Biomedical Engineering Reference
In-Depth Information
protein and/or nucleic acid detection in a single assay without relying on optical
scanning. Lastly, the sensors are compatible with standard silicon integrated circuit
(IC) technology which allows them to be manufactured with a built-in electronic
readout at low cost, in mass quantities, and to be deployed in a one-time use
disposable format.
To our knowledge, the first use of MNPs as labels in immunoassays was
reported in the literature in 1997 by a group of German researchers [
1
]. The
measurement was achieved by use of a superconducting quantum interference
device (SQUID) to detect binding events of magnetically labeled antibodies. While
successful, the operating conditions required liquid helium cooling and magnetic
shielding, limiting the practicality of the SQUID-based biosensors. In 1998, Baselt
first demonstrated detection of MNPs using giant magnetoresistive (GMR) sensors
with GMR multilayers [
2
]. GMR sensors have the advantage of room-temperature
operation and simpler instrumentation, making them more attractive, particularly
for portable applications.
All magnetoresistive sensors share a common principle of operation where the
magnetization of a free magnetic layer (or layers) responds to a change in the
local magnetic field and causes a change in the resistance of the sensor. A material
that exhibits magnetoresistance transduces a change in an external magnetic field
into a change in resistance. This effect was first discovered by Lord Kelvin
in 1856 when he found that the resistance of an iron bar increased when the
current flowing through the bar was in the same direction as the magnetic field.
Furthermore, the resistance decreased when the magnetic field was perpendicular
to the current. In actuality, most conductors exhibit magnetoresistance, albeit
on an incredibly small scale not useful for transduction. This effect, known as
anisotropic magnetoresistance, is commonly used in many sensors today, generally
with more efficient materials such as Permalloy (Ni
0:2
Fe
0:8
/. These sensors have
typical magnetoresistance (MR) ratios on the order of 2 % at room temperature [
3
]
where the MR ratio is defined as
R
max
R
min
R
min
R
R
min
MR
D
D
(7.1)
Many years later came the discovery of GMR which is a quantum mechanical
effect wherein a change in magnetic flux is transduced into a change in electrical
resistance through spin-dependent scattering. GMR was first observed in a Fe/Cr/Fe
thin film stack in 1988 independently by Albert Fert and Peter Gr unberg, both of
whom went on to win the 2007 Nobel Prize in Physics for their discovery. The
most basic device exhibiting this behavior is the multilayer GMR stack where two
or more ferromagnetic layers are separated by a thin non-ferromagnetic spacer. The
thickness of this non-ferromagnetic spacer is typically only a few nanometers and
is critical to the operation of the device. At certain thicknesses, the Ruderman-
Kittel-Kasuya-Yosida (RKKY) coupling between the ferromagnetic layers becomes
antiferromagnetic, thus causing the magnetization of the adjacent layers to align
in an antiparallel state. An external magnetic field rotates the magnetization of the
