A woman arrives at the accident and emergency department with chest pain. A simple finger prick could be enough to diagnose a heart infarct within a few minutes. That can be done with the Minicare I-20, which Philips will launch on the Benelux market in mid-2016. ‘This device is the result of ten years of intensive research,’ says research scientist Matthias Irmscher.
A tube of blood is now standardly taken from patients who arrive at the hospital with chest pain. The blood goes to a laboratory. About one hour later the result is known and this indicates whether the patient has a heart infarct. Meanwhile the patient is kept under observation and waits in anxiety and uncertainty. In 15 to 30% of cases that is not necessary. For example, the patient has muscle pain, joint inflammation or angina pectoris, an annoying condition but not life threatening.
Based on a single drop of blood, the Minicare system provides the result within a few minutes. ‘We measure the presence of the protein troponin,’ explains Irmscher. That protein is released if heart cells die due to a lack of oxygen.
The Minicare I-20 fits in the trend towards point-of-care medical applications. ‘We develop systems that are faster, simpler and more cost-effective than the current laboratory tests. We not only want to speed up clinical decisions but also achieve higher efficiency and quality within healthcare. That applies not just to hospitals but to other locations as well. For example, general practitioners will be able to test for more things themselves and establish a diagnosis straightaway.’
New medical technology must be simple to operate, cheap to use and provide a quick and accurate result, says Irmscher. ‘The result must be comparable with that of the current time-intensive laboratory tests. You must be able to operate the technology without any prior knowledge, for example, without needing to know how to take a blood sample from a vein. We work with a finger prick of blood, which is a volume of just 20 to 30 microliters. This means we need to be able to measure very low concentrations of the protein. That was our greatest challenge.’
The product can be operated by people with little specific prior knowledge: you stick a plastic cartridge in the readout device and place a drop of blood on it. Within a few minutes the device tells you whether the protein troponin is present in the blood and if it is, in what quantity.
When Minicare I-20 is launched on the market, the work on the technology will certainly not be finished yet. ‘Within Philips we are now working together with universities and other companies on a further expansion of the possibilities,’ states research scientist Irmscher. ‘We want to be able to measure several different proteins so that psychological disorders or brain damage, for example, can also be diagnosed with a finger prick of blood. And we want to further improve the sensitivity as well.’
The cartridge of the Minicare I-20 consists of a piece of plastic that contains very small liquid channels that lead the blood to a chamber. The chamber contains the secret: tiny magnetic spheres that are covered with antibodies. As soon as a troponin protein flows past such a sphere the antibodies capture it.
The readout device contains magnets with which the magnetic spheres can be moved. As soon as the spheres have been able to bind enough troponin molecules, they are drawn to the bottom of the cartridge with the help the magnets. The base is also covered with antibodies and so the troponin molecules bind to the base as well. Subsequently the number of spheres attached to the base is taken as a measure for the concentration of troponin molecules in the blood drop. If the non-bound spheres are subsequently drawn upwards by a magnet then only the bound spheres remain on the base. To measure the number of spheres, the base is illuminated from below with light. The amount of shadow on the base finally indicates the quantity of troponin present in the blood.
‘With the magnetic spheres we therefore ensure that the proteins are bound as quickly as possible. With the so-called ‘rinsing step’, we ensure that non-bound spheres are pulled off the base thereby reducing the noise in the measurements. Thanks to these two steps, the sensitivity of this detection method is far better than that of other rapid troponin tests,’ explains Irmscher. ‘With this approach we can measure substances at concentrations of 30 billionths of a gram per litre.’
As the test works with full blood, a number of hurdles had to be overcome. ‘Ultimately we measure the protein concentration in the blood plasma and so we had to develop a filter that separates the plasma from the red and white blood cells.’ That was not easy, explains Irmscher. ‘You need to produce a filter that holds blood cells, for example, while allowing through the proteins you are interested in. The filter must not become clogged up and it must work with very different blood compositions.’
It was therefore pointless working with model liquids, he says. ‘Right from the start we worked with full blood from many different individual patients. The variation in the quantity of red blood cells between different patients is enormous. Producing a filter that is flexible enough to cope with all those extremes was therefore a considerable challenge. Within NanoNextNL researchers produced a theoretical model for that filter.’
Fundamental research has played an important role in the development of the final product, he says. ‘For example within NanoNextNL, a test setup was developed so that we could observe exactly what happened with the spheres. It was like a cross-section of the chamber with an observation window in it so that we could follow the movements of the spheres. This allowed us, for example, to determine the optimum concentration of the spheres. You must have enough spheres in the solution to bind as much of the protein as possible. However, if you use too many spheres then they obstruct each other’s movement and they cannot bind to the base and be detected.’