JP6850504B2 - Analytical device and analytical method - Google Patents

Description

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

Particle organisms such as yeast and fungi are cultured in vitro or incubators and used in a variety of studies. For example, cultured particulate organisms are used to evaluate the effectiveness of pharmaceuticals, toxicity tests of environmental chemicals, functionality of foods, and functionality of cosmetics. Also, in the field of regenerative medicine, research using particulate organisms such as iPS cells (induced pluripotent stem cells) and ES cells (embryonic stem cells) is being conducted.

The quality of a 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 imparted with a fluorescent dye. However, when the quality is evaluated by these methods, the particulate organisms subject to the quality evaluation cannot be the subject of research. Further, in the field of regenerative medicine, a culture expert relies on his / her own "can" to determine whether or not a cultured cell (particulate organism) is a defective product. Therefore, individual differences are likely to occur in the determination of whether or not the product is defective. In the field of regenerative medicine, 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 susceptibility (magnetic susceptibility per unit volume) of a particulate organism (for example, red blood cells, which is a type of blood cell) to obtain quality (characteristics) such as the surface area of the particulate organism. A device and a method for evaluating (analyzing) the particles have been proposed (Patent Document 1).

International Publication No. 2015/030184

The present inventor has completed the present invention as a result of further research on the volume magnetic susceptibility of particulate organisms. That is, an object of the present invention is to provide an analyzer and an analysis method capable of evaluating the quality of a particulate organism in a living state and using the evaluated particulate organism for the next research. It is in.

The 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 generator generates a magnetic field to magnetically run a particulate organism to be analyzed. The observation unit observes the particulate organism to be analyzed. The processing unit measures the magnetic susceptibility and particle size of the particulate organism to be analyzed from the observation results of the observation unit, and based on the measured magnetic susceptibility and particle size, the particles to be analyzed. Measure the volume magnetic susceptibility of the organism. The storage unit stores reference data showing the relationship between the volume magnetic susceptibility and the particle size of the reference particulate organism. The processing unit analyzes 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.

In certain embodiments, the reference data shows the relationship between the volumetric magnetization rate and the particle size of each of a plurality of types of reference particulate organisms, and the processing unit determines the volume magnetization rate and particles of the particulate organism to be analyzed. By comparing the diameter with the reference data, the type of particulate organism to be analyzed is analyzed.

In certain embodiments, the reference data shows the relationship between the volumetric magnetization rate and the particle size of the reference particle organism of the same type as the particle organism to be analyzed, for each state that the reference particle organism can have. The processing unit analyzes the state of the particulate organism to be analyzed by comparing the volume magnetization rate and the particle diameter of the particulate organism to be analyzed with the reference data.

In certain embodiments, the conditions that the reference particulate organism may have correspond to the functions that the reference particulate organism may exhibit.

In certain embodiments, the state that the reference particulate organism may have is at least part of each stage in which the reference particulate organism becomes less functional from a living state to a dead state. Correspond.

In certain embodiments, the states that the reference particulate organism can have correspond to a state in which the reference particulate organism is alive and a state in which the reference particulate organism is dead.

In certain embodiments, the conditions that the reference particulate organism may have correspond to the activity of the reference particulate organism.

In certain embodiments, the activity corresponds to the amount of adenosine triphosphate produced.

In certain embodiments, the particulate organism being analyzed is a yeast, fungus, or cell.

The particle analysis method according to the present invention includes a step of observing a particulate organism to be analyzed magnetically, a step of measuring the magnetic migration rate and particle size of the particulate organism to be analyzed from the observation results, and the measurement. The step of measuring the volume magnetization rate of the particle-like organism to be analyzed based on the magnetic migration rate and the particle size, and the volume magnetization rate and particle size of the particle-like organism to be analyzed are compared with the reference data. Including an analysis step of analyzing the particulate organism to be analyzed, the reference data shows the relationship between the volume magnetization rate and the particle size of the reference particulate organism.

In certain embodiments, the reference data shows the relationship between the volumetric magnetization rate and the particle size of each of a plurality of types of reference particulate organisms, and in the analysis step, the volume magnetization rate and particles of the particulate organism to be analyzed. By comparing the diameter with the reference data, the type of particulate organism to be analyzed is analyzed.

In certain embodiments, the reference data shows the relationship between the volumetric magnetization rate and the particle size of the reference particle organism of the same type as the particle organism to be analyzed, for each state that the reference particle organism can have. In the analysis step, the state of the particulate organism to be analyzed is analyzed by comparing the volume magnetization rate and the particle diameter of the particulate organism to be analyzed with the reference data.

