Sample processing device and method

Abstract

A magnet (30) is placed beneath a nozzle tip (54) that accommodates a magnetic particle liquid. A metal particle aggregate (56) thereby forms in the bottom of an internal space of the nozzle tip (54). Subsequently, as the magnet (30) is placed on the side of the nozzle tip (54), the metal particle aggregate (56) moves upward along the inner surface. Thereafter, the remaining liquid in the nozzle tip 54 is discharged.

Description

[Technical Field]

[0001] FIELD OF THE DISCLOSURE The present disclosure relates to sample processing apparatus and methods, and in particular to the manipulation of magnetic particles. [Background technology]

[0002] A sample processing apparatus is an apparatus that processes samples such as blood and urine taken from a living body. Examples of sample processing apparatus include reagent processing apparatuses, biochemical analyzers, and immunoassay apparatuses. An immunoassay apparatus will be described below.

[0003] An immunoassay device is a device that uses an immune reaction (specifically, an antigen-antibody reaction) to detect a specific substance (antigen or antibody) in a sample or measure the amount of a specific substance in a sample. Immunoassay devices typically use a reagent containing magnetic particles (magnetic particle reagent). Each magnetic particle functions as a solid phase, i.e., a target substance (e.g., an antibody or antigen) that specifically binds to the specific substance is immobilized on its surface.

[0004] Prior to the immune reaction, the specimen and magnetic particle reagent are mixed in a reaction vessel. After the immune reaction, a magnet is brought close to the side of the reaction vessel, and a magnetic force is exerted on the magnetic particles in the reaction vessel. This results in the magnetic particles being captured on the inner surface of the reaction vessel. With the magnetic particles captured, B (Bound) / F (Free) separation is performed on the contents of the reaction vessel. Specifically, the residual liquid after the immune reaction is aspirated and removed, and then a washing solution is supplied into the reaction vessel, and then the washing solution is aspirated and removed from the reaction vessel. Such a washing process is performed multiple times as necessary. If stirring of the magnetic particles in the washing solution is required during the B / F separation process, mechanical vibration is applied to the reaction vessel while the magnetic force is maintained or while the magnetic force is temporarily removed.

[0005] The following Patent Documents 1 and 2 disclose techniques for capturing magnetic particles in a nozzle (specifically, a nozzle tip) using magnetic force. The magnetic particles are captured at a relatively high position in the nozzle. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Patent No. 3115501 Specification [Patent Document 2] Patent No. 4264134 specification Summary of the Invention [Problem to be solved by the invention]

[0007] When magnetic particles are dispersed in the liquid in the nozzle, if a magnetic source such as a magnet is placed next to the nozzle, the magnetic force of the magnetic source can be used to collect the magnetic particles on the inner surface of the nozzle, that is, a group of magnetic particles (hereinafter referred to as a magnetic particle aggregate) can be formed on the inner surface of the nozzle.B / F separation can then be performed.

[0008] Since the inner surface of a nozzle is usually a vertical or inclined surface that extends in the vertical direction, when a magnetic particle aggregate is formed on the inner surface by magnetic forces acting from adjacent nozzles, the magnetic particle aggregate spreads in the vertical direction, i.e., becomes band-like. In order to fill the entire magnetic particle aggregate that has spread in the vertical direction with a treatment liquid such as a reagent and then treat the magnetic particle aggregate, it is necessary to pour a relatively large amount of treatment liquid into the nozzle. Conversely, in order to treat the magnetic particle aggregate in the nozzle with a small amount of treatment liquid, it is necessary to suppress the vertical spread of the magnetic particle aggregate.

[0009] An object of the present disclosure is to suppress the vertical spread of magnetic particle aggregates when magnetic force is used to form them on the inner surface of a nozzle, or to realize a technology that can manipulate the morphology of magnetic particle aggregates when magnetic force is used to form them on the inner surface of a nozzle. [Means for solving the problem]

[0010] The sample processing device according to the present disclosure includes a nozzle that contains a magnetic particle liquid containing magnetic particles that bind to a specific substance in a sample; Directly below and a magnetic system that applies a magnetic force to the magnetic particles from the nozzle, thereby generating a magnetic particle aggregate in the lower portion of the internal space of the nozzle.

[0011] The sample processing method according to the present disclosure includes: a step of: disposing a nozzle containing a magnetic particle liquid containing magnetic particles that bind to a specific substance in a sample; Directly below The method is characterized in that a magnetic force is exerted on the magnetic particles from the nozzle, causing a magnetic particle agglomerate to form at the bottom of the internal space of the nozzle, and a magnetic force is exerted on the magnetic particle agglomerate from the side of the nozzle, causing the magnetic particle agglomerate to move from the bottom to a stopping position on the inner surface of the hollow container. [Brief explanation of the drawings]

[0012] [Figure 1] 1 is a block diagram showing an immunoassay device according to an embodiment. [Figure 2] FIG. 1 shows a B / F separation applied to the contents of a cuvette. [Figure 3] FIG. 10 is a diagram showing the suction of magnetic particle liquid by a nozzle tip. [Figure 4] FIG. 1 is a diagram showing a sample processing method according to an embodiment, specifically showing steps (A) to (D). [Figure 5] FIG. 2 is a diagram showing a sample processing method according to an embodiment, specifically showing steps (E) to (H). [Figure 6]FIG. [Figure 7] 10 is a flowchart showing a part of the operation of the immunoassay device according to the embodiment. [Figure 8] 10 is a flowchart showing the remaining part of the operation of the immunoassay device according to the embodiment. [Figure 9] FIG. 1 is a perspective view showing a magnetic system according to a first embodiment. [Figure 10] FIG. 2 is an enlarged perspective view showing a part of the magnetic system according to the first embodiment. [Figure 11] FIG. 4 is a diagram illustrating horizontal movement of the magnetic system according to the first embodiment. [Figure 12] FIG. 4 is a diagram illustrating a bending motion of the magnetic system according to the first embodiment. [Figure 13] FIG. 2 illustrates the formation of a first magnetic particle aggregate and a second magnetic particle aggregate. [Figure 14] 10A-10C illustrate the movement of the nozzle tip relative to the magnetic system. [Figure 15] FIG. 10 is a diagram showing the introduction of a test liquid into a microchip. [Figure 16] FIG. 10 is a diagram showing a first modified example. [Figure 17] FIG. 10 is a diagram showing a second modified example. [Figure 18] FIG. 10 is a diagram showing a third modified example. [Figure 19] FIG. 10 is a diagram showing a first aspect of a magnetic system according to a second embodiment. [Figure 20] FIG. 10 is a diagram showing a second aspect of the magnetic system according to the second embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0013] Hereinafter, an embodiment will be described with reference to the drawings.

