Waters next generation GTxResolve MaxPeak Premier Microflow Columns represent one such leap forward. Engineered to enhance recovery for challenging biomolecules, including oligonucleotides, they offer a high-sensitivity path to deeper insights even when the sample size is limited.

Why microflow for oligonucleotide analysis?

Oligonucleotide characterization presents unique chromatographic challenges, including:

• Adsorptive losses to metal hardware
• Poor peak shapes for acidic or highly charged analytes
• Sensitivity constraints when working with scarce therapeutic samples

Shrinking column diameter from 2.1 mm to a 1 mm ID microflow format directly addresses these issues by reducing band broadening and concentrating analytes for improved detectability. Waters newest microflow columns deliver up to 2x higher sensitivity than conventional stainless-steel microflow columns, an advantage especially meaningful for low-abundance oligonucleotides, often associated with bioanalysis/DMPK studies.

MaxPeak HPS Technology: Protecting every molecule

As has been clearly shown with traditional 2.1 mm ID analytical columns, MaxPeak High Performance Surfaces (HPS) Technology essentially eliminates the variability associated with non-specific adsorption (NSA) of acidic analytes (including oligonucleotides) to the metal surfaces of a column, thus improving recovery/sensitivity and repeatability.

For oligonucleotides that are often highly negatively charged, this translates into:

• Reduced analyte loss due to minimized metal interactions
• Sharper, taller peaks
• Improved reproducibility and lower limits of detection

These improvements allow analysts to move confidently from method development to validated performance without the lengthy passivation/sample conditioning associated with conventional stainless-steel hardware.

Efficiency with purpose: Lower sample and solvent use

In addition to sensitivity enhancements, microflow formats help laboratories meet sustainability and cost-reduction goals. Transitioning from a 2.1 mm to a 1 mm ID column reduces:

• Solvent use by 4X, lowering waste and operating expenses
• Sample consumption by up to 75%, allowing more data to be captured from precious, limited samples

With reproducibility from the first injection and reduced peak tailing at low flow rates, these columns integrate seamlessly into LC-MS oligo workflows without requiring major system reconfiguration. 

A more sustainable future for oligonucleotide characterization

Beyond performance, MaxPeak Premier Microflow Columns are manufactured with sustainability in mind. They incorporate up to 70% recycled content and come from resource-efficient facilities certified for environmentally responsible design. In addition to the solvent reductions inherent to microflow separations, MaxPeak Premier Microflow Columns received the ACT Label certification for their environmentally responsible design and manufacturing.

Microflow is no longer a compromise, it’s a competitive advantage

As oligonucleotide therapeutics continue their rapid expansion, analytical teams need tools that can keep pace with increasing complexity and decreasing sample volumes. MaxPeak Premier Microflow Columns bring together heightened sensitivity, improved analyte recovery, and meaningful resource savings, delivering the workflow acceleration and data confidence required in modern bioseparations.

Whether you are developing ASOs, siRNAs, CRISPR guides, or mRNA purification strategies, microflow are your high-performance, low-resource path forward.

Are you ready to explore what’s possible with GTxResolve Microflow Columns? Take a deeper dive with these resources:

• Register for our upcoming microflow webinar
• Visit our Microflow Columns product page
• Download our infographic

That’s where advances in Protein A (ProA) affinity chromatography are making a meaningful difference, reshaping how teams measure titer, monitor cultures, and assess product quality throughout development.

How affinity chromatography and Protein A work

Affinity chromatography leverages highly specific biological interactions to isolate a target molecule from a complex mixture. In the case of monoclonal antibodies, Protein A, a bacterial protein, binds strongly to the Fc region of many IgG subclasses.

The workflow is simple and powerful:

1. Antibodies bind to immobilized Protein A
2. Impurities wash through
3. Bound antibodies elute in a concentrated, measurable form

This selectivity has made Protein A the backbone of antibody analytics for decades, widely used for titer measurement, purification, variant analysis, and bioprocess monitoring.

Where modern Protein A affinity chromatography delivers real impact

1. Earlier, more sensitive titer measurement

One of the biggest challenges in upstream development is waiting for cultures to reach concentrations detectable by traditional assays. Newer Protein A workflows allow teams to measure titer from microbioreactors much earlier in cell culture (even as early as day 1), giving them faster visibility into growth trends, clone performance, and culture stability.

This earlier insight helps teams:

• Make informed selections sooner
• Identify issues before they affect yield
• Reduce delays and unnecessary repeat experiments

2. Lower carryover for more trustworthy titer results

Carryover, remnants of mAbs or impurities left behind after elution, can undermine result reliability and contaminate follow-up injections. Updated Protein A column designs now significantly reduce this issue.

Key advantages:

• ~65% lower carryover vs. a comparable alternative, meaning cleaner injection-to-injection performance
• More accurate, reproducible titer data for sequential samples
• Lower risk of cross-contamination during column reuse, protecting downstream analyses

3. Integrated titer and aggregate analysis through 2D ProA–SEC

Traditional workflows require separate assays for titer and aggregate/size-variant analysis. Modern two-dimensional Protein A–SEC methods bring these measurements together, providing both readouts in a single run.

These integrated workflows offer:

• Titer and aggregate data from one injection
• High throughput without adding complexity
• Optimization of speed or resolution depending on your needs

Options range from trap-and-elute formats for speed and high resolution to direct-connect approaches designed for simplicity. Both reduce hands-on work and streamline data collection.

4. Faster, deeper structural insight with ProA-MS

Teams increasingly need structural understanding beyond just titer. Rapid Protein A elution combined with native high-resolution MS now enables intact mass analysis of mAb and msAb variants directly from cell culture media in less than five minutes.

This approach reveals:

• Low-abundance variants
• Oxidation states
• Heavy chain pairing differences
• Other structural attributes normally require additional purification

The ability to pair titer and structural insight so quickly helps scientists make smarter decisions earlier in development.

