JP7022193B2 - Cell culture device management method and cell culture device management system - Google Patents

Description

The present invention relates to a method for managing a cell culture device used for research on various drugs and the like, and a management system for the cell culture device.

In recent years, attempts have been made to use a channel device (cell culture device) having a channel with a width of a micrometer order called a microchannel as an organ model for blood vessels, intestines, liver, lungs, and the like (patented). See Document 1).
For example, Patent Document 1 discloses a cell culture device having a central microchannel (channel) inside and having a plurality of types of cells (living cells) immobilized on a porous membrane as an organ mimicking device. There is.

Further, the organ mimicking device disclosed in Patent Document 1 is used as a system including a sensor, a computer, a display, and other computing devices utilizing software, data components, process steps, and / or data structures. The system can also be run using various operating systems, computing platforms, computer programs, and / or general purpose machines.
This organ mimicking device is a porous organ that reproduces an organ by flowing air, blood, water, cells, compounds, particles, culture solution, etc. through a central microchannel with cells fixed on a porous membrane. Various analyzes can be performed on the membrane by measuring its state with a sensor, displaying it on a display, and controlling it with a computer.

For example, by using a pressure sensor, electrodes, infrared rays, and light detecting means (camera and LED (Light Emitting Diode), porcelain detecting means, etc. as sensors, characteristics of a cell layer formed on a porous membrane, etc.) , And the state, etc. can also be monitored. For example, by measuring electrical characteristics such as potential difference, resistance, and short circuit current using electrodes, the fluid that has passed through the cell layer formed on the porous film, and It is possible to confirm the transport function of ions and the formation of barriers.
Thus, the organ mimicking apparatus disclosed in Patent Document 1 can, for example, treat various diseases, confirm the effects of tests, research and develop various chemical agents, and drugs such as biological agents, and screen cells. It can be used for various screenings including.

Japanese Unexamined Patent Publication No. 2011-528232

By the way, in the technique disclosed in Patent Document 1, since the human body is complicated, only one measurement is insufficient in order to accurately evaluate cells and the like using a cell culture device. That is, in order to accurately evaluate cells and the like using a cell culture device, a plurality of measurements are simultaneously performed, for example, imaging of cells on a porous membrane and measurement of resistance values using electrodes are performed simultaneously. Therefore, it is necessary to make an evaluation based on a plurality of measurement results.
However, with conventional cell culture devices, it is difficult to perform multiple measurements at the same time, especially optical measurements using fluorescent labels and imaging of cells, and electrical measurements using electrodes. Is.
Therefore, there is a problem that the state of the living cells to be cultured in the cell culture device cannot be accurately controlled.

Further, even if the technique disclosed in Patent Document 1 is used, for example, in drug research and development of the prior art, the end user (final user) who evaluates the drug himself / herself, for example, as shown in FIG. Living cells were to be seeded in a cell culture device (organ mimicking device) manufactured in advance in S102, cultured in step S104, matured to a usable state, and subjected to a drug test in step S106. Therefore, it is necessary for the end user to perform all the steps of culturing living cells in the cell culture device, and there is a problem that the end user takes time and labor for drug research and development.
In addition, in other value chains of cell culture devices, cell seeding to initial culture are performed in the factory, followed by shipping inspection and transportation so as to exhibit desired performance and / or properties. Used after a final culture step by the end user. For this reason, the end user does not manage the cells from cell seeding to the initial culture to the final culture, and cannot know the state of the cells during that period, so that the quality of the final cells is controlled. There was a problem that it was difficult.

An object of the present invention is to solve the above-mentioned problems of the prior art, continuously record the measurement data of the living cells of the cell culture device from the seeding of the living cells to the final culture, and centrally manage the history of the measurement data. It is an object of the present invention to provide a method for managing a cell culture device and a management system for the cell culture device, which enables the quality control of living cells in the cell culture device until the timing of use by the user.

In order to achieve the above object, the method for managing a cell culture device according to the first aspect of the present invention is to manufacture at least one cell culture device for culturing living cells in a factory and seed the living cells in the cell culture device. Then, the culture is started, the culture state of the living cells being cultured is measured, the first measurement data is continuously collected, the living cells are cultured in a transport vehicle, and the culture state is measured, and the second measurement is performed. While continuously collecting measurement data, the cell culture device is transported from the factory to the user of the cell culture device, and the user cultivates the living cells, measures the culture state, and continuously collects the third measurement data. The first measurement data, the second measurement data, and the third measurement data indicating the culture state of the living cells are continuously recorded and centrally recorded until the matured living cells are used. It manages and manages cell culture devices that cultivate living cells.

