CN211528427U - Device and equipment for separating magnetic particles - Google Patents
Device and equipment for separating magnetic particles Download PDFInfo
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- CN211528427U CN211528427U CN202020050148.7U CN202020050148U CN211528427U CN 211528427 U CN211528427 U CN 211528427U CN 202020050148 U CN202020050148 U CN 202020050148U CN 211528427 U CN211528427 U CN 211528427U
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Abstract
The present application relates to a device and an apparatus for separating magnetic particles, wherein the device comprises a tubular passage through which the magnetic particles can flow, the tubular passage comprising an inlet and an outlet, the inlet being capable of interfacing with a first container containing a solution comprising the magnetic particles, the outlet being capable of interfacing with a second container receiving the magnetic particles; a magnetic field applying unit configured to apply a magnetic field to form a magnetic force in an axial direction of the tubular passage; wherein the magnetic force is capable of drawing magnetic particles from a solution in a first container, such as a reaction cup, into the tubular passage through the inlet, through the tubular passage, and out of the second container through the outlet. Through the application, magnetic particle separation is realized. Compared with the related art, the method realizes quick online separation and is free from cleaning.
Description
Technical Field
The application relates to the field of magnetic particle separation, in particular to a device and equipment for separating magnetic particles.
Background
Although the enzyme-linked immunosorbent assay, the chemiluminescence assay, the magnetic particle chemiluminescence assay, the electrochemical immunoassay and the mass spectrometry detection which are widely used or appear in the market at present can carry out batch detection, an antigen-antibody immune complex or other target capture objects formed on the magnetic nano-microspheres need to be separated from other substances in liquid, and the detection efficiency cannot be effectively improved through a complicated washing process.
SUMMERY OF THE UTILITY MODEL
To solve the above technical problem or at least partially solve the above technical problem, the present application provides an apparatus and a device for separating magnetic particles.
In a first aspect, the present application provides an apparatus for separating magnetic particles, comprising: a tubular passage through which the magnetic particles can flow, the tubular passage comprising an inlet and an outlet, the inlet being capable of interfacing with a first container containing a solution containing the magnetic particles, the outlet being capable of interfacing with a second container receiving the magnetic particles; a magnetic field applying unit configured to apply a magnetic field to form a magnetic force in an axial direction of the tubular passage; wherein the magnetic force is capable of drawing the magnetic particles out of the solution, into the tubular passage through the inlet, through the tubular passage, and out of the outlet into the second container.
In some embodiments, the magnetic force increases at least partially from the inlet to the outlet.
In some embodiments, the magnetic field applying unit is configured to sequentially apply the magnetic field at a plurality of positions on the tubular passage from the inlet to the outlet to generate the magnetic field at the plurality of positions in time series.
In some embodiments, the tubular passage at least partially spirals from the inlet to the outlet, or the tubular passage is at least partially in the shape of a planar spiral.
In certain embodiments, the magnetic field applying unit comprises one or more induction coils.
In some embodiments, the magnetic field applying unit comprises a plurality of independent induction coils arranged axially along the tubular passage.
In some embodiments, the number of turns of the induction coil at least partially increases from the inlet to the outlet; and/or the induced current passing into the induction coil at least partially increases from the inlet to the outlet.
In some embodiments, adjacent induction coils are arranged in a like polarity opposing manner.
In certain embodiments, the outlet and inlet are vertically disposed.
In a second aspect, the present application provides an apparatus for separating magnetic particles, comprising: the above-mentioned apparatus for arbitrarily separating magnetic fine particles; and the receiving platform is used for placing the second container and is provided with a magnetic element so as to generate magnetic force from the opening of the second container to the bottom.
In a third aspect, the present application provides an apparatus for separating magnetic particles, comprising: a tubular passage through which the magnetic particles can flow, the tubular passage comprising an inlet and an outlet, the inlet being capable of interfacing with a first container containing a solution containing the magnetic particles, the outlet being capable of interfacing with a second container receiving the magnetic particles; a plurality of independent induction coils axially distributed along the tubular passage; a control unit configured to supply an induced current to the plurality of independent induction coils to form a magnetic force in an axial direction of the tubular passage; wherein the magnetic force is capable of separating magnetic particles from the solution and drawing them into the tubular passage through the inlet and out the outlet after passing along the tubular passage.
In some embodiments, the number of turns of the induction coil at least partially increases from the inlet to the outlet, such that the magnetic force at least partially increases from the inlet to the outlet; and/or the control unit is arranged in such a way that the induced current introduced into the induction coil at least partially increases from the inlet to the outlet, so that the magnetic force at least partially increases from the inlet to the outlet.
In some embodiments, the control unit is configured to sequentially supply the induced current to the plurality of independent induction coils from the inlet to the outlet, so as to generate the magnetic field at the positions where the induction coils are located according to the time sequence.
In some embodiments, the tubular passage at least partially spirals from the inlet to the outlet, or the tubular passage is at least partially in the shape of a planar spiral.
In some embodiments, adjacent induction coils are arranged in a like polarity opposing manner.
Compared with the prior art, the technical scheme provided by the embodiment of the application has the following advantages: according to the scheme provided by the embodiment of the application, a magnetic field is applied to the tubular passage through which the magnetic particles can flow, magnetic force in the axial direction of the tubular passage is formed, the magnetic particles are sucked out of the solution in the first container such as a reaction cup through the magnetic force, are sucked into the tubular passage through the inlet, flow to the discharge port along the tubular passage and are discharged to the second container from the outlet, and therefore separation of the magnetic particles and the solution is achieved.
Drawings
The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments consistent with the present application and together with the description, serve to explain the principles of the application.
In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings needed to be used in the description of the embodiments or the prior art will be briefly described below, and it is obvious for those skilled in the art to obtain other drawings without inventive exercise.
