Means and methods for operating a device having multiple magnets - Patents.com

JP2024527409A5Pending Publication Date: 2025-07-23PREOMICS GMBH
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Patent Information

Application Number
JP2024502190
Authority / Receiving Office
JP · JP
Patent Type
Applications
Current Assignee / Owner
Priority Date
2021-07-16
Filing Date
2022-07-15
Publication Date
2025-07-23

AI Technical Summary

Technical Problem

In high-throughput processes using containers with magnets, adjacent magnets in close proximity experience overlapping magnetic fields, leading to interference and reduced or stopped movements, which affects the intended mixing or lysing of samples.

Method used

A method involving fluctuating or oscillating currents through coils to trigger magnet movement, combined with intermittent magnetic pulses to disalign adjacent magnets, ensuring continuous motion.

Benefits of technology

The method maintains consistent magnet movement within containers, effectively mixing or lysing contents by preventing magnetic interference and alignment, suitable for high-throughput applications.

✦ Generated by Eureka AI based on patent content.

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Abstract

The present invention relates to a method of operating an apparatus comprising an array of containers, one or more coils in sufficient proximity to at least two of the containers, where current flowing through the coils exposes the interiors of the containers to a magnetic field, and where the at least two containers each contain at least one first permanent magnet, and a power source connected to the coils, the method comprising: (a) delivering a fluctuating or oscillating current to the coils to trigger movement of the first permanent magnets; and (b) intermittently applying magnetic pulses sufficient to cause the first permanent magnets in adjacent containers to become magnetically out of alignment with each other.
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Description

[Technical field]

[0001] The present invention relates to a method of operating an apparatus comprising an array of containers, one or more coils in sufficient proximity to at least two of the containers, where current flowing through the coils exposes the interiors of the containers to a magnetic field, and where the at least two containers each contain at least one first permanent magnet, and a power source connected to the coils, the method comprising: (a) delivering a fluctuating or oscillating current to the coils to trigger movement of the first permanent magnets; and (b) intermittently applying magnetic pulses sufficient to cause the first permanent magnets in adjacent containers to become magnetically out of alignment with each other. [Background technology]

[0002] In this specification, a number of documents are cited, including patent applications and manufacturer's manuals.The disclosures of these documents are not considered relevant to the patentability of this invention, but are incorporated herein by reference in their entirety.More specifically, all references are incorporated by reference to the same extent as if each individual document was specifically and individually indicated to be incorporated by reference.

[0003] The use of moving magnets in a vessel holding a sample is widespread, including processes for preparing biological and clinical samples for downstream analysis, for example by mass spectrometry. A moving magnet in a vessel holding a sample may be a means for mixing, as well as a means for disrupting biological cells and fragmenting biomolecules, as described, for example, in Applicant's previous applications WO 2020 / 002577 and WO 2021 / 228971. Summary of the Invention [Problem to be solved by the invention]

[0004] When these and other processes are carried out in a high-throughput manner, for example in the wells of a microtiter plate, the magnets of adjacent wells are in spatial proximity. Under such circumstances, the magnetic field exerted on a given magnet by magnets in adjacent vessels may overlap or interfere with the external magnetic field applied to induce the desired motion of each magnet. As a result, the magnets in adjacent wells may be magnetically aligned, and the motion that would be triggered by the external magnetic field may be reduced or completely stopped. [Means for solving the problem]

[0005] To address this technical problem inter alia, the present invention provides in a first aspect a method of operating an apparatus comprising an array of containers, one or more coils in sufficient proximity to at least two of the containers, where a current flowing through the coils exposes the interiors of the containers to a magnetic field, and where the at least two containers each contain at least one first permanent magnet, and a power source connected to the coils, the method comprising: (a) delivering a fluctuating or oscillating current to the coils to trigger movement of the first permanent magnets; and (b) intermittently applying magnetic pulses sufficient to cause the first permanent magnets in adjacent containers to be magnetically out of alignment with each other.