Further, in order to achieve the above object, the cell culture device management system according to the second aspect of the present invention includes a cell culture kit in which at least one cell culture device for culturing living cells is arranged, and a cell culture device. The first condition controller that controls the culture conditions of the living cells to be seeded and cultured, the measurement unit that measures the culture state of the living cells of the cell culture device, and the first measurement data that is measured by the measurement unit are collected. A factory equipped with a first controller having a memory unit, a cell culture kit equipped with a cell culture device for culturing living cells, a second condition controller for controlling the culture conditions of the living cells of the cell culture device, and a cell culture device. A cell culture kit is provided from a factory with a second measurement unit for measuring the culture state of living cells and a second controller having a second memory unit for collecting the second measurement data measured by the second measurement unit. A cell culture kit including a transport vehicle for transporting to the user of the culture device, a cell culture device for culturing living cells and maturing them to a usable state, and a third condition for controlling the culture conditions of the living cells of the cell culture device. The user side including a controller, a third measurement unit for measuring the culture state of living cells of the cell culture device, and a third controller having a third memory unit for collecting the third measurement data measured by the third measurement unit. The equipment and the first measurement data collected at the factory from the first controller were received, the second measurement data collected by the transport vehicle was received from the second controller, and the second measurement data was collected from the third controller by the user-side equipment. The third measurement data is received, and the first measurement data, the second measurement data, and the third measurement data indicating the culture state of the living cell culture are continuously used until the matured living cells are used until they are ready for use. It has a data server that records and centrally manages and manages a cell culture device for culturing living cells.
Here, it is preferable that the factory further has a manufacturing facility for manufacturing at least one cell culture device.

From the first measurement data, the second measurement data, and the third measurement data that are continuously recorded and centrally managed in the first aspect and the second aspect, the living cells can be used. It is preferable to notify the user of the timing of use by judging that the product has matured to the point of maturity.
In addition, a cell culture device for maturing living cells from the first measurement data, the second measurement data, and the third measurement data, which are continuously recorded and centrally managed, to a state in which living cells can be used by the user. It is preferable to obtain the third culture condition of the above and control the cell culture device to the obtained third culture condition.
Further, it is preferable that the first measurement data, the second measurement data, and the third measurement data are recorded in a data server installed at one point.

Further, the first measurement data is collected by the first controller installed in the factory, the first controller transmits the collected first measurement data to the server, and the living cells are selected from the collected first measurement data. It is preferable to obtain the first culture condition of the cell culture device for culturing and to control the cell culture device to the obtained first culture condition.
Further, the second measurement data is collected by the second controller installed in the transport vehicle, the second controller transmits the collected second measurement data to the server, and the server receives the first measurement data and the received first measurement data. From the second measurement data, the second culture condition of the cell culture device for culturing the living cells in the transport vehicle during transportation is obtained, the second culture condition is transmitted to the second controller, and the second controller is the transport vehicle. It is preferable to control the cell culture device being transported in the second culture condition.

Further, the third measurement data is collected by the third controller installed by the user, the third controller transmits the collected third measurement data to the server, and the server receives the first measurement data, the first measurement data. From the 2 measurement data and the 3rd measurement data, the 3rd culture condition of the cell culture device for maturing the living cells to the usable state in the user is obtained, and the 3rd culture condition is transmitted to the 3rd controller. It is preferable that the third controller controls the cell culture device to the third culture condition in the user.
Further, in order to collect the first measurement data, the second measurement data, and the third measurement data, the culture state of the living cells being cultured in the cell culture device is continuously measured electrically and optically. Is preferable.

Further, the cell culture device is provided between the first flow path member having the first flow path, the second flow path member having the second flow path, and the first flow path member and the second flow path member. It is preferable that the flow path device has a porous membrane and a pair of transparent electrodes provided so as to sandwich the first flow path and the second flow path.
Further, it is preferable that the pair of transparent electrodes are planar electrodes.
Further, it is preferable that the first flow path member, or the first flow path member and the second flow path member are made of a polymer material, and the pair of transparent electrodes are carbon nanotubes.

According to the present invention, it is possible to continuously record the measurement data of the living cells of the cell culture device from the seeding of the living cells to the final culture and centrally manage the history of the measurement data, and the user can use the cells. It enables quality control of living cells in the cell culture device until the timing of the cell culture.
Further, according to the present invention, as a cell culture device to be managed, a cell culture device that is used as an organ model or the like and can perform optical measurement and electrical measurement at the same time can be used.

It is a flowchart which shows typically an example of the management method of the cell culture device of this invention. It is a schematic diagram which shows an example of the management system which carries out the management method of the cell culture device of this invention. It is a block diagram which shows an example of the management system shown in FIG. It is a schematic perspective view which shows the whole structure of an example of the flow path device used as a cell culture device in the management method of the cell culture device of this invention. It is a schematic exploded perspective view which shows the whole structure of the flow path device shown in FIG. It is a schematic plan view which shows an example of the porous membrane of the flow path device shown in FIG. FIG. 6 is a schematic cross-sectional view taken along the line BB of FIG. FIG. 5 is a schematic cross-sectional view taken along the line AA in FIG. 4 showing a flow path device before the flow path unit is fixed. FIG. 5 is a schematic cross-sectional view taken along the line AA in FIG. 4 showing a flow path device after the flow path unit is fixed. It is a figure which conceptually shows an example of the measurement method using the flow path device shown in FIG. It is a schematic cross-sectional view which shows the manufacturing process of the flow path device shown in FIG. It is a schematic cross-sectional view which shows the manufacturing process of the flow path device shown in FIG. It is a schematic cross-sectional view which shows the manufacturing process of the flow path device shown in FIG. It is a schematic cross-sectional view which shows the manufacturing process of the flow path device shown in FIG. It is a flowchart which shows the culture method of the prior art.

