JP2022069890A - Analysis device and analysis method - Google Patents

Abstract

To provide an analysis device capable of determining whether or not a particulate substance to be analyzed is an expected particulate substance.SOLUTION: An analysis device 10 includes a magnetic field generation unit 20, an observation unit 30, a processing unit 42 and a storage unit 41. The magnetic field generation unit 20 generates a magnetic field to subject a particulate substance p to be analyzed to magnetic migration. The observation unit 30 observes the substance p to be analyzed. The processing unit 42 measures a magnetic migration speed of the substance p to be analyzed from the observation result by the observation unit 30 to measure volume susceptibility of the substance p to be analyzed on the basis of the magnetic migration speed and a particle size of the substance p to be analyzed. The storage unit 41 stores reference data 43 indicating volume susceptibility of a reference particulate substance. The processing unit 42 compares the volume susceptibility of the substance p to be analyzed with the reference data 43 to analyze the substance p to be analyzed.SELECTED DRAWING: Figure 1

Description

The present invention relates to an analyzer and an analysis method.

In the past, the present inventors have proposed a method for quantitatively evaluating the affinity of a particle for a medium by using the volume magnetic susceptibility of the particle (Patent Document 1). In addition, the present inventors have previously proposed a method for analyzing the amount of functional groups of particles using the volume magnetic susceptibility of the particles (Patent Document 2).

International Publication No. 2016/208723 International Publication No. 2016/208724

The present inventor has continued diligent research on a method for analyzing particulate matter, and has completed the present invention. An object of the present invention is to provide an analyzer and an analysis method capable of determining whether or not a particulate matter to be analyzed is a desired particulate matter.

The analyzer of the present invention includes a magnetic field generation unit, an observation unit, a processing unit, and a storage unit. The magnetic field generation unit generates a magnetic field to magnetically run the particulate matter to be analyzed. The observation unit observes the analysis target. The processing unit measures the magnetic susceptibility of the analysis target from the observation result of the observation unit, and measures the volume magnetic susceptibility of the analysis target based on the magnetic migration speed and the particle size of the analysis target. The storage unit stores reference data indicating the volume magnetic susceptibility of the reference particulate matter. The processing unit analyzes the analysis target by comparing the volume magnetic susceptibility of the analysis target with the reference data.

In a certain embodiment, the processing unit measures the particle size of the analysis target from the observation result of the observation unit.

In certain embodiments, the reference particulate matter has a surface film.

In certain embodiments, the reference data indicate the volume magnetic susceptibility of the particulate matter when the surface film is in the desired state.

In one embodiment, the processing unit analyzes the state of the surface film to be analyzed.

In certain embodiments, the reference data indicate the volume magnetic susceptibility of the particulate matter when the interior is in the desired state.

In certain embodiments, the processing unit analyzes the internal state of the analysis target.

In certain embodiments, the reference data indicate the desired volumetric magnetic susceptibility of the particulate matter.

In certain embodiments, the processing unit determines whether or not the analysis target is the desired particulate matter.

In certain embodiments, the processing unit determines whether or not the analysis target is an extracellular vesicle derived from a cancer cell.

In certain embodiments, the reference data indicates the volume magnetic susceptibility of at least one of the reference particulate matter.

In one embodiment, the processing unit compares the volume susceptibility of the analysis target with the volume susceptibility of the at least one reference particulate matter, and is among the at least one reference particulate matter. One is to determine whether or not the analysis target is applicable.

In one embodiment, the processing unit analyzes the particle size of the analysis target when it is determined that the analysis target corresponds to one of the at least one kind of reference particulate matter.

In certain embodiments, the reference data indicate the volume magnetic susceptibility and particle size of at least one reference particulate matter.

In one embodiment, the processing unit compares the volume magnetic susceptibility and particle size of the analysis target with the volume magnetic susceptibility and particle size of the at least one kind of reference particulate matter, and compares the volume magnetic susceptibility and particle size of the at least one kind of reference. It is determined whether or not the analysis target corresponds to one of the particulate matter.

In certain embodiments, the storage unit further stores cell-specific data. The cell-specific data is data showing the relationship between the volume magnetic susceptibility of at least one type of extracellular vesicle and the cell releasing the extracellular vesicle.

In certain embodiments, the reference data indicates the volumetric magnetic susceptibility of the at least one extracellular vesicle as the volumetric magnetic susceptibility of the at least one reference particulate matter.

In certain embodiments, the subject of analysis is an extracellular vesicle.

In one embodiment, when the processing unit determines that the analysis target corresponds to one of the at least one type of extracellular vesicle, the processing unit releases the analysis target with reference to the cell identification data. Determine cells.

The analysis method of the present invention includes a step of observing a particulate substance to be analyzed magnetically, a first measurement step of measuring the magnetic migration speed of the analysis target from the observation results, and the magnetic migration speed and particles of the analysis target. The second measurement step of measuring the volume magnetization rate of the analysis target based on the diameter and the analysis step of analyzing the analysis target by comparing the volume magnetization rate of the analysis target with the reference data are included. .. The reference data shows the volume magnetic susceptibility of the reference particulate matter.

In one embodiment, in the first measurement step, the magnetic migration speed and the particle size of the analysis target are measured from the observation result.

In certain embodiments, the reference particulate matter has a surface film.

In certain embodiments, the reference data indicate the volume magnetic susceptibility of the particulate matter when the surface film is in the desired state.

In one embodiment, the state of the surface film to be analyzed is analyzed in the analysis step.

In certain embodiments, the reference data indicate the volume magnetic susceptibility of the particulate matter when the interior is in the desired state.

In one embodiment, the analysis step analyzes the internal state of the analysis target.

In certain embodiments, the reference data indicate the desired volumetric magnetic susceptibility of the particulate matter.

In one embodiment, in the analysis step, it is determined whether or not the analysis target is the desired particulate matter.

In one embodiment, in the analysis step, it is determined whether or not the analysis target is an extracellular vesicle derived from a cancer cell.

In certain embodiments, the reference data indicates the volume magnetic susceptibility of at least one of the reference particulate matter.

In one embodiment, in the analysis step, the volume magnetic susceptibility of the analysis target is compared with the volume magnetic susceptibility of the at least one kind of reference particulate substance, and the volume magnetic susceptibility of the at least one kind of reference particulate substance is compared. One is to determine whether or not the analysis target is applicable.

In one embodiment, when it is determined in the analysis step that the analysis target corresponds to one of the at least one kind of reference particulate matter, the particle size of the analysis target is further analyzed.

