Flow cell, measurement device, and cell culture system

The flow cell design with intersecting light paths and varying optical lengths addresses the challenge of high cell concentration by accurately counting cells in culture solutions, enhancing efficiency and reducing costs.

JP2025008480APending Publication Date: 2025-01-20MITSUBISHI HEAVY IND LTD
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Patent Information

Application Number
JP2023110692
Authority / Receiving Office
JP · JP
Patent Type
Applications
Current Assignee / Owner
Filing Date
2023-07-05
Publication Date
2025-01-20

AI Technical Summary

Technical Problem

Existing flow cells struggle to accurately determine the number of cells in culture solutions due to the collapse of the proportional relationship between turbidity and cell number when the cell concentration is high, leading to inaccurate cell counting.

Method used

A flow cell design that utilizes two intersecting light paths with different optical path lengths, allowing for accurate cell counting by switching between light sources based on turbidity measurements, without the need for dilution.

Benefits of technology

Enables efficient and accurate counting of cells in culture solutions with varying turbidities, reducing time and cost by minimizing the need for dilution and optimizing optical path lengths.

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Abstract

To provide a flow cell, measurement device, and cell culture system that can more accurately count the number of cells in a culture solution.SOLUTION: A flow cell for analyzing a solution on the basis of an absorption rate of first light to be irradiated in a first direction, and second light to be irradiated in a second direction comprises a cell main body that has: a first light reception surface the first light transmits; a first light emission surface provided on a side opposite the first light reception surface in the first direction; a second light reception surface the second light transmits, and a second light emission surface provided on a side opposite the second light reception surface in a second direction, and forms a flow passage where the solution flows inside of the first light reception surface, the first light emission surface, the second light reception surface and the second light emission surface. In a plane view from a direction where the solution flows, the first direction and second direction cross each other, and, a distance from the light reception surface to the first light emission surface, and a distance from the second light reception surface to the second light emission surface are mutually different.SELECTED DRAWING: Figure 3
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Description

[Technical field]

[0001] The present disclosure relates to a flow cell, a measuring device, and a cell culture system. [Background technology]

[0002] Patent Document 1 discloses a cell culture system equipped with an isolator (clean bench) in which various operations such as dispensing of culture fluid are performed in a sterile environment, and an incubator in which cell culture is performed in an appropriate environment where the temperature, humidity, carbon dioxide concentration, etc. are controlled.

[0003] In this type of cell culture system, it is necessary to count the number of cells contained in the culture solution at key points. Conventionally, a device using a flow cell has been used to perform such counting. A flow path is formed inside the flow cell, through which the culture solution flows, and the turbidity of the culture solution is measured based on the absorption rate (light absorbance) of light when the light emitted from a light source is irradiated into the flow path, and the number of cells is estimated from the turbidity value. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Utility Model Registration No. 3203002 Summary of the Invention [Problem to be solved by the invention]

[0005] Here, the turbidity of the culture medium and the number of cells (i.e., the concentration of the culture medium) are in principle proportional to each other, but if the number of cells is excessively large, the proportional relationship with the turbidity is lost. Therefore, when using the above-mentioned flow cell, it is necessary to use the turbidity measured in the concentration range where the turbidity and the number of cells are proportional as an official indicator. However, in the past, sufficient measures were not taken to address this issue, and it was sometimes difficult to accurately grasp the number of cells.

[0006] The present disclosure has been made to solve the above-mentioned problems, and aims to provide a flow cell, a measuring device, and a cell culture system that are capable of more accurately analyzing a solution. [Means for solving the problem]

[0007] In order to solve the above problems, the flow cell according to the present disclosure is a flow cell for analyzing a solution based on the absorbance of a first light irradiated in a first direction and a second light irradiated in a second direction, the flow cell having a first light receiving surface through which the first light transmits, a first light exit surface provided on the opposite side of the first light receiving surface in the first direction, a second light receiving surface through which the second light transmits, and a second light exit surface provided on the opposite side of the second light receiving surface in the second direction, and a cell body forming a flow path through which the solution flows inside the first light receiving surface, the first light exit surface, the second light receiving surface, and the second light exit surface, and in a planar view from the direction in which the solution flows, the first direction and the second direction intersect with each other, and a distance from the first light receiving surface to the first light exit surface and a distance from the second light receiving surface to the second light exit surface are different from each other.

