AU2012261555A1 - Magnetic Particle Washing Station - Google Patents

Abstract

Embodiments of the invention relate to a clinical instrument analyzer system for the automatic analysis of patient samples. In one embodiment, the analyzer may be used to 5 analyze bodily fluid samples, such as blood, plasma, serum, urine or cerebrospinal fluid, for example. Embodiments of the invention relate to an apparatus and method, for example, an immunoassay method, for separating out target molecules in a magnetic field and then analyzing those target molecules with a luminometer. -20 3910872_1 (GHMatters) P81537.AU.2 5/12/12

Description

MAGNETIC PARTICLE WASHING STATION FIELD OF THE INVENTION 5 [00011 The present invention relates to a clinical instrument analyzer system and specifically to a magnetic particle washing station. BACKGROUND OF THE INVENTION 10 [00021 Separation, isolation, and concentration are process steps common to a chemical analysis. Often, these steps are taken to remove interfering substances so that a subsequent chemical analysis can be performed. This separation stage can be performed in several ways including solvent extraction, solvent evaporation, and resin exchange. Magnetic separation, another technique for removing interfering substances, 15 is a process of separation, isolation, and concentration where the sought-for substance is attached or bound to magnetic particles. The magnetic particles offer advantages of handling including speed, convenience, and low energy input. The use of magnetic particles is particularly suited to handling samples of small volume. 20 [0003] Previous magnetic separation techniques have involved the movement of a sample substance through a series of magnets. This technique, although effective, is cumbersome and is subject to mechanical failures. Additionally, since during the separation process the samples are moving through a series of magnets, it is difficult to control the environment surrounding the samples, as the samples cannot be completely 25 enclosed. Therefore, it would be desirable to eliminate the series of magnets and provide a magnetic separation technique where samples do not have to be passed through several magnets to complete the separation process. SUMMARY OF THE INVENTION 30 [0004] One aspect of the present invention provides a system for manipulating magnetic particles in a vial comprising: a receiving member for holding the vial containing magnetic particles; and a magnet array comprising a first magnet having an upper horizontal surface, wherein a north pole face of said first magnet is positioned 35 adjacent to said vial, a spacer having an upper horizontal surface, wherein said spacer is positioned on said upper horizontal surface of said first magnet, a second magnet -1 39108721l (GHlMatters)P99 S37,AU.2 4/I2/I2 having an upper horizontal surface, said second magnet is positioned on said upper horizontal surface of said spacer, wherein a north pole face of said second magnet is positioned adjacent to said vial, and a third magnet positioned on said upper horizontal surface of said second magnet, wherein a south pole of said third magnet is positioned 5 adjacent to said vial, wherein, said magnet array generates a magnetic field for use in manipulating said magnetic particles in said vial. [0004a] Another aspect of the invention provides a system for manipulating magnetic particles in a vial comprising: a receiving member for holding the vial containing 10 magnetic particles; and a magnet array comprising a first magnet having an upper horizontal surface, wherein a south pole face of said first magnet is positioned adjacent to said vial, a spacer having an upper horizontal surface, wherein said spacer is positioned on said upper horizontal surface of said first magnet, a second magnet having an upper horizontal surface, said second magnet is positioned on said upper 15 horizontal surface of said spacer, wherein a south pole face of said second magnet is positioned adjacent to said vial, and a third magnet positioned on said upper horizontal surface of said second magnet, wherein a north pole face of said third magnet is positioned adjacent to said vial, wherein, said magnet array generates a magnetic field for use in manipulating said magnetic particles in said vial. 20 [0005] In one embodiment the spacer is manufactured from any of the following materials: aluminum, carbon fiber, polymers, other non-magnetic materials, and combinations thereof. In one embodiment, the magnet array is in a fixed position. In another embodiment, the magnet array is moveable. In some embodiments, the magnet 25 array comprises a material including neodymium-iron-boron (Nd-Fe-B), typically known as neodymium, samarium-cobalt (Sm-Co), alnico, or hard ferrite (ceramic). In one embodiment, the system further comprises any one of the following: a humidity detector, a humidity regulator, a spring finger, a humidity regulated vial chamber, a temperature regulator, an aspirator pipette, or an injector pipette. In some embodiments, 30 the humidity and/or temperature are regulated. In some embodiments, the ratio of the magnet arrays to vial receiving members is 1:1. In certain embodiments, the horizontal surface of the first and second magnets is greater than the vertical surface of those magnets. In some embodiments, the south pole of the first and second magnets face the vial and the north pole of the third magnet faces the vial. 35 [00061 Another embodiment of the present teachings relates to a magnetic washing module for washing magnetic particles in a vial, comprising one or more pipettes, one -2or more magnets, a receiving member, and a humidity detector for determining the humidity in the magnetic washing module. [00071 Another aspect of the present teachings relates to a method for moderating 5 magnetic particular aggregation in a diagnostic assay comprising providing a magnetic washing module comprising one or more pipettes, one or more magnets, and a vial chamber; introducing a vial containing magnetic particles into the vial chamber of the magnetic washing module; and moderating the humidity in the vial chamber to provide a predetermined relative humidity. In one embodiment, the humidity is regulated by 10 controlling the rate of fluid injection into the vial. In another embodiment, the humidity is regulated by controlling the rate of aspiration. In another embodiment, the magnetic washing module further comprises a humidity detector. [0008] Another embodiment relates to a magnetic washing module for washing 15 magnetic particles in a vial comprising one or more pipettes, one or more magnets, and a humidity detector. [00091 Another embodiment relates to a method for luminometric analysis, in which a sample vial contains a patient's sample and magnetic particles which bind the target 20 molecules in the sample, comprising transporting the sample vial to a magnetic washing module, applying a magnetic field to the sample vial containing the target components and magnetic particles through one wall of the sample vial by a magnetic array, injecting and aspirating a wash fluid in the sample vial to wash the magnetic particles, and transporting the sample vial from the magnetic washing module to a luminometer. 