5. Stronger support for upstream and downstream monitoring

Bioprocessing teams need analytics that are fast, stable, and compatible with a wide range of LC conditions. Updated Protein A methods maintain reproducible performance under high-pressure operation and across long study timelines, making them well-suited for:

• Real‑time titer trending on both HPLC and UPLC systems
• Early feedback for process optimization
• Routine monitoring across multiple batches

The consistency they provide is essential for robust process development and PAT initiatives.

6. More consistent performance through routine CIP

Media components inevitably accumulate Protein A resin over repeated injections, affecting backpressure, peak shape, and recovery. Routine clean-in-place (CIP) keeps columns stable and prevents buildup. In controlled testing, Protein A columns remained effective for 1500+ injections when CIP was applied regularly.

Benefits include:

• Sustained performance over long campaigns
• Reduced fouling and drift
• Longer column lifetime
• More consistent titer data

The takeaway: Protein A is evolving alongside modern bioprocessing.

Modern Protein A affinity chromatography has become a multi‑functional analytical engine that helps teams achieve:

• Earlier visibility into process performance
• Cleaner, lower-carryover workflows
• Integrated multi-attribute analysis
• Faster structural insight
• Longer lasting, more stable columns

As biologics pipelines accelerate and diversify, these capabilities are no longer ‘nice to have;’ they’re essential for keeping development on track, minimizing risk, and improving overall process understanding.

Learn more about Waters BioResolve Protein A Affinity Columns featuring MaxPeak Premier Technology.

Global supply chains, the rise of outsourced partnerships, hybrid working models, and the relentless pressure to do more with less are reshaping how laboratories operate. Against this backdrop, many organizations are realizing that the traditional perpetual software model no longer gives them the agility or efficiency they need.

That’s where Empower Subscription options come in. By combining the proven Empower CDS with modern, cloud-enabled capabilities such as the waters_connect System Monitoring Application, Empower Data Viewer, and, in the ES5 top subscription tier,  machine learning-powered Anomaly Detection— the subscription model is built to support the evolving demands of modern science.

So what does this shift mean in practice? Let’s explore what Empower Subscription is, why laboratories are embracing it, and how it can transform the way you work.

A Practical Way to License Empower Software

With Empower Subscription, instead of purchasing perpetual licenses, laboratories subscribe to tiered bundles that include core Empower CDS Software plus cloud-enabled tools and services. This approach delivers easy access to current software while simplifying how labs plan, budget, and scale their informatics.

Predictability and Control of Costs

Budgets are always tight in the lab. Capital-intensive perpetual licenses can put pressure on finances, with heavy upfront costs followed by unpredictable spending on maintenance or upgrade projects. Subscriptions replace this with a smoother, more predictable model.

Instead of dealing with large financial outlays for each individual software product, subscriptions allow labs to pay a steady, manageable subscription fee, often bundling several software products together for ease and value for money. This makes it easier for finance leaders to forecast spending and for lab managers to plan resources. Just as importantly, it aligns cost with value: you’re paying for ongoing access to a service that is always current and continuously improving. Subscriptions can also improve service efficiency. For example, offerings like the Waters Professional Services Subscription Plans reduce the cost of deploying an upgrade and offer reassurance that support is available when you need it.  

Keeping Your Fleet Running Smoothly

Every lab leader knows the frustration of discovering that an instrument has been idle, in error, or under-utilized for hours…or even days. These inefficiencies add up quickly, delaying results and creating bottlenecks.

With the waters_connect System Monitoring Application— included in every Empower Subscription bundle— supervisors gain real-time visibility into instrument status across their fleet. They can see instantly whether a system is running, idle, or in need of attention. Alerts notify staff the moment something goes wrong, allowing issues to be resolved before they cause costly downtime. The result is better throughput, faster troubleshooting, and smarter use of existing assets. Instead of reacting to problems after the fact, labs can take a proactive approach to instrument management.

Collaboration Without Barriers

Science is no longer confined to one lab or one team. Pharmaceutical companies work with CROs and CDMOs, research organizations collaborate across continents, and hybrid working means analysts and reviewers aren’t always on-site. Yet too often, data sharing still relies on outdated practices, exporting chromatograms, emailing PDFs, or juggling multiple Empower Software versions across sites. These methods are slow, cumbersome, and introduce risks.

Empower Data Viewer, available in ES3 and ES5 bundles, changes this dynamic. It allows chromatographic data to be accessed securely through a browser, without the need for local Empower Software installations. Results can be viewed in near real time, and because it supports multiple Empower Software versions, labs can harmonize data across sites even during phased migrations. This improves transparency, accelerates communication with partners, and makes collaboration seamless. Instead of waiting for emailed reports, stakeholders can see results as they happen, wherever they are.

Faster Data Review with Machine Learning

Manual chromatogram review is one of the most time-consuming parts of a laboratory workflow. Analysts spend hours scanning files, even though most chromatograms are routine. With sample volumes only increasing, review often becomes a bottleneck.

The machine learning-powered Anomaly Detection feature in the ES5 bundle addresses this challenge directly. By automatically flagging chromatograms that deviate from expected patterns, it allows analysts to focus their attention where it’s needed most. The system highlights what triggered the anomaly, whether it’s a shift in retention time, an unusual peak, or another irregularity, so the root cause can be investigated quickly.

Future-Proofing Your Laboratory

Perhaps the most compelling reason to move to subscription is the future. Science is accelerating, and laboratories need tools that can evolve with them. Our subscription bundles ensure you’re always positioned to benefit from the next wave of innovation whether that’s machine learning capabilities, broader monitoring across instruments, performance and results, or new ways to visualize and interpret data. By choosing Empower Subscription, you’re not just upgrading your CDS, you’re investing in a model that keeps your laboratory competitive, agile, and ready for whatever comes next.

