<p><strong>An international research team, which included scientists from the Faculty of Science at Palacký University and the Institute of Physics of the Czech Academy of Sciences, has succeeded in unraveling the complex mechanism by which a chemical bond is formed during a collision between molecules. The experts found that the reaction only takes place if the molecules are oriented towards each other within a very narrow range of angles – within the so-called cone of reaction. This joint research has thus provided an answer to one of the fundamental questions of chemistry: under what conditions do chemical bonds form between molecules. The results of the study&nbsp;</strong><i><strong>Spatially resolving the cone of reaction for a single molecule</strong></i><strong>&nbsp;were published in the prestigious scientific journal&nbsp;Science.</strong></p><p>Many chemical reactions begin with the collision of two particles. However, for a new chemical bond to form, it is not enough for the molecules simply to come into contact. Their collision must occur with sufficient energy, in the correct relative orientation and at the right location. Under normal conditions, such as in solutions or gases, molecules collide chaotically, and the precise parameters of these collisions cannot therefore be controlled.</p><h4><strong>Molecules under control</strong></h4><p>Scientists were able to control the collisions of individual molecules on a copper surface and monitored the process using a <strong>scanning tunnelling microscope</strong>. They used the instrument not only to visualise individual molecules, but also to deliberately accelerate the reactants towards one another. They subsequently analysed each collision with atomic-level resolution. This enabled them to determine unequivocally whether a new chemical bond had formed between the molecules.</p><h5><i><strong>“What is hidden in the statistics of billions of collisions in conventional chemistry, we have managed to break down into individual cases and map directly.” Adam Matěj</strong></i></h5><p>A key finding of the study is that the outcome of a collision is determined by the extremely precise orientation of the molecules. A new bond was formed only when the target molecule was oriented within a few degrees of the direction of movement of the other molecule. When rotated by more than fifteen degrees, the molecules simply bounced off each other without any reaction.</p><h4><strong>The precise orientation of the molecules is crucial</strong></h4><p><i>“For the first time, we were able to observe, using a single molecule, exactly how precisely it must be oriented for the reaction to take place at all. What is hidden in the statistics of billions of collisions in conventional chemistry, we have managed to break down into individual cases and map directly,” </i>said Adam Matěj from the Department of Physical Chemistry at the Faculty of Science.</p><p>The theoretical part of the study, in which researchers from<strong> Palacký University </strong>and <strong>the Institute of Physics of the Czech Academy of Sciences</strong> were involved, played a significant role. Using quantum-mechanical calculations, they explained why the ‘reaction cone’ is so narrow. It turned out that the reactive carbon atom is surrounded by hydrogen atoms, which block the access of the reacting molecule from almost all directions.</p><h4><strong>The arrangement of atoms restricts access to the reaction</strong></h4><p>The calculations also shed light on a surprising experimental result. The chemical reaction took place even when the molecule moved along an adjacent row of copper atoms, where, according to the original assumptions, no bond should have formed.</p><h5><i><strong>“The strength of this work lies in the fact that the experiment and theory have been brought together into a single picture. The microscope showed what happens during the collision, and the calculations explained why.” Pavel Jelínek</strong></i></h5><p><i>“The explanation lies in the slight displacement of a single copper atom on the surface. The target’s bond to the surface pulls it out of its position and brings it close enough to the neighbouring row that it can literally take over the projectile and direct it to the correct spot. This shows that the surface is not merely a passive substrate, but actively participates in the reaction itself and can even facilitate pathways that would otherwise be unfavourable,” </i>noted Adam Matěj.</p><h4><strong>The surface also determines the course of the reaction</strong></h4><p>The results are significant for the development of so-called surface reactions, in which new materials and nanostructures are purposefully assembled from individual molecules. A better understanding of the influence of the spatial arrangement of molecules will enable the design of molecular building blocks so that they bond more reliably and efficiently. This represents an important step towards the development of technologies based on the controlled construction of structures atom by atom.