In certain embodiments, the reference data indicate the volume magnetic susceptibility and particle size of at least one reference particulate matter.

In one embodiment, in the analysis step, the volumetric magnetization rate and particle size of the analysis target are compared with the volumetric magnetization rate and particle size of the at least one kind of reference particulate substance, and the at least one kind of reference is compared. It is determined whether or not the analysis target corresponds to one of the particulate substances.

In certain embodiments, the reference data indicates the volumetric magnetic susceptibility of at least one extracellular vesicle as the volumetric magnetic susceptibility of the at least one reference particulate matter.

In certain embodiments, the subject of analysis is an extracellular vesicle.

In one embodiment, when it is determined in the analysis step that the analysis target corresponds to one of the at least one type of extracellular vesicle, the volume magnetization rate of the at least one type of extracellular vesicle is determined. , The cell that released the analysis target is determined with reference to the data showing the relationship with the cell that releases the extracellular vesicle.

According to the analyzer and the analysis method of the present invention, it is possible to determine whether or not the particulate matter to be analyzed is the desired particulate matter.

It is a schematic diagram of the analyzer which concerns on Embodiment 1 of this invention. (A) and (b) are diagrams showing the movement of particulate matter according to the first embodiment of the present invention. It is a figure which shows the structure of the analyzer which concerns on Embodiment 1 of this invention. It is a figure which shows an example of the measurement result of the volume magnetic susceptibility of the particulate matter which concerns on Embodiment 1 of this invention. It is a flowchart which shows the analysis method which concerns on Embodiment 1 of this invention. It is a figure which shows the structure of the modification of the analyzer which concerns on Embodiment 1 of this invention. It is a figure which shows an example of the measurement result of the volume magnetic susceptibility of a plurality of kinds of reference particulate matter which concerns on Embodiment 2 of this invention. It is a schematic diagram of the analyzer which concerns on Embodiment 3 of this invention.

Hereinafter, embodiments of the present invention will be described with reference to the drawings. However, the present invention is not limited to the following embodiments. In addition, the description may be omitted as appropriate for the parts where the explanations are duplicated. Further, in the figure, the same or corresponding parts are designated by the same reference numerals and the description is not repeated.

[Embodiment 1]
First, the analyzer 10 of the present embodiment will be described with reference to FIG. FIG. 1 is a schematic diagram of the analyzer 10 according to the present embodiment. The analyzer 10 analyzes the particulate matter p. More specifically, the analyzer 10 analyzes the state of the surface film of the particulate matter p.

In this embodiment, the particulate matter p is a micelle. The surface film of micelles has a hydrophilic part and a lipophilic (hydrophobic) part. More specifically, the surface film of the micelle has a structure in which the hydrophilic group is directed outward and the lipophilic group is directed inward. For example, micelles have a structure in which an oily component is covered with a surfactant (surface film).

As shown in FIG. 1, the analyzer 10 includes a magnetic field generation unit 20, an observation unit 30, and a calculation unit 40. The cell 21 is arranged in the vicinity of the magnetic field generation unit 20. The magnetic field generation unit 20 generates a magnetic field to magnetically run the particulate matter p in the cell 21. The observation unit 30 observes the particulate matter p in the cell 21. The calculation unit 40 measures the particle size and the magnetic migration speed of the particulate matter p from the results of observation by the observation unit 30. Further, the calculation unit 40 measures the volume magnetic susceptibility of the particulate matter p based on the particle size and the magnetic migration speed of the particulate matter p. Then, the calculation unit 40 analyzes the state of the surface portion of the particulate matter p based on the volume magnetic susceptibility of the particulate matter p. Hereinafter, the analyzer 10 will be described in more detail.

The magnetic field generation unit 20 generates a magnetic field gradient (gradient of magnetic flux density) to apply a magnetic force to the particulate matter p in the cell 21. As a result, the particulate matter p is magnetically electrophoresed. In the present embodiment, the magnetic field generation unit 20 includes a pair of permanent magnets that generate a magnetic field gradient. The two permanent magnets constituting the pair of permanent magnets are arranged, for example, with a gap of 100 μm or more and 500 μm or less at a certain distance. The cell 21 is arranged in the gap between the two permanent magnets.

In this embodiment, the cell 21 is a capillary tube. The capillary tube is an example of a tubular member. The material of the cell 21 is not particularly limited as long as it is a material capable of transmitting visible light or laser light L. For example, the cell 21 can be made of glass or plastic.

The particulate matter p is introduced into the cell 21 together with the medium m by, for example, a microsyringe, a micropump, or an autosampler. Alternatively, the particulate matter p can be introduced into the cell 21 together with the medium m, based on the siphon principle. Alternatively, a droplet containing the particulate matter p may be introduced into the cell 21 (capillary tube) by a capillary phenomenon. When a droplet containing the particulate matter p is dropped on one end of the capillary tube, the droplet flows through the capillary tube due to the capillary phenomenon.

The particulate matter p is present in the medium m. One particulate matter p may be present in the medium m, or a plurality of particulate matter p may be present in the medium m. When a plurality of particulate matter p is present in the medium m, the plurality of particulate matter p may be dispersed in the medium m or unevenly distributed in the medium m. The medium m may be a liquid or a gas. For example, the medium m is an aqueous electrolyte solution, a culture solution, an organic solvent, or air. The analyzer 10 measures the individual volume magnetic susceptibility of the plurality of particulate matter p present in the medium m.

The volume magnetic susceptibility of the particulate matter p depends on the state of the surface film of the particulate matter p. Specifically, the volume magnetic susceptibility of the particulate matter p depends on the amount of surface film. Alternatively, the volume magnetic susceptibility of the particulate matter p depends on whether or not the surface film has disappeared. Therefore, the analyzer 10 can analyze whether or not the surface film of the particulate matter p is in the desired state based on the volume magnetic susceptibility of the particulate matter p. Alternatively, the analyzer 10 can determine whether or not the surface film of the particulate matter p has disappeared based on the volume magnetic susceptibility of the particulate matter p.

The observation unit 30 observes the particulate matter p in the cell 21 and generates a signal indicating the observation result. The calculation unit 40 measures the particle size and the magnetic migration speed of the particulate matter p based on the signal generated by the observation unit 30. The calculation unit 40 includes a storage unit 41 and a processing unit 42.

