WO2019039601A1

WO2019039601A1 - Analyzing device and analysis method

Info

Publication number: WO2019039601A1
Application number: PCT/JP2018/031431
Authority: WO
Inventors: 河野　誠; 清香森
Original assignee: 株式会社カワノラボ
Priority date: 2017-08-25
Filing date: 2018-08-24
Publication date: 2019-02-28
Also published as: JP6850504B2; JPWO2019039601A1

Abstract

An analyzing device (10) is provided with a magnetic field generating unit (20), an observation unit (30), a processing unit (42) and a storage unit (41). The magnetic field generating unit (20) generates a magnetic field to cause magnetophoresis of a particulate organism (p) being analyzed. The observation unit (30) observes the particulate organism (p). The processing unit (42) measures the magnetophoretic velocity and the particle size of the particulate organism (p) from observation results obtained by the observation unit (30), and measures the bulk susceptibility of the particulate organism (p) on the basis of the measured magnetophoretic velocity and particle size. The storage unit (41) stores reference data (43) indicating a relationship between the bulk susceptibility and the particle size of a reference particulate organism. Further, the processing unit (42) analyzes the particulate organism (p) by comparing the bulk susceptibility and the particle size of the particulate organism (p) with the reference data (43).

Description

Analyzer and analysis method

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

Particulate organisms such as yeast and fungi are cultured in vitro or in incubators and used for various studies. For example, cultured particulate organisms are used for evaluating the efficacy of pharmaceuticals, toxicity tests of environmental chemicals, food functional evaluation, and cosmetic functional evaluation. Also in the field of regenerative medicine, studies using particulate organisms such as iPS cells (induced pluripotent stem cells) and ES cells (embryonic stem cells) have been conducted.

The quality of the particulate organism is generally evaluated by a method of analyzing a gene contained in the particulate organism or a method of observing the particulate organism to which a fluorescent dye is added. However, when the quality is evaluated by these methods, particulate organisms targeted for quality evaluation can not be targeted for research. Also, in the field of regenerative medicine, culture experts rely on their own “can” to determine whether cultured cells (particulate organisms) are defective. For this reason, it is easy to produce an individual difference in judgment of whether it is inferior goods. In the regenerative medicine field, when the degree of activation of cultured cells is low or when the cultured cells are malformed, it is judged to be a defective product.

On the other hand, in the past, the present inventors have used the volume magnetic susceptibility (magnetic susceptibility per unit volume) of particulate organisms (for example, red blood cells that are a type of blood cells) to determine the quality (characteristics) such as surface area of particulate organisms. Proposed an apparatus and method for evaluating (analyzing) (Patent Document 1).

International Publication No. 2015/030184

As a result of further studies on the volume magnetic susceptibility of particulate matter, the present inventors have completed the present invention. That is, an object of the present invention is to provide an analysis apparatus and an analysis method which can evaluate the quality of particulate matter in a living state and can use the particulate matter after evaluation for the next research. It is in.

An analyzer according to 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 migrate particulate matter to be analyzed. The observation unit observes the particulate matter to be analyzed. The processing unit measures the magnetic migration velocity and particle diameter of the particulate matter to be analyzed from the observation result of the observation unit, and based on the measured magnetic migration velocity and particle diameter, the particles to be analyzed are Measure the volume susceptibility of the The storage unit stores reference data indicating the relationship between the volume magnetic susceptibility of the reference particulate matter and the particle diameter. The processing unit analyzes the particulate matter to be analyzed by comparing the volume magnetic susceptibility and the particle diameter of the particulate matter to be analyzed with the reference data.

In one embodiment, the reference data indicates a relationship between volume magnetic susceptibility and particle diameter of each of a plurality of types of reference particulate matter, and the processing unit is configured to determine the volume susceptibility and particles of the particulate matter to be analyzed. The type of particulate matter to be analyzed is analyzed by comparing the diameter with the reference data.

In one embodiment, the reference data indicates, for each state that the reference particulate matter can have, the relationship between the volume magnetic susceptibility and the particle diameter of the reference particulate matter of the same type as the particulate matter to be analyzed. The processing unit analyzes the state of the particulate matter to be analyzed by comparing the volume magnetic susceptibility and the particle diameter of the particulate matter to be analyzed with the reference data.

In one embodiment, the state that the reference particulate matter can have corresponds to the function that the reference particulate matter can exhibit.

In one embodiment, the state that the reference particulate matter can possess is at least a part of each stage in which the function declines from the alive state to the dead state of the reference particulate matter. It corresponds.

In one embodiment, the state that the reference particulate matter can have corresponds to the state in which the reference particulate matter is alive and the state in which the reference particulate matter is dead.

In one embodiment, the state that the reference particulate matter may have corresponds to the activity of the reference particulate matter.

In one embodiment, the activity corresponds to the amount of adenosine triphosphate produced.

In one embodiment, the particulate organism to be analyzed is a yeast, a fungus or a cell.

The particle analysis method according to the present invention comprises the steps of observing particulate matter to be analyzed which is to be subjected to magnetophoresis, measuring the magnetic migration velocity and particle diameter of the particulate matter to be analyzed from observation results, and Measuring the volume magnetic susceptibility of the particulate matter to be analyzed based on the determined magnetic migration velocity and the particle size, and comparing the volume susceptibility and particle size of the particulate matter to be analyzed with reference data And the analysis step of analyzing the particulate matter to be analyzed, wherein the reference data indicates the relationship between the volume magnetic susceptibility of the reference particulate matter and the particle size.

In one embodiment, the reference data indicates the relationship between volume magnetic susceptibility and particle diameter of each of a plurality of types of reference particulate matter, and in the analysis step, the volume susceptibility and particles of the particulate matter to be analyzed are determined. The type of particulate matter to be analyzed is analyzed by comparing the diameter with the reference data.

In one embodiment, the reference data indicates, for each state that the reference particulate matter can have, the relationship between the volume magnetic susceptibility and the particle diameter of the reference particulate matter of the same type as the particulate matter to be analyzed. The analysis step analyzes the state of the particulate organism to be analyzed by comparing the volume magnetic susceptibility and the particle diameter of the particulate organism to be analyzed with the reference data.

ADVANTAGE OF THE INVENTION According to this invention, while being able to evaluate the quality of particulate matter in a living state, it becomes possible to utilize the particulate matter after evaluation to the next research.

