METHOD FOR CALIBRATING A PERISTALTIC PUMP, METHOD FOR DISPENSING A QUANTITY OF LIQUID BY MEANS OF A PERISTALTIC PUMP AND DEVICE FOR PRODUCING STERILE PREPARATIONS THAT CAN EXECUTE SAID METHODS

Abstract

A method is for calibrating a peristaltic pump, and for dispensing a quantity of liquid by a peristaltic pump. A device for producing sterile preparations that can execute the methods.

Claims

1. Method for calibrating a peristaltic pump in order to determine a calibrated volume per pumping cycle of said pump, said pump being associated with a hydraulic circuit, comprising the following steps: pumping a quantity of liquid from a source vessel into a calibration vessel by a plurality of pumping cycles of the peristaltic pump, measuring the amount quantity of liquid pumped into the calibration vessel, determining the calibrated volume per pumping cycle of the peristaltic pump, said calibrated volume per pumping cycle being a function of the measured quantity of liquid, said number of pumping cycles and at least one correction coefficient previously stored in a memory of a control device of said pump.

2. Method according to claim 1, wherein the calibration vessel is a variable-volume vessel with a plunger.

3. Method according to claim 1, wherein said at least one correction coefficient is determined by empirical tests and a corresponding statistical analysis thereof.

4. Method according to claim 1, wherein said at least one correction coefficient comprises a coefficient for correcting the expansion of the hydraulic circuit during calibration.

5. Method according to claim 1, wherein said at least one correction coefficient comprises a coefficient for correcting filling resistance of the calibration vessel.

6. Method according to claim 1, wherein said at least one correction coefficient comprises a coefficient for correcting a speed difference between calibration and operation.

7. Method according to claim 6, wherein speed correction coefficient is a ratio of a coefficient that is a function of the pump calibration speed and a coefficient that is a function of pump operating speed.

8. Method according to claim 1, further comprising a step of reusing the liquid injected into the calibration vessel by returning the liquid from the calibration vessel to the hydraulic circuit.

9. Method for dispensing a determined quantity of liquid by a peristaltic pump, said pump being associated with a hydraulic circuit, the method comprising the following steps: calculating the volume per pumping cycle of the peristaltic pump at the operating speed thereof according to claim 6, starting to dispense liquid by the peristaltic pump, counting the number of pumping cycles completed while dispensing is being carried out, determining the pumped volume based on the volume per actual pumping cycle at the dispensing speed and the number of pumping cycles completed, halting the supply of liquid when the pumped volume determined in the previous point reaches a determined quantity of liquid.

10. Method according to claim 9, wherein dispensing is carried out at constant pump speed.

11. Method according to claim 9, wherein dispensing is carried out at variable pump speed.

12. Method according to claim 11, wherein the speed of the pump during dispensing depends on the pressure in the hydraulic circuit downstream of the pump.

13. Method according to claim 9, wherein the method further considers the dead volume of the hydraulic circuit.

14. Device for producing sterile preparations comprising a peristaltic pump and a control device of said peristaltic pump and said device, characterised in that said control device is configured to perform a method for calibrating said peristaltic pump according to claim 1.

15. Device according to claim 14, comprising at least a source vessel, a calibration vessel, a fluid distributor and a dispensing vessel, forming a hydraulic circuit together with the peristaltic pump.

16. Device according to claim 15, wherein the calibration vessel is a variable-volume vessel with a plunger.

17. Device according to claim 16, wherein said plunger is driven by an automatic driver.

18. Device according to claim 14, wherein said control device is configured to execute a dispensing method comprising the following steps: calculating the volume per pumping cycle of the peristaltic pump at the operating speed thereof, wherein said at least one correction coefficient comprises a coefficient for correcting a speed difference between calibration and operation; starting to dispense liquid by the peristaltic pump; counting the number of pumping cycles completed while dispensing is being carried out; determining the pumped volume based on the volume per actual pumping cycle at the dispensing speed and the number of pumping cycles completed; halting the supply of liquid when the pumped volume determined in the previous point reaches a determined quantity of liquid.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0040] A series of drawings representing at least one embodiment of the method for calibrating a peristaltic pump, the method for dispensing liquid and the device for producing sterile preparations object of the present invention are appended to ensure better understanding through explanatory but not limiting examples.

[0041] FIG. 1 is a flowchart of a first exemplary embodiment of a method for calibrating a peristaltic pump according to the present invention.

