Patent Publication Number: US-10314781-B2

Title: Nebulizer, a control unit for controlling the same, and a method of controlling a nebulizer

Description:
TECHNICAL FIELD OF THE INVENTION 
     The invention relates to a nebulizer that nebulizes a liquid stored therein into fine droplets, for example for inhalation by a user of the nebulizer, and in particular relates to a control unit for a nebulizer and a method of controlling a nebulizer that can detect whether a nebulizing element, such as a mesh or membrane, is positioned correctly in the nebulizer. 
     BACKGROUND TO THE INVENTION 
     Nebulizers, or atomizers as they are sometimes called, are devices that generate a fine spray or aerosol from a liquid. A particularly useful application for nebulizers is to provide a fine spray containing a dissolved or a suspended particulate drug for administration to a patient by inhalation. 
     Piezo-mesh based nebulizers are commonly used to generate aerosols in such drug delivery apparatus, whereby a piezoelectric element vibrates a mesh to produce the fine aerosol spray. In particular, droplets dispensed on the mesh are vibrated by the piezoelectric element to create the spray. In some nebulizers the piezoelectric element is bonded to a mesh element, whereas in other nebulizers the mesh element is separate from (i.e. not in contact with) the piezoelectric element (sometimes referred to as piezo-cavity-mesh based nebulizers). An advantage of having the mesh element separate from the piezoelectric element is that the mesh element can be removed from the nebulizer and cleaned or entirely replaced after a certain amount of use. 
     SUMMARY OF THE INVENTION 
     However, it has been found that the performance of the nebulizer, which can be measured in terms of the droplet generation rate, is very sensitive to the separation between the piezoelectric element and the mesh in the nebulizer. In particular, the size of the liquid cavity between the piezoelectric element and the mesh influences the pressure at the mesh, and thereby the droplet generation rate. 
       FIG. 1  illustrates the pressure generated at a mesh in a nebulizer for various frequencies of vibration for a piezoelectric element and various distances between the piezoelectric element and the mesh (also referred to as water height). Thus, it can be seen that a deviation of just tens of microns (tens of micrometers) from an optimum position can have a significant impact on the pressure at the mesh, and therefore on the droplet generation rate. 
     Therefore, consistent performance of the nebulizer relies on the accurate repositioning of the mesh in the nebulizer after cleaning or replacement. Moreover, if the mesh is not repositioned correctly, the nebulizer may not function at all or components of the nebulizer may be damaged during operation. 
     Thus, there is a need for a control unit for a nebulizer and a method of controlling a nebulizer that can detect whether the mesh has been positioned correctly. 
     According to a first aspect of the invention, there is provided a control unit for controlling the operation of a nebulizer, wherein the control unit is configured to measure the impedance of an actuator in the nebulizer and to determine whether a nebulizing element in the nebulizer is positioned correctly with respect to the actuator on the basis of the measured impedance. 
     In one embodiment, the control unit is configured to determine that the nebulizing element is positioned correctly if the measured impedance of the actuator is equal to or within a predetermined range of a predetermined impedance value. 
     In an alternative embodiment, the control unit is configured to measure the impedance of the actuator when the actuator is operating at first and second frequencies, and to determine that the nebulizing element is positioned correctly if both of the measured impedances are equal to or within a predetermined range of respective predetermined impedance values. This embodiment can prevent false-positive errors in the determination of the position of the nebulizing element. 
     Preferably, the control unit is configured to activate the actuator to nebulize liquid if it is determined that the nebulizing element is positioned correctly in the nebulizer. In this way, the nebulizer will be operated at an optimum or near-optimum droplet generation rate. 
     In one implementation, the control unit is configured to deactivate the actuator if it is determined that the nebulizing element is not positioned correctly. In this way, it is possible to avoid any of the components of the nebulizer being damaged through the incorrect positioning of the nebulizing element. 
     In a further implementation, the control unit is configured to provide an indication to a user of the nebulizer that the nebulizing element needs to be repositioned by the user. 
     According to one embodiment, the control unit is configured to adjust a frequency of vibration of the actuator if it is determined that the nebulizing element is not positioned correctly. 
     According to another embodiment, the control unit is configured to adjust the relative position of the actuator and nebulizing element using a second actuator in the nebulizer if it is determined that the nebulizing element is not positioned correctly. 
