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Native Intact Mass Analysis
Get deep structural insight to complex proteins and protein interactions
The complexity of modern therapeutic proteins, such as antibody-drug conjugates (ADCs), presents a significant analytical challenge requiring high resolution chromatography combined with high resolution mass spectrometry. ADCs involving cysteine conjugation present a unique challenge for characterization as proper intact analysis requires native mass spectrometry conditions to preserve structurally-critical non-covalent binding between antibody chains. Intact protein analysis under native mass spectrometric conditions can now be performed routinely using mass spec compatible buffers together with size exclusion (SEC) or ion exchange chromatography (IEC) coupled to Thermo Scientific Orbitrap Exploris BioPharma series mass spectrometers.
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Native intact mass analysis workflow
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Featured chromatography solutions for native intact mass
Superior separations under non-denaturing conditions
Use Thermo Scientific MAbPac SEC-1 Size Exclusion Columns for high-resolution separation of monoclonal antibody (mAb) analysis, including monomers and aggregates. These size-exclusion chromatography (SEC) columns provide superior performance, under non-denaturing conditions, and in high- and low-salt mobile phases and volatile eluents.
Chromatography built for biopharma
Use the innovative architecture of a UHPLC system that has been tailored to the specific and demanding analytical requirements that these essential drugs impose. The Thermo Scientific Vanquish Flex Binary and Quaternary systems have been designed and manufactured to exacting engineering standards to be truly built for biopharma.
Orbitrap mass spectrometers for native intact mass analysis
| Orbitrap Exploris 480 Mass Spectrometer | Orbitrap Eclipse Tribrid Mass Spectrometer | Q Exactive UHMR | Orbitrap Exploris 240 MS | |
|---|---|---|---|---|
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| Advantages | Extraordinary simplified within a compact footprint where next level exploration delivers richer insights gained with intact protein analysis under native mass spectrometric conditions, empowering all by bringing performance and intelligence together. | Go beyond today's discovery with new innovations that deliver the ultimate flexibility to expand experimental scope, with built-in intelligence to ensure the highest data quality and confidence with intact protein analysis under native mass spectrometric conditions. | Go beyond what you thought possible with an outstanding tool for investigating the higher order structure, native-like tertiary and quaternary protein structures with a high resolution accurate mass and an ability to analyze ultrahigh mass range. | Realize complete BioPharma characterization with distinct operational modes optimized for protein analysis, and take advantage of the extended mass range up to m/z 8000 available with the BioPharma Option for native MS analysis for antibody drug conjugates and other heterogeneous antibody samples. |
| Resources | ||||
| Resolving power | 480,000 at m/z 195 | 7,500-500,000 FWHM at m/z 200 (1M option) | 200,000 FWHM at m/z 400 (1M option) | Up to 240,000 FWHM at m/z 200 |
| Scan speed | Up to 40Hz | Up to 40Hz | 12Hz at resolution setting of 12,500 at m/z 400 | Up to 22Hz at resolution setting 15,000 at m/z 200 |
| Mass range | 40 to 6,000 m/z (up to 8,000 m/z with the BioPharma option) | 50 to 6,000 (up to 8,000 with HMRn) | 350 to 80,000 | 40 to 8,000 m/z |
| Dynamic range | >5000:1 | >5000 with a single OTMS spectrum | >5,000 with a single OTMS spectrum | >5000 within a single Orbitrap mass analyzer spectrum |
| Mass accuracy | Internal <1 ppm RMS; External: <3 ppm RMS | Internal <1 ppm RMS; External: <3 ppm RMS | Internal <1 ppm RMS; External: <3 ppm RMS | Internal <1 ppm RMS; External: <3 ppm RMS |
High-Field Asymmetric waveform Ion Mobility Spectrometry (FAIMS) can be used to optimize ion selectivity and reduce chemical backgrounds during mass spectrometry assays. FAIMS selectivity successfully prevents interferences from co-eluting compounds and increases signal to noise ratios by 100-fold or higher.
Featured software for native intact mass analysis
Powerful protein deconvolution algorithms
BioPharma Finder integrated software provides confident protein deconvolution to determine the molecular weight of proteins in both denaturing and native conditions. Protein sequence matching identifies N-linked glycosylation and other common post-translational modifications (PTMs) via intact mass analysis, helping you to fully understand the heterogeneity of your biologic drug.
Affordability made easy
Interested in financing options, purchasing a factory-certified refurbished LC-MS instrument or trading-in your existing mass spectrometer for something better? Choose from a wide selection of high performance systems from the most routine, for all levels of experience, to the most sophisticated and advanced research. We can get you to greater productivity at an affordable price.
Watch videos on native intact mass analysis
Featured intact protein analysis resource
Intact and Native Characterization webinars
Join experts from Genentech and Thermo Fisher to get great structural insight into your drug product using Orbitrap high resolution accurate mass spectrometers.
Featured Case Study
Featured intact protein analysis resource
Learn how Bio-Techne Corporation is delivering protein product quality through characterization expertise by investing in tools that deliver confident characterization.
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