Microbead control in consumables

Abstract

A magnetic separator for a liquid handling system includes a base unit having at least one receiver configured to receive consumables, the at least one receiver being sized to receive consumables at least partially within a predetermined location within the base unit. The magnetic separator also includes a magnet system located within the base unit near the at least one receiver, the magnet system comprising: a first separation magnet configured to separate microspheres located within the consumable when the first magnet is near the consumable; and a movement system configured to move the first magnet in at least two directions to accommodate the shape of the consumable.

Description

[0001] Related applications

[0002] This application claims the benefit of the earlier filing date of U.S. Provisional Patent Application Serial No. 63 / 004,818, entitled “Bead Manipulation in a Consumable,” filed April 3, 2020, the entire contents of which are incorporated herein by reference. Technical Field

[0003] This disclosure generally relates to the field of automation of chemical, biological, and biochemical processes or reactions. More specifically, the present invention relates to apparatus and methods for separating magnetic particles in consumables of liquid handling systems. Background Technology

[0004] The use of microparticles and nanoparticles is ideal for many technological applications: biosensing applications, medical and biological applications, such as the delivery of modified drugs during medical treatment, and the bioseparation, purification and screening of antibodies, proteins and the like.

[0005] These microparticles and nanoparticles are typically referred to as “microbeads.” Generally, in the following text, “microbeads” will be defined as any label, barcode, molecular beacon, sponge, or particle ranging in size from a few angstroms to a few millimeters, capable of selectively transporting one or more specific components under the influence of external forces.

[0006] In particular, magnetic separation technology has become a fundamental part of DNA sequencing. In fact, magnetic separation technology is not only a relatively inexpensive and highly scalable method, but also offers many advantages over similar methods, such as subjecting samples to very little mechanical stress, high recovery efficiency, and sample purification.

[0007] Magnetic microbeads are used as carriers for proteins, cells, antibodies, antigens, and nucleic acids by applying a suitable coating to their outer surface. In order to bind and capture the desired target analyte, the magnetic microbeads must be coated with ligands that bind specifically to the target. The choice of ligand type will depend entirely on the target molecule that must be captured.

[0008] The central core of the microsphere is magnetic and responsible for its ability to respond to an external magnetic field. Metal oxides are generally preferred because they are more stable than pure metals. Microspheres can have single-domain or multi-domain structures depending on the size of the magnetic core. The size of the microsphere primarily affects the coercivity: the smaller the microsphere, the lower the coercivity. In particular, nanoparticles of approximately 5 nm–15 nm are superparamagnetic, while microparticles are ferromagnetic.

[0009] The magnetic and physical properties of the microbeads are chosen according to the application for which the magnetic particles must be used. When the magnetic field is removed, the nanoparticles have the advantage of not containing a remanence; at the same time, the magnetic force is very small so that the viscous force is dominant: this means that the separation and movement of the particles is more difficult.

[0010] In general, the magnetic separation can be carried out using microbeads whose association with the magnetic poles is very weak (paramagnetic), microbeads with high magnetization sensitivity (ferromagnetic), microbeads which tend to magnetize in the direction at 180° to the applied magnetic field (diamagnetic) or using ferromagnetic nanoparticles which exhibit superparamagnetic behaviour.

[0011] In magnetic microbead separation, the first step is the binding of the sample to the external coating of the microbeads. A liquid solution containing the target analyte is dispensed into a magnetic microbead buffer. Generally, the liquid is mixed in order to increase the efficiency of the binding between the magnetic microbeads and the analyte.

[0012] After the binding step, the separation of the analyte is achieved by moving the microbeads by applying an external magnetic field. This will generate a force according to the following formula:

[0013]

[0014] A careful observation of the formula shows that the magnetic force depends on the gradient of the magnetic field B and the magnetic moment m of the microbead. Since the gradient is the change of the quantity m-B per unit distance, the magnetic field depends to a large extent on the distance between the magnet applying the magnetic field and the microbead.

[0015] When the magnetic field is applied, the magnetic microbeads are magnetized and start to form clusters which move in the direction of the magnetic field gradient. After a certain amount of time, which depends on the number and size of the microbeads, the strength of the magnetic field gradient and the viscosity of the solution liquid, the magnetic beads are pelletized in a defined area which depends on the magnetic field lines.

[0016] At this point, the sample separation is achieved by separating the microbeads from the remaining liquid solution. Generally, the remaining liquid solution is either evacuated or the cluster of magnetic microbeads is moved to another container.

[0017] During the separation, it is important to control the distance between the magnetic field and the microbeads. However, this can become difficult in many cases, such as when the container or other consumables are irregularly shaped. For example, some containers or consumables comprise a conical bottom, in which the microbeads can be gathered during the binding phase and before the magnetic field is applied. It can be difficult to apply a magnetic field to the microbeads located at the conical bottom of such consumables.

