GB2435098A

GB2435098A - NMR measurement of sample mass

Info

Publication number: GB2435098A
Application number: GB0602662A
Authority: GB
Inventors: Jozef Antonius Willem M Corver; Johannes Van Veen
Original assignee: BOC Group Ltd
Current assignee: BOC Group Ltd
Priority date: 2006-02-10
Filing date: 2006-02-10
Publication date: 2007-08-15
Also published as: GB0602662D0

Abstract

Apparatus is described for determining a characteristic, such as the mass, of a sample. The apparatus comprises a rotatable device for receiving a sample and for moving the sample through an interrogation zone, means for applying a first magnetic field in a first direction in the interrogation zone for creating a net magnetisation, means for applying an alternating magnetic field in a second direction in the interrogation zone for temporarily changing the net magnetisation of the sample located therein, and means for monitoring energy emitted from the sample as the net magnetisation of the sample returns to its original state. The rotatable device is a star wheel, used for NMR of syringes and other small containers.

Description

METHOD OF DETERMINING THE MASS OF A SAMPLE

The present invention relates to a method of, and apparatus for, determining the mass or other characteristic of a sample, and which may find use in the determination of the mass of a sample conveyed on a conveyor system, for example, between functions of a production line.

In-line filling machines for dispensing products, such as liquid and/or powder drug samples, into containers or vials typically include a conveyor system for conveying the containers between functions. A filling station receives empty vials from the conveyor system, sequentially fills the vials with an accurate : *. amount of one or more products and closes the thus-filled vials with closure members, for example, stoppers. The conveyor system then conveys the closed vials to an inspection station which checks that the vials have been . i5 correctly filled. A reject station is provided downstream from the inspection station for removing incorrectly filled vials from the production line. A sealing : * station may also be provided downstream from the reject station for sealing the vials.

It is known to utilise an inspection station that checks the mass of vials on a production line using NMR techniques. The inspection station includes a magnet for creating a static magnetic field over an interrogation zone to produce a net premagfleti5atb0n within a vial located in the interrogation zone, and an RF probe for applying a pulsed, alternating magnetic field over the interrogation zone and orthogonal to the static magnetic field. The alternating magnetic field causes the net magnetisation of the sample contained within the vial to rotate about the axis of the alternating magnetic field, away from the direction of the static magnetic field.

After the pulse has been applied to the sample, the sample relaxes and emits electromagnetic energy at the Larmor frequency of the molecules of the sample. The magnetic component of the energy emitted from the sample induces a signal, known as the free induction decay (FID), in the form of current in the RF probe. The amplitude of the induced current is considered to be directly proportional to the number of molecules in the sample. The amplitude of the induced current is then compared to that produced by a calibration sample with known mass to determine the mass of the sample under analysis.

Alternative techniques also exist for determining the characteristics of samples other than just mass (or weight). For example, by supplying a train io of pulses and monitoring the responses, usually referred to as "echoes" from the sample, it is possible to obtain information concerning the amount of * ,. ferrous particles within, or other contamination of, the sample. Si. iii'

In such known inspection stations, the RF probe for applying an alternating magnetic field over the interrogation zone extends over and about the interrogation zone, so that the samples under analysis pass beneath the probe. For the detection of the mass of samples contained in elongate containers such as syringes, this would result in a relatively tall and bulky S...

probe for the mass of the samples under analysis. Dueto disproportionate size of the probe in relation to the sample, this would result in a relatively small signal to noise ratio in the energy emitted from the sample.

Furthermore, the presence of metal needles would unduly influence the signal.

In a first aspect, the present invention provides apparatus for determining a characteristic, such as the mass, of a sample, the apparatus comprising a rotatable device for receiving a sample and for moving the sample through an interrogation zone with rotation thereof, means for applying a first magnetic field in a first direction in the interrogation zone for creating a net magnetisation within the sample as it moves through the interrogation zone, means for applying an alternating magnetic field in a second direction in the interrogation zone for temporarily changing the net magnetisation of the sample located therein, and means for monitoring energy emitted from the sample as the net magnetisation of the sample returns to its original state.

