口腔鳞状细胞癌（OSCC）是最常见的口腔癌类型。近年来，研究人员发现microRNA（miRNA）与OSCC之间存在密切关系。此外，miRNA在组织和循环中高度稳定，也被认为是癌症检测和预后的潜在生物标志物。在各种低丰度 miRNA 的工具中，基于 UCNP 的单一发红光生物传感器因其独特的性质（包括深层组织穿透、弱辐射损伤和低自发荧光）而引起了特别的兴趣。此外，通过无酶信号放大来测量低丰度分析物也是一种有效的手段。在此，通过利用发红光的UCNP和酶立足点介导的链置换级联，构建了双信号放大生物传感器。回收的 miRNA 可以被视为多个 H1/H2 双链体组装的催化剂，从而促进增强分析物表达的响应信号。此外，所提出的生物传感器通过双信号响应提高了测量精度，明显避免了假阳性信号。该方法用于测量血清样本中的miRNA-222（一种模型分析物），结果与聚合酶链式反应（PCR）相似，加标回收率为91.2%至101.7%。该方法具有灵敏度高、识别能力强、背景低的优点，表明在测量生物样品中的多种分析物方面具有广阔的潜力。该期刊版权所有©英国皇家化学学会。

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer. In recent years, researchers have found a close relationship between microRNAs (miRNAs) and OSCC. In addition, miRNAs are highly stable in tissues and circulation, and are also considered potential biomarkers for cancer detection and prognosis. Among a variety of tools for miRNAs with low abundance, single red-emitting UCNP-based biosensors have attracted special interest due to their unique properties, including deep organizational penetration, weak radiation damage, and low autofluorescence. Additionally, the measurement of low-abundance analytes via enzyme-free signal amplification is also an effective means. Herein, by taking advantage of red-emitting UCNPs and an enzyme-toehold-mediated strand displacement cascade, a dual-signal amplification biosensor was constructed. The recycled miRNA can be regarded as a catalyst for the assembly of multiple H1/H2 duplexes, which promoted the response signal of augmented analyte expression. Moreover, the proposed biosensors improved the measurement accuracy via a dual-signal response to obviously avert false-positive signals. The proposed method was applied to measure miRNA-222 (a model analyte) in serum samples, and the results were similar to those of polymerase chain reaction (PCR), with spiked recoveries ranging from 91.2% to 101.7%. The proposed assay has the merits of high sensitivity, strong recognition, and low background, indicating broad potential for the measurement of diverse analytes in biological samples.This journal is © The Royal Society of Chemistry.