It is a schematic diagram of the analyzer which concerns on Embodiment 1 of this invention. (A) And (b) is a figure which shows the movement of the particulate-form thing which concerns on Embodiment 1 of this 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 each particle diameter of three types of yeast which concerns on Embodiment 1 of this invention, and a volume magnetic susceptibility. It is a figure which shows an example of the reference data which concern 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 an example of the measurement result of each particle diameter of three types of fungi which concern on Embodiment 1 of this invention, and a volume magnetic susceptibility. It is a figure which shows the other example of the reference data which concern on Embodiment 1 of this invention. It is a figure which shows the measurement result of the particle diameter of the particulate-form object of analysis object which concerns on Embodiment 2 of this invention, and volume magnetic susceptibility. It is a figure which shows an example of the reference data which concern on Embodiment 2 of this invention. It is a flowchart which shows the analysis method which concerns on Embodiment 2 of this invention. It is a figure which shows an example of the measurement result of each particle diameter of three types of animal cells which concern on Embodiment 2 of this invention, and a volume magnetic susceptibility. (A) is a figure which shows the measurement result of the activity of the particulate-form object of analysis object which concerns on Embodiment 3 of this invention, (b) is a particulate-form object of analysis object which concerns on Embodiment 3 of this invention It is a figure which shows the measurement result of the particle diameter of this, and volume magnetic susceptibility. It is a figure which shows an example of the reference data which concern on Embodiment 3 of this invention. It is a flowchart which shows the analysis method 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 the drawings, the same or corresponding portions are denoted by the same reference characters and description thereof will not be repeated.

Embodiment 1
FIG. 1 is a schematic view of an analyzer 10 of the present embodiment. The analyzer 10 of the present embodiment analyzes the type of particulate matter p to be analyzed. For example, the analyzer 10 analyzes the type of yeast, the type of fungus, and the type of cell. Hereinafter, the present embodiment will be described with an example of analyzing the type of yeast. The analyzer 10 includes a magnetic field generation unit 20, an observation unit 30, and a calculation unit 40. The cell 21 is disposed in the vicinity of the magnetic field generation unit 20.

The magnetic field generation unit 20 generates a magnetic field to magnetically migrate 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 (calculates) the particle diameter and the magnetic migration velocity of the particulate matter p from the result of observation by the observation unit 30. In addition, the computing unit 40 measures (calculates) the volume magnetic susceptibility of the particulate organism p based on the particle diameter of the particulate organism p and the magnetic migration velocity. Then, the computing unit 40 analyzes the type of the particulate organism p based on the particle size and volume magnetic susceptibility of the particulate organism 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 exert magnetic force on the particulate matter p in the cell 21. As a result, the particulate organism p magnetically migrates. 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 disposed, for example, with a gap of a fixed distance of 100 μm or more and 500 μm or less. The cell 21 is disposed in the air gap between the two permanent magnets.

In the present 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 the material can transmit visible light or laser light. For example, the cell 21 may be made of glass or plastic.

Particulate organisms p are present in the medium m. One particulate organism p may be present in the medium m, or a plurality of particulate organisms p may be present in the medium m. When a plurality of particulate organisms p exist in the medium m, the plurality of particulate organisms p may be dispersed in the medium m or may be localized in the medium m. The medium m is typically a culture solution.

Particulate organisms p are introduced into the cell 21 together with the medium m, for example by means of a microsyringe, a micropump or an autosampler. Alternatively, the particulate organism p can be introduced into the cell 21 together with the medium m on the basis of the principle of siphon. Alternatively, a droplet containing the particulate organism p may be introduced into the cell 21 (capillary tube) by capillary action. When a droplet containing particulate matter p is dropped on one end of the capillary tube, the capillary flow causes the droplet to flow in the capillary tube.

The volume susceptibility of the particulate organism p varies depending on the type of particulate organism p. The difference in volume magnetic susceptibility is derived from the composition of the surface part (cell wall or cell membrane) and the inside of the particulate organism p. Specifically, due to the fact that the affinity to the medium m differs depending on the composition of the cell wall or cell membrane and the constitution inside the cell, the volume magnetic susceptibility of the particulate organism p differs depending on the type of the particulate organism 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 (calculates) the particle diameter and the magnetic migration velocity of the particulate organism 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 a program, setting information, and the like. The storage unit 41 may be configured by, 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 random access memory (RAM) and a read only memory (ROM) as a semiconductor memory. The processing unit 42 executes various programs such as numerical calculation, information processing, and device control by executing a program stored in the storage unit 41. The processing unit 42 is configured of, for example, a processor such as a CPU (Central Processing Unit). For example, a general-purpose computer such as a personal computer is used as the calculation unit 40.

The processing unit 42 analyzes the temporal change of 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 positions of the particulate matter p at different times are measured. The processing unit 42 measures the magnetic migration velocity of the particulate organism p from the temporal change of the position of the particulate organism p.

Further, the processing unit 42 measures the particle diameter of the particulate organism p from the signal generated by the observation unit 30. The processing unit 42 further measures the volume magnetic susceptibility of the particulate organism p based on the particle size and the magnetic migration velocity of the particulate organism 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 equation (1), v is the magnetic migration velocity of the particulate organism p, χ s is the volume magnetic susceptibility of the particulate organism p, χ m is the volume magnetic susceptibility of the medium m, and r is the particulate organism p Is the radius of the medium m, μ _o is the permeability of a vacuum, B is the flux density, and dB / dx is the magnetic field gradient (gradient of the magnetic flux density). Equation (1) is derived from the fact that the difference between the magnetic force received by the particulate matter p and the medium m in the axial direction (x direction) of the cell 21 (capillary tube) and the viscous resistance are approximately equal.

The storage unit 41 stores reference data 43. In the present embodiment, the reference data 43 indicates the relationship between the standard particle size and the volume magnetic susceptibility of each of a plurality of types of particulate matter. The processing unit 42 analyzes the type of the particulate organism p to be analyzed by comparing the particle size and the volume magnetic susceptibility of the particulate organism p to be analyzed with the reference data 43. In the present embodiment, the reference data 43 indicates the relationship between the standard particle size and the volume magnetic susceptibility of each of a plurality of types of yeast. In the following description, a particulate organism showing a relationship between a standard particle size and a volume magnetic susceptibility may be described as a "reference particulate organism".

Subsequently, the movement of the particulate matter p will be described with reference to FIGS. 2 (a) and 2 (b). Fig.2 (a) and FIG.2 (b) are figures which show the movement of particulate-form organism p. Specifically, FIGS. 2 (a) and 2 (b) 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 of which the magnetic pole is N and a permanent magnet 20b of which the magnetic pole is S. The two

permanent magnets

20 a and 20 b face each other across the cell 21.

As shown in FIG. 2A, when the volume magnetic susceptibility of the particulate matter p is smaller than that of the medium m, the particulate matter 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 organism p is larger than that of the medium m, the particulate organism 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 susceptibility of the particulate matter p and the medium m. The particulate matter p receives a force in the vicinity of the end of the

permanent magnet

20a, 20b. For example, the particulate matter p receives a force in the range of about ± 200 μm from the vicinity of the end of the

permanent magnets

20 a and 20 b.

