Biomedical Engineering Reference
In-Depth Information
direction magnetization in the unpinned magnetic layer to rotate, which induces
a decrease in electrical resistance. A number of reports have described how spin
valves can be used to detect low numbers of magnetic particles, and Graham and
colleagues have used them to detect streptavidin-biotin interactions and DNA
hybridization [22, 23]. Because spin valves are sensitive to the direction of the local
magnetic fi eld as well as its strength, the effect of magnetic labels interacting with
opposite sides of a sensing resistor can cancel out, leading to a reduction in sen-
sitivity. Research groups at Philips Research (Eindhoven, The Netherlands) over-
came this problem by immobilizing probe molecules in the region between two
neighboring spin valves [24], while Wirix-Speetjens and colleagues avoided it by
releasing bound labels from the sensing surface and detecting them after they had
become aligned along one edge of a spin valve [25]. The latter group also compared
the performance of magnetic labels with diameters of 1
m and 300 nm in immu-
noassays, and found the latter to produce a lower limit of detection and a broader
dynamic range. More recently, the teams at Philips Research have carried out
immunoassays with spin valve sensors located in close proximity to current- car-
rying conductors integrated on the same chip [26]. These conductors generate
high-frequency magnetic fi elds that excite those magnetic labels bound to the
sensing surface. Each chip is embodied in a disposable microfl uidic cartridge that
inserts into an electronic reader, with potential for miniaturization into a hand-
held instrument. Hall sensors are based on the Hall effect, whereby when a
magnetic fi eld is applied at right-angles to the movement of charged particles in
a conducting material, a voltage is developed at right-angles to the directions of
their movement and the applied fi eld. For sensing purposes, a small current is
passed through the conductor, after which an alternating magnetic fi eld is applied
along the same axis as the direction of current fl ow and a unidirectional magnetic
fi eld is pulsed on and off at right-angles to it. In the absence of any magnetic labels
bound to the sensing surface, the latter induces a stable Hall voltage; however,
when bound magnetic labels are present, the alternation of their dipole fi eld
superimposes an alternating component on the Hall voltage, which can be detected
by lock-in electronics. Besse and colleagues have demonstrated the detection of
single magnetic microspheres with a Hall sensor [17], while others have used them
to detect DNA [18, 27].
There are a several problems that must be overcome before arrays of magnetic
sensing elements can be used for multiplexed detection. In common with other
detection methods that seek to interface arrays of sensing elements with arrays of
probe molecules, it is necessary to ensure that the latter are immobilized at the
same location as former. Some probe molecules (e.g., oligonucleotides) can be
synthesized
in situ
by employing photolithographic methods similar to those used
to fabricate the sensing elements, although other probe molecules (e.g., antibod-
ies) must be immobilized directly onto the sensing elements. This inevitably
becomes more diffi cult as the dimensions of the sensing elements become smaller.
A possible solution to this problem would be a version of the immobilization
technique developed by Nanogen (San Diego), in which probe molecules are
directed to individual sensing elements by on-chip electric fi elds. Alternatively, the
μ
