GB2547484A

GB2547484A - Device and method for assay processing within an analyzer system

Info

Publication number: GB2547484A
Application number: GB1603021.5A
Authority: GB
Inventors: Grohbuhl Bernd; Zver Martin
Original assignee: Stratec Biomedical AG
Current assignee: Stratec Biomedical AG
Priority date: 2016-02-22
Filing date: 2016-02-22
Publication date: 2017-08-23
Also published as: GB201603021D0

Abstract

A device 10 comprises at least one container 1 containing a fluid and magnetic particles, at least one magnet 2 mounted on a magnet holder 3 wherein the magnet holder is rotatably coupled to a motor unit 4 for rotating the magnet holder around a rotation axis A1 such that the at least one container is arranged so that the at least one magnet rotates around the at least one container (1). The device further comprises a container holder 5 for holding the container in a fixed position with respect to the magnet holder. The device may further comprise an aspiration element (62; fig 3a) which is operatively coupled to a lifting element with lifting drive for moving the aspiration element. The device may further comprise at least one injector element (71; fig 3a) and a measuring unit with sensor. The device is used to perform an assay. A method of assay processing employing the device is also disclosed.

Description

Title:_Device and method for assay processing within an analyzer system

Field of the invention [0001] The field of the invention relates to a device and method for assay processing of patient samples stored in a container within an analyzer system with a mid to high throughput of patent samples and a high number of tests performed with these samples. More specifically, the present invention relates to a device and method for mixing, separating, purifying and measuring of these patient samples within the analyzer system.

Background of the invention [0002] In common automatic analyzer systems the steps of adding samples (e.g., reagents) stored in a container (e.g., a cuvette), mixing or shaking the samples, magnetic separation, waste aspiration, wash liquid injection, incubation and measurement are done by different modules. Therefore, the sample containing container (e.g., the cuvette) will be moved between different modules to perform the necessary process steps. These steps are: Filling the container with a patient sample and reagents. The filling is usually done by a pipetting robot. The container needs to be shaked to get nearly all relevant particles of the sample in contact with the magnetic beads (i.e., shaking the sample.). The process of binding of the relevant sample particles to the magnetic beads needs a certain temperature to start (i.e., incubation.). The incubation module therefore heats up the liquid inside the container. A magnet outside the container is used to separate the relevant particles bonded at the magnetic beads from the rest of the liquid (i.e., separation.). The magnetic field of the magnet forces the magnetic beads to move to one side of the container. After aspiration, the magnetic separation forms a small spot of marked particles called bead pellet. After the separation magnet has pulled the magnetic beads to the container wall, an aspiration probe can aspirate the remaining waste liquid out of the container (i.e., waste aspiration). The washer module injects wash liquid into the container to purify the magnetic bead pellet (i.e., wash liquid injection). The wash liquid will be aspirated by the aspiration probe. The step of washing could be repeated several times. After the washing, the container can be measured (i.e., measuring). This step could be fluorescence/luminescence measurement using a photomultiplier, photodiode, camera, etc.

[0003] However, the movement of the container between the different sub modules is mechanical complex and needs a lot of components. For each transport mechanism several guides, bearings, a drive and sledge is needed. Additionally, the movement needs to be monitored by different sensors. Therefore, the transport mechanism is complex, expensive and error-prone. The transport mechanism will wear out and needs to be replaced after time. Dust and wear could block the mechanics, which results in a complete instrument service. Vibration during transport of a filled container could cause spills. These spills can result in cross contamination of sample, which has to be avoided. Therefore, means have to be taken to avoid spilling. The transport of the container often needs several seconds, which decreases the overall throughput of the instrument. The timing of the different steps and components to each other is complex and therefore designed to a fixed time interval. Therefore, changes of the duration of the single steps are not possible.

Object of the invention [0004] It is an object of the present invention to provide a single device in which all needed sub-modules are combined and no unnecessary handling of the container is needed.

