microRNAs (miRNAs) are key players in the onset and progression of cancer. Tumor-secreted miRNAs can be stably present in the circulation (circulating miRNAs or c-miRNAs) and are therefore considered ideal non-invasive cancer biomarkers. To date, miRNA detection in liquid samples is carried out with lengthy and labor-intensive PCR-based methods which suffer from technical limitations such as poor reproducibility. By exploiting cell-free systems, we aim to build a sensor-actuator device implemented with Boolean logic functions able to reveal the presence of specific miRNAs or miRNA signatures in liquid samples containing an unknown miRNA mixture. This project will have two outcomes: (1) the development of a structured, progressive screening platform for de novo miRNA marker discovery; (2) the development of a multi-input miRNA-sensing platform for identification of cancer-specific miRNA signatures. The miRNA-sensing platform will allow for a rapid, straightforward, and PCR-free detection of miRNAs in liquid samples and will pave the way for miRNA detection in the context of personalized medicine and disease diagnosis.