</p><p><i>“The strength of this work lies in the fact that experiment and theory have been brought together into a single picture. The microscope showed what happens during the collision, and the calculations explained why. Without a theoretical model, we would have found it difficult to discover that the movement of a single surface atom is behind the unexpected course of the reaction,” </i>added Pavel Jelínek from the Institute of Physics of the Czech Academy of Sciences.</p><blockquote><p>The study&nbsp;<i>Spatially resolving the cone of reaction for a single molecule</i>&nbsp;was produced in collaboration between researchers from the University of Graz, the Institute of Physics of the Czech Academy of Sciences, Palacký University in Olomouc, Charles University and Humboldt University in Berlin.</p></blockquote>

Scientists reveal when chemical bonds form in molecular collisions 

<p><strong>Our Library never stops expanding. What are the most recent contributions to LabRulezLCMS Library in the week of 17th August 2026? Check out new documents from the field of liquid phase, especially HPLC and LC/MS techniques!</strong></p><blockquote><p><span style="font-size:20px;">👉 </span><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/library"><span style="font-size:20px;"><strong>SEARCH THE LARGEST REPOSITORY OF DOCUMENTS ABOUT LCMS AND RELATED TECHNIQUES</strong></span></a></p></blockquote><blockquote><p><strong>👉 Need info about different analytical techniques?</strong> Peek into <a target="_blank" rel="noopener noreferrer" href="https://gcms.labrulez.com/library"><strong>LabRulezGCMS</strong></a> or <a target="_blank" rel="noopener noreferrer" href="https://icpms.labrulez.com/library"><strong>LabRulezICPMS</strong></a> libraries.</p></blockquote><p>This week we bring you posters by <strong>Agilent Technologies / ASMS, Thermo Fisher Scientific / ASMS </strong>and<strong> Shimadzu / ASMS </strong>and application note by<strong> Waters Corporation!</strong></p><h3><strong>1. Agilent Technologies / ASMS: Quantitation of N-Nitroso Duloxetine N-Nitrosamine Drug Substance Related Impurities (NDSRI) in API and Formulation by 6475 LC/TQ</strong></h3><ul><li>Poster</li><li><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/po_drug_impurities_lc_tq_tp_402_asms_2026_en_agilent_b933b9bddf.pdf"><strong>Full PDF for download</strong></a></li></ul><p>Nitrosamine impurities are nitroso derivatives where the nitroso group is attached to an amine. The active pharmaceutical ingredient (API) derived from a class of nitrosamines are known as N-nitrosamine drugsubstance-related impurities (NDSRI). Nitrosamine impurities in APIs and drug products pose safety concerns, even in small quantities, and thus are a major concern for drug makers [1].&nbsp;</p><p>Analytical methods must be sufficiently sensitive to quantify the nitrosamine of interest at levels as low as 10% of the specification limit and, where feasible, down to ≤5% of the specification limit, for the determination of the limit of detection. LC/MS/MS is an inherently selective and highly sensitive analytical technique that is well suited for the identification and quantification of trace-level impurities at extremely low concentrations. Consequently, LC/MS/MS has been widely adopted within the pharmaceutical industry, particularly for nitrosamine analysis [2-3].&nbsp;</p><p>Therefore, manufacturers must develop and qualify a dedicated analytical method that is appropriate for the specific sample matrix and targeted NDSRIs. An LC/MS/MS method based on multiple reaction monitoring (MRM) was developed for the detection and quantification of the N-nitroso duloxetine NDSRI impurity over a concentration range of 0.5 to 40 ppb (absolute standard concentration), using an atmospheric pressure chemical ionization (APCI) source on an Agilent 6475A LC/TQ instrument.</p><h4><strong>Experimental</strong></h4><ul><li><strong>MS:</strong> <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/library?mainauthorItems=10&amp;search=6475"><strong>6475 Triple Quadrupole LC/MS System</strong></a></li><li><strong>Column:</strong> <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/library?mainauthorItems=10&amp;search=Poroshell+HPH+C18"><strong>Poroshell HPH C18</strong></a> (4.6*150mm, 2.7µm)</li></ul><h4><strong>Conclusions</strong></h4><ul><li>A highly sensitive and robust MRM LC/MS/MS method was developed for the quantitation of N-nitroso duloxetine in duloxetine hydrochloride API and finished formulation using the Agilent 6475A LC/TQ.&nbsp;</li><li>The optimized chromatographic conditions provided effective separation of the analyte from the API, placebo, and formulation matrices, ensuring reliable quantitation.&nbsp;</li><li>The calibration curve was linear over the concentration range of 0.5-40 ng/mL, with 1/x weighting. R and R2 values were observed for both to be greater than 0.99.