Highly Efficient Dual-Probe Strategy toward Single-Cell Metabolite Analysis

As cancer progresses, detached cancer cells metastasize through the circulatory system, followed by intricate metabolic rewiring for adaptation and propagation. The dynamic process of metastasis, despite being responsible for the majority of cancer-related deaths, still remains inadequately comprehended. Here, we proposed a microfluidic platform combining the dual-probe strategy for the detection of metastasize-related metabolic levels at single-cell resolution. Unique design facilitates intracellular and extracellular detection within the same cell captured at individual chambers, promoting the understanding of single-cell correlation metabolites analyses. Metabolite profiling of the model cells verified the positive correlation between upregulated intracellular NAD(P)H and the increased secretion of matrix metalloproteinases (MMPs). Furthermore, Zn²⁺-mediated metabolite analysis demonstrated the correlation in single cells, which could be utilized as a reference for the development of zinc-based antitumor therapies. The strategy provides valuable evidence of a relatively higher risk of metastasis for malignancies through unraveling the intricate metabolic heterogeneities arising from both intrinsic and extrinsic factors within individual cells.