Rapid Identification of Cell Types and Phenotypic States Using a One-Polymer Multichannel Nanosensor Fabricated via Flash Nanoprecipitation

Cell state transitions are fundamental in biology, determining how cells respond to environmental stimuli and adapt to diseases and treatments. Cell surface-based sensing of geno/phenotypes is a versatile approach for distinguishing different cell types and states. Array-based biosensors can provide a highly sensitive platform for distinguishing cells based on the differential interactions of each sensing element with cell surface components. In this work, a highly modular polymer-based supramolecular multichannel sensor array (FNP sensor) was fabricated by encapsulating a hydrophobic dye (pyrene) into the monolayer of a positively charged fluorescent polymer through flash nanoprecipitation (FNP). We utilized this one-polymer sensor array to discriminate among cell types commonly found in tumors: 4T1 cancer cells, NIH/3T3 fibroblast cells, and RAW 264.7 macrophage cells. The sensor also successfully characterized varying ratios of NIH/3T3 cancer-associated fibroblasts (CAFs) and RAW 264.7 tumor-associated macrophages (TAMs). This single polymer-based sensor array provides effective discrimination and high reproducibility, providing a high-throughput tool for diagnostic screening of cell types and states associated with cancer progression.