&nbsp;</li><li>Recovery studies demonstrated efficient sample extraction, with recoveries ranging from 92-99% in API samples and 109-116% in pellet formulations at the LOQ, specification, and 200% specification levels.&nbsp;</li><li>The method also showed excellent reproducibility across all evaluated concentration levels, confirming its suitability for routine analysis.</li></ul><h3><strong>2. Shimadzu / ASMS: Non-Targeted Analysis of Per- and Polyfluoroalkyl Substances in Environmental Extracts by Microflow LC-QToF Coupled with Multi-spray ESI</strong></h3><ul><li>Poster</li><li><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/TP_562_Non_Targeted_Analysis_of_Per_and_Polyfluoroalkyl_Substances_in_Environmental_Extracts_by_Microflow_LC_Q_To_F_Coupled_with_Multi_spray_ESI_c2a7e1d5bf.pdf"><strong>Full PDF for download</strong></a></li></ul><p>Targeted screening methods are well established for monitoring Perand polyfluoroalkyl substances (PFAS) in environmental samples. However, PFAS comprise a large and evolving class of compounds, creating a need to screen existing, emerging, and transformation products across diverse matrices. Non-targeted Analysis (NTA) allows for the confirmation of suspected PFAS in the environment, but the sample characterization is often limited by analytical sensitivity. Microflow (0.5 – 40 µL/min) coupled with a multi-nozzle emitter enhances sensitivity by improving desolvation. When this is coupled to a high mass accuracy and resolution Quadrupole Time-ofFlight Mass Spectrometer (QToF), capable of data-dependent and independent MS/MS, PFAS characterization of unknown analytes is possible. In this study, various environmental extracts were processed and screened using NTA for PFAS compounds.</p><h4><strong>Methods</strong></h4><p>A <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/library?mainauthorItems=1&amp;search=Nexera+Mikros"><strong>Shimadzu Nexera Mikros LC</strong> </a>was used to introduce the sample to a Newomics DuoESI source with an M3 emitter on a <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/library?mainauthorItems=1&amp;search=9050"><strong>LCMS-9050 QToF MS</strong></a> (Fig. 1). A direct injection on an octadecyl column without delay column was performed. Direct injection was chosen over trapand-elute configuration to minimize selectivity bias caused by the trap column.&nbsp;</p><h4><strong>Conclusion</strong></h4><p>With the increased sensitivity of microflow LC-QToF coupled with multi-spray ESI with DIA acquisition, Insight Explore aided in NTA PFAS analysis. When paired with Insight Discovery and Profiler, a streamlined batch data processing workflow with statistical analysis was shown to effectively handle complex environmental matrices and their analyses.</p><h3><strong>3. Thermo Fisher Scientific / ASMS: Robust and sensitive quantitation of 18 steroids in human serum using Thermo Scientific TSQ Certis Triple Quadrupole mass spectrometer</strong></h3><ul><li>Poster</li><li><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/po_004707_lsms_18_steroids_tsq_certis_clinical_po004707_asms2026_na_en_244c52437b.pdf"><strong>Full PDF for download</strong></a></li></ul><p>Accurate quantification of endogenous steroids in human serum is essential for biomonitoring physiological functions such as hormone regulation, reproduction, and immune response in clinical research laboratories. Liquid chromatography–tandem mass spectrometry (LC–MS/MS) is the gold standard for steroid analysis due to its superior sensitivity, selectivity, and multiplexing capability compared to immunoassays. However, steroid measurements remain challenging because of low endogenous concentrations and complex serum matrices. Here, we describe a robust and sensitive LC–MS/MS method for the simultaneous quantification of 18 steroids in human serum using the Thermo Scientific TSQ Certis triple quadrupole mass spectrometer (Figure 1). The method leverages advanced ion source design and fast acquisition to deliver enhanced sensitivity, stability and throughput suitable for high-volume laboratory workflows.</p><h4><strong>Materials and methods</strong></h4><h5><strong>Liquid chromatograph – mass spectrometry&nbsp;</strong></h5><p>Samples were analyzed on a <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/744"><strong>Thermo Scientific Vanquish Horizon UHPLC system</strong></a> coupled to the <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/2207"><strong>TSQ Certis MS</strong></a><strong> </strong>operated in selected reaction monitoring (SRM) mode. The mobile phase composition, analytical column details, LC gradient, and overlaid extracted ion chromatograms (EICs) are shown in Figure 3.&nbsp;</p><h5><strong>Data analysis&nbsp;</strong></h5><p>Data were acquired and processed using <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/77"><strong>Thermo Scientific TraceFinder software</strong></a> (v 5.2).