[0014] (1) Overview of the embodiment The sample processing device according to the embodiment includes a nozzle and a magnetic system. The nozzle is a component that contains a magnetic particle liquid containing magnetic particles that bind to a specific substance in a sample. The magnetic system exerts a magnetic force on the magnetic particles from below the nozzle, thereby generating a magnetic particle aggregate in the lower part of the internal space of the nozzle.

[0015] The lower part of the internal space of a nozzle is usually a narrow or constricted part. When a magnetic force is applied from the bottom of the nozzle, magnetic particles gather in the lower part of the internal space, forming a magnetic particle aggregate. At that time, the vertical expansion of the magnetic particle aggregate is suppressed, or its vertical width is minimized. The magnetic particle aggregate may then be moved using the action of magnetic force. During the movement process, the magnetic particle aggregate will not expand significantly, or the possibility of this happening is low. In this way, the above configuration utilizes the lower part of the internal space of the nozzle as a mold for the magnetic particle aggregate.

[0016] An opening for discharge or suction is formed at the lower end of the nozzle tip. The magnitude of the magnetic force is determined so that the magnetic particles or droplets do not flow out of the opening. An air cap may be formed below the magnetic particle aggregate within the lower portion. In an embodiment, the nozzle that contains the magnetic particle liquid is a nozzle tip that is detachably attached to the nozzle base. The concept of sample processing can include various processes including measurement, analysis, manipulation, etc. of the sample.

[0017] In an embodiment, the magnetic system includes a magnetic source and a moving mechanism. The moving mechanism is a mechanism for changing the relative positional relationship between the magnetic source and the nozzle. The moving mechanism provides the magnetic source below the nozzle to generate a magnetic particle agglomerate below the nozzle. The magnetic source may be moved relative to the nozzle, or the nozzle may be moved relative to the magnetic source. Both may be moved.

[0018] In an embodiment, the movement mechanism relatively moves the magnetic source from below the nozzle to the side of the nozzle. As the magnetic source moves, the magnetic particle aggregate slides up along the inner surface of the nozzle from below and remains at a stopping position on the inner surface. While the magnetic particle aggregate remains at a stopping position, a liquid passage is created adjacent to the magnetic particle aggregate. Conversely, the magnetic particle aggregate is moved and positioned so as to ensure a liquid passage.

[0019] In an embodiment, the nozzle discharges the residual liquid contained in the internal space while the magnetic particle aggregate remains at the retention position. In this case, the residual liquid flows through the liquid passage. Then, the liquid taken in from the outside flows through the liquid passage in the nozzle.

[0020] In the embodiment, a gap is formed between the lower end of the magnetic particle aggregate remaining at the retention position and the lower end of the nozzle, and this configuration can prevent or reduce the inadvertent leakage of part of the magnetic particle aggregate.

[0021] In an embodiment, the magnetic source includes a first magnetic source and a second magnetic source. The moving mechanism includes a first holding mechanism that holds the first magnetic source and a second holding mechanism that holds the second magnetic source. The first holding mechanism and the second holding mechanism are provided below the nozzle. Then, the first holding mechanism and the second holding mechanism move the first magnetic source to one side of the nozzle and move the second magnetic source to the other side of the nozzle. The stopping positions are stopping positions on one side and the other side on the inner surface of the nozzle. Within the magnetic particle aggregate, the first magnetic particle aggregate moves to the stopping position on one side. Within the magnetic particle aggregate, the second magnetic particle aggregate moves to the stopping position on the other side.

[0022] According to the above configuration, the first magnetic particle aggregate and the second magnetic particle aggregate are formed at the retention position on one side and the retention position on the other side on the inner surface of the nozzle, and the gap between them functions as a liquid passage.

[0023] In an embodiment, the first magnetic source has a first magnetic pole pair. The first magnetic pole pair is composed of adjacent north and south poles. The second magnetic source has a second magnetic pole pair. The second magnetic pole pair is composed of adjacent north and south poles. By arranging the north and south poles adjacent to each other, the magnetic flux density can be increased near their boundary. When the first magnetic pole pair and the second magnetic pole pair are arranged facing upward below the nozzle, the four magnetic poles are two-dimensionally arranged so that two north poles and two south poles alternate in both the first horizontal direction and the second horizontal direction. When the first magnetic pole pair and the second magnetic pole pair are arranged facing each other on both sides of the nozzle, the north pole on one side faces the south pole on the other side, and the south pole on one side faces the north pole on the other side.

[0024] In an embodiment, the first magnetic source has a first magnetic pole set. The first magnetic pole set is composed of a plurality of north poles and a plurality of south poles arranged in a two-dimensional staggered pattern. The second magnetic source has a second magnetic pole set. The second magnetic pole set is composed of a plurality of north poles and a plurality of south poles arranged in a two-dimensional staggered pattern. Each magnetic pole set increases the magnetic flux density. When the first magnetic pole set and the second magnetic pole set are arranged facing upward on the lower side of the nozzle, the north poles and the south poles are arranged two-dimensionally so that they are staggered in both the first horizontal direction and the second horizontal direction. When the first magnetic pole set and the second magnetic pole set are arranged facing each other on both sides of the nozzle, the north poles on one side face each other and the south poles on the other side face each other, and the south poles on one side face each other.

[0025] In the embodiment, the first and second holding mechanisms have a function of orienting the magnetic pole faces of the first and second magnetic sources upward. The first and second holding mechanisms also have a function of orienting the magnetic pole faces of the first and second magnetic sources facing each other with the nozzle therebetween. This configuration allows the first and second holding mechanisms to form and move magnetic particle aggregates.

[0026] The sample processing method according to the embodiment includes an aggregate formation step and an aggregate transfer step. In the aggregate formation step, a magnetic particle liquid containing magnetic particles that bind to a specific substance in a sample is contained in a nozzle, and a magnetic force is applied to the magnetic particles from below the nozzle. This forms a magnetic particle aggregate at the bottom of the internal space of the nozzle. In the aggregate transfer step, a magnetic force is applied to the magnetic particles from the side of the nozzle. This causes the magnetic particle aggregate to move from the bottom to a retention position on the inner surface of the nozzle. If the upper end of the magnetic particle aggregate is at a relatively low position in the internal space, it becomes possible to process the magnetic particles with a small amount of processing liquid. For other purposes or uses, a magnetic particle aggregate may be formed at the bottom of a hollow container such as a nozzle.

