JP6995606B2 - Measuring equipment and culture system - Google Patents

Description

The present invention relates to a measuring device for measuring the pH of a medium for culturing cells.

While culturing cells in an incubator, there is a desire to grasp the state of cultured cells. Therefore, in general, the culture vessel is taken out of the incubator and observed under a microscope when necessary. In addition, the pH of the medium is also of interest as the state of the cultured cells. The pH of the medium is often determined by visually confirming the color of the medium to which phenol red has been added. As a method for quantitatively measuring the pH of a medium, for example, Patent Document 1 discloses a pH measuring device capable of measuring the pH of a medium during cell culture and a dedicated culture container.

Japanese Patent No. 5797911

An object of the present invention is to provide a measuring device having a compact structure for measuring the pH of a medium contained in an existing culture vessel.

The measuring device according to the present invention comprises a lighting unit that emits light of a plurality of colors toward an existing culture vessel containing a medium, a detection unit that detects light reflected after passing through the medium, and the detection unit. It includes a control unit that acquires information on the detected reflected light, and a housing that incorporates the lighting unit , the detection unit, and the control unit. The housing is arranged on one side with respect to the culture vessel.
In one aspect, the measuring device is further configured as follows. The housing has a shape suitable for the culture vessel. The housing is housed in another culture vessel having substantially the same structure as the culture vessel, and the other culture vessel is superposed on the culture vessel. As a result, the housing positions the lighting unit and the detection unit with respect to the culture vessel.
In another aspect, the measuring device is further configured as follows. The lighting unit, the detection unit, the control unit, and the housing constitute a measuring device main body. The measuring device further includes an adapter that accommodates the measuring device body and positions the measuring device body with respect to the culture vessel.

The culture system according to the present invention includes the above-mentioned measuring device and a culture medium exchange device for exchanging the medium in the culture container. The culture medium exchange device controls the culture medium exchange unit that wirelessly receives information from the outside, the culture medium exchange unit that exchanges the culture medium in the culture vessel, and the culture medium exchange unit based on the information received by the reception unit. It is equipped with a control unit.

According to the present invention, there is provided a measuring device having a compact structure for measuring the pH of a medium contained in an existing culture vessel.

FIG. 1 is a perspective view of a measuring device set including the measuring device according to the first embodiment and a sample superimposed on the measuring device set. FIG. 2 is a plan view of the measuring device set shown in FIG. FIG. 3 shows a cross section of the measuring device set and sample shown in FIG. FIG. 4 is a block diagram showing an internal configuration of the measuring device main body shown in FIG. FIG. 5 is a block diagram showing an internal configuration of a measuring device main body according to a modification 1 of the first embodiment. FIG. 6 is a plan view of a measuring device main body according to the second modification of the first embodiment and a part of a multi-well plate accommodating the measuring device main body. FIG. 7 shows a cross section of the measuring device set according to the second embodiment and a sample stacked on the measuring device set. FIG. 8 is a perspective view of a measuring device set including the measuring device according to the third embodiment and a sample superimposed on the measuring device set. FIG. 9 shows a cross section of the measuring device set and sample shown in FIG. FIG. 10 is a perspective view of a measuring device set including the measuring device according to the modified example of the third embodiment. FIG. 11 is a perspective view of the measuring device according to the fourth embodiment and a sample superimposed on the measuring device. FIG. 12 shows a cross section of the measuring device and the sample shown in FIG. FIG. 13 schematically shows the culture system according to the fifth embodiment.

[First Embodiment]
<Constitution>
FIG. 1 is a perspective view of a measuring device set 200 including the measuring device 100 according to the present embodiment and a sample 600 stacked on the measuring device set 200.

In the sample 600, cells, tissues and the like are cultured in the medium CM. The sample 600 is composed of an existing culture vessel 610 and a medium CM for culturing cells contained in the culture vessel 610.

The medium CM is a liquid medium to which a pH indicator such as phenol red is added. The medium CM is not limited to this, and may be another liquid medium or solid medium.

The measuring device set 200 includes an existing culture container 610 and a measuring device 100 housed in the culture container 610.

The measuring device 100 is a device for measuring the pH of the medium CM contained in the culture container 610 of the sample 600 in the sample 600 during cell culture. At the time of measurement, the sample 600 is superposed on the measuring device set 200. In FIG. 1, the measuring device set 200 and the sample 600 are drawn separately in order to facilitate understanding of the structure.

In the present embodiment, the culture vessel 610 is composed of a multi-well plate 620 and a well plate lid 630 that covers the multi-well plate 620.

The multi-well plate 620 has a plurality of wells 622 for accommodating the medium. Each well 622 is configured with a circular recess.

The multi-well plate 620 is not limited to this, but in the present embodiment, it is composed of a 6-well plate. That is, the multi-well plate 620 of the present embodiment is a 6-well plate and has 6 wells 622.

The lower surface of the multi-well plate 620, the bottom surface of the well 622, and the upper surface and the lower surface of the well plate lid 630 are all made of optically transparent and smooth flat surfaces. Here, the optically transparent and smooth plane means a plane that does not exert an undesired optical influence such as scattering and diffraction on the light passing through the plane.

The well 622 of the multi-well plate 620 is essentially for accommodating the medium CM and the cells to be cultured in the medium CM, but in the measuring device set 200, each well 622 of the multi-well plate 620 is used. Contains one measuring device 100.

At the time of pH measurement, the measuring device set 200 is installed in the incubator. Further, the sample 600 is superposed on the measuring device set 200. The incubator is a general incubator for cell culture. For example, the medium CM is a liquid medium to which phenol red is added, and the incubator is a CO ₂ incubator.

Hereinafter, the measuring device 100 will be described with reference to FIGS. 2 to 4. FIG. 2 is a plan view of the measuring device set 200 shown in FIG. In FIG. 2, the illustration of the lid is omitted. FIG. 3 shows a cross section of the measuring device set 200 and the sample 600 shown in FIG. In FIG. 3, the measuring device set 200 and the sample 600 are drawn on top of each other. FIG. 4 is a block diagram showing an internal configuration of the measuring device main body 110 shown in FIG.