[0006] The device, when operated according to step (a), generally provides for the fluctuating, oscillating or irregular movement of the permanent magnet in the vessel. Depending on the contents of the vessel, the movement provides for mixing of components, keeping particulate matter in suspension, lysis of biological material such as cells or viruses, or fragmentation of molecules such as biological molecules including proteins, which can be, but need not be, obtained by lysing cells or viruses. Thus, in the most practical application of the device, at least one of the vessels contains a liquid or sample, preferably a sample of biological origin.

[0007] The array of vessels may be implemented as a microtiter plate. See further below. The vessel has an opening that can be closed by a lid, the lid being optional. The vessel can have any shape, preferably cylindrical, optionally tapering towards the bottom. In a typical embodiment, most or all of the vessels of the array contain one or more, preferably one, of the first permanent magnets.

[0008] The coil may be implemented as described below in relation to further aspects of the invention: A current passing through the coil generates a magnetic field.

[0009] The first permanent magnet is not particularly limited in terms of material, shape or size. Suitable magnets include or consist of ferromagnetic and ferrimagnetic materials, in particular the following elements and their alloys: neodymium-iron, neodymium-iron-boron (e.g. NdFe 14 B), cobalt, gadolinium, terbium, dysprosium, iron, nickel, iron oxide, manganese-bismuth, manganese-antimony, manganese-arsenic, yttrium-iron oxide, chromium oxide, europium oxide, and samarium-cobalt. Particularly preferred materials are neodymium-iron and samarium-cobalt.

[0010] In terms of size, the magnet is preferably dimensioned such that the maximum dimension of the magnet is smaller than the minimum dimension of the vessel, for example less than 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, or 0.1 times the minimum dimension of the vessel. For cylindrical or nearly cylindrical vessels, the minimum dimension of the vessel is generally the circular diameter of the opening. Exemplary sizes (maximum dimensions) of magnets suitable for applications using microtiter plates include sizes from 0.1 to 10 mm, such as 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10 mm, with smaller values ​​being preferred when using high density microtiter plates such as 384 and 1536 well plates. Such relative or absolute sizes allow, or are selected to allow, free movement of the magnets in three-dimensional space, providing the best performance with respect to the envisaged application of the device operated according to the method of the first aspect.

[0011] There are no particular limitations regarding the shape of the magnet, and any shape that does not adversely affect the free movement of the magnet is preferred. Exemplary shapes include rods, bars, poles, poles with rounded ends, cubes, rectangular prisms, spheres, elongated and oblate ellipsoids, disks, tetrahedrons, octahedrons, dodecahedrons, and icosahedrons.

[0012] The term "oscillating" indicates regular motion, while the term "varying" is broader and includes irregular motion. There is no particular preference in that regard. In a preferred embodiment, the amperage of the current as a function of time is (i) a rectangular function, (ii) a sinusoidal function, (iii) a trigonometric function, (iv) a sawtooth function, or (v) a combination or convolution of any one of (i)-(iv). The frequency of the current fluctuation or oscillation is not particularly limited, but may be 50-1000 Hz.

[0013] Depending on the strength of the magnetic field generated by the first permanent magnet, and depending on the degree of miniaturization (the spacing between the centers of adjacent wells decreases from 96-well plates to 384-well plates to 1536-well plates), it may be impossible to avoid interference between the magnetic fields generated by adjacent permanent magnets. Such interference may result in alignment of the magnets, and the external magnetic field generated by the current flowing through the coil may not be able to cause the desired movement of the magnets.

[0014] Application of a pulse according to (b) disrupts the alignment of the magnets and resumes their motion in response to the external magnetic field, see FIG. 1 for a comparison of the undesirable aligned position (A) and the re-establishment of free motion of the first permanent magnet upon application of a pulse (B).