[0027] (2) Details of the embodiment FIG. 1 shows an immunoassay device 10 according to an embodiment. The immunoassay device 10 detects a specific substance (e.g., an antibody or an antigen) in a sample by utilizing an antigen-antibody reaction, or measures the amount of a specific substance in the sample. The immunoassay device 10 is a type of sample processing device. The sample is a biological specimen such as blood or urine collected from a human body. One example of the immunoassay device 10 is a fully automated immunoassay device that complies with chemiluminescent enzyme immunoassay (CLEIA).

[0028] 1 illustrates some of the many components included in the immunoassay device 10. The immunoassay device 10 includes a rack transport mechanism 12, a reagent refrigerator 14, a nozzle transport mechanism 18, a cuvette B / F separation section 26, a nozzle B / F separation section 32, a measurement unit 34, a control unit 36, and the like.

[0029] The rack transport mechanism 12 is a mechanism for transporting multiple sample racks. Each sample rack is a member that holds multiple sample containers. Each sample container contains a sample. The reagent refrigerator 14 is a facility that stores multiple reagent bottles and controls their temperature. The multiple reagent bottles include a bottle 16 that contains a magnetic particle reagent.

[0030] The magnetic particle reagent contains magnetic particles. The body of each magnetic particle is made of a magnetic material and functions as a solid phase. A substance to be bound (e.g., an antigen or antibody) that specifically binds to a specific substance (e.g., an antibody or antigen) in a sample is fixed to the surface of the body. The substance to be bound is also called a molecular probe. The average particle size of the magnetic particles is, for example, in the range of 0.1 μm to 1 mm. All numerical values described in this specification are merely examples.

[0031] The nozzle transport mechanism 18 is a mechanism for transporting the nozzle 20. For example, the nozzle 20 is a nozzle for aspirating a post-reaction magnetic particle liquid from a cuvette (reaction vessel) (described later) and then processing the magnetic particles contained in the aspirated magnetic particle liquid. The magnetic particle liquid contains not only magnetic particles but also a specimen solution (residual liquid) containing a residual specimen.

[0032] As will be described later, in an embodiment, the nozzle 20 is composed of a nozzle base and a nozzle tip. The nozzle tip is a disposable member that is detachably attached to a metal nozzle base. A plurality of nozzle tips with different storage capacities may be prepared, and the nozzle tip to be actually used may be selected from among them. For example, a 2 μl nozzle tip, a 20 μl nozzle tip, a 200 μl nozzle tip, a 1000 μl nozzle tip, a 5000 μl nozzle tip, etc. may be prepared. Various nozzle tips other than dispensing nozzle tips may also be used. The nozzle tip is made of a transparent non-magnetic material, such as synthetic resin (PP, PMMA, PC, etc.).

[0033] In addition to the nozzle 20, the immunoassay device 10 is also provided with a nozzle for aspirating and discharging a sample, a nozzle for aspirating and discharging a reagent, a nozzle for discharging a cleaning liquid, etc., but these are not shown in the figure.

[0034] The cuvette B / F separation section 26 is provided with a cuvette magnet unit 24 and a transport mechanism 22 that transports it. In the cuvette B / F separation section 26, B / F separation is performed on the contents of the cuvette after the immune reaction. At this time, the transport mechanism 22 positions the cuvette magnet unit 24 relative to the cuvette. During B / F separation, the remaining liquid in the cuvette is aspirated and removed, and then a washing solution is injected into the cuvette and then aspirated and removed from the cuvette repeatedly. If it becomes necessary to stir the magnetic particles during B / F separation, mechanical vibrations are transmitted to the cuvette. At this time, the cuvette magnet unit 24 may be temporarily moved away from the cuvette.

[0035] The nozzle B / F separation section 32 is provided with a nozzle magnet section 30 and a transport mechanism 28 that transports it. The nozzle magnet section 30 and the transport mechanism 28 function as a magnetic system (magnetic means). The transport mechanism 28 functions as a transport system (moving means). In the nozzle B / F separation section 32, B / F separation is performed on the contents in the nozzle (specifically, the nozzle tip).

[0036] At this time, the transport mechanism 28 transports and positions the nozzle magnet part 30. Typically, the nozzle magnet part 30 is first provided below the nozzle, and then the nozzle magnet part 30 is transported from below the nozzle to the side (next to) the nozzle. When the nozzle magnet part 30 reaches a predetermined position beside the nozzle, the transport of the nozzle magnet part 30 is stopped. Thereafter, the nozzle magnet part 30 is maintained in a position adjacent to the nozzle.

[0037] In such a series of magnet part movement processes, a magnetic particle aggregate is first formed at the bottom inside the nozzle 20, then the magnetic particle aggregate moves from the bottom along the inner surface of the nozzle 20 to a stopping position, and then the magnetic particle aggregate remains at the stopping position.

[0038] While the magnetic particle aggregates are captured, i.e., magnetically attracted, the remaining liquid in the nozzle 20 is discharged. This corresponds to B / F separation. Then, in an embodiment, a dissociative (cleavable) reagent, which will be described in detail later, is aspirated into the nozzle 20. A washing step may be performed between the discharge of the remaining liquid and the aspirating of the reagent. In the washing step, the aspirating and dispensing of the washing liquid may be repeated. A stirring step may be performed after the aspirating of the reagent. In the stirring step, the aspirating and dispensing of the contents including the reagent may be repeated. During this process, the magnetic action may be maintained, or the magnetic action may be temporarily released. Stirring by periodic movement of the nozzle 20 or by transmitting mechanical vibrations to the nozzle 20 is also possible. It is desirable to adopt a stirring method that does not cause droplets to fall from the nozzle 20.

[0039] In the measurement unit 34, measurement is performed on the test liquid that has undergone a series of processes. For example, the test liquid extracted from the nozzle 20 is irradiated with laser light, and the resulting fluorescence is detected. In this case, as described below, a microchip (microchemical chip, microfluidic chip) equipped with a microchannel through which a small amount of test liquid flows may be used. The fluorescent intensity or pulse number can be used to quantify the labeled substance, i.e., the specific substance in the sample can be quantified. In this embodiment, a photolabile reagent that promotes cleavage of a photocleavable linker by irradiation with light is used as the dissociating reagent. Reagents that cause dissociation by enzymes are also known, and such dissociating reagents may be used. A detection reagent other than the dissociating reagent described above may be sucked into the nozzle. Various known detection methods may be used to quantify the labeled substance.

