GB2484454A

GB2484454A - Sensing a property of a fluid using two resonant elements

Info

Publication number: GB2484454A
Application number: GB201014700A
Authority: GB
Inventors: Angel T-H Lin; Ashwin Seshia; Jize Yan
Original assignee: Cambridge Enterprise Ltd
Current assignee: Cambridge Enterprise Ltd
Priority date: 2010-09-03
Filing date: 2010-09-03
Publication date: 2012-04-18
Anticipated expiration: 2030-09-03
Also published as: GB201014700D0; GB2484454B

Abstract

A sensor for detecting a property of a fluid sample, such as identifying the presence of an analyte in the fluid sample, comprises first and second resonant elements 1, 2 which are coupled together by a mechanical coupling such as a coupling beam 3. The elements 1, 2 are driven to oscillate by a drive means which may include drive electrodes 7. One of the resonant elements 2 is brought into contact with a sample of the fluid and the other resonant element 1 is kept substantially isolated from the fluid. Measuring the resonant behaviour of the elements in comparison to a baseline resonant behaviour can detect the property of the fluid. The sensor may be a microelectromechanical (MEMS) device. The resonant elements 1, 2 may be formed from silicon. The sensor can be used to determine the viscosity of a sample. A linear array (40, Fig 4) of such sensor devices is also disclosed.

Description

SENSOR AND METHOD FOR SENSING A PROPERTY OF A FLUID

Field of the Invention

The invention relates to a device and method for sensing the property of a fluid sample, such as identifying the presence of an analyte in the fluid sample. In particular, the invention relates to a system and device that measures a change in the resonant behaviour of a sensor resulting from the fluid sample being in contact with the sensor.

Background to the Invention

Micromechanical and nanomechanical resonators and cantilevers have been suggested as mass balances for biochemical sensing as they have the potential to provide very high resolution sensing and electrical readout of target analytes in a label free format.

The basic principle of operation of a microresonator sensor is that the presence of a target analyte on the microcantilever changes the mass and/or stiffness of the microresonator.

The microcantilever is driven into oscillation at its resonant frequency at one of its resonant frequencies. Attachment of the target analyte to the resonator changes the mass and/or stiffness of the resonator. The change in mass and/or stiffness of the resonator as a result of the target analyte changes the resonant frequency of the resonator. Sensors operating on this principle have been described in, for example, US5719324.

Electrical transduction offers the most convenient means of driving and providing output signals, particularly as large arrays of sensors are typically used. However, there are several challenges inherent in any practical implementation of this type of system using electrical transduction. In particular, key challenges arise from the necessity of operation in compatible biological buffer solutions or in harsh environments. Difficulties arise with electrochemical reaction with the buffer solutions and with interference with electrical signal transduction. The need to prevent electrochemical reaction with the buffer solution, which might produce unwanted chemical species, limits the voltages that can be used for transduction and so limits the resolution of the sensor. Saline buffer solutions, which are typically used, are conductive and can short out electrical signals or otherwise interfere with electrical signals. Water also gives rise to large capacitances between resonant element and electrodes, limiting sensor resolution.

Accordingly, there is a need for a biochemical sensor that overcomes these implementation challenges.

Summary of the Invention

In a first aspect of the invention, there is provided a sensor for detecting a property of a fluid sample comprising: a first resonant element; a second resonant element coupled to the first resonant element by a mechanical coupling; drive means for oscillating the resonant elements; sensing means for sensing the resonant behaviour of the first resonant element; wherein the sensor is configured to allow the second resonant element to contact the fluid sample, but to substantially isolate the first resonant element from the fluid sample.

Preferably, the sensor is configured to isolate the sensing means from the fluid sample.

Preferably, the sensor is configured to isolate the drive means from the fluid sample.

Preferably, the property of the fluid sample is the presence of a target analyte in the fluid sample. When the target analyte attaches to the second resonant element it alters the mass and or/stiffness of the resonant system and so alters its resonant behaviour. When the mass and/or stiffness of the second resonant element is changed, the resonant frequency of first resonant element is shifted. So the presence of the analyte can be determined by detecting a shift in resonant frequency.