[0015] Thus, the magnetic pulse is different from the magnetic field generated by delivering a fluctuating or oscillating current to the coil, the latter serving to cause a continuous movement of the first permanent magnet. In particular, the latter may not be able to cause a movement of the first permanent magnet when the first permanent magnet is in a magnetically aligned relative position, whereas the magnetic pulse is not. Conversely, the magnetic pulse is designed to dissolve the aligned position. To that end, the magnetic pulse is essentially different from the magnetic field generated by delivering a fluctuating or oscillating current to the coil, e.g. in terms of strength. In particular, the magnetic field delivered by the pulse is stronger than the magnetic field generated by the coil during step (a). Preferably, the magnetic field generated by the pulse is 1.1 times to 1000 times, e.g. 1.5 times, 2 times, 3 times, 4 times, 5 times, 6 times, 7 times, 8 times, 9 times, 10 times, 20 times, 50 times, 100 times, 200 times, or 500 times stronger than the magnetic field generated during step (a). Insofar as the magnetic field is varying, it is preferred to use the average magnetic field for such comparison. Preferably, said average is the arithmetic mean over time. Alternatively, the maximum magnetic field applied in steps (a) and (b), respectively, can be used for said comparison.

[0016] The term "intermittently" refers to said pulses being applied (i) repeatedly at regular or irregular intervals, for example in response to measurements as further detailed below, or at predetermined intervals, and / or (ii) for a period shorter than the period during which the device operates according to step (a). A preferred ratio of the durations of steps (a) and (b) is 1.5 to 100, 2 to 50, 5 to 20, for example 10. The ratio may be constant, i.e. applied to each pulse, or may vary, in which case the above numbers refer to the time-averaged ratio. Furthermore, fine-tuning of said ratios can be performed to optimally suit a given setting or application. Sensor readouts, as further detailed below, can also be utilized for such purposes.

[0017] In a broad sense, a "pulse" according to the present invention is any change in the magnetic field sensed by said first permanent magnet, sufficient to dislodge the magnetic alignment of said magnet. Although conveniently and advantageously achieved by modifying the characteristics of the current used in step (a) (see below for details), said pulse may also be generated by any additional or further means capable of exposing said magnet to a magnetic field.

[0018] In a preferred embodiment, the magnetic pulse is performed by increasing the current for one or more durations of variation or oscillation of the current. This applies to all aspects of the invention that use or refer to a pulse, particularly the third aspect disclosed further below.

[0019] In other words, the pulse may be oscillating or varying, but need not be. The one or more variations or oscillations may be between 1 and 1000, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 50 or 100 oscillations or oscillations. Generally, one oscillation is sufficient. Tailoring the pulse to a given setting or application can be done without further difficulty.

[0020] Alternatively, the duration of the pulse may also be shorter than one oscillation, preferably between 0.001 and 0.99 times the duration of one oscillation, such as 0.01, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8 or 0.9 times the duration of one oscillation. Generally speaking, especially for durations of less than one oscillation, the pulse may be non-oscillating and non-variable and may have any profile, such as a rectangular, triangular or sawtooth profile, said profile may be applied one or more times, preferably between 2 and 100 times, such as 2, 3, 4, 5, 6, 7, 8, 9 or 10 times.

[0021] Said increase in current may be between 1.1 and 100 times, such as 1.5 times, 2 times, 3 times, 4 times, 5 times, 6 times, 7 times, 8 times, 9 times, or 10 times.

[0022] The increase may also be more than 10-fold, such as 20-fold, 50-fold or 100-fold, especially if the duration of the pulse is less than one oscillation.

[0023] Preferably, the pulses are generated by the same means as those used for step (a), albeit more powerful, so that the method of the first step can also be considered as a continuous application of step (a), as the pulses from step (b) trigger or re-establish the movement intended to be triggered by step (a).

[0024] As will be described in further detail below, a pulse may also be applied before the first performance of step (a).

[0025] In a second aspect, the present invention provides an apparatus comprising: (i) an array of removable containers; (ii) at least two of the containers, each containing at least one first permanent magnet; (iii) one or more coils in sufficient proximity to said at least two of the containers, such that a current flowing through said coils exposes the interior of the container to a magnetic field; (iv) a power source connected to said coils; and (v) 1. means for measuring a characteristic of the current flowing through said coils, said characteristic preferably being current and / or phase; 2. a plurality of sensors configured to measure a magnetic field near or within the containers, preferably individually for each of the containers; and / or 3. means for measuring electromagnetic induction generated by a first permanent magnet in the coils, preferably when no current is flowing through said coils.

