ANALYTICAL INSTRUMENT HAVING A SYRINGE SIZE IDENTIFICATION FUNCTIONALITY

Abstract

An analytical instrument having a syringe size identification functionality includes a syringe pump with syringe having size V.sub.syri, an electric drive, a valve downstream of the syringe, a pressure sensor between the syringe and the valve, a constant downstream volume V.sub.c and a processor configured to control the electric drive to move the plunger from L.sub.0 for detecting pressure P1 to a pressure detection position L.sub.d for detecting P2 using the pressure sensor. The processor is configured to calculate the theoretical pressure P2* using a modified version of Boyle's law: P2*=P1(V.sub.syri+V.sub.c)/(V.sub.syri(1x)+V.sub.c) and compare the theoretical pressure P2* with the detected pressure P2. When the theoretical pressure P2* equals the detected pressure P2, the analytical system is released for use.

Claims

1-16. (canceled)

17. An analytical instrument having a syringe size identification functionality comprising: a syringe pump with an installed syringe having a size V.sub.syri, an electric drive for advancing or retracting a plunger in the syringe, a valve located downstream of the syringe, a pressure sensor located between the syringe and the valve, a known and constant volume V.sub.c defined by the downstream volume between the syringe and the valve, a processor operatively connected to the valve, the pressure sensor and the electric drive, wherein the processor is configured to: control the electric drive for moving the plunger from a position L.sub.0 for detecting atmospheric air pressure P1 to a pressure detection position L.sub.d for detecting compressed air pressure P2 using the pressure sensor, calculate the fraction x for the plunger movement to the pressure detection position L.sub.d as: $x=\left(L_d-L_0\right)/L_{\max }$ whereby L.sub.max represents the maximum available plunger movement available in the syringe, calculate the theoretical pressure P2* for the plunger movement to L.sub.d in the installed syringe using a modified version of Boyle's law: $P{2}^{*}=P1\left(V_{\mathrm{syri}}+V_c\right)/\left(V_{\mathrm{syri}}\left(1-x\right)+V_c\right),$ compare the theoretical pressure P2* with the detected pressure P2, and when the theoretical pressure P2* equals the detected pressure P2 then release the analytical system with installed syringe V.sub.syri for use, and when the theoretical pressure P2* deviates from the detected pressure P2 then compare the detected pressure P2 with a lookup table stored in a storage device of the processor, the lookup table comprising theoretical pressures P2** attributed to a list of different syringe sizes V.sub.syr to be used in the syringe pump, and recalibrate the syringe pump by adjusting the parameters for the electric drive according to the syringe size V.sub.syr where there is a match between the theoretical pressures P2** from the lookup table and the detected pressure P2.

18. The analytical instrument according to claim 17 wherein the theoretical pressures P2** attributed to a list of different syringe sizes V.sub.syr are calculated according to the modified version of Boyle's law as: P2**=P1(V.sub.syr+V.sub.c)/(V.sub.syr(1x)+V.sub.c).

19. The analytical instrument according to claim 18, wherein the plunger in the syringe is advanced by a plunger rod driven by the electric drive comprising a stepper motor.

20. The analytical instrument according to claim 19, wherein the forward movement of the plunger rod is controlled by the number of commutating steps directed to the stepper motor thereby defining a pressure sweep P2P1 and the number of commutating steps required for the pressure sweep is listed in the lookup table for each syringe size V.sub.syr.

21. The analytical instrument according to claim 17, wherein recalibration comprises attributing the number of commutating steps of the electric motor to the syringe size V.sub.syr where there is a match between the theoretical pressures P2** and the detected pressure P2.

22. The analytical instrument according to claim 21, wherein the known constant volume V.sub.c (23) is defined by the tubing or connectors connecting the syringe to the valve, the dead volume in the valve and the dead volume in the pressure sensor.

23. The analytical instrument according to claim 21, which is automatically recalibrated when the theoretical pressure P2* deviates from the detected pressure P2

24. The analytical instrument according to claim 21, wherein the syringe pump is filled with air for the syringe size identification testing.

25. The analytical instrument according to claim 21, wherein the processor monitors the motor current MC used by the stepper motor for keeping the plunger in the pressure detection position L.sub.d.

