3-d mixing and particle delivery via movable electromagnets assemblies
12138606 ยท 2024-11-12
Assignee
Inventors
Cpc classification
B03C1/01
PERFORMING OPERATIONS; TRANSPORTING
B01F33/451
PERFORMING OPERATIONS; TRANSPORTING
B03C1/30
PERFORMING OPERATIONS; TRANSPORTING
B03C2201/18
PERFORMING OPERATIONS; TRANSPORTING
B03C1/288
PERFORMING OPERATIONS; TRANSPORTING
B01F2101/23
PERFORMING OPERATIONS; TRANSPORTING
B03C2201/26
PERFORMING OPERATIONS; TRANSPORTING
B01F35/221
PERFORMING OPERATIONS; TRANSPORTING
G01R33/1276
PHYSICS
International classification
B01F33/451
PERFORMING OPERATIONS; TRANSPORTING
B01F35/221
PERFORMING OPERATIONS; TRANSPORTING
B03C1/01
PERFORMING OPERATIONS; TRANSPORTING
B03C1/033
PERFORMING OPERATIONS; TRANSPORTING
B03C1/30
PERFORMING OPERATIONS; TRANSPORTING
Abstract
A fluid processing system that can include a sample container having a sample chamber for containing a fluid and a plurality of magnetic particles and at least one movable magnetic assembly configured to be movably inserted into or out of the sample chamber. The movable magnetic assembly can include a plurality of electromagnets that generate a magnetic field within at least a portion of the sample chamber when the assembly is inserted at least partially into the sample chamber. The fluid processing system can also include a signal generator that applies electrical signals, e.g., AC electrical signals, to the electromagnets of the magnetic assembly and a controller coupled to the signal generator that is configured to control phases of the electrical signals applied to the electromagnets to generate magnetic field gradients within the portion of the sample chamber effective to magnetically influence the plurality of the magnetic particles.
Claims
1. A fluid processing system, comprising, a sample container including at least one sample chamber for containing a fluid and a plurality of magnetic particles, at least one movable magnetic assembly configured to be movably inserted into or out of said sample chamber, said movable magnetic assembly comprising a plurality of electromagnets arranged to generate a magnetic field within at least a portion of the sample chamber when the assembly is inserted at least partially into said sample chamber, at least one magnetic structure comprising a plurality of electromagnets disposed around said sample chamber, at least one signal generator for applying electrical signals to said electromagnets of the magnetic assembly and said plurality of electromagnets of said movable magnetic assembly, where said signal generator is configured to generate AC signals for application to said plurality of electromagnets of said magnetic assembly and said plurality of electromagnets of said at least one magnetic structure, and a controller coupled to said signal generator for controlling phases of the electrical signals applied to said electromagnets so as to generate magnetic field gradients within said at least a portion of the sample chamber effective to magnetically influence the plurality of the magnetic particles.
2. The fluid processing system of claim 1, wherein said AC signals have a frequency in a range of 0.1 Hz to 5000 Hz.
3. The fluid processing system of claim 2, wherein said AC signals are voltage signals with an amplitude in a range of 1 volt to 100 volts.
4. The fluid processing system of claim 1, wherein said electromagnets of said magnetic assembly are arranged so as to cause mixing of the magnetic particles substantially within a plane.
5. The fluid processing system of claim 1, wherein said plurality of electromagnets of said magnetic assembly comprises a first, a second, a third and a fourth electromagnet and wherein said controller is configured to affect the application of a plurality of electrical signals to said electromagnets in accordance with the following relations:
6. The fluid processing system of claim 1, wherein said movable magnetic assembly comprises a shell in which said plurality of electromagnets are incorporated, said shell being shaped and sized for at least partial insertion in said sample chamber.
7. The fluid processing system of claim 1, wherein said controller is configured to cause application of electrical signals having different phases to said electromagnets of the at least one magnetic structure so as to generate magnetic field gradients within at least a portion of said sample chamber effective to magnetically influence the magnetic particles.
8. The fluid processing system of claim 7, wherein said electromagnets of said at least one magnetic structure are vertically spaced from the electromagnets of said movable magnetic assembly and said controller affects application of a pattern of electrical signals to said electromagnets of the magnetic structure and the electromagnets of said movable magnetic assembly so as to generate magnetic field gradients along said vertical direction.
9. The fluid processing system of claim 8, wherein said plurality of electromagnets of the movable magnetic assembly comprises a first, a second, a third and a fourth electromagnet and said electromagnets of said at least one magnetic structure comprises a first, a second, a third and a fourth electromagnet and wherein said controller is configured to affect the application of a plurality of electrical signals to said electromagnets in accordance with the following relations:
10. The fluid processing system of claim 1, wherein said controller comprises at least one memory module configured to store at least one sample processing protocol for execution by the controller.