A Better Way to Run Your Lab

Perpetual software licenses have played a vital role in laboratories worldwide, but they reflect an earlier era of science that was more predictable in terms of funding, resourcing, and pace of scientific advancement. Today, businesses are required to respond to rapidly changing external factors that will affect their capital, resourcing, and resulting scientific outcomes. High upfront investments are now viewed as a risk, so subscriptions are introduced as a flexible way to respond to those changing factors. For laboratories ready to move faster, work smarter, and prepare for the future of informatics, subscription isn’t just a new way to license software, it’s a better way to run your lab.

Discover How Empower Subscriptions can Transform Your Lab Operations

Read our new whitepaper to explore the benefits, features, and real-world impact of Empower Subscriptions.

Ready to talk to someone about making to move to Empower Subscriptions? Click here to arrange to speak to a Waters representative.

Enzymes are nature’s catalysts, enabling precise and efficient biochemical transformations. In analytical workflows, enzymatic digestion is a cornerstone technique for breaking down complex biomolecules into smaller, more manageable fragments. This process is critical for applications such as peptide mapping in protein characterization and oligonucleotide mapping for RNA-based therapeutics. 

Traditional digestion methods, while effective, often require long incubation times and manual intervention, creating bottlenecks that slow down development timelines. Waters RapiZyme Enzymes combine high activity and selectivity with streamlined digestion protocols that deliver enhanced speed, reproducibility, and scalability for optical and LC-MS workflows. 

Introducing Waters RapiZyme Enzymes: Powering Digestion Workflows 

RapiZyme Enzymes are engineered for speed and consistency, enabling digestion workflows that fit modern analytical demands. The catalog includes: 

• RapiZyme Trypsin, for rapid and robust protein digestion in support of peptide mapping and proteomic analyses. 
• RapiZyme MC1 and Cusativin, endoribonucleases that enable more efficient oligonucleotide mapping (fewer ambiguous products, higher sequence coverage). 
• RapiZyme Proteinase K, which thoroughly digests proteins in biomatrices, enabling greater capture and recovery of oligonucleotides and other protein-bound molecules, and supports viral vector genome/payload analyses as well. 

Additionally, these enzymes and digestion protocols are easily automated on most automated liquid handling platforms, including the Andrew+ Pipetting Robot from Waters, reducing hands-on time and variability. 

Case Studies: Peptide Mapping with RapiZyme Trypsin

For protein characterization, enzymatic digestion breaks down large proteins into peptide fragment for LC-MS analysis. Trypsin is the gold standard for peptide mapping because of its predictable cleavage at lysine and arginine residues, delivering high sequence coverage and reproducibility. However, conventional digestion protocols can take hours and require multiple steps, slowing down biopharmaceutical development. 

RapiZyme Trypsin addresses these challenges by delivering: 

• Rapid digestion protocols that shorten incubation times from hours to minutes. 
• High sequence coverage for monoclonal antibodies and other therapeutic proteins. 
• Minimal autolysis ensuring clean and easy-to-analyze chromatograms from homogenously methylated recombinant trypsin. 
• Compatibility with LC-MS workflows for streamlined characterization. 

These features make RapiZyme Trypsin ideal for high-throughput environments and regulatory-compliant workflows. 

Case Studies: Improving Oligonucleotide Mapping with RapiZyme MC1 and Cusativin

For mRNA analysis, endoribonucleases RapiZyme MC1 and RapiZyme Cusativin support efficient digestion of long chain mRNA sequences. These enzymes cleave mRNA at specific sites, generating unique, overlapping products that can be mapped to confirm the sequence as well as the location of any nucleotide modifications with confidence. As mRNA-based therapeutics gain traction, robust digestion strategies remain essential for quality control and regulatory compliance. 

Mapping the sequence of mRNA requires precise cleavage and strong signal. RapiZyme MC1 and Cusativin provide: 

• Novel and specific endoribonuclease activity for mRNA digestion. 
• Improved signal intensity with unique phosphate products. 
• Consistent cleavage and digestion reproducibility for sequence confirmation. 
• Automation-ready protocols on platforms like Andrew+ Pipetting Robot. 
• Pair with IonHance Hexafluoroisopropanol (HFIP) (available in 10 mL and 100 mL) mobile phase additive for a 2x decrease in unwanted sodium and potassium adducts  

Case Studies: Reliable Sample Preparation with RapiZyme Proteinase K 

Therapeutic oligonucleotides often reside in complex biological matrices such as liver or brain tissue, making extraction and analysis challenging. Proteinase K is widely used for its ability to degrade proteins and free-up bound oligonucleotides for more efficient extraction, but traditional protocols are often time-consuming and inconsistent. 

RapiZyme Proteinase K offers: 

• Efficient digestion of proteins in tissue samples for improved oligonucleotide recovery. 
• Compatibility with SPE microplate kits for streamlined workflows. 
• Enhanced reproducibility for bioanalytical extraction of oligonucleotide therapeutics (siRNA, ASOs, et.al.), including lipid-conjugated ASOs. 

In a recent application note, the OligoWorks SPE Microplate Kit with the RapiZyme Proteinase K digestion module achieved highly reproducible analyte recoveries of ≥80% for GEM91 and GEM132 oligonucleotides–demonstrating the protocol’s practicality and scalability for bioanalytical laboratories to meet the growing demands of oligonucleotide therapeutic development. 

By integrating RapiZyme Proteinase K into your workflow, you achieve faster, more reliable sample preparation for oligonucleotide bioanalysis. 

Why Speed Matters with Enzymatic Digestion

Accelerating digestion workflows translates into: 

• Faster development timelines for biopharmaceuticals. 
• Higher throughput in QC and characterization labs. 
• Reduced variability through automation and optimized protocols. 

