Microfluidic Chip for the evaluation of therapeutics and carrier drugs in breast cancer tissue

Introduction: Breast cancer is the most common cancer in women where 1 in 8 will develop over the course of her lifetime. However, some treatments react differently depending on race and ethnicity. Unfortunately, there are no preclinical models capable of studying pharmacoethnicity differences of drugs. Hence, racial differences are found late during clinical trials or after market adoption. The absence of a model that studies pharmacoethnicity differences results in negative outcomes for the affected race. The objective of this project is to design and evaluate a microfluidic in-vitro platform to test therapeutics and carrier drugs, such as Doxil liposomes, in breast tumor tissue and compare properties based on the tissue’s race and other attributes. The microfluidic device is capable of delivering a dual channel fluid system with the intention of emulating blood and interstitial fluid in tissue. The chip is unique from other systems by directly using human tissue and designing a microfluidic chamber specific to a patient’s tumor allowing it to be used for personalized medicine.

Methods: To build a microfluidic platform, a 15 µm tumor section is mounted to a positively charged slide. Then capillary channels are etched at 120 µm diameter with an estimated precision ≤ 10 µm, channel spacing is set to 350 and 500 µm. Channels are etched in glass slides using a 5W UV Laser Marking Machine with 70 mm f-theta lens, at a pulse rate of ≤ 15 ns. Current chip model requires etching two main capillary glass slides. Each slide is then covered by an intermediate thin layer per etched channel side. Afterwards, the slides are assembled with UV resin Loctite 349 and cured under UV light for 20 minutes. Finally, a third slide is used as the interface between the chip and the chromatography tubing. After assembly, the blood and interstitial fluid channels are loaded with deionized water and are flow and pressure tested. As a proof of concept, an acridine orange solution was used with a preliminary chip. Dye penetration was then measured using an inverted microscope.

Results: A total of 8 microfluidic chips have been successfully built, and an additional 19 chips are under development. The initial microfluidic chip prototype demonstrated tumor tissue was stained by an acridine orange solution by a total of up to 75 µm past the capillary channels. The preliminary chips exhibited chamber issues where interstitial fluid merged with the blood channel. This has now been successfully corrected in the current chip model. A total of 6 microfluidic chips will be used with a carrier drug, such as Doxil liposomes.

Conclusions: After method revisions, where are now capable of developing fully working microfluidic chips. Our preliminary studies demonstrate the capabilities of using our chips to test drug penetration in tissue. Our current objective is to measure drug penetration in breast cancer tumors based on race. Future studies will include additional method development to enable live tissue use and to measure additional drug properties.