This article is based on a poster originally authored by Ariane Jonetz-Mentzel et al.
In biopharmaceutical laboratories, there is an increasing demand for label-free, high-throughput screening based on Mass Spectrometry (MS).
Specifically, MALDITOF (Matrix Assisted Laser Desorption/Ionization Time-of-Flight) applications can be used to screen small molecules, peptides, and proteins for enzyme assays in high-throughput (HTS - 10,000 compounds/day) or ultra-high-throughput (Ultra-HTS - 100,000 compounds/day) modes.
The speed of modern analytical instruments, such as Bruker’s rapifleX® with an analysis time of 0.25 seconds per sample, requires faster sample preparation for high-throughput applications.
In cooperation with Bruker, Analytik Jena has developed a novel automated liquid handling system for fast MS sample preparation for high throughput applications.
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Introduction
Analytik Jena and its collaboration partner Bruker built a bridge between the powerful and unique label-free detection capabilities of mass spectrometry and automated uHTS MALDI sample preparation.
Through the integration of the CyBio Well vario 96–1536 pipetting device, Analytik Jena presents more than just a simple spotting tool. This innovative solution works in tandem with Bruker devices like rapifleX® or autofleX® to address specific application bottlenecks.
The liquid handling workstation operates the entire workflow, including sample deposition on MALDI sample plates, MALDI matrix spotting, active drying, and the handling of consumables throughout the process.
Small assay volume and homogenous spot generation
Spot-on-spot pipetting for MALDI sample preparation requires remarkably high precision in positioning and pipetting. This can be achieved, among other reasons, due to the setting of the CyBio Well vario itself and its patented sealing technology.
The fixed pipetting head, combined with the precise plate lifter, ensures the necessary accuracy in positioning during the repeated spotting process.
The tip sealing mat of the pipettor guarantees an airtight seal, maintaining high precision and uniform tip length for the 1 μL ceramic tips. This feature enables the CyBio Well vario to achieve pipetting with a coefficient of variation (CV) of less than 5%, allowing for the creation of small spots as small as 100 nL.
Figure 1. Precision CyBio Well vario 1536 with 1 μL Ceramic Tips, wet Transfer, n=3. Image Credit: Analytik Jena US
Improved measurement conditions and results due to “On-Target-Washing”
The CyBio Well vario 1536 features a distinctive desalting function as part of the MALDI sample preparation process. Known as the "On Target Wash," this process effectively reduces or eliminates adduct formation and ion suppression. Consequently, it positively impacts peak area counts and enhances signal intensity.
Thanks to the 1536 parallel working pipetting channels, the CyBio Well vario 1536 has the potential to increase the assay robustness by adding an essential step to the workflow without exceeding the measuring time of the mass spec reader.1
Figure 2. CyBio Well vario 1536 pipetting head spotting on MALDI target plate. Image Credit: Analytik Jena US
Effective and sustainable workflow
A fully automated dispensing and analysis system for MALDI-TOF analysis has been created by integrating a high-speed liquid handling workstation with ultrafast mass spectrometric detection.
This adaptable platform enables parallel transfer of matrix and sample onto MALDI targets, active drying, and the insertion and removal of plates from the rapifleX® in less than 10 minutes per 1536 density. This system can spot and read up to 130 plates daily through efficient scheduling.
Figure 3. MALDI-TOF Integration: an Ultra-High Throughput Automation Solution. Image Credit: Analytik Jena US
Conclusion
The fully automated dispensing and analysis system demonstrates unparalleled performance in drug discovery screening and early drug development, successfully completing a 2 million molecule diversity screen within just ten days.
This liquid handling automation solution in drug discovery screening effectively addresses application bottlenecks, leading to significant breakthroughs in throughput, assay robustness, and reliability for MALDI-TOF sample preparation. Moreover, it enables ultrahigh throughput screening with the integrated MS System rapifleX® from Bruker.
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References and further reading
- Application Notes Bruker # MT-60 - fl ex series “Prestructured MALDI Sample Supports: Sample Washing and Recrystallization” page 4.
About Analytik Jena US
Analytik Jena is a provider of instruments and products in the areas of analytical measuring technology and life science. Its portfolio includes the most modern analytical technology and complete systems for bioanalytical applications in the life science area.
Comprehensive laboratory software management and information systems (LIMS), service offerings, as well as device-specific consumables and disposables, such as reagents or plastic articles, complete the Group’s extensive range of products.
About life science
The Life Science product area demonstrates the biotechnological competence of Analytik Jena AG. We provide a wide product spectrum for automated total, as well as individual solutions for molecular diagnostics. Our products are focused to offer you a quality and the reproducibility of your laboratory results.
This will surely ease your daily work and speed up your work processes in a certain way. All together we support you through the complete process of the lab work. Besides we offer customized solutions and are able to adapt our products to your needs. Automated high-throughput screening systems for the pharmaceutical sector are also part of this segment’s extensive portfolio.
About analytical instrumentation
Analytik Jena has a long tradition in developing high-performance precision analytical systems which dates back to the inventions made by Ernst Abbe and Carl Zeiss. We have grown to become one of the most innovative manufacturers of analytical measuring technology worldwide.
Our business unit Analytical Instrumentation offers excellent competencies in the fields of optical spectroscopy, sum parameters and elemental analysis. Being proud of our core competency we grant all our customers a long-term warranty of 10 years for our high-performance optics.
About lab automation
With more than 25 years of market experience, Analytik Jena with its CyBio® Product Line is a leading provider for high quality liquid handling and automation technologies. In the pharmaceutical and life science industries, our products enjoy the highest reputation for precision, reliability, robustness and simplicity.
Moreover, the Automation Team designs, produces and installs fully automated systems tailored to our clients' application, throughput and capacity requirements. From stand-alone CyBio® Well up to fully customized robotic systems we handle your compounds, biomolecules and cells with great care.
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