[0040] Although not shown in FIG. 1, the immunoassay device 10 includes a reaction table that functions as a reaction section. The reaction table has a plurality of holes arranged in a circle, and a cuvette is inserted into each hole. B / F separation sections 26 are provided at a plurality of locations on the reaction table. The temperature of each cuvette on the reaction table is maintained at a predetermined temperature. The predetermined temperature is a temperature suitable for the immune reaction, for example, 37°C.

[0041] For example, when the so-called sandwich method is applied, a first immune reaction step, a second immune reaction step, and a detection reaction step are sequentially performed. In the first immune reaction step, a magnetic particle reagent is used, and a specific substance in the specimen binds to a first binding substance (first probe molecule) immobilized on the magnetic particle. In the second immune reaction step, a labeled reagent is used in which a labeling substance such as a fluorescent substance is bound to a second binding substance (second probe molecule). This causes the labeling substance to bind to the specific substance. More specifically, the first probe molecule in the magnetic particle reagent is immobilized on the magnetic particle via a photocleavable linker, or the labeling substance in the labeled reagent is bound to the second probe molecule via a photocleavable linker. In the detection reaction step, a photolabile reagent that promotes cleavage of the photocleavable linker is used. By irradiating the nozzle 20 with light of a specific wavelength, a photodissociation reaction occurs within the nozzle 20. That is, dissociation occurs somewhere between the solid phase and the labeled substance. For example, the action of a photolabile reagent causes dissociation at the binding site between the solid phase and the first probe molecule. Alternatively, the action of a photolabile reagent causes dissociation at the binding site between the labeling substance and the second probe molecule. Note that, as described above, a dissociating reagent that causes dissociation by an enzyme may be used instead of a photolabile reagent.

[0042] The cuvette B / F separation section 26 functions after the first immune reaction step and the second immune reaction step. The nozzle B / F separation section 32 functions after the detection reaction step, specifically after the photodissociation reaction step. However, the immunoassay device 10 shown in FIG. 1 can accommodate various methods. These methods may include a method in which only the cuvette B / F separation section 26 functions, and a method in which only the nozzle B / F separation section 32 functions.

[0043] The control unit 36 controls the operation of each component included in the immunoassay device 10. The control unit 36 includes, for example, a processor that executes programs and processes data. The processor is, for example, a CPU. The control unit 36 exchanges data with a host system via a communication line 38. The configuration of the immunoassay device 10 shown in FIG. 1 is an example. The nozzle B / F separation section 32 may be mounted on other sample processing devices. It is also possible to apply the magnetic particle manipulation according to the embodiment to hollow containers other than the nozzle 20.

[0044] Figure 2 shows an example of the cuvette B / F separation section 26. (A) in Figure 2 shows the transport mechanism 22 in an inoperative state, and (B) in Figure 2 shows the transport mechanism 22 in an operative state.

[0045] In the illustrated example, the magnet unit 24 is composed of two magnets (permanent magnets) 44, 46. They are held by the transport mechanism 22, and their positions are changed by the transport mechanism 22. In the illustrated configuration example, the two magnets 44, 46 can each move only in the up and down directions.

[0046] As shown in (A), the cuvette 40 contains a magnetic particle liquid 42 after the immune reaction. The magnetic particle liquid 42 consists of magnetic particles 42A and residual liquid 42B. A specific substance in the specimen is specifically bound to each magnetic particle 42A. The residual liquid 42B corresponds to the specimen and reagent solution remaining after the immune reaction.

[0047] As shown in (B), magnets 44, 46 are arranged on one side and the other side of the cuvette 40. The magnetic force generated by the magnets 44, 46 attracts the magnetic particles toward the magnets 44, 46, resulting in two magnetic particle populations. Specifically, a first magnetic particle aggregate 48 is generated on one side of the inner surface of the cuvette 40, and a second magnetic particle aggregate 50 is generated on the other side of the inner surface of the cuvette 40. The inner surface (inner side) of the cuvette 40 is close to a cylindrical surface, which is a vertical surface that extends in the vertical direction. Typically, the first magnetic particle aggregate 48 and the second magnetic particle aggregate 50 each extend in the vertical direction, and each has a band-like shape.

[0048] In B / F separation after the immune reaction, the residual liquid 42B is aspirated and removed while the first magnetic particle aggregate 48 and the second magnetic particle aggregate 50 are captured by magnetic force. After that, a washing solution is injected into the cuvette 40, and the washing solution is aspirated and removed. This washing process is repeated the required number of times (see reference numeral 52). If stirring is required during the washing process, mechanical vibration is applied to the cuvette 40. At this time, the magnet unit 24 may be moved away from the cuvette.

[0049] FIG. 3 shows the suction of magnetic particle liquid 52 by nozzle tip 54. (A) in FIG. 3 shows a cuvette 40 containing magnetic particle liquid 52 after an immune reaction. The magnetic particle liquid 52 is composed of magnetic particles 52A and residual liquid 52B. (B) in FIG. 3 shows a state in which magnetic particle liquid 52 is contained in nozzle tip 54. Nozzle tip 54 is a member that is detachably attached to the nozzle base. Nozzle tip 54 is replaced for each sample. The nozzle tip 54 and nozzle base form a nozzle that is the object of transport. Note that in FIG. 3, the magnetic particle liquid 52, nozzle tip 54, etc. are exaggerated. Nozzle tip 54 corresponds to nozzle 20 shown in FIG. 1.

[0050] 3, a dispensing pump 55 is connected via a piping tube to a nozzle base on which a nozzle tip 54 is attached. A nozzle transport mechanism 18 is a mechanism for transporting the nozzle. A syringe pump may be used as the dispensing pump 55. The pressure transmission medium filled in the piping tube is air or a cleaning liquid.

[0051] A sample processing method according to an embodiment is shown in Figures 4 and 5. Figure 4 shows steps (A) to (D), and Figure 5 shows steps (E) to (H).

[0052] 4, as described above, magnetic particle liquid 52 is drawn into nozzle tip 54. Magnetic particle liquid 52 is composed of magnetic particles 52A and residual liquid 52B. In step (B), by the action of transport mechanism 28, magnet unit 30 serving as a magnetic source is disposed below nozzle tip 54, specifically, directly below and in close proximity to nozzle tip 54. Magnet unit 30 is composed of, for example, one or more permanent magnets.

