IC’s Golden Jubilee: Deeper and More Sensitive Analysis

 IC’s Golden Jubilee: Deeper and More Sensitive Analysis

Ion chromatography (IC) is a widely used analytical technique for the separation and determination of anionic or cationic analytes in various sample matrices. Today, it is performed in several separation and detection modes. But that wasn’t always the case, especially when it debuted on the analytical laboratory marketplace in 1975—exactly 50 years ago.

Even as we celebrate IC’s 50th anniversary, the fundamentals of the technique have not changed. The core principle of IC is still conductivity detection. Although modern detectors are highly sensitive and include features like temperature compensation, the fundamental setup remains a straightforward anode-cathode system that measures changes in the conductivity of ions.

Of course, there are many areas in which IC has advanced over the last 50 years, especially considering how overall technology has improved in that time. In Part II of IC’s golden jubilee celebration, Labcompare spoke with Chris Pohl, former Vice President, Chromatography Chemistry, and Yan Liu, Director of Chemistry R&D in ICSP, at Thermo Fisher Scientific.

Labcompare: What overall improvements have been made to IC over the years?

Pohl: Significant advancements have been made in ion chromatography (IC) technology over the years, both in instrumentation and methodology. Early IC systems, such as the Dionex Model 10 in the late 1970s, were limited to operating pressures of around 800–1000 psi due to the mechanical constraints of pump seals and slider valves, which often leaked at higher pressures. Additionally, isocratic methods dominated because the mechanical pumps of the era faced limitations that impacted performance based on the eluents that were used.

Today’s IC systems have evolved to higher pressure instruments that are capable of gradient elution and complex separations that deliver enhanced precision and flexibility. Digital detectors and computer-based data systems provide expanded analytical ranges and superior data handling capabilities that are able to support new scientific breakthroughs. Next-generation IC systems are enabling scientists to solve complex separation problems with better flexibility and precision due to smaller particle sizes and multiple column chemistries that improve resolution and selectivity.

Liu: One critical development in IC is the evolution of suppressor technology – particularly in suppressed conductivity detection, one of the primary detection modes in IC. The IC suppressors have undergone major improvements over the years, becoming more efficient, robust, and easier to maintain. Developments in column technology, stationary phase chemistry, and detection technologies have also contributed to great improvements in the performance and reliability of IC systems and methods.

Labcompare: In your opinion, what is the single biggest advancement to IC technology since its introduction?

Pohl: The most significant advancement in IC is the evolution of suppressor technology. This has fundamentally changed how scientists work by enabling the use of more concentrated eluents. Earlier suppressors limited scientists to low-concentration eluents—typically no more than 5 mM eluents—due to capacity and background issues. The development of hydroxide selective phases is another breakthrough that matches the impact of advances in suppressor technology.

Significant developmental changes were made to make hydroxide a practical eluent with the introduction of hydroxide selective columns. In 1987, academic research by Sandy Dasgupta showed the value of gradients. In this research, he demonstrated the usefulness of gradients with hydroxide, which drove the development of new column chemistry to facilitate this option.

The developments in suppressor technology and hydroxide-selective phases allow researchers to detect low levels of trace level contaminants and, in turn, better support public safety efforts in food and water testing.

Liu: From the laboratory perspective, the invention of reagent-free ion chromatography (RFIC) systems has been one of the most impactful advancements to IC technology. The RFIC systems such as Dionex ICS-2000 System were launched in 2003. The advent of RFIC systems has transformed how IC is practiced in many laboratories globally and revolutionized how users operate IC systems with significantly improved ease of use and reliability, and generate much higher-quality analytical results.

Labcompare: What can IC do now that it couldn't do in the 1970s?

Pohl: In the 1970s, it was not possible to perform gradients or to elute more highly charged ions. This limited functionality hindered the use of IC in labs across industries. Take, for example, labs working on laundry detergents. These detergents contain pyrophosphate, which historically was a problem for IC because carbonate eluents were not effective at elution of tetravalent ions. Modern systems address many of these issues, providing faster and more reliable testing results, such as for samples containing highly hydrophobic or multivalent analytes.

Liu:  The combination of IC with high-resolution in mass spectrometry (MS) allows scientists to determine target analytes with higher sensitivity than previous IC systems allowed. This combination enables expanded IC applications not only into complex carbohydrate analysis in advanced biochemical and pharmaceutical research but also to target organic and inorganic anions and cations in diverse samples such as drinking water, food and beverage, and even lithium-ion batteries.

Labcompare: Application-wise, is there an area that IC works with today that the technology was not suited for decades ago?

