Array-Based Sensing of Metastatic Cells and Tissues Using Nanoparticle-Fluorescent Protein Conjugates

Rapid and sensitive methods of discriminating between healthy tissue and metastases are critical for predicting disease course and designing therapeutic strategies. We report here the use of an array of gold nanoparticle-green fluorescent protein elements to rapidly detect metastatic cancer cells (in minutes), as well as to discriminate between organ-specific metastases and their corresponding normal tissues through their overall intracellular proteome signatures. Metastases established in a new preclinical non-small-cell lung cancer metastasis model in athymic mice were used to provide a challenging and realistic testbed for clinical cancer diagnosis. Full differentiation between the analyte cell/tissue was achieved with as little as 200 ng of intracellular protein (similar to 1000 cells) for each nanoparticle, indicating high sensitivity of this sensor array. Notably, the sensor created a distinct fingerprint pattern for the normal and metastatic tumor tissues. Moreover, this array-based approach is unbiased, precluding the requirement of a priori knowledge of the disease biomarkers. Taken together, these studies demonstrate the utility of this sensor for creating fingerprints of cells and tissues in different states and present a generalizable platform for rapid screening amenable to microbiopsy samples.