25 [0009a] Another aspect of the invention provides a method for using an automated luminometric analysis system to determine presence of a target molecule in a patient's sample contained in a sample vial, said system comprising a magnetic washing module, a luminometer, a carousel, and a magnetic array comprising a first magnet wherein the 30 north pole of said first magnet is positioned to face said vial, a second magnet wherein the north pole of said second magnet is positioned to face said vial, and a third magnet wherein the south pole of said third magnet is positioned to face said vial, said magnets optionally separated by a spacer, the method comprising: a) transporting said sample vial to said magnetic washing module via said carousel; and, b) applying a magnetic 35 field to said sample vial containing said target molecule through one wall of said sample vial by said magnetic array positioned on the same side of said wall of said sample vial as the magnetic field. -3- [0009b] Another aspect of the invention provides a method for using an automated luminometric analysis system to determine presence of a target molecule in a patient's sample contained in a sample vial, said system comprising a magnetic washing module, a luminometer, a carousel, and a magnetic array comprising a first magnet wherein the 5 south pole of said first magnet is positioned to face said vial, a second magnet wherein the south pole of said second magnet is positioned to face said vial, and a third magnet wherein the north pole of said third magnet is positioned to face said vial, said magnets optionally separated by a spacer, the method comprising: a) transporting said sample vial to said magnetic washing module via said carousel; and, b) applying a magnetic 10 field to said sample vial containing said target molecule through one wall of said sample vial by said magnetic array positioned on the same side of said wall of said sample vial as the magnetic field. [0009c] Another aspect of the invention provides a method for moderating magnetic 15 particle aggregation, comprising: providing a magnetic washing module comprising a vial, a magnetic array comprising a first magnet, a second magnet and a third magnet, each of the magnets being positioned to have one of their poles facing the vial wherein the poles of the first and second magnets facing the vial are of the same polarity and the pole of the third magnet facing the vial is of an opposite polarity, and a vial chamber; 20 introducing said vial containing magnetic particles into said vial chamber of said magnetic washing module; and moderating the humidity to provide a predetermined relative humidity in said vial chamber. [0009d] Another aspect of the invention provides a magnetic washing module for 25 washing magnetic particles in a vial, comprising: a magnet station comprising a magnetic array comprising a first magnet a second magnet and a third magnet, each of the magnets being positioned to have one of their poles facing the vial wherein the poles of the first and second magnets facing the vial are of the same polarity and the pole of the third magnet facing the vial is of an opposite polarity; and, a humidity 30 detector. BRIEF DESCRIPTION OF THE DRAWINGS [0010] These embodiments and other aspects of this invention will be readily apparent 35 from the detailed description below and the appended drawings, which are meant to illustrate and not to limit the invention, and in which: [00111 Figure 1 is a top view of the clinical instrument analyzer system according to an exemplary embodiment of the present invention. 40 [0012] Figure 2 is a perspective view of the magnetic washing module according to an exemplary embodiment of the present invention. [00131 Figure 3 is a perspective view of a vial in the vial apparatus of the magnetic 45 washing module according to an exemplary embodiment of the present invention. -3a 3910872_1 (GHMalters) PSI 537,AU2 6/12/12 [0014] Figure 4 is a depiction of the vial locked in the magnet washing station according to an exemplary embodiment of the present invention. [0015] Figure 5 is a depiction of one arrangement of the magnets according to an exemplary embodiment of the present invention. 5 [0016] Figure 6 is a depiction of another arrangement of the magnets according to an exemplary embodiment of the present invention. [0017] Figure 7 is a depiction of two magnet arrangements according to an exemplary embodiment of the present invention. 100181 Figure 8 is a depiction of a vial in the magnet station during a magnetic wash 10 process according to an exemplary embodiment of the invention. [0019] Figures 9 and 10 are depictions of magnetic particle pellets collected in the vial according to an exemplary embodiment of the present invention. DESCRIPTION [00201 The present invention will be more completely understood through the 15 following description, which should be read in conjunction with the attached drawings. In this description, like numbers refer to similar elements within various embodiments of the present invention. Within this description, the claimed invention will be explained with respect to embodiments. The skilled artisan will readily appreciate that the methods and systems described herein are merely 20 exemplary and that variations can be made without departing from the spirit and scope of the invention. [00211 Embodiments of the invention relate to a clinical instrument analyzer system for the automated analysis of patient samples. In one embodiment, the analyzer may be used to analyze bodily fluid samples, such as blood, plasma, serum, urine or 25 cerebrospinal fluid, for example. Embodiments of the invention relate to an apparatus and method, for example, an immunoassay method, for separating out target molecules in a magnetic field and then analyzing those target molecules with a luminometer.