The resonant behaviour of the first resonant element will also change if there is a change in stiffness of the second resonant element or if there is a change in the damping forces on the second resonant element So, for example, the sensor can be used to determine the viscosity of a fluid sample. When measuring dissipative effects such as damping, the resonant behaviour sensed by the sensing means may comprise the phase or Q factor of the first resonant element.

Preferably the sensor is a microelectromechanical systems (MEMS) device. Preferably, the first and second resonant elements are formed from silicon.

A sensor in accordance with the present invention spatially separates transduction (i.e. drive and sensing) of the resonant elements from the fluid sample under test. This has several advantages. The fluid under test does not interfere with electrical drive or sensing of the sensor. Electrical signals in the drive and sensing are not limited in voltage by the need to avoid electrochemical reactions in the fluid under test. For liquid fluid samples, the first resonant element is also able to operate in a less dense fluid environment e.g. air and so may have a higher Q factor, and hence offers greater sensor resolution. There is also no S need for any drive or sensing electrodes surrounding the second resonant element, so reducing squeeze-film damping effects on the second resonant element and improving sensor resolution.

The sensor may be configured to isolate the first resonant element from the fluid under test in several ways. For example, if the fluid is predominantly aqueous, the first resonant element may be coated with a hydrophobic material and/or the second resonant element may be coated with a hydrophilic material. The first resonant element may be held in a first chamber and the second resonant element may be held within a second chamber, the first and second chambers connected by an opening through which the mechanical coupling passes. The opening may be made small enough that fluid cannot readily pass through it owing to the surface tension of the fluid. The second chamber may comprise a microiluidic structure mounted above, below or around the second resonant element, the microfluidic structure comprising a fluid inlet port and a fluid outlet port. The first and second resonant elements may be oriented such that the first resonant element is above the second resonant element so that gravity acts to keep the fluid away from the first resonant element.

Preferably, the second resonant element is coated with a receptor specific to a target analyte. The second resonant element may also be partially coated with a passivation layer.

Preferably, the mechanical coupling is a beam with a length in the range nA/2 ± A/B, where n is an integer and A is the wavelength of oscillation at one of the resonant frequencies of the coupled first and second resonant elements. The frequency at which the sensor is configured to be operated is typically one of the resonant frequencies of the coupled resonant elements. Preferably, the mechanical coupling has a length of substantially half of the wavelength at which the device is configured to be operated, or an integer multiple thereof. A mechanical coupling of this length provides resonant frequencies that are well separated, to allow for selection of one resonant mode for operation.

The drive means may be implemented in several ways. In a preferred implementation, the drive means are electrostatic, comprising one or more electrodes positioned adjacent to the first resonant element, and a voltage applied between the electrode and the first resonant element. Alternatively, the drive means may be a piezoelectric, a magnetic or a mechanical drive (e.g. by using an external piezoelectric transducer coupled to a base of the first resonant element).

The sensing means may also be implemented in several ways. In a preferred embodiment, the sensing means is configured to measure the resistance of the first resonant element as it oscillates. The sensing means may be configured to pass a current across the first resonant element and to detect the resulting voltage, or to develop a voltage across the first resonant element and detect the resulting current. Silicon exhibits a strong piezoresistive effect, so the resistance of a silicon resonant element will change as it oscillates. Alternatively, the sensing means may comprise electrodes mounted adjacent to the first resonant element to allow for capacitive sensing. Other, less preferred, possibilities for the sensing means include optical sensing of the oscillation of the first resonant element or magnetic sensing. Preferably, the sensing means is coupled to the drive means to provide feedback signals so that the first and second resonant elements can be maintained in resonance. The resonant frequency of the coupled resonant elements measured by the sensing means may be monitored and any shift is indicative of attachment of analyte to the second resonant element. Both the presence of a shift in resonant frequency and the amount of the shift in resonant frequency may be recorded.

The first and second resonant elements may be formed in various shapes and sizes, such as square plate resonators, ring resonators or cantilever resonators. The sensor of the present invention is scalable to very small dimensions as it allows for direct electrical drive and readout, with mass sensitivity increasing with reduction in the dimensions of the resonant elements.

The sensor of the present invention may comprise more than two coupled resonant elements. For example, a third resonant element coupled between the first and second resonant elements may be provided. Additional resonant elements may be provided to increase the Q factor of the resonant elements and hence the resolution of the sensor.