Waters developed the RapiZyme Enzyme portfolio to simplify enzymatic digestion workflows, delivering speed, reproducibility, and automation-ready solutions for protein and RNA analysis. But this marks just the beginning. As researchers adopt these enzymes and explore new applications, the possibilities for accelerating biopharmaceutical development continue to expand, with a focus on reducing complexity. 

Whether you’re performing peptide mapping for monoclonal antibodies or oligonucleotide mapping for mRNA-based therapeutics, RapiZyme Enzymes offer a fast, reliable, and reproducible way to achieve high-quality results. They’re not just reagents; they represent a new standard for efficiency in analytical workflows. 

Ready to explore what’s possible with RapiZyme Enzymes? Take a deeper dive with these resources: 

• RapiZyme Trypsin Infographic 
• Peptide Mapping eBook 
• LCGC Online Webinar Peptide Mapping for mAbs 
• OligoWorks Infographic 
• RapiZyme Webpage Landing Page

How Large is the Biosimilars Market? 

Extracting insights from Global Data (4), a database that aggregates companies, therapies, and stages shows the massive scale of this market: 

• 415+ parent companies actively developing biosimilars 
• 575 biosimilars marketed globally 
• ~250 companies marketed (released) biosimilars 

Monoclonal antibodies (mAbs) and proteins dominate with blockbuster drugs like trastuzumab, with 40+ marketed biosimilars (4). Because one innovator often spans many biosimilars, the total number of marketed mAbs and biosimilars are nearly equal, but the count of unique therapies is very different.  

Analytical Characterization to Address Regulatory Expectations for Biosimilars Comparability Studies 

The development of a biosimilar is as complicated as the therapy itself. Unlike small-molecule generics, the goal isn’t chemical identity but, instead, demonstrating “highly similar” characteristics to the Reference Biologic (RB) through a comprehensive analytical package. 

Regulators demand scientifically sound, reproducible methods to assess critical quality attributes (CQAs) (1). Minor differences in modifications of the protein backbone and the higher order structure affect immunogenicity and biological activity.

Guidance also emphasizes “Methods that use different physicochemical or biological principles to assess the same attribute are especially valuable” (1).

For example, pairing size-exclusion with UV absorbance detection (SEC-UV) with multi-angle light scattering (MALS) provides an efficient way to meet these expectations.  

The Role of Robust Method Development in Biosimilar QC and Release 

Success in biosimilar development hinges on developing fit-for-purpose methods that can withstand the scrutiny of regulatory review. Key considerations include: 

1. High resolution and mass accuracy: comprehensive comparative analytical studies. Guidance specifically outlines evaluating physicochemical properties–a combination of analytical (e.g., liquid chromatography (LC) and biophysical (e.g., MALS). 
2. Reproducibility: Guidance emphasizes evaluating multiple lots, sites, which can lead into the case for #3 being an enterprise solution. 
3. Streamlined compliance: Integrating analytics with compliance-ready software. 

LC-MS for Biosimilar Intact Mass, Peptide Mapping, and Glycan Analysis 

It is estimated that more than 90% of biosimilar FDA filings include LC and LC-MS data (5). The combination of chromatographic separation and mass accuracy provides the confidence  developers need to assess molecular similarity and accelerate development timelines. Specifically, LC-MS solutions like the BioAccord System support intact analysis and the ACQUITY QDa II Mass Detector helps ensure simpler peptide mapping. These solutions are ideal for:

• Intact and subunit analysis: Confirming mass with high confidence. 
• Peptide mapping: Detailed sequence coverage and unambiguous ID of PTMs. 
• Glycan analysis: Comprehensive profiling to ensure glycan pattern similarity. 

By standardizing and simplifying these complex characterization assays into robust, compliant-ready workflows, development teams gain confidence in their foundational data, starting with the chemistry prep like RapiZyme Kits. 

Biosimilar HOS, Stability, and Particle Analysis Using DSC, MALS, and BMI 

Biosimilarity proof requires robust analysis of the protein’s three-dimensional shape (higher-order structure, or HOS) and stability. MALS, dynamic light scattering (DLS), and differential scanning calorimetry (DSC)— all instruments in the Waters portfolio— support more than 50% of FDA biosimilar filings (5). Critical technology solutions include: 

• Hydrogen deuterium exchange mass spectrometry (HDX-MS) for confirmation of structural similarity 
• Light scattering, DAWN MALS Photometer: Quantify molecular weight, size, and aggregation
• Calorimetry and light scattering, DSC and DynaPro Plate Reader 4 DLS: Assess thermal stability and conformational integrity
• Particle analysis, Aura Backgrounded Membrane Imaging (BMI) System: Characterize and quantify sub-visible particles for safety and regulatory compliance. 

By integrating data from these diverse analytical platforms—from high-resolution mass spectrometry (HRMS) to thermal analysis and particle sizing— developers gain the complete analytical picture required to confidently submit a biosimilar. 

PAT for Biosimilar and Innovator Consistency Under FDA Guidance 

Consistency between a biosimilar and its reference product – and consistency from batch to batch- is essential to avoid triggering regulatory concerns. This requires a tightly controlled and monitored process, enabled by process analytical technology (PAT) for real-time monitoring of CQAs. With tools like PATROL System in place, comparability assays become easier and reduce pressure on final release testing because the product quality is directly measured at the point of manufacture.  

Streamlining Biosimilar Data for Faster Regulatory Submission with Empower CDS 

Empower Chromatography Data System (CDS) integrates and simplifies data acquisition, analysis, and reporting— accelerating regulatory submissions while enhancing traceability, reproducibility, and operational efficiency. LC, simple mass detection, and MALS are all supported by this globally accepted GMP-ready software solution. Investing in integrated analytical systems results in faster submissions due to streamlined data acquisition on the growing number of instruments supported by Empower CDS.  