</p><h4><strong>Conclusions&nbsp;</strong></h4><p>A sensitive and robust LC–MS/MS method was developed for simultaneous quantification of 18 steroids in human serum using the Vanquish Horizon UHPLC and TSQ Certis MS with OptaMax Plus ion source. The method demonstrated excellent linearity, accuracy, and reproducibility across a wide dynamic range. Optimization of MS conditions, particularly vaporizer temperature, significantly improved sensitivity. Overall, the workflow delivers high sensitivity, selectivity, and long-term stability, providing a reliable solution for high-throughput steroid analysis in clinical and research settings.</p><h3><strong>4. Waters Corporation: Alkaline-hydrolysis Method for PFAS in Textiles and Textiles Products by Xevo™ TQ-S micro with ACQUITY™ UPLC™ H-Class Plus System</strong></h3><ul><li>Application note</li><li><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/720009443_en_0ab4914d72.pdf"><strong>Full PDF for download</strong></a></li></ul><div><div><section><div><div><div><div><div><div><h5><strong>Benefits&nbsp;</strong></h5><ul><li>Alkaline hydrolysis method (EN 17681-1:2025) used for preparing textiles, coated textiles and textile products for PFAS analysis allowed the inclusion of side-chain fluorinated polymers&nbsp;</li><li>Extraction method provided significant advantages in handling complex textile matrices by creating clear extracts free from dispersions, settleable solids and particulates&nbsp;</li><li>Protected the high-value LC-MS/MS components from potential damage&nbsp;</li><li>The method improved analytical sensitivity, reproducibility and accuracy, enabled cost-effective and timeefficient PFAS analysis maintained high analytical quality even for challenging high-matrix samples</li></ul><p>Many PFAS are linked to health concerns because of their ability to interfere with the body’s hormone systems, acting as endocrine disruptors also, linked to other toxic effects. Since textiles come into direct and prolonged contact with the skin, there is an increased risk of human exposure—especially for babies and children.4 In addition, PFAS pose significant environmental concerns. These “forever chemicals” do not readily break down and can be released during manufacturing, washing and disposal, allowing them to enter water pathways and persist in the environment. As a result, testing for PFAS has become increasingly important in the textile industry to demonstrate supply chain transparency, build consumer trust and protect brand reputation.</p><p>Synthetic fluorinated chemicals are categorized into two main groups - non-polymeric PFAS and polymeric PFAS, known for their use as water and grease repellent, heat resistant finishes in textiles, upholstery, leather, apparel, carpet and other industrial applications such as packaging, firefighting foams, non-stick cookware, etc. (Figure 1). PFAS are fluorinated substances contain at least one fully fluorinated methyl or methylene carbon atom (without any H/Cl/Br/I atom attached to it), i.e. with a few noted exceptions, any chemical with at least a perfluorinated methyl group or a perfluorinated methylene group.2 PFAS are classified as long chain and short chain based on their perfluorinated carbon chain length. Short chain fluorinated polymers encompasses a diverse range of chemistries, categorized according to their generic chemical and repeating units structures. Few examples are: derivatives of fluorotelomers, perfluoropolyethers with varying carbon chain lengths and acrylates, epoxylates, urethane, silicones of repeated units based structures.3 Polyfluoroalkyl substances such as fluorotelomer alcohols (FTOHs) contain C–H bonds, rendering them more susceptible to degradation. The ethoxylates in fluorotelomers-methacrylate break down to FTOH whereas polymeric fluorinated urethanes, acrylates break down to PFCAs (non-polymeric and polymeric side chain fluorinated polymers). In contrast, perfluoroalkyl substances such as PFOS and PFOA are extremely persistent due to their fully fluorinated carbon chains.&nbsp;</p><p>In alkaline hydrolysis methods, methanolic aqueous sodium hydroxide is used to break down precursor PFAS such as FTOHs, branched side chain PFAS. This process releases terminal perfluorinated carboxylic acids (PFCAs), which can then be measured. However, the efficiency of hydrolysis varies among different PFAS compounds and the presence of interfering substances such as organic matter or other chemicals in the sample matrix can inhibit the cleavage and detection of these analytes.