The storage unit 41 stores programs, setting information, and the like. The storage unit 41 may be composed of, for example, a storage device and a semiconductor memory. The storage device is, for example, an HDD (Hard Disk Drive). The storage unit 41 may have, for example, a RAM (Random Access Memory) and a ROM (Read Only Memory) as the semiconductor memory. The processing unit 42 performs various processes such as numerical calculation, information processing, and device control by executing the program stored in the storage unit 41. The processing unit 42 is configured by a processor such as a CPU (Central Processing Unit), for example. As the arithmetic unit 40, a general-purpose computer such as a personal computer is used.

The processing unit 42 measures the temporal change in the position of the particulate matter p in the cell 21 from the observation result of the observation unit 30. For example, the processing unit 42 measures the position of the particulate matter p in the cell 21 at predetermined time intervals. In other words, the position of the particulate matter p at different times is measured. The processing unit 42 measures the magnetic migration rate of the particulate matter p from the temporal change in the position of the particulate matter p.

Further, the processing unit 42 measures the particle size of the particulate matter p from the signal generated by the observation unit 30. The processing unit 42 further measures the volume magnetic susceptibility of the particulate matter p based on the particle size and the magnetic migration rate of the particulate matter p.

For example, the processing unit 42 calculates the volume magnetic susceptibility of the particulate matter p based on the following formula (1).
v = {2 (χs-χm) r ² / 9ημ _o } B (dB / dx) ... (1)

In formula (1), v is the magnetic susceptibility of the particulate substance p, χs is the volume magnetic susceptibility of the particulate substance p, χm is the volume magnetic susceptibility of the medium m, and r is the volume magnetic susceptibility of the particulate substance p. Η is the radius, η is the viscosity of the medium m, μ _o is the magnetic susceptibility of the vacuum, B is the magnetic flux density, and dB / dx is the magnetic flux gradient (gradient of the magnetic flux density). Equation (1) is derived from the fact that the difference in magnetic force received by the particulate matter p and the medium m in the axial direction (x direction) of the cell 21 (capillary tube) is substantially equal to the viscous resistance force.

The magnetic susceptibility v and the volume magnetic susceptibility χs of the particulate matter p are measured values measured by the processing unit 42. The radius r of the particulate matter p is calculated, for example, from the particle diameter of the particulate matter p measured by the processing unit 42. The volume magnetic susceptibility χm of the medium m, the viscosity η of the medium m, the magnetic permeability μ _o of the vacuum, the magnetic flux density B, and the magnetic field gradient dB / dx are stored in advance in the storage unit 41. For example, the user operates an input device such as a keyboard, mouse or touch display to control the volume magnetic susceptibility χm of the medium m, the viscosity η of the medium m, the magnetic permeability μ _o of vacuum, the magnetic flux density B, and the magnetic flux gradient. The dB / dx can be stored in the storage unit 41. The volume magnetic susceptibility χm of the medium m, the viscosity η of the medium m, and the magnetic permeability μ _o of the vacuum are, for example, literature values. The magnetic flux density B and the magnetic field gradient dB / dx are, for example, measured values.

The storage unit 41 stores reference data 43 indicating the volume magnetic susceptibility of the reference particulate matter. In the present embodiment, the reference data 43 shows the volume magnetic susceptibility of the particulate matter p when the state of the surface film is the desired state. The processing unit 42 analyzes the state of the surface film of the particulate matter p (analysis target) by comparing the volume magnetic susceptibility of the particulate matter p (analysis target) with the reference data 43. More specifically, the processing unit 42 analyzes whether or not the surface film of the particulate matter p (analysis target) is in the desired state. Alternatively, the processing unit 42 analyzes whether or not the surface film of the particulate matter p (analysis target) has disappeared.

The reference data 43 is created by measuring the volume magnetic susceptibility of the desired particulate matter p. The reference data 43 of the present embodiment is created by measuring the volume magnetic susceptibility of the particulate matter p when the state of the surface film is the desired state.

Subsequently, the movement of the particulate matter p will be described with reference to FIGS. 2 (a) and 2 (b). 2 (a) and 2 (b) are diagrams showing the movement of the particulate matter p. Specifically, FIGS. 2A and 2B show the relationship between the volume magnetic susceptibility of the particulate matter p and the medium m and the moving direction of the particulate matter p. As shown in FIGS. 2A and 2B, the magnetic field generation unit 20 includes a permanent magnet 20a having an N pole as a magnetic pole and a permanent magnet 20b having an S pole as a magnetic pole. The two permanent magnets 20a and 20b face each other with the cell 21 interposed therebetween.

As shown in FIG. 2A, when the volume magnetic susceptibility of the particulate substance p is smaller than the volume magnetic susceptibility of the medium m, the particulate substance p moves in a direction away from the magnetic field (magnetic field generation unit 20). On the other hand, as shown in FIG. 2B, when the volume magnetic susceptibility of the particulate substance p is larger than the volume magnetic susceptibility of the medium m, the particulate substance p moves in a direction approaching the magnetic field (magnetic field generation unit 20). ..

As shown in FIGS. 2 (a) and 2 (b), the movement of the particulate matter p is determined according to the volume magnetic susceptibility of the particulate matter p and the medium m. The particulate matter p receives a force in the vicinity of the ends of the permanent magnets 20a and 20b. For example, the particulate matter p receives a force within a range of about ± 200 μm from the vicinity of the ends of the permanent magnets 20a and 20b.

Subsequently, the analyzer 10 will be further described with reference to FIG. FIG. 3 is a diagram showing the configuration of the analyzer 10. As shown in FIG. 3, the analyzer 10 further includes a light source 50. Further, the observation unit 30 includes an enlargement unit 32 and an image pickup unit 34.

The light source 50 emits light having a relatively high intensity including a visible light component. The light source 50 irradiates the cell 21 with light. As a result, the particulate matter p is irradiated with light. The wavelength spectrum of the light emitted from the light source 50 may be relatively broad. As the light source 50, for example, a halogen lamp is preferably used.

The particulate matter p introduced into the cell 21 is magnified by the magnifying unit 32 at an appropriate magnification and imaged by the imaging unit 34. The position of the particulate matter p can be specified from the image pickup result (image captured by the image pickup unit 34) of the image pickup unit 34. For example, the magnifying unit 32 includes an objective lens, and the imaging unit 34 includes a charge-coupled device (CCD). Alternatively, each pixel of the image pickup unit 34 may be composed of a photodiode or a photomultiplier tube. The image pickup unit 34, for example, takes an image of the particulate matter p at predetermined time intervals. The image pickup unit 34 may take an image of the light emitted from the light source 50 and transmitted through the cell 21, or may take an image of the light emitted from the light source 50 and scattered by the particulate matter p.

