Note: Descriptions are shown in the official language in which they were submitted.
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ACOUSTIC PIEZOELECTRIC RESONATOR SENSOR
FIELD OF THE INVENTION
The present invention relates generally to an acoustic wave sensor, and
particularly
to an acoustic sensor incorporating piezoelectric material.
BACKGROUND OF THE INVENTION
Acoustic wave transducers are conventionally divided into bulk acoustic wave
(BAW) and surface acoustic wave (SAW) devices. The majority of BAW devices
employ
a 0.2 to 0.5 mm thick AT-cut quartz resonator disc coated with metal
electrodes, such as
gold electrodes, on either side of the disc. A high frequency (low MHz)
sinusoidal voltage
is applied across the gold electrodes causing the quartz resonator disc to
oscillate at its
resonant frequency. When used as a mass sensor, this device is referred to as
a quartz
crystal microbalance (QCM). The quartz crystal microbalance has become widely
used as
a biosensor.
Piezoelectric material consists of atoms and/or molecules which all have their
dipole moments aligned in the same direction within a lattice. If an outside
force is
applied to the lattice in such a way as to shift the alignment of the dipole
field alignments,
a voltage is produced. In the case of conventional QCM devices, the quartz
crystal serves
as the piezoelectric material, and the outside force comprises an alternating
high frequency
sinusoidal voltage applied to metal electrodes coated on the quartz crystal
disc. The
stringent conditions under which such quartz crystal discs are produced
results in very
reproducible disc and, therefore, reliable results.
However, conventional QCM acoustic transducers have a number of limitations.
There is a strict requirement to photolithographically apply a metal film onto
the disc of
piezoelectric material. Additionally, hard wire connections to the metal film
are required.
Conventional QCM devices have a detection limit of approximately 1 ng/mL,
which is
inadequate for the monitoring of low molecular weight biomolecules. All of
these
problems impede the development of a practical acoustic sensor based on
conventional
QCM technology.
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A new acoustic sensor, the magnetic resonance sensor (MARS), has recently been
developed which offers an alternative to the QCM device. This technology has
been
described, for example, by Stevenson et al. in U.S. Patent No. 5,869,748,
issued February
9, 1999. The MARS transducer described by Stevenson et al. establishes an
acoustic
resonance in a free-standing metallized silica glass plate using remote
magnetic and
electromagnetic fields. The device exploits magnetic fields for direct
generation of
acoustic waves in a thin metal film coated on one side of the silica glass
plate. A coil
connected to a RF generator, and a permanent magnet are placed on one side of
the
metallized silica glass plate. The magnet is not in direct contact with the
plate and is thus
said to be "remote" from the plate, although the induced magnetic fields
extend to the
plate. The magnetic fields achieve excitation of ions within the metallized
coating on the
plate. Unlike other previously designed electromagnetic-acoustic transduction
sensors
(EMATS), the transduction efficiency of the MARS device benefits from both
electrical
and acoustic resonance effects.
When exposed to an electromagnetic field, acoustic waves are produced in a
metal
film as a consequence of the radial Lorentz forces generated within the film.
These "non-
contact" forces are then conveyed, through momentum conveyed by contact of the
metal
film with a silica glass plate, to cause acoustic resonance in the glass
plate. The process is
described by equation 1, where the Lorentz forcing term, F(z), is coupled to
differential
terms representing the elastic properties of the silica glass plate:
~u - Vs~u - F z (1)
c'~t2 c?xZ C
where C is the elastic modulus of the silica glass plate; a is the particle
displacement; and
VS is the shear velocity. Because only one side of the glass plate is being
driven, both the
asymmetric and symmetric standing waves can be supported by a plate of
thickness d,
where the acoustic wave vector, k, is equal to pm/d, where m is an integer.
The resonance
frequency, fR, can be calculated from the following equation:
fR - mVS m = 1,2,3,...,n (2)
2d
The resonance frequencies occur at harmonics of the fundamental frequency (m=1
) and
occur twice as often in a device such as the MARS device as compared to a QCM
device.