[0022] Figure 1 is a top view of the clinical instrument analyzer system according to an embodiment of the present invention. The illustrated clinical instrument analyzer system 20 contains one or more stations or modules for treatment and analysis of patient samples contained in a vial 46. The vial 46 may be a cuvette, test tube, or 5 any other receptacle for holding a sample. In one embodiment, the clinical instrument analyzer system 20 includes at least the following: a vial loader 22, a sample station (not shown), a reagent station (not shown), a carousel 28, a magnetic washing module 30, a plurality of pipettes 24, a luminometer 32, a humidity regulator (not shown), and a heater or temperature regulator (not shown) to incubate 10 the sample vial 46. [00231 In one embodiment, the vial loader 22 holds a plurality of vials 46. The vial loader 22 may, for example, load vials 46 onto the carousel 28 as described in the concurrently filed U.S. patent application entitled "Apparatus and Methods for Dispensing Sample Holders" (Attorney Docket No, 1NL-098). In some 15 embodiments, the vial loader 22 comprises a rotatable vial loader carousel with vertical slots to hold stacks of vials 46. The vials 46 are stacked in a sleeve and the sleeve may be inserted into the vial loader 22. The vial loader 22 expels vials 46 from the sleeve and loads them on to the carousel 28. [00241 With continued reference to Figure 1, the carousel 28, in one embodiment, 20 holds, and distributes a plurality of vials 46 to various stations or modules in the clinical instrument analyzer system 20. The exemplary carousel 28 rotates via an attached motor and may address any one of a plurality of analyzing stations proximate to the carousel 28. In one embodiment, a transfer arm (not shown) moves vials 46 from the carousel 28 to the various analyzing stations of the clinical 25 instrument analyzer system 20. {0025] The plurality of analyzing stations include, for example, a reagent station (not shown), a magnetic washing module 30, a sample adding station (not shown) and an incubation station (not shown). Other stations for processing the sample may also be available and the invention is not limited to these stations.

