Patent Publication Number: US-2004045979-A1

Title: Particle dispense rate regulator

Description:
[0001] The present invention broadly relates to the dispensing of small quantities of particles to a container or other receptacle. In particular, the present invention relates to a particle dispenser which dispenses particles to a mass measuring device upon the application of mechanical energy to the dispenser.  
       [0002] The present inventors have already proposed in International Patent Application No. PCT/GB00/04220 an apparatus and method for dispensing particles which allows very small masses of particles to be dispensed with high accuracy. The system disclosed in PCT/GB00/04220 is generally similar to that illustrated in FIG. 15 of the accompanying drawings.  
       [0003] The apparatus of PCT/GB00/04220 comprises a particle dispenser  100  containing a quantity of the particles  10  to be dispensed. The particles may be formulations of a pharmaceutical such as Lidocaine having an average diameter of 30 μm, for example. The particles are dispensed to a cassette (receptacle)  20  set on a mass measuring device, such as a balance  30 . The particle dispenser  100  generally has two components; a hopper  110  and a sieve  120  mounted across the bottom cross section  110 . The sieve  120  comprises a plurality of apertures which are each larger than the average particle size of the particles  10 . In the steady state, the particles  10  tend to “clog” the sieve  120  such that they do not pass through it. However, upon the application of mechanical energy to the particle dispenser  100 , the particles are momentarily disturbed and some are able to fall through the plurality of apertures in the sieve  120 . The apparatus is arranged so that these dispensed particles land in the cassette  20 . The term “cassette” should be taken to include all types of container, including containers which may be swallowed whole by the patient for example.  
       [0004] In the apparatus of PCT/GB00/04220, mechanical energy is applied to the particle dispenser  100  by a solenoid  40  which imparts a horizontal force to the side of the hopper  110 . The actuator is controlled by a processor  50  and the processor  50  is in turn connected to the mass measuring device  30 . Thus, closed-loop operation can be obtained by controlling the actuator  40  to tap the particle dispenser  100  so as to dispense particles to the cassette  20  on the mass measuring device  30  until a desired mass of particles has been dispensed.  
       [0005] To achieve dispensing to a very high accuracy, it is necessary to be able to dispense particles at a very low rate. However, using a low dispense rate means that it can take a considerable amount of time to dispense the desired total mass of particles. Thus, it is preferable that dispensing is initiated at a high dispense rate, which dispense rate reduces as the target mass is approached. This allows particles to be dispensed to a high accuracy in a reasonable amount of time.  
       [0006] PCT/GB00/04220 describes two ways of regulating the dispense rate during the dispensing process. Firstly, the intensity of mechanical excitation can be reduced to reduce the dispense rate. For example, if the voltage applied to the solenoid  40  in the accompanying FIG. 15 is reduced, this results in some reduction in the impact energy transmitted to the particle dispenser  100  with a resulting reduction in the number of particles that are dislodged by each actuation. This method is effective over a limited range, but there is a voltage below which little or no powder is delivered and there is a higher voltage above which the amount of powder delivered increases only slightly. Thus, this method of controlling the dispense rate has limitations which it is desired to overcome.  
       [0007] Secondly, the frequency with which the particle dispenser  100  is mechanically excited can be varied. For example, mechanically exciting the particle dispenser  100  half as often results in the apparent time-averaged overall particle dispense rate being reduced to half its previous value. Thus, the time-averaged dispense rate can be reduced by simply waiting for a larger amount of time between successive mechanical actuations. This method has the limitation that reducing the dispense rate in this way does not achieve the goal of increased accuracy. This is because the particles are delivered in discrete “doses” following each mechanical actuation. The final weighing accuracy that can be achieved is no greater than the size of each dose. Controlling the frequency of the mechanical actuator does not change the size of each delivered dose but only the amount of time between successive doses. Thus, to achieve good accuracy, the dose size must be kept small by using a sieve that is found to deliver only a small number of particles for each mechanical actuation. For example, if it is required to dispense particles with a tolerance of +/−10 micrograms, then each dose needs to be less than 20 micrograms. To ensure that all doses are less than 20 micrograms, it is necessary to ensure that the average dose size is about 4 micrograms. This makes it very difficult to dispense relatively large quantities of particles quickly. For example, if the maximum average dose size is 4 micrograms, and the particle dispenser  100  is able to be actuated a maximum of 30 times per second, then the maximum dispense rate of 120 micrograms per second is achievable. At this rate, it would take over one minute to dispense 10 milligrams of particles. If the maximum dose size is increased, then it becomes impossible to deliver the particles to the required accuracy. Thus, changing the frequency does not solve the problem.  