     Preferably, the control unit is configured to re-measure the impedance of the actuator after the adjustments described above to determine if operation of the nebulizer can be permitted. 
     In one embodiment, the control unit is configured to measure the impedance of the actuator by applying a sinusoidal voltage with a known amplitude to the actuator and measuring the amplitude of the resulting current and the phase shift between the resulting current and the applied voltage. 
     According to an alternative embodiment, the control unit is configured to measure the impedance of the actuator by measuring the voltage across the actuator and current through the actuator during operation. 
     According to a second aspect of the invention, a nebulizer is provided that comprises a reservoir chamber for storing a liquid to be nebulized; an actuator for vibrating liquid stored in the reservoir chamber; and a control unit as described above. 
     Preferably, the nebulizer further comprises a nebulizing element positioned in the reservoir for nebulizing the liquid when the actuator vibrates the liquid, and, even more preferably, the nebulizing element is removable from the nebulizer. 
     According to a third aspect of the invention, there is provided a method of controlling a nebulizer, the method comprising: 
     measuring the impedance of an actuator in the nebulizer; and 
     determining whether a nebulizing element in the nebulizer is positioned correctly with respect to the actuator on the basis of the measured impedance. 
     In one embodiment, the nebulizing element is determined to be positioned correctly if the measured impedance of the actuator is equal to or within a predetermined range of a predetermined impedance value. 
     In an alternative embodiment, the step of measuring the impedance of the actuator comprises measuring the impedance of the actuator at first and second frequencies, and wherein the step of determining comprises determining that the nebulizing element is positioned correctly if both of the measured impedances are equal to or within a predetermined range of respective predetermined impedance values. 
     Preferably, the method further comprises the step of activating the actuator to nebulize liquid if it is determined that the nebulizing element is positioned correctly in the nebulizer. 
     In one implementation, the method further comprises the step of deactivating the actuator if it is determined that the nebulizing element is not positioned correctly. Preferably, in this implementation, the method further comprises providing an indication to a user of the nebulizer that the nebulizing element needs to be repositioned by the user. 
     In one embodiment, the method further comprises the step of adjusting a frequency of vibration of the actuator if it is determined that the nebulizing element is not positioned correctly. 
     In another embodiment, the method further comprises the step of adjusting the relative position of the actuator and nebulizing element using a second actuator in the nebulizer if it is determined that the nebulizing element is not positioned correctly. 
     Preferably, the method further comprises the step of re-measuring the impedance of the actuator after the step of adjusting. 
     In one embodiment, the step of measuring the impedance of the actuator comprises applying a sinusoidal voltage with a known amplitude to the actuator and measuring the amplitude of the resulting current and the phase shift between the resulting current and the applied voltage. 
     In another embodiment, the step of measuring the impedance of the actuator comprises measuring the voltage across the actuator and current through the actuator during operation. 
     According to a fourth aspect of the invention, there is provided a computer program product comprising a computer readable medium having computer program code embodied therein, the computer program code comprising code that, when executed by a computer or processor, is configured to cause the computer or processor to perform the steps in any of the methods described above. 
     According to a fifth aspect of the invention, there is provided a control unit for controlling the operation of a nebuliser, wherein the control unit is configured to operate the nebuliser at a non-resonant frequency thereof to provide a required or maximum output rate of nebulised liquid.
 
A nebuliser can be provided that comprises a control unit as described in the fifth aspect; a reservoir chamber for storing a liquid to be nebulised; and an actuator for causing liquid stored in the reservoir chamber to be nebulised. The nebuliser may further comprise a nebulising element positioned in the reservoir for nebulising the liquid when the actuator is activated.
 
According to a sixth aspect of the invention, there is provided a method of controlling a nebuliser that comprises operating the nebuliser at a non-resonant frequency thereof to provide a required or maximum output rate of nebulised liquid.
 
In the fifth and sixth aspects of the invention above, it will be appreciated that the resonant frequency of the nebuliser corresponds to the frequency at which maximum power transfer occurs in the nebuliser (i.e. the frequency at which the impedance is a minimum).