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Acoustic wave generation in the metallized silica glass plate is associated
with a
radio frequency generated in the coil, in the order of l Os of mAs. The
current gives rise to
a series of voltage dips, on the order of mVs, at frequency intervals
corresponding to the
harmonic series of standing waves. The voltage dip corresponds to an acoustic
resonance
because the coil receives reflected RF power from the metal film that reduces
in value
when acoustic power is generated. The received signal voltage can be described
by the
following equation:
V - GB2I a * 2 (3)
pVs(1+(3) ad
where V is the received signal voltage; B is the magnetic field; I is the
source current; Qe
is the quality factor for the parallel resonant circuit; p is the density of
the glass plate; Vs
is the shear velocity for the acoustic wave; a is the attenuation coefficient;
d is the
thickness of the plate; and (3 is an adjustment factor for phase differences
that may exist
across the metal film.
The MARS system offers advantages over the established QCM systems. From
the above equation, it is clear that the received signal voltage can be
increased through a
variety of routes, such as by increasing the magnetic field strength, or by
increasing the
source current. An applicable source current frequency may range from the low
MHz
range up to around 60 MHz. However, the MARS system requires both a permanent
magnet and electromagnetic field generation from the coil in order to induce
appropriate
movement within the metal film which then induces vibration in the plate.
The MARS device involves only indirect generation of vibration in the silica
glass
plate because only the metal film is initially caused to vibrate because of
the magnetic and
electromagnetic fields. The momentum from the vibration of the metal film is
then
imparted to the lattice of the silica glass plate. Thus, the glass plate is
caused to vibrate
only indirectly because of its proximity adjacent to the metal film. Because
the sensing
portion of a MARS device is indirectly caused to resonate through vibration of
the metal
film, a MARS sensors cannot be considered a magnetic direct generation sensor.
The above-described MARS device suffers from problems arising from
reproducibility. Because resonance occurs in both the metal film and the
silica glass plate,
inconsistencies in the shape, thickness or density of either the film or the
plate will effect
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the resulting vibration of the plate, and the shape of the acoustic resonance.
The shape of
the acoustic resonance for either symmetric or asymmetric modes can be
effected. If an
acoustic response does not appear to be a single peak, but rather as a
doublet, at lower
frequencies, or multiple peaks clustered around a main central resonance, this
suggests
that the glass plate faces are not parallel, or that they are acoustically
isotropic.
Inconsistencies in the plate complicates the results obtained from the MARS
sensor
because a shear wave generated in the metal film does not travel in a single
dimension.
Instead the glass plate supports the generation of lateral waves, requiring
the incorporation
of a more complex three-dimensional resonator model to account for the
distorted
resonance envelope. Thus, inconsistencies in plate shape, thickness or density
introduces
a significant amount of error when comparing the results obtained using
different silica
plates. From equation 3, it is clear that differences in plate thickness (d),
non-parallel
plate faces ((3, Vs, a) and plate density (p,a, Vs) profoundly affect the
received signal
voltage.
Although the MARS device traverses the requirement of QCM systems to
photolithographically apply a metal film electrode onto a specially polished
crystal of
piezoelectric material, metallization of the silica glass plate is still
required, and new
problems associated with reproducibility in the plate specifications are
introduced.
It is, therefore, desirable to provide a sensor device which incorporates
magnetic
direct generation of vibration within a sensing portion of the device, and
which is less
susceptible to variability than the above-noted MARS technology.
SUMMARY OF THE INVENTION
It is an object of the present invention to obviate or mitigate at least one
disadvantage of previous acoustic wave sensors.
The invention provides an acoustic wave sensor comprising a sensor plate
formed
of piezoelectric material, a magnetic field fluctuator for inducing a
fluctuating magnetic
field in the piezoelectric material, thereby causing acoustic wave vibration
of the sensor
plate, and a monitor for evaluating vibration of the sensor plate.
In a further embodiment, there is provided a method of evaluating biomolecular
interaction of a probe with a target comprising the steps of (a) tethering the
probe to a
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sensor plate formed of piezoelectric material, (b) imparting a fluctuating
magnetic field to
the piezoelectric material so as to vibrate the piezoelectric material at
resonance
frequency; (c) exposing the sensor plate to a composition suspected of
containing the
target; and (d) evaluating changes in vibration of the piezoelectric material
caused by
interaction of the probe with the target.
The inventive sensor can be considered a "magnetic direct generation" sensor,
because the sensing portion of a device resonates directly as a result of the
application of
electromagnetic field fluctuation.
Other aspects and features of the present invention will become apparent to
those
ordinarily skilled in the art upon review of the following description of
specific
embodiments of the invention in conjunction with the accompanying figures.