Summary of the invention [0005] In view of the state of the known technology and in accordance with a first aspect of the present invention, a device is provided that basically comprises at least one container having a fluid and magnetic particles therein and at least one magnet mounted on a magnet holder. The magnet holder is rotatably coupled to a motor unit for rotating the magnet holder around a rotation axis. The at least one container is arranged such that the at least one magnet rotates around the at least one container.

[0006] Preferably, the device further comprises a container holder for fixing the at least one container in a fixed position.

[0007] Preferably, the device is configured that the at least one container has a conical shape with a non-circular cross-section.

[0008] Preferably, the device further comprises a lifting unit having a lifting drive, which is operatively coupled to at least one aspirating element for moving the at least one aspirating element.

[0009] Preferably, the device is configured that the at least one aspirating element is located above the at least one container for moving the at least one aspirating element into the inner of the at least one container.

[0010] Preferably, the device further comprises an injecting unit having at least one injector element, which is arranged above the at least one container.

[0011] Preferably, the device is configured that the at least one injector element having at least one valve with at least one injector nozzle.

[0012] Preferably, the device further comprises a housing configured to at least partially accommodate the at least one container, wherein the housing has an insulation and at least one shutter element.

[0013] Preferably, the device further comprises a measuring unit having a measuring sensor configured to be arranged near the at least one container.

[0014] Preferably, the device further comprises a controlling unit for controlling at least one of the motor unit, the lifting unit, the injecting unit, and measuring unit.

[0015] In accordance with another aspect of the present invention, a method for assay processing is provided that basically comprises the method steps of placing a fluid and magnetic particles into at least one container, loading the at least one container, fixing the at least one container on a container holder, positioning at least one magnet such that the at least one magnet is rotatably arranged around the at least one container, and generating a magnetic field by rotating the at least one magnet via a magnet holder rotatably coupled to a motor.

[0016] Preferably, the method further comprises the method steps of mixing the fluid and the magnetic particles within the at least one container by the generated magnetic field, separating the magnetic particles form the fluid within the at least one container by placing the at least one magnet in a separation position, moving at least one aspirating element into the inner of the at least one container, aspirating the unneeded fluid from the at least one container via the at least one aspirating element and washing the magnetic particles within the at least one container by dispensing a wash liquid through at least one injector element, and measuring the at least one container by a measuring unit having a measuring sensor configured to be arranged near the at least one container.

[0017] The advantages of the invention of the present invention can be summarized as follows: a. All needed modules are located at one position, therefore, no handling of the container is necessary, only for loading and unloading the container. b. This enables a significant reduction of used parts and thus less costs. c. Since the liquid filled container is not moved but fixedly positioned, no splashing and therefore no risk of contamination occurs. d. Since the aforementioned process is not clocked, a high variability will be enabled.

[0018] Also other objects, features, aspects and advantages of the disclosed device for assay processing and the method for assay processing will become apparent to those skilled in the art from the following detailed description.