26. The analytical instrument according to claim 25, wherein the lookup table comprises predefined motor current values MC* that are attributed to each syringe size V.sub.syr and the syringe pump is recalibrated when the received motor current MC deviates from the predefined motor current value MC* and when the difference in theoretical pressures P2** in the lookup table between two subsequent syringe sizes V.sub.syr is in the same order of magnitude as the tolerance value of the pressure sensor.

27. The analytical instrument according to claim 26, wherein recalibration the syringe pump comprises attributing the number of commutating steps of the electric motor to the syringe size V.sub.syr where there is a match between the predefined motor current value MC* and the received motor current value MC.

28. The analytical instrument according to claim 26, wherein the syringe size identification testing in the is periodically performed or performed upon replacing the syringe in the syringe pump.

29. A method for detecting the size of a syringe in an analytical instrument comprising: a syringe pump with an installed syringe having a volume V.sub.syri, a valve located downstream of the syringe, a pressure sensor located between the valve and the syringe, a known and constant volume V.sub.c representing the downstream volume between the syringe and the valve, an electric drive for advancing or retracting a plunger in the syringe, and a controller with a processor for controlling the analytical instrument; the method comprising the following steps: providing air in the syringe pump at atmospheric pressure P1; closing the valve; moving the plunger in the syringe with volume V.sub.syri using the electric drive from a starting position L.sub.0 for detecting atmospheric pressure P1 to a pressure detection position L.sub.d for detecting pressure P2 using the pressure sensor; using the processor to calculate the fraction x for the plunger movement as x=(L.sub.dL.sub.0)/L.sub.max whereby L.sub.max represents the maximum available plunger movement in the syringe; using the processor to calculate the theoretical pressure P2** for the given plunger movement for different syringe sizes V.sub.syr configured to be used in the analytical instrument (1) using the same constant volume V.sub.c using a modified version of Boyle's law as: $P{2}^{**}=P1\left(V_{\mathrm{syr}}+V_c\right)/\left(V_{\mathrm{syr}}\left(1-x\right)+V_c\right);$ preparing a list of the theoretical pressures P2** for the different syringe sizes and store the list in a lookup table in a storage device of the controller; comparing the theoretical pressures P2** for the given plunger movement for the different syringe sizes V.sub.syr with the detected pressure P2 for the installed syringe having volume V.sub.syri; and automatically recalibrate the syringe pump by adjusting the parameters for the electric drive driving the syringe pump using the lookup table when the theoretical pressure P2** deviates from the detected pressure P2.

30. The method according to claim 29, wherein the plunger in the syringe is advanced by a plunger rod driven by the electric drive comprising a stepper motor and the forward movement of the plunger rod is controlled by the number of commutating steps directed to the stepper motor thereby defining a pressure sweep P2P1 and the number of commutating steps required for the pressure sweep is listed in the lookup table for each syringe size V.sub.syr.

31. The method according to claim 30, wherein adjusting the parameters for driving the syringe pump comprises attributing the number of commutating steps of the electric motor to the syringe size V.sub.syr where there is a match between the theoretical pressures P2** and the detected pressure P2 using the lookup table thereby correcting the pressure sweep.

32. The method according to claim 31, wherein the controller is configured to issue an acoustic and/or visual alarm when the theoretical pressure P2** deviates from the detected pressure P2 and/or the controller is configured to issue an acoustic and/or visual notification when the theoretical pressure P2** equals the detected pressure P2.

33. The method according to claim 31, wherein the processor of the controller monitors the motor current MC used by the stepper motor for keeping the plunger in the pressure detection position L.sub.d and wherein the lookup table comprises predefined motor current values MC* that are attributed to each syringe size V.sub.syr and the syringe pump is recalibrated when the received motor current MC deviates from the predefined motor current value MC* and when the difference in theoretical pressures P2** in the lookup table between two subsequent syringe sizes V.sub.syr is in the same order of magnitude as the tolerance value of the pressure sensor.

34. The method according to claim 33 wherein recalibration the syringe pump comprises attributing the number of commutating steps for the electric motor to the syringe size V.sub.syr where there is a match between the predefined motor current value MC* and the received motor current value MC.