</p><h4><strong>Experimental</strong></h4><ul><li><strong>LC system:</strong> <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/198"><strong>ACQUITY UPLC H-Class Plus System</strong></a> and SMFTN fitted with PFAS kit</li><li><strong>Column(s):</strong> <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/1823"><strong>XBridge™ BEH™ C18 5 µm Column</strong></a>, 4.6 x 100 mm&nbsp;</li><li><strong>MS system: </strong><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/209"><strong>Xevo TQ-S micro Mass Spectrometer</strong></a></li></ul><h4><strong>Conclusion&nbsp;</strong></h4><p>By strictly following the critical steps of the alkaline hydrolysis method using methanolic aqueous sodium hydroxide (NaOH) both freely extractable PFAS and those previously bound within side-chain fluorinated polymers such as esters linked to fluorotelomer alcohols (n:2 FTOHs, where n = 4, 6, 8, 10, 12), can be effectively extracted. This approach also safeguards the LC-MS/MS instrumentation from blockages, damage, or contamination by preventing polymer accumulation and matrix interferences.&nbsp;</p><p>The analytical method using the ACQUITY UPLC H-Class Plus System and Xevo TQ-S micro LC-MS/MS System was found to be sensitive, reproducible and accurate, enabling cost-effective and time-efficient PFAS analysis in chemically processed textiles, coated textiles and textile products whilst maintaining high analytical quality even for challenging high-matrix samples.</p></div></div></div></div></div></div></section></div></div>

News from LabRulezLCMS Library - Week 34, 2026

<h3><strong>What makes capillary LC so powerful—and why are more scientists paying attention to it?</strong></h3><p><strong>In this episode of ‪ChromatographyTalk‬, David sits down with Samuel Foster of Axcend to discuss how capillary liquid chromatography is changing the conversation around LC-MS sensitivity, solvent consumption, instrument footprint, and chromatographic efficiency.</strong></p><p>Sam explains how lower flow rates can dramatically improve electrospray ionization performance, why capillary LC can reduce solvent usage by orders of magnitude, and where the technology is already making an impact in pharmaceutical, environmental, and radiopharmaceutical workflows.</p><p>They also discuss common misconceptions about capillary LC, why older systems gave the technology a mixed reputation, and why modern advances may make now the right time for labs to take another look.</p><h5><strong>Topics Covered:</strong></h5><ul><li>What capillary LC is and how it differs from traditional HPLC</li><li>Why lower flow rates improve LC-MS sensitivity</li><li>Solvent savings and sustainability benefits</li><li>Extra-column effects and hidden performance killers</li><li>Applications in pharma, biologics, drugs of abuse, and radiopharmaceuticals</li><li>Is capillary LC ready for routine lab adoption?</li><li>The future of liquid chromatography</li></ul><h3><strong>Video Transcription</strong></h3><p>Capillary liquid chromatography has existed for decades, but improvements in pumps, fittings, system design, and LC–MS interfaces are giving the technique renewed relevance. In an interview for <i>Concentrating on Chromatography</i>, <strong>Samuel Foster</strong> discussed how capillary LC differs from conventional analytical-scale HPLC, why lower flow rates can improve electrospray ionization sensitivity, and where miniaturized LC systems could have the greatest practical impact.</p><p>Foster also explained the engineering challenges associated with operating at microliter-per-minute flow rates, the importance of controlling extra-column volume, and why applications ranging from radiopharmaceuticals to pharmaceutical analysis could benefit from dramatically lower solvent consumption.</p><h4><strong>From Undergraduate Research to Capillary Chromatography</strong></h4><p>Foster’s interest in chromatography began during his first year of university, when he joined the research group of <strong>Jim Grinias</strong> at Rowan University. What started as an undergraduate research opportunity gradually developed into a long-term focus on separation science.</p><p>According to Foster, Grinias became an important influence on his scientific career and introduced him to many aspects of chromatography, including capillary-scale separations.</p><p>That early exposure eventually shaped Foster’s doctoral research and his current work at <strong>Excend</strong>, where capillary LC plays a central role.</p><h4><strong>What Is Capillary LC?</strong></h4><p>The primary difference between conventional analytical-scale HPLC and capillary LC is the internal diameter of the chromatographic column.</p><p>Typical analytical-scale HPLC commonly uses columns with internal diameters between approximately <strong>2.1 and 4.6 mm</strong>. Capillary LC moves to substantially smaller dimensions, typically around <strong>0.1 to 0.3 mm internal diameter</strong>.</p><p>Reducing column diameter also requires a major reduction in mobile-phase flow.</p><p>An analytical-scale separation that might operate at approximately <strong>1 mL/min</strong> on a 4.6 mm column can translate to flow rates around the <strong>microliter-per-minute range</strong> when using a 0.1 mm capillary column.</p><p>The purpose is to maintain an appropriate linear velocity through the stationary phase while dramatically reducing the absolute volume of mobile phase passing through the system.