Hereinafter, the method for managing the cell culture device and the management system for the cell culture device of the present invention will be described in detail based on the preferred embodiments shown in the attached drawings.
The description of the constituent elements described below is based on the representative embodiments of the present invention, but the present invention is not limited to such embodiments. Further, in order to clearly explain each constituent member, the dimensions of each constituent member in the drawing are appropriately changed. Therefore, the scale in the figure is different from the actual scale.
In the present specification, the numerical range represented by using "-" means a range including the numerical values before and after "-" as the lower limit value and the upper limit value.

The configuration of the cell culture device management method according to the first embodiment of the present invention will be described with reference to FIG.
FIG. 1 is a flowchart schematically showing an example of a method for managing a cell culture device according to the first embodiment of the present invention.
In the method for managing cell culture devices of the present invention, as shown in FIG. 1, first, in step S10, a predetermined number (at least one) of cell culture devices for culturing living cells are manufactured in a factory. In the present invention, a prefabricated cell culture device may be prepared and used. The living cells, cell culture device, factory configuration, etc. will be described later.

Next, in step S12, the living cells are seeded in a cell culture device in the factory.
Seeding of living cells into a cell culture device can be performed, for example, by injecting a cell suspension into a channel and allowing it to stand.

Subsequently, in step S14, the culture of the living cells seeded in the cell culture device in the factory is started, and the initial culture is performed.
In step S14 in which the initial culture is performed, the culture state of the living cells being cultured is electrically and optically measured, and the first measurement data is continuously collected in the first controller installed in the factory. The first measurement data includes culture conditions such as, for example, data such as pressure, temperature, and / or volume of the culture solution in the culture environment of the cell culture device, in addition to the electrical measurement data and the optical measurement data of the living cells. (Culture environment conditions) is preferably included.
Here, it is preferable that the first controller transmits the collected first measurement data to a data server installed at one point different from the first controller. In addition, the first controller obtains the first culture conditions (for example, pressure, temperature, and / or the amount of the culture solution) of the cell culture device for culturing the living cells from the collected first measurement data. It is preferable to control the cell culture device to the obtained first culture conditions. The data server obtains the first culture condition of the cell culture device from the received first measurement data, transmits the obtained first culture condition to the first controller, and the first controller sets the received first culture condition. The cell culture device may be controlled. The control of the cell culture device to the first culture condition may be performed automatically, or the first culture condition may be displayed on a display or the like and manually performed. Further, the optimum measurement conditions of the cell culture device may be obtained from the first measurement data, and the measurement of the cell culture device may be automatically or manually controlled according to the obtained measurement conditions.

Next, in step S16, before transporting the required number of cell culture devices to the user, who are culturing the living cells in the factory, by the transport vehicle, the culture state of the living cells is appropriate in the factory. It is preferable to carry out a shipping inspection. In the shipping inspection, cell culture devices that are culturing cells that are not mature, overmature, or dead in a predetermined state are excluded, and living organisms that have matured to a predetermined state in which the culture state is appropriate are excluded. It is replaced with a cell culture device that is culturing cells. In this way, the required number of cell culture devices are provided for transportation to the user who is culturing living cells in an appropriate culture state.
In the latter step 18, if the transportation time by the transport vehicle is long or is expected to be long, in this step 16, after the shipping inspection, the living cells are brought into a low temperature state together with the cell culture device. For example, it may be frozen to partially pause the culture or substantially stop the culture. Here, in the present invention, the low temperature state also includes a frozen state.

Next, in step S18, the required number of cell culture devices are transported from the factory to the user of the cell culture device by the transport vehicle. During transportation, in the transport vehicle, the temperature of the living cells and the cell culture device was controlled by the cell culture device, the living cells were cultured, the culture state was measured, and the second measurement data was installed in the transport vehicle. It is preferable to collect continuously in the second controller. In addition to the electrical measurement data and the optical measurement data of the living cells, the second measurement data also includes, for example, the second culture conditions (for example, pressure, temperature, and / or the amount of the culture solution) of the cell culture device. It is preferable to include it.
In addition, for example, when the transport time is long or expected to be long, in step S16, when the living cells are brought into a low temperature state including freezing together with the cell culture device at the factory, in this step S18, Receives cold living cells and cell culture devices from the factory, keeps them cold, loads them into transport vehicles, controls the temperature of living cells and cell culture devices, and keeps them cold. Living cells and cell culture devices may be transported by a transport vehicle.
Here, even while the living cells and the cell culture device are being transported in a low temperature state including freezing, the state of the living cells is measured and the second measurement data is continuously transferred to the second controller installed in the transport vehicle. It is preferable to collect. In addition to the electrical measurement data and the optical measurement data of the living cells, this second measurement data also includes, for example, conditions for maintaining the low temperature state of the cell culture device (for example, pressure, temperature, and / or the amount of the culture solution, etc.). ) Is preferably included.