Pohl: It is now possible to analyze highly charged ions or complicated matrices in research areas such as water analysis. With IC technologies, a research team can analyze ammonia in drinking water at a 10,000:1 concentration ratio relative to sodium even though the two ions elute next to each other. The enhanced capacity of new IC technologies has fundamentally changed what is possible with these technologies. Modern IC columns have a higher capacity that allows scientists to inject more concentrated samples and still resolve two ions at dramatically different concentrations, even when they're right next to one another.

Liu: Today’s IC columns have more compatibility with organic solvents, which unlocks new applications that weren’t previously possible. The use of organic solvents enhances the resolving power of the separation, especially for target analytes that may not resolve or separate using pure aqueous eluents. In lithium-ion battery analysis, for example, adding a small amount of organic solvent to the eluent improves resolution of target analytes. As electric vehicles become more prevalent, accurately analyzing the key chemical components that make up lithium-ion batteries, as well as impurities and degradation products will be instrumental to continue advancing the technology.

Labcompare: How has customer demand for IC grown in 50 years?

Pohl: Customer demand is increasingly coming from labs in the environmental sector in areas such as high purity water analysis, renewal energy, power generation and nuclear power, as well as in the pharmaceutical sector. In the pharmaceutical industry, scientists can employ ICs mainly to assess drug stability. The precise measurement of counter ions in drug development is vital for maintaining quality control standards and regulatory requirements. Carbohydrate separation technology serves both biotechnology when developing glycoprotein-based drugs and food industry applications for sugar and carbohydrate analysis in diverse product ranges.

Liu: Another area where customer demand is growing is within industrial applications, driven by advancements in IC column chemistries and sample preparation technologies. For example, the semiconductor industry now leverages IC technology to more easily analyze high purity water and chemicals for trace contaminants. For these applications, advanced sample preparation techniques can handle trace contaminant analysis in either high purity water or complex and challenging samples such as concentrated acids and bases that help make the fabrication of modern semiconductors possible.

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Labcompare: What is something about IC technology that is the same today as it was 50 years ago?

Pohl: Since the beginning, IC has always used an inert flow system. While the materials and design of the flow system have evolved over time, the fundamental principle of avoiding metallic components—and the consistent use of a suppressor—has remained a core aspect of IC from the very beginning. The basic principle of suppression, which removes background conductivity to enhance detection sensitivity, has persisted since the beginning of IC development, even though the technology has advanced and we now see more research on suppressed versus non-suppressed IC.

Labcompare: How have hyphenated methods changed IC technology?

Pohl: Hyphenated methods have changed IC technology by allowing for deeper and more sensitive analysis. IC-MS has had the biggest impact due to the higher sensitivity of the mass spectrometer. One example of this is that if a laboratory team uses IC-MS, they can more easily detect perchlorate below the required detection limit from the EPA.

Other hyphenated methods such as two-dimensional IC require a second column with a diameter that is larger than the first. This method has empowered scientists to achieve better separation and higher sensitivity.

Labcompare: What are some best practices for conducting IC analysis today?

Pohl: There are many best practices in IC, but one that comes to mind is the use of a guard column to protect against contamination. This approach helps protect the integrity and performance of the analytical column by trapping impurities and prevents them from reaching the separator. Additionally, implementing a proper shutdown method is vital to reduce downtime and ensure that laboratory teams can consistently produce reliable results.

Liu: Using high-purity deionized water to prepare eluents either manually or through electrolytic eluent generation can significantly enhance the results from IC methods. It is also critical to ensure proper sample preparation before injecting a sample into an IC system. Although it may take a bit more time to do this, the overall analysis is much more reliable when appropriate sample preparation is performed.

About the authors

Christopher Pohl is a chromatography consultant for CAP Chromatography Consulting and President of Cap Chromatography LLC. He retired from Thermo Fisher Scientific in August 2021 where he was Vice President, Chromatography Chemistry. Christopher joined Dionex, now part of Thermo Fisher Scientific, in 1979 where the focus of his work was new stationary phase design. He is an author or co-author of 114 U.S. patents, in a number of areas including separation methods and stationary phase design. Christopher is the author or co-author of 14 book chapters and more than 157 papers.

Yan Liu is the Director of Chemistry R&D in the Ion Chromatography and Sample Preparation Business Unit at Thermo Fisher Scientific. With over 30 years of experience, Yan has significantly contributed to R&D and new product development in ion chromatography (IC) systems, electrochemical detectors, and IC consumable products, including electrolytic eluent generators, columns, and suppressors. Yan has developed numerous novel electrolytic devices for generating and recycling acid, base, and salt solutions used as eluents in IC systems and has been instrumental in developing capillary IC systems. Yan is an inventor or co-inventor of over 40 U.S. patents and has authored or co-authored more than 45 peer-reviewed scientific papers. In 2011, Yan received the Ion Chromatography Award from the International Ion Chromatography Symposium Scientific Organizing Committee.

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