Additional resonant elements may also be used to provide for better isolation of the first resonant element, drive means and sensing means from the fluid under test. The drive means and sensing means may be coupled to different resonant elements so long as they are substantially isolated from the fluid under test which contacts the second resonant element.

The sensor of the present invention may be used to detect the presence of a target analyte in a buffer solution. The target analyte may be a known chemical species, or a known virus or microorganism, which bonds to a specific coating or receptor on the second resonant element. Alternatively, the sensor may be used to find an unknown target analyte which bonds to a specific receptor on the second resonant element. The sensor may even be used to detect physical properties of the fluid itself, such as viscosity. The fluid may be liquid or gas.

An array of sensors in accordance with the first aspect of the invention may be formed as an integral device. The array of sensors may each be electronically driven and may provide electronic readout. The array may include sensors configured to detect different analytes or may comprise a plurality of sensors configured to detect the same target analyte.

In a second aspect of the invention there is provided a method of detecting a property of a fluid sample using a sensor comprising a first resonant element, a second resonant element coupled to the first resonant element by a mechanical coupling, drive means for oscillating the resonant elements, and sensing means for sensing the oscillation of the first resonant element, comprising the steps of: bringing the fluid sample into contact with the second resonant element but not the first resonant element; measuring a resonant behaviour of the first resonant element; and comparing the measured resonant behaviour with a baseline resonant behaviour measurement to determine a shift in resonant behaviour indicative of a property of the fluid sample.

The resonant behaviour may comprise one or more of resonant frequency, resonant phase or Q factor.

Preferably, the property of the fluid sample is the presence of a target analyte in the fluid sample. The presence of a shift in resonant frequency indicates that the mass and/or stiffness of the coupled first and second resonant elements has been modified owing to attachment of an analyte to the second resonant element. The amount of shift can be recorded and compared with empirical data to provide an indication of analyte concentration within the fluid sample and/or to identify the mass of the analyte.

Preferably, the method further includes the step of determining a baseline resonant behaviour by operating the sensor with the second resonant element in contact with a control fluid sample of known properties.

Preferably, the method further includes the step of coating the second resonant element with a receptor specific to a target analyte. The method may further include the step of partially coating the second resonant element with a passivation layer.

Preferably, the method further includes coating the first resonant element and/or the second resonant element and/or portions of a sensor housing with a material to isolate the first resonant element, the drive means and the sensing means from the fluid sample. For example, if the fluid is predominantly aqueous, the first resonant element may be coated with a hydrophobic material and/or the second resonant element may be coated with a hydrophilic material. The first resonant element may be held in a first chamber and the second resonant element may be held within a second chamber, the first and second chambers connected by an opening through which the mechanical coupling passes. The opening may be coated with a hydrophobic material. The opening may be made small enough that fluid cannot readily pass through it owing to the surface tension of the fluid.

The method may include the step of mounting a microfluidic structure above, below or around the second resonant element, the microfluidic structure comprising a fluid inlet port and a fluid outlet port.

Preferably, the method comprises the step of driving the first and second resonant elements at a resonant frequency. Preferably the step of driving comprises driving the first resonant element electrostatically.

The step of measuring resonant behaviour may comprise monitoring the electrical resistance of the first resonant element. Alternatively, the step of measuring a resonant behaviour may comprise monitoring a capacitance between the first resonant element and an adjacent electrode. In a further alternative, the step of measuring a resonant behaviour may comprise optically or magnetically monitoring the motion of the first resonant element.

The method may comprise using a plurality of sensors in array, each comprising a first resonant element, a second resonant element coupled to the first resonant element by a mechanical coupling, drive means for oscillating the resonant elements, and sensing means for sensing the oscillation of the first resonant element.

The fluid sample may be a liquid sample, such as a saline buffer solution containing target chemicals or microorganisms or viruses. The fluid sample may alternatively be a gaseous sample.