[0042] FIG. 2 is a flowchart of a second exemplary embodiment of a method for calibrating a peristaltic pump according to the present invention.

[0043] FIG. 3 is a flowchart of the calculation of the calibrated volume per pumping cycle of the peristaltic pump according to an exemplary embodiment of the present invention.

[0044] FIG. 4 is a graph showing the variation of the coefficient for correcting the speed difference between calibration and operation of an exemplary embodiment according to the present invention.

[0045] FIG. 5 is a flowchart of an exemplary embodiment of a method for dispensing a quantity of liquid according to the present invention.

[0046] FIG. 6 is a front elevation view of an exemplary embodiment of a device for producing sterile preparations according to the present invention.

[0047] FIG. 7 is a front elevation view of the device of FIG. 6 with an example of a disposable kit for producing sterile preparations.

[0048] FIG. 8 is a cross-section view of the peristaltic pump of the device of FIG. 6 and FIG. 7.

[0049] In the figures, the same or equivalent elements have been identified with identical numerals.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0050] FIG. 1 shows a flowchart of a first exemplary embodiment of a method for calibrating a peristaltic pump according to the present invention. The first step 1000 of this first embodiment comprises pumping a quantity of liquid from a source vessel to a calibration vessel by means of a number of pumping cycles of the peristaltic pump.

[0051] The second step 2000 of this first exemplary embodiment comprises measuring the quantity of liquid pumped into the calibration vessel. Although in this first exemplary embodiment said measurement is by volume, i.e. measuring the volume of liquid contained in the calibration vessel, in other embodiments said measurement can also be by mass, i.e. measuring the mass of the fluid contained therein.

[0052] The third step 3000 of the first exemplary embodiment comprises determining the calibrated volume per pumping cycle of the peristaltic pump, i.e. determining the actual volume supplied by the pump for each pumping cycle thereof. In embodiments in which, in the second step 2000 the measurement is by mass, the parameter that is determined in the third step 3000 is the calibrated mass per pumping cycle of the peristaltic pump, i.e. the mass of fluid supplied by the pump for each pumping cycle of the pump.

[0053] Said calibrated volume, or mass, per pumping cycle is a function of the quantity of liquid measured in the second step 2000, of the number of pumping cycles completed in the first step 1000 for pumping said quantity of liquid, and of at least one correction coefficient previously stored in a memory of a control device of the peristaltic pump. Said at least one correction coefficient is described more clearly in FIG. 3 and can be determined by empirical tests and a corresponding statistical analysis thereof. It is important to mention that said empirical tests and the corresponding statistical analysis are performed prior to the calibration process, i.e. they are not determined during the pump calibration process, as is the case in the known prior art.

[0054] In this first exemplary embodiment, the pumping cycle is understood to be 1/n of a complete revolution of the rotor of the peristaltic pump, where n is an integer representing the number of rollers of the rotor of the pump. However, in other embodiments the pumping cycle can be a complete revolution of said rotor.

[0055] FIG. 2 shows a flowchart of a second exemplary embodiment of a method for calibrating a peristaltic pump according to the present invention. Said second embodiment is essentially like the first one described above, see FIG. 1, with the difference that it comprises a fourth step 4000 that includes returning the liquid contained in the calibration vessel after the completion of the third step 3000 to the hydraulic circuit associated with the peristaltic pump, thus making it possible to reuse the fluid used to calibrate the pump in the productive process, for example, filling bags or vials. This fourth step, although optional, has important economic advantages, especially when the working fluid is expensive, since it avoids wasting fluid during the calibration of the pump.

[0056] The calibration vessel is preferably a variable-volume vessel with a plunger, such as a syringe. In this type of embodiments, the fourth step 4000, if carried out, can be performed by pushing the plunger so that the fluid stored therein is forced out of it and back into the hydraulic circuit associated with the pump. Although the plunger can be driven manually, it is preferably driven by automatic operating means, such as a robotic arm, a piston, etc. In the case that the used pump is reversible, it is also possible to carry out the fourth step 4000 by reversing the direction of rotation of the pump, so that it sucks up the liquid contained in the calibration vessel.

[0057] FIG. 3 shows a flowchart of the calculation of the calibrated volume per pumping cycle of the peristaltic pump according to the present invention. This figure shows three different correction coefficients k, dv, Kv that can be applied in the third step 3000 to determine the calibrated volume, or mass, per pumping cycle of the peristaltic pump.

