only time consuming and burdensome for the patient but can bring about unnecessary costs and hinder the efficacy of treatment. By moving towards a microfluidic, multiple drug administration system, the Akay Lab’s device can potentially identify the ideal chemotherapy regimen in as fast as two weeks.
“When we can tell the doctor that the patient needs a combination of drugs and the exact proportion of each, this is precision medicine,” Metin Akay noted.
How the Microfluidic Brain Cancer Chip Works
First, Metin Akay and colleagues take a biopsy of the tumor, culture this tissue, and put it in the chip. Chemotherapy drugs are then introduced to the tissue through the microvalves in the chip, minimizing waste in this testing process. At the end of the procedure, the best drug combination and proportion is determined by which regimen kills the most tumor cells.
The researchers then cultured 3D tumor spheroids, or clusters, from the glioblastoma cell lines and patient-derived glioblastoma cells in vitro and analyzed the effects of a combination of Temozolomide and a nuclear factor-κB inhibitor on tumor growth. The findings of this combination therapy were very positive regarding brain tumor inhibition. Tissue samples were provided by Jay-Jiguang Zhu, MD, director, Neuro Oncology, McGovern Medical School at UT Health.
“Our study revealed that these drugs have synergistic effects in inhibiting spheroid formation when used in combination, and suggests that this brain cancer chip enables large-scale, inexpensive and sample-effective drug screening to 3D cancer tumors in vitro. Further, this platform could be applied to related tissue engineering drug screening studies,” explained assistant professor Yasmine Akay, who was accompanied by research assistant professor Naze Gul Avci and post-doctoral fellow Hui Xia on the team.
In vitro sample loss was minimized through the incorporation of an additional laminar flow distribution layer into the existing chip system, reducing the sample loss during cell seeding. This also prevents the spheroids from escaping and allows them to form in a uniform manner throughout the chip as well. This ultimately results in consistent drug testing between each of the spheroids, enhancing the chip’s accuracy.
— Art Fridrich (@Ahighervision) January 16, 2020