[0018] Further, it is important that during the binding step (before the magnetic field is applied) no magnetic field acts on the beads within the consumable. Such a magnetic field can jeopardize the workflow during the binding process. Therefore, it is also important to create a system such that the binding process is not affected by the magnetic field of the magnet that will be used for the subsequent separation step. SUMMARY

[0019] In one embodiment, a magnetic separator for a liquid handling system comprises: a base unit having at least one receptacle configured to receive a consumable, the at least one receptacle being sized to receive the consumable at least partially at a predetermined location within the base unit; and a magnet system located within the base unit proximate to the at least one receptacle, the magnet system comprising: a first separation magnet configured to perform separation of beads located within the consumable when the first magnet is located in proximity to the consumable; and a movement system configured to move the first magnet in at least two directions in order to accommodate a shape of the consumable.

[0020] Additionally or alternatively, the magnet system further comprises: a stationary magnet located at a stationary location within the base unit, wherein the stationary magnet is configured to deflect magnetic field lines of the first separation magnet away from the consumable received within the at least one receptacle and to remove residual magnetic field from the first separation magnet from the beads located within the consumable.

[0021] Additionally or alternatively, the movement system comprises a vertical axis configured to move the first separation magnet in a vertical direction and a horizontal axis configured to move the first separation magnet in a horizontal direction.

[0022] Additionally or alternatively, the at least one receptacle is sized to receive the consumable extending in a cylindrical shape having a conical bottom, and wherein the movement system is configured to move the first separation magnet vertically along a side of the cylindrical shape such that a portion of the first separation magnet is in close proximity to the cylindrical shape of the received consumable, and wherein the movement system is configured to move the first separation magnet horizontally along a side of the conical bottom such that the portion or another portion of the first separation magnet is in close proximity to the conical body.

[0023] Additionally or alternatively, the first separation magnet is configured to maintain contact with the consumable or the receptacle along an entire vertical height of the consumable and the receptacle.

[0024] Additionally or alternatively, the base unit comprises at least three receptacles, each receptacle sized to at least partially receive a separate consumable at a predetermined location within the base unit, wherein the first separation magnet is configured to perform separation of microbeads in a consumable located within a first receptacle of the at least three receptacles when the first separation magnet is located in proximity to the consumable, and wherein the magnet system further comprises: a second separation magnet configured to perform separation of microbeads in a second consumable located within a second receptacle of the at least three receptacles when the second separation magnet is located in proximity to the second consumable; and a third separation magnet configured to perform separation of microbeads of a third consumable located within a third receptacle of the at least three receptacles when the third separation magnet is located in proximity to the third consumable.

[0025] Additionally or alternatively, the movement system is configured to move the first separation magnet, the second separation magnet and the third separation magnet in unison.

[0026] Additionally or alternatively, the movement system is configured to move the first separation magnet, the second separation magnet and the third separation magnet independently.

[0027] Additionally or alternatively, the movement system is configured to rotate the first separation magnet in addition to movement in the vertical direction and the horizontal direction.

[0028] Additionally or alternatively, the magnet system further comprises: an opposite separation magnet configured to perform separation of microbeads located within a consumable when the opposite separation magnet is located in proximity to the consumable, wherein the movement system is configured to move the opposite separation magnet in at least two directions in order to accommodate a shape of the consumable, and wherein the opposite separation magnet is located on an opposite side of the at least one receptacle as the first separation magnet.

[0029] Additionally or alternatively, the opposite separation magnet is configured to rotate between a first position and a second position, wherein in the first position a magnetic field of the opposite separation magnet is in a first orientation, and wherein in the second position the magnetic field of the opposite separation magnet is in a second orientation opposite the first orientation.

[0030] Additionally or alternatively, the magnet system further comprises: a control system configured to detect a size of at least one of the at least one receptacle and a received consumable, wherein the control system is configured to automatically determine a movement procedure of the first separation magnet for performing separation of microbeads.

[0031] According to another embodiment, a liquid handling system comprises: a magnetic separator comprising: a base unit having at least one receptacle configured to receive a consumable, the at least one receptacle sized to receive the consumable at least partially at a predetermined location within the base unit; and a magnet system located within the base unit proximate to the at least one receptacle, the magnet system comprising: a first separation magnet configured to perform separation of microbeads located within the consumable when the first separation magnet is located in proximity to the consumable; and a movement system configured to move the first separation magnet in at least two directions in order to accommodate a shape of the consumable; and a liquid handling device comprising: a liquid handling automation movement system; a head configured to be moved by the automation liquid handling movement system; and at least one pipette attached to the head and configured to be insertable into and retractable from the at least one receptacle of the base unit of the magnetic separator, the pipette configured to aspirate and dispense liquid from the consumable received in the at least one receptacle.