[0008] The measurement device according to the present disclosure includes at least one of a first light source that generates the first light and a second light source that generates the second light, and the above-mentioned flow cell.

[0009] The cell culture system of the present disclosure comprises an incubator forming a culture area in which a flask containing culture medium as the solution is housed, a clean bench forming a liquid handling area in which dispensing operations are performed on the flask, a transport device capable of transporting the flask between the culture area and the liquid handling area, a pass box capable of transferring the flask unit between the incubator and the clean bench, and the above-mentioned measuring device into which the culture medium dispensed from the flask in the clean bench is introduced. Effect of the Invention

[0010] The flow cell, measuring device, and cell culture system of the present disclosure enable more accurate analysis of a solution. [Brief description of the drawings]

[0011] [Figure 1] FIG. 1 is a schematic plan view showing a schematic configuration of a cell culture system according to an embodiment of the present disclosure. [Diagram 2] FIG. 1 is a schematic side view illustrating a configuration of a measurement device according to an embodiment of the present disclosure. [Diagram 3] FIG. 2 is a perspective view showing a configuration of a flow cell according to an embodiment of the present disclosure. [Figure 4] 1 is a graph showing an example of the relationship between turbidity and concentration (the reciprocal of the dilution rate) of a culture solution. [Diagram 5] FIG. 11 is a cross-sectional view showing a first modified example of a flow cell according to an embodiment of the present disclosure. [Figure 6] FIG. 11 is a cross-sectional view showing a second modified example of a flow cell according to an embodiment of the present disclosure. [Figure 7] FIG. 13 is a schematic side view illustrating a modified example of the measurement device according to the embodiment of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] Hereinafter, an embodiment of the present disclosure will be described in detail with reference to the drawings. As shown in Fig. 1, a cell culture system 100 of the present embodiment is a system that performs unmanned and automatic cell culture and analysis of the cultured cells, using a flask unit 1 as a processing unit.

[0013] The flask unit 1 has a plurality of (for example, two in this embodiment) flasks 2. The flasks 2 contain cells and a culture solution containing a medium to which nutrients necessary for cell growth and the like have been added.

[0014] <Cell culture system> As shown in FIG. 1, the cell culture system 100 includes a stocker 110, a carry-in booth 120, an incubator 130, a clean bench 140, a pass box 150, a measuring device 160, a culture medium supplying device 161, a waste liquid tank 162, and a transporting device 170.

[0015] <Stocker> The stocker 110 is a facility for storing a plurality of flask units 1. The stocker 110 has a stocker body 111, a rack 112, a first stocker door 113, and a second stocker door 114. Stocker body 111 is a housing that forms storage area R1 as a warehouse inside. Stocker body 111 is made of a transparent material such as acrylic or glass. The rack 112 is disposed within the storage area R1 and is capable of storing a plurality of flask units 1 horizontally and vertically.

[0016] The first stocker door 113 is a door for carrying in the flask unit 1 and the like from the outside, and can be opened and closed by sliding, for example, horizontally. The second stocker door 114 is a door for carrying the flask unit 1 out to the clean bench 140, and can be opened and closed by, for example, sliding horizontally.

[0017] <Delivery Booth> The loading booth 120 is a booth used for loading the flask unit 1 and the like from outside into the stocker 110. The loading booth 120 has a booth body 121 and a loading door 122. The booth body 121 is a housing arranged adjacent to the stocker 110 and is made of a transparent material. The space inside the loading booth 120 is a loading area R2, which can communicate with the storage area R1 via the stocker second door 114. The loading door 122 is a door for loading flask units 1 and the like into the loading booth 120 from the outside, and can be opened and closed, for example, by sliding up and down. The inside of the loading area R2 is controlled, for example, to a negative pressure lower than the atmosphere in the storage area R1. This prevents outside air and the like from entering the stocker 110 when the loading door 122 is open.