       [0008] Both of the above described dispense rate controlling methods are effective over only a limited range. Further, they have a second disadvantage in that they are not necessarily predictable. The dispense rate achieved is not necessarily linearly proportional to the control parameter (such as the level of solenoid voltage or the frequency of actuation).  
       [0009] The present invention aims to alleviate the above mentioned problems by providing that the effective area through which the particles are dispensed can be actively controlled during a dispense cycle. Thus, the invention allows higher individual doses of particles to be dispensed per actuation at the beginning of a dispense cycle and lower individual doses per actuation to be delivered towards the end of a dispense cycle. This allows relatively large quantities of particles to be dispensed to high accuracy in a small amount of time.  
       [0010] According to a first aspect of the present invention there is provided a particle dispenser for dispensing particles to a mass measuring device, said particle dispenser comprising:  
       [0011] a hopper for holding a supply of particles to be dispensed;  
       [0012] a plurality of apertures through which said particles are to be dispensed, said plurality of apertures having a variable effective area defined as the total area of said apertures through which particles can be dispensed at any given time; and  
       [0013] means for varying said effective area over time to vary the rate at which particles can be dispensed from said hopper through said apertures.  
       [0014] According to a second aspect of the present invention there is provided a method of regulating the rate of dispensing of particles from a particle dispenser, the method comprising:  
       [0015] providing a plurality of apertures for the dispensing of particles from a hopper and then varying the effective area of said plurality of apertures through which particles are being dispensed, said effective area being defined as the total area of said apertures through which particles can be dispensed at any given tine.  
       [0016] The effective area through which the particles are dispensed is preferably varied by moving an adjustment member.  
       [0017] The adjustment member may comprise a substrate at the base of the hopper through which the plurality of apertures are provided. For example, in the context of the FIG. 15 apparatus, the sieve  120  may be moved to one side so as to present fewer apertures to the particles in the hopper  110 .  
       [0018] The adjustment member may alternatively or additionally comprise a masking portion for selectively covering some of the plurality of apertures. In this case, either the masking member itself or the substrate comprising the plurality of apertures may be moved relative to one another so that some of the apertures are masked. This provides that the number of apertures presented to the inside of the hopper can be varied.  
       [0019] The adjustment member may comprise a further substrate comprising a further plurality of apertures movable with respect to the first plurality of apertures so as to selectively line up therewith. Thus, the effective aperture area can be controlled by moving one or both of two substrates, each having the same pattern of apertures, with respect to one another. This allows the number of apertures presented to the inside of the hopper to be accurately controlled. Another advantage is that the effective area of apertures can rapidly be reduced to zero, if the space between adjacent apertures is equal to or greater than the diameter of the apertures themselves. This allows the dispense rate to be reduced very quickly.  
       [0020] The adjustment may be carried out by moving the adjustment member in the horizontal plane, perpendicular to the direction in which the particles move as they are dispensed. This may in practice be carried out by either rotating or translating the adjustment member in this plane.  
       [0021] To ensure predictable and repeatable operation, it is useful to provide that the effective area of the plurality of apertures varies linearly with the amount of movement of the adjustment member. Thus, the dispense rate can be linearly controlled using a signal which is varied linearly.  
