Portable and Field-Ready Detection of Circulating MicroRNAs with Paper-Based Bioluminescent Sensing and Isothermal Amplification

We present a paper-based system that integrates bioluminescence resonance energy transfer (BRET) and isothermal amplification for the analysis of tumor-associated circulating microRNAs (miRNAs) in clinical serum samples. The analysis procedure could be easily accomplished with two pieces of functionalized paper and a low-cost smartphone-based device, which enables sequence-specific quantification of femtomolar miRNAs, without the need for tedious handling of aqueous reactions and operation of sophisticated equipment. Furthermore, the analytical performance of the proposed paper-based system was highly stable at room temperature, demonstrating its capability for cold-chain-free and remote deployment. These qualities highlight the practical utility of our method for the portable and field-ready miRNA diagnostic tests in resource-limited settings.