In the present embodiment, the measuring device 100 is composed of the measuring device main body 110. The measuring device main body 110 is detected by a lighting unit 120 that emits light of a plurality of colors toward the culture container 610 of the sample 600, a detection unit 130 that detects the light reflected after passing through the medium CM, and a detection unit 130. Power is supplied to the control unit 140 that acquires the reflected light information, the transmission unit 150 that wirelessly transmits the reflected light related information to the outside, the lighting unit 120, the detection unit 130, the control unit 140, and the transmission unit 150. It includes a power supply unit 160 including a battery, a lighting unit 120, a detection unit 130, a control unit 140, a transmission unit 150, and a housing 170 including a power supply unit 160.

The plurality of colors of light emitted from the lighting unit 120 include, for example, at least three colors of light. The light of at least three colors includes, for example, red light, green light, and blue light. The illumination unit 120 includes, for example, a white light source that emits white light including at least three colors of light. Alternatively, the illumination unit 120 may include at least three monochromatic light sources that independently emit at least three colors of light. Further, the lighting unit 120 may be configured to be capable of irradiating light of three colors by combining a multicolor light source and a monochromatic light source.

The detection unit 130 is configured to detect light of a plurality of colors emitted from the lighting unit 120, respectively. The detection unit 130 is configured to detect, for example, the amount of light of a plurality of colors.

For example, if the lighting unit 120 includes a white light source that emits white light containing at least three colors of light, the detection unit 130 includes, for example, a color sensor that independently detects at least three colors of light. .. The color sensor includes, for example, a light receiving element having a light receiving surface including a plurality of light receiving regions, and a plurality of color filters provided on the light receiving surface of the light receiving element corresponding to the plurality of light receiving regions, for example, a red filter and a green filter. It consists of a blue filter. Alternatively, the detection unit 130 may include a spectroscopic sensor that disperses and detects light of at least three colors. The spectroscopic sensor is composed of, for example, a spectroscopic element such as a grating and a plurality of sensors or linear image sensors that detect light of each color dispersed by the spectroscopic element. Alternatively, the detection unit 130 may include at least three monochromatic sensors that independently detect at least three colors of light.

Alternatively, if the illumination unit 120 includes at least three monochromatic light sources that emit at least three colors of light independently, the detection unit 130 may include, for example, the color sensor or spectroscopic sensor described above, or at least three colors. It contains at least three monochromatic sensors that detect light independently. Alternatively, if the lighting unit 120 contains three monochromatic light sources and emits at least three colors of light independently in each time division, the detection unit 130 includes one monochromatic sensor, which monochromatic sensor. Light may be detected in time divisions in synchronization with the light source.

The control unit 140 controls the operation of each part of the measuring device main body 110. For example, the control unit 140 controls operations such as light emission from the lighting unit 120 and light detection from the detection unit 130. Further, the control unit 140 includes, for example, a calculation section 142 for calculating the pH of the medium based on the information of the reflected light detected by the detection unit 130. It is known that a medium CM containing a pH indicator, which is a dye whose color changes depending on pH, such as phenol red, exhibits a predetermined absorbance depending on the pH. For example, Japanese Patent Application Laid-Open No. 62-115297 describes the pH and wavelength of a Dalveco MEM medium containing 0.001% phenol red, wherein the concentrations of fetal bovine serum are 0%, 10%, and 20%, respectively. The relationship with the absorbance at 430 nm, 558 nm and 630 nm is disclosed. The calculation section 142 uses the relationship between the pH of the known medium CM and the light transmittance of each color to calculate the pH based on the detected light transmittance of each color.

The control unit 140 includes integrated circuits such as a Central Processing Unit (CPU), an Application Specific Integrated Circuit (ASIC), and a Field Programmable Gate Array (FPGA). The control unit 140 may be configured by one integrated circuit or the like, or may be configured by combining a plurality of integrated circuits or the like. The operation of the control unit 140 is performed according to, for example, a program recorded in a recording area in the control unit 140 or a memory (not shown).

When the control unit 140 includes the calculation section 142, the relevant information of the reflected light transmitted from the transmission unit 150 is the pH information of the medium. The control unit 140 outputs the pH information to the transmission unit 150, and the transmission unit 150 transmits the pH information to, for example, an external device 510.

The transmission unit 150 has a function of transmitting information wirelessly. Further, the external device 510 has a function of transmitting information wirelessly. The transmission unit 150 may have a function of wirelessly receiving information such as an operation instruction from the outside in addition to the transmission function. In other words, the transmission unit 150 may be a transmission / reception unit.

Information transmission / reception between the transmission unit 150 and the external device 510 is performed using, for example, wireless communication technology using Wi-Fi (registered trademark), Bluetooth (registered trademark), or the like. Alternatively, both the transmission unit 150 and the external device 510 may be connected to a communication network such as the Internet, and information may be transmitted / received via the communication network. The amount of information related to the reflected light transmitted from the transmission unit 150 is not so large. On the other hand, the measuring device main body 110 must operate for a relatively long time with a limited battery capacity. Therefore, for transmission / reception of information between the transmission unit 150 and the external device 510, it is preferable to use a low power consumption method such as Bluetooth Low Energy.

The external device 510 is configured to, for example, manage the pH information in association with the sample 600 and perform a predetermined process based on the pH information. For example, the external device 510 may output a message recommending a medium change based on the pH information. The external device 510 may be composed of, for example, a so-called personal computer.

The housing 170 is airtight. That is, the housing 170 seals the lighting unit 120, the detection unit 130, the control unit 140, the transmission unit 150, and the power supply unit 160 from the outside air.

Further, the housing 170 has a surface of the sample 600 facing the culture vessel 610, which is optically transparent and has a smooth flat surface. As described above, an optically transparent and smooth plane means a plane that does not exert undesired optical influences such as scattering and diffraction on the light passing through the plane.

The housing 170 has a shape suitable for the multi-well plate 620 of the culture vessel 610. Specifically, the housing 170 has a shape that is accommodated in the well 622 of the multi-well plate 620 without rattling. For example, as shown in FIG. 2, the housing 170 has a cylindrical shape that fits in the well 622 of the multi-well plate 620 with almost no gap. For example, the housing 170 is shaped so that its outer diameter is about 0.1 to 1 mm smaller than the inner diameter of the well 622.