 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Exemplary embodiments of the invention will now be described, by way of example only, with reference to the following drawings, in which: 
         FIG. 1  shows the pressure at a mesh for various frequencies of vibration of a piezoelectric element and various distances between the piezoelectric element and the mesh; 
         FIG. 2  is a block diagram of a nebulizer according to an embodiment of the invention; 
         FIGS. 3A  and B are graphs illustrating the variation in droplet generation rate and impedance of a piezoelectric element with changes in the separation between the piezoelectric element and a nebulizing element; 
         FIG. 4  is a graph illustrating how the power applied to a piezoelectric element changes with the peak-to-peak voltage across the piezoelectric element for various distances between the piezoelectric element and a nebulizing element; 
         FIG. 5  is a graph illustrating how the power applied to a piezoelectric element changes with the peak-to-peak voltage across the piezoelectric element for various different platinum meshes that are each positioned in the correct position in the nebulizer; 
         FIGS. 6A-6D  are flow charts illustrating a method of controlling a nebulizer according to an embodiment of the invention; and 
         FIG. 7  is a flow chart illustrating an alternative method of controlling a nebulizer according to an embodiment of the invention. 
     
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     A nebulizer  2  according to an embodiment of the invention is shown in  FIG. 2 . The nebulizer  2  comprises a body  4  having an inlet  6  and an outlet  8  arranged so that when a user of the nebulizer  2  inhales through the outlet  8 , air is drawn into and through the nebulizer  2  via the inlet  6  and outlet  8  and into the user&#39;s body. In some embodiments, the outlet  8  is provided in the form of a mouthpiece or a facial or nasal mask. Alternatively, the outlet  8  can be configured to allow connection to a separate replaceable mouthpiece or facial or nasal mask. 
     A reservoir chamber  10  for storing a liquid  12 , for example a medication or drug, to be nebulized (i.e. to be turned into a fine mist or spray) is provided in the body  4  of the nebulizer  2  between the inlet  6  and outlet  8 . The nebulizer  2  is configured such that fine droplets of the nebulized liquid  12  combine with the air drawn through the nebulizer  2  when the user inhales to deliver a dose of the medication or drug to the user. This operation is illustrated by arrow  13   a  (which represents the air that is drawn into the nebulizer  2  through the inlet  6 ), arrow  13   b  (which represents the liquid nebulized from the reservoir chamber  10 ) and arrow  13   c  (which represents the air containing the nebulized liquid that is drawn out of the nebulizer  2  by the user through the outlet  8 ). 
     An actuator  14  for agitating or vibrating liquid  12  stored in the reservoir chamber  10  is provided in the reservoir chamber  10  along with a nebulizing element  16  for nebulizing the liquid  12  when the liquid  12  is vibrated. The actuator  14  is provided at, or proximate to, the bottom of the reservoir chamber  10 , and the nebulizing element  16  is located in the reservoir chamber  10  above, and spaced from, the actuator  14 . The nebulizing element  16  is spaced from the actuator  14  by a distance h, which is referred to as the ‘water height’ as the liquid  12  fills the reservoir chamber  10  up to the height of the nebulizing element  16 . It will be appreciated that the liquid  12  in the reservoir chamber  10  will be depleted as the nebulizer  2  is operated, and more liquid  12  must be added to the reservoir chamber  10  to maintain the liquid  12  at the height h for the nebulizer  2  to continue operating. Therefore, the nebulizer  2  may comprise, or be coupled to, a further chamber (not shown in  FIG. 2 ) that stores liquid for replenishing the liquid  12  in the reservoir chamber  10 . The liquid from the further chamber may flow into the reservoir chamber  10  due to the action of gravity and capillary filling. 
     In the embodiments of the invention that are described further below, the actuator  14  is provided in the form of a piezoelectric element. However, those skilled in the art of nebulizers will appreciate that other forms of actuator  14  can be used in nebulizers according to the invention. It will also be appreciated that a piezoelectric element  14  can be covered with a plastic or metal cover layer to avoid direct contact between the piezoelectric element and the liquid  12 . 
     In preferred embodiments of the invention, the nebulizing element  16  is in the form of a mesh or membrane having a plurality of small holes through which small amounts of the liquid can pass. In one specific embodiment, the mesh or membrane comprises in the region of 5000 2 μm holes through which droplets of liquid can pass when the actuator  14  is activated. 
     Referring again to  FIG. 2 , the nebulizer  2  further comprises a control unit  18  that includes circuitry for controlling the operation of the nebulizer  2 . In particular, the control unit  18  is connected to the actuator  14  and activates and deactivates the actuator  14 , as required. 