In certain embodiments, the conditions that the reference particulate organism may have correspond to the functions that the reference particulate organism may exhibit.

In certain embodiments, the state that the reference particulate organism may have is at least part of each stage in which the reference particulate organism becomes less functional from a living state to a dead state. Correspond.

In certain embodiments, the states that the reference particulate organism can have correspond to a state in which the reference particulate organism is alive and a state in which the reference particulate organism is dead.

In certain embodiments, the conditions that the reference particulate organism may have correspond to the activity of the reference particulate organism.

In certain embodiments, the activity corresponds to the amount of adenosine triphosphate produced.

In certain embodiments, the particulate organism being analyzed is a yeast, fungus, or cell.

According to the present invention, the quality of the particulate organism can be evaluated in a living state, and the evaluated particulate organism can be used for the next research.

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 organisms 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 particle diameter and the volume magnetic susceptibility of each of three kinds of yeasts which concerns on Embodiment 1 of this invention. It is a figure which shows an example of the reference data 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 an example of the measurement result of the particle diameter and the volume magnetic susceptibility of each of three kinds of fungi which concerns on Embodiment 1 of this invention. It is a figure which shows another example of the reference data which concerns on Embodiment 1 of this invention. It is a figure which shows the measurement result of the particle diameter and the volume magnetic susceptibility of the particulate organism to be analyzed which concerns on Embodiment 2 of this invention. It is a figure which shows an example of the reference data which concerns 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 the particle diameter and the volume magnetic susceptibility of each of three kinds of animal cells which concern on Embodiment 2 of this invention. (A) is a diagram showing the measurement result of the activity of the particulate organism to be analyzed according to the third embodiment of the present invention, and (b) is the particle organism to be analyzed according to the third embodiment of the present invention. It is a figure which shows the measurement result of the particle diameter and the volume magnetic susceptibility of. It is a figure which shows an example of the reference data which concerns 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 figure, the same or corresponding parts are designated by the same reference numerals and the description is not repeated.

[Embodiment 1]
FIG. 1 is a schematic view of the analyzer 10 of the present embodiment. The analyzer 10 of the present embodiment analyzes the type of particulate organism p to be analyzed. For example, the analyzer 10 analyzes the type of yeast, the type of fungus, and the type of cells. Hereinafter, this embodiment will be described by taking the case of analyzing the type of yeast as an example. 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 organism p in the cell 21. The observation unit 30 observes the particulate organism p in the cell 21. The calculation unit 40 measures (calculates) the particle size and the magnetic migration speed of the particulate organism p from the results of observation by the observation unit 30. Further, the calculation unit 40 measures (calculates) the volume magnetic susceptibility of the particulate organism p based on the particle size and the magnetic migration rate of the particulate organism p. Then, the calculation unit 40 analyzes the type of the particulate organism p based on the particle size and the 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 apply a magnetic force to the particulate organism p in the cell 21. As a result, the particulate organism 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, 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. For example, cell 21 can be made of glass or plastic.

The particulate organism p is 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 are present in the medium m, the plurality of particulate organisms p may be dispersed in the medium m or unevenly distributed in the medium m. The medium m is typically a culture medium.

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

The volume magnetic susceptibility of the particulate organism p differs depending on the type of the particulate organism p. The difference in volume magnetic susceptibility is derived from the composition of the surface layer (cell wall or cell membrane) and the inside of the particulate organism p. Specifically, the volume magnetic susceptibility of the particulate organism p differs depending on the type of the particulate organism p because the affinity for the medium m differs depending on the composition of the cell wall or the cell membrane and the internal composition of the cell differs.

The observation unit 30 observes the particulate organism p in the cell 21 and generates a signal indicating the observation result. The calculation unit 40 measures (calculates) the particle size and the magnetic migration speed 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 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 calculation unit 40, a general-purpose computer such as a personal computer is used.

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

Further, the processing unit 42 measures the particle size 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 rate of the particulate organism p.

For example, the processing unit 42 calculates the volume magnetic susceptibility of the particulate organism 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 organism p, χs is the volume magnetic susceptibility of the particulate organism p, χm is the volume magnetic susceptibility of the medium m, and r is the volume magnetic susceptibility of the particulate organism p. It 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). The formula (1) is derived from the fact that the difference in magnetic force received by the particulate organism 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 storage unit 41 stores the reference data 43. In this embodiment, the reference data 43 shows the relationship between the standard particle size and the volume magnetic susceptibility of each of a plurality of types of particulate organisms. 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 this embodiment, the reference data 43 shows the relationship between the standard particle size and the volume magnetic susceptibility of each of the plurality of types of yeasts. In the following description, a particle-like organism showing a relationship between a standard particle size and a volume magnetic susceptibility may be referred to as a "reference particle-like organism".