[0018] <Incubator> The incubator 130 is a facility for growing cells in a culture solution. The incubator 130 includes an incubator body 131 and a shaking stage 132. The incubator body 131 is a housing that forms a culture area R3 inside. The culture area R3 is controlled to have a temperature, humidity, and carbon dioxide concentration suitable for cell culture. The incubator body 131 is made of a transparent material such as acrylic or glass. The shaking stage 132 is a device for shaking the flask unit 1. A plurality of shaking stages 132 are arranged in the culture area R3, each holding a plurality of flask units 1. The shaking stage 132 is configured to be able to shake the flask unit 1 by, for example, rotating eccentrically about a vertical axis.

[0019] <Clean bench> The clean bench 140 is a facility for performing various operations and treatments on the flask unit 1. The clean bench 140 includes a clean bench main body 141, a dispensing device 142, a waste liquid extracting device 145, and a stage 149.

[0020] The clean bench body 141 is a housing that forms a liquid handling area R4, which is a highly clean and sterile space (bio-clean room) inside. In the clean space, air flows and circulates as a downflow (downward air current) from above to below. The clean bench body 141 is made of a transparent material such as acrylic or glass.

[0021] The dispensing device 142 is provided in the clean room. The dispensing device 142 performs various dispensing operations and other processes to the flask unit 1. It should be noted that not only one but also a plurality of dispensing devices 142 may be provided.

[0022] Waste liquid extractor 145 is provided in liquid handling area R4, and is a device for extracting unused culture liquid from flask 2 of flask unit 1 as waste liquid. A plurality of stages 149 are provided in liquid handling area R4. On stage 149, flask unit 1 is temporarily placed.

[0023] <passbox> The pass box 150 is provided between the incubator 130 and the clean bench 140. The pass box 150 moves the flask unit 1 between the incubator 130 and the clean bench 140. The pass box 150 has a box body 151, a first door 152, and a second door 153.

[0024] The box body 151 is a housing formed so as to be sandwiched between the incubator body 131 and the clean bench body 141 . The first door 152 switches between a communicating state and an unblocked state between the space within the box body 151 and the incubation area R3, for example, by opening and closing in a horizontal direction. Second door 153 switches between a communication state and a non-communication state between the space within box main body 151 and liquid handling area R4, for example, by opening and closing in a horizontal direction. The first door 152 and the second door 153 are never open at the same time. This prevents direct communication between the culture area R3 and the liquid handling area R4. The flask unit 1 is transferred between the culture area R3 and the liquid handling area R4 via this pass box 150.

[0025] <Measurement equipment> The measuring device 160 is disposed adjacent to the clean bench 140. The measuring device 160 is capable of measuring and analyzing the number of cells in the culture solution. The culture solution dispensed from the flask 2 by the dispensing device 142 is transferred to the measuring device 160 via a tube (not shown).

[0026] <Culture supply device> The culture medium supplying device 161 is disposed adjacent to the clean bench 140. The culture medium supplying device 161 is a device capable of supplying the culture medium contained in the flask. The culture medium supplied from the culture medium supplying device 161 is transferred to the dispensing device 142, and is supplied into the flask of the flask unit 1 in the dispensing device 142.

[0027] <Waste tank> The waste liquid tank 162 is disposed adjacent to the clean bench 140. The waste liquid tank 162 is connected to the waste liquid extractor 145 via a tube (not shown). The waste liquid is transferred from the waste liquid extractor 145 to the waste liquid tank 162 via the tube.

[0028] <Transportation equipment> The transfer device 170 is a device for realizing unmanned transfer of the flask unit 1 within the cell culture system 100. The transfer device 170 has a first transfer robot 171, a second transfer robot 172, a third transfer robot 173, a fourth transfer robot 174, and a conveyor 175.

