Miniaturized Drug Sensitivity and Resistance Test on Patient-Derived Cells Using Droplet-Microarray

Abstract

Testing the sensitivity of patient-derived tumor cells ex vivo can potentially help determining the appropriate treatment for each patient and spot the development of resistance to a given therapy. The number of cells obtainable from a biopsy is, however, often insufficient for performing ex vivo tests in conventional microtiter plates. Here, we introduce a novel Droplet-Microarray platform based on a hydrophilic-superhydrophobic patterned surface that enables screenings using only 100 cells and 30 picomoles of a drug per individual nanoliter-sized droplet. We demonstrate that the dose-response of as few as 100 primary patient-derived chronic lymphocytic leukemia (CLL) cells to anticancer compounds on the Droplet-Microarray platform resembles the dose-response obtained in 384-well plates requiring 20,000 tumor cells per experiment. The extremely miniaturized Droplet-Microarray platform thus carries great potential for ex vivo drug sensitivity and resistance tests on patient-derived tumor cells and potentially for implementing such tests in medical practice of precision medicine.