High Throughput Droplet Microfluidic Platform for Single-Cell Lipid Analysis of Human Breast Cancer Cell Lines

Abstract

Lipid metabolism has been viewed as an indicator of breast cancer. We report a single cell high throughput droplet microfluidic platform for lipid profiling of cells. Breast cancer cell lines (MCF7 and LLC1) are individually trapped in nanoliter droplets containing enzyme microbeads. Subsequently, the lipid contents of individual cells are hydrolyzed by the microbeads in the droplet followed by electrochemical detection using a microelectrode array. Our droplet-based microfluidic platform integrates cell lysis and localized hydrolysis within a micron sized aqueous drops (40 µm) in an inert carrier oil (Fig. 1). The quantity of the hydrolyzed products in each droplet correspond to the lipid profile of individual cells. The magnitude of electrochemical impedance variations are characterized and related to tumor progression. The cellular heterogeneity of an apparently homogenous cell population has been identified. The change in electrochemical signals is correlated to the amounts and types of lipids in breast cancer cell lines. Preliminary studies reveal the potential of our droplet microfluidic platform in comparing the chemical composition between cell types and even between individual cells. Cell-to-cell variability, which is not reflected in the ensemble profiles, was preserved in the proposed method. The microfluidic platform is also being integrated with bioimpedance analysis for advanced bioimpedance profiling. We identified that this approach leads to (a) functional identification of lipid variation in cancer cell lines during various stages of growth, (b) Tumor progression related to lipogenesis and fatty acid synthesis. The platform is also being extended to pathogenesis and drug-discovery Figure 1