Summary of the figures [0019] The invention will now be described on the basis of figures. It will be understood that the embodiments and aspects of the invention described in the figures are only examples and do not limit the protective scope of the claims in any way. The invention is defined by the claims and their equivalents. It will be understood that features of one aspect or embodiment of the invention can be combined with a feature of a different aspect or aspects of other embodiments of the invention. This invention becomes more obvious when reading the following detailed descriptions of some examples as part of the disclosure under consideration of the enclosed drawings. Referring now to the attached drawings which form a part of this disclosure: [0020] FIG. 1 is a perspective side elevational view of a device for assay processing in accordance with a first embodiment; [0021] FIG. 2A is a side view of a container for storing a fluid and magnetic particles of the device illustrated in Fig. 1; [0022] FIG. 2B is a top view of the container for storing a fluid and magnetic particles of the container illustrated in Fig. 2A; [0023] FIG. 3A is a schematic side view of parts of a device in accordance with the second embodiment; [0024] FIG. 3B is a schematic perspective view of parts of the device illustrated in Fig. 3A; [0025] FIG. 3C is a rear perspective side elevational view of the device for assay processing in accordance with a first embodiment including a lifting unit and an injecting unit; [0026] FIG. 3D is a front perspective side elevational view of the device illustrated in Fig. 3C; [0027] FIG. 4 an enlarged side view of the injecting unit of the device illustrated in Fig. 3C; [0028] FIG. 5A is a front perspective side elevational view of a device for assay processing in accordance with a third embodiment including a housing; [0029] FIG. 5B is an enlarged view of the housing of the device illustrated in Fig. 5A showing a measuring sensor, in which the lifting unit and injecting unit are removed; [0030] FIG. 5C is an enlarged top view of the housing of the device illustrated in Fig. 5B showing a temperature sensor, in which the measurement sensor is removed; and [0031] FIG. 6 is an enlarged bottom view of the device illustrated in Fig. 5A showing a controlling unit.

Detailed description [0032] The object of the present invention is fully described below using examples for the purpose of disclosure, without limiting the disclosure to the examples. The examples present different aspects of the present invention. To implement the present technical teaching, it is not required to implement all of these aspects combined. Rather, a person skilled in the art will select and combine those aspects that appear sensible and required for the corresponding application and implementation.

[0033] Referring initially to Figure 1, a device 10 for assay processing in accordance with a first embodiment is illustrated. Here, Figure 1 shows a shaking and separation mechanism. The device 10 comprises a container 1, a magnet 2, a magnet holder 3, and a motor unit 4. The container 1 (e.g., a cuvette) is fixed to the device 10 via a container holder 5, which is fixedly mounted on the device 10. In particular, the container 1 comprises a holding structure 11 and is mounted to the container holder 5 via the holding structure 11 by inserting the container 1 into the container holder 5 via a transport mechanism (not shown). The container 1 may contain a fluid, for example a patient sample or primer and reagents, and small particles, which having a structure that is able to dock on the molecular geometry of particles, which are present in the fluid as well as a magnetic component. The small particles, as discussed herein, are configured to work as a special marker for bonding important particles of the containing fluid for separating the important particles of the fluid. While the container 1 is illustrated as a single container 1, the device 10 may have more than one container 1 (e.g., cuvette) as needed and/or desired. A multi cavity reaction cuvette or a microtiter plate as needed and/or desired may replace the container 1. At least one magnet 2 is mounted on the magnet holder 3. In particular, the at least one magnet 2 is angularly mounted on the magnet holder 3. However, the magnet 2 could be mounted on the magnet holder 3 in different angles as needed and/or desired. While the device 10 is illustrated with one magnet 2, the device 10 may have multiple magnets 2 as needed and/or desired. The at least one magnet 2, for example, is configured as a permanent magnet. The permanent magnet could be replaced by several coils arranged around the container 1. The magnet holder 3 is connected to the motor unit 4, for example, a stepper motor via a motor shaft 41. The stepper motor could be replaced by any kind of motor without gear. Thus, the motor holder 3 is rotatably coupled to the motor unit 4 for rotating the magnet holder 3 around a rotation axis Al. The container 1 is mounted above the magnet holder 3 such that the magnet 2 rotates around the container 1 around the rotation axis Al. A light barrier 31 is fixedly arranged on the device 10 for initializing the position of the magnet 2 via the magnet holder 3, before shaking the fluid. In particular, the magnet holder 3 interrupts the light barrier 31 in the proper position.