Further, after receiving the cell culture device for culturing living cells from the factory, for example, when it is found that the transport time is long, or when it is expected to be long, in this step 18, in the transport vehicle. In the above, the living cells may be brought to a low temperature state together with the cell culture device, for example, frozen, and the culture may be partially stopped or substantially stopped and transported in the same low temperature state.
Further, in the transport vehicle, the temperature of the living cells in a low temperature state, for example, in a frozen state, and the temperature of the cell culture device may be controlled, for example, thawed and returned to the cultured state.
That is, in the transport vehicle, the temperature of the living cells and the cell culture device may be controlled to partially or completely transport the living cells in a low temperature state (including a frozen state).

Here, it is preferable that the second controller transmits the collected second measurement data to the data server. Next, the data server uses the received first measurement data and the second measurement data to determine the second culture condition of the cell culture device for culturing the living cells in the transport vehicle during transportation, or the maintenance control condition in a low temperature state. It is preferable to obtain (for example, pressure, temperature, and / or the amount of the culture solution, etc.) and transmit the obtained second culture condition or maintenance control condition to the second controller.
It is preferable that the second controller controls the cell culture device being transported by the transport vehicle under the second culture condition or the maintenance control condition. The control of the cell culture device to the second culture condition or the maintenance control condition may be performed automatically, or the second culture condition or the maintenance control condition may be displayed on a display or the like and manually performed. Further, the optimum measurement conditions of the cell culture device may be obtained from the second measurement data or the first to second measurement data, and the measurement of the cell culture device may be automatically or manually controlled according to the obtained measurement conditions. ..

Next, in step S20, the user receives the required number of in-cultured cell culture devices transported by the transport vehicle, and the user finally cultures the living cells.
When the user receives the living cells in a frozen state together with the cell culture device, it is preferable that the living cells are finally cultured after being thawed by the user.
In the cell culture device, the culture state is measured and the third measurement data is continuously collected in the third controller installed by the user until the living cells mature to a usable state. In addition to the electrical measurement data and the optical measurement data of the living cells, the third measurement data also includes, for example, the third culture conditions (for example, pressure, temperature, and / or the amount of the culture solution) of the cell culture device. It is preferable to include it.
The third controller preferably transmits the collected third measurement data to the data server.

Next, the data server uses the received first measurement data, second measurement data, and third measurement data to mature the cell culture device to a state in which the living cells can be used by the user. For example, it is preferable to obtain the pressure, temperature, and / or the amount of the culture solution, and transmit the third culture condition to the third controller.
It is preferable that the third controller controls the cell culture device being cultured by the user under the third culture conditions.
That is, the data server matures the first measurement data, the second measurement data, and the third measurement data, which are continuously recorded and centrally managed, to a state in which the living cells can be used by the user. The third culture condition of the cell culture device can be obtained, and the cell culture device can be controlled to the obtained third culture condition.
The control of the cell culture device to the third culture condition may be performed automatically, or the third culture condition may be displayed on a display or the like and manually performed. Further, the optimum measurement conditions of the cell culture device may be obtained from the third measurement data or the first to third measurement data, and the measurement of the cell culture device may be automatically or manually controlled according to the obtained measurement conditions. ..

In this way, the data server uses the first measurement data indicating the culture state of the living cell, the second measurement data indicating the culture state of the living cell, or the low temperature state, and the third measurement data indicating the culture state of the living cell as the first controller. , The second controller, and the third controller are continuously received and recorded, and the recorded first measurement data, second measurement data, and third measurement data are centrally managed.
As a result, the data server manages a cell culture device for culturing living cells.
Finally, in the cell culture device, the user can use the living cells that have matured to a usable state for, for example, drug testing, drug evaluation, and the like.
Here, the data server determines from the first measurement data, the second measurement data, and the third measurement data that are continuously recorded and centrally managed, that the living cells have matured to a usable state. Then, the user can be notified of the usage timing.

The configuration of the cell culture device management system according to the second embodiment of the present invention will be described with reference to FIGS. 2 and 3.
FIG. 2 is a schematic diagram showing an example of a cell culture device management system according to a second embodiment of the present invention. FIG. 3 is a block diagram showing an example of a management system for the cell culture device shown in FIG.
As shown in FIGS. 2 and 3, the cell culture device management system 80 seeds living cells in at least one (s) cell culture device 86 arranged in the cell culture unit 84. A maker factory 82 for culturing living cells, a transport vehicle 88 for transporting a cell culture unit 84 including a cell culture device 86 while culturing living cells from the maker factory 82 to a user-side facility 90, and a living body in the cell culture device 86. The cells are cultured and matured into a usable state, and used for drug tests in the drug test unit 92, etc., and the living cells are cultured and used in the user-side equipment 90 for drug evaluation and the cell culture device 86. By the data server 94 that continuously records and centrally manages the measurement data of the cell culture device 86 cultured in the manufacturer's factory 82, the transport vehicle 88, and the user's equipment 90 until it matures to a possible state. It is composed.