[0029] <Cell culture system operation> In the cell culture system 100 configured as above, cell proliferation is promoted by shaking the culture solution in the flask unit 1 in the incubator 130. The flask unit 1 in which cell proliferation has progressed is transferred to liquid manipulation area R4 via the second transport robot 172 and the pass box 150. The flask unit 1 transferred to liquid manipulation area R4 is transferred to the dispensing device 142 via the third transport robot 173. In the dispensing device 142, the culture solution is dispensed from the flask of the flask unit 1, and the culture solution is transferred to the measuring device 160. In the measuring device 160, the number of cells in the culture solution is measured, the liquid properties are analyzed, and the like are performed.

[0030] When adding a medium to the flask 2, the flask 2 is transported into the dispensing device 142. Then, in the dispensing device 142, the medium is supplied from the medium supplying device 161 to the flask 2.

[0031] Furthermore, when cell proliferation is carried out using a new flask unit 1, the following procedure is carried out, for example. That is, the first transport robot 171 transports the flask unit 1 on the rack 112 that does not contain culture medium into the liquid handling area R4 via the second stocker door 114. The flask unit 1 is transferred to the dispensing device 142 via the third transport robot 173, and the culture medium is supplied.

[0032] Thereafter, the proliferated flask unit 1 in which cell proliferation has progressed is transported to the dispensing device 142. Then, the culture medium in the flask 2 of this proliferated flask unit 1 is dispensed into the flask 2 of a new flask unit 1. This completes the subculture operation of the cells into the flask 2 of the new flask unit 1. The flask unit 1 that has undergone the subculture operation is transported to the incubator 130, where the cells are proliferated.

[0033] <Details of the measurement device> Next, the measurement device 160 according to this embodiment will be described in detail with reference to Fig. 2. As shown in the figure, the measurement device 160 has a first light source 201, a first light receiving unit 301, a second light source 202, a second light receiving unit 302, a flow cell 400, a pump 500, a supply line 501, and a discharge line 502.

[0034] The first light source 201 is an oscillator that emits a laser as the first light, and the direction in which this first light travels is called the first direction. The first light traveling in the first direction is irradiated to the first light receiving unit 301. The second light source 202 is an oscillator that emits a laser as the second light, and the direction in which this second light travels is called the second direction. The second light traveling in the second direction is irradiated to the second light receiving unit 302. In a plan view from the direction in which the solution flows, the first direction and the second direction intersect with each other. In particular, in this embodiment, the first direction and the second direction intersect with each other in the same plane. Also, the first direction and the second direction are perpendicular to each other in a horizontal plane. Note that the terms "horizontal" and "perpendicular" refer to substantially horizontal and perpendicular states, and slight errors are allowed.

[0035] (Configuration of flow cell 400) The flow cell 400 is disposed at a position where the optical paths of the first light and the second light intersect. The flow cell 400 has a cell body 401 having a substantially rectangular parallelepiped outer shape, and a flow path 402. The flow path 402 through which the dispensed culture solution flows is formed inside the cell body 401. As shown in Fig. 3, the flow path 402 has a cross shape when viewed from a third direction (vertical direction) perpendicular to the first direction and the second direction.

[0036] The surface of the flow path 402 facing the first light source 201 side in the first direction is a first light receiving surface 403. The surface facing the opposite side to the first light receiving surface 403 in the first direction is a first light emitting surface 404. The surface of the flow path 402 facing the second light source 202 side in the second direction is a second light receiving surface 405. The surface facing the opposite side to the second light receiving surface 405 in the second direction is a second light emitting surface 406. The first light receiving surface 403, the first light emitting surface 404, the second light receiving surface 405, and the second light emitting surface 406 are all wall surfaces formed of translucent glass or resin. The distance from the first light receiving surface 403 to the first light emitting surface 404 (first optical path length) and the distance from the second light receiving surface 405 to the second light emitting surface 406 (second optical path length) are different from each other. Specifically, the first optical path length is set to be longer than the second optical path length.