BRIEF DESCRIPTION OF THE DRAWINGS
Embodiments of the present invention will now be described, by way of example
only, with reference to the attached Figures, wherein:
Fig. 1 is a schematic illustration of a PRIOR ART acoustic wave sensor
according
to MARS technology, incorporating a permanent magnet, an elecromagnetic coil,
and a
metallized silica glass plate; and
Figure 2 is a schematic illustration of an acoustic wave sensor according to
the
invention.
DETAILED DESCRIPTION
Generally, the present invention provides an acoustic wave sensor
incorporating
piezoelectric material. The acoustic wave sensor comprising a sensor plate
formed of
piezoelectric material. The piezoelectric material is exposed to a magnetic
field fluctuator,
which induces a fluctuating magnetic field in the piezoelectric material. This
fluctuation
causing acoustic wave vibration of the sensor plate, which can be monitored.
The
vibrational state of the sensor plate can then be used to determine minute
changes, for
example on the surface of the sensor plate.
The magnetic field fluctuator is used to impart vibration to the piezoelectric
material at resonance frequency. The fluctuator may comprise a coil
electromagnet, such
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as a copper coil wire that may optionally be coated with enamel. Such a coil
is exposed to
alternating AC current. By modulating the current through the coil,
fluctuation of the
aligned dipoles in the piezoelectric material is induced.
The use of a permanent magnet is optional with the invention, since the
fluctuator
imparts adequate energy to the piezoelectric material to generate resonance
vibration. In
the case where a coil serves as a fluctuator, electromagentic energy from the
coil is
modulated so as to cause vibration within the piezoelectric material. The
effect of a
permanent magnet on piezoelectric material would serve to shift the alignment
of the
dipole moments within the piezoelectric material in a static (non-fluctuating)
manner,
which would not in itself cause vibration in the material. This may be
desirable, and thus
it is conceived that a permanent magnet may be a component of the fluctuator
according to
the invention. The presence of a fluctuator, such as a coil through which AC
current flows,
causes dynamic (fluctuating) movement of the aligned dipole moments within the
material, thereby producing vibrations in the material. In the prior art MARS
technology,
such dynamic fluctuations from an electromagnetic coil alone would not be
adequate to
induce vibration in the metallized silica glass plate.
The fluctuator is placed in a location adequately spaced from the sensor plate
so as
to allow appropriate induction of a fluctuating field. The fluctuator is
placed close enough
to ensure vibration is imparted, but not so close that the signal from the
vibration is
reduced to "noise". The appropriate distance can easily be determined for
different sized
sensor plates by observing the signal generated, and the distance can be
optimized by
observing the output signal.
The sensor device may be used as a biosensor with which behavior of biological
molecules (such as proteins, DNA, RNA) can be determined. The device is useful
for
detecting of biological molecules, such as in DNA hybridization,
immunochemical
interactions, and nucleic acid drug interactions. In this context, the
invention also relates
to a method of evaluating biomolecular interaction of a probe with a target.
As used herein, the terms "probe" and "target" refer to molecules capable of
specific interaction with each other. These may be referred to herein as the
probe/target
pair. The probe is a molecule which is tethered, bound, adsorbed to or in some
form of
permanent or temporary contact with the sensor surface. The target is a
molecule capable
CA 02356044 2001-08-28
of interaction with the probe, but which is not bound to the sensor surface.
For example,
one of the probe/target pair may comprise a nucleotide sequence to which the
other of the
probe/target pair is complementary. Further, the probe/target pair may be an
antibody/antigen pair, a protein/small molecule pair, or any number of
biological
molecules capable of specific interaction with each other. Specific
interaction may
comprise, for example: binding, adsorbence, adherence, or hybridization.
The method of evaluating probe/target interaction comprises the steps of
tethering
the probe to the sensor surface. This can be done in a variety of ways. An
exemplary
method for high surface density covalent immobilization of oligonucleotide
monolayers is
described by Thompson et al. in U.S. Patents Nos. 6,159,695 and 6,169,194,
issued on
December 12, 2000 and January 2, 2001, respectively. Of course, any acceptable
method
of tethering can be utilized with the invention.
According to the invention, a fluctuating magnetic field is imparted to the
piezoelectric material so as to vibrate the piezoelectric material at
resonance frequency.