[0032] According to another embodiment, a method of separating microbeads comprises: receiving a consumable by a receptacle of a base unit of a magnetic separator for a liquid handling system; performing separation of microbeads located within the consumable by the magnetic separator by moving a first separation magnet of the magnetic separator into proximity to the consumable; and moving the first separation magnet by a movement system of the magnetic separator in at least two directions during the separation.

[0033] Additionally or alternatively, the method further comprises: deflecting a magnetic field of the first separation magnet away from the consumable by a second magnet of the magnetic separator; and removing a residual magnetic field from the first separation magnet from the microbeads located within the consumable by the second magnet.

[0034] Additionally or alternatively, the second magnet is a stationary magnet within the magnetic separator, and the method further comprises: moving the first separation magnet into proximity to the second magnet.

[0035] Additionally or alternatively, moving the first separation magnet further comprises: moving the first separation magnet in a vertical direction along a vertical axis; and moving the first separation magnet in a horizontal direction along a horizontal axis.

[0036] Additionally or alternatively, the consumable extends in a cylindrical shape having a conical base, wherein moving the first separation magnet further comprises: moving the first separation magnet vertically along a side of the cylindrical shape by the movement system of the magnetic separator such that a portion of the magnet is in close proximity to the cylindrical shape of the received consumable; and moving the first separation magnet horizontally along a side of the conical base by the movement system of the magnetic separator such that the portion or another portion of the magnet is in close proximity to the conical body.

[0037] Alternatively or concurrently, the method may further include: maintaining contact between the first separating magnet and the consumable or receiver along the entire vertical height of the consumable and receiver.

[0038] Alternatively or concurrently, the base unit includes at least three receivers, each receiver being sized to receive individual consumables at least partially within a predetermined location within the base unit, wherein a first separation magnet performs separation of microbeads from consumables located within the first receiver of the at least three receivers, and wherein the method further includes: performing separation of microbeads from the second consumable within the second receiver of the at least three receivers by moving a second separation magnet of a magnetic separator closer to the second consumable, and moving the second separation magnet in at least two directions during separation by a movement system of the magnetic separator; and performing separation of microbeads from the third consumable within the third receiver of the at least three receivers by moving a third separation magnet of a magnetic separator closer to the third consumable, and moving the third separation magnet in at least two directions during separation by a movement system of the magnetic separator. Attached Figure Description

[0039] The above and other advantages of the present invention can be better understood by referring to the following description in conjunction with the accompanying drawings, in which the same reference numerals indicate the same elements and features in each drawing. For clarity, not every element is labeled in every drawing. The drawings are not necessarily drawn to scale, but are intended to illustrate the principles of the invention.

[0040] Figure 1 A schematic diagram of a pipetting robot system with a magnetic separator according to one embodiment is depicted.

[0041] Figure 2 Depicting according to an implementation scheme Figure 1 A side view of the magnetic separator.

[0042] Figure 3 Depicting according to an implementation scheme Figure 1 and Figure 2 A perspective view of a magnetic separator.

[0043] Figure 4 Depicting according to an implementation scheme Figure 1 and 2 A cross-sectional perspective view of a magnetic separator, with the magnet system in its original position.

[0044] Figure 5 Depicting according to an implementation scheme Figure 1 and Figure 2 A perspective view of a magnetic separator, with the magnet system in a lower position.

[0045] Figure 6 depicts a schematic view of a magnetic separator according to one embodiment. Figure 1 and Figure 2 a perspective view of a magnetic separator of

[0046] Figure 7 depicts a schematic view of another magnetic separator according to one embodiment.

[0047] Figure 8 depicts a schematic view of a magnetic separator according to one embodiment. Figure 7 wherein the second magnet is rotated relative to the first magnet. DETAILED DESCRIPTION

[0048] Reference throughout this specification to "one embodiment" or "an embodiment" means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present teachings. The appearances of the phrase "in one embodiment" or "an embodiment" in various places in the specification are not necessarily all referring to the same embodiment.

[0049] The present teachings will now be described in more detail with reference to exemplary embodiments of the present teachings as illustrated in the accompanying drawings. While the present teachings are described in conjunction with various embodiments and examples, it should be understood that the present teachings are not limited to such embodiments. Conversely, the present teachings cover various alternatives, modifications and equivalents, as will be appreciated by those skilled in the art. Additional embodiments, modifications, and embodiments within the scope of the present teachings as described herein will occur to those skilled in the art upon reviewing the disclosure. Persons of ordinary skill in the art will recognize that additional uses within the scope of the present teachings as described herein will occur as a result of the teaching herein.