Advancing Biosimilars with Confident, Analytics-Driven Decisions 

As regulatory expectations evolve, biosimilar developers face increasing pressure to deliver deeper analytical proof faster. Waters technologies enable teams to generate confident, high-quality analytical data across every stage of biosimilar development, from structural confirmation to comparability to QC release. Together, these integrated platforms help developers reduce uncertainty and bring safe, effective biosimilars to patients sooner. 

Visit the Waters Biosimilar page for technical details, methods, case studies and webinars for biosimilar characterization and release. 

Resources

1. FDA Draft Guidance: Scientific Considerations in Demonstrating Biosimilarity to a Reference Product: Updated Recommendations for Assessing the Need for Comparative Efficacy Studies, Draft Guidance for Industry, October 29, 2025. Available from FDA. 
2. McKinsey Consulting Company. An inflection point for biosimilars. Editorial. June 7, 2021 | Article Link 
3. FDA Guidance “Considerations for Demonstrating Interchangeability with a Reference Product: Update”. June 2024. Available from FDA.  
4. Global Data. Data extracted October 2025. All molecules indicated as a biosimilar. 
5. Estimates are a combination of multiple references. AI was used to parse 40+ FDA filings and then manually reviewed. The percentage is an estimate from what was extracted from these documents.  

Additional reading: “Handbook of Analytical Techniques in Biopharmaceutical Development” USP, FDA Briefing Documents, Analytical Procedures and Methods Validation for Drugs and Biologics (2015). 

A Technique Decades in the Making 

First observed in the 1980s by researchers like Barry Boyes and Kenichi Kasai, slalom chromatography intrigued scientists with its reversed elution behavior, like longer DNA fragments eluting later than shorter ones. The concept was visually compelling, likened to DNA molecules weaving through packed particles like skiers navigating slalom gates. Yet, without a clear mechanistic understanding, the technique faded into obscurity. 

Fast forward to 2022, when Waters scientists Fabrice Gritti, Matthew Lauber, and Kevin Wyndham asked a bold question: could slalom chromatography be brought back from the dead? Gritti’s journey into the physics of DNA stretching under shear forces laid the groundwork for a new generation of slalom columns. His research revealed that double-stranded DNA and RNA undergo entropic elastic stretching, uncoiling without breaking bonds, while single-stranded molecules do not. This insight opened the door to separating dsRNA impurities from mRNA vaccine products, addressing a critical need in modern biopharma. 

Where Slalom Chromatography Excels 

Slalom chromatography is transforming nucleic acid workflows with fast, reproducible separation and minimal sample prep. It’s particularly effective in applications such as DNA restriction mapping, plasmid topology analysis, and PCR product verification. Researchers can now isolate pure DNA bands, up to 1 µg, without relying on gels, and detect immunogenic dsRNA contaminants in mRNA production and large-scale mRNA products with greater confidence. 

Its simplicity, often requiring just buffer exchange and dilution, makes it a low-risk, high-reward technique, especially for double-stranded nucleic acids. For many labs, it represents an efficient alternative to DNA gel electrophoresis or DNA ladder gel electrophoresis. With slalom chromatography, you can bypass questions like ‘How does gel electrophoresis separate DNA fragments?’ or ‘How do I interpret DNA data from gel electrophoresis?’, because it offers a more streamlined approach to analyzing double-stranded nucleic acids. Slalom chromatography gives your lab sharp resolution and fast fraction collection without the prep, smears, or guesswork of gels. 

The Science Behind the Separation 

At the heart of slalom chromatography is a unique separation mechanism. Under high-pressure flow, nucleic acid molecules stretch and longer strands interact more with the stationary phase causing them to elute later. This behavior flips the script compared to traditional size-exclusion chromatography (SEC). 

Double-stranded DNA and RNA behave like flexible polymers, making them ideal candidates for slalom separation. In contrast, single-stranded and circular DNA do not stretch in the same way, limiting their interaction with the column. The technique is most effective for molecules in the 3–40 kilobase pair range, offering high-resolution separation based on molecular flexibility and length, critical for characterizing large biopolymers in cell and gene therapy. 

Getting the System Right 

To unlock the full potential of slalom chromatography, your system must be built for performance. UHPLC systems capable of pressures ≥10,000 psi are essential. Elevated temperatures help reduce viscosity and improve reproducibility, while bioinert materials prevent sample loss due to nonspecific adsorption. Standard UV detection at 260 nm works well, though multi-angle light scattering (MALS) can provide additional insights into molecular weight and size. For those looking to purify samples, a fraction collector can be a valuable addition. 

Method Development: Precision Matters 

Developing a robust slalom method requires attention to detail. Buffered mobile phases like tris-acetate-EDTA (TAE) are recommended, and maintaining elevated column temperatures ensures stability. Flow rate and ionic strength should be optimized within pressure limits to achieve sharp selectivity. Periodic column regeneration using low volumes of 1M spermidine helps remove impurities and extend column life. 

Skipping temperature control or under-pressurizing the system can compromise resolution and reproducibility, so thoughtful setup is key. 

From Theory to Impact 

Waters became the first company to commercialize a slalom chromatography column, marking a milestone in separation science. But the journey doesn’t end here. As customers begin to share feedback and explore new applications, the technique will continue to evolve, driven by curiosity, collaboration, and a willingness to think outside the box. 

Whether you’re verifying PCR products or purifying plasmids, slalom chromatography offers a fast, reliable, and reproducible way to separate double-stranded nucleic acids. It’s not just a technique. It’s a testament to the power of interdisciplinary thinking and scientific perseverance. 

Ready to explore what’s possible with slalom chromatography? Take a deeper dive with these resources: 

• A New Alternative to Gel Electrophoresis: App Note 
• The Return of Slalom Chromatography, A New Approach for Separating Nucleic Acids: Webinar 

But here’s the reality: A LIMS alone often isn’t enough to support the expanding operational and scientific needs of evolving laboratories. Let’s break down the differences between LIMS and LMS to discover what’s the right fit for you. 

What is a LIMS? 