[0058] The coefficient k can correct the filling resistance of the calibration vessel. Said coefficient k is especially important when the calibration vessel and the dispensing vessel are not the same. For example, when the calibration vessel is a syringe and the dispensing vessel, the vessel into which the final dosage is supplied, is a vial or a bag. In the case that the calibration vessel is, for example, a syringe, as the fluid fills it, it has to overcome the resistance exerted by the plunger and, if it has any, its automatic means of operation.

[0059] The coefficient dv corrects the possible expansion of the hydraulic circuit during calibration.

[0060] After numerous empirical tests and analyses of the results obtained, the applicant has determined that a particularly preferred calibration setting for similar pump speeds during calibration and operation according to the present invention can have the following form:

[00001]$D=k\frac{N}{\left(S.Math.V+d.Math.v\right)}$

[0061] where D is the dose, i.e. the volume or mass per pumping cycle of the pump, k is the coefficient for correcting the filling resistance, N is the number of pumping cycles, SV is the quantity of liquid measured in the calibration vessel and dv is the coefficient for correcting the possible expansion of the hydraulic circuit during the start of dispensing into the calibration vessel.

[0062] According to the present invention, a coefficient Kv can be used to correct the speed difference between pump calibration and operation. The first step 1000 of the calibration method of the present invention is usually carried out at a determined rotation speed of the pump. Said rotation speed during calibration, or simply, the calibration speed, is usually different from the rotation speed of the pump during the operation thereof, or simply, the operating speed.

[0063] Thus, the relationship between the volume to be dispensed at the operating speed and the speed correction coefficient Kv can be, for example, as follows:

N=VolDKv

[0064] where N is the number of pumping cycles, Vol is the volume to be dispensed, D is the dose per pumping cycle of the pump and Kv is the speed correction coefficient.

[0065] According to the present invention, the coefficient Kv can be expressed, preferably, as the ratio of two different correction coefficients, Kv.sub.cal and Kv.sub.op. Kv.sub.cal refers to the pump calibration speed and Kv.sub.op refers to the pump operating speed. Consequently, the above equation can be expressed as follows:

[00002]$N=V.Math.o.Math.lD\frac{K.Math.v_{\mathrm{cal}}}{K.Math.v_{o.Math.p}}$

[0066] FIG. 4 shows in a graph the variation of the coefficient for correcting the speed difference between calibration and operation of an exemplary embodiment according to the present invention. In this graph, the abscissa axis shows the dispensing speed of the peristaltic pump and the ordinate axis shows the value of the speed correction coefficient Kv. The dispensing speed is shown in counts per second of the rotary encoder. This graph is obtained empirically for each device and the values and/or equations obtained are stored as a table or as an equation in the memory of the control device of the device that is the subject matter of the present invention, ready to be used during operation. As can be seen, in the embodiment shown, the value of Kv initially drops slightly below 1, and then increases its value as the dispensing speed increases, until it reaches a point where its value stabilises and practically does not vary even if the dispensing speed continues to increase.

[0067] In the graph of FIG. 4, Kv is defined as follows:

[00003]$K.Math.v=\frac{K.Math.v_{\mathrm{cal}}}{K.Math.v_{o.Math.p}}$

[0068] FIG. 5 shows a flowchart of an exemplary embodiment of a method for dispensing a determined quantity of liquid by means of a peristaltic pump according to the present invention. The first step 10000 of this embodiment comprises calculating the volume, or mass, per pumping cycle of the peristaltic pump at the operating speed thereof according to the calibration method described above. The second step 20000 comprises the start of dispensing liquid by the peristaltic pump. The third step 30000 includes counting the number of pumping cycles completed while the fluid is being dispensed, i.e. while the second step 20000 is being carried out. According to the foregoing, the second 20000 and third 30000 steps of the dispensing method of the present invention are preferably carried out simultaneously. The fourth step 40000 comprises determining the pumped volume by volume, or mass, per actual pumping cycle at dispensing speed and the number of pumping cycles completed. The fifth step S0000 includes halting the supply of liquid when the volume determined in the fourth step 40000 reaches a determined quantity of liquid, said quantity being the quantity to be dispensed.