The housing 170 is arranged in contact with the bottom surface of the well 622. As a result, the position of the measuring device main body 110 in the vertical direction is accurately positioned with respect to the culture container 610 of the measuring device set 200. Also, the lateral movement of the housing 170 is restricted by the inner wall of the well 622. As a result, the measuring device main body 110 is positioned laterally with respect to the culture container 610 of the measuring device set 200. Therefore, the measuring device main body 110 is three-dimensionally positioned with respect to the culture vessel 610 of the measuring device set 200.

In this way, since the measuring device main body 110 is three-dimensionally positioned with respect to the culture container 610 of the measuring device set 200, the measuring device main body 110 is also tertiary with respect to the sample 600 stacked on the measuring device set 200. Originally positioned. In particular, the lighting unit 120 and the detection unit 130 in the measuring device main body 110 are accurately and optically positioned in the vertical direction with respect to the culture vessel 610 of the sample 600.

At the time of use, as shown in FIG. 3, for example, the measuring device set 200 is installed on the shelf 710 of the incubator, and the sample 600 is superposed on the measuring device set 200. That is, the measuring device set 200 is arranged on one side with respect to the sample 600. Therefore, the measuring device main body 110 (hence, the housing 170) is arranged on one side with respect to the culture vessel 610 of the sample 600.

<Action>
The measuring device set 200 can be easily assembled. Specifically, an empty multi-well plate 620 is prepared, and the measuring device main body 110 is dropped into each well 622 of the multi-well plate 620 one by one. The measuring device main body 110 is a well with the surface from which the light emitted from the lighting unit 120 exits faces up, in other words, the surface from which the light detected by the detection unit 130 enters faces up. It is dropped into 622. Subsequently, the multi-well plate 620 is covered with the well plate lid 630. With just this work, the assembly of the measuring device set 200 is completed. Further, the optical positioning of the lighting unit 120 and the detection unit 130 built in the measuring device main body 110 with respect to the culture vessel 610 is completed.

Further, the measuring device set 200 can be easily disassembled. Specifically, the measuring device main body 110 can be taken out on the well plate lid 630 by turning the multi-well plate 620 upside down with the well plate lid 630 covered and removing the multi-well plate 620.

The pH measurement is performed as follows. Here, for convenience, it is assumed that the measuring device set 200 is already installed in the incubator.

First, an empty culture vessel 610 (here, for convenience, referred to as an empty sample 600) that does not contain the medium CM is placed on the measuring device set 200. In this state, the lighting unit 120 emits light. A part of the light emitted from the lighting unit 120 passes through the well plate lid 630 of the measuring device set 200 and the multi-well plate 620 of the sample 600 and reaches the well plate lid 630 of the sample 600. Part of the light that reaches the well plate lid 630 of the sample 600 is reflected by the well plate lid 630 (top and bottom) of the sample 600, and the multi-well plate 620 of the sample 600 and the well plate lid of the measuring device set 200. It passes through 630 and is incident on the detection unit 130. The detection unit 130 detects the reflected light from the empty sample 600.

Next, instead of the empty sample 600, a culture vessel 610 containing the sample 600, that is, the medium CM (here, referred to as an actual sample 600 for convenience in comparison with the empty sample 600) is used in the measuring device set 200. Layer on top. In this state, the lighting unit 120 emits light. A part of the light emitted from the lighting unit 120 passes through the well plate lid 630 of the measuring device set 200 and the multi-well plate 620 of the sample 600, passes through the medium CM, and then passes through the well plate lid 630 of the sample 600. To reach. Part of the light that reached the well plate lid 630 of the sample 600 was reflected by the well plate lid 630 (upper and lower surfaces) of the sample 600, passed through the medium CM, and then measured with the multi-well plate 620 of the sample 600. It passes through the well plate lid 630 of the device set 200 and is incident on the detection unit 130. The detection unit 130 detects the reflected light from the actual sample 600.

As described above, the illumination unit 120 and the detection unit 130 are such that the light emitted from the illumination unit 120 is reflected by the well plate lid 630 of the sample 600 and then satisfactorily enters the detection unit 130 so that the well plate of the sample 600 is incident. It is optically positioned with respect to the lid 630.

Although the configuration in which the light is reflected by the well plate lid 630 is shown here, a reflective material may be used on the well plate lid 630, and the light may be reflected by the reflective material.

In other words, the "light reflected after passing through the medium CM" detected by the detection unit 130 is assumed here to be the light reflected by the culture container 610 of the sample 600 after passing through the medium CM. Not limited to this, the culture vessel 610 of the sample 600 after passing through the medium CM also contains the reflected light after passing through.

Of course, in any of the configurations, regardless of whether the well plate lid 630 or the reflective material is used, the emission intensity of the lighting unit 120 is sufficient so that the reflected light can be sufficiently detected to calculate the pH described later. It is preferable that the detection sensitivity of the detection unit 130 is adjusted.

The detection information (for example, light amount information) for the empty sample 600 and the detection information (for example, light amount information) for the actual sample 600 are compared, and the absorbance by the medium CM is calculated for the light of each of the plurality of colors. Further, the pH is calculated based on the absorbance of the light of each color.

The detection unit 130 outputs information about the incident light, for example, light amount information to the control unit 140. The control unit 140 calculates the pH based on the input information, for example, the light amount information in the calculation section 142, and outputs the pH information to the transmission unit 150.

The transmission unit 150 wirelessly transmits the input pH information to the outside.

The pH information transmitted from the transmission unit 150 is received, for example, by an external device 510. The external device 510 may output, for example, a message recommending a medium change based on the pH information.

Acquisition of pH information may be repeated during the actual culture of sample 600. The acquisition of pH information may be performed, for example, periodically, at any preset timing, or when an instruction is given by the user. The instruction by the user may be input using, for example, an external device 510 and transmitted to the control unit 140 via the transmission unit 150. Since the detection information for the empty sample 600 only needs to be acquired once, for example, it is acquired once before the start of culturing the actual sample 600, and the information is recorded in a memory (not shown) of the measuring device 100. The calculation section 142 reads the detected information for the recorded empty sample 600 when calculating the pH.