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. As shown in FIG. 3, the analyzer 10 further comprises a light source 50. The observation unit 30 also includes a magnifying unit 32 and an imaging unit 34.

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

The particulate organism 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 imaging result of the imaging unit 34 (the image captured by the imaging 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 imaging unit 34 may be configured by a photodiode or a photomultiplier. The imaging unit 34 images, for example, the particulate matter p at predetermined time intervals. The imaging unit 34 may image light emitted from the light source 50 and transmitted through the cell 21 or may image light emitted from the light source 50 and scattered by the particulate matter p.

The calculation unit 40 (processing unit 42) analyzes the temporal change of the position of the particulate matter p from the imaging result of the imaging unit 34, and the temporal change of the position of the particulate matter p from the temporal change of the position of the particulate matter p. Measure the magnetophoretic velocity.

In addition, the calculation unit 40 (processing unit 42) measures the particle diameter of the particulate matter p from the imaging result of the particulate matter p. For example, the computing unit 40 (processing unit 42) executes the following process. That is, first, the image captured by the imaging unit 34 is converted to monochrome and the luminance thereof is digitized. Next, the boundary of the particulate matter p is set by comparing the derivative 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 measured (calculated) from the radius of the circle corresponding to the area. Alternatively, define the center of the particulate organism p, draw a plurality of straight lines passing through the center of the particulate organism p, and calculate the average of the distance between two points intersecting the boundary of the particulate organism p in each straight line .

Then, with reference to FIG. 4, the measurement result of each particle diameter and volume magnetic susceptibility of several types of particulate matter p is demonstrated. FIG. 4 is a view showing an example of measurement results of particle diameter and volume magnetic susceptibility of each of three types of yeast (analytical target).

In FIG. 4, the horizontal axis represents particle diameter, and the vertical axis represents volume magnetic susceptibility. In addition, the circle marks indicate the measurement results of particle size and volume magnetic susceptibility of beer top fermentation yeast (Saccharomyces cerevisiae (American Ale)), and the triangle marks indicate the measurement results of particle size and volume magnetic susceptibility of soy sauce yeast (Zygosaccharomyces rouxii) The square marks indicate the measurement results of the particle size and volume magnetic susceptibility of a standard strain (Saccharomyces cerevisiae NRIC 1560 ^T (Type strain)). As shown in FIG. 4, the volume magnetic susceptibility of the particulate matter p varies depending on the type of the particulate matter p. Therefore, the type of particulate organism p can be analyzed based on the volume magnetic susceptibility of the particulate organism p. Hereinafter, the case where the particulate organism p is any of beer top surface fermentation yeast (Saccharomyces cerevisiae (American Ale)), soy sauce yeast (Zygosaccharomyces rouxii), and a standard strain (Saccharomyces cerevisiae NRIC 1560 ^T (Type strain)) is taken as an example. The present embodiment will be described.

Subsequently, the reference data 43 will be described with reference to FIG. FIG. 5 is a view showing an example of reference data 43 according to the first embodiment. Specifically, the relationship between the standard particle size and volume magnetic susceptibility of three types of yeast (beer top fermentation yeast, soy sauce yeast, and standard strain) is shown. In the following description, a yeast (a reference particulate organism) showing a relationship between a standard particle diameter and a volume magnetic susceptibility may be described as a "reference yeast".

In FIG. 5, the horizontal axis represents particle diameter, and the vertical axis represents volume magnetic susceptibility. Further, the graph 60 shows the relationship between the particle diameter and the volume magnetic susceptibility of each of a plurality of types of reference yeasts. The storage unit 41 described with reference to FIG. 1 stores data corresponding to the graph 60 as the reference data 43. Specifically, the storage unit 41 stores data indicating the equation of the graph 60 as the reference data 43. Alternatively, the storage unit 41 stores data indicating a table corresponding to the graph 60 as the reference data 43.

For example, as shown in FIG. 5, the graph 60 may include a first graph 61 indicated by an alternate long and short dash line, a second graph 62 indicated by an alternate long and short line, and a third graph 63 indicated by a solid line. In the present embodiment, the first graph 61 shows the relationship between the standard particle size and volume magnetic susceptibility of beer top surface fermentation yeast, and the second graph 62 shows the relationship between the standard particle size and volume magnetic susceptibility of soy sauce yeast And the third graph 63 shows the relationship between the standard particle size and volume magnetic susceptibility of the standard strain. In this case, the reference data 43 includes first data corresponding to the first graph 61, second data corresponding to the second graph 62, and third data corresponding to the third graph 63. For example, the first data is data indicating a formula of the first graph 61 or a table corresponding to the first graph 61, and the second data is a formula corresponding to the formula of the second graph 62 or the second graph 62. The third data is data representing a formula of the third graph 63 or a table corresponding to the third graph 63.

As described with reference to FIG. 4, the beer top surface fermenting yeast, the soy sauce yeast, and the standard strain each have different volume magnetic susceptibility. Therefore, the processing unit 42 refers to the first data corresponding to the first graph 61, the second data corresponding to the second graph 62, and the third data corresponding to the third graph 63. It can be analyzed whether it is a beer top fermentation yeast, a soy sauce yeast or a standard strain.

Specifically, the processing unit 42 refers to the reference data 43 and, for each type of reference particulate matter, the volume magnetization of the reference particulate matter having the same particle size as the particle size of the particulate matter p to be analyzed. Determine the rate. Hereinafter, the volume magnetic susceptibility of the reference particulate matter having the same particle diameter as the particle diameter of the particulate matter p to be analyzed may be referred to as “reference volume magnetic susceptibility”. The processing unit 42 determines the reference volume magnetic susceptibility closest to the volume magnetic susceptibility of the particulate matter p to be analyzed among the reference volume magnetic susceptibility. The processing unit 42 analyzes the type of the particulate matter p to be analyzed based on the result of the determination.

The reference data 43 may indicate the range of volume magnetic susceptibility for each particle diameter. In this case, the processing unit 42 refers to the reference data 43 to determine, for each type of reference particulate matter, the volume magnetic susceptibility of the reference particulate matter having the same particle size as the particle size of the particulate matter p to be analyzed. Determine the range. Hereinafter, the range of the volume magnetic susceptibility of the reference particulate matter having the same particle diameter as the particle diameter of the particulate matter p to be analyzed may be referred to as “the range of the reference volume susceptibility”. The processing unit 42 determines, from the range of the reference volume magnetic susceptibility, the range of the reference volume magnetic susceptibility including the value of the volume magnetic susceptibility of the particulate matter p to be analyzed.