[0069] In embodiments in which the rotor of the pump is associated with a rotary encoder that measures the angular position thereof, the continuous calculation of the volume supplied by the pump according to the present invention can be expressed by the following equation:

[00004]$\mathrm{DispVol}+=\frac{\mathrm{Co}.Math..Math.\mathrm{untIncr}}{E.Math.n.Math.cD}K.Math.v$

[0070] where DispVol is the accumulated volume supplied, CountIncr is the increment of rotary encoder counts, Enc is the number of rotary encoder counts for each pumping to cycle of the pump and Kv is the speed correction coefficient. The += operator is the addition assignment operator used in various computer programming languages, such as C#.

[0071] As explained above, the above equation can also be expressed as:

[00005]$\mathrm{DispVol}+=\frac{\mathrm{CountIncr}}{E.Math.n.Math.cD}\frac{K.Math.v_{o.Math.p}}{K.Math.v_{\mathrm{cal}}}$

[0072] The condition for halting the supply of fluid by means of the pump according to the present invention can be expressed as:

DispVol(Vol+SyrOffset)

[0073] where DispVol is the accumulated volume supplied, Vol is the volume to be supplied or set volume, and SyrOffset is a dead volume that is retained in the hydraulic circuit, especially in the case that said circuit has a filter. A typical value of SyrOffset can be, for example, 1.2 ml.

[0074] Before starting the dispensing process of the first step 10000 it is possible, according to the present invention, to perform an approximate calculation of the number of pumping cycles that will be necessary in order to supply the required volume Vol. This calculation can be made using the following equation:

N=(Vol+SyrOffset)D

[0075] where N is the number of pumping cycles, Vol is the volume to be dispensed, SyrOffset is the dead volume that is retained in the hydraulic circuit and D is the dose per pumping cycle of the pump.

[0076] Although the correction coefficients k, dv and Kv are used in the embodiment shown, only one, a selection of two or any combination thereof may be used in other to embodiments of the present invention. Said correction coefficients can also be combined with one another and/or with other coefficients by means of standard mathematical operations.

[0077] FIG. 6 and FIG. 7 show, in front elevation view, an exemplary embodiment of a device for producing sterile preparations according to the present invention. FIG. 6 shows the device 1 for producing sterile preparations without mounting any disposable kit for producing sterile preparations, while in FIG. 7 the device 1 is provided with a disposable kit for producing sterile preparations. In the exemplary embodiment shown, the device 1 includes a peristaltic pump 10 in the lower portion of one of its sides. Said peristaltic pump can be seen in greater detail in FIG. 8.

[0078] The device 1 comprises, in its upper part, a plurality of supports 50 for infusion bags. Although the shown exemplary embodiment comprises four supports 50 for infusion bags, the number of supports may be different in other embodiments. On the front, the device 1 can comprise a cover 60 which, among other functions, protects the elements housed inside same and, in addition, protects the user of the device 1 against possible splashes of the fluids used therein. Said cover 60 can be transparent, or at least translucent, to allow observation of the elements of the device 1 and any accessories that are placed behind it, while still fulfilling the protective functions described above. The cover 60 can be attached to the device 1 by hinges 62 and can comprise a pull knob 61 to facilitate its opening and closing by the user of the device 1.

[0079] At the top of its front face, the device 1 can include a support 40 for a fluid distributor 5. Said fluid distributor 5 is described in detail in European patent EP 1236644 A1. Although its use is preferred, said support 40 is optional. Under the support 40 and approximately at the middle of the front of the device 1, the device can comprise a support 20 for a calibration vessel. In the exemplary embodiment shown in the figures, said support 20 is complemented with an auxiliary support 21 for the calibration vessel. In this case, both are suitable for holding a syringe 2.

[0080] The embodiment shown in FIG. 6 and FIG. 7 is especially suitable for the use of a syringe 2 as a calibration vessel. Therefore, the shown device 1 comprises means 30 for driving the plunger 200 of the syringe 2. Said driving means 30 can have automatic operation and can be of different types; for example, they can be a robotic arm, a piston, a nut integral with a spindle driven by an electric motor as described in EP 1236644 A1, etc. The driving means 30 can comprise a load cell, not shown, which can convert the force exerted on the plunger 200 into an electrical signal that can be processed in a device control device, not shown, and which will be taken into account by said control device in order to drive the means 30 for driving the plunger 200. Said load cell can also serve to infer the weight of the fluid contained in the syringe 2. The driving means 30 can also include sensors for determining the position of the plunger 200 and thus be able to determine the fluid contained in the syringe 2.