The calculation unit 40 (processing unit 42) measures the temporal change in the position of the particulate substance p from the imaging result of the imaging unit 34, and the temporal change in the position of the particulate substance p is used to determine the particulate substance p. Measure the magnetic migration speed.

Further, the calculation unit 40 (processing unit 42) measures the particle diameter of the particulate matter p from the image pickup result of the particulate matter p. For example, the arithmetic unit 40 (processing unit 42) executes the following processing. That is, first, the image captured by the image pickup unit 34 is monochromeized, and the brightness thereof is quantified. Next, the boundary of the particulate matter p is set by comparing the differential value of the luminance value with the threshold value. Next, the area of the particulate matter p is detected from the set boundary, and the particle diameter is calculated from the radius of the circle corresponding to the area. Alternatively, the center of the particulate matter p is defined, a plurality of straight lines passing through the center of the particulate matter p are drawn, and the average of the distances between two points intersecting the boundary of the particulate matter p in each straight line is calculated. ..

Subsequently, with reference to FIG. 4, the measurement result of the volume magnetic susceptibility of the particulate matter p will be described. FIG. 4 is a diagram showing an example of the measurement result of the volume magnetic susceptibility of the particulate matter p. Specifically, FIG. 4 shows the measurement result of the volume magnetic susceptibility of the first particulate matter p1 and the measurement result of the volume magnetic susceptibility of the second particulate matter p2.

The first particulate matter p1 is a particulate matter p whose surface film is in the desired state. In other words, the first particulate matter p1 is a reference particulate matter. On the other hand, the second particulate matter p2 is a particulate matter p in which the state of the surface film has changed from the intended state. Alternatively, the second particulate matter p2 is the particulate matter p from which the surface film has disappeared.

In FIG. 4, the horizontal axis indicates the volume magnetic susceptibility, and the vertical axis indicates the ratio of the number of particles. Further, in FIG. 4, graph 61 (solid line) shows the measurement result of the volume magnetic susceptibility of the first particulate matter p1, and graph 62 (broken line) shows the measurement result of the volume magnetic susceptibility of the second particulate matter p2.

The graph 61 was created by measuring the individual volume magnetic susceptibility of the plurality of first particulate matter p1 introduced into the cell 21. Similarly, the graph 62 was created by measuring the individual volume magnetic susceptibility of the plurality of second particulate matter p2 introduced into the cell 21. Specifically, the graph 61 was created by measuring the individual volume magnetic susceptibility of the first particulate matter p1 and calculating the ratio of the number of the first particulate matter p1 for each measured volume magnetic susceptibility. Similarly, the graph 62 was created by measuring the individual volume magnetic susceptibility of the second particulate matter p2 and calculating the ratio of the number of the second particulate matter p2 for each measured volume magnetic susceptibility.

Specifically, the first particulate matter p1 is a fresh cream containing a dispersant. The cream containing the dispersant has a micellar structure in the intended state. Specifically, the dispersant constitutes the surface film. The second particulate matter p2 was prepared by leaving fresh cream containing a dispersant in a room temperature environment for 30 minutes. If the fresh cream containing the dispersant is left in a room temperature environment for a certain period of time or longer, the dispersant cannot maintain the surface film, and as a result, the state of the surface film changes from the intended state. Specifically, the amount of surface film is reduced. Alternatively, the surface film disappears.

As shown in FIG. 4, the volume magnetic susceptibility is different between the first particulate matter p1 and the second particulate matter p2. The difference in volume magnetic susceptibility is due to the change in the state of the surface film from the intended state. Specifically, this is because the amount of the surface film has changed. Alternatively, it is because the surface film has disappeared. Therefore, by comparing the volume magnetic susceptibility of the second particulate matter p2 (analysis target) with the volume magnetic susceptibility of the first particulate matter p1 (reference particulate matter) (reference data 43), the second particulate matter p2 The state of the surface film (target of analysis) can be analyzed. Alternatively, it is possible to analyze whether or not the surface film has disappeared.

The analyzer 10 of the present embodiment has been described above. According to this embodiment, the state of the surface film of the particulate matter p can be analyzed. Further, according to the present embodiment, it is possible to analyze and evaluate a food material having a micellar structure.

The particulate matter p may be particles having a surface film, and is not limited to micelles. For example, the particulate matter p can be a vesicle. More specifically, the particulate matter p can be, for example, a liposome or an extracellular vesicle (EV). The surface membrane of the vesicle consists of lipids. More specifically, the surface membrane of the vesicle has a lipid bilayer. Liposomes are vesicles whose surface membrane is composed of phospholipids. Liposomes are used in DDS (drug delivery system) as a capsule material. Extracellular vesicles are vesicles released from cells. The extracellular vesicle contains a portion of the intracellular component of the cell that releases the extracellular vesicle.

In the present embodiment, the state of the surface film of the particulate matter p is analyzed, but the state of the inside of the particulate matter p may be analyzed. Specifically, it may be analyzed whether or not the internal state of the particulate matter p is the desired state. In this case, the reference data 43 shows the volume magnetic susceptibility of the particulate matter p when the internal state is the desired state. In other words, the reference particulate matter is the particulate matter p whose internal state is the intended state.

Alternatively, it may be analyzed whether or not the particulate matter p is the desired particulate matter. In this case, the reference data 43 shows the desired volumetric magnetic susceptibility of the particulate matter.

For example, a capsule material (capsule-like product) used for DDS may contain a specific component (drug or physiologically active substance) inside, but the specific component may not be sealed inside due to manufacturing variations. be. The volumetric magnetic susceptibility is different between the encapsulating material in which a specific component is encapsulated inside and the encapsulating material in which a specific component is not encapsulated inside. Therefore, by creating reference data 43 using the volume magnetic susceptibility of the encapsulating material that encapsulates a specific component inside and comparing the volume magnetic susceptibility of the encapsulating material to be analyzed with the reference data 43, the encapsulating material It is possible to analyze whether or not a specific component is enclosed inside the (whether or not the internal state of the particulate substance p is the desired state). In other words, it is possible to analyze whether or not the capsule material is a non-defective product. The reference data 43 may be created using the volume magnetic susceptibility of a capsule material in which a specific component is not encapsulated.