35. A computer program for detecting the size of a syringe in an analytical system, the computer program when executed by the processor that is part of the analytical instrument is adapted to execute the method of claim 29.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0043] Embodiments of the present invention are described in more detail with reference to the attached drawings presenting:

[0044] FIG. 1: Schematic representation of an analytical instrument having a syringe size identification functionality,

[0045] FIG. 2a: Schematic drawing of a syringe pump with a syringe, an electric drive, a valve, a pressure sensor connected to the outlet of the syringe with a constant volume V.sub.c between the syringe outlet and the valve. The syringe pump being filled with air at atmospheric pressure and the plunger at initial position L.sub.0,

[0046] FIG. 2b: Syringe pump of FIG. 2a with closed valve, the plunger has been moved to the pressure detection position L.sub.d by the electric drive,

[0047] FIG. 3: Syringe pump of FIG. 2a after replacement of the syringe with a different size,

[0048] FIG. 4: Longitudinal section of a rotary valve,

[0049] FIG. 5: Cross sectional view of the rotary valve of FIG. 4, valve in open position,

[0050] FIG. 6: Cross sectional view of the rotary valve of FIG. 4, valve in closed position,

[0051] FIG. 7: Theoretical pressure P2** for a range of syringe sizes,

[0052] FIG. 8: Reaction force for retaining the plunger in the pressure detection position,

[0053] FIG. 9: Block diagram for the method for detecting the size in the analytical instrument.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

[0054] FIG. 1 shows a schematic representation of an analytical instrument 1 with a syringe identification functionality with a syringe pump 2, a pressure sensor 3 and a valve 4. The syringe pump 2 may be prefilled or may be fluidly connected to a container providing the liquid supply. The syringe pump 2 is driven by an electric drive 21 which includes an electric motor, for example a stepper motor. The electric drive may include a gearing mechanism for gearing up or gearing down the rotation of the drive axle of the electric motor. The pressure sensor 3 is located between the valve 4 and an outlet of the syringe pump 2. The valve 4 may be a multi-port valve for selecting between, for example, a waste container 6 or fluidly connecting the syringe pump 2 to a testing device such as a HPLC device 5. Alternatively, the testing device is a GC or GC-MS device. Instead of a testing device 6 also a solid phase extraction device may be used, or a DNA synthesizer or liquid may be supplied to a bioreactor or a DNA sequencer. The analytical instrument 1 may include a robot for liquid handling and moving labware on a working table of the analytical instrument. The analytical instrument may be part of the laboratory automation apparatus. The analytical instrument 1 includes a control unit 22 which is operatively coupled at least to the electric drive 21, the pressure sensor 3 and the valve 4. The control unit 22 may control further units of the analytical instrument such as, for example, the robot for the liquid handling. The control unit includes a processor or microprocessor and at least a storage unit. The control unit may optionally include a communication unit with a transceiver for wireless communication to an external device. The control unit 22 may be connected to a user interface for directing visual or acoustic signals to the user. The control unit 22 may receive or monitor the data from the pressure sensor 3 that correlate to the detected pressures and/or the control unit may receive or monitor the motor current MC required for advancing to and retaining the plunger rod in a certain position in the barrel of a syringe as will be explained below in FIG. 2b. The control unit is furthermore configured to control the electric drive 21 and the valve 4 in that the control unit can start/stop the electric motor and define the commutation of the motor. The control unit is configured to open or close the valve, for example by using a solenoid actuator or using a separate stepper motor for rotating the rotor of a rotary valve.

[0055] FIG. 2a presents a schematic drawing for a syringe pump 2 for use in the analytical instrument 1 with the valve 4 and pressure sensor 3 connected to an outlet 9 of a syringe 7 and the pressure sensor 3 is located between the outlet 9 and the valve 4. A three-way rotary valve 4 is presented in FIG. 2a with an inlet connected to the outlet 9 of the syringe 7 and a rotor that may select between one of the two outlets 18. Alternative options for the valve 4 may include a solenoid valve. Further details for the three-way rotary valve are presented below in FIGS. 4 to 6.