The pH information is acquired, for example, at intervals of several hours. Time required for operations such as light emission from the lighting unit 120, detection of reflected light by the detection unit 130, pH calculation by the calculation section 142, and transmission of the result by the transmission unit 150, which are necessary for one acquisition of pH information. Is a short time. Except for this short operation period, the measuring device main body 110 takes a standby state with low power consumption. When the transmission unit 150 needs to be constantly connected to the external device 510, such as to wait for an instruction from the external device 510, the communication between the transmission unit 150 and the external device 510 may be performed by a low level such as Bluetooth Low Energy. A power-consuming communication method is used. The operating period is short during the culture period that lasts for several days or more, and the power consumption is low during the period other than the operating period. Therefore, even if the measuring device main body 110 is small and the battery included in the power supply unit 160 has a low capacity. The measuring device main body 110 can acquire pH information during a long-term culture period.

<effect>
In the present embodiment, since the component of the measuring device main body 110 is built in the cylindrical housing 170 housed in the well 622 of the multi-well plate 620, the measuring device main body 110 (that is, the measuring device) 100) is configured to be very compact.

Further, by simply dropping the measuring device main body 110 into the well 622 of the multi-well plate 620 and covering the multi-well plate 620 with the well plate lid 630, the lighting unit 120 and the detection unit 130 built in the measuring device main body 110 can be obtained. It is optically positioned with respect to the culture vessel 610. Therefore, the lighting unit 120 and the detection unit 130 are also optically positioned with respect to the sample 600 stacked on the measuring device set 200.

Since the housing 170 of the measuring device main body 110 is airtight and has a cylindrical shape, the work of alcohol sterilization of the measuring device main body 110 can be easily performed.

Further, since the measurement by the measuring device 100 is performed non-contactly by the transmitted light, there is no possibility of contamination with respect to the sample 600. Further, since the measurement by the measuring device 100 is performed by irradiating visible light for a short time, there is almost no damage to the cells in culture. Further, the measurement by the measuring device 100 can be performed on a sample in a state where the existing culture container 610 is used and the sample is left to stand in the incubator for culturing. That is, it is not necessary to use a special culture container for culturing, and no special operation is required for measurement. Further, since the pH information of the medium CM is acquired numerically, the user can make an objective judgment as compared with a general visual judgment.

[Modification 1]
FIG. 5 is a block diagram showing an internal configuration of the measuring device main body 110A according to the present modification. In FIG. 5, the members having the same reference numerals as those shown in FIG. 4 are similar members, and detailed description thereof will be omitted. In the following, the differences will be emphasized.

In the measuring device main body 110A according to this modification, the control unit 140A does not include the calculation section 142 for calculating the pH based on the information of the reflected light detected by the detection unit 130. Therefore, in the measuring device main body 110A, the information related to the reflected light transmitted from the transmission unit 150 is not the pH information but, for example, the light amount information of the reflected light. The transmission unit 150 transmits, for example, the light amount information of the reflected light to the external device 520 including the calculation unit 522 that calculates the pH based on the light amount information of the reflected light.

The external device 520 calculates the pH based on the light amount information by the calculation unit 522, and for example, manages the pH information obtained by the calculation unit 522 in association with the sample 600, or performs a predetermined process based on the pH information. Or something. For example, the external device 520 may output a message recommending a medium change based on the pH information. The external device 520 may be composed of, for example, a so-called personal computer.

[Modification 2]
FIG. 6 is a plan view of a part of the measuring device main body 110B and the multi-well plate 620 accommodating the measuring device main body 110B according to the present modification. In FIG. 6, the members having the same reference numerals as those shown in FIG. 2 are similar members, and detailed description thereof will be omitted. In the following, the differences will be emphasized.

In the measuring device main body 110B, the housing 170B has a shape suitable for the multi-well plate 620 of the culture container 610. Specifically, the housing 170B has a shape that is accommodated in the well 622 of the multi-well plate 620 without rattling. For example, the housing 170B has a rectangular parallelepiped shape that is composed of circular recesses and fits almost inscribed in the well 622 of the multi-well plate 620. For example, the housing 170B is shaped so that the distance from the corner of the rectangular parallelepiped housing 170B to the inner wall of the well 622 is as small as about 0.1 to 1 mm.

Similar to the measuring device main body 110, the measuring device main body 110B is arranged so that the housing 170B is in contact with the bottom surface of the well 622, so that the position of the measuring device main body 110B in the vertical direction is accurately positioned with respect to the multi-well plate 620. Further, the lateral movement of the housing 170B is restricted by the inner wall of the well 622, so that the measuring device main body 110B is positioned laterally with respect to the multi-well plate 620. Therefore, the measuring device main body 110B is three-dimensionally positioned with respect to the multi-well plate 620.

Therefore, the measuring device main body 110B is also three-dimensionally positioned with respect to the sample 600 stacked on the measuring device set 200 including the multi-well plate 620 containing the measuring device main body 110B. In particular, the lighting unit 120 and the detection unit 130 in the measuring device main body 110B are accurately and optically positioned in the vertical direction with respect to the culture vessel 610 of the sample 600.

[Second Embodiment]
FIG. 7 shows a cross section of the measuring device set 200C according to the present embodiment and the sample 600 stacked on the measuring device set 200C. In FIG. 7, the members having the same reference numerals as those shown in FIGS. 1 to 4 are similar members, and detailed description thereof will be omitted. In the following, the differences will be emphasized. That is, the parts not mentioned in the following description are the same as those in the first embodiment.

<Constitution>
The measuring device set 200C according to the present embodiment is superposed on the sample 600. In general, the incubator shelf 710 has a large number of through holes 712. Therefore, when the sample 600 is placed directly on the shelf 710 of the incubator, the reflectance of the lower surface of the sample 600 varies depending on the location and is not uniform. In order to avoid such a situation, the sample 600 is placed on the shelf 710 of the incubator via the sheet member 720 having a uniform reflectance regardless of the location. The sheet member 720 preferably has a high reflectance.

Similar to the measuring device set 200 according to the first embodiment, the measuring device set 200C drops the measuring device main body 110 into each well 622 of the multi-well plate 620 one by one, and drops the well plate lid 630 into the multi-well plate 620. It is assembled by covering it with. However, in the measuring device set 200C, the measuring device main body 110 contains the light detected by the detection unit 130 with the surface from which the light emitted from the lighting unit 120 exits facing down. It is dropped into the well 622 with the coming side down.