[0050] According to embodiments described herein, a liquid handling system is described. More specifically, a magnetic separator for a liquid handling system is described, which is configured to perform a separation process on a liquid, a suspension, etc. contained in a consumable held in the magnetic separator. Hereinafter, a "consumable" can be any container of a liquid or a suspension, such as, but not limited to, a tube, a microtube, a vacutainer, a tube array, a microplate of various sizes, a microchip, a petri dish, a strip, etc. The consumable can be configured to be provided to the magnetic separator by the liquid handling system in an automated manner, or by a technician who can provide the consumable into a receptacle of the magnetic separator.

[0051] A magnetic separator can be configured to apply a magnetic field within a consumable to act on microspheres located within a liquid or suspension contained in the consumable. The magnetic separator is equipped with a movement system for moving a magnet contained within the separator to approach or contact the consumable held by the separator. This movement system can be configured to move the magnet in at least two directions (i.e., along both the vertical and horizontal axes) to adapt the movement of the magnet to the shape of the consumable. Since the magnetic field depends largely on the distance between the magnet and the microspheres within the consumable, the movement system is configured to move the magnet along the external shape of the consumable corresponding to the magnet. This biaxial movement is configured to prevent the magnetic field from decreasing as the magnet moves away from the wall of the consumable, particularly in cases where the consumable is non-uniform, such as a tube with a conical end.

[0052] Furthermore, the embodiments disclosed herein attempt to reduce or remove the magnetic field of the magnets on the microbeads within the consumable during the bonding process prior to the separation process. Residual magnetic fields from the magnetic separator have been found to be problematic during the bonding process and can jeopardize experimental workflows at this stage. The embodiments herein attempt to reduce or eliminate this problem.

[0053] Figure 1 A schematic diagram of a liquid handling system 10 with a magnetic separator 100 according to one embodiment is depicted. The liquid handling system 10 also includes a liquid handling automation device 20. The magnetic separator 100 may include a control system 101 for controlling its function. The liquid handling automation device 20 may also include a control system for controlling its function. In some embodiments, the liquid handling automation device 20 and the magnetic separator 100 may be a single unit having a combined control system for controlling both systems.

[0054] The automated liquid handling device 20 includes a liquid handling movement system 22, one or more heads 24a, 24b, and at least one pipette 26. The automated liquid handling device 20 may include automated arms 28a, 28b or other robotic "tool racks" for moving the one or more heads 24a, 24b. According to one embodiment, the automated arms 28a, 28b can move in any manner, have any size or shape, and have any number of dimensional degrees of freedom. The one or more heads 24a, 24b may include one or more heads 24a configured to engage with and move the consumable 30 into and out of the magnetic separator 100. Further, another head of the one or more heads 24b may have one or more attached pipettes 26. For example, the one or more heads 24b may include one or more aspiration and dispensing channel pipettes. In the case of multiple pipettes, the system may be configured to operate synchronously or independently. The pipettes 26 may be configured to aspirate and dispense fluid. The liquid handling automation device 20 can be configured to move one or more heads 24b such that the pipette 26 can engage with the consumable 30 within the magnetic separator 100 and the liquid or suspension in the consumable.

[0055] Various other mobile systems are envisioned, such as the liquid handling automation device 20, which includes a single robotic arm with different heads selectively attached thereto. In other embodiments, the liquid handling automation device 20 may include any number of automated arms. In yet other envisioned embodiments, liquid handling may not be automated, and the functions attributable to the arms and heads 24a, 24b may be performed manually by a technician. Regardless of the embodiment, the magnetic separator 100 may be configured to receive a consumable 30 containing a liquid or suspension in which microbeads are present, and the magnetic separator 100 may be configured to perform a magnetic bonding process between the microbeads and the fluid or analyte therein.

[0056] Figure 2 Depicting according to an implementation scheme Figure 1A side view of a magnetic separator 100. The magnetic separator 100 is shown as including a base unit 110 having at least one consumable receiver 112, the size of which is configured to at least partially receive consumable 30 within the base unit 110. Within the magnetic separator 100, near the consumable 30, is a movement system 120 configured to move a separating magnet 122. The movement system 120 can be configured to move the magnet in two directions or orientations, such as horizontally and vertically, via a vertical axis 124 and a horizontal axis 126. Thus, the separating magnet 122 can be configured to move close to the consumable 30 and remain in contact with the consumable 30 as the separating magnet 122 moves along the entire height of the consumable 30. Therefore, the movement system 120 can be configured to adapt the movement of the separating magnet 122 to the shape of the consumable 30, which is shown to include a tapered base 32.