Subsequently, the movement of the particulate organism 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 organism p. Specifically, FIGS. 2 (a) and 2 (b) show the relationship between the volume magnetic susceptibility of the particulate organism p and the medium m and the moving direction of the particulate organism 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 organism p is smaller than the volume magnetic susceptibility of the medium m, the particulate organism 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 the volume magnetic susceptibility 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 organism p is determined according to the volume magnetic susceptibility of the particulate organism p and the medium m. The particulate organism p receives a force in the vicinity of the ends of the permanent magnets 20a and 20b. For example, the particulate organism 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 imaging 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 organism 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 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 organism 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 coupling element (Charge Coupled Device: CCD). Alternatively, each pixel of the imaging unit 34 may be composed of a photodiode or a photomultiplier tube. The imaging unit 34 images the particulate organism p at predetermined time intervals, for example. The imaging unit 34 may image the light emitted from the light source 50 and transmitted through the cell 21, or may image the light emitted from the light source 50 and scattered by the particulate organism p.

The calculation unit 40 (processing unit 42) analyzes the temporal change in the position of the particulate organism p from the imaging result of the imaging unit 34, and from the temporal change in the position of the particulate organism p, the particle organism p Measure the magnetic migration rate.

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

Subsequently, with reference to FIG. 4, the measurement results of the particle size and the volume magnetic susceptibility of each of the plurality of types of particulate organisms p will be described. FIG. 4 is a diagram showing an example of measurement results of particle size and volume magnetic susceptibility of each of the three types of yeast (analysis target).

In FIG. 4, the horizontal axis represents the particle size and the vertical axis represents the volume magnetic susceptibility. The circles indicate the measurement results of the particle size and volume magnetic susceptibility of Saccharomyces cerevisiae (American Ale), and the triangles indicate the measurement results of the particle size and volume magnetic susceptibility of brewer's yeast (Zygosaccharomyces rouxii). Shown and squares indicate the measurement results of particle size and volume magnetic susceptibility of the standard strain (Saccharomyces cerevisiae NRIC1560 ^{T (Type strain)).} As shown in FIG. 4, the volume magnetic susceptibility of the particulate organism p differs depending on the type of the particulate organism 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 one of brewer's top fermenting yeast (Saccharomyces cerevisiae (American Ale)), soy sauce yeast (Zygosaccharomyces rouxii), and standard strain (Saccharomyces cerevisiae NRIC1560 ^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 diagram showing an example of the reference data 43 according to the first embodiment. Specifically, the relationship between the standard particle size and the volume magnetic susceptibility of three types of yeast (beer top-fermenting yeast, soy sauce yeast, and standard strain) is shown. In the following description, yeast (reference particulate organism) showing the relationship between the standard particle size and volume magnetic susceptibility may be referred to as "reference yeast".

In FIG. 5, the horizontal axis represents the particle size and the vertical axis represents the volume magnetic susceptibility. Further, Graph 60 shows the relationship between the particle size and the volume magnetic susceptibility of each of the plurality of types of reference yeasts. The storage unit 41 described with reference to FIG. 1 stores the data corresponding to the graph 60 as the reference data 43. Specifically, the storage unit 41 stores the data showing the formula of the graph 60 as the reference data 43. Alternatively, the storage unit 41 stores data indicating the 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 dashed line 61, a second dashed line 62, and a solid third graph 63. In the present embodiment, the first graph 61 shows the relationship between the standard particle size and the volume magnetic susceptibility of the beer top-fermenting yeast, and the second graph 62 shows the relationship between the standard particle size and the volume magnetic susceptibility of the soy sauce yeast. The third graph 63 shows the relationship between the standard particle size and the volume magnetic susceptibility of the standard strain. In this case, the reference data 43 includes 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. For example, the first data is the data indicating the formula of the first graph 61 or the table corresponding to the first graph 61, and the second data is the formula of the second graph 62 or the table corresponding to the second graph 62. The third data is the data indicating the formula of the third graph 63 or the table corresponding to the third graph 63.

As described with reference to FIG. 4, the beer top-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, and the particulate organism p , Beer top-fermenting yeast, soy sauce yeast, or standard strain can be analyzed.