[0026] This device comprises means and / or sensors according to item (v) in addition to the components of the device operated according to the first aspect, and it is therefore understood that said device is capable of carrying out the method of the first aspect.

[0027] A prototype device of the invention is shown in Figure 2. A device of the invention including shielding (see below for further details) is shown in Figure 4. An exemplary sensor readout is shown in Figure 3.

[0028] In particular, the apparatus is configured to deliver a fluctuating or oscillating current to the coil to induce a magnetic field that triggers movement of a first permanent magnet, the apparatus is configured to apply a magnetic pulse sufficient to release the first permanent magnet so long as it is mounted in a predetermined position within each vessel and / or to release the first permanent magnet from its magnetically aligned relative position, and / or the apparatus is configured to generate the magnetic pulse by increasing the current, preferably for the duration of the current or during one or more fluctuations or oscillations.

[0029] As disclosed as the first aspect of the invention above, the device can operate normally without the means or sensor according to item (v), but the device according to the second aspect is preferred, given that it provides a more targeted application of the pulse. Said targeted application of the pulse may be performed by a control element that controls the current. Said control element is preferably a component of said power supply. Preferred means for returning the readout of the means or sensor of item (v) to the power supply are further detailed below in relation to the third aspect.

[0030] The means and sensors according to (v) are preferably such that there is one per vessel. With regard to (v)1, this may be implemented by surrounding each vessel with a coil, which is preferred but not essential (see further below). However, in alternative embodiments, one means or sensor (v) can be used per group of adjacent vessels, such as one per two vessels or one per four vessels.

[0031] It is understood that the means and sensor (v) are sufficiently close to the respective vessel in which the magnetic field generated by the first magnet is to be measured.

[0032] Bringing the means and sensor (v) sufficiently close to the vessels can be achieved by incorporating said means and sensor in a plate included in the device, said plate being configured to allow placing an array of vessels thereon. The plate may also comprise said coil or coils (iii). Alternatively, said plate does not comprise said coil or coils. The coil or coils may then be included in a further plate or may not be part of any plate.

[0033] (v) The sensor according to 2. may be implemented as a Hall sensor or a second coil. Hall sensors are known in the art and are available from various manufacturers. They utilize the Hall effect to measure a magnetic field. The second coil measures the magnetic induction generated by the first permanent magnet.

[0034] In a preferred embodiment of the device of the second aspect, the sensor of (v)2. is configured or used to measure one or more of the strength of the magnetic field, the uniformity of the magnetic field, the presence or absence of the first permanent magnet, and the movement of the first permanent magnet. Measuring magnetic field properties is an inherent property of Hall sensors. Since the first permanent magnet generates a magnetic field, the latter magnetic field is sensitive to the position and movement of the first permanent magnet.

[0035] In a further preferred embodiment, the apparatus further comprises one or both of: (vi) means for determining a temperature of the coil; and (vii) means for holding the first permanent magnet in a fixed position.

[0036] Measuring the temperature of the coil is particularly interesting for applications in which containers are used and / or samples sensitive to high temperatures are processed. Alternatively or additionally, the temperature within the container may be measured and suitable means may be included in the device of the second aspect.

[0037] Preferably, the means (vii) comprises: a. one or more pieces of magnetic material; b. one or more second permanent magnets; c. One or more electromagnets; one or more electromagnets, wherein the means a., b. and c. are located outside the vessel in the vicinity of the first permanent magnet to hold the first permanent magnet in a predetermined position within the vessel, and preferably the positions of the pieces of a. and the permanent magnets of b. are adjustable such that after adjustment a. and b. do not significantly interact with the first permanent magnet; and d. Non-magnetic means for attaching said first permanent magnet to a predetermined location within each vessel.