[0026] A sample is introduced into the vial 46 at the sample adding station. Then, the reagent station (not shown), in one embodiment, deposits the required reagents into the vial 46 on which a desired analysis will be performed. [0027] In one embodiment, the reagent station includes a plurality of reagent 5 containers. The reagent containers may contain one or more reagents which may be injected from the reagent container into a vial 46. Depending on the analysis to be conducted on the sample and which target molecule is to be analyzed, the reagent station may provide one or more of rinse fluids, antibodies against the sample substance, a marker substance containing luminogens, and/or carrier particles that 10 are magnetizable. In one embodiment, the marker substance attaches to specific antibodies directed to the target molecule in the sample. In some embodiments, the magnetizable carrier particles (magnetic particles) are made of iron or any other magnetic or magnetizable material. In certain embodiments, the magnetizable particles are paramagnetic. The magnetizable particles may have a grain size, for 15 example, in the range of about 0.5-6.0 pn, for example, 0.9-1.3 gim, 2.6-3.0 pn or 4.5-5.0 gm, preferably. In yet another embodiment, the exterior of the magnetizable particles are coated with a latex layer that contains specific antibodies against the target molecule. The antibodies attached to the magnetic particles and the antibodies attached to the marker substance recognize the target molecules and bind to them in 20 an immunochemical reaction. As a result, specific complexes of magnetic particles, markers, and target molecules are formed. These specific complexes then may be examined in the luminometer. [0028] The clinical instrument analyzer system 20 according to one embodiment of the invention includes a plurality of pipettes 24 as shown in Figure 1. In one 25 embodiment, one or more pipettes 24 transfer fluids, including e.g., sample fluid, reagents, water, or a wash fluid between, for example, the reagent containers and the vials 46, sample containers and the vials 46, a wash fluid container and the vials 46, or vials 46 to a wash fluid receptacle for used wash fluid. [0029] With continued reference to Figure 1, the luminorneter 32 may be any device 30 that measures luminescence, such as the luminescence of the luminescent marker in the specific complexes. The intensity of the luminescence serves as an indication of the presence or absence of the target molecule in the fluid sample. The luminescence radiation passes through the vial 46 and can be detected by, for example, a photodetector in the luminometer 32. In order not to distort the measurement results, the free luminogens that are not bonded to the sample 5 molecules are removed prior to the luminescence measurement. In one embodiment, the unbonded luminogens are removed through a series of washing cycles in the magnetic washing station as described below. Once the luminescence is measured for the sample, the intensity of the luminescence is evaluated taking into account calibration relationships and calibration measurements for the concentration of the 10 target molecule. [0030] Figure 2 is a perspective view of the magnetic washing module 30 according to an embodiment of the present invention. The exemplary magnetic washing module 30 includes the following: a base 38, one or more magnet stations 35, for example, eight magnet stations, and a vial apparatus 41, including one or more 15 receiving members 42. According to one embodiment of the invention, each magnet station 35 comprises a magnet array 34, a magnet holder 36 and a spring finger 40. The number of stations 35 per magnetic washing module 30 is not limited to the number illustrated, but may be any number. For example, two, three, four, five, six, eight or more magnet stations 35 may be positioned in the magnetic washing module 20 30 (not shown). [0031] With continued reference to Figure 2, the exemplary magnet holder 36 holds a magnet array 34. The magnet holder 36 of the magnet station 35 may be made of, for example, stainless steel, aluminum, other metals, plastics, or ceramics. In one embodiment, the magnet holder 36 is L-shaped with the magnet array 34 affixed to 25 interior surface of the vertical section of the L. [0032] With continued reference to Figure 2, the base 38 of the magnet station 35 may be made of, for example, stainless steel, aluminum, other metals, plastics, or ceramics. The magnet station 35 may be releasably attached to the base 38 or the magnetic station 35 may be fixed to the base 38. 30 100331 With continued reference to Figure 2, the spring finger 40 may be attached to the magnet holder 36 at the end of the horizontal section of the L via a spring mechanism (not shown), The spring mechanism permits the magnet holder 36 to securely hold a vial 46 against the magnet array 34. In one embodiment, the spring finger 40 is comprised of plastic, but its composition is not limited to plastic and may include any polymer, ceramic, or metal. In another embodiment, the spring 5 finger 40 is biased towards the magnet array 34. When the vial 46 is introduced into the magnet holder 35, the spring finger 40 moves away from the magnet array 34 to accommodate the vial 46. [0034] Figure 3 is a perspective view of a vial 46 in the vial apparatus 41 of the magnetic washing module 30 according to an embodiment of the present invention. 10 The vial apparatus 41 includes a receiving member 42 with chamfers 47, one or more aspirator pipettes 44, a vial cover 48, one or more spacers 50, an injector plate 52, and one or more injector pipettes 54. The vial apparatus 41 is positioned above the magnet stations 35. The exemplary vial apparatus 41 receives the vials 46 from the carousel 28 via a transfer arm (not shown). 