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Native mass spectrometry analysis service provides a powerful platform for the structural and functional characterization of proteins, protein complexes, and biotherapeutics in their native-like states. By preserving non-covalent interactions and higher-order assemblies throughout the analytical process, this service delivers accurate molecular weight determination, complex stoichiometry, and detailed structural insights without compromising biological integrity. Unlike conventional mass spectrometry methods that often require harsh, denaturing conditions, our native MS workflow maintains the natural conformation of biomolecules, enabling more physiologically relevant data.

This service is grounded in the pioneering work of electrospray ionization (ESI), developed by John Fenn in the late 1980s—a landmark achievement that earned the Nobel Prize in Chemistry in 2002. Today, native MS has evolved into a critical tool in structural biology, ADC characterization, and next-generation proteomics, especially when integrated with techniques like size-exclusion chromatography (SEC) for enhanced separation and sample stability.

At MtoZ Biolabs, we combine high-resolution instruments such as Exactive Plus EMR with optimized native-compatible buffers and rigorous QC protocols to support a wide spectrum of applications—from early-stage drug discovery to complex biologics analysis. Our native mass spectrometry analysis service is tailored to meet the demands of researchers and developers who require high fidelity, high sensitivity, and data they can trust for both scientific insight and regulatory compliance.

Technical Principles of Native Mass Spectrometry

Native mass spectrometry operates under non-denaturing conditions that retain the natural structure, interactions, and stoichiometry of biomolecules during ionization and analysis. The technique is powered by electrospray ionization (ESI), a soft ionization method that gently transfers proteins and complexes from solution into the gas phase with minimal fragmentation. By employing volatile buffers such as ammonium acetate at physiological pH, native MS preserves disulfide bonds, metal coordination, and non-covalent interactions essential to biological function.

To further reduce structural perturbation and improve signal clarity, native MS is frequently combined with size-exclusion chromatography (SEC). SEC pre-separates proteins and assemblies based on hydrodynamic radius, helping isolate target species, remove aggregates, and stabilize transient interactions before MS analysis. Once ionized, biomolecules are analyzed using high-resolution platforms like Orbitrap or Q-TOF systems, which offer broad m/z detection range (up to 20,000), precise mass accuracy, and exceptional resolution. These integrated techniques allow researchers to characterize intact proteins, profile heterogeneity, quantify conjugation levels, and detect structural variants—all while preserving native-like conformational states.

This combination of gentle sample handling, optimized separation, and advanced detection forms the foundation of MtoZ Biolabs’ native MS platform, enabling accurate, reproducible, and biologically meaningful characterization of complex protein systems.

Native Mass Spectrometry Applications 

The versatility of native mass spectrometry analysis service enables precise characterization of complex biomolecules under near-physiological conditions, addressing a wide range of challenges across therapeutic development, structural biology, and advanced proteomics research.

1. Antibody–Drug Conjugate (ADC) Characterization

Antibody–drug conjugates are intricate biotherapeutics requiring accurate assessment of drug-to-antibody ratio (DAR) and structural integrity. Traditional denaturing MS often disrupts disulfide- or cysteine-linked ADCs, leading to inaccurate DAR measurements and loss of quaternary structure. MtoZ Biolabs’ native mass spectrometry analysis service enables:

• Direct analysis of intact ADCs, preserving native configurations

• Accurate DAR quantification for both lysine- and cysteine-conjugated ADCs

• Batch-to-batch consistency verification and aggregation profiling

2. PEGylated and Polysaccharide-Modified Proteins

PEGylation and polysaccharide modifications improve pharmacokinetics but introduce structural heterogeneity and mass variability. These challenges hinder accurate characterization by conventional MS techniques. Leveraging high-resolution native mass spectrometry, MtoZ Biolabs can:

• Precisely determine the intact molecular weight of modified proteins

• Identify isomeric and glycoform variants

• Quantify site occupancy and monitor conformational shifts induced by modification

3. Protein Complexes and Oligomeric States

Many biological processes are governed by non-covalent protein assemblies that are easily disrupted under denaturing conditions. Native MS provides a powerful tool to:

• Characterize oligomeric states and stoichiometry of protein complexes

• Detect and quantify weak protein–protein and protein–ligand interactions

• Study transient assemblies in solution, including equilibrium dynamics

4. Structural Biology and Conformational Integrity

Mapping protein conformation under native-like conditions is critical for understanding folding mechanisms, functional states, and structural transitions.
Our service supports:

• Comparative analysis of folded, misfolded, and intermediate states

• Profiling of protein topology under native versus denatured conditions

• Evaluation of domain flexibility, compaction, and post-translational impact

5. Sample Integrity and SEC-Associated Effects

Pre-analytical steps such as SEC can introduce artifacts like non-specific binding or protein dissociation. Integrating SEC with native MS allows for real-time evaluation of such effects. MtoZ Biolabs’ integrated workflow enables:

• Assessment of sample aggregation and SEC-induced alterations

• Confirmation of sample homogeneity throughout the analytical pipeline

• Optimization of buffer systems to maintain protein structure and minimize artifacts

High-Resolution Native Mass Spectrometry Workflow

MtoZ Biolabs' native mass spectrometry analysis service utilizes a rigorous five-step analytical workflow:

1. Sample Preparation

Samples are prepared in high-ionic-strength ammonium acetate buffer (typically pH 6.8–7.4), with optional buffer exchange provided for compatibility. Non-reducing conditions preserve disulfide bonds and complex integrity.