Alternatively, the reference data 43 may indicate the range of the volume magnetic susceptibility and the median value of the volume magnetic susceptibility for each particle diameter. In this case, the processing unit 42 refers to the reference data 43 to determine, for each type of reference particulate matter, the volume magnetic susceptibility of the reference particulate matter having the same particle size as the particle size of the particulate matter p to be analyzed. Determine the range (range of reference volume susceptibility) and the median. The processing unit 42 determines, from the range of the reference volume magnetic susceptibility, the range of the reference volume magnetic susceptibility including the value of the volume magnetic susceptibility of the particulate matter p to be analyzed. When the plurality of reference volume magnetic susceptibility ranges include the value of the volume magnetic susceptibility of the particulate matter p to be analyzed, the processing unit 42 calculates the volume susceptibility of the particulate matter p to be analyzed from the median. Determine the closest median. The reference data 43 may indicate an average value instead of the median value.

Subsequently, the analysis method of the present embodiment will be described with reference to FIG. FIG. 6 is a flowchart showing the analysis method of the present embodiment. The analysis method of the present embodiment can be carried out using the analysis device 10 described with reference to FIGS.

As shown in FIG. 6, first, a particulate organism p (analytical target) to be magnetically electrophoresed is observed (step S1). Next, the magnetic migration velocity and particle diameter of the particulate organism p are measured from the observation result (step S2). Next, the volume magnetic susceptibility of the particulate organism p is measured based on the measured magnetophoretic measurement and the particle diameter (step S3). Next, the type of particulate organism p is analyzed by comparing the particle size and volume magnetic susceptibility of particulate organism p with reference data 43 (step S4).

When measuring the particle size and volume magnetic susceptibility of the particulate organism p, the magnetic field generating unit 20 causes the particulate organism p in the cell 21 to undergo magnetic migration, and the observation unit 30 causes the particulate organism p in the magnetic migration to occur. Observe. Then, the processing unit 42 measures the particle diameter and volume magnetic susceptibility of the particulate organism p from the result of observation by the observation unit 30.

When analyzing the type of particulate organism p, the processing unit 42 compares the particle size and volume magnetic susceptibility of the particulate organism p with the reference data 43 stored in the storage unit 41. The reference data 43 indicates the relationship between the standard particle size and volume magnetic susceptibility of each of a plurality of types of particulate matter, as described above.

The first embodiment has been described above. According to Embodiment 1, the quality of the particulate matter p can be evaluated. Specifically, the type of particulate organism p can be analyzed. Moreover, according to Embodiment 1, the particle size and volume magnetic susceptibility of the particulate organism p can be measured by observing the particulate organism p during magnetophoresis. Therefore, the type of particulate matter p can be analyzed in the living state. Therefore, it becomes possible to utilize the particulate matter p after evaluation for the next study.

In addition, although the kind of yeast was analyzed in this embodiment, the particulate-form organism p is not limited to yeast. The particulate organism p may, for example, be a cell. When the particulate organism p is a cell, for example, it can be analyzed whether the particulate organism p is an iPS cell or an ES cell. Particulate organisms p may also be, for example, fungi. Hereinafter, analysis of the type of fungi will be described with reference to FIGS. 7 and 8. When analyzing the type of fungi, the reference data 43 described with reference to FIG. 1 shows the relationship between the standard particle size and the volume magnetic susceptibility of each of a plurality of types of fungi.

FIG. 7 is a diagram showing an example of the measurement results of the particle size and volume magnetic susceptibility of each of three types of fungi (analytical target). In FIG. 7, the horizontal axis indicates particle diameter, and the vertical axis indicates volume magnetic susceptibility. Also, black triangles indicate the measurement results of particle diameter and volume magnetic susceptibility of Staphylococcus aureus (Staphylococcus aureus ATCC 12600), and squares indicate measurement results of particle diameter and volume magnetic susceptibility of lactic acid bacteria (Lactobacillus delbrueckii subsp. Bulgaricus) The white triangles indicate the measurement results of particle size and volume magnetic susceptibility of beer top fermentation yeast (Saccharomyces cerevisiae (American Ale)).

As shown in FIG. 7, the volume magnetic susceptibility of fungi varies depending on the type of fungi. Thus, the type of fungus can be analyzed based on the volume susceptibility of the fungus. In the following, for the analysis of the type of fungi, the particulate organism p is any of Staphylococcus aureus (Staphylococcus aureus ATCC 12600), lactic acid bacteria (Lactobacillus delbrueckii subsp. Bulgaricus), and beer top fermented yeast (Saccharomyces cerevisiae (American Ale)) A case will be described as an example.

FIG. 8 is a diagram illustrating another example of the reference data 43 according to the first embodiment. Specifically, the relationship between the standard particle size and volume magnetic susceptibility of three kinds of fungi (S. aureus, lactic acid bacteria and beer top fermented yeast) is shown. In the following description, a fungus (reference particulate organism) showing a relationship between a standard particle size and a volume magnetic susceptibility may be described as a "reference fungus".

In FIG. 8, the horizontal axis represents particle diameter, and the vertical axis represents volume magnetic susceptibility. Further, the graph 70 shows the relationship between the particle size and the volume magnetic susceptibility of each of a plurality of types of reference fungi. The storage unit 41 described with reference to FIG. 1 stores data corresponding to the graph 70 as the reference data 43. Specifically, the storage unit 41 stores, as the reference data 43, data indicating an expression of the graph 70 or data indicating a table corresponding to the graph 70.

For example, as shown in FIG. 8, the graph 70 may include a fourth graph 71 indicated by an alternate long and short dash line, a fifth graph 72 indicated by an alternate long and short dash line, and a sixth graph 73 indicated by a solid line. In the present embodiment, the fourth graph 71 shows the relationship between the standard particle diameter and volume magnetic susceptibility of Staphylococcus aureus, and the fifth graph 72 shows the relationship between the standard particle diameter and volume magnetic susceptibility of lactic acid bacteria. The sixth graph 73 shows the relationship between the standard particle size and volume magnetic susceptibility of beer top fermentation yeast. In this case, the reference data 43 includes fourth data corresponding to the fourth graph 71, fifth data corresponding to the fifth graph 72, and sixth data corresponding to the sixth graph 73. For example, the fourth data is data indicating a formula of the fourth graph 71 or a table corresponding to the fourth graph 71, and a fifth data is a formula corresponding to the formula of the fifth graph 72 or the fifth graph 72. The sixth data is data representing a formula of the sixth graph 73 or a table corresponding to the sixth graph 73.