Brief Description of the Drawings

Embodiments of the present invention will now be described in detail, by way of example only, with reference to the accompanying drawings, in which: Figure 1 is an optical micrograph of a mass sensor in accordance with the present invention; Figure 2 is a schematic diagram illustrating an open loop readout implementation of the sensor shown in Figure 1; Figure 3 is a schematic diagram of a closed loop readout and control implementation of the sensor shown in Figure 1; Figure 4 illustrates a linear array of sensors of the type shown in Figure 1; Figure 5 illustrates an NxM array of sensors of the type shown in Figure 1; and Figure 6 is a flow diagram illustrating the step of a method of sensing in accordance with the present invention.

Detailed Description

Figure 1 is an optical micrograph of a sensor in accordance with the present invention. The sensor comprises a first resonant element 1 coupled to second resonant element 2 by a coupling beam 3. The first and second resonant elements are suspended from a frame 4 by flexures 5 and are free to oscillate in a plurality of different modes. The frame 4 effectively defines first and second chambers respectively housing the first and second resonant elements 1, 2. The chambers are linked by an opening 6, through which coupling beam 3 passes.

The first and second resonant elements and the coupling beam are formed from silicon.

The sensor shown in Figure 1 can be fabricated from a single semiconductor wafer, such as a silicon on insulator (SQl) wafer, and can be fabricated using conventional MEMS fabrication techniques, such as etching.

The first and second resonant elements are square plate resonators, but it should be apparent that any suitable shape of resonant element can be used. The square plate resonant elements in Figure 1 are each approximately 800pm wide, but it should be apparent that smaller and larger resonant elements may be used, dependent on the sensitivity required and the operating environment.

The first resonant element I is the transduction resonator as it is the first resonant element that is both excited by a drive system and sensed by a sensing system. The second resonant element 2 is the resonator that comes into contact with the sample to be analysed.

In order to make the first and second resonant elements resonate an electrostatic drive system is used. The drive system includes drive electrodes 7 mounted adjacent the first resonant element. In the sensor shown in Figure 1 the electrodes 7 are mounted to oscillate the resonant elements in plane, so that the square plates expand and contract in plane. Other arrangements of the electrodes and other resonant element shapes are possible to excite other modes of oscillation, such as transverse oscillations.

Two resonant modes of interest exist for the arrangement shown in Figure 1: the in-phase square-extensional mode, in which the resonant elements both expand and contract symmetrically in-phase, and the out-of-phase mode in which the two resonant elements vibrate 180 degrees out of phase. The coupling beam 3 is designed to separate the frequency of these two modes sufficiently far apart that one mode can be precisely selected for measurement at a given time. In practice, this means that the coupling beam should ideally have a length of half of the wavelength at the frequency of operation or an integer multiple of half a wavelength. Acceptable performance can be achieved with a beam length that is not exactly an integer multiple of a haH wavelength, so manufacturing tolerances can be readily accommodated, but performance is affected when the beam length is closer to nA/2 + A/4 than to nA/2, where n is an integer and A is the wavelength of operation.

The resonant frequency of the first resonant element in the selected mode is monitored using the piezoresistive effect. The first resonant element is connected to ground at electrode 9 and a predetermined current is applied across it from electrode 8. As the silicon resonant element I expands and contracts its resistance changes. The frequency of oscillation can therefore be monitored by monitoring the voltage at electrode 8.

Other means of monitoring the frequency of oscillation are possible, as is known in the art.

For example, capacitive sensing or optical sensing may be used.

The second resonant element 2 is configured to come into contact with a fluid sample containing a target analyte. The second chamber housing the second resonant element 2 has a microfluidic interface (not shown in Figure 1) allowing fluid samples in and out. The microfluidic interface may include a structure formed on top of the frame 4, having a fluid inlet port and a fluid outlet port. The microfluidic structure may substantially block the opening 6, without interfering with the mechanical performance of the coupling beam 3, so that sample fluids, typically predominantly saline buffer solution, cannot contact the first resonant element or the drive electrodes 7 or sensing electrodes 8, 9, owing to the surface tension of the fluid.

In order to ensure that a target analyte of interest (which may be for example a chemical, a virus or a microorganism) attaches to the second resonant element 2, the second resonant element is at least partially functionalised by a coating of a receptor specific to the target analyte. This is a well known technique in MEMS biochemical sensor technology, and is described for example in US? 141 385, and there are many possible types of receptor coating. The second resonant element may first be coated with a metal layer, such as gold, before attaching specific receptors to the gold layer. A passivation layer, such as a an mPEG (Methoxy Polyethylene glycol) layer, may also be deposited on the second resonant element 2, so that only a portion or portions of the second resonant element are functionalised by the specific receptor.