</p><p>In simple terms, capillary LC combines <strong>smaller columns with much lower flow rates</strong>.</p><h4><strong>The Major Benefit: Dramatically Lower Solvent Consumption</strong></h4><p>One of the clearest advantages of capillary LC is solvent savings.</p><p>Because flow rates are orders of magnitude lower than in conventional HPLC, the total amount of mobile phase required for an analysis can be reduced dramatically.</p><p>Foster described reaction-monitoring experiments in which a reaction was followed continuously for approximately <strong>72 hours</strong> while consuming less than a microliter of total sample and less than a milliliter of mobile phase.</p><p>That difference can become especially important when a laboratory uses expensive, hazardous, or difficult-to-dispose-of solvents.</p><p>The benefits extend beyond the purchase price of mobile phases. Lower solvent consumption can also reduce:</p><ul><li>Waste generation</li><li>Disposal requirements</li><li>Storage requirements</li><li>Environmental burden</li><li>Handling of hazardous materials</li></ul><p>For laboratories operating many chromatographic systems continuously, even relatively small reductions per analysis can translate into substantial savings over time.</p><h4><strong>Why Lower Flow Can Increase LC–MS Sensitivity</strong></h4><p>Reducing flow does not necessarily mean sacrificing analytical sensitivity. When capillary LC is coupled to electrospray ionization mass spectrometry, the opposite can occur.</p><p>Foster explained that <strong>lower flow rates can improve ESI efficiency</strong>.</p><p>In conventional electrospray at analytical-scale flow rates, comparatively large droplets are generated. These droplets must undergo multiple evaporation and desolvation processes before gas-phase ions reach the mass spectrometer.</p><p>Heated gases and other source parameters are commonly used to accelerate this process.</p><p>At capillary-scale flow rates, much less solvent reaches the source. Smaller initial droplets can be generated, meaning less solvent must evaporate before ions are transferred into the gas phase.</p><p>The result can be improved ionization efficiency.</p><p>Although the precise improvement depends on the analyte and instrument configuration, Foster cited literature values suggesting approximately a <strong>four- to tenfold improvement in ESI-MS sensitivity</strong> when capillary LC is properly implemented.</p><p>This combination of reduced solvent consumption and potentially improved MS sensitivity is one of the major arguments for miniaturized LC–MS workflows.</p><h4><strong>Translating an Existing HPLC Method</strong></h4><p>Moving a method from analytical-scale HPLC to capillary LC is not necessarily as simple as reducing the flow rate.</p><p>Theoretical calculations can provide a strong starting point. Foster noted that Excend uses a method-translation calculator that allows users to enter parameters from an analytical-scale method and obtain corresponding capillary-scale conditions.</p><p>However, the calculated conditions may still require experimental optimization.</p><p>For example, a translated method may predict a flow rate of 1 µL/min, while practical testing could show that 1.5 µL/min provides the optimum separation.</p><p>Method translation can therefore bring the user close to the final conditions, but some fine-tuning is often necessary.</p><p>This is one of the practical barriers laboratories must consider when adopting capillary LC. Existing methods may not always transfer perfectly without further development.</p><h4><strong>Why Solvent Delivery Becomes More Difficult</strong></h4><p>Delivering mobile phase reproducibly at very low flow rates creates different engineering requirements from conventional HPLC.</p><p>Traditional analytical HPLC systems typically use <strong>reciprocating piston pumps</strong>. While one piston delivers solvent, another refills, allowing essentially continuous flow.</p><p>Such systems also commonly incorporate components including:</p><ul><li>Check valves</li><li>Pulse dampeners</li><li>Additional tubing and connections</li></ul><p>At analytical-scale flow rates, the additional volume created by these components may have relatively little impact.</p><p>In capillary LC, however, every microliter becomes important.</p><p>Foster explained that the Excend system uses a <strong>syringe-based pumping architecture</strong>. Instead of continuously cycling reciprocating pistons, a syringe is filled with enough solvent for the chromatographic run and then dispenses that mobile phase in a controlled step.</p><p>This approach can eliminate components such as pulse dampeners and check valves, reducing both internal system volume and the number of components that can potentially contribute to problems.</p><h4><strong>Extra-Column Volume Can Destroy a Separation</strong></h4><p>Controlling extra-column volume is one of the most important requirements in capillary LC.