[0034] In case of the shaking mechanism of the device 10, by rotating the magnet holder 3 via the motor shaft 41, the magnet 2 rotates around the fixed container 1 with a defined speed and acceleration profile. The magnet particles in the fluid are trying to follow the generated magnetic field, while the fluid itself stands still. Therefore, the number of magnetic particles getting in contact with the relevant particles of the fluid stored in the container 1 increases. Hence, a homogenous fluid mixture is provided. The magnet movement can be continuous or alternating. In case of an alternating movement of the magnet, less space around the container 1 is needed and the insulation can be closer to the container 1. This results in a better incubation performance at less energy. The present invention is not limited on the above arrangement, the number and position of the magnets 2 can be modified for different applications with different liquid levels and viscosities as needed and/or desired.

[0035] In case of the separation mechanism of the device 10, the magnet holder 3 will be moved into a separation position. In this position, the magnetic particles (e.g., special markers) bonded with the important particles of the fluid will be forced by the magnet 2 to move to the side wall of the container 1. As a result, the magnetic bead pellets are separated from the liquid.

[0036] Figure 2A shows a side view of the container 1 for storing the fluid and magnetic particles of the device 10 illustrated in Figure 1. With the first illustrated embodiment, the container 1 has a conical geometry. For example, the container 1 could be formed as a cuvette with a pyramidal shape. However, the present invention is not limited to such shape and can be formed in different shapes as needed and/or desired. The container 1 comprises the holding structure 11 and a container body 12. The holding structure 11 is configured to be hold by the container holder 5 in a fixed position on the device 10 (see FIG. 1). The pyramidal shape of the container body 12 may have curved edges 13, as can be seen best in FIG. 2B, which shows a top view of the container 1 illustrated in Figure 2A. Due to the curved edges 13 of the container body 12, the magnet 2 can be closer to the center of the container 1. By providing a pyramidal shape of the container 1, the residual volume during waste aspiration, which will be discussed below in more detail, will be reduced and several containers 1 can be stacked together. Further, by providing such conical geometry of the container 1, there is more turbulence within the containing fluid compared to a cylindrical shape, which results in a faster magnet-particle binding process. As can be seen in Figure 2B, the container body 12 has a non-circular cross-section. Thus, the distance between the magnet 2 and the fluid contained in the container 1 changes several times during one rotation of the magnet 2, which results in a changing magnetic field strength causing turbulences.

[0037] Referring now to Figures 3A to 3D, a device 100 for assay processing in accordance with a second embodiment is illustrated. The device 100 comprises the same configuration as the device 10 in accordance with the first embodiment except for the additional components of a lifting unit 6 and an injecting unit 7. Thus, elements having substantially the same function as those in the first embodiment will be numbered the same here, and will not be described and/or illustrated again in detail here for the sake of brevity.

[0038] As can be seen in Figures 3C and 3D, the device 100 further comprises the lifting unit 6 and the injecting unit 7. The lifting unit 6 has a lifting drive 61, which is operatively coupled to an aspirating element 62 (e.g., an aspiration probe). The lifting unit 5, in particular the aspirating element 62 is configured to be located above the container 1 of the device 100. The lifting drive 61 may be formed as a Z-lift mechanism (e.g., aspiration probe Z-lift drive) for moving the aspirating element 62 into the inner of the container 1 in a vertical direction for waste aspiration. While the lifting drive 61 as illustrated is configured as a Z-lift mechanism, the lift drive 61 of the lifting unit 6 may be formed a different lifting mechanism as needed and/or desired. When the magnet 2 is used for magnetic separation and the magnet 2 is placed in the separation position with the magnetic particles located at the side wall of the container 1, the aspirating element 62 is moving downwards by the lifting unit 6 to the bottom of the container 1 and the unneeded fluid/liquid will be aspirated from the container 1.