[0056] The syringe 7 in FIG. 2a includes a barrel 8 with an opening for receiving a plunger 11. The barrel 8 has a cylindrical shape and the center of the barrel defines a Z-axis. The barrel 8 defines the syringe volume V.sub.syri for the installed syringe in the syringe pump. The plunger 11 can be moved along the Z-axis towards the outlet 9 of the syringe by a plunger rod 13. The plunger rod is driven by the electric drive 21. The electric drive includes the stepper motor and a gearing mechanism for gearing up or down the rotation of the drive axle of the electric motor. The gearing mechanism is operatively coupled to the plunger rod 13 for driving the plunger 11 in the syringe. The plunger 11 in FIG. 2a is located at the starting position L.sub.0 and the valve 4 is open such that air can flow into the syringe and the pressure sensor 3 detects atmospheric pressure P1. The syringe pump 2 includes a constant volume V.sub.c 23 defined by the volume of the outlet 9 of the syringe, the tubing connecting the outlet 9 to the valve 4 and the sensor 3 (in the example in FIG. 2a represented as a T-shaped connector), and the dead volumes present in the valve and sensor respectively. The syringe 7 includes a shoulder section connecting the barrel 8 to the outlet 9 and the shoulder section provides a hard stop for the movement of the plunger 11 and thereby defines the maximum travel path L.sub.max 15 for the syringe.

[0057] The valve 4 is closed in FIG. 2b and the electric drive 21 has advanced the plunger 11 to a pressure detection position L.sub.d thereby compressing the air that was initially present in the syringe with size V.sub.syri and in the constant volume V.sub.c 23. The pressure sensor 3 detects the pressure P2 for the compressed air. The electric drive has advanced the plunger rod 13 according to the number of steps that were directed by the control unit 22 to the stepper motor in the electric drive. The number of steps required for advancing the plunger rod 13 thereby correlates to the pressure sweep P2P1 that can be provided and the number of steps is thus linked to the size (for example internal diameter) of the installed syringe. A syringe with a larger diameter is presented in FIG. 3 and the same plunger movement from L.sub.0 to L.sub.d as presented in FIG. 2b will lead to a higher internal pressure P2. In the state of the art, the user may correct the controller by programming a different number of commutating steps using the user interface, or an automatic recalibration utilizes the color-coded syringes in combination with optical sensors as presented in US20210121885A1. In the example of FIG. 3, less commutating steps for the electric motor are required for reaching the same pressure level as presented in FIG. 2b. The present disclosure refers to an automatic recalibration of the analytical system or apparatus using the existing firmware as will be presented further below.

[0058] An example for the valve 4 is a rotary valve 10 as presented in FIGS. 4, 5 and 6. The rotary valve 10 includes a conical shaped rotor member 14 that fits into a conical shaped passage 16 of a stator member 12. The rotor member 14 can rotate around axis A to different rotational positions for selectively coupling an inlet 17 in the stator 12 via a channel in the rotor 14 to one of a plurality of outlets 18 of the stator. The inlet 17 may be coupled to the outlet of the syringe. The rotor member 14 includes an axle 20 that is coupled to, or may be coupled to a drive mechanism for rotating the rotor member 14 with respect to the stator member 12 to predefined angular positions. A cross sectional view B-B of the rotary valve 10 of FIG. 4 is presented in FIG. 5. The rotor 14 includes a channel 19 selectively coupling the inlet 17 via the rotor channel 19 to an outlet 18 (FIG. 5). The valve is closed when the rotor member 14 is rotated to a rotary position where the channel 19 is unable to couple the inlet 17 to one of the outlets 18. The rotor 14 and/or the stator member may be constructed from a polymeric material. Alternatively, the rotor and/or stator member may be constructed from a ceramic material.

[0059] The syringe size identification functionality will be explained for the following range of syringe sizes: 50 l, 100 l, 250 l, 1000 l, 2500 l and 5000 l. The constant volume V.sub.c 23 occupied by the tubing, valve and sensor amounts to 74 l in this exemplary embodiment.