       [0022] It is advantageous to decrease smoothly the effective area and therefore also the dispense rate as the target mass is approached. Decreasing the dispense rate increases the tolerance and so a dispense cycle can be set up in which the rate of dispensing is set to be proportional to the amount of mass left to be dispensed. Thus, smaller and smaller doses of particles are delivered upon successive actuations as the target mass is approached. It can therefore be arranged that the present maximum dose size is never larger than the mass to be dispensed plus the tolerance. In such cases, the dispense rate reduces substantially exponentially over time. It is then useful that the effective aperture area varies exponentially in reaction to a linearly time-varying control signal. In this way, the adjustment member can be linearly moved at a constant velocity to achieve a substantially exponential reduction of the dispense rate with time.  
       [0023] To ensure predictability, the apertures are preferably grouped together in a regular pattern.  
       [0024] According to a third aspect of the present invention there is provided a dispensing apparatus comprising the particle dispenser of the above described first aspect of the present invention, a mass measuring device for receiving particles from the particle dispenser and a particle release actuator for causing some of the supply of particles to be dispensed from the particle dispenser. 
     
    
    
     [0025] The present invention will be further described, by way of non-limitative example only, with reference to the accompanying schematic drawings in which:  
     [0026]FIGS. 1A and 1B show a cross-sectional side view and plan view, respectively, of a particle dispenser according to a first embodiment of the present invention when in the fully open state;  
     [0027]FIGS. 2A and 2B show a cross-sectional side view and a plan view, respectively, of a particle dispenser according to the first embodiment of the present invention when in a partially open state;  
     [0028]FIGS. 3A and 3B show a cross-sectional side view and plan view, respectively, of a particle dispenser according to the second embodiment of the present invention when in the fully open state;  
     [0029]FIGS. 4A and 4B shows a cross-sectional side view and a plan view, respectively, of a particle dispenser according to the second embodiment of the present invention when in a fully closed position;  
     [0030]FIGS. 5A and 5B show a cross-sectional side view and plan view, respectively, of a particle dispenser according to a third embodiment of the present invention when in the fully open state;  
     [0031]FIGS. 6A and 6B show a cross-sectional side view and a plan view, respectively, of a particle dispenser according to the third embodiment of the present invention when in a partially open state;  
     [0032]FIGS. 7A and 7B shows a cross-sectional side view and plan view, respectively, of a particle dispenser according to a fourth embodiment of the present invention when in the fully open state;  
     [0033]FIGS. 8A and 8B show a cross-sectional side view and a plan view, respectively, of a particle dispenser according to the fourth embodiment of the present invention when in a partially closed position;  
     [0034]FIGS. 9A and 9B show a cross-sectional side view and plan view, respectively, of a particle dispenser according to a fifth embodiment of the present invention when in the fully open state;  
     [0035]FIGS. 10A and 10B show a cross-sectional side view and a plan view, respectively of a particle dispenser according to the fifth embodiment of the present invention when in a partially closed position;  
     [0036]FIGS. 11A and 11B show a cross-sectional side view and plan view, respectively, of a particle dispenser according to a sixth embodiment of the present invention when in the fully open state;  
     [0037]FIGS. 12A and 12B show a cross-sectional side view and a plan view, respectively of a particle dispenser according to the sixth embodiment of the present invention when in a partially closed position; and  
     [0038]FIGS. 13A and 13B show a cross-sectional side view and plan view, respectively, of a particle dispenser according to a seventh embodiment of the present invention when in the fully open state;  
     [0039]FIGS. 14A and 14B show a cross-sectional side view and a plan view, respectively, of a particle dispenser according to the seventh embodiment of the present invention when in a partially open state;  
     [0040]FIG. 15 shows apparatus for dispensing particles according to the present invention. 
    
    
     [0041] First Embodiment  
     [0042] A first embodiment of the particle dispenser of the present invention is shown in FIGS. 1A, 1B,  2 A and  2 B. In these Figures, and in all of the other Figures showing embodiments of the invention, the particles  10  are not shown for the sale of clarity.  