Also, for example, extracellular vesicles derived from cancer cells may contain tumor antigens. Alternatively, the types of proteins that make up extracellular vesicles may differ between extracellular vesicles derived from cancer cells and extracellular vesicles derived from non-cancerous cells. Alternatively, the amount of specific proteins that make up extracellular vesicles may differ between extracellular vesicles derived from cancer cells and extracellular vesicles derived from non-cancerous cells. As a result, cancer cell-derived extracellular vesicles have a different volume magnetic susceptibility than non-cancerous cell-derived extracellular vesicles. Therefore, by creating reference data 43 using the volume magnetization rate of extracellular vesicles derived from cancer cells and comparing the volume magnetization rate of the extracellular vesicles to be analyzed with the reference data 43, the extracellular vesicles are small. Whether or not the vesicles are extracellular vesicles derived from cancer cells (whether or not the particulate matter p is the intended particulate matter) can be analyzed. In other words, it is possible to diagnose whether a patient has cancer. The reference data 43 may be created using the volume magnetic susceptibility of extracellular vesicles derived from non-cancerous cells.

Subsequently, the analysis method of the present embodiment will be described with reference to FIG. FIG. 5 is a flowchart showing the analysis method of the present embodiment. The analysis method of this embodiment can be carried out using the analysis apparatus 10 described with reference to FIGS. 1 to 4.

As shown in FIG. 5, first, the particulate matter p (analysis target) to be magnetically electrophoresed is observed (step S1). Next, the magnetic migration speed and the particle size of the particulate matter p are measured from the observation results (step S2). Next, the volume magnetic susceptibility of the particulate matter p is measured based on the measured magnetic migration speed and particle size (step S3). Next, the particulate matter p is analyzed by comparing the measured volume magnetic susceptibility with the reference data 43 (step S4). More specifically, the state of the surface film of the particulate matter p is analyzed. Alternatively, the internal state of the particulate matter p is analyzed. Alternatively, it is analyzed whether or not the particulate matter p is the desired particulate matter.

When measuring the volume magnetic susceptibility of the particulate matter p, the magnetic field generation unit 20 magnetically migrates the particulate matter p in the cell 21, and the observation unit 30 observes the particulate matter p during the magnetic migration. Then, the processing unit 42 measures the volume magnetic susceptibility of the particulate matter p from the result of the observation by the observation unit 30.

When analyzing the particulate matter p, the processing unit 42 compares the volume magnetic susceptibility of the particulate matter p with the reference data 43 stored in the storage unit 41. As described above, the reference data 43 shows the volume magnetic susceptibility of the particulate matter p when the state of the surface film is the desired state. Alternatively, the reference data 43 shows the volume magnetic susceptibility of the particulate matter p when the internal state is the desired state. Alternatively, the reference data 43 shows the volume magnetic susceptibility of the desired particulate matter p.

The first embodiment of the present invention has been described above with reference to FIGS. 1 to 5. According to this embodiment, the particulate matter p to be analyzed can be analyzed. Specifically, it is possible to analyze whether or not the state of the surface film to be analyzed is the desired state. In addition, it is possible to analyze whether or not the inside of the analysis target is in the desired state. In addition, it is possible to analyze whether or not the analysis target is the desired particulate matter.

When measuring the particle size of less than 1 μm, the laser beam L is irradiated on the particulate matter p to analyze the Brownian motion of the particulate matter p. For example, vesicles such as liposomes and extracellular vesicles have a particle size of less than 1 μm.

FIG. 6 is a diagram showing a configuration of a modified example of the analyzer 10 of the present embodiment. As shown in FIG. 6, the analyzer 10 may further include a laser device 60. The laser device 60 emits the laser beam L. The laser device 60 irradiates the cell 21 with the laser beam L. As a result, the particulate matter p is irradiated with the laser beam L. The observation unit 30 observes the particulate matter p by the laser light L (scattered light) scattered by the particulate matter p in the cell 21. Specifically, the imaging unit 34 captures the laser beam L scattered by the particulate matter p via the magnifying unit 32.

The calculation unit 40 (processing unit 42) measures the particle size from the image pickup result of the image pickup unit 34. Specifically, the mass diffusivity is calculated from the dispersion of the change (displacement) in the position of the particulate matter p in the direction (y direction) orthogonal to the axial direction (x direction) of the cell 21 (capillary tube), and this mass diffusivity is calculated. The particle size of the particulate matter p is measured from. Specifically, the particulate matter p is affected by the magnetic field gradient in the axial direction (x direction) of the cell 21 (capillary tube), but is affected by the magnetic field gradient in the direction orthogonal to the axial direction of the cell 21 (y direction). I hardly receive. Therefore, the diffusion coefficient D can be calculated from the dispersion of the displacement of the position of the particulate matter p in the y direction. Specifically, the diffusion coefficient D can be calculated by dividing the square of the movement distance of the particulate matter p that performs Brownian motion in the y direction by twice the time.

The calculation unit 40 (processing unit 42) measures the particle diameter of the particulate matter p from the diffusion coefficient D based on the following equation (2). In the formula (2), d is the particle size of the particulate matter p, k is the Boltzmann constant, T is the absolute temperature, and η is the viscosity of the medium m.
d = kT / (3πηD) ... (2)

The analyzer 10 shown in FIG. 6 stops the emission of the laser beam L from the laser apparatus 60 when emitting light from the light source 50, and stops the emission of the laser beam L from the laser apparatus 60 when emitting the laser beam L from the laser apparatus 60. The emission of light from the light source 50 is stopped.

[Embodiment 2]
Subsequently, the second embodiment of the present invention will be described with reference to FIGS. 1 to 3, 5 and 7. However, matters different from those of the first embodiment will be described, and explanations of the same matters as those of the first embodiment will be omitted. The second embodiment is different from the first embodiment in that the type of analysis target is analyzed.

First, the analyzer 10 of the present embodiment will be described with reference to FIG. In the present embodiment, the reference data 43 indicates the volume magnetic susceptibility of a plurality of types of reference particulate matter. The processing unit 42 analyzes the type of the particulate matter p to be analyzed by comparing the volume magnetic susceptibility of the particulate matter p to be analyzed with the reference data 43. More specifically, the processing unit 42 determines whether or not the analysis target corresponds to one of a plurality of types of reference particulate matter. When the analysis target corresponds to one of a plurality of types of reference particulate matter, the processing unit 42 specifies the type of analysis target from the types of the corresponding reference particulate matter. In the present embodiment, the processing unit 42 further analyzes the particle size of the analysis target.

More specifically, the reference data 43 of the present embodiment shows the volume magnetic susceptibility and the particle diameter of each of the plurality of types of reference particulate matter. The processing unit 42 analyzes the type of the particulate matter p to be analyzed by comparing the volume magnetic susceptibility and the particle diameter of the particulate matter p to be analyzed with the reference data 43. Further, when the analysis target corresponds to one of a plurality of types of reference particulate matter, the processing unit 42 specifies the particle size of the analysis target. For example, the processing unit 42 acquires a measured value of the particle size of the analysis target as the particle size of the analysis target.