[0037] 2, a supply line 501 for supplying a solution from the first dispensing device 142 and a discharge line 502 for discharging the solution to the outside are connected to the flow path 402. Specifically, the supply line 501 is connected to the lower end of the cell body 401, and the discharge line 502 is connected to the upper end. A pump 500 is provided on the discharge line 502. By driving the pump 500, the solution is pumped from the supply line 501 through the flow path 402 of the cell body 401 to the discharge line 502.

[0038] (Action and effect) An example of a procedure for counting the number of cells contained in a culture solution as a solution will be described. When the solution is a culture solution, the number of cells contained in the culture solution can be obtained by measuring absorbance. First, the culture solution passing through the flow path 402 is irradiated with lasers from the first light source 201 and the second light source 202, respectively, to measure the turbidity (or apparent absorbance) of the culture solution. The absorbance is measured by the first light receiving unit 301 and the second light receiving unit 302. The number of cells contained in the culture solution can be obtained by measuring the absorbance.

[0039] Here, the turbidity of the culture solution and the number of cells (i.e., the concentration of the culture solution) are in principle proportional to each other, but if the number of cells is excessively large, the proportional relationship with the turbidity (or apparent absorbance) is lost. Specifically, it is necessary to measure the turbidity (absorbance) in the proportional region X shown in FIG. 4. On the other hand, since the absorbance is expressed as the product of the concentration and the optical path length, it is possible to measure the turbidity even in a culture solution with a high concentration by shortening the optical path length. According to the above configuration, the distance of the first optical path from the first light receiving surface 403 to the first light emitting surface 404 (first optical path length) is different from the distance of the second optical path from the second light receiving surface 405 to the second light emitting surface 406 (second optical path length).

[0040] As a result, for example, when the concentration of the culture solution does not satisfy the above-mentioned proportional relationship with the turbidity on the first optical path, the light source can be switched and the turbidity can be measured on the second optical path. Therefore, the number of cells contained in culture solutions having various turbidities can be counted efficiently and accurately with a single flow cell 400 without diluting the culture solution. In other words, a dilution device or other auxiliary equipment is not required. As a result, the time and cost required for counting the number of cells can be minimized.

[0041] Furthermore, according to the above configuration, since the first direction connecting the first light receiving surface 403 and the first light emitting surface 404 and the second direction connecting the second light receiving surface 405 and the second light emitting surface 406 are perpendicular to each other, it is possible to realize a flow cell 400 having two types of optical path lengths simply by arranging the light sources at an angular interval of 90°. Furthermore, since the flow channel 402 has a cross-shaped cross section, it is possible to minimize the amount of culture solution (sample amount) to be introduced into the flow cell 400. This makes it possible to further reduce the cost required for counting the number of cells.

[0042] The embodiment of the present disclosure has been described above. However, various changes and modifications can be made to the above configuration without departing from the gist of the present disclosure.

[0043] For example, as a first modified example of the flow cell 400, as shown in Fig. 5, the flow cell 400 may have a polygonal shape when viewed from the third direction. More specifically, the flow cell 400 has a scalene octagonal cross-sectional shape so that the optical path lengths in the first and second directions are different, and further the optical path lengths in the fourth and fifth directions are different. Note that the polygon may also have other shapes such as a hexagon. In any case, it is preferable that the shape be scalene.

[0044] According to the above configuration, the first direction connecting the first light receiving surface 403 and the first light emitting surface 404 and the second direction connecting the second light receiving surface 405 and the second light emitting surface 406 are perpendicular to each other, so that the flow cell 400 having two kinds of optical path lengths can be realized by simply arranging the light sources at an angular interval of 90°. In addition, since the flow path 402 has a polygonal shape, optical paths can be formed from further directions different from the above-mentioned first direction and second direction. This makes it possible to realize the flow cell 400 having even more optical path lengths. In other words, the number of cells contained in culture solutions having various turbidities can be counted efficiently and accurately without diluting the culture solution.

