Overview
Reveal biomolecular signatures in unprecedented detail
The Thermo Scientific Direct Mass Technology mode redefines mass spectrometry by equipping Thermo Scientific Q Exactive UHMR Hybrid Quadrupole-Orbitrap mass spectrometers with charge detection. This revolutionary parallel individual ion measurement technique provides direct, accurate mass determination, enabling you to decipher protein complexes, biotherapeutics, and viral particles that are too complex to resolve using ensemble methods. As a result, small changes to large molecules, for example post-translational modifications, can be revealed in exquisite detail. With a charge-detection enabled Orbitrap mass analyzer, unravel complexity and unlock new insights into proteoforms, biotherapeutics, and next-generation drug modalities.
- Direct mass determination, eliminating need for m/z-based deconvolution
- Up to 20-fold increase in resolution relative to traditional ensemble ion measurements
- Requires less sample or less concentrated samples
- Access to measurements up to 80,000 m/z and mass measurements in the megadalton range
Direct Mass Technology mode
See how Direct Mass Technology mode adds charge detection for the simultaneous measurement of m/z and z for individual ions
A solution to match the challenge of biological complexity
"One of the most exciting things about Direct Mass Technology mode is it can make the impossible seem very possible. And then, once possible, you get the belief that you can understand protein-level biology. And this is what proteomics needs. We need to understand that we're not overwhelmed by the scale of complexity in the human proteome, that we can actually build tools that match the scale of our biology with the scale of the solution."
Neil Kelleher, Ph.D.
Director, Northwestern Proteomics & the Chemistry of Life Processes Institute
Northwestern University
Direct Mass Technology mode for charge detection
Transform m/z spectrometry to mass spectrometry with simultaneous parallel individual ion measurement of both mass to charge and charge.
Go beyond with native MS
Perform the highest quality native intact mass and top-down analysis in structural biology and biopharma research with the Q Exactive UHMR mass spectrometer.
Key benefits
Charge determination
The Direct Mass Technology mode adds charge detection capabilities to enable simultaneous measurement of both mass-to-charge (m/z) and charge (z) for hundreds of individual ions in parallel. This allows for the calculation of the mass of the ions directly, without the traditional need for m/z dependent deconvolution that relies on resolved signals in ensemble measurements.
Increase resolution
The Direct Mass Technology mode measures individual ions directly, resulting in 10-20-fold increases in resolution compared to ensemble measurements with the same resolution settings. Individual ion measurements with the Direct Mass Technology mode can allow the isotopic resolution of large and complex analytes typically not possible with ensemble measurements.
Use less sample
Since the Direct Mass Technology mode uses individual ion measurements, the number of ions required for a single measurement is drastically reduced. This means samples can be hundreds of times diluted compared to ensemble measurements, saving precious sample.
Go big
Measurements are read out directly in the mass domain with the Direct Mass Technology mode, renabling measurements up to 80,000 m/z and mass measurements in the megadalton range. Go beyond the capabilities of native ensemble measurements to explore the redefined limits of addressable size and complexity.
Overview of the Direct Mass Technology mode workflow
Available on the Q Exactive UHMR mass spectrometer, the Direct Mass Technology mode adds:
- Automated ion population control to maximize throughput and signal quality for parallel individual ion measurements
- A charge calibration procedure
- STORIboard processing software to perform charge calibration, data processing, and data visualization developed in collaboration with Proteinaceous, Inc.
Step 1: As with traditional Orbitrap measurements, the mass to charge ratio m/z is determined by the frequency of axial rotation around the central electrode.
Step 2: With the Direct Mass Technology mode every ion is also analyzed individually in parallel. The integrated signal for each individual ion is plotted over time through measuring the rate of the induced charge on the outer electrode at the specific frequency of the ion and is known as the Selective Temporal Overview of Resonant Ions (STORI).
Step 3: The slope of the STORI plot for each individual ion is then compared to the charge calibration curve to determine the charge (z). The mass of each individual ion can then be directly calculated using the mass to charge (m/z) and charge (z) information generated by the measurements.
The Direct Mass Technology mode adds extra dimensionality to Orbitrap measurements with parallel individual ion measurements to produce high-resolution results directly in the mass domain.
Applications
Glycoform analysis
Reveal exquisite details
Standard native ensemble measurements can be restricted by spatial resolution and dynamic range, resulting in limited detection of glycoforms. With the Direct Mass Technology mode more masses can be resolved through simultaneous charge detection to more than double the number of uniquely assigned glycoforms.
Membrane proteins and complexes
Increase sensitivity and resolution
Membrane proteins and complexes require considerable sample preparation and have unique analytical challenges. The Direct Mass Technology mode provides higher sensitivity and resolution through individual ion measurements, allowing for less sample consumption and delivering confidence in results from a single analysis.
Biotherapeutic characterization
Turn complexity into clarity
Complex biotherapeutics present analytical challenges that can require multiple experiments and very careful sample processing and handling. The Direct Mass Technology mode allows for charge state and mass determination to reveal a wider molecular weight distribution and more detailed insights into complex analytes.
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