     [0043] As can be seen from the cross-sectional side views, the particle dispenser comprises a hopper  110  having a generally frusto-conical shape and an open top. The open top allows a fresh supply of particles to be supplied to the hopper. At the base of the hopper, a substrate  121  having a plurality of apertures  122  is provided. The substrate  121  and hopper  110  are relatively movable in the horizontal plane in the left/right direction as shown in FIGS. 1 and 2. It is preferred to keep the hopper  110  stationary and to move the substrate  121  relative to the hopper. Means for supporting and moving the substrate  121  relative to the hopper  110  are not shown also for the sake of clarity, but may for example take the form of a stepper motor or solenoid supported on a frame.  
     [0044]FIGS. 1A and 1B show the state in which all of the apertures  122  are opened to the inside of the hopper. The plurality of apertures have an effective area defined as the total area of the apertures through which particles can be dispensed at any given time. In FIG. 1B, this effective area corresponds to the sum of the area of each of the individual apertures. In this configuration, the maximum possible particle dispense rate may be achieved.  
     [0045]FIGS. 2A and 2B show an arrangement whereby the substrate  121  has been translated to the left so that some of the formerly open apertures  122  are now obscured from the inside of the hopper by the edge of the hopper  110 . In FIG. 2B, only twenty of the fifty-two apertures are now presented to the inside of the hopper. Accordingly, the effective area is the total area of those twenty apertures and the reduction in this effective area ill result in a corresponding reduction in the dose of particles dispensed, when the particle dispenser is mechanically excited. This in turn serves to reduce the time-averaged dispense rate. This embodiment has a number of settings. FIG. 1B shows the most open setting in which all fifty-two of the apertures are presented to the inside of the hopper. The substrate  121  may then be moved so as to obscure the leftmost four apertures and the two outer apertures in the second and third columns. Thus, the number of apertures can be reduced from 52 to 44, and then 36, to 28, to 20, to 14, to 8 and finally to 4. This provides eight settings with which the number of apertures may be approximately linearly reduced, at least initially. More linearity can be achieved by providing less apertures on the substrate  121  or by changing the pattern of holes and the internal shape of the hopper so that the same number of apertures are obscured with each movement of the substrate. Of course, there exists a number of further settings in which some of the apertures are only partially obscured by the edge of the hopper which provides for a smooth transition between one setting and the next.  
     [0046] Second Embodiment  
     [0047]FIGS. 3A, 3B,  4 A and  4 B respectively show the fully open and fully closed position for a second embodiment of the particle dispenser. FIG. 3A shows the hopper  110  which is substantially the same as that shown in FIG. 1. In this embodiment, the substrate  121  comprising the apertures  122  is fixed with respect to the hopper  110 . The adjustment member comprises a masking plate  123  which is arranged to slide linearly across the substrate  121 . In this way, some or all of the plurality of apertures  122  may be blocked so that particles cannot pass therethrough.  
     [0048]FIGS. 4A and 4B show the configuration in which the masking plate  123  blocks all of the apertures  122 . In practice, when dispensing particles, it is preferable not to block all of the apertures because otherwise dispensing cannot be carried out. However, it may be useful to block all of the apertures in periods in which dispensing is not being carried out, for example when the cassette being filled is removed and replaced or in between batches or during periods when the apparatus is switched off.  
     [0049] Third Embodiment  
     [0050]FIGS. 5A, 5B,  6 A and  6 B show a third embodiment of the present invention.  
     [0051] A substrate  121  comprising the apertures  122  is fixed relative to the hopper  110  so the particles can pass from the hopper  100  through the apertures  122 . A second substrate  123  has a second plurality of apertures  124  and is provided adjacent to the first substrate  121  so that it may be translated in the horizontal plane. Moving substrate  123  varies the number of apertures  124  which line up with the static apertures  122 . Thus, the effective area of apertures can be predictably and reliably controlled, resulting in predictable and reliable controlling of the overall dispense rate.  
