Inaccuracies in measuring hemoglobin led to poor patient care

Jan Lilja and Sven-Erik Nilsson spent a great deal of time traveling to doctors’ offices to service laboratory instruments and photometers used for hemoglobin measurement.

It was the 1970s, and measuring hemoglobin at the time was a time-consuming, labor-intensive process.

There were many manual steps, which led to errors and inaccurate results. This meant that doctors could not rely on the results, and therefore did not have an complete picture of their patients’ health.

Jan and Sven-Erik experienced these inadequacies regularly on their service visits. They agreed that it was unacceptable and set out to find a better way.

There was no flash of genius – a slow methodical process

The development of what was to become the HemoCue hemoglobin system was not the result of any single “Aha!” moment or a flash of genius. It was a slow, methodical process.

The most pressing issue was getting a precise amount of blood and chemical reagent to spread evenly on a cuvette, so that it could be analyzed in a photometer. They had read about microcuvettes and believe they could use this new technology. Their idea was to create a microcuvette with a small cavity which would encase the mixture to be analyzed.

The manufacturer of cuvettes told them it was impossible because the tolerances required for such a device could never be achieved. So they made the cuvettes on their own.

After overcoming many obstacles, Jan and Sven-Erik’s dream is realized

Along the way, the pair experienced the same issues many other startups encounter, including raising funds, which was always challenging. In 1979 they entered a partnership with Swedish pharmaceutical company Leo, which provided financing and lab facilities.

After two more years of fine tuning, developing a stable chemical reagent, and solving production challenges, they finally had a device that was ready for commercialization.

On October 26, 1982, the first photometers were sold to the Kristianstad Municipal Health District.

Jan Lilja and Sven-Erik Nilsson had realized their dream. They could provide a safe, effective, lab-accurate hemoglobin measurement device to the doctors and laboratories they had supported so many years earlier.

Even groundbreaking innovations can be improved

HemoCue’s method for analyzing hemoglobin in blood was groundbreaking when it was launched in 1982. But that doesn’t mean it could not be improved upon.

The HemoCue analyzers provided lab-accurate hemoglobin results in around 60 seconds. In an emergency medical situation, however, every second counts.

Joakim Pettersson started as a Quality Assurance Specialist at HemoCue in 1993 and moved to R&D in 1996. Joakim believed that, even though HemoCue’s analyzers had a solid reputation for high quality and accuracy, they needed to be faster.

His solution took some unconventional thinking.  

First, a quick chemistry lesson

HemoCue’s original hemoglobin systems work by mixing a drop of blood with a chemical reagent in a microcuvette. The reagent separates hemoglobin from the red blood cells in a process called hemolysis and then a chemical reaction takes place to form a new stable hemoglobin complex.

Once hemolysis is achieved and the reaction complete, the mixture is analyzed with a photometer to measure how much hemoglobin is present.

In the early 2000s, it was thought that a photometer would not be able to get an accurate reading without hemolysis. There would be too much interference from whole blood cells and results would be skewed. This was considered to be settled fact.

Where there’s a will there’s a way

Yet Joakim believed it could be done and knew that taking the hemolysis step out would dramatically speed up the process.

In 2001, he set out to develop a new method to measure hemoglobin without hemolysis. He just had one challenge to overcome: he was already working on other projects that took up all of his time.

Undeterred, Joakim decided that, if he couldn’t work on his idea during normal work hours, he would just come to the lab in the evenings and see what he could figure out on his own.

Sometimes, an idea that sucks is exactly what you need

Joakim started out by adjusting the optics of the built-in photometer of HemoCue’s hemoglobin analyzer. Soon he realized that, with the right algorithm, a photometer could indeed measure hemoglobin in whole blood. So far so good.

The next hurdle he encountered was getting a drop of blood into a “dry” cuvette with only capillary force. Cuvettes filled with reagent are hydrophilic, which means they attract water, creating a natural suction that draws blood into the cuvette.

Joakim figured he could recreate this by using a detergent-like solution, which had the same hydrophilic properties as a reagent.

He injected the solution into a cuvette, dried it out, and it did indeed work to draw in blood. However, he realized that it was difficult to inject the right amount of solution into the cuvette without risking hemolysis or interfering with hemoglobin measurement. Only a tiny amount was needed, but it still had to coat the inner cavity of the cuvette.

Inspiration struck one night, and he grabbed a vacuum cleaner as he was leaving his house.

Back at the lab, he injected a cuvette with the solution as usual, but then used his vacuum cleaner to immediately suck it out again. This removed most of the solution, but just enough residue was left in the cuvette to create the needed suction.

So, Boss, you’ll never guess how I’ve been spending my evenings…

Now he had a working prototype: an analyzer and cuvette that could measure hemoglobin without reagent. But he still hadn’t told his boss what he was working on.

A bit nervous, Joakim approached his manager and told him what he had been up to. There had been no reason to be worried. His manager immediately saw the value of what Joakim had done and told him to drop everything else and focus exclusively on this invention.

From an impossibility to industry standard

Now working in the light of day, Joakim was able to speed up the development of his new hemoglobin system. He and a team of researchers transformed the prototype into a working product.

The HemoCue Hb 301, an analyzer using Joakim’s non-reagent cuvettes, was launched in 2006. The product was extremely stable and drastically cut down the time it takes to measure hemoglobin. In 2018, an updated version, the Hb 801, was launched. It can provide lab-accurate hemoglobin results in less than one second.

Joakim’s innovations formed the basis for several other medical measurement devices. What had been considered impossible is now industry standard.