11. The fluid processing system of claim 1, further comprising a DC signal generator operating under control of the controller for applying one or more DC signals to one or more of said electromagnets of said magnetic assembly for trapping said magnetic particles.
12. The fluid processing system of claim 1, wherein said at least one sample chamber comprises a plurality of fluidically-isolated sample chambers.
13. The fluid processing system of claim 12, wherein said at least one magnetic structure comprises a plurality of magnetic structures associated with said plurality of sample chambers, and wherein at least at least two of said magnetic structures have at least one electromagnet in common.
14. The fluid processing system of claim 1, wherein said at least one sample chamber has a volume in a range of 1 microliter to 1 liter.
15. A fluid processing system, comprising, a sample container including at least one sample chamber for containing a fluid and a plurality of magnetic particles, at least one movable magnetic assembly comprising one electromagnet and configured to be movably inserted into or out of said sample chamber, a magnetic structure comprising a plurality of electromagnets disposed around said sample chamber, at least one signal generator for applying electrical signals to said one electromagnet of said movable magnetic assembly and said electromagnets of the magnetic structure, where said at least one signal generator is configured to generate AC signals for application to said one electromagnet of said magnetic assembly and said electromagnets of the magnetic structure, and a controller coupled to said signal generator for controlling phases of the electrical signals applied to said electromagnets of the magnetic structure and said one electromagnet of said movable magnetic assembly so as to generate magnetic field gradients within at least a portion of the sample chamber effective to magnetically influence the plurality of the magnetic particles.
16. The fluid processing system of claim 15, wherein said controller is configured to affect application of a signal to said electromagnet of the movable magnetic assembly having a phase different than phases of the signals applied to said electromagnets of the magnetic structure.
17. A method for processing fluids, comprising delivering a fluid sample and a plurality of magnetic particles to a fluid chamber having a magnetic structure comprising a plurality of electromagnets disposed around said fluid chamber, inserting a movable electromagnetic assembly at least partially into said fluid chamber, said movable electromagnetic assembly comprising at least one electromagnet, applying AC electrical signals of varying phases to said electromagnets of said magnetic structure and said at least one electromagnet of the movable electromagnetic assembly so as to generate magnetic field within at least a portion of said fluid chamber effective to magnetically influence the magnetic particles, thereby causing mixing of the fluid.
18. The method of claim 17, further comprising: subsequent to mixing of said fluid, terminating application of the AC electrical signals to said electromagnets, and applying at least one DC signal to said at least one electromagnet of the movable electromagnetic assembly for trapping at least a portion of said magnetic particles in said movable electromagnetic assembly.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
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(5)
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DETAILED DESCRIPTION
(9) The present invention generally relates to systems and methods for mixing fluids in which magnetic field gradients are employed to agitate magnetic particles dispersed in a fluid, thereby mixing the fluid. More specifically, in many embodiments, the combination of one or more movable electromagnetic assemblies configured for insertion into one or more of sample wells containing the fluid and the dispersed magnetic particles and magnetic structures associated with those samples wells are employed to cause three-dimensional (3D) mixing of the fluid. For example, the application of RF signals to the movable electromagnetic assemblies and/or the magnetic structures associated with the sample wells can generate magnetic fields gradients that cause the magnetic particle to move, spin, vibrate, or otherwise be agitated, thereby mixing the fluid. Various terms are used herein according to their ordinary meanings in the art. As used herein, an electromagnet of a magnetic structure associated with a sample well (electromagnet A) is vertically adjacent to an electromagnet of a movable electromagnetic assembly (electromagnet B), which is inserted into the sample well, when that the lateral separation of the electromagnet A relative to electromagnet B is less than a respective lateral separation of the electromagnet A relative to the other electromagnets of the magnetic structure. In other words, while in some cases two vertically adjacent electromagnets exhibit no lateral offset, in other cases two vertically adjacent electromagnets can exhibit a lateral offset. The term a magnetic sample, as used herein, refers to a sample that contains magnetic particles, or is otherwise magnetic.
(10) With reference to
(11) The fluid processing system 100 further includes a plurality of movable electromagnetic assemblies 200 that can be placed at least partially within the sample wells to cause three-dimensional (3D) mixing of magnetic samples contained in the sample wells, as discussed in more detail below. In this embodiment, the magnetic assemblies 200 are coupled to a back plate 201 (shown in
(12) With reference to
(13) In some embodiments, the shell can be formed of a material that exhibits a low absorption of the magnetic fields generated by the electromagnets 212a-212d. By way of example, in some embodiments, the shell can be formed of a polymeric material, such as polypropylene and polyethylene.