Modern analytical laboratories generate a growing amount of data. A LIMS is designed to manage structured data related to sample tracking and workflow automation. LIMS support record-keeping and reporting, reducing the risks associated with human errors and streamline workflows. While a LIMS can provide timely access to data and assist laboratory staff in decision making, their primary focus remains on structured data management for routine workflows rather than the management of unstructured data, unique workflows, or complex protocols. 

The Strengths of a LIMS  

There’s no denying the core benefits a LIMS brings to laboratory environments: 

• Centralized data management: LIMS provide a structured way to manage samples, results, and metadata in a centralized system. 
• Workflow automation: Repetitive tasks are streamlined, reducing manual input and human error. 
• Data integrity and security: Controlled access and audit trails support both internal quality standards and regulatory requirements. 
• Regulatory compliance: Many LIMS are designed to help labs comply with frameworks such as GLP, CLIA, and 21 CFR Part 11. 
• Operational efficiency: Reducing paper-based processes and manual tracking improves overall lab productivity. 

These are essential functions, but they represent only part of what labs need today. 

The Limitations of LIMS  

As today’s analytical laboratories evolve and face increasing demands for efficiency, integration, and scientific insight, the limitations of traditional LIMS are becoming more apparent. Despite their strengths, LIMS are not comprehensive solutions for every lab challenge. Many fall short when it comes to broader scientific data management and business integration.  

Key limitations include: 

• Limited scope: LIMS are structured for sample and workflow management, not unstructured data like free-text notes, experimental iterations, or contextual information. 
• Advancing technology: LIMS has been around for a while, having been implemented in many labs ten or even twenty years ago. However, many have failed to keep pace with new technological enhancements, limiting a laboratory’s digital transformation evolution.  
• Integration complexity: Connecting a LIMS with electronic lab notebooks (ELNs), enterprise resource planning (ERP) systems, or other enterprise tools can be time-consuming and costly. 
• Scientific flexibility: Research-focused labs, especially those in R&D, often require adaptable solutions to support complex protocols. 
• Scalability: Some LIMS struggle to scale or adapt quickly as lab needs evolve. 
• Cost of customization: Tailoring a LIMS to fit unique workflows can be expensive and resource intensive. Often, the expertise needed to configure the system no longer exists in the organization. 

A LIMS can be an excellent tool, but it is only one piece of the digital lab puzzle. Relying solely on a LIMS may be preventing your lab from reaching its full potential. In a digital era where labs are expected to be more agile, data-driven, and collaborative, relying solely on a LIMS may be more of a bottleneck than a benefit. 

When Should You Look Beyond LIMS? 

Here are clear signs that your lab may have outgrown a LIMS-only approach: 

• You manage complex research workflows: Advanced or exploratory science requires more flexibility than a LIMS can offer alone. 
• You generate a lot of unstructured data: Scientific narratives, experimental observations, image files, or annotated graphs are difficult to capture in LIMS. 
• You face integration hurdles: Struggling to link your LIMS with ERP, QC systems, or data lakes? An LMS offers seamless integration across systems. 
• You need to scale quickly: Growing lab teams, expanding research focus, or increasing regulatory demands require solutions that evolve with you

LIMS vs. LMS: Differences and Advantages 

If your lab is generating a significant amount of unstructured data, dealing with complex scientific workflows, or rapidly scaling operations, it may be time to consider a broader, integrated solution. Labs no longer want (or need) multiple disjointed systems to handle different parts of their operations. Enter the laboratory management system (LMS). 

What is an LMS? 

Unlike traditional LIMS, an LMS offers a holistic, end-to-end approach that includes sample management and scientific data management, business process oversight, documentation control, and more. It combines the strengths of LIMS and ELNs, while offering greater flexibility and scalability, enabling labs to manage their operations, scientific data, and compliance requirements in one unified environment. 

How NuGenesis LMS from Waters Helps Labs Work Efficiently and Stay Compliant  

NuGenesis LMS offers a unified solution that bridges the gap between LIMS, ELNs, and business systems. Designed specifically for scientific environments that demand more than data logging, NuGenesis LMS enables labs to contextualize scientific data across instruments and workflows while also maintaining compliance through robust audit trails, secure access controls, and standardized processes.  

Its flexible architecture allows it to adapt seamlessly to a wide range of laboratory settings, from tightly regulated quality control environments to fast-paced, exploratory R&D labs. Rather than forcing teams to patch together separate LIMS, ELNs, CDS and ERP solutions, NuGenesis LMS delivers a connected, efficient environment where scientific and operational needs align. 

NuGenesis LMS enhances lab operations by providing: 

• Improved collaboration through standardized documentation, version control, and centralized access to data. 
• Greater efficiency by ensuring that teams can work more efficiently, make informed decisions faster, and maintain scientific integrity across the board. 
• Seamless connectivity to Empower CDS, enabling an integrated approach to data capture, management, and analysis. 
• Enhanced compliance with secure analytical workflows that improve data integrity, compliance, and overall laboratory efficiency. 

Is Your LIMS Holding Your Lab Back? Consider Your Next Step  

LIMS systems have their place, but they are not a one-size-fits-all solution. As labs grow more complex and data-driven, a more comprehensive approach is needed. 

If your lab is being held back by the limitations of your LIMS, it might be time to consider a laboratory management system like NuGenesis LMS. It’s not just about managing data, it’s about unlocking the full potential of your lab operations. 

Explore how NuGenesis LMS can transform your lab today.  

What Are the Challenges in Sample Preparation?

The importance of sample preparation and cleaning up your samples comes down to one major challenge: matrix interferences. These interferences can introduce data variability, compromise method reliability, and cause problematic issues with instrumentation— especially in LC-MS workflows. Cleaning up your samples provides the added benefit of increased sensitivity by concentrating analytes of interest, improving the accuracy and precision of analytical results, and removing interfering substances.