The rotatable device preferably comprises at least one disc or annulus for receiving a sample and for moving the sample through an interrogation zone with rotation thereof. In a preferred embodiment, the rotatable device comprises a star wheel, which typically receives containers from a first conveyor and dispatches the containers to a second conveyor. The use of a star wheel can enable the apparatus to be readily retro-fitted to existing io conveyor systems.

As is usual with star wheels, the device preferably has a plurality of container-engaging elements spaced about the periphery thereof. In the preferred embodiment, each element comprises a suction holder for releasably is receiving a container to be conveyed, although an alternative arrangement, for example an array of recesses or springloaded mechanical devices, may : * be provided. *I.* es's

The rotatable device is preferably arranged to rotate at a substantially constant angular velocity, and preferably about an axis that is substantially parallel to the first direction, which is preferably substantially vertical.

Means such as a permanent magnet, electromagnets, current carrying coils or superconducting magnets, may be provided for applying a first magnetic field in a first direction in the interrogation zone for creating a net magnetisation within a sample located within the interrogation zone. The means for applying an alternating magnetic field preferably comprises a probe located adjacent the interrogation zone.

By monitoring energy emitted from the sample as the net magnetisation of the sample returns to its original state, for example by monitoring the amplitude of a current induced in at least one of the coils, an indication of the mass or -4---other characteristic of the sample can be provided. For example, by applying the alternating magnetic field from a single probe located adjacent the interrogation zone, the magnitude of the alternating magnetic field is not homogeneous across the interrogation zone. This can enable characteristics of the sample, such as product homogeneity, to be investigated, as the influence on the measurement from magnetic or electrically conductive elements of the container, such as a needle or piston, may be readily filtered from the signal received as the net magnetisation of the sample returns to its original state.

When a probe is used to produce an inhomogeneoUs magnetic field across * ** the interrogation zone, the rotating device is preferably formed from non- ::::: magnetic, non-electrically conducting material so as to not influence the measurement made by the apparatus. S. *e * S S * .

The alternating magnetic field may be applied to a sample a plurality of times.

By subsequently monitoring the energy emitted from the sample as it returns to its original state, a characteristic of the sample other than mass, such as *5** the level of contamin'atiOn of the sample, may be determined. The application of pulse-sequences is also preferred for the measurement of the weight of solid material and in the case of liquids improves the accuracy of the measurement.

The present invention also provides a conveyor system comprising an infeed conveyor, apparatus as aforementioned for receiving containers from the infeed conveyor, and an outfeed conveyor for receiving containers from said apparatus. Containers that have passed through the apparatus can be individually identified on the ouffeed conveyor, and this can enable any container having a different mass or other characteristic to the other containers to be readily identified on, and rejected from, the outfeed conveyor.

The system may comprise an infeed starwheel for transferring containers from the infeed conveyor to the apparatus, and an outfeed conveyor for transferring containers from the apparatus to the outfeed conveyor. The containers may be releasably retained by the conveyors and the starwheels by any suitable mechanism, such as suction holders or a suspension mechanism.

As the infeed and outfeed conveyors, and the infeed and outfeed star wheels, do not pass through the interrogation zone, the material from which these components are formed is not critical. For example, in order to reduce costs these components may be formed from stainless steel.

io In a related aspect, the present invention provides a method of determining a characteristic, such as the mass, of a sample, the method comprising the : ** steps of causing the sample to move through an interrogation zone, applying S... . . . . . . . . a first magnetic field in a first direction in the interrogation zone for creating a net magnetisation within the sample as it moves through the interrogation zone, applying an alternating magnetic field in a second direction in the interrogation zone for temporarily changing the net magnetisation of the sample located therein, and monitoring energy emitted from the sample as the : .:. net magnetisatiOn of the sample returns to its original state, wherein the S.., sample is located on a rotating device as it is moved through the interrogation zone.

The method and apparatus described above are particularly suitable for determining the mass of samples located within elongate containers, such as syringes or ampoules.

Features described above in relation to method aspects of the invention are equally applicable to apparatus aspects, and vice versa.