The maker factory 82 includes a cell culture unit 84 including the cell culture device 86, and a first controller 96 for controlling the culture of living cells in the cell culture device 86 of the cell culture unit 84, and further manufactures the cell culture device 86. It is preferable to include equipment 98.
The manufacturing facility 98 is installed in the factory to manufacture a plurality of (preferably a large amount) cell culture devices 86, and one or more cell culture units 84 having the plurality of cell culture devices 86.
It is preferable that the maker factory 82 mass-produces the cell culture device 86 and performs mass-culture. Therefore, it is preferable that the maker factory 82 also manufactures a large amount of the cell culture unit 84 having a plurality of cell culture devices 86 for mass culture of the cell culture device 86.

The first controller 96 is the living cells of the first condition controller 100 and the cell culture device 86, which control the culture conditions of the living cells to be seeded and initially cultured in the cell culture device 86 to the first culture conditions (initial culture conditions). It has a first measurement unit 102 for measuring a culture state, and a first memory unit 104 for collecting first measurement data measured by the first measurement unit 102.
The first controller 96 is preferably a mass-produced culture controller that controls the culture state of the cell culture device 86 that is mass-produced and mass-cultured in the manufacturer's factory 82.
The first controller 96 is composed of a personal computer (PC) computer or the like, and may further include a display, a keyboard, a mouse, or the like.

The first condition controller 100 is a culture condition (for example, pressure, temperature, and / or a solution of a culture solution) of a plurality of (preferably a large amount) cell culture device 86 for culturing a plurality of (preferably a large amount) living cells. The amount, etc.) is controlled to the first culture condition set in advance or obtained from the first measurement data by the first controller 96. Specifically, the first condition controller 100 controls a gas pump, a heater, a liquid pump, and the like for controlling the environment in the cell culture unit 84. It is preferable that the first condition controller 100 controls the culture conditions of the cell culture device 86 for each cell culture unit 84 (that is, the plurality of cell culture devices 86 in the cell culture unit 84 are uniformly controlled at the same time). It may be controlled for each individual cell culture device 86.

The first measurement unit 102 is shown as one block in FIG. 3, but as shown in FIG. 2, in one cell culture unit 84, individual living cells are used for each individual cell culture device 86. It is equipped with a sensor that electrically measures the culture state of the cell, a light source that performs optical measurement, a sensor, and the like. It is preferable that one or more measurements can be performed for both electrical measurement and optical measurement, and measurement capable of constructing a multi-validation method is preferable.
Examples of the electrical measurement include measurement of electrical resistance such as transepithelial electrical resistance (TEER) of living cells, impedance, dielectric constant, and capacitance.
Examples of the optical measurement include measurement of cell shape by ordinary visible light, optical interference tomography using infrared light, and measurement of particles injected into the flow path of the cell culture device 86. The particles used are, for example, RBC (Red Blood Cell) (6-8 μm) imaging (405 nm light absorption imaging), BB (Bright Blue) polystyrene beads (1.75 μm) imaging (420 nm fluorescence imaging), and FITC (Fluorescein). Examples thereof include dextran (0.07 μm) imaging (540 nm fluorescence imaging) of isothiocyanate) labels, PC (Polychromatic) Red blood cell beads (0.50 μm) imaging (600 nm fluorescence imaging), and the like.
Further, the first measurement unit 102 may include a sensor or the like for measuring the culture conditions (for example, pressure, temperature, and / or the amount of the culture solution) in the cell culture unit 84.

The first memory unit 104 continuously records and collects the first measurement data indicating the culture state of the cell culture unit 84, including the electrical measurement data measured by the measurement unit 102 and the optical measurement data. , The collected first measurement data is transmitted to the data server 94.
The first measurement data collected by the first memory unit 104 may include measurement data of the culture conditions (for example, pressure, temperature, and / or the amount of the culture solution) in the cell culture unit 84. good.

Here, the first controller 96 obtains the culture conditions of the cell culture device 86 in the maker factory 82 from the first measurement data, and according to the obtained culture conditions, the first condition controller 100 and the culture conditions are set in the cell culture unit 84. It is preferable to control a plurality of cell culture devices 86.
The first controller 96 receives the culture conditions of the cell culture device 86 in the maker factory 82 obtained from the first measurement data in the data server 94 from the data server 94, and the first condition controller according to the received culture conditions. The 100 may control the culture conditions to a plurality of cell culture devices 86 in the cell culture unit 84.
At the maker factory 82, it is preferable to carry out a shipping inspection as to whether or not the culture state of the living cells in the plurality of cell culture devices 86 in the cell culture unit 84 is appropriate. A cell culture unit 84 including a plurality of cell culture devices 86 culturing living cells in an appropriate culture state that has passed the shipping inspection is transported to the user-side equipment 90.
Although not shown, it is preferable that the maker factory 82 further has a freezing unit such as a refrigerator that freezes the living cells and the cell culture device 86 to bring the living cells and the cell culture device 86 into a low temperature state. .. The first condition controller 100 may control a freezing unit such as a refrigerator to control the temperature of the living cells and the cell culture device 86 to freeze and control the temperature to a low temperature state including freezing.