[0057] As shown, the stationary magnet 130 is located below the consumable 30. The stationary magnet 130 can be located at a vertical position or height above the bottom of the base unit 110. The moving system 120 can move the separating magnet 122 to the same vertical position near the stationary magnet 130. The stationary magnet 130 can be configured to deflect the magnetic field lines of the separating magnet 122 away from the consumable 30 received within the receiver 112 and remove residual magnetic fields from the microbeads located within the consumable 30. When brought to this position, the separating magnet 122 can be considered to be in its original position, during which time a binding process may occur between the analytes and microbeads found within the consumable 30 before separation by the separating magnet 122. Therefore, the separating magnet 122 and the stationary magnet 130 can include the same magnetic poles facing each other, rather than having opposite magnetic poles facing each other. As shown, the north pole of the separating magnet 122 is oriented toward the north pole of the stationary magnet 130.

[0058] Figures 3 to 6 An exemplary embodiment of the magnetic separator 100 is depicted. Figure 3 A perspective view of a magnetic separator 100 is depicted. The magnetic separator 100 is shown as including a base unit 110 having a housing 114, which is shown as at least partially within... Figures 4 to 6The base unit 110 is shown to include three separate receivers 112, each sized to receive one of the consumables 30. When received in a receiver 112, the consumable may be at least partially located within the housing 114 of the base unit 110. Although the receivers 112 are shown to have the same size in the illustrated embodiment, the invention is not limited in this respect. Other embodiments may include any number of receivers; some embodiments may include receivers of different sizes relative to the other receivers in the base unit 110. The base unit 110 may be configured to receive any type of consumable. Furthermore, the receivers 112 may be adapted to expand or retract automatically or by the manipulation of a technician to flexibly receive consumables of different shapes and sizes.

[0059] Figure 4 Depicting according to an implementation scheme Figure 1 and 2 A cross-sectional perspective view of the magnetic separator 100, with the magnet system 140 in its original position. In the original position, the separating magnet 122 is close to the stationary magnet 130. As shown, in the original position, the stationary magnet 130 is configured to deflect the magnetic field lines of the separating magnet 122 away from the consumable (not shown) received within the receiver 112, and to remove residual magnetic fields from the microspheres located within the consumable. This original position can be utilized when the microspheres bind to the analytes within the consumable prior to the magnetic separation process. Because the separating magnet 122 is close to the stationary magnet 130, which is configured to reduce or otherwise remove residual magnetic fields from the microspheres located within the consumable, the separating magnet 122 can remain closer to the consumable in its original position without the stationary magnet 130 acting on a magnetic field. In other words, without the action of the fixing magnet 130 to reduce the magnetic field of the separating magnet 122, the separating magnet 122 may need to be moved further away from the consumable in its original position during the bonding process to achieve the same effect on the consumable position (i.e. no residual magnetic field or a significantly reduced residual magnetic field).

[0060] Each of the three individual receivers 112 is shown as including a main portion 116 having a cylindrical profile extending from the top of the housing 114 of the base unit 110. Each of the individual receivers 112 includes a tapered base 118 extending from the main portion 116. The receivers 112 can thus be configured to receive and hold consumables of the same shape. The receivers 112 contemplated herein are not limited to this shape or size characteristic. Receivers of any shape are contemplated. For example, adaptable receivers capable of receiving consumables of multiple shapes are also contemplated. Regardless of the implementation, the individual receivers 112 can provide a predetermined location in which consumable 30 can be placed and held in a manner by a magnetic separator 100, in which way a pipette 26 from the liquid handling system 10 can interact with the received consumable 30 by dispensing and drawing liquid therein.

[0061] As shown in the figure, the magnet system 140 includes a moving system comprising a vertical axis 124 and a horizontal axis 126. The moving system also includes a linear screw drive system 128 about the vertical axis 124. A frame 150 supports the linear screw drive system 128. Attached to the frame is a magnet holder 123, which holds the separator magnet 140 in a fixed vertical position relative to the frame 150. The frame 150 is configured to move up and down along the vertical axis 124 to provide vertical movement of the separator magnet 122. Similarly, the magnet holder 123 is further configured to move along the horizontal axis 126, as described below. Figures 5 to 6 As shown in the figure, a vertical track 129 with a supporting bearing system is shown for supporting the vertical movement of the frame 150.

[0062] Figure 4 The magnetic separator 100 shown includes three separate receivers 112. Therefore, although not shown, there may be three separate separator magnets 122, two of which are concealed. In one embodiment, the three separator magnets 122 can be configured to move uniformly. For example, the frame 150 may be a single frame extending across each of the three separate receivers 112 along its width within the magnetic separator 100. The concealed separator magnets can be attached to the frame 150 at each of the other two locations in the same manner as the separator magnets 122 are shown. In other embodiments, for each of the two concealed separator magnets, a separate, controllable, and independent shaft system may be included, allowing for completely independent movement.