15 [0035] With continued reference to Figure 3, in one embodiment, the receiving member 42 holds the vials 46 in position while the vials 46 are processed in the magnetic washing station 30. The receiving member 42 is sized and shaped to fit a vial. For example, the vial receiving member 42 may be rectangular, square, circular, or semi-circular in shape with an inlet 45 to receive the vial 46 of like or 20 similar shape. The receiving member 42 may be composed of, for example, plastic, ceramic or metal. The vial 46 may be guided into place at the receiving member 42 by, for example, chamfers 47, i.e. small grooves or channels, at the inlet 45 of the receiving member 42. A transfer arm (not shown) may use, for example, a proximity sensor to confirm that it has delivered a vial 46 to each receiving member 42 that 25 can be used. In one embodiment, the number of receiving members 42 is such that the ratio of vials 46 in a receiving member 42 to magnet stations 35 is one to one. [0036] With continued reference to Figure 3, each vial 46 may be placed under an aspirator pipette 44 and an injector pipette 54. The aspirator pipette 44, for example, transfers excess or residual gas, air, and/or fluid from the vial 46. The injector 30 pipette 54, for example, supplies liquid wash solution to the vials 46. In one embodiment, both the aspirator pipette 44 and the injector pipette 54 pass through the injector plate 52 to the vial 46. In one embodiment, the aspirator pipettes 44 and injector pipettes 54 assist to keep the magnetic particles moist during the magnetic washing process, A series of washes and aspirations, for example, deposit a thin layer of liquid on the magnetic particles protecting the magnetic particles and the 5 specific complexes from clumping and drying together. In some embodiments, a plate spacer 50 is located between the receiving member 42 and the injector plate 52. The plate spacer 50 and the injector plate 52 may be composed of, for example, plastic, ceramic, or metal. [0037] Referring back to Figure 2, the vial apparatus 41 and the magnet stations 35 10 on the base 38 each may move relative to the other in order to engage the vial 46 in the magnet station 35. In one embodiment, the base 38, including the magnetic array 34, is fixed and the vial apparatus 41 moves, for example downwards, to the base 38. In another embodiment, the vial apparatus 41 is fixed and the base 38, including the magnetic array 34, moves, for example, upwards to the vials 46 in the 15 vial apparatus 41. The base 38 may, for example, move between a first position and a second position, relative to the vial apparatus 41. The first position may be a position in which the magnet station 35 and the vial apparatus 41 are separated by a predetermined distance. The second position may be a position in which the magnet station 35 has moved toward the vial apparatus 41 sufficiently to permit the magnet 20 station 35 to engage the vial 46 in the vial apparatus 41. In yet another embodiment, both the vial apparatus 41 and the base 38 move. 10038] Figure 4 depicts the vial 46 locked in the magnet station 35 according to an embodiment of the present invention. In the exemplary embodiment, when the vial 46 is locked in the magnet station 35, the wall 73 of the vial 46 proximate to the 25 magnet array 34 is flush (i.e. in the same plane) with the magnet array 34. As the vial 46 engages the magnet station 35, the vial 46 engages and compresses a spring (not shown) contained within the spring finger 40 pushing the spring finger 40 away from the magnet array 34. The tension of the spring in the spring finger 40 holds the vial 46 in place in the magnet station 35. 30 [0039] Figures 5 and 6 are schematics of two embodiments of magnet array 34 configurations. The magnets may be composed of, for example, neodymium-ironboron (Nd-Fe-B), typically known as neodymium, samarium-cobalt (Sm-Co), alnico, or hard ferrite (ceramic). [0040] Figure 5 depicts one embodiment of the magnet array 34 configuration including three magnets. This embodiment consists of a first magnet 56, a second 5 magnet 60, a third magnet 62, and a spacer 58. The first magnet 56 is positioned at the bottom. The third magnet is positioned at the top, and the second magnet 60 is positioned between the first magnet 56 and the third magnet 62. [0041] With continued reference to Figure 5, the side of the magnet array 34 that faces the vial 46 is depicted. In one embodiment, the first magnet 56, the largest of 10 the three magnets, has an upper horizontal surface and is positioned such that the north pole of the first magnet 56 faces the vial 46 (not shown). A spacer 58, having an upper horizontal surface, is positioned on the upper horizontal surface of the first magnet 56 between the first magnet 56 and the second magnet 60. The second magnet 60, positioned on the upper horizontal surface of the spacer 58, has an upper 15 horizontal surface and has its north pole oriented in the same manner as the first magnet 56, i.e., facing the vial 46. The third magnet 62 is on the upper horizontal surface of the second magnet 60 and has its south pole oriented in a direction opposite to the second magnet 60 and the first magnet 56, i.e., facing the vial. In another embodiment, the magnets are arranged such that the first magnet 56 south 20 pole and the second magnet 60 south pole face the vial 46 and the third magnet 62 north pole faces the vial 46. In other words, the orientation of the polarity of the third magnet 62 is opposite to the orientation of the polarity of the first magnet 56 and the second magnet 60. [0042] In one embodiment, with continued reference to Figure 5, the second magnet 25 60 and third magnet 62 are configured such that the horizontal axis of each magnet exceeds the vertical axis of the magnet. This orientation of the magnets produces few interactions with the magnets in the other magnet stations 35 (not shown). Thus, when arranged in the magnetic washing module 30, the magnet arrays 34 all may, for example, have the same orientation. However, the magnet arrays 34 may 30 be arranged in varying orientations and the orientations are not limited to those illustrated.