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

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

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 size. In this case, the processing unit 42 refers to the reference data 43 and determines the volume magnetic susceptibility of the reference particulate organism having the same particle diameter as the particle diameter of the particulate organism p to be analyzed for each type of the reference particulate organism. Determine the range (range of reference volume magnetic susceptibility) and median value. The processing unit 42 determines the range of the reference volume magnetic susceptibility including the value of the volume susceptibility of the particulate organism p to be analyzed from the range of the reference volume magnetic susceptibility. When the range of a plurality of reference volume magnetic susceptibility includes the value of the volume magnetic susceptibility of the particulate organism p to be analyzed, the processing unit 42 sets the volume magnetic susceptibility of the particulate organism p to be analyzed from the median value. Determine the closest median. The reference data 43 may show 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 this embodiment can be carried out using the analyzer 10 described with reference to FIGS. 1 to 5.

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

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

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

The first embodiment has been described above. According to the first embodiment, the quality of the particulate organism p can be evaluated. Specifically, the type of particulate organism p can be analyzed. Further, according to the first embodiment, the particle size and the volume magnetic susceptibility of the particulate organism p can be measured by observing the particulate organism p during magnetic migration. Therefore, it is possible to analyze the type of particulate organism p in a living state. Therefore, the evaluated particulate organism p can be used for the next research.

Although the type of yeast was analyzed in this embodiment, the particulate organism p is not limited to yeast. The particulate organism p can be, for example, a cell. When the particulate organism p is a cell, for example, it is possible to analyze whether the particulate organism p is an iPS cell or an ES cell. Further, the particulate organism p can be, for example, a fungus. Hereinafter, analysis of fungal types will be described with reference to FIGS. 7 and 8. When analyzing the types 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 the plurality of types of fungi.

FIG. 7 is a diagram showing an example of measurement results of particle size and volume magnetic susceptibility of each of the three types of fungi (analysis target). In FIG. 7, the horizontal axis represents the particle size and the vertical axis represents the volume magnetic susceptibility. The black triangle indicates the measurement result of the particle size and volume magnetic susceptibility of Saccharomyces cerevisiae (Staphylococcus aureus ATCC12600), and the square mark indicates the measurement result of the particle size and volume magnetic susceptibility of lactic acid bacterium (Lactobacillus delbrueckii subsp.bulgaricus). , White triangles indicate the measurement results of particle size and volume magnetic susceptibility of Saccharomyces cerevisiae (American Ale).

As shown in FIG. 7, the volume magnetic susceptibility of fungi varies depending on the type of fungus. Therefore, the type of fungus can be analyzed based on the volume magnetic susceptibility of the fungus. In the following, regarding the analysis of fungal types, the particulate organism p is either Staphylococcus aureus ATCC12600, Lactobacillus delbrueckii subsp.bulgaricus, or Saccharomyces cerevisiae (American Ale). A case will be described as an example.

FIG. 8 is a diagram showing another example of the reference data 43 according to the first embodiment. Specifically, the relationship between the standard particle size and the volume magnetic susceptibility of three types of fungi (Staphylococcus aureus, lactic acid bacteria, and beer top-fermenting 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 referred to as a "reference fungus".

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

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

As described with reference to FIG. 7, Staphylococcus aureus, lactic acid bacteria, and beer top-fermenting 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, and the particulate organism p , Staphylococcus aureus, lactic acid bacteria, or beer top-fermenting yeast can be analyzed.

[Embodiment 2]
Subsequently, the second embodiment of the present invention will be described with reference to FIGS. 1 and 9 to 11. 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 state of the particulate organism p to be analyzed is analyzed.

In the present embodiment, the reference data 43 shows the relationship between the volume magnetic susceptibility and the particle size of the reference particle organism of the same type as the particle organism p to be analyzed for each state that the reference particle organism can have. The processing unit 42 analyzes the state of the particulate organism p by comparing the volume magnetic susceptibility and the 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 organism. Specifically, the reference data 43 corresponds to at least a portion of each stage in which the function of the reference particulate organism declines from a living state to a dead state. Therefore, it is possible to analyze which stage of each stage in which the function declines from the living state to the dead state the particulate organism p belongs to. For example, the reference data 43 corresponds to a state in which the reference particulate organism is alive and a state in which the reference particulate organism is dead. In this case, the life or death of the particulate organism p can be analyzed. The state in which the particulate organism p is alive and the state in which the particulate organism p is dead are among the stages in which the function of the particulate organism p declines from the living state to the dead state. Two stages are shown.

Hereinafter, the present embodiment will be described by taking as an example the case of analyzing the life and death of the particulate organism p. In this case, the reference data 43 includes the relationship between the volume magnetic susceptibility and the particle size shown when the reference particle organism p of the same type as the particle organism p to be analyzed is alive, and the particle organism p to be analyzed. The relationship between the volume magnetic susceptibility and the particle size shown when the same kind of reference particulate organism 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 the particle size of the particulate organism p with the reference data 43.