This fluctuation can be induced by using a coil electromagnet, such as a
copper coil wire
that may optionally be coated with enamel. Such a coil is exposed to
alternating AC
current. By modulating the current through the coil, fluctuation of the
aligned dipoles in
the piezoelectric material is induced.
The sensor surface is then exposed to a test composition suspected of
containing
the target. This may be, for example, an aqueous solution comprising a diluted
or non-
diluted amount of a test sample. The test sample may be derived from any
source to be
tested for the presence of the target. For example, the test sample may
comprise a
biological fluid or a homogenized, purified, and/or diluted biological tissue.
Should the
target be present in the composition, interaction between the target and the
probe
occurnng on the sensor surface will effect the vibration of the piezoelectric
material in a
detectable manner.
By evaluating changes in vibration of the piezoelectric material caused by
interaction of the probe with the target, information can be derived to
determine the
quantity and/or quality of the probe present in the test composition.
Detection of the frequency change due to the occurrence of a bio-recognition
or
bio-interaction event is achieved by specific signal processing methods. The
actual output
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signal is comprised of a high frequency carrier (in the order of tenths of a
MHz),
modulated by a low frequency signal (for example, about 1 kHz). This complex
signal is
filtered using specific RC circuits to remove: 1) the carrier signal and
modulation to obtain
the offset baseline; and 2) the Garner signal only. By subtracting the above
signals 1) and
2) with offset removal, useful information contained in the amplitude of the
modulation is
isolated and then further amplified.
Figure 1 depicts a PRIOR ART sensor according to the MARS technology. A
silica glass plate 20 having an aluminum film 22 coated thereon is exposed to
a permanent
magnet 24 and an electrical coil 26. The electrical coil 26 has oscillating
current passing
therethrough to induce oscillating eddy currents in the aluminum film 22
through
movement of electrons in the film. In this example of prior art, the fields
induced by the
permanent magnet 24 and the electromagnetic coil 26 are perpendicular. Both
the
permanent magnet and the electromagnetic coil are required in this apparatus.
The
vibrations induced in the film 22 cause vibration of the silica glass plate 20
because of the
contacting proximity of the film to the plate.
Figure 2 provides a schematic illustration of a sensor according to the
invention. A
sensor plate 30 formed of AT-cut quartz is placed in proximity to a copper
wire coil 36,
through which AC current flows. The electromagnetic fields generated from the
coil shifts
the alignment of the dipole field alignments in the quartz crystal sensor
plate, thereby
directly inducing resonance in the crystal. Vibration of the sensor plate 30
is evaluated by
a monitoring device, not shown, which derives feedback from the coil.
Quartz crystal is the most commonly used piezoelectric material. However
materials having piezoelectric characteristics, such as lithium niobate, can
be used with the
invention.
According to the invention, the piezoelectric crystal plate itself is directly
vibrated,
not vibrated merely because of intimate contact with a metallized component,
such as the
metal film in MARS technology. The invention reduces problems associated with
distortion of the wave travelling through the metal film. Further, by negating
the
requirement for application of a metal film on the sensor, cost is reduced and
variability
between crystal plates is decreased. In the inventive sensor, the use of a
permanent
magnet is optional, which reduces the cost of the sensor components.
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The invention is advantageous over traditional QCM sensor technology because
the piezoelectric material does not require a metal film coated thereon, nor
electrodes in
contact with the film. This significantly reduces manufacturing costs of the
piezoelectric
material, which for QCM is often in the form of a disc having gold film
electrodes coated
thereon.
The direct vibration of a piezoelectric crystal plate in an electromagnetic
field
causes resonance vibration in the plate. If an electromechanical coupling
constant and
electric field are substituted for the forcing term in equation (1), an
equation of the same
form for the piezoelectric generation of acoustic waves appears. Thus, the
invention
incorporates magnetic direct generation of vibration in the piezoelectric
material, and
produces similar conditions for the production of acoustic waves as compared
to QCM.
Advantageously, the invention incorporates the fluctuating magnetic fields
from
electromagnetic having AC current flowing therethrough. The fluctuation is
caused to an
extent adequate to shift the alignment of the dipole field alignments, thereby
inducing
resonance. By directly exciting resonance in the piezoelectric crystal, the
device utilizes a
magnetic direct generation event.
The above-described embodiments of the present invention are intended to be
examples only. Alterations, modifications and variations may be effected to
the particular
embodiments by those of skill in the art without departing from the scope of
the invention,
which is defined solely by the claims appended hereto.
