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To Upgrade or not to Upgrade?

Nowhere is the controversy over instrument upgrades more animated than in HPLC, or more correctly, in the debate over switching from HPLC to UHPLC.

Angelo DePalma, PhD

Angelo DePalma is a freelance writer living in Newton, New Jersey. You can reach him at

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Nowhere is the controversy over instrument upgrades more animated than in HPLC, or more correctly, in the debate over switching from HPLC to UHPLC. Before delving into that controversy, it is useful to note that more users than ever view upgradeability almost as a legal right. It ensures that ordinary operators will be able to swap out a column, replace a 10 Hz detector with an 80 Hz model, or substitute a higher-pressure pump as needed, without calling the service organization.

One aspect of upgradeability is backward/forward compatibility, which Agilent’s Stefan Schuette refers to as “investment protection that provides a stepwise upgrade path.” Instruments with these capabilities are attractive for obvious reasons, provided the price tag for added functionality is reasonable.

On the HPLC/UHPLC question, it is safe to say that opinions are quite diverse. LC Resources’ Tom Jupille has long believed that plenty of life remains in older LC technology. He nevertheless appreciates UHPLC for what it is, the benefits it provides, and its inevitability.

“It’s hard to make a business case for rushing to upgrade from HPLC, but when you do replace
your equipment, that instrument you replace it with will probably have UHPLC capability.”

UHPLC’s future is perhaps best explained demographically. According to surveys, the prevalence of 10μ columns is asymptotically approaching zero, and 5μ technology peaked around five years ago; 3μ technology is still increasing but will begin to wane over the next few years, while sub-2μ technology is increasing inexorably. “The shifts are not revolutionary, but are evolutionary toward smaller particles,” Mr. Jupille says.

Adoption of UHPLC, moreover, follows historical trends in that end-user complaints about sub-2μ technology sound eerily similar to grumbles regarding 3μ particle columns. “We’re hearing the same issues,” Jupille tells Lab Manager Magazine, “that the new systems are more difficult to use, the columns clog, and solvents must be filtered.”


Another skeptic, Bill Letter of Chiralizer, follows a similar script: “In my opinion, many chromatographers do not need to change or upgrade to a new UHPLC system. The high operating pressures are not for everyone.”

However he admits that if analysis speed is critical and sub-2μ columns are available with the appropriate reproducibility and ruggedness, then users should consider UHPLC systems. “As with everything in life, you must consider how the changes will benefit you from a cost and time basis, including time for revalidating methods.”

Liquid Chromatograph | EASY-nLC 1000
Thermo Fisher Scientific |

Vendors of course want to sell new instruments, but to their eternal credit LC companies take great pride in their established instrument base and their ability to service decades-old installations. As PerkinElmer’s April DeAtley observes, “65 percent of the market is still running and purchasing HPLC. We still have to support this group.”

For Shimadzu’s Simon Robinson, the most compelling business case for upgrading to UHPLC is compressed method development times. “And the benefits flow downstream from there, to data quality and throughput. But if it works, don’t change it! We have installed instruments that are 20 years old and the customer is still very happy with them.”

Method transfer is perhaps co-equal with acquisition cost and high-pressure operation as a justification for not upgrading to UHPLC. “Chromatographers want the latest and greatest, and they also want to execute legacy methods on these systems and obtain the same result,” observes Stefan Schuette. Yet strange things happen when an uncorrected HPLC method is attempted on a UHPLC. “Peaks elute at different times, resolution may change, peaks appear and disappear or switch positions.”

The easiest fix is to use an HPLC column on the UHPLC system, but here the smaller system volumes will skew results. This has led some to suggest adding volume to the UHPLC system to approximate that of the older technique. Dr. Schuette likens this “old column on a new instrument” approach to “pulling a caravan with a Ferrari. It works, but it’s not smart.”

Several manufacturers offer strategies that compensate for differences in column size and system volumes by adjusting injection volumes, flow rate, and time program. These approaches, based on sub-2μ particles at modest (less than 600 bar or about 9000 psi) pressures, comprise what one vendor refers to as “UHPLC-style” analysis. Agilent appears to be the only vendor that offers an internal method, Intelligent System Emulation, that automatically reproduces HPLC methods on a
modern UHPLC platform.

HPLC Liquid Flowmeter | FlowCal 5000
Tovatech |

The upgrade imperative is ultimately a business decision, according to Tom Jupille. “If you can reduce run times from 15 minutes to 3 minutes, that’s a genuine productivity boost.” Yet run times
are only part of the picture. Users must still log samples in, prepare samples, and process the data. In some workflows the actual chromatographic run is negligible, in terms of time, compared with reequilibration, sample and solvent preparation, and data processing.

One gets the strong impression, from talking to industry experts, that LC manufacturers truly want to provide no more than what customers need. But the story doesn’t always end there. “You can tell a customer, based on their methods and workflows, that they really don’t need a UHPLC system,” says April DeAtley, “but the customer wants what the customer wants, and of course that is what you sell them.”

Triple Quad LC/MS | 6490
Agilent Technologies |