[0053] The internal space of the nozzle tip 54 includes a lower portion 54A, and an opening 54B is formed at the lower end of the nozzle tip 54. The opening 54B functions as a suction opening and a discharge opening. By disposing the magnet portion 30 below the nozzle tip 54, the magnetic force of the magnet portion 30 acts on the individual magnetic particles inside the nozzle tip 54 in addition to the gravitational force, causing the magnetic particles to gather at the lower portion 54A and forming a magnetic particle aggregate 56.

[0054] The lower portion 54A is a narrow portion, i.e., has a constricted shape. The magnetic particles gather there, forming a lump-shaped or columnar magnetic particle aggregate 56. From the perspective of the magnetic particles, the lower portion 54A acts as a mold or aggregation space. The vertical width of the magnetic particle aggregate 56 naturally becomes smaller. Surface tension acts at the opening 54B, preventing magnetic particles or droplets from falling. In other words, the arrangement and magnetic action of the magnet portion 30 are determined to prevent such problems, and the material constituting the nozzle tip 54 and the size of the opening 54B are also determined. If there is a possibility of magnetic particles or droplets falling, a shutter, as described below, may be provided. The horizontal distance between the nozzle tip surface and the surface of the magnet portion (magnetic pole face) is, for example, within the range of several tens of μm to several mm.

[0055] Subsequently, in step (C), the magnet section 30 is transported from below the nozzle tip 54 to the side of the nozzle tip 54 by the action of the transport mechanism 28. As a result, the magnet section 30 is positioned at a predetermined position on the side of the nozzle tip 54. The predetermined position is a position close to but not in contact with the lower part of the nozzle tip 54. The shape of the motion path of the magnet section 30 can be an L-shape, a J-shape, or an arc-shape.

[0056] The magnet unit 30 has a magnetic pole face from which magnetic field lines emerge or enter. During the movement of the magnet unit 30, the orientation of the magnet unit 30 may be changed so that the magnetic pole face always faces directly toward the magnetic particle aggregate 56 moving within the nozzle tip 54.

[0057] The magnetic particle aggregate after moving to a stopping position on the inner surface of the nozzle tip 54 is indicated by the symbol 57. The vertical width of the magnetic particle aggregate 57 may be slightly wider than the vertical width of the initial magnetic particle aggregate 56. However, the vertical width of the magnetic particle aggregate 57 will be significantly smaller than when the magnet section 30 is initially positioned to the side of the nozzle tip 54 (without going through step (B) of forming the magnetic particle aggregate 56 on the lower part 54A).

[0058] A certain gap 58 is generated between the level of the lower end of the magnetic particle aggregate 57 and the level of the lower end of the nozzle tip 54 (the level of the opening 54B). The gap 58 reduces the possibility of a portion of the magnetic particle aggregate 57 leaking out.

[0059] Within nozzle tip 54, magnetic particle aggregate 57 remains on one side of its inner surface. A passage 59 is formed as a gap between the other side of the inner surface and magnetic particle aggregate 57 (i.e., on the back side of magnetic particle aggregate 57). Conversely, magnetic particle aggregate 57 is moved or the position at which magnetic particle aggregate 57 remains is determined so as to ensure such a passage 59.

[0060] In step (B), the magnet portion 30 has an upward orientation, and in step (C), the magnet portion 30 has a horizontal orientation. In step (C), the magnet portion 30 may be slightly tilted upward depending on the inclination angle of the outer surface of the nozzle tip 54. The inclination angle of the outer surface is slight, and such an orientation can also be considered as one aspect of the horizontal orientation.

[0061] In step (D), residual liquid 52B in nozzle tip 54 is discharged. In this case, residual liquid 52B flows down through passage 59. At this time, the captured state, i.e., the magnetically attracted state, of magnetic particle aggregate 57 is maintained. Step (D) corresponds to the B / F separation step or corresponds to the main part of the B / F separation step.

[0062] If necessary, a cleaning step is carried out following step (D). In this step, cleaning liquid is sucked into the nozzle tip 54, and then the cleaning liquid is discharged from the nozzle tip 54. After the cleaning liquid is sucked, the captured state of the magnetic particle aggregate 57 may be temporarily released if necessary. The pressure inside the nozzle tip 54 may be repeatedly decreased and increased to periodically move the contents of the nozzle tip 54 up and down. The nozzle tip 54 may repeatedly suck and discharge the cleaning liquid while maintaining the captured state or by temporarily releasing the captured state.

[0063] 5, after the remaining liquid is discharged from the nozzle tip 54, the dissociating reagent 62 is aspirated by the nozzle tip 54 (see reference numeral 64). The dissociating action of the dissociating reagent 62 is activated by irradiation with ultraviolet light.

[0064] When the dissociative reagent 62 is attracted, the vertical spread of the magnetic particle aggregate 57 is suppressed, and the amount of the dissociative reagent 64 to be attracted can be minimized. This makes it possible to reduce the amount of dissociative reagent 64 used. At the same time, the concentration of the detection target substance in the detection liquid can be increased. Note that the magnetic force of the magnet unit 30 is maintained when step (E) is performed.

[0065] In step (F), the magnet unit 30 is retracted, that is, magnetic attraction is temporarily stopped. The magnetic particles 57A are suspended in the dissociative reagent 62. In this state, stirring is performed, and then the magnetic particles 57A are irradiated with ultraviolet light.

[0066] Stirring may be performed by repeatedly discharging and suctioning the contents from the nozzle tip 54, or by periodically moving the contents up and down within the nozzle tip 54. Alternatively, the contents may be stirred by horizontal circular motion of the nozzle tip 54, etc. In either case, stirring is performed so as to prevent problems such as droplets from falling. Stirring may be performed while maintaining the magnetic force of the magnet unit 30. A variant in which ultraviolet light is irradiated while maintaining the magnetic force is also possible. Irradiation with ultraviolet light causes the target substance (labeled substance) to detach from the magnetic particles, which are a solid phase. The target substance is taken up into the liquid in the nozzle tip 54.

[0067] Subsequently, in step (G), magnet section 30 is again positioned in the vicinity of nozzle tip 54. This causes magnetic particle aggregate 57B to be formed again. In this case, magnet section 30 may be first positioned below nozzle tip 54, and then moved to the side of nozzle tip 54. A gap 65 is generated between the lower end level of magnetic particle aggregate 57B and the lower end level of nozzle tip 54.

[0068] In step (H), the liquid in nozzle tip 54, i.e., the liquid containing the target substance, is discharged as the target liquid while maintaining the state in which magnetic particle aggregate 57B is captured by magnet portion 30. A microchip or the like can be used as a discharge destination.