FIG. 9 is a diagram showing the measurement results of the particle size and the volume magnetic susceptibility of the particulate organism p. Specifically, the measurement results of the particle size and volume magnetic susceptibility of the standard strain (Saccharomyces cerevisiae NRIC1560 ^{T (Type strain)) are shown.}

In FIG. 9, the horizontal axis represents the particle size and the vertical axis represents the volume magnetic susceptibility. The white circles indicate the volume magnetic susceptibility of the dead particulate organism p. Black circles indicate the volume magnetic susceptibility of living particulate organisms p. As shown in FIG. 9, the volume magnetic susceptibility of the particulate organism p depends on whether the particulate organism p is alive or dead. Therefore, the life or death of the particulate organism p can be analyzed based on the volume magnetic susceptibility of the particulate organism p. Hereinafter, the present embodiment will be described by taking the case where the particulate organism p is a standard strain (Saccharomyces cerevisiae NRIC1560 ^{T (Type strain)) as an example.}

The difference in volume magnetic susceptibility reflects the degree of vital activity (enzymatic reaction) inside the cell. In addition, the difference in volume magnetic susceptibility reflects changes in the substances (components) that make up the cell. Specifically, when life activity (function) decreases or stops, cell decomposition begins, and as a result, substances (components) that make up the cell change. 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 is reduced. It is also possible to analyze whether the particulate organism p is alive or dead.

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

As shown in FIG. 10, the graph 100 includes two types of graphs (7th graph 101 and 8th graph 102). For example, the seventh graph 101 shown by the chain line shows the relationship between the volume magnetic susceptibility and the particle size shown when the reference particle-like organism is dead, and the eighth graph 102 shown by the solid line shows the reference particle-like organism alive. The relationship between the volume magnetic susceptibility and the particle size shown in this case is shown. In this case, the reference data 43 includes the seventh data corresponding to the seventh graph 101 and the eighth data corresponding to the eighth graph 102. For example, the seventh data is the formula of the seventh graph 101 or the data indicating the table corresponding to the seventh graph 101, and the eighth data is the formula of the eighth graph 102 or the table corresponding to the eighth graph 102. It is the data which shows.

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

As described with reference to FIG. 9, the dead standard strain and the living standard strain have different volume magnetic susceptibilitys. 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. Can be analyzed.

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

Subsequently, the 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 analyzer 10 described with reference to FIGS. 1, 9, and 10.

As shown in FIG. 11, the processes from step S1 to step S3 are the same as the analysis method described with reference to FIG. 6, and therefore the description thereof will be omitted. In the analysis method according to the second embodiment, when the volume magnetic susceptibility of the particulate organism p (analysis target) is measured (step S3), the particle size and the volume magnetic 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 the volume magnetic susceptibility of the particulate organism p with the reference data 43 stored in the storage unit 41. As described above, the reference data 43 corresponds to at least a part of each stage in which the function of the reference particulate organism deteriorates from the living state to the dead state.

The second embodiment has been described above. According to the second embodiment, the quality of the particulate organism p can be evaluated as in the first embodiment. Specifically, the degree of deterioration of the function of the particulate organism p can be analyzed. In addition, after the evaluation, the living particulate organism p can be separated and used for the next research.

In this embodiment, the state of yeast (standard strain) (degree of deterioration of function) was analyzed, but the particulate organism p is not limited to yeast. The particulate organism p can be a cell other than yeast. For example, the particulate organism p can be an animal cell.

FIG. 12 is a diagram showing an example of measurement results of particle size and volume magnetic susceptibility of each of the three types of animal cells. Specifically, FIG. 12 shows an example of the measurement results of the particle size and volume magnetic susceptibility of each of the three types of Jurkat cells (acute T-cell leukemia derived from humans) having different degrees of functional deterioration. Specifically, MES (2-morpholinoetan sulfonic acid) medium was used, and Jurkat cells were cultured in an environment with an ambient temperature of 37 ° C. and a carbon dioxide concentration of 7% without changing the medium. As the cells at the start of culturing, cells obtained by subculturing frozen cells for 3 generations were used. When animal cells are cultured without medium exchange, the cells become oligotrophic and deteriorate over time. The degree of deterioration of animal cells corresponds to the degree of deterioration of animal cell function.

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

As shown in FIG. 12, when the Jurkat cells are cultured without changing the medium, the volume magnetic susceptibility of the Jurkat cells changes depending on the culture time. In other words, the volume magnetic susceptibility of Jurkat cells depends on the degree of deterioration (degree of functional deterioration) of Jurkat cells. Specifically, the longer the culture time, the weaker the diamagnetism of Jurkat cells. In other words, the greater the decline in Jurkat cell function, the weaker the diamagnetism. Therefore, the state of the animal cell (degree of functional deterioration) can be analyzed based on the volume magnetic susceptibility of the animal cell.

