Native Mass Spectrometry Workflows

To support a broad range of native MS workflows, Thermo Scientific native MS platforms can be paired with flexible UHPLC configurations. High-flow LC options enable faster analysis and increased sample throughput, while microflow configurations improve sensitivity when sample amounts are limited or lower-abundance species need to be detected.

Customizable modules allow the LC system to be tailored to specific analytical needs, including online separation, desalting, and more advanced sample-handling workflows. Optional fraction-collection capabilities also enable selected LC fractions to be retained for further characterization, orthogonal analysis, or method development. This modular approach allows laboratories to balance throughput and sensitivity while adapting the LC–MS workflow to changing research needs.

Reduce workflow complexity, improve compatibility across each step, accelerate method development, and support more consistent and reproducible results with a streamlined solution from a single provider. Thermo Scientific native MS platforms provide integrated, end-to-end workflows that support every stage of analysis, from reagents, sample preparation solutions, mass spectrometry instrumentation, software, to technical support. 

Thermo Scientific Q Exactive UHMR Hybrid Quadrupole-Orbitrap Mass Spectrometer and Thermo Scientific Orbitrap Tribrid Apex Strutural Biology Mass Spectrometer provide flexible native MS workflows that support ensemble measurements and single-particle charge detection mass spectrometry (CDMS) on a single platform.

This dual capability enables you to characterize heterogeneous protein complexes, large biomolecular assemblies, oligos and other high-mass analytes with greater confidence, from population-level mass distributions to individual ion measurements. In addition, advanced top-down capabilities and diverse fragmentation options support direct structural characterization of intact macromolecules, helping deliver deeper insight into composition, stoichiometry, and higher-order structure.

Experience sensitive, high-confidence analysis of protein complexes and other large biomolecular assemblies under near-native conditions. To help preserve noncovalent interactions while delivering the spectral quality needed for confident detection, characterization, and quantification, Thermo Scientific native MS workflows combine optimized sample preparation, highly reproducible chromatographic separations, and high-resolution accurate-mass (HRAM) Orbitrap mass spectrometers.

Enhance macromolecular characterization with the Orbitrap Tribrid Apex Structural Biology Mass Spectrometer, with advanced capabilities, including high-m/z scans, high-m/z quadrupole isolation, and diverse fragmentation options. These capabilities support deeper structural biology insights, more efficient data acquisition, and greater confidence in complex sample analysis, particularly for challenging biomolecules and resource-constrained projects.

Native MS, an important tool for large biomolecule analysis, preserves noncovalent interactions during measurement, enabling rapid, sensitive access to structural information. However, nonvolatile salts and buffer components, which can interfere with MS analysis, typically must be removed through a time-consuming offline buffer exchange that is difficult to automate.

Online buffer exchange native MS (OBE-nMS) enables direct screening of structural features in large biomolecules, including pre-purified proteins, protein complexes, and clarified cell lysates, even when these biomolecules are not highly stable in MS-compatible buffers. The information obtained by OBE-nMS can support fast quality control in less than five minutes and guide downstream processes such as protein expression protocol development and purification optimization.

High-throughput native MS ligand screening is an emerging approach for accelerating the discovery and characterization of small-molecule interactions with proteins and protein complexes. By preserving noncovalent interactions and enabling direct observation of ligand-bound states, native MS can provide rapid insight into binding events, complex formation, and interaction specificity without requiring labels or extensive assay development.

When combined with automated sample handling, multiplexed analysis, and advanced gas-phase characterization, high-throughput native MS workflows can screen large compound libraries efficiently while also supporting downstream identification and validation of promising binders. This capability is especially valuable for challenging drug discovery applications, including molecular glue and targeted protein degradation workflows, where weak or transient interactions and ternary complex formation are central to mechanism of action.

CDMS extends native MS analysis by enabling direct mass measurement of individual ions, making it especially powerful for heterogeneous, high-mass, and analytically challenging biomolecules. Applied at the MS1 level, CDMS can resolve complex mass distributions that may be difficult to interpret using conventional ensemble measurements. 

When extended to MS2, CDMS can support top-down characterization by measuring high-mass fragment ions and providing additional insight into composition, sequence, and structural features. Together, CDMS-MS1 and CDMS-MS2 workflows expand characterization capabilities for large protein complexes, oligonucleotides, glycoproteins, membrane proteins, and other complex biomolecular systems.