高通量筛选
Unique speed and specificity offered by label-free MALDI-TOF mass spectrometry
全新的Rapiflex®MALDI飞行时间质谱仪是MaldiPharmapulse®的核心,它结合了Brukers最新的10 kHz扫描激光技术,每秒可以读取多个样品。系统的所有组件共同用于全自动HTS操作。新设计的筛选软件套件支持HTS工作流程,并与专有测定开发模块合并,该模块使测定者能够加速MALDI质谱法的无标签测定开发。Rapiflex®MPP的最新综合筛选'软件模块为例如在高速度下监测化学反应或在无与伦比的高吞吐量和特异性下对结合测定的分析。
质谱法的使用允许测量主要屏幕中未修饰的底物,以避免误报或假阴性,从而使确认屏幕冗余。该系统设计用于全自动处理384和1536个样品板,以筛选一周中超过一百万种化合物,以支持药物发现。
超高通量筛查标签的“命中”标识的新标准
By combining the speed of Bruker’s patented smartbeam 3D laser technology with the direct-detection capability of mass spectrometry, the rapifleX®MPP提供了前所未有的筛选能力,用于对生化和细胞测定的超高通量筛查。它使您可以以每周超过一百万个化合物的速度筛选大型和多样化的化合物库,从而代表了自动化和微型化的完美平衡。
我们很荣幸能成为第一个将Bruker集成的Rapiflex质谱仪作为读出技术进入我们的UHTS系统的CRO。质谱允许直接测量无标签测定法,并减少屏幕上的假阳性和假阴性的数量,从而使我们的药物发现计划的领先阶段更加时间和成本效益。
与Cybio兼容®- 与384或1536通道的同时移液器保持较高精度和超快速样品板制备。
Single digit cost per sample
全自动1536样品板更改
New disposable MALDI HTS sample plates
The MPP system allows for the measurement of unmodified substrates in primary biochemical screens, and offers several advantages:
Pharmapulse溶液
The PharmaPulse Solution is based on Bruker´s advanced MALDI-TOF technology and on a dedicated software package. Ease of use and time to result were key drivers during the development resulting in an intuitive but yet powerful software solution to measure and analyze millions of samples in full automation. Two workflows guide the user from adapting an assay to MALDI mass spectrometry to readily exported results for further analysis in LIMS systems.
在生化筛选实验中,Rapiflex®MPP决定了生物化学的转化率ical assay when performed in the presence of potential inhibitors. In such a screen, a distinct MS peak ratio comparing product and substrate intensities is monitored throughout large numbers of sample spots, where each spot represents the same biochemical conversion reaction, but measures the effectiveness of a different inhibitor molecule.
In addition to this screening functionality, the new MPP software module supports “Synthesis Screening”, a methodology that requires more flexibility with regard to m/z values to be targeted by MALDI-TOF MS. Here, m/z values of interest may vary from spot to spot as each sample may represent a different chemical reaction. Accordingly, the new MPP “Synthesis Screening” software module allows scientists to screen for a large number of compounds per individual sample spot. This new MALDI-TOF based high-throughput analysis workflow could, therefore, enable highly time-efficient surveying of chemical reactivity landscapes at previously unseen mapping depth.
完整的库屏幕
Rafiflex®MPP is the only mass spectrometer for large primary screens of millions of compounds with high diversity. Full automation supports screening of more than one million compounds per week, avoiding time-consuming confirmatory screens. [1]
集中的库屏幕
用Rapiflex获得的数据质量®MPP满足了继发性和验证性筛选的要求,使其成为集中库筛选的理想检测器,例如从较小的库中识别靶蛋白的激酶抑制剂。[2]
片段筛选
The mass range and resolution accessible by MALDI-TOF mass spectrometry enables screening of fragments and other low molecular weight compounds. [3]
[1]冬季,M。;Ries,R。;克莱纳(C.)Bischoff,d。;Luippold,A。H。;Bretschneider,T。Buettner,F。H。;自动化的MALDI目标制备概念:提供基于药物发现的超高通量质谱法筛查。SLAS Technology 2018,https://doi.org/10.1177/2472630318791981
[2] Beeman,K。;Baumgartner,J。;Laubenheimer,M。;K. Hergesell;霍夫曼(M。)pehl,u。Fischer,F。;Pieck,J.C。;基于原位MALDI的高通量筛查过程的整合:与受体酪氨酸激酶C-MET的案例研究。SLAS光盘。 2017, 22, 1203–1210.
[3] Vanderporten,E。;Scholle,M。;Sherrill,J。;等。利用SAMDI技术的小分子非分子粘合剂的鉴定。Slas Discov。2017,22(10):1211-1217。
对酶生物化学和动力学的透彻了解对于开发和验证强大的HTS分析至关重要。Rapiflex®MPP通过线性测试,底物选择,KI测量和IC50测定有助于测定开发并进行确认。
半最大抑制剂浓度(IC50)是药物发现过程中的关键参数。MALDI PHARMAPULSE®软件通过具有专用方法开发模块来支持测定开发。使用方法开发模块获得的最佳测定条件是在MALDI-TOF筛选期间应用的,例如,针对IC50确定,该确定是在软件的专用筛选模块中设置和执行的。
每周使用Rapiflex一百万样品®MALDI PHARMAPULSE®
新的Rafiflex®MPP是Bruker创新的MALDI质谱仪的结果。它反映了我们对这项技术及其独特应用的热情和知识。Rapiflex的飞行时间质谱仪(TOF MS)®MALDI PHARMAPULSE®在HTS模式下监测高达30块质量:从小分子到大蛋白。Rapiflex的分辨率和灵敏度的提高®TOF MS允许,例如对乙酰胆碱(ACH)和胆碱的监测以鉴定乙酰胆碱酯酶(ACHE)抑制剂中数百万物质。巧妙的探测器设计可显着提高信号与噪声比,以提高整个质量范围的灵敏度。全新的HTS软件套件可轻松设置HTS屏幕,专有测定开发模块可确保快速适应MALDI质谱的无标签测定法。
Automation of rapifleX®MALDI PHARMAPULSE®
Rafiflex®MALDI PHARMAPULSE®旨在与实验室自动化系统无缝集成以执行全自动筛选活动。Maldi Pharmapulse®软件解决方案提供了一个开放的接口,可以从外部调度软件(例如Analytik Jena Lab Automation,Hightr Res Biosolutions,Beckman Coulter,Thermo Scientific Automation)控制其操作的一部分。Rapiflex的新高速自动装箱®MPP与机器人系统并驾齐驱,可快速加载和卸载样品板。
仅用于研究。不用于临床诊断程序。