[0069] In step (E), the vertical width of magnetic particle aggregate 57 is relatively small, making it possible to minimize the amount of reagent to be aspirated. As a result, in step (H), the concentration of the target substance in the target liquid to be discharged can be increased. Furthermore, in step (H), the outflow of magnetic particles is prevented, making it possible to avoid various problems caused by the outflow of magnetic particles.

[0070] FIG. 6 shows a comparative example. A magnetic particle liquid 52 is contained within a nozzle tip 54. If a magnet portion 70 is simply provided on the side of the nozzle tip 54 without first providing a magnet portion 70 below the nozzle tip 54, the magnetic particles will gather on the inner surface of the nozzle tip 54 to form a cluster, but the cluster will spread significantly in the vertical direction. When ejecting the remaining liquid while maintaining the cluster's capture and then aspirating the reagent, a relatively large amount of reagent must be aspirated to immerse the entire cluster in the reagent. In contrast, according to the above embodiment, a magnetic particle aggregate with reduced vertical spread can be formed on the inner surface of the nozzle tip, allowing for a smaller amount of reagent to be used when treating the aggregate with a reagent. This increases the concentration of the target substance in the target liquid.

[0071] 7 and 8 are flowcharts showing the operation of the immunoassay device according to the embodiment, which includes the sample processing method described above.

[0072] In S10, a magnetic particle reagent (first reagent) is injected into the cuvette. In S12, a specimen is injected into the cuvette. In S14, the contents of the cuvette are stirred. In S16, the temperature of the entire cuvette is maintained at a predetermined temperature, and the first reaction step (first immune reaction step) is carried out.

[0073] Reference numeral 76 denotes a part corresponding to B / F separation. In S18, the magnetic particles are magnetically attracted using the magnet part, i.e., a captured state of the magnetic particles is formed. Then, in S20, the remaining liquid in the cuvette is aspirated and removed. In S22, a washing solution (buffer solution) is injected into the cuvette, and in S24, the washing solution in the cuvette is aspirated and removed. Stirring may be performed between the injection and removal of the washing solution. The washing process consisting of S22 and S24 is performed m times, where m is an integer greater than or equal to 1. In S26, the magnet part is moved away from the cuvette, thereby releasing the captured state of the magnetic particles.

[0074] In S28, a labeled reagent (second reagent) is injected into the cuvette. In S30, the contents of the cuvette are stirred. In S32, the temperature of the entire cuvette is maintained at a predetermined temperature, and a second reaction step (second immune reaction step) is carried out.

[0075] Reference numeral 78 denotes a part corresponding to B / F separation. In S34, a captured state of the magnetic particles is formed. In S36, the remaining liquid in the cuvette is aspirated and removed. In S38, a washing liquid is injected into the cuvette, and in S40, the washing liquid in the cuvette is aspirated and removed. Stirring may be performed between the injection and removal of the washing liquid. The washing process consisting of S38 and S40 is performed n times, where n is an integer greater than or equal to 1. In S42, the captured state of the magnetic particles is released by moving the magnet part away from the cuvette.

[0076] In the illustrated example of operation, to generate the magnetic particle liquid to be contained in the nozzle tip, a solution (e.g., a cleaning solution) is injected into the cuvette in S44, and stirring is performed in S46. After the final cleaning solution is injected into the cuvette in S38, S44 (and S46) can be omitted by not aspirating it.

[0077] In S50 shown in Figure 8, the magnetic particle liquid in the cuvette is accommodated in the nozzle tip. Reference numeral 80 denotes the part corresponding to B / F separation. In S52, a magnet part is placed below the nozzle tip as a magnetic force source. This causes magnetic particle aggregates to form in the lower part of the nozzle tip. In S54, the magnet part is transported from the lower side of the nozzle tip to the side. This creates a state in which the magnetic particle aggregates are captured at a retention position on the inner surface of the nozzle tip. In S56, the remaining liquid is ejected from the nozzle tip while the captured state is maintained.

[0078] In S58, a dissociating reagent is aspirated into the nozzle tip. In S62, the contents of the nozzle tip are stirred. Then, in S64, ultraviolet light is irradiated onto the nozzle tip. This causes the target substance to be detected to detach from each magnetic particle. In S64, the capture state is temporarily released.

[0079] Reference numeral 81 denotes the part corresponding to B / F separation. In the illustrated example, in S66, a magnet part is placed below the nozzle tip. This causes a magnetic particle aggregate to be formed at the bottom of the nozzle tip. In S68, the magnet part is transported from the bottom to the side of the nozzle tip. This causes the magnetic particle aggregate to move from the bottom along the inner surface within the nozzle tip and be positioned at a stopping position on the inner surface. In S70, the detectable liquid is ejected from the nozzle tip in a state in which the magnetic particle aggregate is captured. In S74, laser light is irradiated onto the detectable liquid, and the resulting fluorescence is measured. In S72, the capture state is released. Simultaneously with or after this, the nozzle tip is discarded.

[0080] A first embodiment of the magnetic system (magnetic means) will be described with reference to Figures 9 to 15. The nozzle 106 is made up of a nozzle base 108 and a nozzle tip 110. The nozzle base 108 is made of metal.

[0081] The magnetic system is composed of a magnet section 112 and a transport mechanism 114. Specifically, the magnet section 112 is composed of a first magnet section 116 and a second magnet section 118. Specifically, the transport mechanism 114 is composed of a first transport mechanism 120 and a second transport mechanism 122.

[0082] From another perspective, the magnetic system is composed of a first magnetic system 111A and a second magnetic system 111B. The first magnetic system 111A is composed of a first magnet unit 116 and a first transport mechanism 120, and the second magnetic system 111B is composed of a second magnet unit 118 and a second transport mechanism 122.

[0083] The first magnet section 116 is composed of two permanent magnets, with the end face of one permanent magnet corresponding to the south pole and the end face of the other permanent magnet corresponding to the north pole. The two end faces form a first magnetic pole face (first magnetic pole pair). In FIG. 9, the first magnetic pole face faces upward. The second magnet section 118 is also composed of two permanent magnets, with the end face of one permanent magnet corresponding to the north pole and the end face of the other permanent magnet corresponding to the south pole. The two end faces form a second magnetic pole face (second magnetic pole pair). In FIG. 9, the second magnetic pole face faces upward. In the two magnetic pole faces, the magnetic flux density is increased at the boundary between adjacent north and south poles. Note that in FIG. 9, the first and second magnetic pole faces are each facing upward and aligned in a first horizontal direction. In this state, the two north poles and two south poles are arranged alternately in the first horizontal direction and a second horizontal direction perpendicular thereto.