[0045] 6, as a second modified example of the flow cell 400, the flow cell 400 may have an elliptical shape when viewed from the third direction. That is, the flow cell 400 has an elliptical cross-sectional shape with the major axis in the first direction and the minor axis in the second direction.

[0046] According to the above configuration, since the first direction connecting the first light receiving surface 403 and the first light emitting surface 404 and the second direction connecting the second light receiving surface 405 and the second light emitting surface 406 are perpendicular to each other, the flow cell 400 having two kinds of optical path lengths can be realized only by arranging the light sources at an angular interval of 90°. In addition, since the flow channel 402 has an elliptical shape, optical paths can be formed from further directions different from the above-mentioned first direction and second direction. This makes it possible to realize the flow cell 400 having even more optical path lengths. In other words, the number of cells contained in culture solutions having various turbidities can be counted efficiently and accurately without diluting the culture solution.

[0047] 7, a modified example of the measuring device 160 may further include a rotation drive unit 600 that rotates the cell body 401 around a rotation axis O extending in the third direction. In this case, it is desirable to provide only one of the first light source 201 and the second light source 202.

[0048] According to the above configuration, by rotating the cell body 401, the first light receiving surface 403 or the second light receiving surface 405 can be selectively opposed to the light from a single light source. This makes it possible to reduce the number of light sources and realize a flow cell 400 having many optical path lengths. In other words, the number of cells contained in culture solutions having various turbidities can be counted efficiently and accurately without diluting the culture solution. Furthermore, by reducing the number of light sources, it is possible to significantly reduce the maintenance and manufacturing costs of the entire device.

[0049] Furthermore, the type of solution is not limited to a culture solution, and the above-described flow cell 400 and measuring device 160 can be applied to any other solution that contains a medium and a liquid.

[0050] <Additional Notes> The flow cell 400, the measuring device 160, and the cell culture system 100 described in each embodiment can be understood, for example, as follows.

[0051] (1) A flow cell 400 according to a first embodiment is a flow cell 400 for analyzing a solution based on an absorbance of a first light irradiated in a first direction and a second light irradiated in a second direction intersecting the first direction, and includes a first light receiving surface 403 through which the first light passes, a first light exiting surface 404 provided on the opposite side of the first light receiving surface 403 in the first direction, a second light receiving surface 405 through which the second light passes, and a second light exiting surface 404 provided on the opposite side of the second light receiving surface 405 in the second direction. The liquid crystal display device includes a cell body 401 having a second light exit surface 406 formed inside the first light receiving surface 403, the first light exit surface 404, the second light receiving surface 405, and the second light exit surface 406, and forming a flow path through which the solution flows inside the first light receiving surface 403, the first light exit surface 404, the second light receiving surface 405, and the second light exit surface 406, and in a plan view from the direction in which the solution flows, the first direction and the second direction intersect with each other, and a distance from the first light receiving surface 403 to the first light exit surface 404 and a distance from the second light receiving surface 405 to the second light exit surface 406 are different from each other.

[0052] Here, when a culture solution is used as the solution, the turbidity of the culture solution and the number of cells (i.e., the concentration of the culture solution) are in principle proportional to each other, but if the number of cells is excessively large, the proportional relationship with the turbidity (or apparent absorbance) is lost. On the other hand, since absorbance is expressed as the product of the concentration and the optical path length, it is possible to measure the turbidity of a culture solution with a high concentration by shortening the optical path length. According to the above configuration, the distance (optical path length) of the first optical path from the first light receiving surface 403 to the first light emitting surface 404 is different from the distance (optical path length) of the second optical path from the second light receiving surface 405 to the second light emitting surface 406. As a result, for example, when the concentration of the culture solution does not satisfy the above-mentioned proportional relationship with the turbidity on the first optical path, the light source can be switched and the turbidity can be measured by the second optical path. As a result, the number of cells contained in culture solutions having various turbidities can be efficiently and accurately counted using a single flow cell 400 without diluting the culture solution. In other words, it is possible to accurately analyze the solution.