As described with reference to FIG. 7, S. aureus, lactic acid bacteria, and beer top fermented yeast each have different volume magnetic susceptibility. Therefore, the processing unit 42 refers to the fourth data corresponding to the fourth graph 71, the fifth data corresponding to the fifth graph 72, and the sixth data corresponding to the sixth graph 73. It can be analyzed whether it is Staphylococcus aureus, lactic acid bacteria, or beer top fermented yeast.

Second Embodiment
A second embodiment of the present invention will now be described with reference to FIGS. 1 and 9 to 11. However, items different from the first embodiment will be described, and description of the same items as the first embodiment will be omitted. Embodiment 2 differs from Embodiment 1 in that the state of particulate matter p to be analyzed is analyzed.

In the present embodiment, the reference data 43 indicates the relationship between the volume magnetic susceptibility and the particle diameter of the reference particulate matter of the same type as that of the particulate matter p to be analyzed, for each state that the reference particulate matter may have. The processing unit 42 analyzes the state of the particulate organism p by comparing the volume magnetic susceptibility and particle diameter of the particulate organism p with the reference data 43.

Specifically, the reference data 43 according to the present embodiment corresponds to the degree of deterioration of the function of the reference particulate matter. Specifically, the reference data 43 corresponds to at least a part of each stage in which the function of the reference particulate matter decreases from the living state to the dead state. Therefore, it is possible to analyze to which of the stages in which the function declines from the living state to the dead state to which the particulate matter p belongs. For example, the reference data 43 corresponds to the state in which the reference particulate matter is alive and the state in which the reference particulate matter is dead. In this case, life and death of the particulate matter p can be analyzed. The state in which the particulate matter p is alive, and the state in which the particulate matter p is dead are states in which the function of the particulate matter p decreases from the alive state to the dead state. Two stages are shown.

Hereinafter, the present embodiment will be described by way of example of analyzing the life and death of the particulate matter p. In this case, the reference data 43 indicates the relationship between the volume magnetic susceptibility and the particle diameter shown when the same kind of reference particulate matter as the particulate matter p to be analyzed is alive, and the particulate matter p to be analyzed The relationship between the volume magnetic susceptibility and the particle size shown when the same kind of reference particulate matter is dead is shown. The processing unit 42 analyzes whether the particulate organism p is alive or dead by comparing the volume magnetic susceptibility and particle diameter of the particulate organism p with the reference data 43.

FIG. 9 is a view showing measurement results of the particle size and volume magnetic susceptibility of the particulate organism p. Specifically, the measurement results of the particle size and volume magnetic susceptibility of a standard strain (Saccharomyces cerevisiae NRIC 1560 ^T (Type strain)) are shown.

In FIG. 9, the horizontal axis indicates particle diameter, and the vertical axis indicates volume magnetic susceptibility. Also, the white circles indicate the volume magnetic susceptibility of the dead particulate matter p. Black circles indicate the volume magnetic susceptibility of the living particulate matter p. As shown in FIG. 9, the volume susceptibility of the particulate organism p differs depending on whether the particulate organism p is alive or dead. Therefore, based on the volume magnetic susceptibility of the particulate matter p, the life and death of the particulate matter p can be analyzed. Hereinafter, the present embodiment will be described by way of example in which the particulate organism p is a standard strain (Saccharomyces cerevisiae NRIC 1560 ^T (Type strain)).

The difference in volume magnetic susceptibility reflects the degree of biological activity (enzyme reaction) inside the cell. Also, the difference in volume magnetic susceptibility reflects the change in the substance (component) that constitutes the cell. Specifically, when life activity (function) is reduced or stopped, cell decomposition starts, and as a result, substances (components) constituting the cell are changed. Therefore, according to the present embodiment, by measuring the volume magnetic susceptibility, it is possible to monitor how the function of the particulate organism p declines. Also, it can be analyzed whether the particulate matter p is alive or dead.

Subsequently, reference data 43 according to the second embodiment will be described with reference to FIG. FIG. 10 is a diagram of an example of reference data 43 according to the second embodiment. In FIG. 10, the horizontal axis indicates particle diameter, and the vertical axis indicates volume magnetic susceptibility. Further, the graph 100 shows the relationship between the volume magnetic susceptibility and the particle diameter shown when the reference particulate matter is alive, and the relationship between the volume magnetic susceptibility and the particle diameter when the reference particulate matter is dead. Show. The storage unit 41 illustrated in FIG. 1 stores data corresponding to the graph 100 as the reference data 43. Specifically, the storage unit 41 illustrated in FIG. 1 stores, as the reference data 43, data indicating an expression of the graph 100 or data indicating a table corresponding to the graph 100.

As shown in FIG. 10, the graph 100 includes two types of graphs (seventh graph 101 and eighth graph 102). For example, a seventh graph 101 indicated by a chain line indicates the relationship between volume magnetic susceptibility and particle diameter shown when the reference particulate matter is dead, and an eighth graph 102 indicated by a solid line indicates that the reference particulate matter is alive. The relationship between the volume magnetic susceptibility and the particle diameter shown in FIG. In this case, the reference data 43 includes seventh data corresponding to the seventh graph 101 and eighth data corresponding to the eighth graph 102. For example, the seventh data is data indicating a formula of the seventh graph 101 or a table corresponding to the seventh graph 101, and a eighth data is a formula corresponding to the formula of the eighth graph 102 or the eighth graph 102. Is data indicative of

In the present embodiment, the seventh graph 101 shows the relationship between the standard particle diameter and volume magnetic susceptibility of the dead standard strain, and the eighth graph 102 shows the standard particle diameter of the live standard strain and The relationship with the volume magnetic susceptibility is shown.

As described with reference to FIG. 9, the dead standard strain and the live standard strain have different volume magnetic susceptibility. Therefore, the processing unit 42 refers to the seventh data corresponding to the seventh graph 101 and the eighth data corresponding to the eighth graph 102 to determine whether the standard strain (particulate organism p) is alive or dead. It can be analyzed.

For example, as in the first embodiment, the processing unit 42 refers to the reference data 43 and determines the reference volume magnetic susceptibility closest to the volume magnetic susceptibility of the particulate matter p to be analyzed. The processing unit 42 analyzes the degree of deterioration of the function of the particulate matter p based on the result of this determination. As described in the first embodiment, the processing unit 42 analyzes the degree of deterioration of the function of the particulate organism p using the range of the reference volume magnetic susceptibility or the range and the median of the reference volume magnetic susceptibility. You may Alternatively, as described in the first embodiment, the range and the average value of the reference volume magnetic susceptibility may be used to analyze the degree of the decrease in the function of the particulate organism p.

Subsequently, an analysis method according to the second embodiment will be described with reference to FIG. FIG. 11 is a flowchart showing an analysis method according to the second embodiment. The analysis method according to the second embodiment can be performed using the analysis device 10 described with reference to FIGS. 1, 9 and 10.