[0039] As can be seen in Figures 3A, 3D, and 4, the device 100 further comprises the injecting unit 7 for providing a wash liquid injection. After the aspiration of the unneeded fluid/liquid from container 1, washing of the magnetic bead pellets is needed to purify the magnetic beads. Therefore, the injecting unit 7 comprises at least one injector element 71, which is arranged in the near vicinity of the top portion of the container 1. As can be seen best in Figures 3D and 4, the injector element 71 has at least one valve 72 with at least one injector nozzle 73. After the aspiration, wash liquid is dispensed through the injector nozzle 73 of the injector element 71 of the injector unit 7 into the container 1, in particular to the side wall of the container body 12 of the container 1. Several washing steps are used to purify and insulate the necessary information and to get a reliable result in the following measuring process.

[0040] Now mainly referring to Figures 5A to 5C, a device 200 for assay processing in accordance with a third embodiment is illustrated. The device 200 comprises the same configurations as the device 10 and 100 in accordance with the first and second embodiments except for the additional components of a housing 8 and a measuring unit 9. Thus, elements having substantially the same function as those in the first and second embodiments will be numbered the same here, and will not be described and/or illustrated again in detail here for the sake of brevity.

[0041] As can be seen in Figure 5A, the device 200 comprises a housing 8, which is configured to at least partially accommodate the components of the device 200. The device 200 further comprises a shutter element 81. The assay process requires a certain liquid temperature over a defined time. Therefore, the device 200, in particular at least the container 1, is surrounded by the housing 8 having an insulation for providing an incubator function.

[0042] As can be seen best in Figure 5C, the device 200 further comprises a heating element 83 (e.g., a heating foil) and a temperature sensor 82, which are arranged inside the housing 8 to get the temperature to a defined range. As can be seen in Figures 5B and 5C, a housing opening 84 is formed at the front of the housing 8. The housing opening 84 is covered by a shutter element 81 to load and unload the device 200 with the container 1. The shutter element 81 reduces the temperature loss and avoids incoming ambient light. Since the housing 8 completely covers the container 1, the rotation of the magnet holder 3 including the at least one magnet 2 also swirls the tempered air inside of the housing 8, which results in an homogenous temperature around the container 1 of the device 200.

[0043] Now mainly referring to Figure 5B, the device 200 further comprises a measuring unit 9 having a measuring sensor 91, which is configured to be arranged near the vicinity of the container 1 in the housing 8. After the washing process, the measurement is started. The analysis result can be measured using one of a photomultiplier, a photodiode, a camera or by similar means, as needed and/or desired.

[0044] Now referring to Figure 6, the device 200 for assay processing in accordance with the second embodiment further comprises a controlling unit 20 for controlling at least one of the motor unit 4, the lifting unit 6, the injecting unit 7, and the measuring unit 9. The controlling unit 20 comprises a printed circuit board and a controller. The controlling unit 20 is arranged on the housing 8 of the device 200. However, the controlling unit 20 may be located on a different component of the device 200 as needed and/or desired.

[0045] Another aspect of the present invention is to provide a method for assay processing. The method comprises the steps of placing a fluid and magnetic particles into the container 1 and loading the container 1 through the shutter element 81 into the device 10, 100, 200. The method further comprises the steps of fixing the container 1 on the container holder 5 in the fixed position, positioning the magnet 2 such that the magnet 2 is rotatably arranged around the container 1, and generating a magnetic field by rotating the at magnet 2 via the magnet holder 3, which is rotatably coupled to the motor 4.The method further comprises the step of mixing the fluid and the magnetic particles within the container 1 by the generated magnetic field, separating the magnetic particles form the fluid within the container 1 by placing the magnet 2 in the separation position.

[0046] The method also comprises the step of moving the aspirating element 62 in a vertical direction into the inner of the container 1 and aspirating the unneeded fluid from the container 1 via the aspirating element 62 located inside of the container body 12. Further, the method comprises the step of washing the magnetic particles within the container 1 by dispensing the wash liquid through the injector element 71, and measuring the container 1 by the measuring unit 9 with the measuring sensor 91 configured to be arranged near container 1.

[0047] From the above description of the present invention, those skilled in the art will perceive improvements, changes, and modifications on the present invention. Such improvements, changes, and modifications within the skill in the art are intended to be covered by the appended claims.