</p><p>At conventional analytical-scale flow rates, one microliter of additional tubing volume is generally insignificant because the mobile phase passes through it almost immediately.</p><p>At a flow rate of approximately <strong>1 µL/min</strong>, however, the same microliter represents roughly one minute of additional residence time outside the column.</p><p>That difference can severely broaden chromatographic peaks and reduce separation efficiency.</p><p>Foster therefore identified treating a capillary system like a conventional analytical HPLC system as one of the most common mistakes.</p><p>A piece of unnecessary tubing, excessive connection volume, or poorly designed fitting may have little impact in analytical-scale LC but can become a major source of dispersion in capillary chromatography.</p><p>Careful system configuration is therefore essential.</p><h4><strong>Radiopharmaceuticals as a Particularly Attractive Application</strong></h4><p>Among the potential applications discussed during the interview, Foster highlighted <strong>radiopharmaceutical analysis</strong> as one of the most promising.</p><p>The reason again comes down to solvent consumption.</p><p>Mobile phases used in radiochemical analysis may become contaminated with radioactive material and can require controlled storage until radioactivity has decayed sufficiently for disposal.</p><p>Reducing a waste volume from liters to milliliters can dramatically simplify storage, handling, and disposal.</p><p>Instead of managing large containers of radioactive mobile phase for extended periods, a laboratory could potentially reduce the waste volume by orders of magnitude.</p><p>Foster also sees broader potential across the pharmaceutical industry, particularly when standardized methods are operated on many instruments at multiple sites.</p><p>If comparable analytical performance can be obtained using substantially less solvent, the cumulative economic and environmental impact can become significant.</p><h4><strong>Lower Consumption of Challenging Mobile-Phase Additives</strong></h4><p>Miniaturization may also help laboratories reduce the amount of problematic mobile-phase additives used during LC analysis.</p><p>Foster specifically mentioned <strong>TFA and HFIP</strong>, compounds that can be required in certain chromatographic methods and that are increasingly receiving attention from an environmental perspective.</p><p>Rather than completely redesigning an established separation, capillary LC could potentially allow laboratories to retain an effective method while reducing the absolute amount of these chemicals consumed by several orders of magnitude.</p><p>This illustrates a broader advantage of miniaturization: greener chromatography does not always require replacing the chemistry of an existing method. In some cases, reducing the scale of the separation itself can substantially decrease chemical consumption.</p><h4><strong>Is Capillary LC Ready for Routine Laboratories?</strong></h4><p>Foster believes the technology is already technically ready for routine use.</p><p>Many of the problems historically associated with capillary chromatography have been reduced through improvements in instrumentation and system components.</p><p>The more difficult challenge may be regulatory acceptance.</p><p>Pharmaceutical laboratories in particular can be cautious about changing validated analytical methods. Even when method translation is scientifically straightforward, concerns over regulatory revalidation can discourage adoption.</p><p>Foster described work involving <strong>USP monograph methods</strong>, where analytical-scale procedures were translated to capillary conditions while remaining within the permitted framework.</p><p>The next important step, in his view, is wider implementation in regulated environments and greater confidence among laboratories that miniaturization does not necessarily require rebuilding a method from the beginning.</p><h4><strong>Why Some Chromatographers Remain Skeptical</strong></h4><p>Capillary LC is not a new concept. Early versions of the technology were already being investigated decades ago.</p><p>However, Foster believes that those historical experiences may actually slow current adoption.</p><p>Earlier systems could suffer from:</p><ul><li>Poor pump reproducibility</li><li>Long equilibration times</li><li>Frequent clogging</li><li>Excessive dead volume</li><li>Limited fitting technology</li><li>Insufficient robustness</li></ul><p>Researchers who used capillary LC during the 1980s, 1990s, or early 2000s may therefore remember it as technically difficult and unreliable.</p><p>Many of those limitations have since been addressed through better pumps, lower-volume connections, improved fittings, and more mature system design.</p><p>Foster’s message to users with disappointing past experiences is therefore simple: modern capillary LC deserves another look.