(14) With continued reference to
(15) Referring back to
(16) Referring back to
(17)
(18)
(19) The AC signal generator 300 (shown in
(20) In various aspects, the actuation of the electromagnets (e.g., electromagnets 104a-104d) according to the above exemplary phase delay equations causes the magnetic particles (not shown) in the sample well 102a that are influenced by the magnetic field gradients generated by these electromagnets to mix in a counterclockwise motion in the x-y plane associated with these electromagnets (in
(21)
(22) It will thus be appreciated in light of the present teachings that different mixing patterns can be effectuated by controlling the AC waveforms applied to the electromagnets of 104a-104d and 212a-212d. By way of example, another fluid mixing pattern can be obtained by applying the following exemplary AC signals of different phase delays to the electromagnets 104a-104d and 212a-212d, where the substrate a, b, c, d denote the application of particular signal to the electromagnets 104a/212a, 104b/221b, 104c/212c, and 104d/212d, respectively:
I.sub.A=I.sub.0 sin(ft)Eq. (5),
I.sub.B=I.sub.0 sin(ft/2)Eq. (6),
I.sub.C=I.sub.0 sin(ft)Eq. (7),
I.sub.D=I.sub.0 sin(ft3/2)Eq. (8), wherein I=electrical current, f=frequency, and t=time.
(23) The application of the RF signals denoted by above Eqs. (5)-(8) can cause a magnetic fluid in the sample well 102a to be mixed in a generally counterclockwise manner.
(24) Although in the above embodiment, sinusoidal RF waveforms are applied to the electromagnets 104a-104d and 212a-212d, the present teachings are not so limited. Indeed, it will be appreciated that any type of waveform may be supplied to electromagnets capable of operating according to applicant's teachings. By way of non-limiting example, the number of electromagnets surrounding each fluid container, the phase shifts between adjacent electromagnets (e.g., a 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, and 330 phase shifts), and the waveform shape can be varied in accordance with variance aspects of the present teachings. Non-limiting examples of electrical current waveforms may include square, rectangular, triangular, asymmetrical, saw-tooth, or any combinations thereof. In some embodiments, the type of current supplied to the electromagnets may be modified during operation of a fluid processing system configured according to some embodiments. For instance, at least a portion of the electromagnets may receive an AC waveform with a 90 phase shift, while another portion may receive an AC waveform with a 180 phase shift. In such an embodiment, the phase shift of each portion may be modified during operation of the fluid processing system (e.g., the phase shifts may be switched, synchronized, or the like). In some embodiments, at least a portion of the electromagnets may be operated in parallel, sequence, pulsed, or the like. In various aspects, the current supplied to the electromagnets may be controlled according to a processing protocol. In some embodiments, the processing protocol may be dynamically altered during operation of the fluid processing system based on various factors, such as feedback, operator input, detection of mixing efficiency, analysis results, or the like.
(25) Additionally or alternatively, a DC signal can be applied to the electromagnets 104a-104d and 212a-212d via a DC signal generator (such as the DC signal generator 220 schematically depicted in
(26) With reference to
(27) Agitating the magnetic particles according to various aspects of the present teachings causes the magnetic particles to be dispersed homogeneously horizontally and vertically within each fluid container, providing for optimal exposure and enhanced mixing of the fluid. Any number of mixing patterns can be provided by altering the phase and/or amplitude of the AC signals applied to the electromagnets 104a-104d and 212a-212d. By way of example, the pattern of the AC signals applied to the electromagnets 104a-104d of the movable electromagnetic assembly 200a can be selected such that the magnetic fields generated thereby can cause a clockwise mixing of the magnetic particles while the pattern of the AC signals applied to the electromagnets 212a-212b can cause a counter-clockwise mixing of the magnetic particles while the phase shifts between the AC signals applied to the electromagnets of 104a-104d and 212a-212d can cause a vertical mixing of the magnetic particles, e.g., in a manner discussed above.
(28) With reference to
(29) With reference to
I.sub.MEMA=I.sub.0 sin(ft+0.75)Eq. (9)
where I.sub.MEMA denotes a time-varying current in the electromagnet 512, I.sub.0 denotes the current amplitude, and f is the signal frequency.
(30) Similar to the previous embodiment, a DC magnetic field can be used for particle trapping and delivery. The single movable electromagnetic assembly has a simple design and in some embodiments it can be formed with a smaller size than a movable electromagnetic assemblies having more electromagnets.
(31) In some embodiments, the signals applied to the electromagnets of the movable magnetic assemblies and/or those of the magnetic structures associated with the sample wells can have a frequency in a range of about less than 1 Hz (e.g., 0.5 Hz) to about 5000 Hz.
(32) With reference to
(33) The controller 400 can be implemented in hardware, software and/or firmware. For example, with reference to
(34) As noted above, in some embodiments, a movable electromagnetic assembly according to the present teachings can be employed to transfer magnetic particles, e.g., magnetic beads from one sample chamber, e.g., a sample vial, to another. By way of further illustration and with reference to