FIG. 1 is a schematic structural diagram of an embodiment of an apparatus for separating magnetic particles according to an embodiment of the present disclosure;
FIG. 2 is a schematic view of the apparatus shown in FIG. 1 in a docked state;
FIG. 3 is a schematic structural diagram of another embodiment of an apparatus for separating magnetic particles according to an embodiment of the present disclosure;
FIG. 4 is a schematic view of the docking state of the apparatus shown in FIG. 3;
FIG. 5 is a schematic diagram of the induction coils arranged in opposite polarity according to an embodiment of the present disclosure;
FIG. 6 is a schematic diagram of the induction coils arranged in opposite directions with the same polarity according to the embodiment of the present application;
FIG. 7 is a schematic diagram of the structure of one embodiment of the apparatus for separating magnetic particles according to the present application; and
FIG. 8 is a flow chart of one embodiment of a method for separating magnetic particles according to an embodiment of the present disclosure.
Detailed Description
It should be understood that the specific embodiments described herein are merely illustrative of the present application and are not intended to limit the present application.
In the following description, suffixes such as "module", "component", or "unit" used to denote elements are used only for the convenience of description of the present application, and have no specific meaning by themselves. Thus, "module", "component" or "unit" may be used mixedly.
Referring to fig. 1 to 4, an apparatus for separating magnetic particles in an embodiment of the present application includes a tubular passage 1 and a magnetic field applying unit 2. The tubular passage 1 comprises an inlet 11 and an outlet 12, the inlet 11 being capable of interfacing with a first container 3 containing magnetic particles, the outlet 12 being capable of interfacing with a second container 4 receiving magnetic particles; the magnetic field applying unit 2 applies a magnetic field to form a magnetic force in the axial direction of the tubular passage 1, by which magnetic particles are sucked out of the solution, and are sucked into the tubular passage 1 through the inlet 11, pass along the tubular passage 1 to the outlet 12, and are discharged from the outlet 12 to the second container 4.
By means of the device, the magnetic particles in the first container are separated from the solution due to the action of the magnetic force and enter the tubular passage through the inlet of the tubular passage, in which the magnetic particles are subjected to the magnetic force in the axial direction of the tubular passage to flow along the tubular passage, while the solution on the surface of the magnetic particles is at least partially gradually separated from the magnetic particles without being subjected to the magnetic force. The magnetic particles flow from the tubular passage inlet to the outlet and are discharged through the outlet into the second container. Thereby achieving separation of the magnetic particles.
It should be understood that the term "magnetic particles" may also be referred to herein as magnetic microspheres or magnetic beads. Unless otherwise specified, the magnetic particles in the solution herein include not only the magnetic particles themselves but also a combination of the surfaces of the magnetic particles, but are not limited thereto. Magnetic particles include, but are not limited to, magnetic particles in electrochemical immunoassay, magnetic particle chemiluminescence, mass spectrometry immunoassay, chemiluminescence immunoassay, or enzyme-linked immunoassay. The magnetic particles include, but are not limited to, superparamagnetic microspheres with a capture function, and can capture a target substance to be detected in a solution. The superparamagnetic microsphere with the capture function comprises, but is not limited to, an immunomagnetic microsphere, an antigen, an antibody or an immune complex after reaction, wherein the antigen, the antibody or the immune complex is used as a surface binding marker of a solid phase carrier. The superparamagnetic microspheres with the capture function can be used as a solid phase carrier to directly capture ions, substances containing the ions or substances chelating the ions in a solution. The superparamagnetic microspheres with the capture function are used as solid phase carriers to directly capture metal ions, substances containing the metal ions or substances chelating the metal ions in a solution.
Illustratively, the material of the magnetic particles is magnetic Fe3O4、γ-Fe2O3Pt, Ni or Co microspheres, or Fe which is magnetic3O4、γ-Fe2O3Pt, Ni or Co and inorganic matter or organic matter to form core/shell structure or doped structure. The magnetic particles can be magnetic polystyrene microspheres and magnetic silicon dioxide microspheres; or silicon hydroxyl magnetic microspheres, amino magnetic microspheres, carboxyl magnetic microspheres, epoxy magnetic microspheres, dextran nano magnetic beads, aldehyde group magnetic microspheres and tosyl magnetic beads; or streptavidin magnetic beads, immunoprecipitation magnetic beads, biological ligand rapid coupling magnetic beads, protein purification magnetic beads, antibody purification magnetic beads, ion exchange magnetic beads, nucleic acid extraction magnetic beads, and the like. The embodiment of the present application does not limit this.
In some embodiments, the first container 3 may be a cup having a cavity to hold a solution and an opening to enable the solution to be placed into or removed from the cavity. The first container 3 is illustratively, but not limited to, a reagent cup, a reaction cup, or the like. The second receptacle 4 may be a cup having a cavity for receiving magnetic particles. The second container 4 is exemplified by a magnetic particle receiving cup or an electrode, etc., but is not limited thereto.
In some embodiments, the magnetic force increases at least partially from the inlet 11 to the outlet 12, thereby accelerating the movement of the magnetic particles in the tubular passage 1 and further promoting the separation between the magnetic particles and the solution on the surface thereof. In the embodiments of the present application, the term "increasing trend" refers to a rule of increasing as a whole, including but not limited to the case of increasing one by one/in sequence.
In some embodiments, referring to fig. 1 and 2, the tubular passage 1 is at least partially in a planar spiral shape from the inlet 11 to the outlet 12, such that the magnetic particles rotate in the tubular passage 1 and the solution on the surface of the magnetic particles is further detached by the centrifugal force of the rotation. Although only the inlet 11 is shown in fig. 1 and 2 as being located at the center of the planar spiral, a planar spiral form is formed from the inlet 11 to the outlet 12 from the inside to the outside. However, in the present embodiment, the outlet 12 may be located at the center of the planar spiral, forming a planar spiral shape from the inlet 11 to the outlet 12 from the outside inward. The embodiment of the present application is not limited to a specific form of the spiral, and any form that can realize rotation of the magnetic particles in the tubular passage is conceivable.