[0038] The electromagnet can be turned on and off depending on whether it is holding the first permanent magnet in place or moving it.

[0039] The non-magnetic means are such that the attachment can be dissolved by a magnetic pulse. This can be achieved, for example, by attaching the magnet to the inside of the lid of the container (as long as the container has a lid) or to the wall of the container with an adhesive. Alternatively or additionally, the container may be provided with ridges designed to hold the magnet.

[0040] Items a., b. and c. above may also be used as means for generating pulses according to the method of the first aspect.

[0041] In a further preferred embodiment, (i) the array of vessels is a microtiter plate, preferably having 96, 384 or 1536 wells; (ii) the coil is a single coil, preferably a Helmholtz coil, surrounding the array of vessels, or a plurality of coils, e.g. comprised on a printed circuit board, or a plurality of Helmholtz coils, preferably such that each vessel of the array of vessels is surrounded by a coil; and / or (iii) the power supply is configured for pulse width modulation.

[0042] Helmholtz coils are preferred as they deliver a uniform magnetic field. A printed circuit board (PCB) on which the coil is printed is advantageous in terms of ease of manufacture and compact design, and such a PCB is a preferred embodiment of the above-mentioned plate housing said coil.

[0043] Pulse width modulation is a well-established means in the art of controlling the temporal profile of electrical current, with preferred temporal profiles being disclosed above.

[0044] Preferably, the apparatus further comprises: (viii) a housing that 1. provides electromagnetic shielding; and / or 2. has an opening or is configured to be opened to allow insertion and removal of the array of containers.

[0045] In terms of geometry, the opening is preferably such that insertion and removal of the array of vessels occurs along a plane defined by the array, which facilitates processing by automated systems designed for high-throughput processing of samples.

[0046] In a third aspect, the present invention provides a method of operating the apparatus according to the second aspect, the method comprising: (a) optionally applying magnetic pulses sufficient to release a first permanent magnet to the extent that it is attached in a predetermined position within each vessel and / or to release said first permanent magnets from their magnetically aligned relative position; (b) delivering a fluctuating or oscillating current to said coil to induce a magnetic field that moves the first permanent magnets; (c) analysing a readout produced by the means and / or sensor defined in item (v) of the apparatus; and (d) if said analysis of step (c) indicates that the first permanent magnets in nearby vessels are magnetically aligned, intermittently applying magnetic pulses sufficient to cause the first permanent magnets in nearby vessels to become unmagnetically aligned with each other.

[0047] In a preferred embodiment, the analysis in (c) comprises comparing readouts of the means and / or sensors described in item (v) of the apparatus taken in the vicinity of a first permanent magnet with readouts at a distance from any first permanent magnet, the distance being sufficient such that magnetic interference by any first permanent magnet is negligible.

[0048] The readout at a distance provides a characteristic of the magnetic field generated by the coil alone, and can be obtained from a means or sensor placed in the vicinity of the vessel, for example under a vessel that is intentionally left empty, i.e. does not contain the first permanent magnet.

[0049] In a further preferred embodiment, the method further comprises one or both of: (a) modulating the current in response to the temperature determined by means (vi) of the device; and (b) adjusting the position of the piece of a. or the second permanent magnet of b., preferably so that they do not interact with the first permanent magnet when the current is being delivered.

[0050] If there is a risk of overheating the vessel or the sample contained therein, the current amperage can be reduced or set to zero.

[0051] The adjustment serves to allow a first permanent magnet, initially fixed in place, to begin to move, and involves an increase in the spatial distance of the piece or the second permanent magnet from the first permanent magnet.

[0052] In a fourth aspect, the present invention provides a computer program comprising instructions for causing an apparatus of the second aspect to carry out the steps of the method of the third aspect.

[0053] In a fifth aspect, the present invention provides a computer readable medium having stored thereon a computer program according to the fourth aspect.