In order to prevent an aqueous fluid sample in contact with the second resonant element from contacting the first resonant element and the drive and sensing electrodes 7,8,9, the second resonant element may additionally be coated in a hydrophilic coating, such as a thin gold film deposited by thermal evaporation. The first resonant element I and portions of the frame 4, particularly around the opening 6, may be coated with a hydrophobic material such as I H, 1 H,2H,2H-Perfluorodecyltrichlorosilane, which can be self assembled on the surface using vapour deposition. Clearly, the type of coating required depends on the nature of the fluid sample being analysed.

Example drive and sensing arrangements for a sensor as shown in Figure 1, will now be described. Figure 2 is a schematic illustration of an open loop read-out system. In Figure 2, the drive electrodes 7 are driven by an AC voltage from a network analyser tool 20, such as the Agilent 4936B network analyser. A DC voltage, VdC, is superposed on the AC drive voltage Vac. A voltage difference 1d is applied across the first resonant element 1 via electrodes 8 and 9 and the resulting variation in current Im is amplified by a transimpedance amplifier 21 to provide a voltage output signal which can be analysed by the network analyser 20 to compare the frequency response of the system before and after introduction of the fluid sample to the second resonant element 2, as will be described in detail with reference to Figure 6. The frequency of the drive voltage V can be altered to select a particular resonant mode.

Figure 3 illustrates a closed loop drive and sensing arrangement in which a feedback loop is used to maintain the system in one of the resonant modes. The closed loop control system comprises a first stage 30 coupled to the electrode 8, which is a transimpedance amplifier that converts the resonator motional current to a voltage signal. This is followed by further signal amplification in a second gain stage 31. A bandpass filter 32 then removes the unwanted oscillator modes, and the filtered signal is then fed into a comparator 33. The comparator 33 is a hard voltage limiter, which allows for control over the actuation signal amplitude. The output of the comparator 33 is V011 and this voltage is analysed to determine frequency shifts or shifts in phase or Q-factor. The output from comparator 33 is also applied to a single-ended-to-differential drive amplifier 34, which produces two 1800 out-of-phase AC signals for differential capacitive actuation of the resonant element 1. The phase shift in the loop can be tuned in the amplifier cascade, and the feedback gain is controlled using a voltage divider at the comparator output.

It should be clear that the drive and sensing arrangements shown in Figures 2 and 3 are examples only. Different arrangements may be used as required for different types of resonant element and different modes of oscillation. Many different types of resonant elements can be used, such as cantilever elements, as well as different means of driving the resonant elements, different means of sensing the first resonant element and different modes of oscillation. The spatial separation of the resonant element in contact with the target mass from the drive and sensing systems provides advantages in many different sensor configurations.

In many applications it is desirable to have an array of sensors operating simultaneously so that different analytes can be identified and to improve confidence in the detection of analytes. Mass sensors in accordance with the present invention are well suited to implementation and operation in arrays, as they can operate with simple electronic drive and readout. Figure 4 illustrates a linear array 40 of sensor devices of the type shown in Figure 1. The sensors each comprise first and second resonant elements, as described, and are arranged so that the second resonant elements 2 of the sensors are adjacent to one another. This arrangement allows a microfluidic interlace structure 41 to be simply mounted above the second resonant elements 2 to allow fluid samples to be injected into contact with each of the second resonant elements, and subsequently flushed out following completion of measurement. A single electronic controller 24 may be used to drive the resonant elements and to record the frequency, phase or 0-factor measurements from each of the sensors in the array.

Figure 5 illustrates an NxM array of sensors, essentially consisting of M linear arrays of the type shown in Figure 4, all driven from a single electronic controller 51.

Figure 6 is a flow diagram illustrating the steps taken in a method of setting up and operating a mass sensor in accordance with the present invention. In a first step 600 the two resonant elements are coated with the desired coatings. As previously described, the second resonant element is functionalised with receptors for a specific target analyte. The second resonant element may also be coated with a material that attracts the buffer fluid which forms the majority of the fluid sample under test. In the case of a saline buffer solution, the coating would be a hydrophilic material. Similarly, if the buffer fluid is oil, then the coating would be a lipophilic material. The first resonant element, and/or portions of the frame or housing may be coated with a material that repels the buffer fluid.