[0053] (2) The flow cell 400 of the second aspect is the flow cell 400 of (1), wherein the first direction and the second direction are perpendicular to each other, and when viewed from a third direction perpendicular to the first direction and the second direction, the flow path 402 is cross-shaped.

[0054] According to the above configuration, since the first direction connecting first light receiving surface 403 and first light emitting surface 404 and the second direction connecting second light receiving surface 405 and second light emitting surface 406 are perpendicular to each other, it is possible to realize flow cell 400 having two types of optical path lengths simply by arranging the light sources at an angular interval of 90°. In addition, since flow path 402 has a cross-shaped cross section, it is possible to minimize the amount of culture solution (sample amount) to be introduced into flow cell 400.

[0055] (3) The flow cell 400 of the third aspect is the flow cell 400 of (1), wherein the first direction and the second direction are perpendicular to each other, and when viewed from a third direction perpendicular to the first direction and the second direction, the flow path 402 has a polygonal shape having at least the first light receiving surface 403 and the second light receiving surface 405 as sides.

[0056] According to the above configuration, the first direction connecting the first light receiving surface 403 and the first light emitting surface 404 and the second direction connecting the second light receiving surface 405 and the second light emitting surface 406 are perpendicular to each other, so that the flow cell 400 having two kinds of optical path lengths can be realized by simply arranging the light sources at an angular interval of 90°. In addition, since the flow path 402 has a polygonal shape, optical paths can be formed from further directions different from the above-mentioned first direction and second direction. This makes it possible to realize the flow cell 400 having even more optical path lengths. In other words, the number of cells contained in culture solutions having various turbidities can be counted efficiently and accurately without diluting the culture solution.

[0057] (4) The flow cell 400 of the fourth aspect is the flow cell 400 of (1), wherein the first direction and the second direction are perpendicular to each other, and when viewed from a third direction perpendicular to the first direction and the second direction, the flow path 402 has an elliptical shape with either the first direction or the second direction as the major axis and the other direction as the minor axis.

[0058] According to the above configuration, since the first direction connecting the first light receiving surface 403 and the first light emitting surface 404 and the second direction connecting the second light receiving surface 405 and the second light emitting surface 406 are perpendicular to each other, the flow cell 400 having two kinds of optical path lengths can be realized only by arranging the light sources at an angular interval of 90°. In addition, since the flow channel 402 has an elliptical shape, optical paths can be formed from further directions different from the above-mentioned first direction and second direction. This makes it possible to realize the flow cell 400 having even more optical path lengths. In other words, the number of cells contained in culture solutions having various turbidities can be counted efficiently and accurately without diluting the culture solution.

[0059] (5) The flow cell 400 of the fifth aspect is the flow cell 400 of any one of the aspects (1) to (4), further comprising a rotation drive unit 600 that supports the cell body 401 rotatably around a rotation axis O extending in a third direction perpendicular to the first direction and the second direction.

[0060] According to the above configuration, by rotating the cell body 401, the first light receiving surface 403 or the second light receiving surface 405 can be selectively opposed to the light from a single light source. This makes it possible to reduce the number of light sources and realize a flow cell 400 having many optical path lengths. In other words, the number of cells contained in culture solutions having various turbidities can be counted efficiently and accurately without diluting the culture solutions.

[0061] (6) A measuring device 160 according to a sixth aspect includes at least one of a first light source 201 that generates the first light and a second light source 202 that generates the second light, and a flow cell 400 according to any one of the aspects (1) to (5).

[0062] According to the above configuration, it is possible to realize the measuring device 160 that is capable of counting the number of cells accurately and efficiently without diluting the culture solution.

