Charge Variant Analysis
Make unidentified peaks a thing of the past
Don’t be restricted by your charge variant method.
Accelerate Charge Variant Analysis with ZipChip
The development of therapeutic proteins such as monoclonal antibodies (mAbs), bispecific antibodies, fusion proteins, and antibody-drug conjugates (ADCs) continues to grow rapidly but these proteins are much more heterogeneous than small molecule drugs. Understanding the biotherapeutic profile and identifying charge variants are critical to the safety, efficacy, and potency of the therapeutics and must be assessed throughout the development and the commercialization to meet regulatory requirements.
Charge variant analysis (CVA), at the intact protein level, is a powerful tool to distinguish protein isoforms based on differential surface charge, requiring minimal sample preparation and short analysis times. Traditional methods for charge variant analysis, such as capillary isoelectric focusing (cIEF) are not compatible with Mass Spectrometry (MS), and ion-exchange chromatography (IEX) techniques may require extensive method development to achieve separation of charge variants without destroying the analyte of interest.
Get More Data and More Efficiency with ZipChip
- High Resolution – Separation under native conditions with charge variant identification
- Rapid – Charge variant separation in under 15 minutes
- Easy – No method development with dedicated kits
- Salt & Detergent Friendly – No complex sample prep
- Flexible – ZipChip can be used for multiple CQAs
High-Resolution Separation
Get high-resolution charge variant separations of intact antibodies backed by the power of Native-MS characterization. In a single run, you can get mass information, assess charge heterogeneity, characterize glycoforms, identify basic and acidic variants, and more. The added mass spec information means you can finally pinpoint the identity of each peak every time, even species below 1% relative abundance.
Turnaround Time 100x Faster Than LC-MS
Maximize return on your MS instrument investment and boost your analytical throughput and the core-lab capacity with rapid charge variant separation. ZipChip enabled charge heterogeneity speciation and identification in as little as 2 minutes – 100 times faster than LC-MS.
1. Grab Your Kit
2. Dilute Sample and Prepare BGE
3. Load ZipChip
4. Run Mass Spec
No Method Development and Minimal Sample Prep
ZipChip provides a fast, accurate, and flexible approach to charge variant analysis. Assay kits take the guesswork out of method development and come with background electrolyte and sample diluent that are optimized for each application, so you don’t have to waste time on method development or extensive sample prep.
On-chip desalting and removal of detergents means minimal sample prep. Switch molecules without having to change conditions or instrumentation. Queue it all up, ignore your salt and polymeric buffer components, and hit go.
Take Guesswork Out Of Method Development
ZipChip consumables take the guesswork out of method development. Assay kits come with background electrolyte and sample diluent that’s optimized for each application. Just put the bottle of background electrolyte in the autosampler, prep your samples with the sample diluent and you’re off!
How to Find Your Assay & Consumables Kit:
Pick a BGE Kit
Then a Chip
Super-charge Your Mass Spec
Struggling with increased workloads? Increase your throughput with plug and play applications for multiple Critical Quality Attributes (CQAs). Maximize your MS investment and boost your lab’s productivity with multiple characterization assays. Whether you’re running intact charge variant analysis, subunit analysis, peptide mapping, metabolites analysis, or oligonucleotides analysis, ZipChip works at every level.
Charge Variant Analysis
ZipChip
Pop ZipChip on your mass spec as the source. It separates your samples and electrosprays them into your mass spec for analysis. There’s no optimization to do or connections to make. Click the chip in place and you’re off. Ready to go assay kits are optimized for each application, all you do is dilute-and-shoot. From peptide mapping to native charge variants analysis, ZipChip can do it all. And you don’t have to lift a single finger for method development.
Suggested Resources
Charge Variant Analysis of Native Antibodies for In-depth Characterization of mAb-based Biotherapeutics
A ZipChip Based CZE-MS Analysis for Quick Assessment of Biotherapeutics
Charge variant analysis with ZipChip and maXisII
A ZipChip capillary zone electrophoresis system coupled to Bruker maXis II UHR-QTOF offers an alternative selectivity to separate charge variants prior to MS analysis and affords a more complete intact mass characterization without adding complexity or high salt eluents.
Frequently Asked Questions
Sample preparation on ZipChip is minimal. Since the system is tolerant towards both salts and detergents, the only recommendation is to dilute your sample with our provided diluent. Then you can load it on the autosampler and it is ready to run.
Our Charge Variant Analysis protocol includes guidelines for sample preparation, system suitability testing, mass spectrometry method parameters, and ZipChip method parameters. This information coupled with our application-specific consumable kits, allows for very minimal method development to analyze your samples with ZipChip.
The benefits of using ZipChip over techniques such as Imaging Capillary Isoelectric Focusing (iCiEF), Ion Exchange Chromatography (IEX), or Cation Exchange Chromatography (CEX), is that the ZipChip uses a mass spectrometer as the detector. This allows for true identification of any basic or acidic species found in your sample. Compared to Liquid Chromatography coupled to Mass Spectrometry, ZipChip provides the benefit of low sample preparation and method development time. Fractionation of the sample is not needed before mass spec analysis. There is also very little sample needed for ZipChip CE-MS analysis, compared to most other methods, and essentially no carryover between analyses.
The run time varies depending on the isoelectric point of your protein. It is usually between 7 to 15 minutes for Monoclonal Antibodies (mAbs).
Running CVA using ZipChip allows you to separate any protein variants with Post-Translational Modifications that induces a charge difference when compared to the main protein variant. This allows you to separate and identify CQAs such as Lysine Clippings, Deamidation, Succinimide Intermediates, and different Glycoforms of each charge variant.
email Subscribe to Our Communications Signup to receive new product updates, technical tips and more.