In other embodiments, the tubular passage 1 at least partially spirals from the inlet 11 to the outlet 12 as shown in fig. 3 and 4, such that the magnetic particles rotate in the tubular passage 1, the solution on the surface of the magnetic particles is further detached by the centrifugal force of the rotation, and the liquid on the surface of the magnetic particles is further detached by the action of gravity during the ascent. The ascending angle is not limited in the embodiment of the application, and any angle which is in the ascending trend can be conceived. Although fig. 3 and 4 illustrate the uniform spiral ascending, the embodiment of the present application is not limited thereto, and non-uniform or other spiral patterns with ascending trend are conceivable, which are not described in detail in the embodiment of the present application.
In some embodiments, the magnetic particles are specifically adsorbed to some substances in the solution and non-specifically adsorbed to other substances, and the solution or non-specifically adsorbed substances on the surfaces of the magnetic particles are separated from the magnetic particles by magnetic force.
In some embodiments, the magnetic field applying unit 2 is configured to sequentially apply the magnetic field at a plurality of positions on the tubular passage 1 from the inlet 11 to the outlet 12 to generate the magnetic field at the plurality of positions in time series. Preferably, no magnetic field is applied at a position adjacent to the position where the magnetic field is applied at the same time. As a non-limiting example, a magnetic field is applied at a first location a near the inlet 11 at a first moment in time, by which magnetic particles are separated from the solution and sucked into the tubular passage 1 via the inlet 11; at a second moment, a magnetic field is applied at a second location close to the first location, by which magnetic force the magnetic particles are attracted out of the first location to the second location.
In other embodiments, the magnetic field applying unit 2, arranged to apply magnetic fields simultaneously at a plurality of locations (e.g. a plurality of independent induction coils) on the tubular passage 1 from the inlet 11 to the outlet 12. Preferably, the magnetic force in the direction from the inlet 11 to the outlet 12 of the tubular passage 1 at least partly increases.
In some embodiments, adjacent induction coils are arranged in a like polarity opposing manner to facilitate acceleration of the magnetic particles. Especially when the magnetic field is applied simultaneously at a plurality of locations (e.g. a plurality of independent induction coils) on the tubular passage 1, the arrangement in opposite manner with the same polarity can increase the magnetic field strength to facilitate the movement of magnetic particles in the tubular passage 1 from the inlet 11 to the outlet 12.
In certain embodiments, the magnetic field application unit 2 comprises an induction coil. An induction coil is wound on the outer surface of the tubular passage 1, and the induction coil can generate a magnetic field under the action of induced current, and the magnetic field forms magnetic force in the axial direction of the tubular passage 1. In some embodiments, a plurality of independent induction coils may be included, which are axially disposed along the tubular passage 1, and which may be spaced apart. The plurality of induction coils may have different numbers of coil turns, at least in part. The magnitude of the generated magnetic force is related to the number of turns of the coil of the induction coil, and the magnitude of the generated magnetic force is related to the magnitude of the induced current led into the induction coil.
In some embodiments, the induction current is sequentially applied to a plurality of independent induction coils from the inlet 11 to the outlet 12 to generate a magnetic field at the position of the induction coil according to a time sequence. In other embodiments, a plurality of induction coils are simultaneously fed with induced current through the tubular passage 1 from the inlet 11 to the outlet 12, the plurality of independent induction coils forming a multi-stage induction coil. Preferably, the magnetic force in the direction from the inlet 11 to the outlet 12 of the tubular passage 1 at least partly increases.
In some embodiments, the number of turns of the induction coil at least partially increases from the inlet 11 to the outlet 12 of the tubular passage 1, such that the magnetic force in the direction from the inlet to the outlet of the tubular passage 1 at least partially increases.
In other embodiments, the induced current to the induction coil increases at least partially from the inlet 11 to the outlet 12 of the tubular passage 1, so that the magnetic force increases at least partially in the direction from the inlet 11 to the outlet 12 of the tubular passage 1.
In other embodiments, the number of turns of the induction coil at least partially increases from the inlet 11 to the outlet 12 of the tubular passage 1, and the induced current into the induction coil at least partially increases such that the magnetic force in the direction from the inlet 11 to the outlet 12 of the tubular passage 1 at least partially increases.
In some embodiments, the number of induction coils increases along the same length from the inlet 11 to the outlet 12 of the tubular passage 1, so that the magnetic force increases at least partially in the direction from the inlet 11 to the outlet 12 of the tubular passage 1.
In some embodiments, a receiving platform 5 is further included, the receiving platform 5 is configured to receive the second container 4, and the receiving platform 5 is configured with a magnetic element 51 to generate a magnetic force from the opening 41 of the second container 4 toward the bottom. The magnetic element 51 may be an induction coil or an electromagnet. Referring to fig. 1 to 4, the magnetic element is an induction coil and is disposed below the receiving platform 5, but the application is not limited thereto. In certain embodiments, the magnetic field of the receiving platform 5 is greater than the magnetic field at the outlet 12.
In some embodiments, the inlet 11 is vertically arranged so as to interface with the first container 3 and allow the magnetic particles in the solution in the first container 3 to rise vertically into the tubular passage 1 under the action of magnetic force, while the solution on the surface of the magnetic particles is at least partially detached from the surface of the magnetic particles by the action of gravity. It should be understood that the embodiments of the present application are not limited to being completely vertically disposed, and that having a certain tilt angle is also permissible.
As one non-limiting example, as shown with reference to fig. 1 to 4, the inner diameter of the inlet 11 is larger than the outer diameter of the opening of the first container 3 so that the inlet 11 can be housed in the opening of the first container 3 (as shown with reference to fig. 2 and 4, the inlet 11 is shown housed over the opening of the first container 3). In fig. 1 to 4, the lower end of the inlet 11 is shown to be trumpet-shaped, it should be understood that the present embodiment is not limited thereto, and the lower end of the inlet 11 may have any shape capable of being butted against the first container 3, for example, a cylindrical shape, a prismatic shape, a rectangular parallelepiped shape, or a square shape, the outer diameter of the cylindrical shape is larger than the outer diameter of the first container 3, and the inner diameter of the prismatic shape, the rectangular parallelepiped shape, or the square shape is larger than the outer diameter of the first container 3.