The transport vehicle 88 is a cell culture unit 84 including a cell culture device 86 that is culturing a living cell having a proper culture state that has passed the shipping inspection, or a living cell that is maintained or controlled at a low temperature state including freezing. And the cell culture device 86 is transported from the manufacturer's factory 82 to the user's equipment 90.
The transport vehicle 88 includes a cell culture device 86 for culturing appropriate living cells, a living cell maintained at a low temperature, a cell culture unit 84 containing the cell culture device 86, and a cell culture of the cell culture unit 84. It includes a second controller 106 that controls the culture of living cells in the device 86 or the low temperature state of living cells.
It is preferable that the transport vehicle 88 further has a refrigerating unit such as a refrigerator that freezes the living cells and the cell culture device 86 to bring the living cells and the cell culture device 86 into a low temperature state including freezing. ..
Further, the transport vehicle 88 further has a thawing unit such as a heater for thawing the living cells in a low temperature state including freezing and the cell culture device 86 to return the living cells and the cell culture device 86 to the culturing state. Is preferable.
Since the cell culture device 86 during culture in the cell culture unit 84 transported by the transport vehicle 88 or in a low temperature state is used by the user for drug testing, drug evaluation, etc., a limited number of cell cultures are performed. Device 86. In the example shown in FIG. 2, the cell culture device 86 being cultured or in a low temperature state in the cell culture unit 84 is shown as one, but it may contain one or more cell culture devices 86. Of course. Further, in the example shown in FIG. 3, the number of cell culture devices 86 during culture or in a low temperature state in the cell culture unit 84 is the same in the maker factory 82 and the transport vehicle 88, but the maker factory 82. Of course, the quantity is large in the transport vehicle 88, and the quantity is limited in the transport vehicle 88.

The second controller 106 controls the culture conditions of the living cells being cultured in the cell culture device 86 to the second culture conditions, or the control conditions or states of the living cells maintained in the low temperature state, that is, the low temperature state. A second memory for collecting the second measurement data measured by the condition controller 108, the second measurement unit 110 for measuring the culture state or state of the living cells of the cell culture device 86, that is, the low temperature state, and the second measurement unit 110. It has a unit 112.
Since the second controller 106 controls the culture state or the low temperature state of the cell culture device 86 in a limited quantity during transportation by the transport vehicle, it is preferable to use a simple culture controller. The second controller 106 may have the same configuration as the first controller 96.

The second condition controller 108 sets the culture conditions of the plurality of cell culture devices 86 for culturing the plurality of living cells, or the maintenance control conditions in a low temperature state (for example, pressure, temperature, and / or the amount of the culture solution). , Which is set in advance, or is obtained from the first measurement data and the second measurement data in the data server 94, and is controlled by the second culture condition or the maintenance control condition which is transmitted to the second controller 106. Like the first condition controller 100, the second condition controller 108 controls a gas pump, a heater, a refrigerating unit such as a refrigerator, a liquid pump, and the like for controlling the environment in the cell culture unit 84. .. The second condition controller 108 preferably controls the culture conditions of the cell culture device 86 for each cell culture unit 84, but may be controlled for each individual cell culture device 86.
The second condition controller 108 may control a unit such as a refrigerator to control the temperature of the living cells and the cell culture device 86 to freeze and control the temperature to a low temperature state including freezing.
Further, the second condition controller 108 controls a thawing unit such as a heater to control the temperature of the living cells in a low temperature state including freezing and the cell culture device 86 so as to thaw and return to the culture state. You can do it.

The second measurement unit 110, like the first measurement unit 102, is shown as one block in FIG. 3, but as shown in FIG. 2, in one cell culture unit 84, individual cells. Each culture device 86 is provided with a sensor for electrically measuring the culture state or low temperature state of individual living cells, a light source for optical measurement, a sensor, and the like. As with the first measurement unit 102, it is preferable that the second measurement unit 110 can perform one or more measurements, both as an electrical measurement and as an optical measurement, and a multi-validation method is constructed. Possible measurements are preferred.
Further, the second measurement unit 110 may include a sensor or the like for measuring the culture conditions or maintenance control conditions (for example, pressure, temperature, and / or the amount of the culture solution) in the cell culture unit 84. ..

The second memory unit 112 continuously transmits the second measurement data indicating the culture state or the low temperature state of the cell culture unit 84, including the electrical measurement data measured by the second measurement unit 110 and the optical measurement data. The second measurement data collected is transmitted to the data server 94.
The second measurement data collected by the second memory unit 112 includes measurement data of the culture conditions in the cell culture unit 84 or the maintenance control conditions (for example, pressure, temperature, and / or the amount of the culture solution). May include.
Here, the second controller 106 sets the second culture conditions of the cell culture device 86 in the transport vehicle 88 obtained from the first measurement data continuously recorded in the data server 94 and the second measurement data in the data server 94. The second condition controller 108 may control the plurality of cell culture devices 86 in the cell culture unit 84 according to the second culture condition received from the cell culture unit 84.