TABLE-US-00001 TABLE 1 Syringe sizes and added volume V.sub.c V.sub.syr (l) V.sub.c (l) V.sub.syr + V.sub.c (l) Ratio V.sub.c/V.sub.syr 50 74 124 1.48 100 74 174 0.74 250 74 324 0.30 1000 74 1074 0.07 2500 74 2574 0.03 5000 74 5074 0.01
The calculation of the fraction x from the distance L.sub.d travelled in the syringe is listed in Table 2

TABLE-US-00002 TABLE 2 Calculation of the fraction x for the movement of the plunger distance (mm) L.sub.d (mm) x 30 0 0 25 5 0.167 20 10 0.333 15 20 0.5 10 30 0.667
The theoretical pressures P2** are calculated according to the modified Boyle's equation:

[00003]$P{2}^{**}=P1\left(V_{\mathrm{syr}}+V_c\right)/\left(V_{\mathrm{syr}}\left(1-x\right)+V_c\right)$

The theoretical pressures P2** for the 50 l and 5000 l syringes are listed in the following tables for a constant volume V.sub.c of 74 l and an initial pressure P1 of 1 Bar.

TABLE-US-00003 TABLE 3 Calculation of the theoretical pressure P2** for a 50 l syringe 50 l/x (V.sub.syr(1 x) + V.sub.c) P1(V.sub.syri + V.sub.c) P2** (Bar) 0 124.00 124.00 1.00 0.167 115.67 124.00 1.07 0.333 107.33 124.00 1.16 0.5 99.00 124.00 1.25 0.667 90.67 124.00 1.37

TABLE-US-00004 TABLE 4 Calculation of the theoretical pressure P2** for a 5000 l syringe 5000 l/x (V.sub.syr(1 x) + V.sub.c) P1(V.sub.syri + V.sub.c) P2** (Bar) 0 5074.00 5074.00 1.00 0.167 4240.67 5074.00 1.20 0.333 3407.33 5074.00 1.49 0.5 2574.00 5074.00 1.97 0.667 1740.67 5074.00 2.91
The theoretical pressures P2** for the range of different syringe sizes is presented in the table 5 below and graphically displayed in FIG. 7:

TABLE-US-00005 TABLE 5 Theoretical pressure P2** (Bar) for a range of syringe sizes; x 50 l 100 l 250 l 1000 l 2500 l 5000 l 0 1.00 1.00 1.00 1.00 1.00 1.00 0.167 1.07 1.11 1.15 1.18 1.19 1.20 0.333 1.16 1.24 1.35 1.45 1.48 1.49 0.5 1.25 1.40 1.63 1.87 1.94 1.97 0.667 1.37 1.62 2.06 2.64 2.84 2.91

[0060] The difference in theoretical pressures P2** between two subsequent syringe sizes for a given fraction of the plunger movement x decreases for larger syringe sizes. The theoretical pressure difference between a 100 l and 50 l syringe amounts 0.25 Bar for plunger movement x=0.667 whereas the theoretical pressure difference amounts 0.07 Bar between a 5000 l and 250 l syringe for the same plunger movement. This is affected by the fact that the ratio between the constant volume V.sub.c and the syringe volume V.sub.syr reduces with increasing syringe size. Once the variation in the effectively detected pressure P2, which is defined by the accuracy of the pressure sensor, is within the range of the difference in theoretical pressure P2**between two subsequent syringe sizes, then the syringe size identification functionality may not benefit from the calculated pressures P2**.

[0061] The motor current MC used for driving the stepper motor is monitored by the control unit and the motor current may be used for distinguishing between different syringe sizes as well. The plunger 11 is moved forward from the starting position L.sub.0 to the pressure detection position L.sub.d thereby compressing the air in the syringe since the valve 4 is in the closed position. The compressed air will provide a reactive force F (in Newtons) which can be calculated by multiplying the surface area of the plunger (mm.sup.2) with the pressure (1 Bar equals 0.1 N/mm.sup.2) and the results are presented in FIG. 8. The difference in reactive force between two subsequent syringe sizes increases with increasing size contrary to the difference in pressure P2** which decreases with increasing size (FIG. 7). The motor current MC required for maintaining the plunger in the pressure detection position L.sub.d may be capable of distinguishing between different syringe sizes where the accuracy of the pressure sensor limits the use of the pressure calculation method.

