Label-Free ultra-HTS Mass Spectrometry

rapifleX MALDI PharmaPulse

Innovation with IntegrityMALDI-TOF

The rapifleX MALDI PharmaPulse (MPP) accelerates label-free hit finding in drug discovery: rapifleX MPP combines the unambiguousness of mass spectrometry with the speed required to comb through large compound libraries of millions of substances.

Mass spectrometry allows measuring unmodified substrates in primary screens to avoid false positives or false negatives, making confirmation screens redundant. The system is designed to fully automate handling of 1536 sample plates and screen more than a million compounds in a week in support of drug discovery.

The all new rapifleX MALDI Time-of-Flight mass spectrometer is the heart of the MALDI PharmaPulse.

rapifleX is the only MALDI mass spectrometer with 10 kHz scanning laser technology and measures up to 10 samples per second. All components of the system work in concert for fully automated 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 assays for MALDI mass spectrometry.

rapifleX MALDI PharmaPulseLabel-Free ultra-HTS Mass Spectrometry

CyBio®-Well vario

The power to do more

1536 sample spots on a MALDI sample plate

Results from the assay condition optimization are subsequently transferred to the “Screening Workflow”.

The new standard for ultra-HTS label-free ‘Hit’ identification

By combining the speed of Bruker’s patented Smartbeam™ 3D laser technology with the direct-detection capability of mass spectrometry, the rapifleX MALDI PharmaPulse (MPP) delivers unprecedented screening capability for HTS of biochemical assays. The system allows you to screen through large and diverse compound libraries at a pace of over a million compounds per week, epitomizing the perfect balance of automation and miniaturization.

The MPP system allows measuring unmodified substrates in primary biochemical screens, and offers several advantages:

• It effectively eliminates confirmatory assays typical of traditional fluorescence-based screening techniques

• Saves the cost of developing specific fluorescence probes or antibodies

• Does not require expensive solvents or consumables for continuous operation

• Works with sample volumes down to 25 nl

The MPP system is specifically designed to fully automate handling of 384, 1536, 3072 and 6144 samples per plate, including automated method development and instant export to LIMS.

New dedicated HTS software

The new HTS software suite supports easy setup of HTS screens, and the proprietary assay development module ensures fast adaption of label-free assays for MALDI mass spectrometry. In the course of developing biochemical assays, buffers and supplementary components are mandatory to aid enzymatic activity although those assay components can adversely influence the sensitivity of the MALDI mass spectrometer. The rapifleX MALDI PharmaPulse software solution assists assay developers to determine optimal assay conditions by measuring hundreds of different assay compositions and dilutions within minutes and simultaneously correlating them with various instrument parameters. The algorithm instantly identifies the optimal assay composition using the corresponding instrument parameter set.

Chandler, J.; Haslam, C.; Hardy, N.; Leveridge, M.; Marshall, P. A Systematic Investigation of the Best Buffers for Use in Screening by MALDI–Mass Spectrometry. J. of biomolecular screening, SLAS Discovery 2016, 1–8.

PharmaPulse Solution

The PharmaPulse Solution is based on Bruker´s advanced MALDI TOF technology and a dedicated software package. Ease-of-use and time-to-result were key drivers in the software development, resulting in an intuitive but yet powerful 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 exporting results for further analysis in LIMS.

Bringing added value to drug discovery:

Robustness to analyze 2-3 million samples without intervention • New source and ion optical design • No source / ion optic cleaning during

primary screens • Easy and fast cleaning if required

Economical cost per sample • No solvent, no waste, no labeling • 0.025 to 1 µL sample volume • Low-cost disposable sample plates

New disposable MALDI HTS sample plates • Tailored for HTS operation • Fulfill all requirements for reliable

MALDI ionization • Suitable for 384, 1536, 3072 or 6144

geometries • Compatible with CyBio®-Well vario with

384- or 1536-channel simultaneous pipettor for high precision and ultra-fast sample plate preparation

Fully automated 1536-well plate change • New ultra-fast autoloader that seamlessly

integrates with common robot systems • Rugged design tailored to uHTS operation

Dedicated HTS software for MALDI mass spectrometry

The assay development workflow allows for easy and seamless transfer of biochemical assays to Bruker´s MALDI TOF mass spectrometers.

Using a multidimensional approach, serial dilutions, buffer concentrations and other assay components are analyzed in the context of various instrument conditions to identify optimal assay composition and instrument setup.

The rapifleX MALDI PharmaPulse monitors up to 30 masses in HTS mode: from small molecules to large proteins. Therefore, substrates and products, as well as standards if required, can be monitored simultaneously. Analyte masses, areas, and intensities are exported to a LIMS for further review and analysis.

Drug discovery workflow with rapifleX MALDI PharmaPulse

Target Identification

Target Validation

LeadOptimization

rapifleXMPP

LeadCandidate

HitIdentification

6 6

5

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44

1

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3

2

2

1

Label-free uHTSby mass spectrometry

Seamless connectivity with automation systems

The rapifleX MALDI PharmaPulse seamlessly integrates with laboratory automation systems to perform fully automated screening campaigns.

The 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.

Customized rapifleX MPP automation layout with Analytik Jena lab automation

Bruker rapifleX MALDI TOF High-speed automated sample tray CyBio®-Well vario 1536 Multi-channel pipettor PreciseFlexRobot Cytomat C10 Storage for assay plates CyBio®

-QuadStack Storage MALDI sample plates

Accelerate lead candidate discovery

A million samples per week with rapifleX MALDI PharmaPulse

The new rapifleX MPP is the outcome of Bruker’s innovative development of MALDI mass spectrometers. This unique instrument reflects our knowledge and passion for this technology and its unique applications. The improved resolution and sensitivity of the rapifleX TOF-MS allows e.g. the monitoring of acetylcholine (ACh) and choline to identify acetylcholinesterase (AChE) inhibitors out of millions of substances. An ingenious detector design delivers significantly improved signal-to-noise ratios for enhanced sensitivity across the mass range. Finally, a completely new HTS software suite supports easy setup of HTS screens, and the proprietary assay development module ensures fast adaptation of label-free assays for MALDI mass spectrometry.

Measure disappearance Measure appearance

Product ProductSubstrate Enzyme

FluorescenceLabel

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Acetylcholinesterase

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pIC50 384 well RapidFire Assay

Correlation between MALDI mass spectrometry (1536 plate geometry) with SPE mass spectrometry (384 plate geometry)

The evolution of MALDI-TOF based methods and advances in liquid handling makes this a viable option for uHTS applications in 1536-well format and beyond.

Haslam, C.; Hellicar, J.; Dunn, A.; Fuetterer, A.; Hardy, N.; Marshall, P.; Paape, R.; Pemberton, M.; Resemann, A.; Leveridge, M. The Evolution of MALDI-TOF Mass Spectrometry toward Ultra-High-Throughput Screening: 1536-Well Format and Beyond. J. Biomol. Screen. 2016, 21, 176-186.

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For research use only. Not for use in diagnostic procedures.

Bruker Daltonik GmbH

Bremen · GermanyPhone +49 (0)421-2205-0 Fax +49 (0)421-2205-103

Bruker Daltonics Inc.

Billerica, MA · USAPhone +1 (978) 663-3660 Fax +1 (978) 667-5993

ms.sales.bdal@bruker.com – www.bruker.com

MALDI PharmaPulseLabel-Free ultra-HTS Mass Spectrometry

Label-free

uHTS MS

Fully automated

YEARS MALDI25