Hybrid mass spectrometer with liquid chromatography system

质谱（MS）是生物医学和基础研究中的核心技术。定义的标准，协议和软件使其可供广泛的研究社区使用。高通量质谱（HT-MS）在蛋白质组学和代谢组学中形成了一个新的分支，并且能够为流行病学研究以及复杂的系统生物学实验生成高质量的数据集（100 s-1000 s的样品）。统计学、系统医学和计算机科学（机器和深度学习）的新方法使HT-MS具有巨大的潜力，例如，随着时间的推移详细绘制发育过程，了解微生物组，预测疾病的进程，对患者进行分层（例如个性化治疗）以及研究复杂的疾病机制。高通量蛋白质组学平台的结构在关键要素上与传统方法不同。由于样本数量多，单独分析可能更快，更便宜。为了确保多年来数据的可比性，可变性的技术来源，批次效应，可以精确地确定。这是通过专门的实验、技术和组织过程来实现的。在过去的18个月里，“设施HT-质谱”能够建立高分析物浓度样品（例如血浆/血清，培养细胞）的基础设施。正在进行的分析已经涵盖了10，000多个人类和其他真核生物蛋白质组，包括对COVID 19的研究，麻醉后影响认知的因素以及化合物筛选。目前，来自10万个基因组项目的6 000份样本、来自CHRIS研究（EURAC研究所的阿尔卑斯山人群研究）的4 000名受试者以及用于2型糖尿病EPIC-Interact研究（MRC剑桥）的1 400份样本正在进行中。因此，Charité核心设施HT-MS已迅速成为欧洲少数几个具有高通量能力的蛋白质组学中心之一。我们正在申请的工具补充了源材料有限的项目平台。由于目前缺乏这种能力，无法开展基础研究的核心项目（例如流式细胞仪分选的细胞、原代培养物、干细胞、FFPE切片、液体和微生物）。

Mass spectrometry (MS) is a central technology in biomedical and basic research. Defined standards, protocols, and software make it accessible to a broad research community. High-throughput mass spectrometry (HT-MS) forms a new branch within proteomics and metabolomics and enables the generation of high-quality data sets (100s – 1000s of samples) for epidemiological studies as well as complex systems biology experiments. New methods of statistics, systems medicine and computer science (machine and deep learning) boost HT-MS with immense potential, e.g. to map developmental processes in detail over time, to understand microbiomes, to predict the course of diseases, to stratify patients (e.g. for personalized therapy) and to investigate complex disease mechanisms. The structure of a high-throughput proteomics platform differs in key elements from conventional processes. Due to the high number of samples, individual analyses med to be faster and cheaper. To assure comparability of data over the years, technical sources of variability, e.g., batch effects, can be precisely determined. This is achieved by specialized experimental, technical and organizational processes. In the last 18 months, the ‘Facility HT-Mass Spectrometry’ was able to establish the infrastructure for samples of high analyte concentration (e.g. plasma/serum, cells from culture). Ongoing analyses already cover more than 10,000 human and other eukaryotic proteomes, including studies on COVID19, the factors influencing cognition after anesthesia, and compound screens. Currently, 6,000 samples from the 100,000 Genomes Project, 4,000 subjects from the CHRIS study (Alpine population study by the EURAC Institute), and 1,400 samples for the EPIC-Interact study on type 2 diabetes (MRC Cambridge) are in progress. As a result, the Charité Core Facility HT-MS has quickly established itself as one of the few European proteomics centers with high-throughput capacity. The instrument we are applying for complements the platform for projects with limited source material. The current lack of such a capacity excludes central projects of basic research (e.g. FACS-sorted cells, primary cultures, stem cells, FFPE sections, liquid, and microbiospies).