There are many sample preparation techniques, ranging from simple methods like filtration and protein precipitation to more selective and sensitive techniques like solid-phase extraction (SPE), which produces the cleanest extracts. While there are many sample preparation techniques, SPE stands out for its ability to deliver cleaner extracts, reduce matrix interferences, and improve sensitivity, especially in challenging applications. Let’s take a closer look.

How Does Solid-Phase Extraction Work?

SPE works by passing a liquid sample through a solid adsorbent material (sorbent) that retains the analytes of interest by selecting appropriate solvents and sorbents selective per the analyte. Different sorbent chemistries, such as silica-based, polymer-based, and ion-exchange materials, are used depending on the nature of the analytes and the sample matrix.   

Common SPE protocols typically work in one of two ways:

• Load-wash-elute, which consists of loading the sample, washing away interferences, and eluting, or
• pass-through, where interferences are captured in the sorbent and cleaned analytes pass through.

Choosing Your SPE Sorbent

At Waters, we provide a diverse range of Sep-Pak Sorbents, including many silica-based options designed to help you tackle even the most complex challenges in the lab. Oasis Sorbents are polymeric sorbents, all based on the backbone of Oasis HLB, each designed to handle different types of analytes and sample matrices with simplified protocols.

• Oasis HLB Sorbent is a hydrophilic-lipophilic balanced sorbent that provides high capacity for acids, bases, and neutrals, making it ideal for a wide range of applications.
• Oasis PRiME HLB Sorbent adds additional capabilities to further remove complex matrix interferences, like phospholipids and salts, when preparing a sample for LC-MS analysis.
• Oasis Mixed-Mode Ion Exchange Sorbents (MM-IEX, MCX, MAX, WCX, WAX) offer the highest level of specificity and sensitivity for analytes demanding more selectivity.

SPE is widely used in various fields, including environmental analysis, pharmaceuticals, food safety, and clinical diagnostics. Routine sorbents used in SPE include Oasis HLB, MM-IEX, C18, C8, and Silica Sorbents, each selected based on specific application and analyte properties. Some unique examples include using WAX sorbents for PFAS due to the ability to bind to the acidic nature of many PFAS, MCX for basic drugs and tryptic peptides, or even Sep-Pak PSA Sorbent for fatty acid cleanup.

Choosing Your SPE Device Format and Sample Processing Options

Selecting the appropriate device format, such as cartridges, 96-well plates, or µElution Plates, depends on the sample volume, sample throughput requirements, and the nature of the analytes.

• Easy sample prep of one individual sample – A syringe-based plus-style cartridge can be used for quick cleanup of a sample, such as potentially with food
• Large sample batch size – 96-well options can increase efficiency, such as with bioanalytical assays
• Peptide samples – Peptides could undergo non-specific binding, reducing sensitivity. µElution Plates provide additional concentration to increase sensitivity with a unique design that minimizes analyte loss attributable to sticking to the walls of collection plates.
• Versatile sample prep – Traditional vacuum cartridges are a widely used format across all industries. They are well-suited for processing individual samples or small batches, with a variety of sorbent capacities to fit different analytical needs.

Proper vial selection for labs is also a crucial aspect of sample preparation. Sample processing options include manual, semi-automated, and fully automated systems, each offering different levels of efficiency and convenience.

How to Evaluate Your SPE Protocol 

Evaluating your SPE protocol involves measuring three key parameters to determine success. 

• % recovery: The percentage of analyte recovered from the sample.
• Matrix effect: The impact of other substances in the sample on the analyte’s detection.
• Mass balance: The total amount of analyte accounted for in the extraction process.

If recovery is low, matrix effects high, and reproducibility poor, you may need to troubleshoot the protocol. This involves adjusting the sorbent type, elution solvents, and sample loading conditions. With method optimization, you can ensure that your SPE protocol is robust and reliable for routine use.

Getting Started with SPE

Solid-phase extraction is a powerful sample preparation technique, offering versatility and efficiency in various analytical applications. Waters comprehensive line of Oasis and Sep-Pak SPE Products provide unmatched purity, consistency, and quality, making them the preferred choice for analytical chemists.

For more information on how to optimize your SPE protocols and to explore our full range of SPE products, including our sample prep kits and vials for labs, visit our page on sample preparation. For more on getting started with SPE, check out our Beginner’s Guide to SPE or watch our recent webinar.

This accomplishment reflects our unwavering commitment to safeguarding customer data, building trust, and upholding the highest standards of security, availability, and confidentiality across our cloud software platform. 

What is AICPA SOC 2 Type II? 

SOC 2 (Service Organization Control 2) is an internationally recognized auditing framework developed by the AICPA. It evaluates a company’s ability to manage customer data securely across five “Trust Service Criteria”: 

• Security
• Availability
• Processing integrity
• Confidentiality
• Privacy

While a Type I report reviews the design of controls at a single point in time, a SOC 2 Type II certification report goes further. It independently validates that controls were effectively implemented and consistently operated over an extended review period (often 6 –12 months). 

Our SOC 2 audit focused on the Security element of the Trust Service Criteria. Achieving this attestation provides our customers with ongoing assurance that our policies, processes, and technologies do not just exist on paper but are reliably executed in practice. 

Why SOC 2 Type II Compliance Matters for Our Customers 

As a provider of cloud software for analytical laboratories, many of which operate in highly regulated environments such as pharmaceuticals, life sciences, and healthcare, security and compliance aren’t optional, they’re essential. 

• Regulatory alignment: Laboratories operating under frameworks such as FDA 21 CFR Part 11 compliance, EMA guidance, and Good Laboratory Practice (GLP) must demonstrate that their data systems meet stringent requirements for security and integrity. Our SOC 2 Type II attestation provides assurance that our platform adheres to industry-recognized standards that align with these expectations. 
• Risk management: By undergoing independent audit, we provide our customers with verified assurance that their critical and often highly sensitive data is protected against unauthorized access, tampering, and service disruption.  
• Audit support: For our customers, vendor qualification and compliance audits are routine but resource-intensive activities. Our SOC2 Type II report serves as objective evidence of our control environment, reducing the burden of vendor due diligence and supporting smoother audit readiness. 