The user-side equipment 90 finally cultivates the living cells by the cell culture device 86 in the cell culture unit 84 transported by the transport vehicle 88, matures the living cells to a state in which they can be used for drug testing, etc., and matures the drug test unit 92. The matured living cells are used for drug testing and the like to evaluate the drug.
When the user-side equipment 90 receives the living cells in a low temperature state including freezing and the cell culture device 86 from the transport vehicle 88, the living cells in the low temperature state and the cell culture device 86 are thawed. It is preferable to have a thawing unit such as a heater that returns the living cells and the cell culture device 86 to the culture state.
The user-side equipment 90 includes a cell culture unit 84 including a cell culture device 86 for culturing living cells and maturing them to a usable state, and cells of the cell culture unit 84 until the living cells mature to a usable state. The third controller 114 that controls the final culture of the living cells in the culture device 86 and the living cells that have matured to a usable state are taken out from the cell culture device 86, and the mature living cells are subjected to a drug test or the like to evaluate the drug. Includes drug test unit 92.
In the equipment 90 on the user side, the cell culture device 86 being cultured is a limited number of cell culture devices 86 because the user uses them for a drug test or the like. Therefore, in the equipment 90 on the user side, the relationship between the number of cell culture devices 86 in culture in the cell culture unit 84 in FIGS. 2 and 3 is the same as in the case of the transport vehicle 88.

The third controller 114 measures the culture state of the living cells of the third condition controller 116 and the cell culture device 86, which controls the culture conditions of the living cells being cultured in the cell culture device 86 to the third culture conditions (final culture conditions). It has a third measurement unit 118 and a third memory unit 120 for collecting the third measurement data measured by the third measurement unit 118.
When the living cells are in a low temperature state including freezing, the third condition controller 114 sets a thawing unit such as a heater before controlling the culture conditions of the living cells to the third culture conditions (final culture conditions). The temperature of the living cells in a low temperature state including freezing and the cell culture device 86 may be controlled to be thawed and returned to the culture state.
The third controller 114 is preferably a precision culture controller because it precisely controls the culture state of the limited number of cell culture devices 86 in the cell culture unit 84 until it matures into a usable state. Although the accuracy of the third controller 114 is different, the controller configuration may be the same as that of the first controller 96.

The third condition controller 116 presets or data the culture conditions (for example, pressure, temperature, and / or the amount of the culture solution) of the plurality of cell culture devices 86 for culturing the plurality of living cells. The server 94 controls the third culture conditions obtained from the first measurement data, the second measurement data, and the third measurement data and transmitted to the third controller 114.
Similar to the first condition controller 100, the third condition controller 116 controls a gas pump, a heater, a liquid pump, and the like for controlling the environment in the cell culture unit 84. The third condition controller 116 preferably controls the culture conditions of the cell culture device 86 for each cell culture unit 84, but may be controlled for each individual cell culture device 86.

The third measurement unit 118, like the first measurement unit 102, is shown as one block in FIG. 3, but as shown in FIG. 2, in one cell culture unit 84, individual cells. Each culture device 86 is provided with a sensor for electrically measuring the culture state of individual living cells, a light source for optically measuring, a sensor, and the like. As with the first measurement unit 102, it is preferable that the third measurement unit 118 can perform one or more measurements both as an electrical measurement and as an optical measurement, and a multi-validation method is constructed. Possible measurements are preferred.
Further, the third measurement unit 118 may include a sensor or the like for measuring the culture conditions (for example, pressure, temperature, and / or the amount of the culture solution) in the cell culture unit 84.

The third memory unit 120 continuously records the third measurement data indicating the culture state of the cell culture unit 84, including the electrical measurement data measured by the third measurement unit 118 and the optical measurement data. Collect and transmit the collected third measurement data to the data server 94.
The third measurement data collected by the third memory unit 120 may include measurement data of the culture conditions (for example, pressure, temperature, and / or the amount of the culture solution) in the cell culture unit 84. good.
Here, the third controller 114 is the first measurement data, the second measurement data, and the cell culture device 86 in the user-side equipment 90 obtained from the third measurement data continuously recorded in the data server 94. The three culture conditions may be received from the data server 94, and the third condition controller 116 may control the plurality of cell culture devices 86 in the cell culture unit 84 according to the received third culture conditions.

The data server 94 receives the first measurement data collected at the manufacturer's factory 82 from the first controller 96, receives the second measurement data collected by the transport vehicle 88 from the second controller 106, and receives the second measurement data collected by the transport vehicle 88 from the third controller 114. The third measurement data collected by the user-side equipment 90 is received, and the first measurement data, the second measurement data, and the third measurement data indicating the culture state or the low temperature state of the living cells are transmitted to the cell culture device 86. The cell culture device 86 for culturing the living cells is managed by continuously recording and centrally managing the living cells until the mature living cells are used until they are ready for use.
Further, the data server 94 determines from the first measurement data, the second measurement data, and the third measurement data that are continuously recorded and centrally managed, that the living cells have matured to a usable state. Then, the user in the user-side equipment 90 can be notified of the usage timing.