     In some embodiments, the control unit  18  is an integral component of the nebulizer  2  within the body  4  of the nebulizer  2 . However, in alternative embodiments, the control unit  18  can be provided in a unit that is separate to, and even detachable from, the body  4  of the nebulizer  2 . 
     As described above, obtaining consistent performance from a nebulizer  2  relies on the accurate repositioning of the nebulizing element  16  in the nebulizer  2  after cleaning or replacement. Furthermore, if the nebulizing element  16  is not repositioned correctly, the nebulizer  2  may not function at all or components of the nebulizer  2  may be damaged when operation is attempted. Therefore, in accordance with the invention, the control unit  18  is configured to determine whether the nebulizing element  16  is positioned correctly in the nebulizer  2 , and in particular positioned correctly relative to the actuator  14 . 
     As described above,  FIG. 1  illustrates the pressure generated at a nebulizing element  16  in the nebulizer  2  for various frequencies of vibration for the piezoelectric element  14  and various distances between the piezoelectric element  14  and the nebulizing element  16 , and it can be seen that a deviation of just tens of microns (tens of micrometers) from an optimum position can have a significant impact on the pressure at the nebulizing element  16 , and therefore on the droplet generation rate. 
     These results are illustrated in an alternative form in  FIG. 3A  shows the variation in the droplet generation rate with the distance between the piezoelectric element  14  and the nebulizing element  16  for three different frequencies of vibration for the piezoelectric element  14 . 
     It has been found that the impedance of the piezoelectric element  14  in the nebulizer  2  (and more specifically the real part of the complex impedance of the piezoelectric element  14 ) is related to the position of the nebulizing element  16  in the nebulizer  2  relative to the piezoelectric element  14 . These findings are illustrated in the combination of the graphs in  FIGS. 3A  and B, which share the same x-axis. Thus, it can be seen from  FIG. 3B  that the impedance of the piezoelectric element  14  varies with the separation between the piezoelectric element  14  and the nebulizing element  16  (and also with the frequency of operation of the piezoelectric element  14 ). It can also be seen that the impedance of the piezoelectric element  14  has a specific value when the droplet generation rate is optimal (and it will be noted that this impedance value is not a maximum or minimum value for the impedance, but an intermediate value). Therefore, according to the invention, a measurement of the impedance can be used to determine whether the nebulizing element  16  is positioned correctly in the nebulizer  2  (i.e. the nebulizing element  16  is in a position where optimal or near-optimal droplet generation performance is realized). 
     It will also be appreciated that the minimum value for the impedance occurs when the nebuliser  2  (particularly the reservoir chamber  10 , piezoelectric element  14  and nebulising element  16 ) is in resonance, which occurs at a specific frequency where maximum energy is transferred (i.e. the power is at a maximum). Thus, it can be seen from  FIGS. 3( a ) and ( b )  that the optimal droplet generation rate corresponds to an intermediate value for the impedance, and therefore the optimal droplet generation rate is achieved by operating the nebuliser  2  at a frequency other than the resonant frequency (and thus where the impedance is not at a minimum and the power is not at a maximum). 
     In addition, it has been found that the optimal impedance value for the piezoelectric element  14  (i.e. the impedance value for the piezoelectric element  14  that corresponds to the correct positioning of the nebulizing element  16  in the nebulizer  2  relative to the piezoelectric element  14 ) is nebulizing element-specific, i.e. it varies for different types and/or configurations of nebulizing element  16 . In this respect, the different types and/or configurations can relate to the material used to make the nebulizing element  16 , the thickness of the nebulizing element  16  and the number and/or size of the holes in the nebulizing element  16 . In some embodiments of the invention, the control unit  18  can be programmed with the appropriate impedance value for the nebulizing element  16  by a user of the nebulizer  2 , or the control unit  18  can automatically obtain the information from an electronic data chip (not shown in  FIG. 2 ) associated with the particular liquid (i.e. medication) in the reservoir chamber  10  and/or nebulizing element  16  (for example as used in the currently available Philips Respironics I-neb nebulizer). 
     The graph in  FIG. 4  illustrates how the power (in Watts) applied to the piezoelectric element  14  changes with the peak-to-peak voltage (Vpp) across the piezoelectric element  14  for various distances between the piezoelectric element  14  and a platinum mesh having a particular thickness that is used as the nebulizing element  16 . 
