Philips has developed a novel biosensor that uses nanomagnetic particles and optical technology to detect disease, diagnose clinical conditions and test for illegal drugs.
Lab-on-a-chip technology to allow rapid, single-step in-vitro testing away from the laboratory has been available for about 20 years. Traditionally, it replicates the pipette fluid exchange steps carried out manually or by robots in the laboratory, but on a miniaturised scale: introducing a sample, incubation, washing step, adding a reagent and so on.
In Philips’ Magnotech device (pictured below) the sample is added to a cartridge containing magnetic nanoparticles chemically bonded to a ligand — a substance such as an antibody designed to attach to the target protein.
The cartridge is inserted into a hand-held analyser, which applies a magnetic field attracting the molecules to the active surface of the sensor, where more ligands attached to the surface bind them in place. Another magnet then draws the unbound molecules away.
A visualisation technique called frustrated total internal reflection (FTIR) then gives an accurate reading of the amount of analyte present.
In FTIR, light shines onto an optically flat plastic surface in the cartridge and bounces off into an imaging sensor in what is known as the condition of internal reflection.
It is caused by the fact that the optical refractive index of the plastic is higher than the optical refractive index of the material in the chamber — initially air then the biological sample.
Where the magnetic particles bind to the surface, they scatter and absorb the light. The grey value, or darkness, of the spots where they gather is a measure of the amount of magnetic particles on the surface, which in turn is a measure of the concentration of the original target molecules.
Philips claims the Magnotech is compact, easy to use and can work on tiny volumes — as little as a pinprick of blood. Prof Menno Prins, a Philips Research fellow, explained: ‘Anything you can raise an antibody against is a molecule you can in principle detect in this type of biosensor, known as an immuno-assay. There are approaching 100 molecules for which clinical biosensors already exist, and in life science research and development it is much larger.’
Immunoassays characteristically allow sensitive detection in a complex matrix, such as blood or saliva. Competition immunoassay used in drug detection can detect towards the lower nanomolar concentrations (one billionth of a mole of solute per litre of solution).
In the other type, the so-called sandwich immunoassays, two different types of antibodies are used, typically for the detection of proteins. The detection goes to picomolar (a millionth of a millionth of a mole of solute per litre) and even lower.
To detect more than one substance in a single Magnotech assay, the antibodies for different proteins can be attached to different areas in the cartridge with separate optical analyses carried out in each location. Alternatively, to detect substances that require reactions in different environments — different pH levels, for instance — a cartridge can be made integrating several chambers, each with a different environment.
Prins said the time to get a result using Magnotech depends to some extent on the assay, the analyte, the species to be measured and the concentration of the species. It goes from below a minute for certain assays to more than a minute for others. This compares with traditional robotic pipetting immunoassays, which can take from 20 minutes to an hour.
‘The reason ours is much faster is we don’t do such a sequence of pipetting steps,’ he said. ‘Rather than replacing fluid, we have a static fluid through which magnetic particles are moved. We do similar process steps, like binding, separation and mixing, but using electromagnetic forces.’
The Magnotech cartridge used for blood analysis is 8mm wide and 3cm long, similar to commercial glucose sensor strips. The saliva cartridge is somewhat bigger because saliva diagnostics require the sample of saliva to be collected from the mouth with a swab stick, which is pressed into the cartridge. The reaction chamber for both types is the same size, just a microlitre in volume.
The proof-of-concept testing so far has displayed a high level of accuracy for Magnotech, and the entire process is monitored to give more information about the assay.
‘We control the movement of the particles by external fields and monitor the particles approaching the sensor surface, so we can very accurately time the different process steps and include the process information in the results data,’ said Prins.
‘We need to carry out tests in the field with real user conditions, real samples and large statistical sets of measurements to give a fair comparison to existing technology. In the laboratory environment, the coefficients of variance are very comparable, and in some cases better than, what is currently available in rapid testing equipment.’
Philips has formed a partnership with UK company Concateno, which specialises in rapid roadside saliva testing for illegal drugs, to bring Magnotech jointly to market in the second half of 2009.
Cardiologists from Amsterdam, Utrecht and Maastricht universities are also contributing knowledge on detecting biomarkers for cardiac conditions.