70. modular integrated organ-on-a-chip systems for cancer drug testing
Name: Han Liang Lim
Grad Year: 2017
As many as 95% of all cancer drug candidates fail to make it through clinical trials and to market, resulting in great losses to pharmaceutical companies. One of the biggest reasons behind this is the biological discrepancy between the animals used in preclinical studies (eg. rodents, canines, etc.) and humans. These differences have led to the failure of preclinical studies in translating clinical success. To provide an alternative testing platform that more closely mimics the human physiological condition, we have combined tissue fabrication techniques and microfluidic technology to create functional organoids in flow-thru microfluidic chips. Human cells are incorporated into these organoids, hence allowing us to draw closer parallels between these chips and the human body. As these organoids mature, they recreate the most essential aspects of the organ they represent. Different organoids can then be further integrated into a closed circuit to mimic blood flowing through the body. Here we present a system that includes the cancer-on-a-chip, liver-on-a-chip and the heart-on-a-chip platform. As a functional test, we have introduced a chemotherapeutic drug, Adriamycin, into the system. As a result, we have not only observed its ability to arrest growth in the cancer, but also its induction of key cytochrome p450 proteins expressed in the liver-on-a-chip device, as well as its known effects on cardiac toxicity in our heart-on-a-chip device. This highly physiologically relevant system can be used in conjunction with other preclinical studies to provide more rigor in identifying candidates for clinical studies.