[0063] Figure 5 Depicting according to an implementation scheme Figure 1 and Figure 2A perspective view of the magnetic separator 100, with the magnet system 140 in a lower position. As shown, relative to their original positions, the frame 150 and the separator magnet 122 have been moved vertically upward along the vertical axis 124. Further, the separator magnet 122 has been moved along the horizontal axis 126 in the direction of the receiver 112 to accommodate the tapered shape of the outer wall of the consumable and / or the receiver 112. Therefore, the separator magnet 122 is shown in contact with or very close to the receiver 112. In particular, the upper right corner of the separator magnet 122 is shown in contact with or very close to the outer wall of the receiver 112. In other embodiments where the receiver 112 does not include a fully enclosed outer wall separating the consumable from the separator magnet 122, the separator magnet 122 may be in direct contact with or very close to the consumable. In yet other embodiments, the movement system may be configured to impart rotational motion to the separator magnet 122. For example, it is desirable to rotate the separating magnet 122 such that the entire side of the cubic magnet contacts the conical outer wall of the receiver 112, rather than just the top edge.

[0064] Figure 6 Depicting according to an implementation scheme Figure 1 and Figure 2 A perspective view of the magnetic separator 100, with the magnet system 140 in a higher position. As shown, relative to... Figure 5 At a lower position, the frame 150 and the separator magnet 122 have moved further vertically upward along the vertical axis 124. Further, the separator magnet 122 has moved rearward along the horizontal axis 126 in the direction of the vertical axis 124 to accommodate the expanded shape of the outer wall of the consumable and / or receiver 112. This can be the highest position that the separator magnet 122 can achieve relative to the receiver 112. In this position, the separator magnet 122 can be in contact with or very close to the body 116 of the receiver.

[0065] Figure 7A schematic diagram of another magnetic separator 200 according to one embodiment is depicted. Magnetic separator 200 may be similar to magnetic separator 100. Therefore, the magnetic separator may include a movement system for moving a first separating magnet 222 via a vertical axis 224 and a horizontal axis 226. For example, this movement may be achieved in the manner described above. Unlike the embodiment described above, the stationary magnet has been replaced by a second movement system for moving a second separating magnet 232 via a second vertical axis 234 and a second horizontal axis 236. The second separating magnet 232 may be located on opposite sides of the receiver 112 and / or on the consumable 30 received within the receiver, serving as the first separating magnet 222. During separation, the first separating magnet 232 and the second separating magnet 232 may include opposite magnetic poles facing each other to enhance the magnetic field in the consumable 30 located within the receiver 212. The first magnet 222 and the second magnet 232 may each move in at least two directions (e.g., horizontally and vertically) to adapt to the shape of the consumable.

[0066] Figure 8 Depicting according to an implementation scheme Figure 7 A schematic diagram of a magnetic separator 200 is shown, in which a second magnet 236 rotates relative to a first magnet 222. Therefore, it is further envisioned that the second magnet 236 can rotate instead of comprising a fixed magnet, such that the magnetic poles of the second magnet 236 become oriented 180 degrees to the first magnet 222 during the separation process. In this way, the first separating magnet 222 and the second separating magnet 232 can include the same magnetic poles facing each other to reduce the residual magnetic field during the bonding step. Once the bonding process is complete and the separation process begins, the second separating magnet 232 can be configured to rotate back to its separation orientation, in which the opposite magnetic poles of the first magnet 222 and the second magnet 232 again face each other.

[0067] The present invention also envisions a method for separating microspheres. The method described herein can be performed using a magnetic separator. The function of the magnetic separator according to the method described herein can be controlled by the control system of the magnetic separator and / or the liquid handling system, such as the control system 101 of the magnetic separator 100 and / or the control system 21 of the liquid handling system 20.

[0068] The method may first include receiving a consumable (e.g., consumable 30) by a receiver (e.g., receiver 112) of a base unit (e.g., base unit 110) of a magnetic separator (e.g., magnetic separator 100) for use in a liquid handling system (e.g., liquid handling system 10). The method may include performing separation of microspheres located within the consumable by moving a first separating magnet (e.g., magnet 122) of the magnetic separator closer to the consumable. The method may include moving the first separating magnet in at least two directions during the separation process via a moving system (e.g., moving system 120).

[0069] The method may further include deflecting the magnetic field of the first separating magnet away from the consumable using a second magnet (such as a stationary magnet 130) of the magnetic separator. The method may also include removing residual magnetic fields from the first separating magnet from microspheres located within the consumable using the second magnet. To achieve this, the method may include moving the first separating magnet closer to the second magnet such that the magnetic poles of the first magnet face the matching magnetic poles of the second magnet.