[0084] The first transport mechanism 120 is composed of a first pedestal 124 equipped with a first magnet section 116 and a first arm 125 supporting the first pedestal 124. The first pedestal 124 is rotatably mounted on the upper end of the first arm 125. A rotation drive mechanism is not shown. The second transport mechanism 122 is composed of a second pedestal 126 equipped with a second magnet section 118 and a second arm 127 supporting the second pedestal 126. The second pedestal 126 is rotatably mounted on the upper end of the second arm 127. As with the above, the rotation drive mechanism is not shown.

[0085] In the embodiment, when forming a magnetic particle aggregate in the lower part of the nozzle tip 110, the first magnet part 116 and the second magnet part 118 are connected in the horizontal direction as shown in Fig. 9. The connected magnet part 112 is placed directly below the nozzle tip 110 and facing upward.

[0086] FIG. 10 shows an enlarged view of the magnet unit 112. The magnet unit 112 is composed of four permanent magnets, namely, two permanent magnets with their south poles facing upward and two permanent magnets with their north poles facing upward. The two north poles and two south poles are arranged alternately in a two-dimensional array. The center of the magnet unit 112 is indicated by the reference numeral 130. The magnet unit 112 is positioned so that the center 130 is located directly below the nozzle tip 110. Magnetic particles gather below the nozzle tip 110 due to magnetic force and gravity, thereby forming a magnetic particle aggregate 132.

[0087] 11 and 12 show the operation of the magnetic system according to the first embodiment. The state shown in FIG. 11 occurs from the state shown in FIG. 9. That is, the first magnetic system 111A and the second magnetic system 111B move horizontally in directions away from each other. Thereafter, the state shown in FIG. 12 occurs. That is, in the first magnetic system 111A, after a certain upward movement, the first pedestal 124 rotates around the rotation axis 134, causing the first magnet unit 116 to assume a horizontal position. Similarly, in the second magnetic system 111B, after a certain upward movement, the second pedestal 126 rotates around the rotation axis 136, causing the second magnet unit 118 to assume a horizontal position.

[0088] When the first magnet portion 116 and the second magnet portion 118 are in a horizontal position, the magnetic pole surface 116A of the first magnet portion 116 and the magnetic pole surface 118A of the second magnet portion 118 face each other across the nozzle tip 110. Specifically, the north pole on one side of the nozzle tip 110 faces the south pole on the other side of the nozzle tip 110, and the south pole on one side of the nozzle tip 110 faces the north pole on the other side of the nozzle tip 110.

[0089] 13, as described above, magnetic pole surface 116A and magnetic pole surface 118A face each other, with gap 134 formed between them. The tip portion of nozzle tip 110 is inserted into gap 134. In other words, magnetic pole surface 116A is provided on one side of nozzle tip 110, and magnetic pole surface 118A is provided on the other side of nozzle tip 110. Inside nozzle tip 110, first magnetic particle aggregate 136A is formed on one side of the inner surface, and second magnetic particle aggregate 136B is formed on the other side of the inner surface. Both have a band-like shape, but their vertical width is limited.

[0090] 14, the nozzle 106 may be moved relative to the magnet assembly 112. Horizontal movement of the nozzle 106 is indicated at 140, and vertical movement of the nozzle 106 is indicated at 138. Of course, both the nozzle and the magnetic system may be moved.

[0091] 15 illustrates an example of the state when the detection liquid is being ejected in Example 1. A first magnet portion 116 and a second magnet portion 118 are disposed on either side of the tip of nozzle tip 110 in nozzle 106. As a result, a first magnetic particle aggregate and a second magnetic particle aggregate are formed in the lower part of nozzle tip 110.

[0092] Microchip 142 has a plate-like main body 144, and a microchannel 150 is formed in main body 144. An inlet opening 152 is formed at one end of microchannel 150, and an outlet opening 154 is formed at the other end. Main body 144 has a narrow protrusion 146, in which inlet opening 152 is formed.

[0093] With the first magnetic particle aggregate and the second magnetic particle aggregate formed within the nozzle tip 110, the detection liquid is ejected from the nozzle tip 110 to the inlet opening 152. To enable such ejection, the convex portion 146 is inserted between the first magnet portion 116 and the second magnet portion 118. Prior to this insertion, the gap between the first magnet portion 116 and the second magnet portion 118 may be widened.

[0094] The detection liquid is introduced into the microchannel through the inlet opening 152. Then, the detection liquid is irradiated with a laser beam, and the resulting fluorescence is detected. The detection liquid may be discharged into another container such as a well.

[0095] A first modified example is shown in Figure 16. A nozzle tip 160 contains a magnetic particle liquid 162. The magnetic particles contained therein are attracted to the lower part of the nozzle tip 160 by the magnetic action of a magnet portion 166, forming a magnetic particle aggregate 164. Before or after the formation of the magnetic particle aggregate 164, an air cap 168 is formed as an air layer within the tip of the nozzle tip 160, specifically below the magnetic particle aggregate 164. The air cap 168 effectively prevents the magnetic particle liquid or the magnetic particles from flowing downward. The air cap 168 can be easily formed by creating a slight negative pressure within the nozzle tip.

[0096] A second modified example is shown in Figure 17. A shutter 172 is provided between the lower end of the nozzle tip 160 and the magnet portion 166. A drive mechanism 174 moves the shutter 172 forward or backward. The shutter 172 actually functions as a tray for droplets. In other words, when droplets fall from the nozzle tip, the shutter 172 captures the droplets, preventing contamination of the magnet portion 166 and other components due to the falling droplets. The shutter may function while the nozzle tip 160 is moving.

[0097] A third modified example is shown in Fig. 18. When magnetic particle liquid 162 is contained in nozzle tip 160, a magnet portion is scanned from above to below along nozzle tip 160 (see symbols 166A, 166B, and 166C) in order to efficiently collect magnetic particles without leakage at the bottom of nozzle tip 160. During this process, the orientation of the magnet portion may be changed.

[0098] A magnetic system according to a second embodiment is shown in Figures 19 and 20. In Figure 19, the magnetic system has an upward orientation (first orientation), and in Figure 20, the magnetic system has an opposing orientation (second orientation).

[0099] 19, the magnetic system is composed of a first magnetic system 180A and a second magnetic system 180B. The configuration is basically the same as that of the first embodiment shown in FIG. 9 etc., but the configuration of the two magnet parts is different.

