基于新型锆元素MOF（UIO-66）探针的单细胞质谱流式(CyTOF)标签研究

单细胞质谱流式技术（Mass Cytometry, CyTOF）将流式细胞术与电感耦合等离子体飞行时间质谱相结合，以质量数在75-209的稳定金属同位素作为检测信号，可以实现单细胞、高维度、多组学的检测。然而，这项技术目前全球都依赖于欧美科学家开发的Maxpar X8 poly-mer作为金属同位素标签体系。这种体系的缺陷包括：1）金属担载量低，因此对低表达抗原的敏感性较差；2）能够利用的金属通道仅有40余个，无法完全覆盖现有硬件中近150个检测通道。..鉴于此，本课题拟研发一种CyTOF新结构金属探针。相比传统CyTOF探针，锆（90Zr，91Zr，92Zr，94Zr）MOF金属标签：1）合成简单环保，节约成本；2）可拓宽4个CyTOF检测通道；3）可增加1000倍金属担载量，放大金属信号，从而实现生物样本中低丰度蛋白的检测。

Single-cell Mass Cytometry (CyTOF) combines flow cytometry with inductively coupled plasma time-of-flight mass spectrometry, and uses stable metal isotopes with mass numbers of 75-209 as detection signals to achieve single-cell, high-dimensional and multi-omics detection. It has been claimed by Nature as one of the most prospective biotechnologies in 2018. The technology advancement has promoted research areas such as developmental biology, stem cell differentiation, tumor heterogeneity, and immune cell populations. However, this technology currently relies on Maxpar X8 polymer developed by European and American scientists as a metal isotope labeling system. Such system has the following limitations: 1) low metal loading capability, as a result, the sensitivity to low-expressing antigens is poor; 2) only 40 metal channels can be used, which cannot completely cover nearly 150 detections in existing hardware aisle. . In view of this, this project aims to develop a new structure metal probe for CyTOF. The precursor of the probe is a metal-organic framework UIO-66 (Zr) synthesized by solvothermal method. The zirconium MOF surface carboxyl group is activated by the EDC/NHS system and the antibody is coupled to synthesize a UIO-66-based zirconium metal probe. Compared with traditional CyTOF probes, zirconium (90Zr，91Zr，92Zr，94Zr) MOF metal tags have the following enhanced features: 1) more simply synthesized, environmentally protective, and cost effective; 2) can add 4 more CyTOF detection channels; 3) can increase the metal loading capacity by 1000 times, which facilitate the amplification of metal signal to achieve low-expressing protein detection.