Strengthening the Waters Foundation for Growth 

While this attestation is a significant achievement, it is not an end point. SOC 2 Type II compliance reflects a continuous commitment to security and operational excellence. As we continue to innovate and expand our technologies and solutions for analytical labs, we remain dedicated to: 

• Maintaining a cycle of ongoing monitoring, review, and improvement of our control environment 
• Ensuring all stakeholders, including employees and external resources, remain trained and accountable for upholding industry best practices 
• Engaging in periodic independent audits to provide customers with updated assurance 

Continuing the Waters Commitment to Security 

In addition to achieving SOC 2 Type II attestation, and as evidence of our continuing commitment to security, we are proud to share that our CyberVadis rating (as detailed in our blog Protecting Your Laboratory Data: Cybersecurity at Waters) has recently advanced from ‘developed’ to ‘mature’, now awarding us a Platinum Medal. This rating goes beyond our waters_connect Cloud software platform and covers the entire organization.  

Cybervadis provides independent assessments of cybersecurity management systems, benchmarking organizations against international standards and best practices. This upgrade reflects the progress we have made in implementing a more advanced, integrated, and proactive cybersecurity program.  

SOC 2 Type II Compliance: Your Trust is Our Highest Priority

For organizations that entrust us with their critical laboratory data, this AICPA certification achievement underscores a simple message: your trust is our highest priority. 

We’re proud to have reached this milestone, and we look forward to continuing to deliver secure, reliable, and compliant cloud solutions that enable analytical labs to focus on what they do best – advancing science. 

Explore how Waters Cloud Software Solutions are transforming laboratory informatics. Visit our Cloud Software Solutions page to learn more.  

Waters Xevo^TM MRT Mass Spectrometer is redefining expectations in high-resolution mass spectrometry (HRMS). In the “Xevo MRT System in Action” webinar series, Waters scientists take participants behind the scenes to explore the instrument’s cutting-edge hardware, intuitive software, and real-world applications across pharmaceutical, environmental, and metabolomics workflows. 

Hardware Innovation Meets Analytical Power 

The Challenge: Traditional mass spectrometry approaches can require compromises, either in data quality or in analytical efficiency, making it harder for scientists to meet demanding timelines with full confidence in their results. 

In this session, Jason Wildgoose, Technology and Engineering Lead, walks through the Xevo MRT system architecture, from the universal ion source and MS1 region to the novel gas cell and Phase Volume Manipulator (PVM). These components work together to deliver exceptional ion transmission, resolution, and sensitivity. The multi-reflecting time-of-flight analyzer, with its gridless design, enables over 4 meters of flight path in a compact footprint, achieving 100% ion transmission and sub-ppm mass accuracy. 

Rachel Sanig, Senior Scientist, introduces the waters_connect Software Platform, which streamlines acquisition and data processing. Users can set up methods, calibrate instruments, process data with the LC-MS Toolkit, and export into mzML format for third-party software. Features such as real-time data viewing, elemental composition analysis, and compatibility with UNIFI ensure flexibility and accelerate time-to-result. 

Real-World Applications – From Metabolites to PFAS 

The Challenge: When deadlines are tight, no one has time for workflows that can’t handle sample complexity. 

“We can get sub-PPM mass accuracy for most of the metabolites that we see on the analysis.” – Isabel Riba 

“The mass accuracy of the Xevo MRT is unprecedented for a benchtop instrument … with a root mean square lower than 700 parts per billion.” – Dr. Hania Khoury-Hollins

In this session, Isabel Riba, Principal Applications Chemist, demonstrates a metabolite identification workflow using verapamil. She highlights the ease of system setup, calibration, and data acquisition on the Xevo MRT System, with sub-ppm mass accuracy across metabolites in complex biotransformation studies. 

Dr. Hania Khoury-Hollins, Principal Scientist, presents a PFAS analysis case study. Using waters_connect^TM Software and the UNIFI^TM Application, she shows how the Xevo MRT Mass Spectrometer maintains mass accuracy below 700 ppb across hundreds of injections. The Pattern Analysis application further enhances non-targeted screening reliability by leveraging PFAS-specific characteristics such as mass defects and carbon ratios, enabling confident identification of unknowns in environmental samples.

Advanced Acquisition Strategies for Deeper Insights 

The Challenge: High-stakes analyses demand methods that can adapt to both qualitative analysis and quantitative validation. 

In the Part 3 session, Martin Palmer, Principal Consulting Scientist, compares data-independent acquisition (MSE) with data-dependent acquisition (DDA), showing how each can be tailored to specific analytical goals. DDA benefits from Xevo MRT MS’s improved duty cycle and high-speed switching, enabling both qualitative and quantitative analysis in a single run. 

Dr. Susan Slade presents pesticide data, demonstrating high-confidence MS/MS spectra and accurate quantitation—even at sub-ppb levels in complex matrices. The LC-MS Toolkit Application allows users to interrogate DDA switch tables, extract spectra, and refine acquisition strategies, illustrating how Xevo MRT MS’s flexibility directly supports efficiency in high-stakes workflows. 

Conclusion

The Xevo MRT MS is more than a mass spectrometer—it’s a complete analytical platform that empowers scientists to push the boundaries of discovery. Whether you’re identifying trace-level contaminants, characterizing biopharmaceuticals, or exploring unknown metabolites, the Xevo MRT MS delivers unmatched performance, flexibility, and confidence. 

Explore the full “Xevo MRT System in Action” webinar series to see how Waters scientists can help you turn analytical challenges into confident results and learn more about the Xevo MRT Mass Spectrometer on Waters.com.