In certain embodiments, the outlet 12 is vertically disposed to facilitate docking with the second container 4. It should be understood that the embodiments of the present application are not limited to being completely vertically disposed, and that having a certain tilt angle is also permissible. As a non-limiting example, referring to fig. 1 to 4, the inner diameter of the lower end of the outlet 12 is smaller than the inner diameter of the upper end of the outlet, thereby preventing magnetic particles from being scattered from the outlet 12 to overflow the outside of the second container 4.
In certain embodiments, referring to fig. 1 to 4, the tubular passage 1 comprises a helical conduit section 13, the inlet 11 and the helical conduit section 13 being transited by an inlet conduit section 14, and the outlet 12 and the helical conduit section 13 being transited by an outlet conduit section 15. With further reference to fig. 1 to 4, the inlet conduit section 14 and the outlet conduit section 15 are arranged vertically, and the inlet 11 and the outlet 12 are arranged vertically.
Referring to fig. 1 to 4, induction coils are arranged on the helical pipe section 13, the inlet pipe section 14 and the outlet pipe section 15. In some embodiments, one or more induction coils are disposed on inlet conduit section 14 to provide a magnetic force that separates and lifts magnetic particles from the solution in first vessel 3 into inlet 11. In some embodiments, a plurality of induction coils are disposed on the spiral pipe section 13, and induced current is introduced into the plurality of induction coils to form magnetic force in an increasing trend from the inlet pipe section 14 to the outlet pipe section 15 in the axial direction of the spiral pipe section 13, so that magnetic particles move in an accelerating manner in the spiral pipe section 13 and rotate in a spiral manner. In some embodiments, one or more induction coils are disposed on outlet conduit section 15 to provide a magnetic force that expels magnetic particles through outlet 12.
The magnetic particles contained in the solution in the first container 3 are separated from the solution by the magnetic force in the axial direction of the inlet pipe section 14, rise through the inlet 11 into the inlet pipe section 14, then into the spiral pipe section 13, rotate in the spiral pipe section 13, and flow through the spiral pipe section 13 in the axial direction to the outlet 12, and then are discharged into the second container 4 through the outlet 12.
In some embodiments, the magnetic force increases at least partially in sequence from the inlet 11 to the outlet 12, but this is not limited by the embodiments of the present application, and variations conforming to the increasing trend may be allowed.
An embodiment in which the magnetic force at least partially increases from the inlet 11 to the outlet 12 will be described.
Example 1
In example 1, the magnetic particles were accelerated by increasing the current in sequence.
22 induction coils are arranged on the inlet conduit section, the spiral conduit section, the outlet conduit section and the receiving platform, the induction coils are sequentially marked as "L1, L2, L3, L4, L5, … …, L20, L21 and L22", the number of turns of the coil in each induction coil is the same and is respectively set as 50 turns, the adjacent induction coils are arranged in a mode of opposite polarities (shown in a reference figure 5), the induction current intensity is sequentially marked as "I1-2A, I2-4A, I3-6A, I4-8A, I5-10A, … …, I20-40A, I21-42A and I22-44A".
In the using process, a first container of the solution containing the magnetic particles is placed below the inlet 11, 22 induction coils of 'L1, L2, L3, L4, L5, … …, L20, L21 and L22' in the device for separating the magnetic particles are sequentially subjected to pulse energization, and the magnetic field intensity generated under the action of induction current is as follows: e1 < E2 < E3 < E4 < E5 < … … < E20 < E21 < E22, under the action of the magnetic field, magnetic particles in the solution are sucked into the inlet pipe section through the inlet 11, are gradually accelerated under the action of the magnetic field which is increased in sequence in the spiral pipe section, are quickly separated from liquid attached to the surface and unbound substances in the spiral pipe section, and are finally collected to the second container 4 arranged above the receiving platform under the action of the strong magnetic field generated by the induction coil L22 below the receiving platform.
Example 2
In embodiment 2, the magnetic particles are accelerated by increasing the number of turns of the induction coil in order.
22 induction coils are arranged on the inlet pipe section, the spiral pipe section, the outlet pipe and the receiving platform, the induction coils are sequentially marked as "L1, L2, L3, L4, L5, … …, L20, L21 and L22", the current magnitude designed in each induction coil is 10A, the adjacent induction coils are arranged in the same polarity opposite mode (shown in a reference figure 6), the number of turns of the coils in the induction coils is sequentially designed as "S1-50 turns, S2-80 turns, S3-110 turns, S4-140 turns, S5-170 turns, … …, I20-620 turns, I21-650 turns and I22-680 turns.
In use, a first container of a solution containing magnetic particles is placed below the inlet 11, 22 induction coils of 'L1, L2, L3, L4, L5, … …, L20, L21 and L22' designed in the device for separating magnetic particles are sequentially electrified in a pulse mode, the magnetic field intensity generated under the action of induction current is 'E1 < E2 < E3 < E4 < E5 < … … < E20 < E21 < E22', under the action of magnetic field, the magnetic particles in the solution are sucked into the inlet pipe section through the inlet 11, gradual acceleration is realized under the action of the magnetic field sequentially increased in the spiral pipe section, rapid separation is realized in the spiral pipe with liquid attached to the surface and unbound substances, and finally the magnetic particles are collected to a second container arranged above a receiving platform under the action of the strong magnetic field generated by the induction coil L22 below the receiving platform.
Example 3
In embodiment 3, the magnetic particles are accelerated by increasing the number of turns of the induction coil in sequence and by increasing the intensity of current in the induction coil in sequence at the same time.