2. Gentle SEC Separation

Mild SEC is applied to fractionate proteins and complexes without disrupting weak interactions. Buffer composition is optimized to minimize aggregation.

3. Native ESI-MS Acquisition

Utilizing the advanced Exactive Plus EMR platform, this workflow supports a wide m/z detection range (350–20,000), high mass accuracy, sensitivity, and fine-tuned conditions that minimize molecular dissociation.

4. Spectral Deconvolution and Data Processing

Dedicated software deconvolutes multiply charged spectra, determines molecular weights, and quantitatively profiles heterogeneous components. All results are reviewed by experts to ensure scientific validity.

5. Reporting and Interpretation

Clients receive detailed, publication-ready reports, including molecular weight distributions, stoichiometry, assembly analysis, DAR quantification, structural insights, and recommendations for further analysis as needed.

Seamless Submission and Comprehensive Deliverables

To ensure a smooth analytical workflow and high-confidence results, MtoZ Biolabs provides clear guidance on sample preparation and offers a comprehensive set of deliverables tailored to each project.

I. Sample Preparation Guidelines

These recommendations help maximize data quality and compatibility with native mass spectrometry workflows:

1. Accepted Sample Type: Proteins, small molecules, bioconjugates, and protein complexes.

2. Purity and Form: High-purity samples recommended; both solid and liquid forms accepted.

3. Buffer Exchange: Optional transfer into non-denaturing, MS-compatible buffers available as needed.

4. Required Sample Amount: Project-specific recommendations provided to ensure sufficient quantity and concentration.

II. Project Deliverables

Each project is supported with complete documentation and professionally curated analytical results:

1. Comprehensive Experimental Details: Full documentation of sample prep, SEC separation, and MS acquisition.

2. Materials, Instruments, and Methods: Detailed platform specs, chromatographic systems, ion sources, and QC benchmarks.

3. Total Ion Chromatogram and Quality Control Assessment (project-dependent): Chromatograms and ion spectra with internal QC metrics.

4. Data Analysis, Preprocessing, and Estimation (project-dependent): Processed mass spectra, deconvoluted molecular weight distributions, DAR calculations, structural analyses, and visualization tools.

5. Bioinformatics Analysis: In-depth bioinformatics for data interpretation, expert recommendations, and support for regulatory or academic submissions.

6. Raw Data Files: Access to all original and processed MS data ensures full transparency.

Why Choose MtoZ Biolabs' Native Mass Spectrometry Analysis Service?

1. Advanced Analytics Platform

The advanced high-resolution native mass spectrometry platform, featuring the SEC-coupled Exactive Plus EMR system, guarantees reliable, rapid, and highly accurate analytical service. A mature and validated workflow ensures optimal analysis of proteins and complexes in their non-denatured, native states.

2. One-Time-Charge

Pricing is transparent, with no hidden fees or additional costs. Clients benefit from a straightforward, client-centered approach, rapid project turnaround, and open, proactive communication at every stage.

3. High Data Quality

Deep data coverage is ensured through multi-tiered quality assurance and state-of-the-art spectral deconvolution technology. An AI-powered bioinformatics platform integrates all native mass spectrometry data, providing clients with a comprehensive and in-depth data report. Continuous access to experienced scientific experts supports personalized data review, project consultation, and ongoing support.

FAQ

Q1: How does MtoZ Biolabs ensure the preservation of protein structure during native mass spectrometry analysis?

Throughout the entire SEC and MS workflow, proteins and complexes are maintained in high-ionic-strength ammonium acetate buffer at physiological pH. Instrument parameters, including temperature, voltage, and pressure, are precisely controlled to preserve native conformations and prevent disruption of biologically relevant interactions.

Q2: What advantages does Native MS offer over standard MS?

Native MS maintains non-covalent interactions and enables the analysis of intact complexes and heterogeneously modified proteins. It provides broader m/z detection, higher biological relevance, and more accurate structural data for functional studies.

Accelerate Your Discovery with MtoZ Biolabs' Native Mass Spectrometry Analysis Service

MtoZ Biolabs, an integrated chromatography and mass spectrometry (MS) services provider, provides advanced proteomics, metabolomics, and biopharmaceutical analysis services to researchers in biochemistry, biotechnology, and biopharmaceutical fields. Our ultimate aim is to provide more rapid, high-throughput, and cost-effective analysis, with exceptional data quality and minimal sample consumption.

MtoZ Biolabs' native mass spectrometry analysis service empowers biopharmaceutical and structural biology research with high-resolution, physiologically relevant data. By integrating advanced native MS workflows and expert analytical platforms, we deliver accurate molecular characterization, consistent data quality, and biologically meaningful insights across a wide range of complex biomolecules. Whether your goal is therapeutic development, structural validation, or mechanistic discovery, MtoZ Biolabs is your trusted partner in achieving impactful results.

Contact our expert team or visit the MtoZ Biolabs website today to discuss your project and discover how our native mass spectrometry analysis service can drive your research forward.

Get in Touch

Name: Terry

Company: MtoZ Biolabs

Email: marketing@mtoz-biolabs.com

Phone: +1-857-362-9535

Address: 155 Federal Street, Suite 700, Boston, MA 02110, USA

Country: United States

Website: https://www.mtoz-biolabs.com/