Label-free biosensor for non-invasive and low-cost detection of metastatic risk through urine biopsy

Abstract

Metastasis is a major challenge in cancer treatment, and early detection is critical for improving patient outcomes. Here, we present a label-free microfluidic biosensor based on urine biopsy that allows for the non-invasive and low-cost detection of metastatic status in clinical cancer patients (SmartCM). The ultrasensitive smart biosensor employs nematode movement visualisation to provide results within 60 min with a low sample volume requirement of 1 mL. We validated the SmartCM platform in non-metastatic and metastatic breast cancer patients (n = 30) and healthy controls (n = 6). Our unique chemotaxis index thresholds (CI MCF-7; metastasis > 2) showed that the SmartCM platform had high sensitivity (87.5%). Furthermore, we demonstrated that the CI value in urine samples from metastatic breast cancer patients was significantly higher than in non-metastatic breast cancer patients (2.9-folds; CI MCF-7). Nematode preference for metastatic urine samples was associated with lower urea and L-proline concentrations. The SmartCM platform was enhanced with an amplification system based on a Z stage with a chip holder, droplet lens, and smartphone, enabling automated operations for portable analysis. We envision that the SmartCM biosensor offers a means for remote or home-based testing, supplementing clinical assays for immediate intervention or promoting remote monitoring.