In step 610, the baseline conditions are established. This means setting up the sensor with the second resonant element 2 in contact with a buffer fluid containing no target analyte so that the resonant frequency of the sensor can be determined in the absence of an analyte attached to the second resonant element, but with all other condition the same as would be during a test of the sample containing the target analyte. In the case of biological detection, this typically means running the sensor with a saline solution in contact with the second resonant element 2. Baseline conditions can be established before or after testing the sample of interest in some instances where there is no permanent attachment of analytes to the second resonant element, but in practice it is convenient to do it beforehand.

In step 620 the electrical drive is activated so that the resonant elements oscillate in a selected resonant mode. In step 630, recording of the frequency response is started. As previously explained, phase and*Q factor may alternatively or additionally recorded as appropriate. It may be a continuous or intermittent recording process. After the frequency response in the absence of a target analyte has been recorded, the sample to be tested is injected into contact with the second resonant element 2 in step 640. The frequency response continues to be recorded and once equilibration is reached with the sample under test, the sample can be flushed from the sensor (i.e. unattached analytes removed from the second resonant element) in step 650 and recording stopped in step 660. In step 670 the recorded frequency response can be analysed to determine if a target analyte attached to the second resonant element, and if so to identify the target analyte or the concentration of target analyte. The process is then at an end.

Arrays of sensors can be used using the same method steps. Different sensors in an array can be used to establish different reference conditions and so allow quantitative analysis to be made.

As described, a sensor in accordance with the present invention may be used to detect a variety of different target analytes and is readily implemented in an array of sensors. It offers the advantage of being simple to manufacture from silicon using known processes, while allowing direct electrical drive and readout, without severely limited voltage constraints. A sensor with spatially separated transduction and sample contact elements also provides increased Q factors over sensors in which the transduction element must be immersed in a buffer solution.

As described, changes in the phase and/or Q-factor of the resonant elements can be measured to provide a measure of the physical properties of an analyte adsorbed on the second resonant element or of a fluid in contact with the second resonant element. As an example, the Q-factor parameter can be used to provide an indication of dissipation of the system1 which provides information about the structural (visco-elastic) properties of the adsorbed layer.