The measuring device set 200C thus assembled is superposed on the sample 600 placed on the incubator shelf 710 via the seat member 720. The lighting unit 120 and the detection unit 130 built in the measuring device main body 110 are optically positioned with respect to the multi-well plate 620 by dropping the measuring device main body 110 into the well 622. The multi-well plate 620 in which the measuring device main body 110 is dropped into the well 622 is superposed on the sample 600. As a result, the illumination unit 120 and the detection unit 130 are optically positioned with respect to the sample 600.

<Action>
At the time of pH measurement, a part of the light emitted from the lighting unit 120 passes through the multi-well plate 620 of the measuring device set 200 and the well plate lid 630 of the sample 600, and if it is an empty sample 600, it remains as it is. In the case of the actual sample 600, after further permeating the medium CM, it reaches the bottom of the well 622 of the multi-well plate 620 of the sample 600.

Part of the light that reaches the bottom of the well 622 of the sample 600 is the bottom surface of the well 622 of the sample 600 or the bottom surface of the multi-well plate 620 (or the interface between the multi-well plate 620 and the sheet member 720, in other words, the sheet member 720). Reflected by.

After that, the reflected light is left as it is in the case of the empty sample 600, while it is transmitted through the medium CM in the case of the actual sample 600, and then the well plate lid 630 of the sample 600 and the multi-well plate 620 of the measuring device set 200 are used. It penetrates and enters the detection unit 130.

The processing of the information regarding the light incident on the detection unit 130 is the same as that of the first embodiment.

<effect>
In the present embodiment, the measuring device main body 110 is simply dropped into the well 622 of the multi-well plate 620, and the lighting unit 120 and the detection unit 130 built in the measuring device main body 110 are optical with respect to the multi-well plate 620. Positioning. Therefore, the lighting unit 120 and the detection unit 130 are also optically positioned with respect to the sample 600 placed under the multi-well plate 620 of the measuring device set 200.

In addition, the same effect as that of the measuring device according to the first embodiment can be obtained in the measuring device according to the present embodiment.

[Third Embodiment]
FIG. 8 is a perspective view of a measuring device set 200D including the measuring device 100D according to the present embodiment and a sample 600D superposed on the measuring device set 200D. In FIG. 8, the measuring device set 200D and the sample 600D are drawn separately in order to facilitate understanding of the structure. Further, FIG. 9 shows a cross section of the measuring device set 200D and the sample 600D shown in FIG. In FIG. 9, the measuring device set 200D and the sample 600D are drawn on top of each other. In FIGS. 8 and 9, the members having the same reference numerals as those shown in FIGS. 1 to 4 are similar members, and detailed description thereof will be omitted. In the following, the differences will be emphasized. That is, the parts not mentioned in the following description are the same as those in the first embodiment.

<Constitution>
The sample 600D is composed of an existing culture vessel 640 and a medium CM for culturing cells contained in the culture vessel 640.

The measuring device set 200D is composed of an existing culture container 640 and a measuring device 100D housed in the culture container 640.

The measuring device 100D is a device for measuring the pH of the medium CM contained in the culture container 640 of the sample 600D. At the time of measurement, the sample 600D is superposed on the measuring device set 200D.

In the present embodiment, the culture vessel 640 is composed of a Petri dish 650 having a recess 652 for accommodating the medium CM, and a Petri dish lid 660 covering the Petri dish 650. Both the petri dish 650 and the petri dish lid 660 are shaped like a bottomed cylinder. The petri dish 650 and the petri dish lid 660 are designed so that the petri dish lid 660 is one size larger than the petri dish 650 and the petri dish 650 can be inserted inside the petri dish lid 660.

The lower surface of the petri dish 650, the lower surface of the recess 652 of the petri dish 650, and the upper and lower surfaces of the petri dish lid 660 are all made of optically transparent and smooth flat surfaces. As described above, an optically transparent and smooth plane means a plane that does not exert undesired optical influences such as scattering and diffraction on the light passing through the plane.

The petri dish 650 is essentially for accommodating the medium CM and the like, but in the measuring device set 200D, the petri dish 650 accommodates the measuring device 100D.

In the present embodiment, the measuring device 100D is composed of the measuring device main body 110 according to the first embodiment and the adapter 180 accommodating the measuring device main body 110. The details of the measuring device main body 110 are as described in relation to the first embodiment.

The adapter 180 has a recess 182 that accommodates the measuring device main body 110 without rattling. That is, the recess 182 of the adapter 180 is composed of a circular recess having an inner diameter slightly larger than the outer diameter of the cylindrical housing 170 of the measuring device main body 110. The measuring device main body 110 is an adapter with the surface from which the light emitted from the lighting unit 120 exits faces up, in other words, the surface from which the light detected by the detection unit 130 enters faces up. It is housed in a recess 182 of 180. The adapter 180 three-dimensionally positions the measuring device main body 110 by accommodating the measuring device main body 110 in the recess 182. The principle of positioning the adapter 180 with respect to the measuring device main body 110 is the same as the principle of positioning the well 622 with respect to the measuring device main body 110 in the first embodiment.

The adapter 180 has a height adjusting portion 184 at the bottom of the recess 182 for adjusting the height position (vertical position) of the measuring device main body 110 housed in the recess 182. In the height adjusting unit 184, the vertical positions of the lighting unit 120 and the detection unit 130 of the measuring device main body 110 housed in the recess 182 of the adapter 180 are appropriately positioned with respect to the sample 600D superimposed on the measuring device set 200D. It is designed to have a thickness that can be used.

The adapter 180 has a shape suitable for the Petri dish 650 of the culture vessel 640. Specifically, the adapter 180 has a shape that is accommodated in the recess 652 of the petri dish 650 without rattling. For example, the adapter 180 has a cylindrical appearance that fits in the recess 652 of the petri dish 650 with almost no gap. For example, the adapter 180 is shaped so that its outer diameter is smaller than the inner diameter of the recess 652 of the petri dish 650 by about 0.1 to 1 mm.

The adapter 180 is three-dimensionally positioned by being housed in the recess 652 of the Petri dish 650. The principle of positioning the petri dish 650 with respect to the adapter 180 is the same as the principle of positioning the well 622 with respect to the measuring device main body 110 in the first embodiment.

