用于完整细胞分析的可见光MALDI质谱新方法的建立

Cell is the fundamental unit of life, so the in-depth study of its structure and function is of great importance to the early diagnosis and treatment of diseases. Comparing with the size, the mass of the cell can reveal the amount of biomolecules and cell activity with a significantly higher accuracy. However, how to achieve the accurate and rapid mass measurement of intact cells is still challenging. To solve this problem, we propose to establish a novel cell mass spectrometric platform including a visible-wavelength MALDI ion source, an ion trap mass analyzer and a charge detector. The visible-wavelength MALDI, which is much softer than conventional UV-MALDI, can prevent the disintegration of cells efficiently. To further guarantee the cell integration, the visible-wavelength MALDI will be designed with a transmission geometry, the sample will be prepared layer by layer, and new matrices will be screened. Using the ion trap mass analyzer and charge detector, the cell mass and mass distribution can be obtained. The success of the research will provide new method for performing applications such as the rapid discrimination of cells, the characterization of cell growth and pathology, as well as the understanding of cell-medicine interactions, thereby giving new insights into the life science and clinical medicine.

细胞是生命的基本单元，对其结构与功能的深入研究是实现疾病早期诊断和治疗的重要途径。细胞的质量，相比尺寸和密度，能够更加准确地反映细胞内生物分子的含量及细胞的活性。然而，如何实现完整细胞质量的准确和快速测定依然富有挑战性。针对这一难题，本项目拟建立一个包括可见光MALDI源、离子阱质量分析器和电荷检测器的细胞质谱平台。可见光MALDI比传统的紫外光MALDI更加“软”，有利于避免细胞的破碎。为了进一步保证细胞的完整性，拟采用透射式的可见光MALDI构造和逐层点样的制样方法，并筛选出新型的基质分子。离子阱质量分析器和电荷检测器的配合使用可以得到单个完整细胞的质量和质量分布。本项目的成功预期将为细胞的表征提供新方法，有助于实现诸如细胞快速区分、细胞生长和病变过程表征以及药物与细胞的相互作用研究等，为生命科学及临床医学的发展提供新的依据。

完整细胞的质量测定对于理解细胞的生长发育及分化等过程至关重要。通过构建可见光MALDI源及颗粒质谱装置，我们实现了多种细胞及细胞混合物的高效解吸电离以及准确质谱分析。另外，我们还利用MALDI质谱实现了对细胞表面糖蛋白、二糖等生物分子以及纳米载体药物、光催化剂等纳米材料的分析。取得的主要成果包括：.1，开发了可见光MALDI新基质9-羟基-3-异吩恶嗪酮，实现了完整细胞的高效解吸。开发了N-苯基-2-萘胺、氟化石墨烯和石墨炔新基质，实现了多种生物小分子的MALDI质谱分析。.2，构建了可同时测定颗粒尺寸、密度及质量的多参数表征颗粒质谱装置及小型化颗粒质谱装置。.3，利用MALDI质谱实现了对完整细胞的准确及快速测定、纳米载体药物原位释放的成像研究、纳米光化学催化剂的快速筛选、细胞表面唾液酸类糖蛋白的原位分析、二糖异构体的区分、定量及成像分析、热诱导的乳球蛋白二硫键重排的表征以及北京有机气溶胶的成分分析等。