An Enzyme-Loaded Metal-Organic Framework-Assisted Microfluidic Platform Enables Single-Cell Metabolite Analysis

Colonization of cancer cells at secondary sites, a decisive step in tumor metastasis, is strongly dependent on the formation of metastatic microenvironments regulated by intrinsic single-cell metabolism traits. Herein, we report a single-cell microfluidic platform for high-throughput dynamic monitoring of tumor cell metabolites to evaluate tumor malignancy. This microfluidic device empowers efficient isolation of single cells (>99 %) in a squashed state similar to tumor extravasation, and employs enzyme-packaged metal-organic frameworks to catalyze tumor cell metabolites for visualization. The microfluidic evaluation was confirmed by in vivo assays, suggesting that the platform allowed predicting the tumorigenicity of captured tumor cells and screening metabolic inhibitors as anti-metastatic drugs. Furthermore, the platform efficiently detected various aggressive cancer cells in unprocessed whole blood samples with high sensitivity, showing potential for clinical application.

Automated summary

Colonization of cancer cells at secondary sites relies on the formation of metastatic microenvironments regulated by single-cell metabolism traits. A microfluidic platform has been developed for high-throughput monitoring of tumor cell metabolites, allowing evaluation of tumor malignancy and screening of anti-metastatic drugs. The platform shows potential for clinical application by efficiently detecting aggressive cancer cells in unprocessed blood samples.