高通量筛选
无标签的MALDI-TOF质谱法提供的独特速度和特异性
The all new rapifleX® MALDI Time-of-Flight mass spectrometer is the heart of the MALDI PharmaPulse®, it incorporates Brukers latest 10 kHz scanning laser technology and can read multiple samples per second. All components of the system work in concert for fully automatic HTS operation. The newly designed screening software suite supports HTS workflows and works in combination with a proprietary assay development module which empowers assay developer to accelerate label-free assay development for MALDI mass spectrometry. The latest ‚Synthesis Screening‘ software module of the rapifleX® MPP opens a new application space for e.g. monitoring of chemical reactions at high pace or analysis of binding assays at incomparable high throughput and specificity.
The use of mass spectrometry allows the measurement of unmodified substrates in primary screens to avoid false positives or false negatives, making confirmation screens redundant. The system is designed for fully automatic handling of 384 and 1536 sample plates to screen more than a million compounds in a week in support of drug discovery.
超高通量筛查标签的“命中”标识的新标准
通过将Bruker专利的SmartBeam 3D激光技术的速度与质谱的直接检测能力相结合,Rapiflex®MPP delivers unprecedented screening capability for ultra high-throughput screening of biochemical and cellular assays. It allows you to screen through large and diverse compound libraries at a pace of over a million compounds a week, epitomizing the perfect balance of automation and miniaturization.
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®-Well vario with 384 or 1536 channel simultaneous pipettor for high precision and ultra-fast sample plate preparation.
每个样本的单位数字
全自动1536样品板更改
新的一次性Maldi HTS样品板
MPP系统允许在原发性生化筛选中测量未修饰的底物,并提供多个优点:
Pharmapulse溶液
Pharmapulse解决方案基于Bruker的高级MALDI-TOF技术和专用软件包。在开发过程中,易于使用和时间是关键驱动因素,从而产生了直观但功能强大的软件解决方案,以测量和分析数百万个完全自动化的样本。两个工作流程指导用户从对MALDI质谱进行调整,以便在LIMS系统中进一步分析结果。
在生化筛选实验中,Rapiflex®MPP确定在存在潜在抑制剂的情况下进行生化测定时的转化率。在这样的屏幕中,比较产物和底物强度的明显MS峰值比在大量样品斑中进行监测,其中每个斑点代表相同的生化转化反应,但测量了不同抑制剂分子的有效性。
除了此筛选功能外,新的MPP软件模块还支持“综合筛选”,该方法学需要更高的灵活性,以实现MALDI-TOF MS的目标。在这里,感兴趣的M/Z值可能因点而异,因为每个样品可能代表不同的化学反应。因此,新的MPP“合成筛选”软件模块允许科学家筛选每个样品点的大量化合物。因此,这项新的基于MALDI-TOF的高通量分析工作流可以使高度及时的化学反应性景观的测量深度在以前看不见的映射深度上进行测量。
Full library screens
The rapifleX®MPP是数百万种具有高度多样性化合物的大主筛网的唯一质谱仪。完全自动化支持每周超过一百万种化合物的筛查,避免了耗时的确认屏幕。[1]
Focused library screens
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]
Fragment screening
通过MALDI-TOF质谱法可以访问质量范围和分辨率,可以筛选片段和其他低分子量化合物。[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.; Hergesell, K.; Hoffmann, M.; Pehl, U.; Fischer, F.; Pieck, J.C.; Integration of an In Situ MALDI-Based High-Throughput Screening Process: A Case Study with Receptor Tyrosine Kinase c-MET. SLAS Disc. 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。
Thorough understanding of enzyme biochemistry and kinetics is essential to develop and validate robust HTS assays. 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。
Half-maximal抑制剂浓度(IC50)是一个key parameter in the drug discovery process. 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。
A million samples per week with rapifleX®MALDI PharmaPulse®
The new rapifleX®MPP is the result of Bruker’s innovative development of MALDI mass spectrometers. It reflects our passion for and knowledge about this technology and its unique applications. The time-of-flight mass spectrometer (TOF MS) of the rapifleX®MALDI PharmaPulse®monitors up to 30 masses in HTS mode: from small molecules to large proteins. The improved resolution and sensitivity of the rapifleX®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。
Rapiflex的自动化®MALDI PharmaPulse®
The rapifleX®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®software solution offers an open interface to control parts of its operation from external scheduling software (e.g. Analytik Jena lab automation, HighRes Biosolutions, Beckman Coulter, Thermo Scientific automation). The new high-speed autoloader of the rapifleX®MPP works hand in hand with robot systems for quick loading and unloading of sample plates.
仅用于研究。不用于临床诊断程序。