[0043] Figure 6 depicts another embodiment of the magnet array 34 configuration. The illustrated embodiment includes a vertical configuration of the individual magnets including a first vertical magnet 64, a second vertical magnet 65, a third vertical magnet 67, a first spacer 66, a fourth vertical magnet 68, a second spacer 70 5 and a fifth vertical magnet 72. In one embodiment, the first vertical magnet 64, second vertical magnet 65, the third vertical magnet 67, the fourth vertical magnet 68, and the fifth vertical magnet 72, each have a longer vertical axis than horizontal axis. [00441 With continued reference to Figure 6, the first vertical magnet 64, second 10 vertical magnet 65, and third vertical magnet 67 are arranged in a Halbach array. A Halbach array is an arrangement of magnets in which the magnetic field can be augmented on one side of the array, the side facing the vial 46 (not shown), and near zero on the opposite side of the array. In one embodiment, illustrated in Figure 6, this array may be positioned such that the first magnet 64 having its south pole 15 facing the vial 46, a second magnet 65 adjacent the first magnet 63 with neither north nor south pole facing the vial 46, and a third magnet 67 adjacent the second magnet 65 but not the first magnet 63, having its north pole facing the vial 46. The first vertical magnet 64, second vertical magnet 65, and third vertical magnet 67 may be arranged in any other configuration that produces a magnetic field on the side of 20 the array facing the vial 46 and a near zero magnetic field on the opposite side. Furthermore, the present teachings are not limited to three magnets on the bottom of the array, For example, four, five, six, or more could be implemented so long the magnetic field is augmented on the side facing the vial 46 and near zero on the opposite side. 25 100451 With continued reference to Figure 6, in one embodiment, the first spacer 66 is positioned on the upper horizontal surface, of the first vertical magnet 64, the second vertical magnet 65, and the third vertical magnet 67. Positioned on top of the first spacer 66 are the fourth vertical magnet 68, including a north pole facing the vial 46, a fifth vertical magnet 72, including a south pole facing the vial 46, and a 30 second spacer 70 positioned between the fourth vertical magnet 68 and the fifth vertical magnet 72. This embodiment of the magnet array 34 configuration may cause interference effects if several magnet arrays 34 of this configuration are proximate to each other. Therefore, as shown in Figure 7, magnet arrays 34 with this configuration should be used in mirror configurations, such that one magnet array 34 is a mirror image of an adjacent magnet array 34. [0046] With reference to Figures 5 and 6, the spacers 58, 66, and 70 are sized in the 5 range of, for example, .5 mm to 1.5 mm in width. The spacers 58, 66, and 70 are composed of, for example, aluminum, plastic, ceramics, carbon fiber, polymers, combinations of the foregoing, or any other non-magnetic material. [0047) Figure 8 depicts a vial 46 positioned in a magnet station 35 during a magnetic wash process according to one embodiment of the invention. Once the 10 vial 46 is engaged by the magnet station 35, the magnetic field generated by the magnet array 34 attracts the specific complexes 43 of magnetic particles, markers, and target molecules.. Thus, the specific complexes 43 in the vial 46 are held on the interior wall 73 of the vial 46 proximate to the magnet array 34. A series of washes and aspirations via the aspirator pipettes 44 and the injector pipette 54 coupled with 15 the magnetic field application produces a pellet 74 of the specific complexes 43 in the vial as shown, for example, in Figures 9 and 10. In order to facilitate the production of the pellet 74, the magnet array 34 and the vial 46 may move relative to each other. For example, if the vial 46 is stationary, the magnet array 34 may move up and down to assist in creating the pellet 74. 20 [0048] Figure 9 depicts an exemplary pellet 74 formed with the use of the magnet array in Figure 5. Figure 10 depicts an exemplary pellet 74 formed with the use of the second magnet array 34 depicted in Figure 6. The pellet 74 is formed in the same location with the use of either of the exemplary magnetic arrays 34 (not shown). The pellet 74 is formed by concentrating the magnetic field lines from the 25 magnetic array 34 at the location of the vial wall 73 where the pellet 74 forms. Because of the high concentration of magnetic field lines, the specific complexes 43 (containing the magnetic particles, target molecules and markers) will be attracted to that region of the wall 73 and will clump together, eventually forming the pellet 74. The pellet 74, once extracted from the vial 46 and analyzed in the luminometer 32, 30 may facilitate the analysis of the target molecules in the luminometer 32 (not shown).