As shown in FIG. 11, the processing from step S1 to step S3 is the same as the analysis method described with reference to FIG. In the analysis method according to the second embodiment, when the volume magnetic susceptibility of the particulate organism p (analytical target) is measured (step S3), the particle size and volume susceptibility of the particulate organism p are compared with the reference data 43. The degree of deterioration of the function of the particulate organism p is analyzed (step S5). When analyzing the particulate organism p, the processing unit 42 compares the particle size and volume magnetic susceptibility of the particulate organism p with the reference data 43 stored in the storage unit 41. The reference data 43 corresponds to at least a part of each stage in which the function of the reference particulate matter decreases from the living state to the dead state, as described above.

The second embodiment has been described above. According to Embodiment 2, as in Embodiment 1, the quality of the particulate organism p can be evaluated. Specifically, the degree of decline in the function of the particulate organism p can be analyzed. Also, after the evaluation, it becomes possible to separate the living particulate matter p and use it for the next study.

In addition, in this embodiment, although the state (the grade of the fall of a function) of yeast (standard stock | strain) was analyzed, the particulate-form organism p is not limited to yeast. Particulate organisms p may be cells other than yeast. For example, the particulate organism p may be an animal cell.

FIG. 12 is a view showing an example of measurement results of particle diameter and volume magnetic susceptibility of each of three types of animal cells. Specifically, FIG. 12 shows an example of the measurement results of the particle size and volume magnetic susceptibility of three types of Jurkat cells (acute T cell leukemia of human origin) with different degrees of functional decline. Specifically, Jurkat cells were cultured using a MES (2-morpholinoethanesulfonic acid) medium at an atmosphere temperature of 37 ° C. under a carbon dioxide concentration of 7% without medium exchange. As cells at the start of culture, cells obtained by subculturing frozen cells for 3 passages were used. When the animal cells are cultured without changing the medium, the cells become hypotrophic and deteriorate over time. The degree of deterioration of the animal cells corresponds to the degree of decline of the function of the animal cells.

In FIG. 12, the horizontal axis indicates particle diameter, and the vertical axis indicates volume magnetic susceptibility. Further, in FIG. 12, triangular marks indicate the measurement results of particle diameter and volume magnetic susceptibility of Jurkat cells at the start of culture. Squares indicate the measurement results of particle size and volume magnetic susceptibility of Jurkat cells cultured for 24 hours. The diamond marks indicate the measurement results of particle size and volume magnetic susceptibility of Jurkat cells cultured for 264 hours.

As shown in FIG. 12, when Jurkat cells are cultured without medium replacement, the volume susceptibility of Jurkat cells changes according to the culture time. In other words, the volume susceptibility of Jurkat cells differs depending on the degree of deterioration of Jurkat cells (the degree of loss of function). Specifically, the longer the culture time, the weaker the diamagnetism of Jurkat cells. In other words, the greater the loss of function of Jurkat cells, the weaker the diamagnetism. Therefore, based on the volume susceptibility of animal cells, it is possible to analyze the state of the animal cells (the degree of decline in function).

Third Embodiment
A third embodiment of the present invention will now be described with reference to FIGS. 1 and 13 to 15. However, matters different from the first and second embodiments will be described, and the description of the same matters as the first and second embodiments will be omitted. Embodiment 3 differs from

Embodiments

1 and 2 in that the degree of the ability of the particulate organism p is analyzed as the state of the particulate organism p to be analyzed. The ability of the particulate organism p includes, for example, a bioactive ability (activity), a differentiation ability, or a generation ability of a protein or the like.

In the present embodiment, the reference data 43 indicates the relationship between the volume magnetic susceptibility and the particle diameter of the reference particulate matter of the same type as that of the particulate matter p to be analyzed, for each degree of the ability of the reference particulate matter. The processing unit 42 analyzes the degree of the ability of the particulate organism p by comparing the volume magnetic susceptibility and particle diameter of the particulate organism p with the reference data 43. In the following, the present embodiment will be described by way of example in which the activity of the particulate organism p is analyzed. In this case, the reference data 43 indicates the relationship between the volume magnetic susceptibility and the particle diameter of the reference particulate matter of the same type as that of the particulate matter p to be analyzed for each activity.

FIG. 13 (a) is a view showing the measurement results of the activity of the particulate organism p. Specifically, the measurement results of the activity of a standard strain (Saccharomyces cerevisiae NRIC 1560 ^T (Type strain)) are shown. Specifically, the measurement results of the degree of activity after 7 hours from the start of culture of the standard strain are shown.

In FIG. 13 (a), the horizontal axis indicates the measurement time, and the vertical axis indicates the activity. Specifically, the vertical axis shows the absorbance of light at 450 nm. Specifically, since the formazan dye is reduced by NADPH to absorb light of 450 nm, the absorbance at this wavelength was measured. NADPH is a coenzyme produced at the time of synthesis of ATP (adenosine tri-phosphate: adenosine triphosphate), and the larger the amount of NADPH produced, the higher the absorbance. In other words, the larger the amount of synthesized ATP, the higher the absorbance. The amount of ATP synthesized corresponds to the activity of the particulate organism p, and the larger the amount of ATP synthesized, the higher the activity of the particle organism p. Thus, the absorbance corresponds to the activity of the particulate organism p. Specifically, the higher the activity of the particulate organism p, the higher the absorbance.

Also, in FIG. 13 (a), square marks indicate the activity of standard strains cultured in a culture solution containing 5% by weight of sodium chloride (NaCl). Further, triangle marks indicate the activity of standard strains cultured in a culture solution adjusted to pH (hydrogen ion index) of 1.0. On the other hand, the circle indicates the activity of the standard strain cultured without applying stress. As shown in FIG. 13 (a), application of stress lowers the activity (the amount of ATP synthesis) of the particulate organism p.

FIG. 13 (b) is a view showing measurement results of particle diameter and volume magnetic susceptibility of the particulate matter p to be analyzed. Specifically, the measurement results of the particle size and volume magnetic susceptibility of a standard strain (Saccharomyces cerevisiae NRIC 1560 ^T (Type strain)) cultured for 7 hours are shown.

In FIG. 13 (b), the horizontal axis indicates particle diameter, and the vertical axis indicates volume magnetic susceptibility. Also, in FIG. 13 (b), square marks indicate volume magnetic susceptibility of standard strains cultured for 7 hours in a culture solution containing 5% by weight of sodium chloride (NaCl). Further, triangle marks indicate volume magnetic susceptibility of standard strains cultured for 7 hours in a culture solution adjusted to pH (hydrogen ion index) of 1.0. On the other hand, the circle indicates the volume susceptibility of a standard strain cultured for 7 hours without applying stress.