Claims

Claims 1. A sensor for detecting a property of a fluid sample comprising: a first resonant element; a second resonant element coupled to the first resonant element by a mechanical coupling; drive means for oscillating the resonant elements; sensing means for sensing the resonant behaviour of the first resonant element; wherein the sensor is configured to allow the second resonant element to contact the fluid sample, but to substantially isolate the first resonant element from the fluid sample.
2. A sensor according to claim 1, wherein the sensor is configured to isolate the sensing means from the fluid sample.
3. A sensor according to claim I or 2, wherein the sensor is configured to isolate the drive means from the fluid sample.
4. A sensor according to any preceding claim, wherein the property of the fluid sample is the presence of a target analyte in the fluid sample.
5. A sensor according to any preceding claim, wherein the sensor is a microelectromechanical systems (MEMS) device.
6. A sensor according to any preceding claim, wherein the first and second resonant elements are formed from silicon.
7. A sensor according to any preceding claim, wherein the first resonant element, the coupling beam or a porton of a sensor housing, or any combination of these elements, is coated with a material that repels the fluid sample.
8. A sensor according to claim 7, wherein the first resonant element, the coupling beam or a portion of the sensor housing is coated with a hydrophobic material
9. A sensor according to any preceding claim, wherein the second resonant element is coated with a material that attracts the fluid sample.
10. A sensor according to claim 9, wherein the second resonant element is coated with a hydrophilic material.
11. A sensor according to any preceding claim, wherein the first resonant element is held in a first chamber and the second resonant element is held within a second chamber, the first and second chambers connected by an opening through which the mechanical coupling passes, and wherein the dimensions of the openingare small such that aqueous liquids cannot readily pass through the opening.
12. A sensor according to any preceding claim, further comprising a microfluidic structure mounted above, below or around the second resonant element, the microfluidic structure comprising a fluid inlet port and a fluid outlet port.
13. A sensor according to any preceding claim, wherein the first and second resonant elements are oriented such that the first resonant element is above the second resonant element.
14. A sensor according to any preceding claim, wherein the second resonant element is coated with a receptor specific to a target analyte.
15. A sensor according to any preceding claim, wherein the second resonant element is partially coated with a passivation layer.
16. A sensor according to any preceding claim, wherein the mechanical coupling is a beam with a length in the range nA/2 ± £18, where n is an integer and A is the wavelength of oscillation at one of the resonant frequencies of the coupled first and second resonant elements.
17. A sensor according to any preceding claim, wherein the mechanical coupling has a length of substantially half of the wavelength of one of the resonant frequencies of the coupled first and second resonant elements, or an integer multiple thereof.
18. A sensor according to any preceding claim, wherein the drive means comprises one or more electrodes positioned adjacent to the first resonant element.
19. A sensor according to any preceding claim, wherein the sensing means is configured to measure the resistance of the first resonant element.
20. A sensor according to any preceding claim, wherein the sensing means is coupled to the drive means to provide feedback signals to the drive means.
21. A sensor according to any preceding claim, further comprising an electronic controller configured to record the presence of a shift in resonant behaviour and/or the amount of the shift in resonant behaviour of the first resonant element.
22. A sensor according to any preceding claim, further comprising a third resonant element coupled to the first and second resonant elements.
23. A sensor according to any preceding claim, wherein the resonant behaviour comprises one or more of resonant frequency, resonant phase or Q factor
24. An array of sensors, formed as an integral device, comprising a plurality of sensors each according to any one of the preceding claims.
25. A method of detecting a property of a fluid sample using a sensor comprising a first resonant element, a second resonant element coupled to the first resonant element by a mechanical coupling, drive means for oscillating the resonant elements, and sensing means for sensing the oscillation of the first resonant element, comprising the steps of: bringing the fluid sample into contact with the second resonant element but not the first resonant element; measuring a resonant behaviour of the first resonant element; and comparing the measured resonant behaviour with a baseline resonant behaviour measurement to determine a shift in resonant behaviour indicative of a property of the fluid sample.
26. A method according to claim 25, wherein the resonant behaviour comprises one or more of resonant frequency, resonant phase or Q factor.
27. A method according to claim 25 or 26, wherein the property of the fluid sample is the presence of a target analyte in the fluid sample.
28. A method according to claim 27, further comprising the step of recording an amount of the shift in resonant frequency of the first resonant element and comparing the amount with empirical data to provide an indication of an analyte concentration within the fluid sample and/or to identify the mass of the analyte.
29. A method according to any one of claims 25 to 28, further comprising the step of determining a baseline resonant behaviour by operating the sensor with the second resonant element in contact with a control fluid sample of known properties.
30. A method according to any one of claims 25 to 29 further comprising the step of coating the second resonant element with a receptor specific to a target analyte.
31. A method according to any of claims 25 to 30, further comprising the step of partially coating the second resonant element with a passivation layer.
32. A method according to any of claims 25 to 31, further comprising the step of coating the first resonant element and/or the second resonant element and/or a portion of a sensor housing with a material to isolate the first resonant element, the drive means and the sensing means from the fluid sample.
33. A method according to any of claims 25 to 32, further comprising the step of mounting a microfluidic structure above, below or around the second resonant element, the microfluidic structure comprising a fluid inlet port and a fluid outlet port.
34. A method according to any of claims 25 to 32, wherein the step of driving comprises driving the first resonant element electrostatically.
35. A method according to any of claims 25 to 34, wherein the step of measuring a resonant behaviour comprises monitoring the resistance of the first resonant element.
36. A method according to any of claims 25 to 35, further comprising using a plurality of sensors in an array, each sensor comprising a first resonant element, a second resonant element coupled to the first resonant element by a mechanical coupling, drive means for oscillating the resonant elements, and sensing means for sensing the oscillation of the first resonant element.
37. A sensor substantially as described herein with reference to the accompanying drawings.
38. A method of detecting a property of a fluid sample substantially as described herein with reference to the accompanying drawings.