Micro-NMR for Rapid Molecular Analysis of Human Tumor Samples

Abstract

Although tumor cells obtained from human patients by image-guided intervention are a valuable source for diagnosing cancer, conventional means of analysis are limited. Here, we report the development of a quantitative micro-NMR (nuclear magnetic resonance) system for rapid, multiplexed analysis of human tumors. We implemented the technology in a clinical setting to analyze cells obtained by fine-needle aspirates from suspected lesions in 50 patients and validated the results in an independent cohort of another 20 patients. Single fine-needle aspirates yielded sufficient numbers of cells to enable quantification of multiple protein markers in all patients within 60 min. Moreover, using a four-protein signature, we report a 96% accuracy for establishing a cancer diagnosis, surpassing conventional clinical analyses by immunohistochemistry. Our results also show that protein expression patterns decay with time, underscoring the need for rapid sampling and diagnosis close to the patient bedside. We also observed a surprising degree of heterogeneity in protein expression both across the different patient samples and even within the same tumor, which has important implications for molecular diagnostics and therapeutic drug targeting. Our quantitative point-of-care micro-NMR technique shows potential for cancer diagnosis in the clinic.