FIG. 7 is a diagram showing an example of measurement results of the volume magnetic susceptibility of a plurality of types of reference particulate matter. In other words, FIG. 7 shows an example of the reference data 43 of the present embodiment. Specifically, FIG. 7 shows the measurement results of the volume magnetic susceptibility of each of the first reference particulate matter to the third reference particulate matter.

In FIG. 7, the horizontal axis represents the particle diameter and the vertical axis represents the volume magnetic susceptibility. Further, in FIG. 7, the graph 71 shows the measurement result of the volume magnetic susceptibility of the first reference particle substance pr1, the graph 72 shows the measurement result of the volume magnetic susceptibility of the second reference particle substance pr2, and the graph 73 shows the measurement result of the volume magnetic susceptibility. 3 The measurement result of the volume magnetic susceptibility of the reference particulate matter pr3 is shown.

The graph 71 was created by measuring the individual volume magnetic susceptibility and the particle diameter of the plurality of first reference particulate matter pr1 introduced into the cell 21. Specifically, in the graph 71, the individual volume magnetic susceptibility and the particle size of the first reference particle-like substance pr1 are measured, and the average value of the volume magnetic susceptibility and the average value of the particle size are obtained in increments of 0.5 μm. Created by calculation. Graph 72 and Graph 73 were also created in the same manner as Graph 71.

Specifically, graph 71 shows the measurement results of the volume magnetization rate and the particle size of the commercial coffee beverage A, graph 72 shows the measurement results of the volume magnetization rate and the particle size of the commercial coffee beverage B, and graph 73 shows the measurement results of the commercial coffee beverage C. The measurement results of the volume magnetization rate and the particle size of the above are shown. The commercial coffee beverage A to the commercial coffee beverage C were all products containing a milk component.

As shown in FIG. 7, the commercial coffee beverage A to the commercial coffee beverage C had different relationships between the volume magnetic susceptibility and the particle size. Therefore, by comparing the volume magnetic susceptibility and particle size of the analysis target with the reference data 43, it is possible to determine whether or not the analysis target corresponds to one of the commercial coffee beverage A to the commercial coffee beverage C. can. Further, when the analysis target corresponds to one of the commercial coffee beverage A to the commercial coffee beverage C, the type of the analysis target can be specified as one of the commercial coffee beverage A to the commercial coffee beverage C. .. Further, after specifying the type of the analysis target, the particle size of the analysis target can be analyzed. Specifically, the distribution of the particle size to be analyzed can be specified.

Subsequently, the analysis method of the present embodiment will be described with reference to FIG. As shown in FIG. 5, first, the particulate matter p (analysis target) to be magnetically electrophoresed is observed (step S1). Next, the magnetic migration speed and the particle size of the particulate matter p are measured from the observation results (step S2). Next, the volume magnetic susceptibility of the particulate matter p is measured based on the measured magnetic migration speed and particle size (step S3). Next, by comparing the measured volume magnetic susceptibility and the particle size with the reference data 43, the type of the particulate matter p to be analyzed is analyzed, and the particle size to be analyzed is analyzed (step S4).

The second embodiment of the present invention has been described above with reference to FIGS. 1 to 3, 5 and 7. According to this embodiment, the type and particle size of the particulate matter p (analysis target) can be analyzed.

The analysis target to be introduced into the cell 21 may be one type or a plurality of types. According to the present embodiment, a plurality of types of analysis targets can be introduced into the cell 21 to analyze the types and particle sizes of each analysis target.

Further, in the present embodiment, the reference data 43 shows the volume magnetic susceptibility and the particle diameter of a plurality of types of reference particulate matter, while the reference data 43 shows the volume magnetic susceptibility and the particle diameter of one kind of reference particulate matter. May be shown.

Further, in the present embodiment, the processing unit 42 compares the volume magnetic susceptibility and the particle size of the analysis target with the reference data 43, while the processing unit 42 compares the volume magnetization of the analysis target with the reference data 43. May be good.

Further, in the present embodiment, the reference data 43 shows the volume magnetic susceptibility and the particle size of the reference particle-like substance, while the reference data 43 shows the volume of the volume magnetic susceptibility and the particle size of the reference particle-like substance. Only the magnetic susceptibility may be shown.

Further, in the present embodiment, the processing unit 42 acquires the measured value of the particle size of the analysis target as the particle size of the analysis target, but the particle size of the analysis target is not limited to the measured value of the particle size of the analysis target. For example, the processing unit 42 may acquire the particle size to be analyzed from the reference data 43.

Further, in the present embodiment, the processing unit 42 analyzes the particle size of the analysis target, but the process of analyzing the particle size of the analysis target may be omitted.

[Embodiment 3]
Subsequently, the third embodiment of the present invention will be described with reference to FIGS. 5 and 8. However, the matters different from those of the first and second embodiments will be described, and the same matters as those of the first and second embodiments will be omitted. The third embodiment differs from the first and second embodiments in that the cells that release extracellular vesicles are determined.

FIG. 8 is a schematic diagram of the analyzer 10 of the present embodiment. In the present embodiment, the reference data 43 shows the volume magnetic susceptibility and the particle size of the plurality of types of extracellular vesicles as the volume magnetic susceptibility and the particle size of the plurality of types of the reference particulate matter.

Similar to the second embodiment, the processing unit 42 compares the volume magnetic susceptibility and the particle diameter of the particulate matter p to be analyzed with the reference data 43, so that the analysis target is a plurality of types of reference particulate matter (extracellular small). It is determined whether or not it corresponds to one of the particles). In this embodiment, the particulate matter p to be analyzed is an extracellular vesicle.

When the analysis target corresponds to one of the plurality of types of reference particulate matter (extracellular vesicles), the processing unit 42 performs the corresponding reference particulate matter (extracellular vesicles) as in the second embodiment. The type of analysis target (extracellular vesicle) is specified from the type of. In the present embodiment, the processing unit 42 determines the type of cell that has released the analysis target from the type of the identified analysis target (extracellular vesicle).