22 induction coils are arranged on the inlet conduit section, the spiral conduit section, the outlet conduit section and the receiving platform, wherein the induction coils are sequentially marked as "L1, L2, L3, L4, L5, … …, L20, L21, L22", the number of turns of the coils in the induction coils is "S1 ═ 50 turns, S2 ═ 80 turns, S3 ═ 110 turns, S4 ═ 140 turns, S5 ═ 170 turns, … …, I20 ═ 620 turns, I21 ═ 650 turns, I22 ═ 680", the connected induction coils are arranged in opposite polarities, and the induction current intensities are sequentially marked as "I1 ═ 2A, I1 ═ 4A, I1 ═ 6A, I1 ═ 8A, I1 ═ 1 a, I1 a ═ 3644".
In use, a first container of a solution containing magnetic particles is placed below the inlet 11, 22 induction coils of a device for separating the magnetic particles, namely L1, L2, L3, L4, L5, … …, L20, L21 and L22, are sequentially electrified in a pulse mode, the magnetic field strength generated under the action of induction current is E1 < E2 < E3 < E4 < E5 < … … < E20 < E21 < E22', under the action of the magnetic field, the magnetic particles in the solution are sucked into the inlet pipe section through the inlet 11, are gradually accelerated under the action of sequentially increased magnetic field, are rapidly separated from liquid attached to the surface and unbound substances in the spiral pipe section, and are finally collected into a second container arranged above the receiving platform under the action of the strong magnetic field generated by the induction coil L22 below the receiving platform.
Fig. 7 is a schematic diagram of a hardware structure of an embodiment of an apparatus for separating magnetic particles according to an embodiment of the present application, as shown in fig. 7, the apparatus includes: a device 100 for separating magnetic particles and a controllable unit 200. In the embodiments of the present application, the apparatus includes an apparatus for collecting magnetic particles by magnetic separation, and an electrochemical immunoassay, a magnetic particle chemiluminescence, a mass spectrometry immunoassay, a chemiluminescence immunoassay, or an enzyme-linked immunoassay detection apparatus, but is not limited thereto.
The apparatus 100 for separating magnetic particles is described with reference to fig. 1 to 5 and the foregoing description, and will not be described again. The control unit 200 may include a microcontroller, etc. capable of controlling the induction current to the induction coil to control the induction coil to generate the magnetic force.
In certain embodiments, referring to fig. 1-4, an apparatus 100 for separating magnetic particles includes: a tubular passage 1 through which magnetic particles can flow, the tubular passage 1 comprising an inlet 11 and an outlet 12, the inlet 11 being capable of interfacing with a first container 3 containing a solution containing magnetic particles, the outlet 12 being capable of interfacing with a second container 4 receiving magnetic particles. A plurality of independent induction coils, distributed axially along the tubular passage 1. And a control unit 200 configured to apply current to the plurality of independent induction coils to form a magnetic force in the axial direction of the tubular passage, separate magnetic particles from the solution by the magnetic force, suck the magnetic particles into the tubular passage 1 through the inlet 11, and discharge the magnetic particles from the outlet 12 after passing through the tubular passage 1.
In some embodiments, referring to fig. 1 and 2, the tubular passage 1 is at least partially in a planar spiral shape from the inlet 11 to the outlet 12, such that the magnetic particles rotate in the tubular passage 1 and the solution on the surface of the magnetic particles is further detached by the centrifugal force of the rotation. Although only the inlet 11 is shown in fig. 1 and 2 as being located at the center of the planar spiral, a planar spiral form is formed from the inlet 11 to the outlet 12 from the inside to the outside. However, in the present embodiment, the outlet 12 may be located at the center of the planar spiral, forming a planar spiral shape from the inlet 11 to the outlet 12 from the outside inward.
In other embodiments, the tubular passage 1 at least partially spirals from the inlet 11 to the outlet 12 as shown in fig. 3 and 4, such that the magnetic particles rotate in the tubular passage 1, the solution on the surface of the magnetic particles is further detached by the centrifugal force of the rotation, and the liquid on the surface of the magnetic particles is further detached by the action of gravity during the ascent.
In some embodiments, the magnetic particles are superparamagnetic microspheres with a capture function, and can capture a target substance to be detected in a solution. In certain embodiments, the superparamagnetic microspheres with capture function are immunomagnetic microspheres, which are used as antigen, antibody or immune complex after reaction of binding label on the surface of solid phase carrier. In certain embodiments, superparamagnetic microspheres with a trapping function as solid phase carriers are capable of directly trapping ions, ion-containing substances or ion-chelating substances in a solution. In certain embodiments, the superparamagnetic microspheres with a capture function serve as a solid phase carrier to directly capture metal ions, a substance containing metal ions or a substance chelating metal ions in a solution.
In some embodiments, the control unit 200 is configured to sequentially supply an induction current to the plurality of independent induction coils from the inlet 11 to the outlet 12, so as to generate a magnetic field at the positions of the induction coils according to a time sequence. Preferably, the induction coil adjacent to the induction coil which is supplied with the induction current does not supply the induction coil at the same time. As a non-limiting example, the control unit 200 at a first moment in time passes an induced current to the induction coil in a first position a close to the inlet 11, by which magnetic force the magnetic particles are separated from the solution and sucked into the tubular passage 1 through the inlet 11; at a second time, an induced current is applied to the induction coil at a second position close to the first position, and the magnetic particles are attracted from the first position to the second position by the magnetic force.
In some embodiments, the control unit 200 sequentially increases the current level in the associated induction coil to cause the magnetic force to at least partially increase from the inlet to the outlet, thereby accelerating the movement of the magnetic particles in the tubular passage and further promoting the separation between the magnetic particles and the solution on the surface thereof.
The device is characterized in that a magnetic induction coil is arranged outside a spiral conduit, magnetic particles are subjected to multi-stage continuous acceleration through the arranged magnetic induction coil, the magnetic particles rotate along the conduit at a high speed, and liquid or unbound substances on the surfaces of the magnetic particles are separated from the magnetic particles due to inertial motion. The magnetic particles can be quickly separated from the solution, the nonspecific adsorption is effectively reduced, and the detection sensitivity is greatly improved.
