Chemical analysis is a critical need in our high-tech industrial world. Mass spectrometry, with its high sensitivity and high selectivity, occupies a pivotal role in the detection and quantitation of a vast array of chemical substances. It is the approach of choice for the characterization of biopharmaceutical products and potential impurities, and allows for accurate product development, rapid regulatory approval, and expeditious entry into production.
Biopharmaceuticals generated through recombinant DNA technology are becoming more and more significant in the therapeutic landscape. Because they are synthesized by living cells, their production is profoundly affected by minor variations in culture conditions. Regulations demand precise monitoring of their constituent properties, and mass spectrometry is well-suited as the optimal analytical tool.
The term “analyze by mass spectrometry,” particularly when attached to a biopharmaceutical sample, does not reference a singular tool or technique but rather any number of a wide variety of mass analyzers and sampling techniques, each with unique characteristics, advantages, and disadvantages. For many mass spectrometry techniques, collection, separation, and preconcentration of the sample are necessary and often followed by derivatization of targeted compounds to optimize their chemical properties to enhance their measurement.
Mass spectrometry systems often combine two mass analyzers as combinations of different basic types. Their overall design can be highly versatile in terms of the ionization methods and the types of measurements they are programmed to perform. Often the total time needed for the mass analysis step is measured in seconds but the sample preparation and pretreatment steps can take hours to execute. It is here where MALDI-TOF analyses offer a considerable advantage owing to the relative simplicity of sample preparation and of the mass analyzer.
The Bruker Daltonics ultrafleXtreme™ is a MALDI-TOF/TOF mass spectrometer designed to address a wide range of analytical problems. With features such as panoramic PAN™ technology, which provides high resolving power across a wide mass range; the Flash Detector™, which enables fast response with minimal saturation; and the 2kHz smartbeam™ II laser ultrafleXtreme can be applied into a variety of research areas. These include proteomics research, quantitation, top-down sequencing, and MALDI imaging.
For peptide analysis the system can exceed 40,000 FWHM resolution with corresponding measurement accuracy of <1.5 ppm. It will accommodate protein analysis with unit resolution for proteins up to 13 kDa and detection for proteins as large as an intact α-2-macroglobulin dimer, at 700 kDa (Figure 1). For all these experiments ultrafleXtreme provides improved data acquisition speeds, spatial resolution, and better mass accuracy than other MALDI-TOF systems.
An additional component that improves the speed and accuracy of the system is the self-cleaning Perpetual™ ion source. This push-button function works in minutes for all MALDI matrixes to provide maximum up-time.
The software accompanying the ultrafleXtreme was specifically designed to be method-driven but also allow flexibility for any novel experiments. It can be operated in high-throughput at up to 2,000 Hz in MS mode and up to 1,000 Hz in TOF/TOF mode. In addition, the optimized Smartbeam-II laser delivers constant high output energy, independent of the selected repetition frequency across long acquisition runs.