[00491 In another embodiment (not shown), the magnetic washing module 30 comprises a vial chamber, which may be humidity regulated. The vial chamber is, for example, a rectangular box that encloses the magnetic washing module 30. The vial chamber may be sealed once the vials 46 are placed in the vial receiving 5 members 42. The sealed vial chamber does not permit the transfer of air in and out of the chamber. Alternatively, the clinical instrument analyzer system 20 is maintained within a housing and the humidity of the interior of the housing is regulated. [0050] In one embodiment, the vial chamber prevents, for example, the vial 46 from 10 contacting the ambient air and enables the moderation of the humidity in the vials 46 to provide a predetermined relative humidity. Humidity regulation or moderation may prevent unwanted particle aggregation prior to the desired aggregation into a pellet 74 of the specific complexes caused by the action of the magnetic field in the magnetic washing station 35. Sealing the vials 46 from outside air permits, for 15 example, the monitoring of the humidity of the air immediately surrounding the vials 46. The level of humidity affects the performance of the magnetic washing module 30. In certain embodiments, a humidity detector determines the humidity inside the vial chamber. Once the humidity has been determined by the humidity detector, the humidity of the vial chamber may be altered and regulated, for example, by 20 controlling the rate of fluid injection by the injector pipette 54 or the rate of aspiration by the aspirator pipette 44 into the vial 46. [0051] In some embodiments, the aspirator 44 and injector pipettes 54 are used to ensure that the particles do not dry out or clump together prior to the application of the magnetic field. In one embodiment, after aspiration the injector pipette 44 25 dispenses a small amount of liquid into the vial 46 in the range of 15 to 20 R'. [0052] In another embodiment, the aspirator pipette 44 is used to regulate the humidity. For example, the aspirator pipette 44 is submerged in the liquid contained within the vial 46. The depth of the aspirator pipette 44 ranges from, for example, just below the surface of the liquid contained within the vial to about .5 mm from the 30 vial bottom. Once the aspirator pipette 44 is submerged, the aspirator pipette 44 removes liquid from the vial 46. The flow of liquid through the aspirator pipette 44 is in the range of, for example, 400 ml of liquid in .5 seconds to 400 l in 5 seconds, alternatively 5 mL/min to 20 mL/min, preferably 10 mL/min. This low, gentle rate of flow may be accomplished through the use of, for example, a vacuum or peristaltic pump. 5 [0053] In some embodiments, the aspirator pipette 44 or the injector pipette 54 contain wash solution. The wash solution also may contain, for example, surfactants to reduce the surface tension in the solution thereby mitigating particle clumping. [00541 The humidity control is not limited to these examples, but may be controlled by any known means of regulating humidity, such as injecting humid and/or dry air 10 into the chamber, spraying a mist of water into the chamber and various other methods. The fluid may be injected into the chamber at a rate of 25 m/min or 60 mL/min, depending on the diameter of the injector, or preferably in the range of 20 mL/min to 100 mL/min. [0055] In another embodiment, the magnetic washing module 30 comprises a 15 temperature regulator (not shown). The temperature regulator may insure that the temperature of the vial chamber remains at a predetermined, constant, and desired level. [0056) In another aspect, the invention is directed to a method of washing magnetic particles used in a diagnostic assay conducted by a clinical instrument analyzer 20 system 20. According to the method of the invention, an automated clinical instrument analyzer system 20 including a vial loader 22, a sample station (not shown), a reagent station (not shown), a carousel 28, a magnetic washing module 30, a plurality of pipettes 24, a luminometer 32 and a heater is provided. For example, the vial loader 22 loads a vial 46 onto the carousel 28. The vial 46 is carried from 25 the vial loader 22 via the carousel 28 to a sample station, In an embodiment, the humidity is regulated. [00571 At the sample station, a patient's sample, including the target molecules to be analyzed, is introduced to the vial 46. At the reagent station, antibodies against the target molecule, a marker substance containing, for example, luminogens and 30 magnetizable particles are introduced to the vial 46. The marker substance and the magnetic particles are coated with specific antibodies to the target substance. The antibodies recognize and bind to the target molecule in the patient's sample in an immunochemical reaction. As a result, specific complexes 43 of magnetic particles, markers, and target molecules are formed. The vial 46 is incubated for a predetermined period of time and temperature according to the requirements of the assay. 5 10058] Following incubation of the vial 46, the carousel 28 then transports the vial 46 to the magnetic washing module 30. The vial 46 is positioned in a vial holder 42, the vial holder 42 may be lowered or raised, and the magnetic field is applied. The magnetic field of the magnet array 34 in the magnet station 35 attracts the specific complexes 43 to the interior wall 73 of the vial 46 proximate to the magnet array 34. Then, the vial 46 10 is injected and aspirated one or more times with wash fluid through the aspirator pipette 44 and injector pipette 54. The vial 46 is rinsed one or more times by injection or aspiration to remove all remaining particles except for the particles complexed in the specific complexes 43. [0059] Once the vial 46 has been washed several times, the magnetic field is removed 15 by moving the magnet station 35, or the vial 46, or by moving the magnet station 35 and vial 46. Then, the carousel 22 transports the vial 46 to a luminometer 32. The luminometer 32 analyzes the vial sample for the specific complexes 43. Since the luminogen is attached to the target molecule in the patient sample in the specific complex 43, the user can readily ascertain the amount of target molecules in the sample, 20 based on the luminescence of the pellet 74. [0060] Variations, modification, and other implementations of what is described herein will occur to those of ordinary skill in the art without departing from the spirit and scope of the invention as claimed. Accordingly, the invention is to be defined not by the preceding illustrative description but instead by the spirit and scope of the following 25 claims. t0061] In the claims which follow and in the preceding description of the invention, except where the context requires otherwise due to express language or necessary implication, the word "comprise" or variations such as "comprises" or "comprising" is used in an inclusive sense, i.e. to specify the presence of the stated features but not to -15preclude the presence or addition of further features in various embodiments of the invention. [0062] It is to be understood that, if any prior art publication is referred to herein, such reference does not constitute an admission that the publication forms a part of the 5 common general knowledge in the art, in Australia or any other country. -16-