     [0052] The apparatus of the third embodiment may be operated in a plurality of ways. In a first way, as shown in FIGS. 5A, 5B,  6 A and  6 B, the substrate  123  can be moved so as to selectively line up apertures in the substrate  121  with apertures in the substrate  123 . In this way, the total number of apertures effective for particle dispensing can be varied. In a second way, the substrate  123  can be moved by relatively small amounts so as to partially obscure all of the apertures. In this way, the effective size of all the apertures in substrate  121  can be varied.  
     [0053] Fourth Embodiment  
     [0054]FIGS. 7A, 7B,  8 A and  8 B illustrate a fourth embodiment of the present invention.  
     [0055] In this embodiment, the substrate  121  is provided to rotate relative to the hopper  110  in the horizontal plane. The apertures  122  are provided over approximately half of the area of the substrate  121  which is visible from inside the hopper. A masking substrate  123  is provided adjacent to the rotatable substrate  121  so as to mask approximately half the area which is visible inside the hopper. The effective area of the apertures can be varied by rotating the substrate  121  about the centre line of the hopper so that an increasing proportion of the apertures in the substrate  121  are masked by the masking substrate  123 . Alternatively, the masking substrate  123  may be turned relative to a stationary substrate  121 .  
     [0056] This apparatus has the advantage that the components  121  and  123  are smaller than are required if translation is used to adjust the effective area rather than rotation. However, it has the disadvantage that the whole area at the bottom of the hopper cannot be used to dispense particles. A maximum of half the area can be used for this purpose.  
     [0057] Fifth Embodiment  
     [0058]FIGS. 9A, 9B,  10 A and  10 B illustrate a fifth embodiment of the present invention.  
     [0059] In this embodiment, the substrate  121  having a plurality of apertures  122  is fixed relative to the hopper  110 . A movable masking member  125  is provided inside the hopper and, as can be seen from the top views, it has a substantially semi-circular cross-section. Rotation of the member  125  selectively masks certain of the apertures  122  so as to adjust the effective aperture area.  
     [0060] This embodiment has the advantage that no extra components external to the hopper are required, but has the disadvantage that space in the hopper for particles  10  is taken up by the member  125 .  
     [0061] Sixth Embodiment  
     [0062]FIGS. 11A, 11B,  12 A and  12 B illustrate the sixth embodiment of the present invention.  
     [0063] In this embodiment, two substrates  121  and  123  are provided which are identical in that they both comprise a plurality of apertures having the same configuration. In this embodiment the substrate  121  is fixed relative to the hopper  100  and the substrate  123  is rotatable, relative to the substrate  121  and the hopper  100 , about the centre line of the hopper. In this way, the plurality of apertures  124  can be made to selectively line up with some of the plurality of apertures  122  so as to vary the effective area of the apertures. The area can be varied from fully open, as shown in FIGS. 11A and 11B to a position in which only thirteen of the apertures line up as shown in FIGS. 12A and 12B. There also exists a fully closed position. Different pattens of apertures can provide that there are a plurality of possible settings between fully open and fully closed. Although not shown, it is possible to devise aperture patterns which cover more than 50% of the hopper base area.  
     [0064] It is also to be noted that the substrate  121  could be made movable relative to the substrate  123  and the apparatus would still operate.  
     [0065] Seventh Embodiment  
     [0066] The above embodiments all show particle dispensers in which movement of one of the substrates  121 ,  123 , results in a corresponding generally linear reduction in the effective aperture area present. However, in some cases it may be desirable for this relationship to be non-linear, especially exponential.  
     [0067] An exponential relationship means that a linear movement of the adjustment member results in an exponential reduction in the effective aperture area, for example the effective aperture area could halve for each millimetre that the adjustment member is moved.  