Specifically, as shown in FIG. 8, the storage unit 41 further stores the cell specific data 44. The cell-specific data 44 shows the relationship between the type of extracellular vesicle (reference particulate matter) and the type of cell that releases extracellular vesicles. When the type of the analysis target (extracellular vesicle) is specified, the processing unit 42 determines the type of the cell that released the analysis target with reference to the cell identification data 44. For example, reference data 43 may indicate the volume magnetic susceptibility of plankton-derived extracellular vesicles. In this case, the cell identification data 44 shows the relationship between the type of extracellular vesicles and the type of plankton that releases extracellular vesicles. Alternatively, the reference data 43 may indicate the volume magnetic susceptibility of extracellular vesicles derived from lactic acid bacteria. In this case, the cell identification data 44 shows the relationship between the type of extracellular vesicle and the type of lactic acid bacterium that releases extracellular vesicle.

Subsequently, the analysis method of the present embodiment will be described with reference to FIG. As shown in FIG. 5, first, the particulate matter p (extracellular vesicle) to be analyzed magnetically migrated is observed (step S1). Next, the magnetic migration speed and the particle size of the particulate matter p are measured from the observation results (step S2). Next, the volume magnetic susceptibility of the particulate matter p is measured based on the measured magnetic migration speed and particle size (step S3). Next, by comparing the measured volume susceptibility and particle size with the reference data 43, the type of the particulate matter p (extracellular vesicle) is analyzed, and the particle size of the particulate matter p is analyzed (step). S4). In the present embodiment, further, with reference to the cell identification data 44, the type of the cell that released the particulate matter p is determined from the type of the identified particulate matter p (extracellular vesicle) (step S4).

The third embodiment of the present invention has been described above with reference to FIGS. 5 and 8. According to this embodiment, the type and particle size of the analysis target (extracellular vesicle) can be analyzed.

The analysis target (extracellular vesicle) to be introduced into the cell 21 may be one type or a plurality of types. According to this embodiment, a plurality of types of analysis targets can be introduced into the cell 21 to analyze the type and particle size of each analysis target (extracellular vesicle).

Further, in the present embodiment, the reference data 43 shows the volume magnetic susceptibility and the particle size of a plurality of types of reference particulate matter (extracellular vesicles), whereas the reference data 43 indicates one type of reference particulate matter (extracellular vesicles). The volume magnetic susceptibility and particle size of (extracellular vesicles) may be shown.

Further, in the present embodiment, the processing unit 42 compares the volume magnetic susceptibility and particle size of the analysis target (extracellular vesicle) with the reference data 43, but the processing unit 42 compares the volume magnetization and the reference data of the analysis target. It may be compared with 43.

Further, in the present embodiment, the reference data 43 shows the volume magnetic susceptibility and the particle size of the reference particle-like substance (extracellular vesicles), while the reference data 43 shows the volume magnetic susceptibility and the particles of the reference particle-like substance. Of the diameter, only the volume magnetic susceptibility may be shown.

Further, in the present embodiment, the processing unit 42 has acquired a measured value of the particle size of the analysis target (extracellular vesicle) as the particle size of the analysis target, but the particle size of the analysis target is the particle size of the analysis target. Not limited to measured values. For example, the processing unit 42 may acquire the particle size of the analysis target (extracellular vesicle) from the reference data 43.

Further, in the present embodiment, the processing unit 42 analyzes the particle size of the analysis target (extracellular vesicle), but the process of analyzing the particle size of the analysis target may be omitted.

The embodiments of the present invention have been described above with reference to the drawings. According to the embodiment of the present invention, it is possible to determine whether or not the particulate matter to be analyzed is the desired particulate matter. The present invention is not limited to the above embodiment, and can be implemented in various embodiments without departing from the gist thereof.

For example, in the embodiment of the present invention, the magnetic field generation unit 20 includes a pair of permanent magnets 20a and 20b, but the magnetic field generation unit 20 includes a pair of magnetic pole pieces to generate a magnetic field gradient. May be good. Alternatively, the magnetic field generator 20 may include an electromagnet, a magnetic circuit, or a superconducting magnet to generate a magnetic field gradient. When the magnetic field generation unit 20 includes a pair of magnetic pole pieces, the two magnetic pole pieces constituting the pair of magnetic pole pieces are arranged, for example, with a gap of 100 μm or more and 500 μm or less at a constant distance. The cell 21 is arranged in the gap between the two magnetic pole pieces. The magnetic pole piece can be, for example, a magnetized piece of iron. The iron pieces can be magnetized by, for example, permanent magnets, electromagnets, magnetic circuits, or superconducting magnets.

Further, in the embodiment of the present invention, the cell 21 is a capillary tube, but the cell 21 may be a glass cell or a plastic cell. The glass cell and the plastic cell have recesses for holding the medium m containing the particulate matter p. Alternatively, the glass cell and the plastic cell have a flow path through which the medium m containing the particulate matter p flows. When the cell 21 is a glass cell or a plastic cell having a microchannel, when a droplet containing the particulate matter p is dropped on one end of the microchannel, the droplet flows through the microchannel due to a capillary phenomenon. ..

Further, in the embodiment described with reference to FIG. 6, the analyzer 10 includes the light source 50 and the laser device 60, but the analyzer 10 includes only the laser device 60 among the light source 50 and the laser device 60. You may prepare.

When the laser device 60 is used, the particle size of the particulate matter p may be measured based on, for example, a dynamic light scattering method or a static light scattering method. Further, when irradiating the particulate matter p with the laser beam L, the capillary tube is preferably a square-shaped capillary having a square cross-sectional shape orthogonal to the axial direction thereof. By using the square capillary, it becomes easy to mirror-finish the side surface of the cell 21 to which the laser beam L is irradiated.

Further, in the embodiment of the present invention, the calculation unit 40 (processing unit 42) measures the particle size of the particulate matter p, but the image captured by the imaging unit 34 is displayed on the display, and the image displayed on the display is used. , The analyst may measure the particle size of the particulate matter p. Alternatively, the image captured by the imaging unit 34 may be printed, and the analyst may measure the particle size of the particulate matter p from the printed image. In this case, the analyst operates the input device to store the data indicating the particle size in the storage unit 41.

Further, in the embodiment of the present invention, the reference particulate matter and the particle size of the analysis target are measured, but the literature values may be used for at least one of the reference particulate matter and the particle size of the analysis target. In this case, the analyst operates the input device to store the data indicating the particle size (literature value) in the storage unit 41.

Further, in the embodiment of the present invention, the calculation unit 40 (processing unit 42) measures the volume magnetic susceptibility of the reference particulate matter, but the volume magnetic susceptibility of the reference particulate matter is determined by using a SQUID element, a magnetic balance, or the like. May be measured. In this case, the analyst operates the input device to store data indicating the volume magnetic susceptibility of the reference particulate matter in the storage unit 41. Alternatively, the volume magnetic susceptibility of the reference particulate matter may be a literature value. In this case, the analyst operates the input device to store data indicating the volume magnetic susceptibility (literature value) of the reference particulate matter in the storage unit 41.