[Embodiment 3]
Subsequently, the third embodiment of the present invention will be described with reference to FIGS. 1 and 13 to 15. 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 is different from the first and second embodiments in that the degree of ability of the particulate organism p as a state of the particulate organism p to be analyzed is analyzed. The ability of the particulate organism p includes, for example, a physiological activity ability (activity), a differentiation ability, or a protein producing ability.

In the present embodiment, the reference data 43 shows the relationship between the volume magnetic susceptibility and the particle size of the reference particle organism of the same type as the particle organism p to be analyzed, for each degree of ability of the reference particle organism. The processing unit 42 analyzes the degree of ability of the particulate organism p by comparing the volume magnetic susceptibility and the particle size of the particulate organism p with the reference data 43. Hereinafter, the present embodiment will be described by taking the case of analyzing the activity of the particulate organism p as an example. In this case, the reference data 43 shows the relationship between the volume magnetic susceptibility and the particle size of the reference particulate organism of the same type as the particulate organism p to be analyzed for each activity.

FIG. 13A is a diagram showing the measurement results of the activity of the particulate organism p. Specifically, the measurement result of the activity of the standard strain (Saccharomyces cerevisiae NRIC1560 ^T (Type strain)) is shown. Specifically, the measurement result of the activity 7 hours after the start of culturing the standard strain is shown.

In FIG. 13A, the horizontal axis represents the measurement time and the vertical axis represents 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 at 450 nm, the absorbance at this wavelength was measured. NADPH is a coenzyme produced during the synthesis of ATP (adenosine tri-phosphate), and the larger the amount of NADPH produced, the higher the absorbance. In other words, the greater the amount of ATP synthesized, 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 particulate organism p. Therefore, 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.

Further, in FIG. 13A, the square marks indicate the activity of the standard strain cultured in the culture medium containing 5% by weight of sodium chloride (NaCl). Further, the triangular mark indicates the activity of the standard strain cultured in the culture medium in which the pH (hydrogen ion index) is adjusted to 1.0. On the other hand, the circles indicate the activity of the standard strain cultured without applying stress. As shown in FIG. 13 (a), the activity (ATP synthesis amount) of the particulate organism p is lowered by applying stress.

FIG. 13B is a diagram showing the measurement results of the particle size and the volume magnetic susceptibility of the particulate organism p to be analyzed. Specifically, the measurement results of the particle size and the volume magnetic susceptibility of the standard strain (Saccharomyces cerevisiae NRIC1560 ^{T (Type strain)) cultured for 7 hours are shown.}

In FIG. 13B, the horizontal axis represents the particle size and the vertical axis represents the volume magnetic susceptibility. Further, in FIG. 13B, the square marks indicate the volume magnetic susceptibility of the standard strain cultured for 7 hours in a culture solution containing 5% by weight of sodium chloride (NaCl). Further, the triangular mark indicates the volume magnetic susceptibility of the standard strain cultured for 7 hours in the culture medium whose pH (hydrogen ion index) was adjusted to 1.0. On the other hand, the circles indicate the volume magnetic susceptibility of the 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 activity. Therefore, the activity of the particulate organism p can be analyzed based on the particle size and the volume magnetic susceptibility of the particulate organism p. Hereinafter, the present embodiment will be described by taking the case where the particulate organism p is a standard strain (Saccharomyces cerevisiae NRIC1560 ^{T (Type strain)) as an example.}

The difference in volume magnetic susceptibility reflects the degree of vital activity inside the cell. The difference in volume magnetic susceptibility reflects the strength of material dynamics in the surface layer (surface-modified molecule) of the cell membrane. The strength of the physical dynamics on the surface layer of the cell membrane corresponds to the amount of ATP produced.

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

For example, as shown in FIG. 14, graph 130 may include three types of graphs (9th graph 131, 10th graph 132, and 11th graph 133). In this case, the reference data 43 includes the ninth data corresponding to the ninth graph 131, the tenth data corresponding to the tenth graph 132, and the eleventh data corresponding to the eleventh graph 133. For example, the ninth data is the formula of the ninth graph 131 or the data indicating the table corresponding to the ninth graph 131, and the tenth data is the formula of the tenth graph 132 or the table corresponding to the tenth graph 132. The eleventh data is the data indicating the formula of the eleventh graph 133 or the table corresponding to the eleventh graph 133.