Claims (24)

1. A method for moderating magnetic particle aggregation, comprising: providing a magnetic washing module comprising a vial, a magnetic array 5 comprising a first magnet, a second magnet and a third magnet, each of the magnets being positioned to have one of their poles facing the vial wherein the poles of the first and second magnets facing the vial are of the same polarity and the pole of the third magnet facing the vial is of an opposite polarity, and a vial chamber; introducing said vial containing magnetic particles into said vial chamber of said 10 magnetic washing module; and moderating the humidity to provide a predetermined relative humidity in said vial chamber.

2. The method of claim 1 wherein the humidity is moderated by controlling the 15 rate of a fluid injection into the vial.

3. The method of claim 1 wherein the humidity is moderated by controlling the rate of aspiration of the fluid in the vial. 20

4. The method of any one of claims 1 - 3 wherein said magnetic washing module further comprises a humidity detector.

5. The method according to any one of claims 1 - 4 comprising separating the first, second and third magnets with respective spacers. 25

6. A magnetic washing module for washing magnetic particles in a vial, comprising: a magnet station comprising a magnetic array comprising a first magnet a second magnet and a third magnet, each of the magnets being positioned to have one of 30 their poles facing the vial wherein the poles of the first and second magnets facing the vial are of the same polarity and the pole of the third magnet facing the vial is of an opposite polarity; and, a humidity detector. 35

7. The magnetic washing module of claim 6 further comprising a vial apparatus comprising one or more receiving members, a vial cover, and/or an injector plate. -17 3910872_ (GHMatters) P81537.AU.2 5/12/12

8. The magnetic washing module of claim 7 wherein said receiving member comprises chamfers.

9. The magnetic washing module of any one of claims 6 - 8 wherein said magnet 5 station further comprises a magnet holder and a spring finger.

10. The magnetic washing module of any one of claims 6 - 9 further comprising a means for transporting the vial from the magnetic washing module to a luminometer. 10

11. The magnetic washing module of any one of claims 6 - 10 further comprising a temperature regulator.

12. The magnetic washing module of claim 11 wherein said temperature regulator comprises regulating temperature of a vial chamber to a predetermined, and/or a 15 constant level.

13. The magnetic washing module of claim 12 wherein said vial chamber comprises a humidity regulated vial chamber. 20

14. The magnetic washing module of claim 13 wherein the humidity of said humidity regulated vial chamber is at a predetermined relative humidity.

15. The magnetic washing module of claim 13 wherein the humidity in said humidity regulated vial chamber is regulated by controlling rate of a fluid injection into 25 the vial.

16. The magnetic washing module of claim 13 wherein humidity in said humidity regulated vial chamber is regulated by controlling rate of aspiration of a fluid in the vial. 30

17. The magnetic washing module of any one of claims 6 - 16 wherein said humidity detector is for determining humidity in the magnetic washing module.

18. The magnetic washing module of any one of claims 6 - 16 wherein said 35 humidity detector is for determining humidity in said vial chamber. -18 3910872_ l (G HMatters) P81537.AU.2 5/12/12

19. The magnetic washing module of claim 18 wherein once said humidity in the vial chamber is determined, the humidity in the chamber may be altered and/or regulated. 5

20. The magnetic washing module of claim 19 wherein said humidity alteration and/or regulation prevents particle aggregation prior to a desired aggregation into a pellet.

21. The magnetic washing module of any one of claims 6 - 8 wherein the vial 10 apparatus receives the vials from a carousel via a transfer arm.

22. The magnetic washing module any one of claims 6 - 21 comprising one or more pipettes. 15

23. The magnetic washing module of claim 6 comprising: one or more pipettes; a receiving member; and wherein the humidity detector is operable for determining the humidity in said magnetic washing module. 20

24. The magnetic washing module any one of claims 6 - 23 comprising respective spacers positioned to separate the first, second and third magnets form each other. -19 3910872_ l (G HMatters) P81537.AU.2 5/12/12