As shown in FIGS. 13 (a) and 13 (b), the volume magnetic susceptibility of the particulate organism p varies depending on the degree of activity. Therefore, based on the particle size and volume magnetic susceptibility of the particulate organism p, the activity of the particulate organism p can be analyzed. Hereinafter, the present embodiment will be described by way of example in which the particulate organism p is a standard strain (Saccharomyces cerevisiae NRIC 1560 ^T (Type strain)).

The difference in volume magnetic susceptibility reflects the degree of biological activity inside the cell. In addition, the difference in volume magnetic susceptibility reflects the dynamics of the dynamics in the surface layer (surface modifying molecule) of the cell membrane. The dynamics in the surface layer of the cell membrane corresponds to the amount of ATP produced.

Subsequently, reference data 43 according to the third embodiment will be described with reference to FIG. FIG. 14 is a diagram of an example of the reference data 43 according to the third embodiment. In FIG. 14, the horizontal axis represents particle diameter, and the vertical axis represents volume magnetic susceptibility. Further, the graph 130 shows the relationship between the volume magnetic susceptibility and the particle diameter of the reference particulate matter for each activity. The storage unit 41 illustrated in FIG. 1 stores data corresponding to the graph 130 as the reference data 43. Specifically, the storage unit 41 illustrated in FIG. 1 stores, as the reference data 43, data indicating an expression of the graph 130 or data indicating a table corresponding to the graph 130.

For example, as shown in FIG. 14, the graph 130 may include three types of graphs (a ninth graph 131, a tenth graph 132, and an eleventh graph 133). In this case, the reference data 43 includes ninth data corresponding to the ninth graph 131, tenth data corresponding to the tenth graph 132, and eleventh data corresponding to the eleventh graph 133. For example, the ninth data is data indicating a formula of the ninth graph 131 or a table corresponding to the ninth graph 131, and a tenth data is a formula corresponding to the formula of the tenth graph 132 or the tenth graph 132. The eleventh data is data indicating a formula of the eleventh graph 133 or a table corresponding to the eleventh graph 133.

In the present embodiment, the ninth graph 131 shows the relationship between the standard particle size and volume magnetic susceptibility of a standard strain cultured for 7 hours in a culture solution containing 5% by weight of sodium chloride (NaCl), and the tenth graph 132 shows the relationship between the standard particle size and volume magnetic susceptibility of a standard strain cultured for 7 hours in a culture solution adjusted to pH (hydrogen ion index) of 1.0, and the eleventh graph 133 gives stress The relationship between the standard particle diameter and volume magnetic susceptibility of a standard strain cultured without 7 hours is shown.

As described with reference to FIG. 13, the standard strain has different volume susceptibility depending on the degree of activity. Therefore, the processing unit 42 refers to the ninth data corresponding to the ninth graph 131, the tenth data corresponding to the tenth graph 132, and the tenth data corresponding to the eleventh graph 133, The degree of activity can be analyzed.

For example, as in the first embodiment, the processing unit 42 refers to the reference data 43 to determine the reference volume magnetic susceptibility closest to the volume magnetic susceptibility of the particulate matter p. The processing unit 42 analyzes the degree of the ability of the particulate matter p based on the result of this determination. As described in the first embodiment, the processing unit 42 analyzes the degree of the ability of the particulate organism p using the range of the reference volume magnetic susceptibility or the range and the median of the reference volume magnetic susceptibility. It is also good. Alternatively, as described in the first embodiment, the range and the average value of the reference volume magnetic susceptibility may be used to analyze the degree of the ability of the particulate organism p.

Subsequently, an analysis method according to the third embodiment will be described with reference to FIG. FIG. 15 is a flowchart showing an analysis method according to the third embodiment. The analysis method according to the third embodiment can be performed using the analysis device 10 described with reference to FIGS. 1, 13 and 14.

As shown in FIG. 15, the processing from step S1 to step S3 is the same as the analysis method described with reference to FIG. In the analysis method according to the third embodiment, when the volume magnetic susceptibility of the particulate organism p (analytical target) is measured (step S3), the particle size and volume magnetic susceptibility of the particulate organism p are compared with the reference data 43. The degree of ability of the particulate organism p is analyzed (step S6). When analyzing the particulate organism p, the processing unit 42 compares the particle size and volume magnetic susceptibility of the particulate organism p with the reference data 43 stored in the storage unit 41. The reference data 43 shows, as already described, the relationship between the volume magnetic susceptibility and the particle diameter of the reference particulate matter of the same type as that of the particulate matter p to be analyzed, for each degree of the ability of the reference particulate matter. .

The third embodiment has been described above. According to the third embodiment, as in the first and second embodiments, the quality of the particulate organism p can be evaluated. Specifically, the degree of ability of the particulate organism p can be analyzed. In addition, it becomes possible to use the particulate organism p after evaluation for the next study.

In the present embodiment, the degree of ability of yeast (standard strain) was analyzed, but the particulate organism p is not limited to yeast. Particulate organisms p may be cells other than yeast. For example, the particulate organism p may be an animal cell.

Further, in the present embodiment, the degree of the ability of the particulate organism p was analyzed, but based on the degree of the ability of the particulate organism p (eg, physiologically active ability, differentiation ability, or ability to produce proteins etc.) It may be further analyzed whether the rod-like organism p is non-defective (normal) or defective (abnormal). Alternatively, by comparing the particle size and volume magnetic susceptibility of the particulate organism p with the reference data 43, it is analyzed whether the particulate organism p is good or defective as the state of the particulate organism p. Good. For example, it can be analyzed whether the particulate organism p is a normally differentiated iPS cell or a cancerous iPS cell.

The embodiments of the present invention have been described above with reference to the drawings. However, the present invention is not limited to the above embodiment, and can be implemented in various modes without departing from the scope of the invention.

For example, in the embodiment of the present invention, the magnetic field generation unit 20 includes the pair of

permanent magnets

20a and 20b, but the magnetic field generation unit 20 includes a pair of pole pieces (pole pieces) to generate a magnetic field gradient. It is also 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 pole pieces, two pole pieces constituting the pair of pole pieces are arranged with a gap of a predetermined distance, for example, not less than 100 μm and not more than 500 μm. The cell 21 is located in the air gap between the two pole pieces. The pole pieces may be, for example, magnetized iron pieces. The iron piece may be magnetized by, for example, a permanent magnet, an electromagnet, a magnetic circuit, or a superconducting magnet.

Moreover, 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 a recess 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 to one end of the microchannel, the droplet flows in the microchannel by capillary action. .

In the embodiment of the present invention, the particle size of the particulate organism p is measured by image analysis, but the Brownian motion of the particulate organism p may be analyzed to measure the particle size of the particulate organism p.

