Worm-Based Microfluidic Biosensor for Real-Time Assessment of the Metastatic Status

SIMPLE SUMMARY: We proposed a high-throughput screening and low-cost worm-based (WB) microfluidic biosensor to monitor biochemical cues related to metastasis. Caenorhabditis elegans placed in the WB biosensor chambers and exposed to samples conditioned with cancer cell clusters reflect differences in the chemotactic preference of worms. We observed a higher distribution of worms associated with samples of higher metastatic potential (p < 0.005). A chemotaxis index (CI) was defined to standardize the quantitative assessment from the WB biosensor, where increased metastatic potential was associated with higher CI levels (6.5 ± 1.37). We found that the secreted metabolite glutamate was a chemorepellent, and lower glutamate levels were associated with samples derived from more metastatic cancer cell clusters. In conclusion, WB biosensors could evaluate patient status in real time, thereby facilitating early detection of metastases and routine management. ABSTRACT: Background: Metastasis is a complex process that affects patient treatment and survival. To routinely monitor cancer plasticity and guide treatment strategies, it is highly desired to provide information about metastatic status in real-time. Here, we proposed a worm-based (WB) microfluidic biosensor to rapidly monitor biochemical cues related to metastasis in a well-defined environment. Compared to conventional biomarker-based methods, the WB biosensor allowed high throughput screening under low cost, requiring only visual quantification of outputs; Methods: Caenorhabditis elegans were placed in the WB biosensor and exposed to samples conditioned with cancer cell clusters. The chemotactic preference of these worms was observed under discontinuous imaging to minimize the impact on physiological activity; Results: A chemotaxis index (CI) was defined to standardize the quantitative assessment from the WB biosensor, where moderate (3.24–6.5) and high (>6.5) CI levels reflected increased metastasis risk and presence of metastasis, respectively. We demonstrated that the secreted metabolite glutamate was a chemorepellent, and larger clusters associated with increased metastatic potential also enhanced CI levels; Conclusions: Overall, this study provided a proof of concept for the WB biosensors in assessing metastasis status, with the potential to evaluate patient-derived cancer clusters for routine management.