Matrix metalloproteinase (MMP) is a key marker and target molecule for cancer diagnosis, as MMP is able to cleave peptide chains resulting in degradation of extracellular matrix (ECM), a necessary step for cancer development. In particular, MMP2 has recently been recognized as an important biomarker for lung cancer. Despite the important role of detecting MMP molecules in cancer diagnosis, it is a daunting task to quantitatively understand a correlation between the status of cancer development and the secretion level of MMP in a blood droplet. Here, we demonstrate a nanoscale cancer diagnosis by nanomechanical quantitation of MMP2 molecules under cancer progression with using a blood droplet of lung cancer patients. Specifically, we measured the frequency dynamics of nanomechanical biosensor functionalized with peptide chains mimicking ECM in response to MMP2 secreted from tumors in lung with different metastasis level. It is shown that the frequency shift of the biosensor, which exhibits the detection sensitivity below 1 nM, enables the quantitation of the secretion level of MMP2 molecules during the progression of cancer cells or tumor growth. More importantly, using a blood droplet of lung cancer patients, nanomechanical biosensor is shown to be capable of depicting the correlation between the secretion level of MMP2 molecules and the level of cancer metastasis, which highlights the cantilever-based MMP2 detection for diagnosis of lung cancer. Our finding will broaden the understanding of cancer development activated by MMP and allow for a fast and point-of-care cancer diagnostics.

中文翻译：

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通过蛋白水解活性测量在癌症进展中基于血滴的癌症诊断。

基质金属蛋白酶（MMP）是癌症诊断的关键标志物和靶分子，因为MMP能够裂解肽链，导致细胞外基质（ECM）降解，这是癌症发展的必要步骤。特别是，MMP2最近被公认为是肺癌的重要生物标志物。尽管检测MMP分子在癌症诊断中起着重要的作用，但是定量了解癌症发展状态与液滴中MMP分泌水平之间的关系是一项艰巨的任务。在这里，我们通过使用肺癌患者的血滴，通过对癌症进展下MMP2分子的纳米机械定量证明了纳米级癌症的诊断。具体来说，我们测量了模拟ECM的肽链功能化的纳米机械生物传感器对不同转移水平的肺肿瘤分泌的MMP2的响应的频率动态。结果表明，生物传感器的频移表现出低于1 nM的检测灵敏度，可以量化癌细胞进展或肿瘤生长过程中MMP2分子的分泌水平。更重要的是，使用肺癌患者的血滴，纳米机械生物传感器被证明能够描绘MMP2分子的分泌水平与癌症转移水平之间的相关性，这突出了基于悬臂的MMP2检测对肺癌的诊断。 。