It should be understood that the apparatus or device in the embodiments of the present application may also include or have one or more other components, such as a power supply, a housing, etc., which are not limited by the embodiments of the present application.
Fig. 8 is a flowchart of an embodiment of a method for separating magnetic particles according to an embodiment of the present application, and as shown in fig. 8, the method includes steps S802 to S806.
Step S802, an inlet of the tubular passage is docked with a first container containing a solution containing magnetic particles.
Step S804, the outlet of the tubular passage is docked with a second receptacle that receives the magnetic particles.
Step S806, applying a magnetic field to the tubular passage to form a magnetic force in an axial direction of the tubular passage, wherein the magnetic particles are sucked out of the solution by the magnetic force, and are sucked into the tubular passage through the inlet, and flow through the tubular passage and are discharged from the outlet to the second container.
In certain embodiments, the step S806 of applying a magnetic field to the tubular passage to form a magnetic force in an axial direction of the tubular passage comprises: the magnetic field is applied sequentially at a plurality of positions on the tubular passage from the inlet to the outlet of the tubular passage to generate the magnetic field at the plurality of positions in time series.
In some embodiments, the magnetic force increases from the inlet to the outlet, thereby accelerating the movement of the magnetic particles in the tubular passage and further promoting the separation between the magnetic particles and the solution on the surface thereof. In the embodiments of the present application, the term "increasing trend" refers to a rule of increasing as a whole, including but not limited to the case of increasing one by one/in sequence.
In some embodiments, the tubular passage is at least partially in a planar spiral (as shown with reference to fig. 1 and 2) from the inlet to the outlet such that the magnetic particles rotate in the tubular passage and the centrifugal force of the rotation further detaches the solution on the surface of the magnetic particles.
In some embodiments, the tubular passage at least partially spirals from the inlet to the outlet (as shown in fig. 3 and 4) such that the magnetic particles rotate in the tubular passage, the solution on the surface of the magnetic particles is further detached by the centrifugal force of the rotation, and the liquid on the surface of the magnetic particles is further detached by gravity during the ascent.
In certain embodiments, as illustrated with reference to fig. 1-4, the magnetic field application unit comprises a plurality of independent induction coils disposed axially along the tubular passage. The plurality of induction coils may have different numbers of coil turns, at least in part. The magnitude of the generated magnetic force is related to the number of turns of the coil of the induction coil, and the magnitude of the generated magnetic force is related to the magnitude of the induced current led into the induction coil.
In some embodiments, the induction current is sequentially supplied to a plurality of independent induction coils from the inlet to the outlet of the tubular passage, so as to generate a magnetic field at the position of the induction coil according to the time sequence.
In some embodiments, the number of turns of the induction coil at least partially increases from the inlet to the outlet such that the magnetic force at least partially increases from the inlet to the outlet.
In some embodiments, the induced current into the induction coil at least partially increases from the inlet to the outlet, such that the magnetic force at least partially increases from the inlet to the outlet.
In some embodiments, the number of turns of the induction coil at least partially increases from the inlet to the outlet, and the induced current into the induction coil at least partially increases such that the magnetic force at least partially increases from the inlet to the outlet.
In some embodiments, the magnetic particles are superparamagnetic microspheres with a capture function, and can capture a target substance to be detected in a solution.
In certain embodiments, the superparamagnetic microspheres with capture function are immunomagnetic microspheres, which are used as antigen, antibody or immune complex after reaction of binding label on the surface of solid phase carrier.
In certain embodiments, superparamagnetic microspheres with a trapping function as solid phase carriers are capable of directly trapping ions, ion-containing substances or ion-chelating substances in a solution.
In certain embodiments, the superparamagnetic microspheres with a capture function serve as a solid phase carrier to directly capture metal ions, a substance containing metal ions or a substance chelating metal ions in a solution.
The following is a description of the application of the magnetic particle separation in the examples of the present application.
Example 4
Application in magnetic particle chemiluminescence immune analysis detection
In addition to the detection of Myoglobin (MPO), alkaline phosphatase may be used as a labeled marker, and horseradish peroxidase, acridinium esters, fluorescein, biotin, ruthenium terpyridyl, glucose oxidase, and the like may be used as a labeled marker.
(1) Immune response
Firstly, a mouse anti-human MPO monoclonal antibody is marked by alkaline phosphatase;
marking another mouse anti-human MPO monoclonal antibody by biotin;
marking the magnetic microspheres with streptavidin;
adding a sample containing MPO, one mouse anti-human MPO monoclonal antibody marked by alkaline phosphatase, the other mouse anti-human MPO monoclonal antibody marked by biotin and magnetic microspheres marked by streptavidin into a reaction cup, and forming reaction liquid containing the magnetic microspheres with the MPO immune complex marked by the alkaline phosphatase combined on the surface after incubation reaction.
(2) On-line separation
And arranging a magnetic particle receiving cup on a receiving platform at the outlet of the device for separating magnetic particles, placing a reaction cup at the inlet of the device for separating magnetic particles, and collecting the magnetic microspheres of the MPO immune complex marked by alkaline phosphatase in the reaction solution under the action of the device for separating magnetic particles.
(3) Detection of
Adding an alkaline phosphatase luminescent substrate into the magnetic particle receiving cup, detecting a luminescent signal through a magnetic particle chemiluminescence apparatus, establishing a standard curve by utilizing the relation between the luminescent signal of the alkaline phosphatase and the concentration of MPO, and calculating the content of MPO through the standard curve.
Example 5
Mass spectrometric immunoassay detection
Taking metal material as a marker (such as gold nanoparticles), for example, to detect 25-hydroxyvitamin D (25-OH-D), and Cd2+、Cu2+、Zn2+、Mn2+、Pb2+、Ag+、Li+、Hg2+、Co2+、Cr3+、Ni2+、Au3+、Ba2+And the like are used as markers.