<Action>
The measuring device set 200D is assembled by dropping the adapter 180 accommodating the measuring device main body 110 into the recess 652 of the petri dish 650 and covering the petri dish 650 with the petri dish lid 660. The adapter 180 is dropped into the recess 652 of the petri dish 650 with the exposed portion of the measuring device main body 110 facing up. The adapter 180 is positioned with respect to the petri dish 650 by being dropped into the recess 652 of the petri dish 650. The principle of positioning the petri dish 650 with respect to the adapter 180 is the same as the principle of positioning the well 622 with respect to the measuring device main body 110 in the first embodiment.

As a result, the measuring device main body 110 that has been positioned and housed in the adapter 180 is positioned with respect to the culture vessel 640 of the measuring device set 200D. That is, the adapter 180 positions the measuring device main body 110 with respect to the culture vessel 640 of the measuring device set 200D.

Therefore, the lighting unit 120 and the detection unit 130 built in the measuring device main body 110 are optically positioned with respect to the culture vessel 640 of the measuring device set 200D. At the time of measurement, the sample 600D is superposed on the measuring device set 200D. As a result, the illumination unit 120 and the detection unit 130 are also optically positioned with respect to the sample 600D.

Further, in the measuring device set 200D, the measuring device main body 110 can be taken out on the petri dish lid 660 by turning the petri dish upside down with the petri dish 650 covered with the petri dish lid 660 and removing the petri dish 650.

<effect>
In the present embodiment, the adapter 180 accommodating the measuring device main body 110 is dropped into the recess 652 of the petri dish 650, and the petri dish 650 is covered with the petri dish lid 660 to detect the lighting unit 120 built in the measuring device main body 110. The unit 130 is optically positioned with respect to the culture vessel 640. Therefore, the lighting unit 120 and the detection unit 130 are also optically positioned with respect to the sample 600D stacked on the measuring device set 200D.

Further, since the measuring device 100D has the adapter 180, the measuring device main body 110 designed for, for example, a multi-well plate 620 of φ35 mm can be applied to a petri dish 650 of φ90 mm, for example.

In addition, the same effect as that of the measuring device according to the first embodiment can be obtained in the measuring device according to the present embodiment.

[Modification example]
FIG. 10 is a perspective view of a measuring device set 200E including the measuring device 100E according to the present modification. In FIG. 10, the members having the same reference numerals as those shown in FIG. 8 are similar members, and detailed description thereof will be omitted. In the following, the differences will be emphasized.

The measuring device set 200E according to the present modification is composed of the measuring device 100E according to the present modification and the culture container 640 containing the measuring device 100E. As described above, the culture container 640 is composed of a Petri dish 650 and a Petri dish lid 660.

The measuring device 100E according to the present modification is composed of the measuring device main body 110B according to the modified example 2 of the first embodiment and the adapter 180 accommodating the measuring device main body 110B. The details of the measuring device main body 110B are as described in relation to the modification 2 of the first embodiment.

The adapter 180E has a recess 182E that accommodates the measuring device main body 110B without rattling. That is, the recess 182E of the adapter 180E is composed of a recess slightly more rectangular than the rectangular parallelepiped housing 170B of the measuring device main body 110B. As shown in the figure, the depth of the recess 182E is smaller than the height of the measuring device main body 110B, but the depth is not limited to this, and may be larger than that.

The adapter 180E three-dimensionally positions the measuring device main body 110B by accommodating the measuring device main body 110B in the recess 182E. The principle of positioning the adapter 180E with respect to the measuring device main body 110B is the same as the principle of positioning the well 622 with respect to the measuring device main body 110 in the first embodiment.

Like the adapter 180, the adapter 180E has a shape suitable for the petri dish 650 of the culture vessel 640. Specifically, the adapter 180E has a shape that is accommodated in the recess 652 of the petri dish 650 without rattling. For example, the adapter 180E has a cylindrical appearance that fits in the recess 652 of the petri dish 650 with almost no gap.

The adapter 180E is three-dimensionally positioned by being housed in the recess 652 of the Petri dish 650. The principle of positioning the petri dish 650 with respect to the adapter 180E is the same as the principle of positioning the well 622 with respect to the measuring device main body 110 in the first embodiment.

As a result, the measuring device main body 110B positioned and housed in the adapter 180E is positioned with respect to the culture vessel 640 of the measuring device set 200E. Therefore, the lighting unit 120 and the detection unit 130 built in the measuring device main body 110B are optically positioned with respect to the culture vessel 640 of the measuring device set 200E. At the time of measurement, the sample 600D is superposed on the measuring device set 200E. As a result, the illumination unit 120 and the detection unit 130 are also optically positioned with respect to the sample 600D.

[Fourth Embodiment]
FIG. 11 is a perspective view of the measuring device 100F according to the present embodiment and the sample 600F superimposed on the measuring device 100F. In FIG. 11, the measuring device 100F and the sample 600F are drawn separately in order to facilitate understanding of the structure. Further, FIG. 12 shows a cross section of the measuring device 100F and the sample 600F shown in FIG. In FIG. 12, the measuring device 100F and the sample 600F are drawn on top of each other. In FIGS. 11 and 12, the members having the same reference numerals as those shown in FIGS. 1 to 4 are similar members, and detailed description thereof will be omitted. In the following, the differences will be emphasized. That is, the parts not mentioned in the following description are the same as those in the first embodiment.

<Constitution>
The sample 600F is composed of an existing culture vessel 670 and a medium CM for culturing cells contained in the culture vessel 670.

The measuring device 100F is a device for measuring the pH of the medium CM contained in the culture container 670 of the sample 600F. At the time of measurement, the sample 600F is superposed on the measuring device 100F.

In the present embodiment, the culture vessel 670 is composed of a flask 680 for accommodating the medium CM and a cap 690 for closing the mouth of the flask 680.

Both the inner and outer surfaces of the flask 680 are made up of optically transparent and smooth flat surfaces. As described above, an optically transparent and smooth plane means a plane that does not exert undesired optical influences such as scattering and diffraction on the light passing through the plane.

In the present embodiment, the measuring device 100F is composed of the measuring device main body 110 according to the first embodiment and the adapter 180F accommodating the measuring device main body 110. The details of the measuring device main body 110 are as described in relation to the first embodiment.

Like the adapter 180 according to the third embodiment, the adapter 180F has a recess 182F for accommodating the measuring device main body 110 without rattling. The details of the recess 182F are the same as those of the recess 182 described in relation to the third embodiment.