     In theory, for a voltage-independent impedance, the relation between power and voltage should be a quadratic function completely determined by the real part of the impedance. Experimentally, as shown in  FIG. 4 , quadratic relations are observed, from which impedance values between 130Ω and 500Ω were determined. Thus,  FIG. 4  illustrates how the impedance of the piezoelectric element  14  depends on the distance between the piezoelectric element  14  and the platinum mesh  16 . 
     The graph in  FIG. 5  illustrates how the power (in Watts) applied to the piezoelectric element  14  changes with the peak-to-peak voltage (Vpp) across the piezoelectric element  14  for various (fifteen) different platinum meshes that are each positioned in the correct (optimal) position, or near optimal position, in the nebulizer  2 . Thus, it can be seen from  FIG. 5  that for maximum (or near-maximum) droplet generation for these platinum meshes, the impedance of the piezoelectric element  14  is a value at or around 310Ω. 
     As described above, the optimal impedance value for a particular nebulizing element  16  depends on the composition of the nebulizing element  16 . For example, it has been found that meshes made of nickel-palladium (NiPd) exhibit similar behavior to the platinum meshes described above, but the optimum impedance value for those meshes was found to be 600Ω. 
     In general, the optimal impedance value for a particular nebulizing element  16  will be determined through testing prior to any use of that type of nebulizing element  16  in a nebulizer  2 . Once an optimal impedance value has been determined, the value will be applicable to all other meshes produced from the same material and having the same geometry. 
     The operation of the control unit  18  in accordance with the invention will be described in more detail below with reference to  FIGS. 6A-6D . The method described below can be initiated by the control unit  18  when a nebulizing element  16  is first positioned in the nebulizer  2 , when a user tries to use the nebulizer  2  and/or during use of the nebulizer  2 . 
     Firstly, referring to  FIG. 6A , the operation according to the invention begins in step  101  in which the impedance of the piezoelectric element  14  in the nebulizer  2  is measured by the control unit  18 . In particular, the control unit  18  measures the real part of the complex impedance of the piezoelectric element  14 . It will be appreciated that this measurement is performed while liquid  12  is present in the reservoir chamber  10 . 
     It will be appreciated that step  101  can be performed by the control unit  18  before the nebulizer  2  is activated (i.e. before sufficient current is provided to the piezoelectric element  14  to cause the liquid  12  to be nebulized), or during operation of the nebulizer  2  (i.e. when the piezoelectric element  14  is causing the liquid  12  to be nebulized). 
     In the first instance, the control unit  18  can apply a small sinusoidal voltage having a known amplitude V amp  to the piezoelectric element  14  (the voltage being small in the sense that it is below the voltage required to cause the piezoelectric element  14  to nebulize the liquid  12 ) and measure the resulting current I amp  and the phase shift φ amp  between the applied voltage signal and the resulting current signal. 
     The control unit  18  can then calculate the real part of the impedance of the piezoelectric element  14  using: 
     
       
         
           
             
               
                 
                   
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     Alternatively, in the second instance described above (i.e. measuring the impedance during operation of the nebulizer  2 ), the control unit  18  can determine the impedance during operation for arbitrary driving signals. In this case, the control unit  18  determines the real part of the impedance of the piezoelectric element  14  from the voltage applied to the element  14  over time, V(t), and the measured current through the element  14  over time, I(t), using: 
     
       
         
           
             
               
                 
                   
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     Once the impedance of the piezoelectric element  14  has been measured, the control unit  18  then uses the measured impedance value to determine whether the nebulizing element  16  is positioned correctly in the nebulizer  2  (step  103 ). Following an analysis such as that illustrated in  FIG. 5  above, an optimal impedance value for the nebulizing element  16  that results in optimal or near-optimal droplet generation performance will be known before the nebulizing element  16  is positioned in the nebulizer  2 . Therefore, in step  103  the control unit  18  can compare the measured impedance value to the known optimal impedance value to determine whether the nebulizing element  16  is positioned correctly in the nebulizer  2 . 