Further, in the embodiment of the present invention, the imaging unit 34 measures the magnetic migration rate of the particulate substance p by imaging the particulate substance p at predetermined time intervals, but the laser device 60 is used. For example, the magnetic migration rate of the particulate matter p may be measured based on the laser Doppler method.

The present invention is useful in the fields of pharmaceuticals, environmental chemistry, foods, cosmetics, regenerative medicine and the like.

10 Analytical device 20 Magnetic field generation unit 21 Cell 30 Observation unit 40 Calculation unit 41 Storage unit 42 Processing unit 43 Reference data m Medium p Particulate matter

Claims (20)

A magnetic field generator that generates a magnetic field to magnetically run the particulate matter to be analyzed,
An observation unit for observing the analysis target and
A processing unit that measures the magnetic susceptibility of the analysis target from the observation results of the observation unit and measures the volume magnetic susceptibility of the analysis target based on the magnetic susceptibility of the analysis target and the particle size.
It is equipped with a storage unit that stores reference data indicating the volume magnetic susceptibility of the reference particulate matter.
The processing unit is an analyzer that analyzes the analysis target by comparing the volume magnetic susceptibility of the analysis target with the reference data. The analyzer according to claim 1, wherein the processing unit measures the particle size of the analysis target from the observation result of the observation unit. The reference particulate matter has a surface film and has a surface film.
The reference data show the volume magnetic susceptibility of the particulate matter when the surface film is in the desired state.
The analyzer according to claim 1 or 2, wherein the processing unit analyzes the state of the surface film to be analyzed. The reference data show the volume magnetic susceptibility of particulate matter when the interior is in the desired state.
The analyzer according to any one of claims 1 to 3, wherein the processing unit analyzes the internal state of the analysis target. The reference data show the desired volumetric magnetic susceptibility of the particulate matter.
The analyzer according to any one of claims 1 to 4, wherein the processing unit determines whether or not the analysis target is the desired particulate matter. The analyzer according to claim 5, wherein the processing unit determines whether or not the analysis target is an extracellular vesicle derived from a cancer cell. The reference data show the volume magnetic susceptibility of at least one of the reference particulate matter.
The processing unit compares the volume magnetic susceptibility of the analysis target with the volume magnetic susceptibility of the at least one kind of reference particulate substance, and analyzes the analysis in one of the at least one kind of reference particulate substance. The analyzer according to any one of claims 1 to 6, which determines whether or not the target is applicable. The analyzer according to claim 7, wherein the processing unit analyzes the particle size of the analysis target when it is determined that the analysis target corresponds to one of the at least one kind of reference particulate matter. The reference data show the volume magnetic susceptibility and particle size of at least one reference particulate matter.
The processing unit compares the volume magnetic susceptibility and the particle size of the analysis target with the volume magnetic susceptibility and the particle size of the at least one kind of reference particulate substance, and is among the at least one kind of reference particulate substance. The analyzer according to any one of claims 1 to 6, which determines whether or not the analysis target corresponds to one of the above. The storage unit further stores cell-specific data, which is data showing the relationship between the volume magnetic susceptibility of at least one type of extracellular vesicle and the cell releasing the extracellular vesicle.
The reference data indicates the volume magnetic susceptibility of the at least one type of extracellular vesicle as the volume magnetic susceptibility of the at least one type of reference particulate matter.
The analysis target is extracellular vesicles.
When the processing unit determines that the analysis target corresponds to one of the at least one type of extracellular vesicle, the processing unit determines the cell that released the analysis target with reference to the cell identification data. The analyzer according to any one of claims 7 to 9. The step of observing the particulate matter to be analyzed magnetically and
The first measurement step of measuring the magnetic migration speed of the analysis target from the observation results,
A second measurement step of measuring the volume magnetic susceptibility of the analysis target based on the magnetic migration speed and the particle size of the analysis target,
By comparing the volume magnetic susceptibility of the analysis target with the reference data, the analysis step of analyzing the analysis target is included.
The reference data is an analysis method showing the volume magnetic susceptibility of the reference particulate matter. The analysis method according to claim 11, wherein in the first measurement step, the magnetic migration speed and the particle size of the analysis target are measured from the observation result. The reference particulate matter has a surface film and has a surface film.
The reference data show the volume magnetic susceptibility of the particulate matter when the surface film is in the desired state.
The analysis method according to claim 11 or 12, wherein the state of the surface film to be analyzed is analyzed in the analysis step. The reference data show the volume magnetic susceptibility of particulate matter when the interior is in the desired state.
The analysis method according to any one of claims 11 to 13, which analyzes the internal state of the analysis target in the analysis step. The reference data show the desired volumetric magnetic susceptibility of the particulate matter.
The analysis method according to any one of claims 11 to 14, wherein in the analysis step, it is determined whether or not the analysis target is the desired particulate matter. The analysis method according to claim 15, wherein in the analysis step, it is determined whether or not the analysis target is an extracellular vesicle derived from a cancer cell. The reference data show the volume magnetic susceptibility of at least one of the reference particulate matter.
In the analysis step, the volume magnetic susceptibility of the analysis target is compared with the volume magnetic susceptibility of the at least one kind of reference particulate matter, and the analysis is performed on one of the at least one kind of reference particulate matter. The analysis method according to any one of claims 11 to 16, wherein it is determined whether or not the target is applicable. The analysis method according to claim 17, wherein when it is determined in the analysis step that the analysis target corresponds to one of the at least one kind of reference particulate matter, the particle size of the analysis target is further analyzed. The reference data show the volume magnetic susceptibility and particle size of at least one reference particulate matter.
In the analysis step, the volume magnetization rate and particle size of the analysis target are compared with the volume magnetization rate and particle size of the at least one kind of reference particulate substance, and among the at least one kind of reference particulate substance. The analysis method according to any one of claims 11 to 16, wherein it is determined whether or not the analysis target corresponds to one of the above. The reference data indicates the volume magnetic susceptibility of at least one type of extracellular vesicle as the volume magnetic susceptibility of the at least one type of reference particulate matter.
The analysis target is extracellular vesicles.
When it is determined in the analysis step that the analysis target corresponds to one of the at least one type of extracellular vesicle, the volume magnetization rate of the at least one type of extracellular vesicle and the extracellular vesicle are small. The analysis method according to any one of claims 17 to 19, wherein the cells that have released the analysis target are determined with reference to the data showing the relationship with the cells that release the vesicles.

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