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.
A Biosensor System Based on Thermally Blocked
Magnetic Nanoparticles
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.
An Homogenous Assay Based Magnetic Nanparticles
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.
Brownian Motion Reveals the Particle Size
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.
An Instrument for Many Tasks
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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