[0070] According to some methods, the movement of the first separating magnet may include moving the first separating magnet in a vertical direction along a vertical axis and in a horizontal direction along a horizontal axis. Therefore, the method includes moving the first separating magnet with at least two degrees of freedom or along two axes.

[0071] According to the method described herein, the consumable may extend in a cylindrical shape having a conical base. In this case, moving the first separating magnet further includes vertically moving the first separating magnet along one side of the cylinder via a moving system of a magnetic separator, such that a portion of the magnet is brought close to the cylindrical shape of the received consumable. The method may also include horizontally moving the first separating magnet along one side of the conical base via a moving system of a magnetic separator, such that one or more portions of the magnet are close to the cone. This may include the first separating magnet maintaining or otherwise keeping in contact with the consumable or receiver along the entire vertical height of the consumable and receiver. In some embodiments, the method may include a moving system that, in addition to moving the first separating magnet in the vertical and horizontal directions, also rotates the first separating magnet.

[0072] In some methods, the base unit may include more than one receiver. For example, in the case where the base unit includes at least three receivers, each receiver is sized to at least partially receive a single consumable in a predetermined location, and the method includes a first separation magnet performing separation of microbeads located in the consumable within the first receiver of the at least three receivers. The method may also include performing separation of microbeads located in the second consumable within the second receiver of the at least three receivers by moving a second separation magnet of a magnetic separator close to the second consumable, and moving the second separation magnet in at least two directions during separation by a movement system of the magnetic separator. Furthermore, the method may include performing separation of microbeads located in the third consumable within the third receiver of the at least three receivers by moving a third separation magnet of a magnetic separator close to the third consumable, and moving the third separation magnet in at least two directions during separation by a movement system of the magnetic separator. In some embodiments, the method may include moving each of the first, second, and third separation magnets in a consistent manner. Other methods may include independently moving each of the first, second, and third separating magnets.

[0073] Other methods may include separating microbeads located within a consumable, wherein two opposing magnets are located on each side of the consumable and have opposite magnetic poles facing each other. The method may include uniformly moving each of the magnets, with one or both magnets moving in a manner that conforms to the shape of the consumable. The method may also include rotating one of the magnets between a first position and a second position to change the orientation of its magnetic poles by 180 degrees, such that the magnetic field at the second position is opposite to that at the first position. This rotation can be accomplished by the second magnet to remove residual magnetic fields from the microbeads located within the consumable from the first separating magnet.

[0074] In other embodiments, the method includes the control system detecting the size of the receiver or the received consumable and automatically determining the movement of the first separating magnet for performing the separation of the microbeads.

[0075] Although the invention has been shown and described with reference to specific embodiments, those skilled in the art will understand that various changes in form and detail may be made without departing from the spirit and scope of the invention as set forth in the appended claims.

Claims

1. A magnetic separator for use in a liquid handling system, the magnetic separator comprising: a base unit having at least one receptacle configured to receive a consumable, the at least one receptacle sized to receive the consumable at least partially at a predetermined location within the base unit; and a magnet system located within the base unit proximate to the at least one receptacle, the magnet system comprising: a first separation magnet configured to perform separation of beads located within the consumable when the first separation magnet is located proximate to the consumable; and a movement system configured to move the first separation magnet in at least two directions so as to accommodate a shape of the consumable, wherein the movement system comprises a vertical axis configured to move the first separation magnet in a vertical direction and a horizontal axis configured to move the first separation magnet in a horizontal direction, wherein the at least one receptacle is sized to receive the consumable extending in a cylindrical shape having a tapered bottom, and wherein the movement system is configured to move the first separation magnet vertically along a side of the cylindrical shape such that a portion of the first separation magnet is immediately proximate to the cylindrical shape of the received consumable, and wherein the movement system is configured to move the first separation magnet horizontally along a side of the tapered bottom such that the portion or another portion of the first separation magnet is immediately proximate to the tapered bottom.

2. The magnetic separator of claim 1, wherein the magnet system further comprises: a stationary magnet located at a stationary location within the base unit, wherein the stationary magnet is configured to deflect magnetic field lines of the first separation magnet away from the consumable received within the at least one receptacle and remove residual magnetic field from the first separation magnet from beads located within the consumable.

3. The magnetic separator of claim 1, wherein the first separation magnet is configured to remain in contact with the consumable or the receptacle along an entire vertical height of the consumable and the receptacle.