[0054] In a sixth aspect, the present invention provides a kit-of-parts comprising: (a) an apparatus comprising: (i) one or more coils configured to receive an array of containers; (ii) a power source connected to said coils; and (iii) 1. means for measuring a characteristic of a current flowing through said coils, said characteristic being preferably current and / or phase; 2. a plurality of sensors configured to measure a magnetic field in the vicinity of or within the containers, preferably individually for each of said containers; and / or 3. means for measuring an electromagnetic induction generated by a first permanent magnet in said coils, preferably when no current is flowing through said coils; And (b) an array of containers, at least two of the containers each including at least one first permanent magnet, optionally each magnet mounted at a predetermined position inside each container and configured to be released by a magnetic pulse.

[0055] Preferred embodiments of the device of the second aspect apply mutatis mutandis to the kit of the sixth aspect.

[0056] The figure shows: [Brief description of the drawings]

[0057] [Figure 1] A pulse according to the invention disaligns the permanent magnets as shown in (A) so that motion resumes (B). The "+" and "-" represent the north and south poles of the magnets, respectively. [Diagram 2] 1 shows an exemplary setup according to the present invention: A series of Hall sensors are attached to the bottom of a microtiter plate. [Diagram 3] Magnetic field as a function of time. (A) Baseline. (B) During operation. Top row: magnetic field generated by the coil, bottom row: sum of the magnetic fields of the coil and the permanent magnet, middle row: difference (only the magnetic field of the magnet). [Figure 4] 1 shows an external view of the device of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0058] The examples illustrate the invention. EXAMPLES

[0059] Example 1 Equipment and Protocols A set of Hall sensors (ratiometric linear Hall effect magnetic sensors DRV5055A1-TI) are mounted at the bottom of a 96-well microtiter plate, see Figure 2.

[0060] Most of the wells of the microtiter plate each contain a permanent magnet (cylindrical 2x2 mm Nd magnet N48, magnetized along the cylindrical axis).

[0061] A USB digital oscilloscope (IDSO1070A Hantek) is used to read out the signals delivered by the sensors.

[0062] One of the Hall sensors is placed in a location where the magnetic field of the permanent magnet in the well is negligible, for example at the bottom of an empty well. This defines the baseline. When the device is operating, the magnetic field generated by the coil is the baseline.

[0063] At least one Hall sensor is placed under a well containing a permanent magnet, and at least one of the wells with a Hall sensor under it is surrounded by wells each also containing a permanent magnet. This corresponds to a real-life situation where most wells contain liquid and / or sample as well as a permanent magnet for sample preparation. This defines the measured value. The magnetic field is the sum of the magnetic field generated by the coil and the magnetic field generated by the permanent magnet.

[0064] Measurements As shown in FIG. 3, the oscilloscope shows (i) the baseline, (ii) the measured value, and (iii) the difference between the measured value minus the baseline. The difference is the magnetic field generated by the permanent magnet only. This difference is sensitive to the position and movement of the magnet. In the case of an aligned position of the magnet (FIG. 1A), the Hall sensor does not detect the field emanating from the magnet. In the case of misalignment or movement, the magnet delivers a magnetic field that is detectable by the sensor.

[0065] As can be seen in Figure 3(B), the pulses (i) successfully initiate the motion of the magnet when starting from the aligned position, and (ii) reduce the motion after a period of free motion and successfully resume the motion if the magnet stops at the aligned position. The intermittent application of pulses ensures constant motion of the magnet.

Claims

1. A method of operating a device, comprising: the device includes an array of containers, one or more coils sufficiently close to at least two of the containers, a current flowing through the coils exposes the interior of the containers to a magnetic field, and at least two of the containers each include at least one first permanent magnet; one or more coils; and a power source connected to the coils, the method includes: (a) delivering a varying or oscillating current to the coils to trigger movement of the first permanent magnets; and (b) intermittently applying a magnetic pulse sufficient to prevent the first permanent magnets in adjacent containers from magnetically aligning with each other.

2. The method according to claim 1, wherein the magnetic pulse is performed by increasing the current over one or more durations of the variation or oscillation of the current.