     [0068]FIGS. 13A, 13B,  14 A and  14 B show views similar to FIGS. 1A, 1B,  2 A and  2 B in which the substrate  121  is provided with a plurality of apertures  122  that provide for a substantially non-linear increase in the effective aperture area in response to a linear movement of the substrate  121 . As can be seen, this is achieved by ensuring that the number of revealed apertures increases exponentially as the substrate  121  moves. In the Figures it is possible to reveal either 1, 2, 4, 8, 16 or 32 apertures in total, the number of revealed apertures doubling each time the substrate  121  moves a set distance. The same exponential performance can be achieved by equivalent modification to any of the second to sixth embodiments too.  
     [0069] A preferred dispensing apparatus is shown in FIG. 15. The particle dispenser  100  is constructed substantially as arranged in any of the described embodiments. Means to adjust the effective area of the apertures is provided although not shown in FIG. 13 for clarity. Such means may comprise a linear actuator or stepper motor for example.  
     [0070] The above described embodiments show particle dispensers which allow for continuous variation in the effective area of the apertures. This allows the apparatus of FIG. 15 to be used in an optimal fashion such that high dispense rate, low accuracy dispensing can be used at the start and low dispense rate, high accuracy dispensing can be used near the end of the cycle when accuracy is required. This change of dispense rate can span a considerable range, eg. a ratio of 10:1 is easily obtainable. A further advantage is that the change is highly predictable, since the amount of dose delivered per unit effective aperture area tends to be repeatable. Thus, the control algorithm used in the processor  50  to control the solenoid  40  can make an accurate prediction of the effect on the dispense rate of changing the effective aperture area.  
     [0071] In each of the embodiments above, the particles  10  in hopper  100  may be dislodged by tapping the side of the hopper  100  (as shown in FIG. 15), or alternatively by tapping or vibrating the substrates  121  or  123  themselves. In this latter case, the device which adjusts the effective area of the apertures can be combined with the means for tapping/vibrating the particle dispenser to provide an advantageous use of equipment.  
     [0072] The above embodiments show particle dispensers in which all the apertures  122  or  124  have the same diameter. However, it can be provided that apertures having a range of different diameters are provided together on the same substrate. This helps to mitigate the limitation described above that there is a small window between the minimum possible dispense rate and maximum possible dispense rate when the apertures are static and fixed in size. This arrangement of differently sized apertures extends the window because the larger apertures tend to dispense particles even with very light taps, lowering the minimum dispense rate and the smaller apertures start dispensing at higher tap voltages, increasing the maximum dispense rate. Using differently sized apertures therefore also meets the objective of providing a more controllable particle dispense cycle because it increases the range of dispense rates possible.  
     [0073] A preferred method of dispensing particles will now be described, by way of example only, with reference to FIG. 15. Firstly, the particle dispenser is adjusted to ensure that the maximum possible effective aperture area is presented to the inside of the hopper  100 . The processor  50  then causes the actuator  40  to mechanically agitate the particle dispenser so that a dose of particles falls through the apertures and into the cassette  20 . The dose is weighed by the balance  30  and this weighing signal is relayed to the processor  50 . The processor continues to supply a signal to the actuator  40  until some predetermined mass of particles has been dispensed. The processor then adjusts the particle dispenser to reduce the effective aperture area and thus the dose of particles that will be dispensed upon future taps by the actuator  40 . This allows greater accuracy to be achieved in the final stages of dispensing.  
     [0074] An alternative method comprises continuously adjusting the particle dispenser to reduce the dispense rate in proportion to the total mass of particles dispensed. In this way, an optimum method in which the dose to be dispensed on the next actuation is equal to or smaller than the remaining mass to be dispensed can be achieved.  
     [0075] In the final stages of dispensing, it is useful that the maximum mass of particles in a dose is less than the tolerance value. This can be achieved by arranging that the particle dispenser has a minimum possible deliverable dose less than the tolerance value. Similarly, ensuring that the dispenser has a maximum possible deliverable dose much bigger (eg 5 or 10 times bigger) than the tolerance value is useful to ensure that large doses may be delivered in the early stages of the dispense cycle.