The measuring device main body 110 is an adapter with the surface from which the light emitted from the lighting unit 120 exits faces up, in other words, the surface from which the light detected by the detection unit 130 enters faces up. It is housed in the recess 182F of 180F. The adapter 180F three-dimensionally positions the measuring device main body 110 by accommodating the measuring device main body 110 in the recess 182F. The principle of positioning the adapter 180F with respect to the measuring device main body 110 is the same as the principle of positioning the well 622 with respect to the measuring device main body 110 in the first embodiment.

The adapter 180F has a height adjusting portion 184F at the bottom of the recess 182F for adjusting the height position (vertical position) of the measuring device main body 110 housed in the recess 182F. The details of the height adjusting unit 184F are the same as those of the adjusting unit 184 described in relation to the third embodiment.

The adapter 180F has a shape suitable for the flask 680 of the culture vessel 670. During the measurement, the flask 680 and the adapter 180F are aligned and stacked. In that state, the adapter 180F is shaped to have at least one side, preferably two or more sides, flush with the sides of the flask 680. Here, the side surface of the flask 680 is intended to be a laterally facing surface in the state depicted in FIGS. 11 and 12.

<Action>
The adapter 180F and the flask 680 are aligned and overlapped so that the side surface of the adapter 180F and the side surface of the flask 680 are flush with each other. As a result, the measuring device main body 110 that has been positioned and housed in the adapter 180F is positioned with respect to the culture vessel 670 composed of the flask 680 and the cap 690. That is, the adapter 180F positions the measuring device main body 110 with respect to the culture vessel 670 of the sample 600F. Therefore, the lighting unit 120 and the detection unit 130 built in the measuring device main body 110 are optically positioned with respect to the sample 600F.

<effect>
In the present embodiment, the flask 680 of the sample 600F is aligned and superposed on the adapter 180F accommodating the measuring device main body 110, so that the lighting unit 120 and the detection unit 130 built in the measuring device main body 110 are the sample 600F. Optically positioned with respect to the culture vessel 670 of.

Further, since the measuring device 100F has the adapter 180F, the measuring device main body 110 designed for the multi-well plate 620 can be applied to the flask 680 as well.

In addition, the same effect as that of the measuring device according to the first embodiment can be obtained in the measuring device according to the present embodiment.

Further, when this embodiment is considered together with the first embodiment and the third embodiment, the adapters 180, 180E and 180F have the shapes of the housings 170 and 170B of the measuring device main bodies 110, 110A and 110B and the existing ones. It can be said that it is selected and applied from a plurality of types of adapters prepared in advance corresponding to the shape of a plurality of types of culture vessels, for example, a petri dish 650 or a flask 680.

[Fifth Embodiment]
FIG. 13 schematically shows the culture system according to the present embodiment. In FIG. 13, the members having the same reference numerals as those shown in FIGS. 1 to 4 are similar members, and detailed description thereof will be omitted. In the following, the differences will be emphasized. That is, the parts not mentioned in the following description are the same as those in the first embodiment.

<Constitution>
The culture system according to the present embodiment is, for example, the measuring device set 200D according to the third embodiment, the medium changing device 300 for exchanging the medium of the sample 600G stacked on the measuring device set 200D, the measuring device set 200D, and the medium. It has an external device 530 that exchanges information with and from the exchange device 300.

As described above, the measuring device set 200D is composed of the culture container 640 and the measuring device 100D housed in the culture container 640, and the culture container 640 is composed of the petri dish 650 and the petri dish lid 660 for measurement. The device 100D includes a measuring device main body 110 and an adapter 180. The measuring device main body 110 has a transmission unit 150 that wirelessly transmits information related to the reflected light detected by the detection unit 130 to the outside.

At the time of measurement, the measuring device set 200D is installed on the shelf 710 of the incubator, and the sample 600G is superposed on the measuring device set 200D.

The sample 600G is composed of a culture container 640G and a medium CM contained in the culture container 640G. The culture container 640G is composed of a Petri dish 650 and a Petri dish lid 660G.

At the time of measurement, the medium exchange device 300 is superposed on the sample 600G.

The culture medium exchange device 300 is a medium based on the information related to the receiving unit 310 that wirelessly receives information from the outside, the medium exchange unit 320 that exchanges the medium in the culture vessel 640G, and the reflected light received by the receiving unit 310. A control unit 330 for controlling the exchange unit 320 is provided.

The medium exchange unit 320 has, for example, a suction pipe 322 and a supply pipe 324 extending through a petri dish lid 660G of the culture container 640G of the sample 600G, and sucks the old medium in the sample 600G through the suction pipe 322. , Is configured to feed the sample 600G with fresh medium through the supply pipe 324.

The external device 530 is configured to receive information from the transmission unit 150 in the measuring device main body 110 and transmit the received information to the receiving unit 310 in the culture medium exchange device 300.

<Action>
As described above, the transmission unit 150 in the measuring device main body 110 transmits the pH information of the medium CM in the culture container 640G of the sample 600G, and the external device 530 receives the pH information transmitted from the transmission unit 150. , The received pH information is transmitted to the receiving unit 310 in the medium exchange device 300.

The receiving unit 310 in the medium exchange device 300 receives the pH information transmitted from the external device 530, and supplies the received pH information to the control unit 330. The control unit 330 determines whether or not the medium CM in the culture vessel 640G of the sample 600G needs to be replaced based on the supplied pH information.

When it is determined that the medium CM needs to be replaced, the control unit 330 causes the medium exchange unit 320 to suck the old medium and supply the new medium to replace the medium CM in the culture container 640G of the sample 600G. Let me.

<effect>
According to the culture system according to the present embodiment, the culture medium is automatically exchanged based on the pH information of the culture medium CM, so that the cells are stably maintained in a constant culture environment.

In the culture system according to the present embodiment, the pH information is provided from the transmission unit 150 in the measuring device main body 110 to the receiving unit 310 in the medium exchange device 300 via the external device 530, but the transmission unit 150 is used. May be configured to transmit pH information directly to the receiving unit 310.