     In one embodiment, the control unit  18  can determine that the nebulizing element  16  is positioned correctly if the measured impedance value is within a predetermined range of the optimal impedance value. It will be appreciated that the predetermined range can be specified in terms of being within a particular percentage value of the optimal impedance value (i.e. the measured impedance must be within, for example, 1%, 5% or 10% of the optimal impedance value for the control unit  18  to determine that the nebulizing element  16  is positioned correctly), or in terms of a particular range of impedance values around the optimal impedance value (i.e. for the platinum mesh described above, the predetermined range for determining correct positioning can be, for example, between 280Ω and 340Ω). 
     If the control unit  18  determines that the nebulizing element  16  is positioned correctly in the nebulizer  2  (steps  103  and  105 ) then the control unit  18  can initiate (or continue) operation of the nebulizer  2  by supplying a sufficient voltage signal to the piezoelectric element  14  (step  107 ). The control unit  18  allows operation of the nebulizer  2  until the user stops breathing through the nebulizer  2  or the required dosage of the medication or drug in the liquid has been nebulized. 
     If the control unit  18  determines that the nebulizing element  16  is not positioned correctly in the nebulizer  2  on the basis of the measured impedance (steps  103  and  105 ) then the control unit  18  takes further action, as described in more detail below. 
     In one implementation of the nebulizer  2 , as illustrated in  FIG. 6B , on determining that the nebulizing element  16  is not positioned correctly, the control unit  18  prevents or ceases operation of the nebulizer  2  (i.e. by not providing a voltage signal to the piezoelectric element  14 ), in order to prevent sub-optimal droplet generation performance, and to avoid any possible damage to the components of the nebulizer  2  (step  109 ). 
     The control unit  18  can then notify the user of the nebulizer  2  that the nebulizing element  16  is positioned incorrectly and needs to be repositioned before the nebulizer  2  can be operated properly. The control unit  18  may notify the user of this in any conventional manner, for example by initiating an audible alarm, warning signal or spoken message, and/or by providing a visual indication such as a warning light or LED, or by providing a written message or symbol on a display of the nebulizer  2  (not shown in  FIG. 2 ). 
     If the user repositions the nebulizing element  16  in the nebulizer  2 , the control unit  18  can return to step  101  and repeat the measurement of the impedance of the piezoelectric element  14 . If that measurement indicates that the nebulizing element  14  is positioned correctly in the nebulizer  2 , then the control unit  18  can initiate the operation of the nebulizer  2  as shown in step  107 . 
     In an alternative implementation of the nebulizer  2 , as illustrated in  FIG. 6C , on determining that the nebulizing element  16  is not positioned correctly, the control unit  18  can adjust the voltage signal applied to the piezoelectric element  14  to change the frequency of vibration of the piezoelectric element  14 , thereby improving the performance of the nebulizer  2  (step  113 ). In particular, as demonstrated by the graphs in  FIGS. 1 and 3 , as there is a correlation between the distance between the piezoelectric element  14  and the nebulizing element  16  (the water height) and the frequency at which the piezoelectric element  14  is vibrating, small deviations of the water height from the optimal value can be compensated by the control unit  18  adjusting the frequency of vibration of the piezoelectric element  14 . 
     In one embodiment, the control unit  18  can adjust the frequency of vibration of the piezoelectric element  14  by an amount determined using the measured impedance value and a look-up table. In an alternative embodiment, the control unit  18  can adjust the frequency of vibration of the piezoelectric element  14  by an amount based on the magnitude of the difference between the measured impedance value and the optimal impedance value. In an another alternative embodiment, the control unit  18  can adjust the frequency of vibration of the piezoelectric element  14  by a fixed amount, regardless of the difference between the measured impedance value and the optimal value. 
     In the embodiments described in the paragraph above, the control unit  18  can then return to step  101  and re-measure the impedance of the piezoelectric element  14  to determine if operation of the nebulizer  2  can be permitted. If not, the control unit  18  can loop through steps  101 ,  103 ,  105  and  113  until the droplet generation performance of the nebulizer  2  reaches an acceptable value. 
     In one embodiment, since the frequency of vibration of the piezoelectric element  14  has changed, it is possible for the re-measuring step described to use a modified optimal impedance value. In the embodiment where a look-up table is used, it is possible for the look-up table to contain data corresponding to that shown in  FIGS. 3A and 3B , which means that the control unit  18  uses the measured impedance to look up (i) the actual separation between the piezoelectric element  14  and nebulizing element  16 , (ii) the optimal driving frequency, and (iii) the corresponding modified optimal impedance. 