Preferred features of the present invention will now be described, by way of example only, with reference to the accompanying drawings, in which: Figure 1 illustrates a first perspective view of a conveyor system including apparatus for determining the mass of a sample; Figure 2 illustrates a second perspective view of the conveyor system of Figure 1; Figure 3 illustrates a third perspective view of the conveyor system of Figure 1, with the internal components of the apparatus partially exposed; and io Figure 4 is a block diagram illustrating a control system forming part of and controlling the apparatus. * S.

With reference first to Figures 1 and 2, a conveyor system 10 for conveying S...

containers, for example between stations of a production line, comprises an infeed conveyor 12, measurement apparatus 14 for determining a characteristic of a sample contained within a container, an infeed star wheel 16 for transferring containers from the infeed conveyor 12 to the : .:. measurement apparatus, an outfeed conveyor 18 and an ouffeed star wheel S...

for transferring the containers from the measurement apparatus 14 to the outfeed conveyor 16. In this illustrated embodiment, the apparatus is used to determine the mass of pharmaceutical samples located within sterile glass or plastics syringes 22. However, the apparatus is also suitable to use with containers of other shapes and sizes, such as vials and ampoules, and to determine the mass of other types of sample, for example biological samples, industrial chemicals and food products.

Each of the infeed and ouffeed conveyors 12, 18 comprises a conveyor belt 24 generally comprising an endless chain driven by motor-driven gear wheels (not shown) to move about a vertical axis. Each belt 24 may be constructed 30. from materials selected from a group including Kevlar , Teflon , polyester, polyurethane, aramide, glass, stainless steel or other thermoplastic materials.

Each belt 24 may have a series of spaced pockets, recesses, suction holders or other suitable holders (not shown) for releasably retaining the syringes during transportation by the belt 24.

Each of the infeed and outfeed star wheels 16, 20 has a number of syringe-receiving elements 26 spaced about the periphery thereof for receiving syringes from, or transferring syringes to, a respective one of the infeed and outfeed conveyors 12, 18. The infeed and outfeed star wheels 16, 20 may be conveniently formed from stainless steel, or any other suitable material. Each element may be provided by a pocket, recess, suction holder or other suitable io holder for releasably retaining a syringe during transportation by the star wheel. The holders 26 of the star wheels 16, 20 have the same pitch as the holders of the belts 24. Each star wheel 16, 20 is rotated at a substantially ::::: constant angular velocity and about a vertical axis passing through its centre by a suitable drive mechanism (not shown) located beneath the star wheels.

* :* 15 This drive mechanism may also drive the movement of the belts 24 of the infeed and outfeed conveyors 12, 18.

The measurement apparatus 14 comprises a rotating device 30, in this **** *1S* embodiment in the form of a central disc or star wheel 30 forreceiving syringes 22 from the infeed star wheel 16 and subsequently transferring the syringes 22 to the outfeed star wheel 20. The star wheel 30 is preferably formed from non-magnetic, non-conductive material, such as Kevlar , Teflon , polyester, polyurethane, aramide, glass or other thermoplastic materials.

The star wheel 30 is rotated at a substantially constant angular velocity and about a vertical axis passing through the centre 32 thereof by a suitable drive mechanism (not shown) located beneath the central star wheel 30. This drive mechanism may be the same drive mechanism that is used to rotate the infeed and outfeed star wheels 16, 20, or it may be a separate drive mechanism operated synchronously with that drive mechanism so that the central star wheel 30 rotates synchronously with the infeed and outfeed star wheels 16, 20 during use.

The central star wheel 30 comprises a plurality of syringe-receiving elements located about the outer periphery thereof. In this embodiment, the syringe-receiving elements of the central star wheel 30 are provided by a plurality of suction holders 34 spaced about the outer periphery of the central star wheel with the same pitch as the syringe-receiving elements located on the infeed and outfeed star wheels 16, 20. The suction holders 34, and the mechanism io used to actuate the suction action of the holders, is preferably also formed from non-magnetic, non-electrically conductive material. The suction holders : * 34 may be continually operated to produce a suction force that enables each suction holder 34 to take a syringe from the infeed star wheel 16 when it is positioned adjacent thereto, but yet enables a holder 26 of the ouffeed conveyor 20 to take a syringe 22 from the central star wheel 30.