(1) Immune response
Firstly, marking a 25-OH-D complete antigen strain by gold nanoparticles;
marking a mouse anti-human 25-OH-D monoclonal antibody by using biotin;
marking the magnetic microspheres with streptavidin;
adding a sample containing 25-OH-D, a mouse 25-OH-D complete antigen marked by gold nanoparticles, a mouse antihuman 25-OH-D monoclonal antibody marked by biotin and magnetic microspheres marked by streptavidin into a reaction cup, and forming reaction solution containing magnetic microspheres with the surface combined with the gold nanoparticle marked 25-OH-D immune complex and the surface combined with the 25-OH-D immune complex in the sample after incubation reaction.
(2) On-line separation
The magnetic particle receiving cup is arranged on a receiving platform at the outlet end of the device for separating the magnetic particles, the reaction cup is arranged at the inlet of the device for separating the magnetic particles, the magnetic microspheres of the gold nanoparticle-labeled 25-OH-D immune complex and the magnetic microspheres of the 25-OH-D immune complex in the sample are combined on the surface in the reaction solution, and the magnetic microspheres are collected into the magnetic particle receiving cup under the action of the device for separating the magnetic particles.
(3) Detection of
Adding aqua regia into a magnetic particle receiving cup to dissolve the magnetic microspheres and the gold nanoparticles, then pumping the dissolved solution into an inductively coupled plasma mass spectrometer (ICP-MS) for detection to obtain a pulse signal of gold ions, establishing a standard curve according to the relation between the content of the gold ions and 25-OH-D, and calculating the content of the 25-OH-D through the standard curve.
Example 6
Application in electrochemical immunoassay detection
Metal material is used as a marker (such as copper oxide), and Cd is contained in the metal material to detect alpha fetoprotein as an example2+、Cu2+、Zn2+、Mn2+、Pb2+、Ag+、Li+、Hg2+、Co2+、Cr3+、Ni2+、Au3+、Ba2+And the like are used as markers.
(1) Immune response
Firstly, a mouse anti-human AFP monoclonal antibody is marked by CuO;
marking another mouse anti-human monoclonal antibody with biotin;
marking the magnetic microspheres with streptavidin;
and fourthly, adding a sample containing AFP, one mouse anti-human AFP monoclonal antibody marked by CuO, the other mouse anti-human AFP monoclonal antibody marked by biotin and magnetic microspheres marked by streptavidin into a reaction cup, and forming reaction liquid containing the magnetic microspheres with the AFP immune complex of which the surfaces are combined with the CuO marks after incubation reaction.
(2) On-line separation
The working electrode is arranged on a receiving platform at the outlet end of the device for separating the magnetic particles, the reaction cup is arranged at the inlet of the device for separating the magnetic particles, and the CuO-labeled magnetic microspheres of the AFP immune complex are combined on the surface of the reaction solution and are enriched on the surface of the working electrode under the action of the device for separating the magnetic particles.
(3) Detection of
Connecting a working electrode (graphene electrode), a counter electrode (platinum electrode) and a reference electrode (calomel electrode) on an electrochemical workstation, determining a voltammetry curve of copper ions on an immune complex on the surface of the magnetic microsphere by using a voltammetry method, establishing a standard curve according to the relationship between the current intensity (peak height) or the half-peak area of the copper ions and the concentration of an AFP to be detected, and calculating the content of the AFP according to the standard curve.
Example 7
For detecting ions in solution
Using superparamagnetic Fe3O4@ polyethylene imine core-shell microsphere as solid phase carrier for detecting Cd in solution2+For example, Cu in solution may be treated in addition to the above2+、Zn2+、Mn2+、Pb2+、Ag+、Li+、Hg2+、Co2+、Cr3+、Ni2+、Au3+、Ba2+、Mg2+、Ca2+、Br-、I-Or Cl-And so on.
(1) Reaction of
firstly, preparing superparamagnetic Fe3O4@ polyethyleneimine core-shell microspheres;
② containing Cd2+Adding the solution to be measured into a reaction cup, and then adding superparamagnetic Fe3O4@ polyethylene imine core-shell microsphere for adsorbing Cd in solution2+；
(2) On-line separation
Arranging a magnetic particle receiving cup on a receiving platform at the outlet end of a device for separating magnetic particles, placing a reaction cup at the inlet of the device for separating magnetic particles, and adsorbing Cd on the surface of reaction liquid2+Superparamagnetic Fe of3O4The @ polyethylene imine core-shell microspheres are collected in the magnetic particle receiving cup under the action of a device for separating magnetic particles.
(3) Detection of
Chloroform is added into the magnetic particle receiving cup to dissolve polyethyleneimine, and thenAdding aqua regia to dissolve magnetic microspheres, and then injecting the dissolved solution into a microwave plasma torch mass spectrometer (MPT-MS) for detection to obtain Cd2+The Cd in the solution is calculated through a standard curve2+The content of (a).
Example 8
Detecting substances containing ions or chelated ions
In addition to trypsin (Ca), chymotrypsin (Ca), carboxypeptidase (Zn), neutral protease (Zn), thermolysin (Ca, Zn), collagenase (Ca, Zn), cyanin, bromophenol cyanin, metallothionein, hemoglobin binding copper ions or iron ions, chelating agents for chelating metal ions (xanthate metal chelating agents, dithiocarbamate derivative metal chelating agents, ethylenediaminetetraacetic acid, ethylenediamine, 2' -bipyridine, 1, 10-phenanthroline, oxalate, and the like) can be detected.
(1) Reaction of
Firstly, processing magnetic microspheres by adopting a surfactant containing carboxyl or amino to prepare magnetic microspheres with activated surfaces;
② adding the solution containing trypsin (Ca) into a reaction cup, and then adding magnetic microspheres with activated surfaces to adsorb the trypsin (Ca) in the solution.
