Is Sub-2 Micron Worth It?
For Simon Robinson, HPLC product manager at Shimadzu Scientific Instruments, the most significant trend in HPLC is fast instrumentation that delivers rapid results at higher resolution. “Fast LC has stimulated a lot of instrument sales, and is causing users to look closely at what they’re doing, how their columns work, and which stationary or mobile phases are best for their application.”
Shimadzu’s Prominence HPLC product line includes the Prominence UFLC, an “extremely fast” system operating at standard pressures, the higher-pressure Prominence XR, and the Prominence Nano, a nanoflow system for proteomics.
Robinson delineates cutting edge HPLC instrumentation as those in the 2–3 micron particle size range and sub-2 micron. The former, he says, is optimal in terms of physics, specifically with respect to the ratio of height-equivalent theoretical plates and backpressure. Shimadzu has long played down sub-2 micron systems as too complex for the average user.
“Higher backpressures present more consequences you have to deal with, not to mention higher initial investment and maintenance.” Separating fact from fantasy on particle size, he says, is simple. “The hard part is getting people to believe it. What they learn is that running at 10,000 psi and up is an absolute nightmare on your sanity and wallet. The worst part is when the customer finds out optimizing at a lower pressure can frequently produce better results.”
Tom Jupille, an LC trainer and consultant with LC Resources, is another advocate of optimizing larger particle size systems to avoid the complexities and costs of ultrahigh pressure operation.
Firm in its convictions, Shimadzu promotes LC systems optimized for columns employing 2.2 micron particles which, says Robinson, may be run under normal-pressure conditions.
Bioprocess quality efforts have traditionally been after-the-fact activities rather than pro-active. The notion of Quality by Design, versus testing-in quality, was the impetus behind FDA’s process analytic technology (PAT) initiative. PAT projects have been occurring, particularly at large bioprocessors, but not with the frequency, fanfare, or urgency that might be expected.
For example Shimadzu has an ongoing collaboration, with a major pharmaceutical company, to interface one of its HPLC systems to a bioreactor through an auto-sampler. But this project is “still in the prototype stage,” according to Robinson.
What’s holding back HPLC-based PAT, says DeLand, is “lack of confidence” by an increasingly conservative market. “These reactions and fermentations are worth a lot of money, and a lot is invested in process development,” he says. “But thanks to initiatives from regulators, companies are beginning to open up and embrace the idea of PAT.”
Nevertheless, the tools for PAT exist. Last December, Dionex introduced a new system, the Integral™ process analyzer platform, that works with the company’s ion chromatography and rapid separation LC systems. Integral draws a sample and passes it on to the LC for analysis. The system is suitable for use in process development, pilot, and production systems.