Functional Precision Oncology Approach Using Nanoliter Droplet Array for Drug Sensitivity Testing in Lung Cancer.

Abstract

Functional precision oncology aims to support personalized cancer therapy by assessing drug sensitivity in patient-derived tumor cells ex vivo. However, conventional drug sensitivity and resistance testing (DSRT) platforms typically require large numbers of cells, limiting their applicability to surgically resected tumors and posing challenges for patients diagnosed at advanced stages, where only small biopsy samples are available. To address this limitation, we developed a miniaturized DSRT workflow based on a Droplet Microarray (DMA) chip, which comprises 672 hydrophilic spots separated by superhydrophobic borders and enables high-throughput screening in nanoliter volumes. Using 300 cells per 200-nL droplet, lung cancer cells freshly isolated from surgical specimens were tested against 12 compounds across five concentrations and five replicates (360 experimental conditions). This required approximately 120,000 cells total, including additional cells for handling and processing. The approach generated drug-specific dose-response profiles and variable IC₅₀ values across tumors of the same subtype. Comparable drug responses were also observed across three spatially distinct regions of the same tumor, indicating consistent assay performance. Overall, these results demonstrate that DSRT on the DMA platform is feasible with limited numbers of cells derived from clinical samples and may be useful for functional drug testing when tissue availability is constrained.