     In some embodiments, if the control unit  18  determines that the adjustment of the frequency of vibration of the piezoelectric element  14  will not provide an acceptable droplet generation performance (for example based on the difference between the measured impedance value and the optimal impedance value exceeding a threshold or following one or more loops of steps  101 ,  103 ,  105  and  113  that do not result in the required performance being achieved), the control unit can then perform steps  109  and  111  and notify the user of the nebulizer  2  that the nebulizing element  16  needs to be manually repositioned in the nebulizer  2 . 
     In yet another alternative implementation of the nebulizer  2 , as illustrated in  FIG. 6D , the control unit  18  can itself adjust the position of the nebulizing element  16  in the nebulizer  2  if it determines that the nebulizing element  16  is not positioned correctly in the nebulizer  2 . In this embodiment the nebulizer  2  is provided with a further actuator that can be used to adjust the relative positions of the nebulizing element  16  and piezoelectric element  14  in the nebulizer  2 . Preferably, the further actuator is configured to move the nebulizing element  16  in the nebulizer  2  under the control of the control unit  18 , but it will be appreciated that in alternative implementations the further actuator can be used to move the piezoelectric element  14  instead. Those skilled in the art will be aware of suitable actuators that can be provided in a nebulizer  2  for moving the nebulizing element  16  or piezoelectric element  14 , and therefore further details will not be provided herein. 
     On determining that the nebulizing element  16  is not positioned correctly, the control unit  18  can control the further actuator to adjust the relative position of the nebulizing element  16  relative to the piezoelectric element  14  (i.e. by moving the nebulizing element  16  closer to or further away from the piezoelectric element  14 ), thereby causing the impedance of the piezoelectric element  14  to approach the optimal impedance value and improving the performance of the nebulizer  2  (step  115  of  FIG. 6D ). 
     In one embodiment, the control unit  18  can control the further actuator to adjust the position of the nebulizing element  16  by an amount based on the magnitude of the difference between the measured impedance value and the optimal impedance value. In an alternative embodiment, the control unit  18  can control the further actuator to adjust the position of the nebulizing element  16  by a fixed amount, regardless of the difference between the measured impedance value and the optimal value. 
     In both embodiments described in the paragraph above, the control unit  18  can then return to step  101  and re-measure the impedance of the piezoelectric element  14  to determine if operation of the nebulizer  2  can be permitted. If not, the control unit  18  can loop through steps  101 ,  103 ,  105  and  115  until the droplet generation performance of the nebulizer  2  reaches an acceptable value. 
     In some embodiments, if the control unit  18  determines that the adjustment of the position of the nebulizing element  16  will not provide an acceptable droplet generation performance (for example based on the difference between the measured impedance value and the optimal impedance value exceeding a threshold or following one or more loops of steps  101 ,  103 ,  105  and  115  that do not result in the required performance being achieved), the control unit can then perform steps  109  and  111  and notify the user of the nebulizer  2  that the nebulizing element  16  needs to be manually repositioned in the nebulizer  2 . 
     It will also be appreciated that a control unit  18  can be provided that can implement both of the embodiments shown in  FIGS. 6C and 6D . In this case, when the control unit  18  determines that the nebulizing element  16  is not positioned correctly in the nebulizer  2 , the control unit  18  can adjust both the frequency of vibration of the piezoelectric element  14  and the position of the nebulizing element  16  in the nebulizer  2  in order to improve the droplet generation performance of the nebulizer  2 . 
     Referring again to  FIG. 3B , it will be noted that the maximum droplet generation rate for a piezoelectric element  14  operating at a frequency f is obtained with a separation of h f , and the piezoelectric element  14  has an impedance Z f . As described in the embodiments above, it is possible to determine whether the nebulizing element  16  is positioned correctly by measuring the impedance of the piezoelectric element  14  and comparing it to the optimal value (i.e. Z f ). However, it will be noted from  FIG. 3B  that the ‘optimal’ impedance value Z f  actually corresponds to two possible distances, h f  and h f ′, between the piezoelectric element  14  and nebulizing element  16 . 
     Now, it may be that the second possible distance h f ′ cannot occur in the nebulizer  2  (for example h f ′ may be greater than the dimensions of the reservoir chamber  10 ) in which case the possibility that the nebulizing element  16  and piezoelectric element  14  are separated by this distance (h f ′) can be ignored in the implementation of the method illustrated in  FIG. 6A . 