Reference Number List 1 container 2 magnet 3 magnet holder 4 motor unit 5 container holder 6 lifting unit 7 injecting unit 8 housing 9 measuring unit 10, 100, 200 device 11 holding structure 12 container body 13 curved edges 20 controlling unit 31 light barrier 41 motor shaft 61 lifting drive 62 aspirating element 63 lift mechanism 71 injector element 72 valve 73 injector nozzle 81 shutter element 82 temperature sensor 83 heating element 84 housing opening 91 measuring sensor

Claims

1. A device (10) for assay processing comprising at least one container (1) having fluid and magnetic particles therein; and at least one magnet (2) mounted on a magnet holder (3), wherein the magnet holder (3) is rotatably coupled to a motor unit (4) for rotating the magnet holder (3) around a rotation axis (Al), and wherein the at least one container (1) is arranged such that the at least one magnet (2) rotates around the at least one container (1).

2. The device (10) according to claim 1, further comprising a container holder (5) for fixing the at least one container (1) in a fixed position with respect to the magnet holder (3).

3. The device (10) according to claim 1 or 2, wherein the at least one container (1) has a conical shape.

4. The device (10) according to claim 3, wherein the at least one container (1) has a non-circular cross-section.

5. The device (10) according to any one of claims 1 to 4, further comprising a lifting unit (6) having a lifting drive (61), which is operatively coupled to at least one aspirating element (62) for moving the at least one aspirating element (62).

6. The device (10) according to claim 5, wherein the lifting unit (6) is arranged such that the at least one aspirating element (61) is located above the at least one container (1) for moving the at least one aspirating element (61) into the inner of the at least one container (1).

7. The device (10) according to one of the above claims, further comprising an injecting unit (7) having at least one injector element (71), which is arranged above the at least one container (1).

8. The device (10) according to claim 8, wherein the at least one injector element (71) having at least one valve (72) with at least one injector nozzle (73).

9. The device (10) according to one of the above claims, further comprising a housing (8) configured to at least partially accommodate the at least one container (1).

10. The device (10) according to claim 9, wherein the housing (8) has an insulation.

11. The device (10) according to claim 9 or 10, wherein the housing (8) has at least one shutter element (81).

12. The device (10) according to one of the above claims, further comprising a measuring unit (9) having a measuring sensor (91) configured to be arranged near the at least one container (1).

13. The device (10) according to one of the above claims, further comprising a controlling unit (20) for controlling at least one of the motor unit (4), the lifting unit (6), the injecting unit (7), and the measuring unit (9).

14. A method for assay processing, the method comprising the steps of: a. placing a fluid and magnetic particles into at least one container (1); b. loading the at least one container (1); c. fixing the at least one container (1) on a container holder (5); d. positioning at least one magnet (2) such that the at least one magnet (2) is rotatably arranged around the at least one container (1); and e. generating a magnetic field by rotating the at least one magnet (2) via a magnet holder (3) rotatably coupled to a motor (4).

15. The method according to claim 14, further comprising the step of mixing the fluid and the magnetic particles within the at least one container (1) by the generated magnetic field.

16. The method according to claim 14 or 15, further comprising the step of separating the magnetic particles form the fluid within the at least one container (1) by placing the at least one magnet (2) in a separation position.

17. The method according to claim 15 or 16, further comprising the step of moving at least one aspirating element (62) into the inner of the at least one container (1).

18. The method according to claim 17, further comprising the step of aspirating the unneeded fluid from the at least one container (1) via the at least one aspirating element (62) and washing the magnetic particles within the at least one container (1) by dispensing a wash liquid through at least one injector element (71).

19. The method according to one of the above claims, further comprising the step of measuring the at least one container (1) by a measuring unit (9) having a measuring sensor (91) configured to be arranged near the at least one container (1).