Philips has been working on a disposable biosensor that is capable of detecting picomolar concentrations of proteins to be able to do molecular disease marker detection at the point of care. Currently clinicians send samples to the lab that practices traditional chemistry, often a laborious and time consuming process. The new system uses a cartridge that contains ligand molecules, attached to magnetic nanoparticles, that hone in on a protein in question. A magnetic field inside facilitates the sorting of nanoparticles carrying the target protein out of the rest of the liquid, and an optical unit to detect their concentration.
Philips explains:
The magnetic nanoparticles are preloaded into the cartridge during its manufacture and automatically disperse into the sample as the cartridge fills with blood. Coated with appropriate ligand molecules, they bind to target protein molecules in the sample blood. After a short time, typically around a minute, a large fraction of the target protein molecules end up being bound to the surface of the magnetic nanoparticles.
A small electromagnet situated beneath the cartridge then generates a magnetic field that attracts all the magnetic nanoparticles to the biosensor’s active surface, which is coated with ligand molecules that bind to a second binding site on the target protein. As a result of this magnetic attraction, the surface concentration of the target protein is significantly increased, which speeds up the binding process. The target protein molecules end up locked in a sandwich between the active surface on one side and attached nanoparticles on the other. This type of assay is therefore often referred to as a ‘sandwich assay’.
An electromagnet situated above the cartridge then generates a magnetic field that pulls unbound magnetic nanoparticles away from the active surface. In this way, a very fast and accurately controlled separation between bound and unbound magnetic nanoparticles is achieved, which replaces traditional washing steps. Because each magnetic nanoparticle that remains on the surface is bound there by a target protein molecule, the number of nanoparticles remaining at the surface is a measure of the target protein concentration in the blood sample.
In the final phase, the number of bound nanoparticles is measured using an optical technique based on frustrated total internal reflection. Illuminated at the correct angle, light hitting the underside of the sensor’s active surface is normally reflected without any loss in intensity (total internal reflection). However, when nanoparticles are bound to the opposite side of the surface they scatter and absorb the light, reducing the intensity of the reflected beam. These intensity variations in the reflected beam, which correspond to the number of bound nanoparticles, are detected by a CMOS image sensor similar to that used in a digital camera.
In the final phase, the number of bound nanoparticles is measured using an optical technique based on frustrated total internal reflection. Illuminated at the correct angle, light hitting the underside of the sensor’s active surface is normally reflected without any loss in intensity (total internal reflection). However, when nanoparticles are bound to the opposite side of the surface they scatter and absorb the light, reducing the intensity of the reflected beam. These intensity variations in the reflected beam, which correspond to the number of bound nanoparticles, are detected by a CMOS image sensor similar to that used in a digital camera.Images: Top: A) The magnetic nanoparticles are preloaded into the cartridge during its manufacture and automatically disperse into the sample as the cartridge fills with blood. Coated with appropriate ligand molecules, they bind to target protein molecules in the sample. B) A small electromagnet situated beneath the cartridge generates a magnetic field that attracts all the magnetic nanoparticles to the biosensor’s active surface, which is coated with ligand molecules that bind to a second binding site on the target protein. C) An electromagnet situated above the cartridge generates a magnetic field that pulls unbound magnetic nanoparticles away from the active surface. Bottom: The target protein molecules end up locked in a sandwich between the active surface on one side and attached nanoparticles on the other. The number of attached nanoparticles is measured using an optical technique based on frustrated total internal reflection.
Press release: Magnotech: Philips’ magnetic biosensor platform designed for point-of-care testing…