In the present embodiment, the ninth graph 131 shows the relationship between the standard particle size and the volume magnetic susceptibility of the standard strain cultured for 7 hours in a culture solution containing 5% by weight of sodium chloride (NaCl), and is shown in the tenth graph. 132 shows the relationship between the standard particle size and volume magnetic susceptibility of the standard strain cultured for 7 hours in a culture solution having a pH (hydrogen ion index) adjusted to 1.0, and FIG. 113 shows stress. The relationship between the standard particle size and the volume magnetic susceptibility of the standard strain cultured for 7 hours without any charge is shown.

As described with reference to FIG. 13, the standard strain has different volume magnetic susceptibility depending on the 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, and refers to the particulate organism p. The activity can be analyzed.

For example, the processing unit 42 determines the reference volume magnetic susceptibility closest to the volume magnetic susceptibility of the particulate organism p with reference to the reference data 43, as in the first embodiment. The processing unit 42 analyzes the degree of ability of the particulate organism p based on the result of this determination. As described in the first embodiment, the processing unit 42 analyzes the degree of ability of the particulate organism p using the range of the reference volume magnetic susceptibility, the range of the reference volume magnetic susceptibility, and the median value. May be good. Alternatively, as described in Embodiment 1, the degree of ability of the particulate organism p may be analyzed using the range and average value of the reference volume magnetic susceptibility.

Subsequently, the 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 analyzer 10 described with reference to FIGS. 1, 13, and 14.

As shown in FIG. 15, the processes from step S1 to step S3 are the same as the analysis method described with reference to FIG. 6, and therefore the description thereof will be omitted. In the analysis method according to the third embodiment, when the volume magnetic susceptibility of the particulate organism p (analysis target) is measured (step S3), the particle size and the 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 the volume magnetic susceptibility of the particulate organism p with the reference data 43 stored in the storage unit 41. As described above, the reference data 43 shows the relationship between the volume magnetic susceptibility and the particle size of the reference particle organism p of the same type as the particle organism p to be analyzed, for each degree of ability of the reference particle organism. ..

The third embodiment has been described above. According to the third embodiment, the quality of the particulate organism p can be evaluated as in the first and second embodiments. Specifically, the degree of ability of the particulate organism p can be analyzed. In addition, the evaluated particulate organism p can be used for the next research.

In this embodiment, the degree of ability of yeast (standard strain) was analyzed, but the particulate organism p is not limited to yeast. The particulate organism p can be a cell other than yeast. For example, the particulate organism p can be an animal cell.

Further, in the present embodiment, the degree of ability of the particulate organism p is analyzed, but the particles are based on the degree of the ability of the particulate organism p (for example, bioactivity ability, differentiation ability, or protein production ability). It may be further analyzed whether the state organism p is a good product (normal) or a defective product (abnormal). Alternatively, by comparing the particle size and volume magnetic susceptibility of the particulate organism p with the reference data 43, it is possible to analyze whether the particulate organism p is a good product or a defective product as the state of the particulate organism p. Good. For example, it is possible to analyze 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-described 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 (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 with a gap of a certain distance of, for example, 100 μm or more and 500 μm or less. The cell 21 is arranged in the gap between the two magnetic pole pieces. The magnetic pole piece can be, for example, a magnetized iron piece. 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 organism p. Alternatively, the glass cell and the plastic cell have a flow path through which the medium m containing the particulate organism p flows. When the cell 21 is a glass cell or a plastic cell having a microchannel, when a droplet containing the particulate organism p is dropped on one end of the microchannel, the droplet flows through the microchannel due to a capillary phenomenon. ..

Further, in the embodiment of the present invention, the particle size of the particulate organism p was 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) in the position of the particulate organism p in the direction (y direction) orthogonal to the axial direction (x direction) of the cell 21 (capillary tube), and this diffusion coefficient is calculated. The particle size of the particulate organism p can be measured from. Specifically, the particulate organism 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 (y direction) of the cell 21. I hardly receive. Therefore, the diffusion coefficient D can be calculated from the dispersion of the displacement of the position of the particulate organism p in the y direction. Specifically, the diffusion coefficient D can be calculated by dividing the square of the movement distance of the particulate organism p that performs Brownian motion in the y direction by twice the time.

The processing unit 42 measures the particle size of the particulate organism p from the diffusion coefficient D based on the following formula (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)

Further, in the embodiment of the present invention, the analyzer 10 is provided with the light source 50, but the analyzer 10 may be provided with a laser instead of the light source 50, or may be further provided with a laser in addition to the light source 50. .. When the analyzer 10 includes the light source 50 and the laser, when the light is emitted from the light source 50, the emission of the laser light from the laser is stopped, and when the laser light is emitted from the laser, the emission from the light source 50 is performed. Stops the emission of light. When a laser is used, the particulate organism p introduced into the cell 21 is irradiated with a laser beam. The observation unit 30 observes the particulate organism p by the laser light (scattered light) scattered by the particulate organism 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 via the magnifying unit 32.