[0081] In this exemplary embodiment, the user of the device 1 enters the commands for its operation via the touchscreen 70. Said touchscreen 70 can also display status information for the device 1. Said screen 70 can be replaced, among others, by a keyboard or keypad. It is also possible to connect the device 1 to a computer in a wired or wireless manner, in order to control the device 1 via a specific computer program installed therein.

[0082] FIG. 7 shows how two source vessels 3, 3 containing fluids for producing sterile preparations hang from the supports 50. These vessels 3, 3 are connected to the distributor 5 via flexible pipes 6, and said distributor 5 is connected in turn to the syringe 2 and to the bag 4 that acts as a final vessel, i.e. as the vessel in which the sterile preparation prepared by the device is stored 1. The example of a bag 4 shown comprises a filter 400 as disclosed in Spanish utility model ES 1019546 U. The control device of the device 1, not shown, can be configured to perform a bubble point test as described, at least, in European patents EP 0624359 A1 and EP 1236644 A1.

[0083] The device 1 of the embodiment shown can fill the final vessel, in this case the bag 4, at constant or variable rotation speed of the pump 10. In the event of operating at variable speed, the rotation speed of the pump 10 can be the highest that allows the pressure inside the flexible ducts 6 to remain below a certain limit. This is especially important when filling bags 4 that comprise a filter 400, since said filter 400 can become clogged and increase the pressure loss that it introduces to the hydraulic circuit.

[0084] FIG. 8 shows the peristaltic pump 10 of the device shown in FIG. 6 and FIG. 7. As can be seen, the peristaltic pump 10 of the shown exemplary embodiment comprises a rotor 11 with three rollers 111A, 111B, 111C responsible for compressing the flexible tube 6 against the circular casing 12. For this, the rollers 111A, 111B, 111C have respective springs 112A, 112B, 112C that act as resilient means. When the rotor 11 and its respective rollers 111A, 111B, 111C rotate, an effect known as peristalsis occurs, causing the fluid contained in the flexible tube 6 to move forward. The pump 10 can be reversible, i.e. capable of turning in the clockwise and anticlockwise directions.

[0085] Although in the shown example the rotor 11 of the peristaltic pump 10 comprises three rollers 111A, 111B, 111C, in other embodiments, the number of rollers may be different, for example 2, 4, 5, etc.

[0086] The following shows, by way of example, some values of the parameters described above for the embodiment shown in FIG. 6 to FIG. 8.

TABLE-US-00001 Pumping cycle of a full revolution of the rotor k 1.00547 dv 0.65469 ml K.sub.Vcal 0.998664574 K.sub.Vop 1.02313852 Enc 2882 SyrOffset 1.2 ml

[0087] k and dv have been determined empirically using a device 1 as shown in FIG. 6 to FIG. 8, in order to then be stored in the memory of the control device of said device 1. The shown value of Kv.sub.cal corresponds to a rotation speed of the peristaltic pump 10 of 6,400 rotary encoder counts per second. The shown value of Kv.sub.op corresponds to a rotation speed of the peristaltic pump 10 of 40,000 rotary encoder counts per second. The values of Kv.sub.cal and Kv.sub.op for different speeds were calculated empirically beforehand and stored in the memory of the device control device 1 and are selected according to the actual calibration and operation conditions, respectively. If the operation is carried out at variable speed, i.e. if the rotation speed of the pump varies during the operation, the calculations are carried out again by selecting the value of Kv.sub.op appropriate to the speed. The value of Enc depends on the structural features of the rotary encoder associated with the pump and the rotor thereof.

[0088] Although the device 1 shown above is configured for use in the production of sterile preparations, said device can also be used for producing non-sterile preparations. The device is specially configured to work, among others, with fluids derived from the blood, i.e. blood products, drugs and other types of products for medical and/or pharmaceutical use. However, it can also be used for producing other types of sterile preparations.

[0089] Although the invention was presented and described in reference to its embodiments, it is understood that these have no limiting effect on the invention, so that multiple structural details or others that may be obvious for a person skilled in the art may vary after interpreting the subject matter that is disclosed in the present description, claims and drawings. In particular, in principle and unless explicitly stated otherwise, all the features of each of the different embodiments and alternatives shown and/or suggested can be combined with one another. Therefore, all the variants and equivalents will fall within the scope of the present invention if they can be considered to be comprised in the broader scope of the following claims.