[0100] The first magnetic system 180A has a first magnet portion 182, and the second magnetic system 180B has a second magnet portion 184. The first magnet portion 182 has a first magnetic pole face 186, and the second magnet portion 184 has a second magnetic pole face 188. The first magnetic pole face 186 corresponds to a magnetic pole set consisting of two north poles and two south poles, and the second magnetic pole face 188 also corresponds to a magnetic pole set consisting of two north poles and two south poles. Specifically, the first magnetic pole face 186 has two north poles and two south poles arranged in a staggered two-dimensional pattern, and the second magnetic pole face 188 also has two north poles and two south poles arranged in a staggered two-dimensional pattern. This configuration makes it possible to further increase the magnetic flux density below the nozzle tip.

[0101] 19, the first magnetic pole face 186 and the second magnetic pole face 188 are aligned facing upward, and as a whole, they have alternating polarities. That is, north and south poles are aligned alternately in both the first horizontal direction in which the first magnetic system 180A and the second magnetic system 180B are aligned, and the second horizontal direction perpendicular to the first horizontal direction. Although not shown, magnetic particle aggregates have formed below the nozzle tip 110.

[0102] 20, first magnetic system 180A and second magnetic system 180B are each bent. A first magnet portion 182 is provided on one side of nozzle tip 110, and a second magnet portion 184 is provided on the other side of nozzle tip 110. A first magnetic pole face 186 of first magnet portion 182 and a second magnetic pole face 188 of second magnet portion 184 face each other, with convex portion 146 of microchip 142 and a lower portion of nozzle tip 110 provided between them. Although not shown, two band-shaped magnetic particle aggregates are formed on the inner surface of nozzle tip 110.

[0103] 20, each north pole provided on one side of the nozzle tip 110 faces each south pole provided on the other side of the nozzle tip 110, and each south pole provided on one side of the nozzle tip 110 faces each north pole provided on the other side of the nozzle tip 110. In the second embodiment as well, the magnetic flux density can be further increased below the nozzle tip.

[0104] According to the above embodiment, the first immune reaction step and the second immune reaction step can be performed using a relatively large amount of the first reagent and the second reagent, while the dissociation reaction can be promoted using a small amount of the dissociative reagent. The latter allows the concentration of the target substance in the target liquid to be increased. In the above embodiment, an electromagnet may be used instead of a permanent magnet. The technology according to the embodiment may be applied to a nozzle other than a nozzle tip or a hollow vessel.

Claims

1. a nozzle that contains a magnetic particle liquid containing magnetic particles that bind to a specific substance in a sample; a magnetic system that applies a magnetic force to the magnetic particles from directly below the nozzle, thereby generating a magnetic particle aggregate in a lower portion of an internal space of the nozzle; A sample processing apparatus comprising:

2. 2. The sample processing apparatus according to claim 1, The nozzle is a nozzle tip that is detachably attached to a nozzle base. A specimen processing apparatus characterized by:

3. 2. The sample processing apparatus according to claim 1, The magnetic system comprises: a magnetic source having a magnetic pole face; a moving mechanism for changing a relative positional relationship between the magnetic source and the nozzle; Including, the moving mechanism provides the magnetic source directly below the nozzle with the magnetic pole surface facing upward in order to generate the magnetic particle aggregate in the lower portion; A specimen processing apparatus characterized by:

4. 4. The sample processing apparatus according to claim 3, the movement mechanism relatively moves the magnetic source from directly below the nozzle to a side of the nozzle, the magnetic source is positioned on the side of the nozzle with the magnetic pole surface facing horizontally, the magnetic particle aggregate slides up along the inner surface of the nozzle from the lower portion as the magnetic force source moves relative to the nozzle, and remains at a rest position on the inner surface. A specimen processing apparatus characterized by:

5. 5. The sample processing apparatus according to claim 4, the nozzle discharges the residual liquid contained in the internal space while the magnetic particle aggregate remains at the retention position. A specimen processing apparatus characterized by:

6. 5. The sample processing apparatus according to claim 4, a gap is generated between a lower end of the magnetic particle aggregate remaining at the retention position and a lower end of the nozzle; A specimen processing apparatus characterized by:

7. 5. The sample processing apparatus according to claim 4, the magnetic source includes a first magnetic source and a second magnetic source; the movement mechanism includes a first holding mechanism that holds the first magnetic source and a second holding mechanism that holds the second magnetic source, the first holding mechanism and the second holding mechanism include providing the first magnetic source and the second magnetic source directly below the nozzle, and then moving the first magnetic source to one side of the nozzle and moving the second magnetic source to the other side of the nozzle; the stop positions are stop positions on one side and stop positions on the other side of the inner surface of the nozzle, a first magnetic particle aggregate among the magnetic particle aggregates moves to a stopping position on the one side, and a second magnetic particle aggregate among the magnetic particle aggregates moves to a stopping position on the other side; A specimen processing apparatus characterized by:

8. 8. The sample processing apparatus according to claim 7, the pole faces include a first pole pair and a second pole pair; the first magnetic source has the first magnetic pole pair; The first magnetic pole pair is composed of adjacent north and south poles, the second magnetic source has the second magnetic pole pair; The second magnetic pole pair is composed of adjacent north and south poles. A specimen processing apparatus characterized by:

9. 8. The sample processing apparatus according to claim 7, the pole face includes a first pole set and a second pole set; the first magnetic source has the first magnetic pole set; the first magnetic pole set is composed of a plurality of north poles and a plurality of south poles arranged in a staggered two-dimensional array; the second magnetic source has the second magnetic pole set; The second magnetic pole set is composed of a plurality of north poles and a plurality of south poles arranged in a staggered two-dimensional arrangement. A specimen processing apparatus characterized by:

10. 8. The sample processing apparatus according to claim 7, the magnetic pole faces include a magnetic pole face of the first magnetic source and a magnetic pole face of the second magnetic source, the first holding mechanism and the second holding mechanism have a function of directing the magnetic pole surfaces of the first magnetic source and the second magnetic source upward, and a function of directing the magnetic pole surfaces of the first magnetic source and the second magnetic source to face each other with the nozzle therebetween. A specimen processing apparatus characterized by:

11. In a state where a magnetic particle liquid containing magnetic particles that bind to a specific substance in a specimen is contained in a nozzle, a magnetic force is exerted on the magnetic particles from directly below the nozzle, thereby generating a magnetic particle aggregate in the lower part of an internal space of the nozzle, applying a magnetic force to the magnetic particle aggregate from a side of the nozzle, and moving the magnetic particle aggregate from the lower portion to a stopping position on the inner surface of the nozzle; A sample processing method characterized by:

Images