Peroxynitrite (ONOO^–) plays important roles in the progression of important disease such as inflammation, cancer, and diabetes, which made it an attractable target for biosensor development. However, to detect ONOO^– solely is highly dependent on the sensitivity of the detection method and may be disturbed by unwillingly false-positive signal. Cellular viscosity is an important microenvironmental parameter and its abnormal changes are closely related to diseases such as diabetes and cancer. In this case, to construct a “dual-locked” molecular tool for both ONOO^– and viscosity sensing and to evaluate the performance of such strategy in disease diagnosis is of great importance. We herein firstly reported the construction of a novel “dual-locked” probe DCI-OV which showed capability for simultaneous measuring ONOO^– concentration and system viscosity with high sensitivity (LOD = 4.7 nM) and high specificity. Moreover, both exogenous and low level of endogenous ONOO^– in living cells could be detected using DCI-OV due to viscosity amplified signal. Furthermore, cancer cells and insulin-resistant cells could be easily distinguished using DCI-OV. By taking advantage of the “dual-locked” sensing strategy, a total of 85 samples of human serum were screened using DCI-OV based rapid disease screening method and it was capable of differentiated and subdivided patients into specific type of disease, indicating the great potential of application of DCI-OV into clinical related disease diagnosis.

过氧亚硝酸盐（ONOO ^-）在炎症、癌症和糖尿病等重要疾病的进展中发挥着重要作用，这使其成为生物传感器开发的一个有吸引力的目标。然而，检测 ONOO ^–高度依赖于检测方法的灵敏度，可能会受到不情愿的假阳性信号的干扰。细胞黏度是重要的微环境参数，其异常变化与糖尿病、癌症等疾病密切相关。^{在这种情况下，为 ONOO和}粘度传感构建“双锁”分子工具并评估这种策略在疾病诊断中的性能非常重要。我们在此首次报道了一种新型“双锁”探针的构建DCI-OV显示了同时测量 ONOO ^–浓度和系统粘度的能力，具有高灵敏度 (LOD = 4.7 nM) 和高特异性。此外，由于粘度放大信号，可以使用 DCI-OV 检测活细胞^中外源性和低水平的内源性 ONOO 。此外，使用DCI-OV可以轻松区分癌细胞和胰岛素抵抗细胞。利用“双锁”传感策略，采用基于DCI-OV的疾病快速筛查方法共筛选出85份人血清样本，能够将患者区分和细分为特定的疾病类型，表明应用潜力DCI-OV进入临床相关疾病诊断。