(2) On-line separation
The magnetic particle receiving cup is arranged on a receiving platform at the outlet end of the device for separating the magnetic particles, the reaction cup is placed at the inlet of the device for separating the magnetic particles, and the magnetic microspheres with trypsin (Ca) adsorbed on the surface in the reaction liquid are collected into the magnetic particle receiving cup under the action of the device for separating the magnetic particles.
(3) Detection of
Adding aqua regia into a magnetic particle receiving cup to dissolve magnetic microspheres, and injecting the dissolved solution into an inductively coupled plasma emission spectrometer (ICP-OES) for detection to obtain Ca2+The Ca in the solution is calculated by a standard curve2+The content of (a).
It should be understood that the above embodiments 4 to 8 are only exemplary illustrations of separating magnetic particles in the embodiments of the present application, and the method, the apparatus and the device for separating magnetic particles in the embodiments of the present application can be applied to in vitro diagnosis, food safety, environmental monitoring, etc., and no further description is given in the embodiments of the present application.
Through this application embodiment, through set up the magnetic induction coil in the spiral pipe outside, carry out multistage continuous acceleration to the magnetic particle through the magnetic induction coil who sets up, the magnetic particle is along the high-speed rotation of pipe, and the liquid on magnetic particle surface or the material that does not combine because inertial motion and with the magnetic particle separation, have saved loaded down with trivial details washing step. On one hand, the detection time is saved, and the detection efficiency is greatly improved; on the other hand, the washing liquid is saved, and the production cost is reduced. Not only can separate the magnetic particles from the solution quickly, but also can effectively reduce the nonspecific adsorption and greatly improve the detection sensitivity.
It should be noted that, in this document, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. Without further limitation, an element defined by the phrase "comprising an … …" does not exclude the presence of other like elements in a process, method, article, or apparatus that comprises the element.
The above-mentioned serial numbers of the embodiments of the present application are merely for description and do not represent the merits of the embodiments.
While the present embodiments have been described with reference to the accompanying drawings, it is to be understood that the invention is not limited to the precise embodiments described above, which are meant to be illustrative and not restrictive, and that various changes may be made therein by those skilled in the art without departing from the spirit and scope of the invention as defined by the appended claims.
Claims (13)
1. An apparatus for separating magnetic particles, comprising:
a tubular passage through which magnetic particles can flow, the tubular passage comprising an inlet that can be docked with a first container containing a solution containing magnetic particles and an outlet that can be docked with a second container that receives the magnetic particles;
a magnetic field applying unit configured to apply a magnetic field to form a magnetic force in an axial direction of the tubular passage; wherein the magnetic force is capable of drawing the magnetic particles out of the solution, into the tubular passage through the inlet, through the tubular passage, and out of the outlet to the second container.
2. The device of claim 1, wherein the magnetic force at least partially increases from the inlet to the outlet.
3. The apparatus according to claim 1, wherein the magnetic field applying unit is configured to sequentially apply the magnetic field at a plurality of positions on the tubular passage from the inlet to the outlet to generate the magnetic field at the plurality of positions in time series.
4. A device according to claim 1, 2 or 3, wherein the tubular passage is at least partially helical from the inlet to the outlet, or wherein the tubular passage is at least partially planar helical.
5. The apparatus of claim 1, 2 or 3, wherein the magnetic field applying unit comprises a plurality of independent induction coils arranged axially along the tubular passage.
6. The apparatus of claim 5, wherein from the inlet to the outlet, the number of turns of the induction coil at least partially increases; and/or the induced current passing into the induction coil at least partially increases from the inlet to the outlet.
7. The apparatus of claim 5, wherein adjacent induction coils are arranged in a like polarity opposing manner.
8. An apparatus for separating magnetic particles, comprising:
the device of any one of claims 1 to 7;
a receiving platform configured to receive the second container, the receiving platform being configured with a magnetic element to generate a magnetic force from an opening to a bottom of the second container.
9. An apparatus for separating magnetic particles, comprising:
a tubular passage through which magnetic particles can flow, the tubular passage comprising an inlet that can be interfaced with a first container containing a solution containing magnetic particles and an outlet that can be interfaced with a second container receiving magnetic particles;
a plurality of independent induction coils axially distributed along the tubular passage;
a control unit configured to supply an induced current to the plurality of independent induction coils to form a magnetic force in an axial direction of the tubular passage; wherein the magnetic force is capable of separating the magnetic particles from the solution and drawing the magnetic particles into the tubular passage through the inlet and discharging the magnetic particles from the outlet after flowing along the tubular passage.
10. The apparatus of claim 9, wherein from the inlet to the outlet, a number of turns of an induction coil at least partially increases such that the magnetic force at least partially increases from the inlet to the outlet; and/or the control unit is arranged to increase at least part of the induced current passing through the induction coil from the inlet to the outlet, so that the magnetic force increases at least part of the induced current from the inlet to the outlet.
11. The apparatus of claim 9, wherein the control unit is configured to sequentially pass an induced current through the plurality of independent induction coils from the inlet to the outlet to generate a magnetic field at a location where the induction coils are located according to a time sequence.
12. The apparatus according to any one of claims 9 to 11, wherein the tubular passage is at least partially helical up from the inlet to the outlet, or wherein the tubular passage is at least partially planar helical.
13. The apparatus of claim 9, wherein adjacent induction coils are arranged in a like polarity opposing manner.
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| CN114354591A (en) * | 2022-01-10 | 2022-04-15 | 军事科学院军事医学研究院环境医学与作业医学研究所 | Colorimetric/fluorescent dual-mode biosensing detection method for rapidly detecting aflatoxin B1 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN114354591A (en) * | 2022-01-10 | 2022-04-15 | 军事科学院军事医学研究院环境医学与作业医学研究所 | Colorimetric/fluorescent dual-mode biosensing detection method for rapidly detecting aflatoxin B1 |
| CN114354591B (en) * | 2022-01-10 | 2023-06-02 | 军事科学院军事医学研究院环境医学与作业医学研究所 | Colorimetric/fluorescent double-mode biosensing detection method for rapidly detecting aflatoxin B1 |
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