With the conveyor system 10 in operation, syringes 22 conveyed by the infeed *.:.. conveyor 12 are transferred to the infeed star wheel 16, which transfers syringes to the central star wheel 30. The syringes conveyed by the central star wheel 30 are subsequently transferred to the outfeed star wheel 20, which transfers the syringes 22 to the outfeed conveyor 18.

As the syringes 22 are conveyed by the central star wheel 30 between the infeed and outfeed star wheels, they pass in turn through an interrogation zone of the measurement apparatus 14. With reference also to Figure 3, the measurement apparatus 14 comprises a casing 40 having a mouth 42 through which the syringes 22 pass as they are conveyed by the central star wheel 30, the interrogation zone being located within the mouth 42 of the casing 40.

The casing 40 houses a magnetic assembly 44 for creating a homogenous direct current, or static, magnetic field in the z direction illustrated in Figure 3, through the interrogation zone. This has the effect of magnetising a sample contained within a syringe 22 located within the interrogation zone. The magnetic assembly 44 may be conveniently provided by a pair of permanent magnets, electromagnets, current carrying coils or superconducting magnets located on opposing sides of the mouth 42 of the casing 40.

The casing 40 also houses an RF probe 46 located adjacent the mouth 42 of the casing 40, and thus adjacent the interrogation zone. In use, as a syringe 22 located on the central star wheel 30 enters the interrogation zone, a pulse of alternating current at the sample's Larmor frequency is applied to the RF probe 46. This current causes an alternating magnetic field at the sample's Larmor frequency and oriented in the x direction, that is, orthogonal to the ::::: static magnetic field, to be applied to the sample contained within the syringe 22. This has the effect of exciting the sample by causing the sample's net magnetisation to rotate. After this pulse has been applied, the sample is in a high-energy, non-equilibrium state, from which the sample relaxes back to its equilibrium state. As the sample relaxes, electromagnetic energy at the Larmor frequency is emitted, the magnetic component of which induces a current in the RF probe46. Thepeak amplitude of the current varies with, among other things, the number of magnetic moments in the sample, and hence the number of molecules in the sample. Therefore, by monitoring the current induced in the RF probe 46 as the net magnetisation of the sample returns to its original state, a characteristic of the sample contained within the syringe 22, such as the mass or sample homogeneity, may be determined.

Figure 5 is a block diagram illustrating a control system 50 forming part of and controlling the measurement apparatus 14. The control system 50 comprises a connection terminal 52 for connecting the control system 50 to the RF probe 46. A switch 54 connects the terminal 52 to a signal generator 56 and a power amplifier 58 which are operable to generate and amplify respectively an AC pulse which can be applied to the RF probe 46.

-10---The connection terminal 52 is also connectable, through switch 54, to circuitry for amplifying the signal received by the RF probe 46 from the sample under analysis, and for removing noise components from that signal. The circuitry 60 also includes an AID converter for converting the signal to a digital signal before it is passed to a microprocessor 62. The microprocessor 62 compares the peak amplitude of the signal with the peak amplitude of a signal received from a calibration sample with a known mass (or weight), homogeneity or other characteristic, to determine that characteristic of the sample under analysis. As shown in Figure 5, the control system 60 may also comprise a user interface 64 for allowing the user to input into the control system 50 the correct mass or other characteristic of each sample for a given : * batchof samples.

As shown by the dashed control lines 66, 68, the microprocessor 52 controls the operation of the signal generator 56 and the switch 54. This enables the microprocessor 62 to control the signal generator to generate an AC pulse when a syringe 22 containing a sample under analysis is located within the :::,. interrogation zone. For example, the microprocessor 62 may control a drive S...

mechanism 70 for driving the rotationof the central star wheel 30, with the generation of pulses being synchronised with the rotation to the central star wheel 30 to coincide with the location of a syringe 22 within the interrogation zone.