     However, it is also possible that the second possible distance h f ′ can occur, in which case executing the method shown in  FIG. 6A  could result in a false-positive result (i.e. the control unit  18  may determine that the nebulizing element  16  is positioned correctly, when it is not). Therefore, an alternative method of operating a nebulizer  2  is presented in  FIG. 7 . 
     In step  201 , the piezoelectric element  14  is operated at a first frequency of vibration. In some cases, this may be frequency f, i.e. the frequency at which the best droplet generation performance is obtained (note the different maximum droplet generation rates for the different frequencies of vibration in  FIG. 3A ). 
     Then, in step  203 , the impedance of the piezoelectric element  14  is measured. This measurement step can be carried out in the same way as step  101  in  FIG. 6A . 
     The control unit  18  then determines whether the measured impedance is equal to or within a predetermined range of a desired impedance value for the first frequency f (i.e. Z f ) in step  205 . If not, the control unit  18  can proceed as shown in any of  FIGS. 6B, 6C and 6D  described above, with the process returning to step  201  if the impedance needs to be remeasured. 
     If the measured impedance is equal to or close to the desired impedance value Z f , the control unit  18  operates the piezoelectric element  14  at a second frequency of vibration different to the first frequency (step  207 ), for example f+Δf or f−Δf shown in  FIGS. 3A and 3B  and re-measures the impedance of the piezoelectric element  14  (step  209 ). In one embodiment, the second frequency can differ from the first frequency by around 0.2%, although it will be appreciated the smaller and larger frequency differences can be used. 
     In step  211 , the control unit  18  determines whether the impedance value measured in step  209  is equal to or within a predetermined range of an impedance value appropriate for the second frequency and the separation h f . For example, if the second frequency is f+Δf, the control unit  18  determines whether the impedance value measured in step  209  is equal to or within a predetermined range of Z f+Δf . 
     If the impedance value measured in step  209  is within the predetermined range of the impedance value appropriate for the second frequency and separation h f , the control unit  18  can initiate or continue operation of the nebulizer  2  (step  213 ). If not, the control unit  18  can proceed as shown in any of  FIGS. 6B, 6C and 6D  described above, with the process returning to step  201  if the impedance needs to be remeasured. 
     Those skilled in the art will appreciate that it is possible to implement variations of the method shown in  FIG. 7 . For example, the measurements of the impedances at both of the operating frequencies (steps  203  and  207  in  FIG. 7 ) can be carried out before any comparison with the respective predetermined impedance values (steps  205  and  211  in  FIG. 7 ). 
     There is therefore provided a control unit for a nebulizer and a method of controlling a nebulizer that can detect whether the nebulizing element has been positioned correctly. In addition, specific embodiments of the invention provide a control unit and method that can improve the performance of the nebulizer in the event that it is determined that the nebulizing element has not been positioned correctly. 
     It will also be appreciated that, in addition to the control unit described above, the invention can be provided in the form of a computer program carried on a computer readable medium that is configured to cause a processor in a control unit for a nebulizer to execute the steps shown in  FIG. 6A  and any of  FIGS. 6B-6D . 
     Those skilled in the art will appreciate that the word “nebulizer” can be used interchangeably with the term drug delivery apparatus or atomizer, and the use of the word “nebulizer” is intended to cover forms and designs of nebulizer other than the specific type of nebulizer described above and illustrated in the Figures. 
     While the invention has been illustrated and described in detail in the drawings and foregoing description, such illustration and description are to be considered illustrative or exemplary and not restrictive; the invention is not limited to the disclosed embodiments. 
     Variations to the disclosed embodiments can be understood and effected by those skilled in the art in practicing the claimed invention, from a study of the drawings, the disclosure and the appended claims. In the claims, the word “comprising” does not exclude other elements or steps, and the indefinite article “a” or “an” does not exclude a plurality. A single processor or other unit may fulfill the functions of several items recited in the claims. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage. A computer program may be stored/distributed on a suitable medium, such as an optical storage medium or a solid-state medium supplied together with or as part of other hardware, but may also be distributed in other forms, such as via the Internet or other wired or wireless telecommunication systems. Any reference signs in the claims should not be construed as limiting the scope.