Early diagnosis of cancer can be facilitated by detecting microRNA (miRNA) biomarkers that are dysregulated during tumor development. Here we present a general-purpose whole-cell biosensor platform for miRNA detection, engineered in Escherichia coli and compatible with the International Genetically Engineered Machine (iGEM) standard. The biosensor design is modular, allowing it to be retargeted to different miRNA sequences (for example, oncogenic miR-21 and miR-155, which are upregulated in diverse cancers). The core sensing element is an RNA-based switch (toehold riboregulator) that translationally activates a reporter gene only in the presence of the target miRNA. We augmented this circuit with synthetic biology strategies – including high-copy plasmids for signal amplification, optimized ribosome binding sites, and alternative output reporters (green fluorescent protein, luciferase, and chromogenic enzymes) – to maximize sensitivity and dynamic range. We also explore CRISPR-based recognition modules as an alternative sensing mechanism to enhance specificity. In silico and experimental characterizations indicate that the biosensor can detect miRNA concentrations in the low nanomolar to picomolar range, with a large fold-change between the “off” and “on” states. We outline a cloning and assay workflow for constructing the miRNA sensor and calibrating its response in both laboratory media and complex samples. Preliminary results show sequence-specific responses to synthetic miRNA analogs, and negligible crosstalk between sensors for different miRNA targets. Potential applications of this platform include point-of-care cancer diagnostics (e.g. paper-based test strips or dipstick assays) and even in vivo monitoring using probiotic sensor bacteria. In the Discussion, we examine challenges such as ensuring specificity among closely related miRNA family members, achieving clinically relevant sensitivity, and addressing biosafety for clinical deployment. This work establishes a foundation for plug-and-play whole-cell miRNA sensors, illustrating how synthetic biology can repurpose microbial gene circuits for non-invasive early cancer detection.