In the example described above, a single pulse is applied to the RF probe 46 so that a determination of the mass of the sample contained within a syringe 22 may be made. Alternatively, a series of pulses may be applied to the syringe 22 as it moves through the interrogation zone so that an alternating magnetic field is applied to the sample a plurality of times. By subsequently monitoring the energy emitted from the sample as it returns to its original state, a characteristic of the sample other than mass, such as the level of contamination of the sample, may be determined. The application of pulse- -11 -sequences is also preferred for the measurement of the weight of solid material and in the case of liquids improves the accuracy of the measurement. * .* * S * S... *5*S * . *5*S ** S. * . S * . * . * S S S... *55* SS S*

Claims

CLAIMS

1. A method of determining a characteristic, such as the mass, of a sample, the method comprising the steps of: causing the sample to move through an interrogation zone; applying a first magnetic field in a first direction in the interrogation zone for creating a net magnetisation within the sample as it moves through the interrogation zone; applying an alternating magnetic field in a second direction in the interrogation zone for temporarily changing the net magnetisation * of the sample located therein; and monitoring energy emitted from the sample as the net *I..

magnetisation of the sample returns to its original state; wherein the sample is located on a rotating device as it is moved through the interrogation zone.

2. A method according to Claim 1, wherein the rotating device has a *::::* plurality of samples located about a perimeter thereof.

3. A method according to Claim 2, wherein the samples are held by a plurality of sample-engaging elements spaced about the periphery of the rotating device.

4. A method according to Claim 3, wherein each element comprises a suction holder for releasably receiving a container containing a sample.

5. A method according to any preceding claim, wherein the rotating device comprises a rotating disc.

6. A method according to any preceding claim, wherein the rotating device rotates at a substantially constant angular velocity.

7. A method according to any preceding claim, wherein the rotating device rotates about an axis that is substantially parallel to the first direction.

8. A method according to Claim 7, wherein said axis extends substantially vertically.

9. A method according to any preceding claim, wherein the alternating : * magnetic field is applied by a probe located adjacent the interrogation zone * S * S* * 10. Apparatus for determining a characteristic, such as the mass, of a sample, the apparatus comprising: a rotatable device for receiving a sample and for moving the :.::.. sample through an interrogation zone with rotation thereof; *:::: means for applying a first magnetic field in a first direction in the interrogation zone for creating a net magnetisation within the sample as it moves through the interrogation zone; means for applying an alternating magnetic field in a second direction in the interrogation zone for temporarily changing the net magnetisation of the sample located therein; and means for monitoring energy emitted from the sample as the net magnetisation of the sample returns to its original state.

11. Apparatus according to Claim 10, wherein the rotatable device has a perimeter configured to receive a plurality of samples.

-14 - 12. Apparatus according to Claim 11, wherein the rotatable device comprises a plurality of sample-engaging elements spaced about the periphery thereof.

13. Apparatus according to Claim 12, wherein each element comprises a suction holder for releasably receiving a container containing a sample.

14. Apparatus according to any of Claims 11 to 13, wherein the rotatable device comprises at least one disc for receiving a sample and for moving the sample through an interrogation zone with rotation thereof.

15. Apparatus according to any of Claims 11 to 14, wherein the rotatable device is arranged to rotate at a substantially constant angular velocity. *... * . ***S

16. Apparatus according to any of Claims 11 to 15, wherein the rotatable device is arranged to rotate about an axis that is substantially parallel to the first direction. * * * I * I...

17. Apparatus according to Claim 16, wherein said axis extends substantially vertically.

18. Apparatus according to any of Claims 11 to 17, wherein the means for applying an alternating magnetic field comprises a probe located adjacent the interrogation zone.

19. A conveyor system comprising an infeed conveyor, apparatus according to any of Claims 11 to 18 for receiving samples from the infeed conveyor, and an outfeed conveyor for receiving samples from said apparatus.

20. A conveyor system according to Claim 19, comprising an infeed star wheel for transferring articles from the first conveyor to the rotatable device, and an outfeed star wheel for transferring articles from the rotatable device to the second conveyor. * S. *5 S * I I... S. * S I * S * I $1 S S... a...

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