The method steps for detecting the size of a syringe in an analytical system including the syringe pump 2, the valve 4, the pressure sensor 3, the controller 22 and the electric drive 21 are presented in the block diagram in FIG. 9.
The method comprising the following steps: [0062] Step 24: Providing air in the syringe pump at atmospheric pressure P1, [0063] Step 25: Closing the valve, [0064] Step 26: Moving the plunger in the syringe with volume V.sub.syri using the electric drive from a starting position L.sub.0 for detecting atmospheric pressure P1 to a pressure detection position L.sub.d for detecting pressure P2 using the pressure sensor, [0065] Step 27: Using the processor to calculate the fraction x for the plunger movement as x=(L.sub.dL.sub.o)/L.sub.max whereby L.sub.max represents the maximum available plunger movement in the syringe, [0066] Step 28: Using the processor to calculate the theoretical pressure P2** for the given plunger movement for different syringe sizes V.sub.syr configured to be used in the analytical instrument using the same constant volume V.sub.c as:

[00004]$P{2}^{**}=P1\left(V_{\mathrm{syr}}+V_c\right)/\left(V_{\mathrm{syr}}\left(1-x\right)+V_c\right)$ [0067] preparing a list of the theoretical pressures P2** for the different syringe sizes and store the list in a lookup table in the storage device. [0068] Step 29: Comparing the theoretical pressures P2** for the given plunger movement for the different syringe sizes V.sub.syr with the detected pressure P2 for the installed syringe having volume V.sub.syri, and, [0069] Step 30: Automatically recalibrate the syringe pump by adjusting the parameters for the electric drive driving the syringe pump using the lookup table if the theoretical pressure P2** deviates from the detected pressure P2.

[0070] The plunger in the syringe pump is advanced by a plunger rod driven by the electric drive including a stepper motor and the forward movement of the plunger rod is controlled by the number of commutating steps directed to the stepper motor thereby defining a pressure sweep P2P1 and the number of commutating steps required for the pressure sweep is listed in the lookup table for each syringe size V.sub.syr. Furthermore, adjusting the parameters for driving the syringe pump includes attributing the number of commutating steps to be directed to the electric motor to the syringe size V.sub.syr where there is a match between the theoretical pressures P2** and the detected pressure P2 using the lookup table. The pressure sweep is corrected if there is a mismatch between the detected pressure and the calculated pressure. The pressure sweep may start with pressure P1 representing atmospheric pressure or, alternatively pressure P1 is for an already compressed gas in the syringe pump with a P1 value that is below P2.

[0071] The method may include an optional step: [0072] Step 31: The method wherein the controller receives the motor current MC used by the stepper motor for keeping the plunger in the pressure detection position L.sub.d and wherein the lookup table includes predefined motor current values MC* that are attributed to each syringe size V.sub.syr and the syringe pump is recalibrated if a) the received motor current MC deviates from the predefined motor current value MC* and b) when the difference in theoretical pressures P2** in the lookup table between two subsequent syringe sizes V.sub.syr is in the same order of magnitude as the tolerance value of the pressure sensor.

LIST OF REFERENCE SIGNS

[0073] 1 Analytical instrument [0074] 2 Syringe pump [0075] 3 Pressure sensor [0076] 4 Valve [0077] 5 HPLC [0078] 6 Waste container [0079] 7 Syringe [0080] 8 Barrel [0081] 9 Outlet [0082] 10 Rotary valve [0083] 11 Plunger [0084] 12 Stator member [0085] 13 Plunger rod [0086] 14 Rotor member [0087] 15 Maximum travel path L.sub.max [0088] 16 Conical passage [0089] 17 Inlet [0090] 18 Outlet [0091] 19 Channel [0092] 20 Axle [0093] 21 Electric drive [0094] 22 Control unit, processor [0095] 23 Constant volume Vc [0096] 24 Method step for syringe [0097] 25 Method step for valve closure [0098] 26 Method step for plunger movement [0099] 27 Method step for calculation x [0100] 28 Step for pressure P2** calculation [0101] 29 Method step for comparison of pressure [0102] 30 Method step for recalibration [0103] 31 Method step for using motor current [0104] A Rotor axis