[0063] (7) A cell culture system 100 according to a seventh aspect includes an incubator 130 forming a culture area R3 in which a flask containing culture fluid as the solution is housed, a clean bench 140 forming a liquid handling area R4 in which dispensing operations are performed on the flask, a transport device 170 capable of transporting the flask between the culture area R3 and the liquid handling area R4, a pass box 150 capable of transferring the flask between the incubator 130 and the clean bench 140, and a measuring device 160 according to claim 6 into which the culture fluid dispensed from the flask in the clean bench 140 is introduced.

[0064] According to the above configuration, the number of cells can be counted accurately, thereby providing a cell culture system 100 with higher productivity and accuracy. [Explanation of symbols]

[0065] 1...Flask unit 100...Cell culture system 110...Stocker 111...Stocker body 112...Rack 113...Stocker first door 114...Stocker second door 120...Loading booth 121...Booth body 122...Loading door 130...Incubator 131...Incubator body 132...Shaking stage 140...Clean bench 141...Clean bench body 142...Dispensing device 145...Waste liquid extraction device 149...Stage 150...Pass box 151...Box body 152...First door 153...Second door 160...Measuring device 161...Culture medium supply device 162...Waste liquid tank 170...Transport device 171...First transport robot 172...Second transport robot 173...Third transport robot 174...Fourth transport robot 175...Conveyor 201...First light source 202...second light source 301...first light receiving section 302...second light receiving section 400...flow cell 401...cell body 402...flow path 403...first light receiving surface 404...first light emitting surface 405...second light receiving surface 406...second light emitting surface X...proportional area 500...pump 501...supply line 502...discharge line 600...rotation drive section O...rotation axis R1...storage area R2...carry-in area R3...culture area R4...liquid handling area

Claims

1. A flow cell for analyzing a solution based on an absorbance of a first light irradiated in a first direction and a second light irradiated in a second direction, comprising: a cell main body including a first light-receiving surface through which the first light is transmitted, a first light-emitting surface provided on the opposite side of the first light-receiving surface in the first direction, a second light-receiving surface through which the second light is transmitted, and a second light-emitting surface provided on the opposite side of the second light-receiving surface in the second direction, and which forms a flow path through which the solution flows inside the first light-receiving surface, the first light-emitting surface, the second light-receiving surface, and the second light-emitting surface; When viewed in a plan view from a direction in which the solution flows, the first direction and the second direction intersect with each other, A flow cell in which the distance from the first light receiving surface to the first light exit surface and the distance from the second light receiving surface to the second light exit surface are different from each other.

2. 2. The flow cell according to claim 1, wherein the first direction and the second direction are perpendicular to each other, and the flow channel has a cross shape when viewed from a third direction perpendicular to the first direction and the second direction.

3. The flow cell described in claim 1, wherein the first direction and the second direction are perpendicular to each other, and when viewed from a third direction perpendicular to the first direction and the second direction, the flow path has a polygonal shape having at least the first light receiving surface and the second light receiving surface as sides.

4. The flow cell described in claim 1, wherein the first direction and the second direction are perpendicular to each other, and when viewed from a third direction perpendicular to the first direction and the second direction, the flow path has an elliptical shape with one of the first direction and the second direction as its major axis and the other direction as its minor axis.

5. The flow cell according to claim 1 , further comprising a rotation drive unit that supports the cell body rotatably around a rotation axis extending in a third direction perpendicular to the first direction and the second direction.

6. At least one of a first light source that generates the first light and a second light source that generates the second light; A flow cell according to claim 1; A measuring device comprising:

7. an incubator forming a culture area in which a flask containing a culture solution as the solution is accommodated; a clean bench forming a liquid handling area in which a dispensing operation is performed on the flask; a transport device capable of transporting the flask in each of the culture area and the liquid handling area; a pass box capable of transferring the flask between the incubator and the clean bench; The measuring device according to claim 6 , wherein the culture medium dispensed from the flask is introduced into the clean bench; A cell culture system comprising:

Citation Information

Patent Citations

  • cell culture system

    JP3203002U