Further, similarly to the first modification of the first embodiment, the transmission unit 150 may be configured to transmit the light amount information of the reflected light detected by the detection unit 130 instead of the pH information. In this case, for example, the external device 530 may be configured to calculate the pH information based on the received light amount information and transmit the calculated pH information to the receiving unit 310. Alternatively, the receiving unit 310 receives the light amount information transmitted from the transmitting unit 150 via the external device 530, or directly receives the light amount information from the transmitting unit 150, and the control unit 330 receives the pH information based on the received light amount information. May be configured to control the medium exchange unit 320 based on the calculated pH information.

Although the embodiments of the present invention have been described with reference to the drawings, the present invention is not limited to these embodiments, and various modifications and changes are made without departing from the gist thereof. May be good. The various modifications and changes referred to herein also include implementations in which the above-described embodiments are appropriately combined.

In the above description, it is exemplified that the sheet member 720 is arranged under the culture vessel 610, but the sheet member 720 may be arranged on the optical path between the lighting unit 120 and the detection unit 130, and the measuring device 100 may be used. May be placed above the culture vessel 610 if the sheet member 720 is placed below the culture vessel 610.

100, 100D, 100E, 100F ... Measuring device, 110, 110A, 110B ... Measuring device body, 120 ... Lighting unit, 130 ... Detection unit, 140, 140A ... Control unit, 142 ... Calculation section, 150 ... Transmission unit, 160 ... Power supply unit, 170, 170B ... housing, 180, 180E, 180F ... adapter, 182, 182E, 182F ... recess, 184, 184F ... height adjustment unit, 200, 200C, 200D, 200E ... measuring device set, 300 ... medium Exchange device, 310 ... Receiving unit, 320 ... Medium exchange unit, 322 ... Suction pipe, 324 ... Supply pipe, 330 ... Control unit, 510, 520, 530 ... External device, 522 ... Calculation unit, 600, 600D, 600F, 600G ... sample, 610 ... culture vessel, 620 ... multi-well plate, 622 ... well, 630 ... well plate lid, 640, 640G ... culture vessel, 650 ... petri dish, 652 ... recess, 660, 660G ... petri dish lid, 670 ... culture vessel , 680 ... Flask, 690 ... Cap, 710 ... Shelf, 712 ... Through hole, 720 ... Sheet member.

Claims (20)

It is a measuring device for measuring the pH of the medium contained in the existing culture vessel.
A lighting unit that emits light of multiple colors toward the culture vessel,
A detection unit that detects the reflected light after passing through the medium, and
A control unit that acquires information on the reflected light detected by the detection unit, and
It is provided with a housing incorporating the lighting unit, the detection unit, and the control unit.
The housing is arranged on one side with respect to the culture vessel.
The housing has a shape suitable for the culture container, and the housing is housed in another culture container having substantially the same structure as the culture container. A measuring device that is stacked on the culture vessel, whereby the housing positions the lighting unit and the detection unit with respect to the culture vessel . It is a measuring device for measuring the pH of the medium contained in the existing culture vessel.
A lighting unit that emits light of multiple colors toward the culture vessel,
A detection unit that detects the reflected light after passing through the medium, and
A control unit that acquires information on the reflected light detected by the detection unit, and
It is provided with a housing incorporating the lighting unit, the detection unit, and the control unit.
The housing is arranged on one side with respect to the culture vessel.
The lighting unit, the detection unit, the control unit, and the housing constitute a measuring device main body.
A measuring device further comprising an adapter for accommodating the measuring device main body and positioning the measuring device main body with respect to the culture vessel . The adapter has a shape suitable for the culture vessel, the adapter is housed in another culture vessel having substantially the same structure as the culture vessel, and the other culture vessel is the culture. The measuring device according to claim 2 , wherein the adapter is stacked on a container, whereby the adapter positions the measuring device main body with respect to the culture container. The adapter has a shape suitable for the culture vessel, and the adapter and the culture vessel are aligned and overlapped, whereby the adapter positions the measuring device main body with respect to the culture vessel. , The measuring device according to claim 2 . The adapter according to claim 3 or 4 , wherein the adapter is selected and applied from a plurality of types of adapters prepared in advance, corresponding to the shape of the housing and the shape of the existing plurality of types of culture vessels. Measuring device. The measuring device according to any one of claims 1 to 5, further comprising a transmission unit for transmitting information related to the reflected light to the outside. The measuring device according to claim 6, wherein the transmission unit wirelessly transmits the related information to the outside. The measuring device according to claim 6 or 7, wherein the housing further includes a lighting unit, a detection unit, a control unit, and a power supply unit that supplies electric power to the transmission unit. The measuring device according to claim 8, wherein the housing includes the transmitting unit and the power supply unit. The measuring device according to any one of claims 1 to 9, wherein the housing has airtightness, and the surface facing the culture vessel is an optically transparent and smooth flat surface. The control unit includes an arithmetic section that calculates the pH of the medium based on the reflected light information.
The related information of the reflected light is pH information, and is
The measuring device according to any one of claims 6 to 9 , wherein the transmitting unit transmits the pH information. The related information of the reflected light is the light amount information of the reflected light.
The measuring device according to any one of claims 6 to 9 , wherein the transmitting unit transmits the light amount information to an external device including an arithmetic unit that calculates pH information based on the light amount information. The measuring device according to any one of claims 1 to 12 , wherein the plurality of colors of light emitted from the lighting unit include at least three colors of light. 13. The measuring device according to claim 13 , wherein the lighting unit includes a white light source that emits white light including light of at least three colors. 13. The measuring device according to claim 13 , wherein the lighting unit includes at least three monochromatic light sources that independently emit light of at least three colors. The measuring device according to claim 14 or 15 , wherein the detection unit includes at least three monochromatic sensors that independently detect each of the at least three colors of light. The measuring device according to claim 14 or 15 , wherein the detection unit includes a spectroscopic sensor that disperses and detects light of at least three colors. The measuring device according to claim 14 or 15 , wherein the detection unit includes a color sensor that independently detects light of at least three colors. The measuring device according to claim 15 , wherein the detection unit includes one monochromatic sensor that independently detects light of at least three colors in a time division manner. The measuring device according to any one of claims 1 to 19 .
A culture system including a medium exchange device for exchanging the medium in the culture container.
The culture medium exchange device controls the culture medium exchange unit that wirelessly receives information from the outside, the culture medium exchange unit that exchanges the culture medium in the culture vessel, and the culture medium exchange unit based on the information received by the reception unit. A culture system equipped with an exchange control unit.

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