3. A device, comprising: (i) an array of removable containers; (ii) at least two of the containers, each including at least one first permanent magnet; (iii) one or more coils sufficiently close to the at least two containers, the current flowing through the coils exposing the interior of the containers to a magnetic field; (iv) a power source connected to the coils; and (v) 1. means for measuring a characteristic of the current flowing through the coils; 2. a plurality of sensors configured to measure a magnetic field in the vicinity or inside the containers; and / or 3. means for measuring electromagnetic induction generated by the first permanent magnets in the coils.

4. The device according to claim 3, wherein the sensors of (v) 2 are configured to measure one or more of the strength of the magnetic field, the uniformity of the magnetic field, the presence or absence of the first permanent magnets, and the movement of the first permanent magnets.

5. further comprising (vi) means for determining the temperature of the coils, and (vii) means for holding the first permanent magnets in a fixed position, wherein the means (vii) includes: a. one or more pieces of magnetic material; b. one or more second permanent magnets; c. one or more electromagnets, The means a., b., and c. are located outside the container in the vicinity of the first permanent magnet in order to hold the first permanent magnet at a predetermined position within the container. The position of the piece of a. and the second permanent magnet of b. can be adjusted so that after adjustment, a. and b. do not significantly interact with the first permanent magnet. One or more electromagnets, and d. non-magnetic means for attaching the first permanent magnet at a predetermined position within each container, the apparatus according to claim 3, selected from.

6. (i) The array of containers is a microtiter plate having 96, 384, or 1536 wells, (ii) The coil is a Helmholtz coil surrounding the array of containers, or a plurality of coils included in a printed circuit board, or a plurality of Helmholtz coils, and / or (iii) The power supply is configured for pulse width modulation. The apparatus according to claim 3.

7. The apparatus is (viii) 1. providing electromagnetic shielding, and / or 2. further comprising a housing having an opening or configured to be opened to enable insertion and removal of the array of containers. The apparatus according to claim 3.

8. (a) optionally applying a magnetic pulse sufficient to release the first permanent magnet to the extent that it is attached at a predetermined position within each container and / or to release the first permanent magnet from a magnetically aligned relative position; (b) delivering a varying or oscillating current to the coil to induce a magnetic field that moves the first permanent magnet; (c) analyzing the readings generated by the means and / or sensors defined in claim 3(v); (d) when the analysis of step (c) indicates that the first permanent magnets in neighboring containers are magnetically aligned, intermittently applying a magnetic pulse sufficient to cause the first permanent magnets in neighboring containers not to be magnetically aligned with each other. A method of operating the apparatus according to any one of claims 3 to 7, comprising.

9. The analysis of (c) includes comparing the reading of the means and / or sensor according to claim 3(v) obtained in the vicinity of the first permanent magnet with the reading at a distance from any first permanent magnet, the distance being sufficient such that magnetic interference by any first permanent magnet can be ignored, the method according to claim 8.

10. (e) modulating the current in response to the temperature determined by means (vi) of the device, and (f) adjusting the position of the piece according to claim 5a. or the second permanent magnet according to claim 5b., preferably such that they do not interact with the first permanent magnet when the current is being delivered, further comprising one or both of these, the method according to claim 8.

11. A computer program comprising instructions for causing the device according to any one of claims 3 to 7 to perform the steps of the method according to any one of claims 8 to 10.

12. A computer-readable medium storing the computer program according to claim 11.

13. A kit of parts comprising (a) a device comprising (i) one or more coils configured to receive an array of containers, (ii) a power supply connected to the coils, and (iii) 1. means for measuring the characteristics of the current flowing through the coils, 2. a plurality of sensors configured to measure the magnetic field in the vicinity or inside the containers, and / or 3. means for measuring the electromagnetic induction generated by a first permanent magnet in the coils, a device comprising and (b) an array of containers, at least two of the containers each comprising at least one of the first permanent magnets, optionally each magnet being attached at a predetermined position inside each container and configured to be released by a magnetic pulse, an array of containers.