4. The magnetic separator of claim 1, wherein the base unit comprises at least three receptacles, each receptacle sized to receive a separate consumable at least partially at a predetermined location within the base unit, wherein the first separation magnet is configured to perform separation of beads in the consumable located within a first receptacle of the at least three receptacles when the first separation magnet is located proximate to the consumable, and wherein the magnet system further comprises: a second separation magnet configured to perform separation of beads within a second consumable located within a second receptacle of the at least three receptacles when the second separation magnet is located proximate to the second consumable; and a third separation magnet configured to perform separation of beads of a third consumable located within a third receptacle of the at least three receptacles when the third separation magnet is located proximate to the third consumable. ​ 5. The magnetic separator of claim 4, wherein the movement system is configured to move the first separation magnet, the second separation magnet, and the third separation magnet in unison.

6. The magnetic separator of claim 4, wherein the movement system is configured to move the first separation magnet, the second separation magnet, and the third separation magnet independently.

7. The magnetic separator of claim 1, wherein the movement system is configured to rotate the first separation magnet in addition to movement in the vertical direction and the horizontal direction.

8. The magnetic separator of claim 1, wherein the magnet system further comprises: an opposing separation magnet configured to perform separation of microbeads located within a consumable when the opposing separation magnet is located in proximity to the consumable, wherein the movement system is configured to move the opposing separation magnet in at least two directions in order to accommodate a shape of the consumable, and wherein the opposing separation magnet is located on an opposite side of the at least one receptacle as the first separation magnet.

9. The magnetic separator of claim 8, wherein the opposing separation magnet is configured to rotate between a first position and a second position, wherein in the first position a magnetic field of the opposing separation magnet is in a first orientation, and wherein in the second position the magnetic field of the opposing separation magnet is in a second orientation opposite the first orientation.

10. The magnetic separator of claim 1, wherein the magnet system further comprises: a control system configured to detect a size of at least one of the at least one receptacle and a received consumable, wherein the control system is configured to automatically determine a movement process of the first separation magnet for performing separation of microbeads.

11. A liquid handling system, the liquid handling system comprising: a magnetic separator of claim 1; and a liquid handling device comprising: a liquid handling automation movement system; a head configured to be moved by the liquid handling automation movement system; and at least one pipette attached to the head and configured to be insertable into and retractable from the at least one receptacle of the base unit of the magnetic separator, the pipette configured to aspirate and dispense liquid from the consumable received in the at least one receptacle.

12. A method of separating microbeads, the method comprising: receiving a consumable by a receptacle of a base unit of a magnetic separator for a liquid handling system; performing, by the magnetic separator, separation of microbeads located within the consumable by moving a first separation magnet of the magnetic separator in proximity to the consumable; and ​ During the separation, a movement system of the magnetic separator moves the first separation magnet in at least two directions according to a movement procedure to accommodate the shape of the consumable, wherein the movement system comprises a vertical axis configured to move the first separation magnet in a vertical direction and a horizontal axis configured to move the first separation magnet in a horizontal direction; wherein the consumable extends in a cylindrical shape having a tapered bottom, wherein moving the first separation magnet further comprises: vertically moving, by the movement system of the magnetic separator, the first separation magnet along a side of the cylindrical shape such that a portion of the magnet is in close proximity to the cylindrical shape of the received consumable; and horizontally moving, by the movement system of the magnetic separator, the first separation magnet along a side of the tapered bottom such that the portion or another portion of the magnet is in close proximity to the tapered bottom.

13. The method of claim 12, further comprising: deflecting, by a stationary magnet of the magnetic separator, the magnetic field of the first separation magnet away from the consumable; and removing, by the stationary magnet, residual magnetic field from the first separation magnet from the microbeads located within the consumable.

14. The method of claim 13, further comprising: moving the first separation magnet into close proximity to the stationary magnet.

15. The method of claim 12, further comprising: maintaining, by the first separation magnet, contact with the consumable or the receptacle along an entire vertical height of the consumable and the receptacle.

16. The method of claim 12, wherein the base unit comprises at least three receptacles, each receptacle sized to at least partially receive a separate consumable at a predetermined location within the base unit, wherein the first separation magnet performs separation of microbeads in the consumable located within a first receptacle of the at least three receptacles, and wherein the method further comprises: performing, by the magnetic separator, separation of microbeads in a second consumable located within a second receptacle of the at least three receptacles by moving a second separation magnet of the magnetic separator into close proximity to the second consumable and moving, by a movement system of the magnetic separator, the second separation magnet in at least two directions during the separation; and performing, by the magnetic separator, separation of microbeads in a third consumable located within a third receptacle of the at least three receptacles by moving a third separation magnet of the magnetic separator into close proximity to the third consumable and moving, by a movement system of the magnetic separator, the third separation magnet in at least two directions during the separation. ​

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