</p><h4><strong>A Broader Trend Toward Smaller LC Columns</strong></h4><p>Capillary LC also fits within a much longer trend in liquid chromatography.</p><p>Historically, conventional HPLC frequently used <strong>4.6 mm internal-diameter columns</strong>. Over time, laboratories moved toward smaller dimensions.</p><p>Columns around 3.0 mm were promoted as solvent-saving alternatives, followed by the widespread adoption of <strong>2.1 mm narrow-bore columns</strong>. More recently, some manufacturers have continued pushing toward approximately <strong>1.5 mm internal diameters</strong>.</p><p>From Foster’s perspective, capillary LC is a logical continuation of this progression.</p><p>Chromatography has consistently moved toward smaller columns, lower solvent volumes, and more efficient separations. His ideal future would see this evolution continue until capillary dimensions become a routine rather than specialized choice.</p><h4><strong>Portable HPLC and Higher Throughput</strong></h4><p>Excend itself originated from the laboratory of <strong>Milton Lee at Brigham Young University</strong>, where one of the original ideas was to develop an HPLC system compact enough to be transported to the point of analysis.</p><p>A portable chromatograph could potentially be taken directly to a contaminated environmental site, crime scene, or other location where immediate chemical analysis would be useful.</p><p>In practice, however, Foster said customers have shown particularly strong interest in two other advantages: <strong>solvent savings and compact instrument size</strong>.</p><p>If three or four capillary LC systems can occupy the same laboratory space as one conventional analytical-scale instrument, laboratories could potentially increase chromatographic throughput without expanding their physical footprint.</p><p>The result is a different value proposition from the one originally envisioned: rather than mobility alone, compact capillary LC can combine lower solvent costs with increased instrument density.</p><h4><strong>The Future of Capillary LC</strong></h4><p>Foster sees capillary LC becoming increasingly important as laboratories seek to reduce solvent use, improve sustainability, increase LC–MS sensitivity, and make better use of laboratory space.</p><p>Its advantages are particularly compelling when solvent or sample quantities are limited, when waste is difficult to manage, or when electrospray mass spectrometry is used for detection.</p><p>Challenges remain. Methods still require thoughtful translation, extra-column volume must be controlled carefully, and adoption in regulated laboratories will require confidence that performance and compliance can be maintained.</p><p>Yet the fundamental direction of LC technology already points toward miniaturization.</p><p>For laboratories interested in evaluating the approach, Foster recommends learning from groups already working with capillary systems, reviewing the available literature, and—most importantly—gaining direct hands-on experience with modern instrumentation.</p><p>After decades of technical development, capillary LC may be moving from a specialized technique toward a practical option for routine separation science.</p><blockquote><p><strong>This text has been automatically transcribed from a video presentation using AI technology. It may contain inaccuracies and is not guaranteed to be 100% correct.</strong></p></blockquote><blockquote><h4><strong>Concentrating on Chromatography Podcast</strong></h4><p>Dive into the frontiers of chromatography, mass spectrometry, and sample preparation with host David Oliva. Each episode features candid conversations with leading researchers, industry innovators, and passionate scientists who are shaping the future of analytical chemistry. From decoding PFAS detection challenges to exploring the latest in AI-assisted liquid chromatography, this show uncovers practical workflows, sustainability breakthroughs, and the real-world impact of separation science. Whether you’re a chromatographer, lab professional, or researcher you'll discover inspiring content!</p><p>You can find <strong>Concentrating on Chromatography Podcast </strong>in podcast apps:</p><ul><li><a target="_blank" rel="noopener noreferrer" href="https://open.spotify.com/show/1wZg67rCjoGju4yhqxI3tL"><strong>Spotify</strong></a></li><li><a target="_blank" rel="noopener noreferrer" href="https://podcasts.apple.com/tz/podcast/concentrating-on-chromatography/id1788429185"><strong>Apple podcast</strong></a></li><li><a target="_blank" rel="noopener noreferrer" href="https://podscan.fm/podcasts/concentrating-on-chromatography"><strong>podscan</strong></a></li></ul><p>and on <a target="_blank" rel="noopener noreferrer" href="https://www.youtube.com/@ChromatographyTalk/videos"><strong>YouTube channel</strong></a></p></blockquote>

 Why Capillary LC Is the Future of LC-MS Sensitivity

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