Customized Hydrogel Films for MicroRNA Super‐Resolution Imaging in Liquid Biopsies

Tissue biopsy for early diagnosis and monitoring comes with several challenges, such as its invasiveness, and issues related to tissue heterogeneity in sampling. To address these issues, researchers have proposed a noninvasive approach called liquid biopsy, which uses blood samples to detect specific noncoding RNA (microRNA, miRNA). However, the current process of isolating and amplifying miRNA can be time‐consuming and yield nonspecific results. In this study, a new super‐resolution imaging tool is introduced that utilizes a thin, hydrogel‐based liquid view (LV) film. This film can undergo a ninefold expansion and allows the analysis of cells obtained from liquid biopsy. The potential of the LV film is validated as a tool for early diagnosis and prognosis by testing biofluids derived from a variety of diseases. This method is confirmed to accurately analyze a greater number of miRNAs with higher sensitivity in a shorter time compared to other analytical methods. These findings suggest that the LV film provides high specificity, and multiplexing in detecting small amounts of miRNAs within cells, making it suitable for 3D implementation. It is proposed that liquid biopsy with LV films can be a solution to limitations related to the invasiveness, cost, and time‐consuming nature of molecular analysis. A hydrogel‐based liquid view (LV) film is introduced, which incorporates liquid absorption and possesses the capability to expand cell morphology and subcellular organelles through iterative incubation and embedding reactions. The advantages of utilizing dried LV film facilitate the exploration of microRNA (miRNA) expression patterns in diverse physiological conditions and disease states, thereby enriching the understanding of cellular signaling and disease mechanisms.