Maldi Pharmapulse的Timstof^®

The timsTOF MPP represents the flagship member of the Bruker PharmaPulse^®product line. It features the extreme speed and proven robustness of MALDI and, for the first time ever in HTS, takes advantage of Bruker´s innovative Trapped Ion Mobility Spectrometry (TIMS) technology. TIMS enables rapid gas-phase separation of isobars, and even isomers, by exploiting the molecular collisional cross-section. This, in combination with routine 50,000 mass resolution in QTOF-MS detection enables revolutionary levels of assay specificity at HTS speed.
TimStof MPP使用双重MALDI / ESI离子源，具有行业领先的10 kHz SmartBeam™3D激光器来启用UHTS兼容速度和吞吐量，并且可以提供扩展的化学空间的独特MALDI-2选项。

作为解决方案的一部分，新的Maldi Pharmapulse^®2023软件支持范围广泛的高温超导品ations for drug discovery. Its automation interface allows for timsTOF MPP integration in high-throughput environments and works in concert with scheduling software from various vendors. Furthermore, MPP 2023 enables seamless transfer of data and results to downstream analysis software, e.g., to Genedata Screener^®。

TimStof MPP以高分辨率的高分辨率QTOF-MS数据以高分辨率分析速度在整个大型收购活动中提供了高分，这是UHTS成功的关键要求。以高分辨率MS或MS / MS模式读数1536个格式的样品板通常需要少于10分钟（通常最高3孔 /秒的读数）。在整个大规模测量过程中保持出色的数据质量，可确保精确的定量特征提取，以供各种靶标分子，范围从小型药物样化合物到转化为最小化的错误发现率（FDR）的大尺寸肽（FDR）。

在一个超过5小时的时间窗口中监测了两个肽离子的质量精度：

Titration curve obtained for perphenazine (MW 403 Da) over 3 orders of magnitude concentration range (0.001 – 1 µM):

在2个数量级浓度范围（0.01 - 1 µm）上获得泛素（MW 8558 DA）获得的滴定曲线：

TIMS is capable of separating isobars and even isomers on a timescale significantly faster than SPE (typically ≤ 1 sec per separation cycle) enabling interference-free quantitation of target compounds indistinguishable by mass spectrometry alone.

例子：葡萄糖的定量MALDI-TIMS-MS分析（C₆H₁₂o₆）在存在异构果糖的情况下（C₆H₁₂o₆）

In HTS, quantitation of target compounds can be affected by the complex sample matrices typically present in biochemical or cellular assays. timsTOF MPP offers unique possibilities to overcome such background interferences: Engaging Trapped Ion Mobility Spectrometry (TIMS) for fast separation in the gas phase and exploiting the increased specificity provided by high-resolution MS and MS/MS, advanced timsTOF MPP operation modes enable efficiently minimized levels of background interference resulting in enhanced quantitation at HTS speed.

例子：药物样分子的定量分析（MW 543 DA）
MALDI-MS模式下的定量由于与测定背景的频谱重叠而受到破坏。在MALDI-TIMS-MS/MS模式下进行相同的分析可以使目标分子无干扰定量。

As part of the timsTOF MPP solution, MALDI PharmaPulse 2023 software supports a broad range of HTS applications in early drug discovery. The software provides an easy-to-use interface for seamless setup and execution of screening campaigns utilizing various timsTOF MPP operation modes engaging TIMS and MS/MS. The automation interface provided with MPP 2023 allows for system integration in HTS environments and works in concert with automation scheduling software from various vendors. Furthermore, MPP 2023 enables direct transfer of data and results to third-party downstream analysis software, for example to Genedata Screener^®。

The core of the solution is Bruker´s timsTOF mass spectrometer equipped with:

• Dual MALDI / ESI ion source
• Autoloader for MALDI plate exchange by robot
• MALDI-2（可选）

轻量重量板适配器确保在全自动样品制备和随后的数据采集活动中，通过实验室机器人技术安全处理MALDI板。

具有成本效益的一次性MALDI样品板允许以96至1536年及以后的任何格式通过高性能液体处理程序进行自动化的MALDI制备。

In search of new drug molecules, high-throughput experimentation (HTE) creates vast libraries of newly designed compounds through multi-variant high-throughput chemistry. A key bottleneck in this process is the rapid analysis and confirmation of chemical reaction products.

TimStof MPP能够通过HTE化学来保持步伐，并通过测量多个物理特性，即准确的分子质量，同位素模式，碰撞横截面（CCS）和，在高处，在高尚水平上实时验证合成产物，并在上面进行实时验证。- 按需，CID-MS/MS碎片数据，减少了HTE反馈时间和化学成本。

MALDI-2是一种基于激光后离子化的开创性新技术，可增强某些类型的化合物的可检测性，这些化合物曾经超出传统MALDI的范围，从而为扩展的化学空间提供了分析访问。