CA2356044A1 - Acoustic piezoelectric resonator sensor - Google Patents
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N29/00—Investigating or analysing materials by the use of ultrasonic, sonic or infrasonic waves; Visualisation of the interior of objects by transmitting ultrasonic or sonic waves through the object
- G01N29/02—Analysing fluids
- G01N29/036—Analysing fluids by measuring frequency or resonance of acoustic waves
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- H—ELECTRICITY
- H04—ELECTRIC COMMUNICATION TECHNIQUE
- H04R—LOUDSPEAKERS, MICROPHONES, GRAMOPHONE PICK-UPS OR LIKE ACOUSTIC ELECTROMECHANICAL TRANSDUCERS; DEAF-AID SETS; PUBLIC ADDRESS SYSTEMS
- H04R17/00—Piezoelectric transducers; Electrostrictive transducers
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2291/00—Indexing codes associated with group G01N29/00
- G01N2291/02—Indexing codes associated with the analysed material
- G01N2291/025—Change of phase or condition
- G01N2291/0256—Adsorption, desorption, surface mass change, e.g. on biosensors
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Abstract
The invention relates to an acoustic wave sensor formed of piezoelectric material.
The sensor comprises a piezoelectric sensor plate spaced apart from an induced dynamic magnetic field, such as from an electromagnetic coil through which AC current flows.
The dynamic magnetic field induces vibration in the sensor plate by fluctuating the aligned dipole moments of the piezoelectric material. The invention represents an improvement over conventional sensor methodologies in that no metallization of the sensor surface is required. The sensor may be used to detect biomolecular interactions between probe and target molecules.
The sensor comprises a piezoelectric sensor plate spaced apart from an induced dynamic magnetic field, such as from an electromagnetic coil through which AC current flows.
The dynamic magnetic field induces vibration in the sensor plate by fluctuating the aligned dipole moments of the piezoelectric material. The invention represents an improvement over conventional sensor methodologies in that no metallization of the sensor surface is required. The sensor may be used to detect biomolecular interactions between probe and target molecules.
Description
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.
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.
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.
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.
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 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 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 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 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 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.
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.
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 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 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 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 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 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.
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.
Claims (5)
1. 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.
2. The sensor of claim 1, wherein the magnetic field fluctuator comprises a coil through which AC current flows to induce a fluctuating electromagnetic field.
3. The sensor of claim 2, wherein the magnetic field fluctuator additionally comprises a magnet.
4. A biosensor comprising the sensor of claim 1 having a biomolecule tethered to the sensor plate.
5. A method of evaluating biomolecular interaction of a probe with a target comprising:
tethering the probe to a sensor plate formed of piezoelectric material, imparting a fluctuating magnetic field to the piezoelectric material so as to vibrate the piezoelectric material at resonance frequency;
exposing the sensor plate to a composition suspected of containing the target; and evaluating changes in vibration of the piezoelectric material caused by interaction of the probe with the target.
tethering the probe to a sensor plate formed of piezoelectric material, imparting a fluctuating magnetic field to the piezoelectric material so as to vibrate the piezoelectric material at resonance frequency;
exposing the sensor plate to a composition suspected of containing the target; and evaluating changes in vibration of the piezoelectric material caused by interaction of the probe with the target.
Priority Applications (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA 2356044 CA2356044A1 (en) | 2001-08-28 | 2001-08-28 | Acoustic piezoelectric resonator sensor |
| EP02754077A EP1423990A2 (en) | 2001-08-28 | 2002-08-28 | Electromagnetic piezoelectric acoustic sensor |
| CA002493389A CA2493389A1 (en) | 2001-08-28 | 2002-08-28 | Electromagnetic piezoelectric acoustic sensor |
| AU2002322938A AU2002322938A1 (en) | 2001-08-28 | 2002-08-28 | Electromagnetic piezoelectric acoustic sensor |
| US10/488,356 US7207222B2 (en) | 2001-08-28 | 2002-08-28 | Electromagnetic piezoelectric acoustic sensor |
| PCT/CA2002/001320 WO2003019981A2 (en) | 2001-08-28 | 2002-08-28 | Electromagnetic piezoelectric acoustic sensor |
| US11/738,861 US20080163689A1 (en) | 2001-08-28 | 2007-04-23 | Electromagnetic piezoelectric acoustic sensor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA 2356044 CA2356044A1 (en) | 2001-08-28 | 2001-08-28 | Acoustic piezoelectric resonator sensor |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2356044A1 true CA2356044A1 (en) | 2003-02-28 |
Family
ID=4169826
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2356044 Abandoned CA2356044A1 (en) | 2001-08-28 | 2001-08-28 | Acoustic piezoelectric resonator sensor |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2356044A1 (en) |
-
2001
- 2001-08-28 CA CA 2356044 patent/CA2356044A1/en not_active Abandoned
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