When a laser is used, the particle size of the particulate organism p may be measured based on, for example, a dynamic light scattering method or a static light scattering method. Further, when irradiating the particulate organism p with laser light, the capillary tube is preferably a square 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 be irradiated with the laser beam.

Further, in the embodiment of the present invention, the calculation unit 40 (processing unit 42) measures the particle size of the particulate organism 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 organism p. Alternatively, the image captured by the imaging unit 34 may be printed, and the analyst may measure the particle size of the particulate organism p from the printed image.

Further, in the embodiment of the present invention, the imaging unit 34 measures the magnetic migration rate of the particulate organism p by imaging the particulate organism p at predetermined time intervals. The magnetic migration rate of the particulate organism p may be measured based on the 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 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 Particle-like organism m Medium

Claims (18)

A magnetic field generator that generates a magnetic field to magnetically run the particulate organism to be analyzed,
An observation unit for observing the particulate organism to be analyzed,
The magnetic susceptibility and particle size of the particulate organism to be analyzed are measured from the observation results of the observation unit, and the volume magnetization of the particulate organism to be analyzed is based on the measured magnetic susceptibility and particle size. A processing unit that measures the rate and
It is equipped with a storage unit that stores reference data showing the relationship between the volume magnetic susceptibility of the reference particulate organism and the particle size.
The processing unit is an analyzer that analyzes 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. The reference data shows the relationship between the volume magnetic susceptibility and the particle size of each of a plurality of types of reference particulate organisms.
The analyzer according to claim 1, wherein the processing unit analyzes the type 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. .. The reference data shows the relationship between the volume magnetic susceptibility and the particle size of the reference particle organism of the same type as the particle organism to be analyzed for each state that the reference particle organism can have.
The analyzer according to claim 1, wherein the processing unit 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. .. The analyzer according to claim 3, wherein the state that the reference particulate organism can have corresponds to a function that the reference particulate organism can exhibit. The state that the reference particulate organism may have corresponds to at least a part of each stage in which the function of the reference particulate organism deteriorates from a living state to a dead state. The analyzer according to 4. The analyzer according to claim 5, wherein the state that the reference particle organism can have corresponds to a state in which the reference particle organism is alive and a state in which the reference particle organism is dead. The analyzer according to claim 4, wherein the state that the reference particulate organism can have corresponds to the activity of the reference particulate organism. The analyzer according to claim 7, wherein the activity corresponds to the amount of adenosine triphosphate produced. 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. Steps to observe the particulate organism to be analyzed by magnetism,
From the observation results, the step of measuring the magnetic migration rate and the particle size of the particulate organism to be analyzed, and
A step of measuring the volume magnetic susceptibility of the particulate organism to be analyzed based on the measured magnetic migration rate and the particle size.
It includes an analysis step of analyzing 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.
The reference data is an analysis method showing the relationship between the volume magnetic susceptibility of a reference particulate organism and the particle size. The reference data shows the relationship between the volume magnetic susceptibility and the particle size of each of a plurality of types of reference particulate organisms.
The analysis method according to claim 10, wherein in the analysis step, the type of the particulate organism to be analyzed is analyzed by comparing the volume magnetic susceptibility and the particle diameter of the particulate organism to be analyzed with the reference data. .. The reference data shows the relationship between the volume magnetic susceptibility and the particle size of the reference particle organism of the same type as the particle organism to be analyzed for each state that the reference particle organism can have.
The analysis method according to claim 10, wherein in the analysis step, the state of the particulate organism to be analyzed is analyzed by comparing the volume magnetic susceptibility and the particle diameter of the particulate organism to be analyzed with the reference data. .. The analysis method according to claim 12, wherein the state that the reference particulate organism can have corresponds to a function that the reference particulate organism can exhibit. The state that the reference particulate organism may have corresponds to at least a part of each stage in which the function of the reference particulate organism deteriorates from a living state to a dead state. 13. The analysis method according to 13. The analysis method according to claim 14, wherein the state that the reference particle organism can have corresponds to a state in which the reference particle organism is alive and a state in which the reference particle organism is dead. The analysis method according to claim 13, wherein the state that the reference particulate organism can have corresponds to the activity of the reference particulate organism. The analytical method according to claim 16, wherein the activity corresponds to the amount of adenosine triphosphate produced. 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.

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