Specifically, the diffusion coefficient is calculated from the dispersion of the change (displacement) of 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 diffusion coefficient The particle size of the particulate organism p can be 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 in the direction (y direction) orthogonal to the axial direction of the cell 21 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 moving distance in the y direction of the particulate matter p performing Brownian motion by a time twice as long.

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

In the embodiment of the present invention, the analysis device 10 includes the light source 50. However, instead of the light source 50, the analysis device 10 may include a laser, or may further include a laser in addition to the light source 50. . When the analyzer 10 includes the light source 50 and the laser, when emitting light from the light source 50, the emission of the laser beam from the laser is stopped, and when the laser beam is emitted from the laser, the light from the light source 50 Stop the light emission. When a laser is used, the particulate matter p introduced into the cell 21 is irradiated with a laser beam. The observation unit 30 observes the particulate matter p by the laser light (scattered light) scattered by the particulate matter p in the cell 21. For example, the imaging unit 34 described with reference to FIG. 3 images the laser light scattered by the particulate organism p through the enlargement unit 32.

In addition, when using a laser, you may measure the particle diameter of particulate-form thing p based on a dynamic light scattering method or a static light scattering method, for example. In addition, when irradiating the particulate matter p with a laser beam, the capillary tube is preferably a square capillary having a square cross-sectional shape orthogonal to the axial direction. By using a square capillary, it becomes easy to mirror-finish the side to which a laser beam is irradiated among the side surfaces of the cell 21.

Further, in the embodiment of the present invention, the computing unit 40 (processing unit 42) measures the particle diameter of the particulate matter p, but the image captured by the imaging unit 34 is displayed on the display, and from the image displayed on the display An analyzer may measure the particle size of the particulate matter p. Alternatively, the image taken by the imaging unit 34 may be printed, and the analyst may measure the particle diameter of the particulate matter p from the printed image.

In the embodiment of the present invention, the imaging unit 34 images the particulate matter p at predetermined time intervals to measure the magnetophoretic velocity of the particulate matter p. However, using a laser, for example, a laser is used. The magnetic migration velocity of the particulate organism p may be measured based on the Doppler method.

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

10 analyzer 20 magnetic field generation unit 30 observation unit 32 enlargement unit 34 imaging unit 40 calculation unit 41 storage unit 42 processing unit 43 reference data 50 light source p particulate matter medium

Claims

A magnetic field generation unit that generates a magnetic field to cause magnetism of the particulate matter to be analyzed;
An observation unit for observing the particulate matter to be analyzed;
The magnetic migration velocity and the particle diameter of the particulate organism to be analyzed are measured from the observation result of the observation section, and the volume magnetization of the particulate organism to be analyzed is determined based on the measured magnetic migration velocity and particle diameter. A processing unit that measures the rate,
A storage unit for storing reference data indicating the relationship between the volume magnetic susceptibility of the reference particulate matter and the particle diameter;
The analysis unit analyzes the particulate matter to be analyzed by comparing the volume magnetic susceptibility and the particle diameter of the particulate matter to be analyzed with the reference data.
The reference data indicates the relationship between volume magnetic susceptibility and particle diameter of each of a plurality of types of reference particulate matter,
The analyzer according to claim 1, wherein the processing unit analyzes the type of particulate matter to be analyzed by comparing the volume magnetic susceptibility and the particle diameter of the particulate matter to be analyzed with the reference data. .
The reference data indicates, for each state that the reference particulate matter can have, the relationship between the volume magnetic susceptibility and the particle diameter of the reference particulate matter of the same type as the particulate matter to be analyzed;
The analyzer according to claim 1, wherein the processing unit analyzes the state of the particulate matter to be analyzed by comparing the volume magnetic susceptibility and the particle diameter of the particulate matter to be analyzed with the reference data. .
The analyzer according to claim 3, wherein the state that the reference particulate matter can have corresponds to the function that the reference particulate matter can exhibit.
The state that the reference particulate matter may have corresponds to at least a part of each stage in which the function is reduced from the alive state to the dead state of the reference particulate matter. The analyzer according to 4.
The analyzer according to claim 5, wherein the state that the reference particulate matter can have corresponds to the state in which the reference particulate matter is alive and the state in which the reference particulate matter is dead.
The analyzer according to claim 4, wherein the state that the reference particulate matter can have corresponds to the activity of the reference particulate matter.
The analyzer according to claim 7, wherein the activity corresponds to the amount of produced adenosine triphosphate.
The analyzer according to any one of claims 1 to 8, wherein the particulate organism to be analyzed is a yeast, a fungus or a cell.
Observing the particulate matter to be analyzed which is to be magnetophoresed;
Measuring the magnetic migration velocity and the particle size of the particulate matter to be analyzed from the observation result;
Measuring the volume magnetic susceptibility of the particulate matter to be analyzed based on the measured magnetic migration velocity and particle diameter;
Analyzing the particulate matter to be analyzed by comparing the volume magnetic susceptibility and the particle size of the particulate matter to be analyzed with reference data;
The reference data is an analysis method showing a relationship between volume magnetic susceptibility and particle diameter of reference particulate matter.
The reference data indicates the relationship between volume magnetic susceptibility and particle diameter of each of a plurality of types of reference particulate matter,
The analysis method according to claim 10, wherein in the analysis step, the type of particulate matter to be analyzed is analyzed by comparing the volume magnetic susceptibility and the particle diameter of the particulate matter to be analyzed with the reference data. .
The reference data indicates, for each state that the reference particulate matter can have, the relationship between the volume magnetic susceptibility and the particle diameter of the reference particulate matter of the same type as the particulate matter to be analyzed;
The analysis method according to claim 10, wherein in the analysis step, the state of the particulate matter to be analyzed is analyzed by comparing the volume magnetic susceptibility and the particle diameter of the particulate matter to be analyzed with the reference data. .
The analysis method according to claim 12, wherein a state that the reference particulate matter can have corresponds to a function that the reference particulate matter can exhibit.
The state that the reference particulate matter may have corresponds to at least a part of each stage in which the function is reduced from the alive state to the dead state of the reference particulate matter. The analysis method as described in 13.
The analysis method according to claim 14, wherein the state that the reference particulate matter can have corresponds to the state in which the reference particulate matter is alive and the state in which the reference particulate matter is dead.
The analysis method according to claim 13, wherein the state that the reference particulate matter can have corresponds to the activity of the reference particulate matter.
The analysis method according to claim 16, wherein the activity corresponds to the amount of produced adenosine triphosphate.
The analysis method according to any one of claims 10 to 17, wherein the particulate organism to be analyzed is a yeast, a fungus or a cell.