Magnetic
Biodetection

Magnetic biodetection constitutes a large area of research and development at Imego. Besides the use of magnetic sensor techniques for analyses of biological sam ples, approaches utilizing magnetic forces are also used at Imego to manipulate samples, i.e. for concentrating, mixing and handling samples. One analytical technique platform uses magnetoelastic films that changes magnetic resonance properties when external material is deposited on it or molecules bind to its surface. The other main magnetic technique platform developed at Imego is based on detection of changes in Brownian motions of magnetic nanoparticles as a consequence of interactions between the particles and the substance or environment we want to analyze.
   

An ideal biosensor should detect target molecules directly without use of labeled ligands or washing steps. We have overcome these obstacles by designing a sensor system based on magnetic nanoparticles with a surface modified to bind any specific molecule we want to detect. Upon binding of target molecules (i.e. antibodies) to the particles, the hydrodynamic particle volume increases which can be detected using dynamic magnetic measurements.

Nanoparticles in suspension undergo Brownian motion that is a chaotic motion due to collisions with water molecules. The frequency of Brownian motion is dependent on the size of the particles, the motion of smaller particles occurs at higher frequencies than larger particles. For thermally blocked magnetic particles in colloidal suspension, one can monitor Brownian rotational motion by measuring the frequency dependent magnetic susceptibility of the particle system. Since the frequency can be detected in this way, so can also the particle size be determined and most important, a change in particle size can be observed upon binding of target molecules.

We have designed an instrument to measure the frequency dependent magnetic susceptibility of nanoparticle systems and find experimentally for protein G particles a good correlation between antibody concentration in a sample and the observed change in hydrodynamic volume of the particles. The technique can be used for a wide variety of analyzes with biological applications. Detection of disease markers in patient samples constitute one area, other areas can be analyses of environmental samples or to follow chemical reactions or synthesis in (bio-) chemical industry.
 

Most biosensors are designed to detect presence of certain molecules (e.g. disease markers) in a sample. In a common and very frequently used assay in laboratories all around the world, the disease markers are first immobilized on a surface and in a second step detected by a labeled antibody after extensive washing. It would simplify the assay, and shorten the time required, if one could detect the immobilized molecules per se, without a second (or even a third) binding reaction and several washing steps in between, i.e. an homogenous assay . By using magnetic nanoparticles we have been able to achieve this. Binding of the analyte to particles leads to an increase in size of the nanoparticles. This can be detected directly as a change in magnetic response of the particles.
 

Magnetic nanoparticles can be kept in a colloidal suspension, this means that particles are moving around in a liquid, such as water, but do not sediment. Such particles undergo “Brownian motion” that is a chaotic motion, both translational (sideways) and rotational, due to collisions with water molecules. The frequency of Brownian motion is dependent on the size of the particles, the motion of smaller particles occurs at higher frequencies than larger particles. For magnetic particles in colloidal suspension, one can monitor Brownian rotational motion by measuring the frequency dependent magnetic susceptibility of the particle system. Since the frequency can be detected in this way, so can also the particle size be determined and most important, a change in particle size can be observed upon binding of analyte to particles.

The magnetic nanoparticles used are very small, in the range of 30-100 nm in diameter. When molecules (such as protein) bind to the surface of the nanoparticles their size increases. The size increase can be analyzed by measuring the magnetic susceptibility of the sample. For this type of analyzes Imego has developed a portable instrument with unique properties, allowing us to study particles in the “nano” size range not accessible with conventional instruments.
 

The technique can be used for a wide variety of analyzes with biological applications. Detection of disease markers in patient samples constitute one area, another is analyses of environmental samples or to follow chemical reactions or synthesis in (bio-) chemical industry.

In order to measure the frequency dependent magnetic susceptibility, it is necessary to use magnetic beads with specific magnetic properties. The particles must be “thermally blocked”, i.e. the magnetic moment direction within a particle has to be locked with respect to the particle. This will force the magnetic moment to rotate with the same rate as the particle. This leads us into another use of the instrument and the measuring technique, i.e. characterization of magnetic nanoparticles. With the instrument one can determine to what extent nanoparticles are thermally blocked. If the particles are thermally blocked one can also determine their size and size distribution.

Particle manufacturers are interested to know if their manufacturing procedure leads to the desired product, both for product development and for quality control. Magnetic particles used in magnetic memories should be thermally blocked (show Brownian relaxation) while many producers of magnetic particles for bio-applications prefer to use superparamagnetic particles (show Néel, not Brownian relaxation). By analyzing the magnetic susceptibility both questions can be answered using our portable instrument.

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