The data server 94 may be installed in the manufacturer's factory 82, installed in the user's equipment 90, or may be installed at another point that is neither of them. In addition, a data server 94 is provided on the cloud, and all measurement data (first to third measurement data) of living cells in all cultures from the initial culture to the final culture are stored in the cloud from the manufacturer's factory 82. However, it may be possible to access from the equipment 90 on the user side so that all the measurement data can be viewed.
In addition, in order to provide users with living cells that are well-cultured and mature better, all measurement data (first to third measurement data) of all-cultured living cells from the initial culture to the final culture are centralized. In order to manage the data, it is preferable to install it in the manufacturer's factory 82, but it is preferable to allow the user to access the data server 94 so that all the centrally managed measurement data can be viewed.

Here, the first culture condition (initial culture condition), the second culture condition, or the maintenance control condition in a low temperature state, and the third culture condition by the first condition controller 100, the second condition controller 108, and the third condition controller 116, respectively. The control of the cell culture device 86 to (final culture condition) may be performed automatically, or at least one of the first culture condition, the second culture condition, the low temperature maintenance control condition, and the third culture condition. May be displayed manually on a display or the like. In addition, the optimum measurement conditions for the cell culture device 86 in the manufacturer's factory 82, the transport vehicle 88, and the user's equipment 90 are obtained from at least one of the first to third measurement data, and the measurement conditions are obtained respectively. The measurement of the cell culture device 86 in the manufacturer's factory 82, the transport vehicle 88, and the user-side equipment 90 may be controlled automatically or manually.
As described above, the present invention further uses a cell culture device that is used as an organ model or the like as a cell culture device to be managed and that can simultaneously perform optical measurement and electrical measurement. It is also an object of the present invention to provide a method for managing a cell culture device and a management system for the cell culture device.

Below, the cell culture device management method of the present invention and the cell culture device used as a management target in the management system are preferably channel devices.
Hereinafter, the channel device used as the cell culture device in the present invention will be described based on the preferred embodiment shown in the attached drawings.

<Flower path device>
FIG. 4 is a schematic perspective view showing the overall structure of the management method of the cell culture device of the present invention and an example of the flow path device used as the cell culture device in the management system. FIG. 5 is a schematic exploded perspective view showing the overall structure of the flow path device shown in FIG.
The illustrated example is merely an embodiment of the present invention, and the flow path device of the present invention is not limited to this embodiment.
As shown in FIGS. 4 and 5, the flow path device 10 has a flow path unit 16 composed of a first flow path member 12 and a second flow path member 14 laminated in the thickness direction. There is. In the following description, the upper side (first flow path member 12 side) in FIGS. 4 and 5 is "upper", and the lower side (second flow path member 14 side) in FIGS. 4 and 5 is "lower". ], Also called.

The material of the first flow path member 12 and the second flow path member 14 is preferably a transparent material having elasticity such as PDMS (polydimethylsiloxane) as an example.
In addition to PDMS, the materials constituting the first flow path member 12 and the second flow path member 14 include epoxy-based resin, urethane-based resin, styrene-based thermoplastic elastomer, olefin-based thermoplastic elastomer, and acrylic-based heat. Examples thereof include thermoplastic elastomers and polymer materials (resin materials, polymers) such as polyvinyl alcohol.

Here, the rubber hardness of the first flow path member 12 and the second flow path member 14 is preferably 20 to 80 degrees, more preferably 50 to 70 degrees.
"Rubber hardness" can be evaluated by measuring the hardness of the first flow path member 12 and the second flow path member 14 with a type A durometer by the method specified in JIS K6253: 2012.

As shown in FIG. 5, the lower surface of the first flow path member 12, that is, the concave portion 20 defining the first flow path (first micro flow path) 18 on the surface 12A facing the second flow path member 14. Is formed. The recess 20 has an inlet 20A, an outlet 20B, and a flow path portion 20C communicating the inlet 20A and the outlet 20B. Further, the first flow path member 12 is formed with through holes 22A and 22B that penetrate the first flow path member 12 in the thickness direction and have a lower end communicating with the inflow port 20A and the outflow port 20B, respectively. .. The width and depth of the first flow path 18 (recessed portion 20) may be appropriately set according to the size of the flow path device 10, the application, and the like.
Further, as will be described in detail later, a first transparent electrode 60 is formed on the entire surface including the recess 20 (first flow path 18) on the lower surface of the first flow path member 12 (excluding through holes).

On the other hand, the second flow path member 14 is formed with a through hole 26 that penetrates the second flow path member 14 in the thickness direction and defines the second flow path (second micro flow path) 24. .. The second flow path 24 is in contact with the lower surface of the second flow path member 14 (opposite to the first flow path member 12), and a holding plate 38B described later is provided to close the lower surface side of the through hole 26. Formed by. The width and depth of the second flow path 24 (through hole 26) may be appropriately set according to the size of the flow path device 10, the application, and the like.
The through hole 26 has an inlet 26A and an outlet 26B, and a flow path portion 26C communicating the inlet 26A and the outlet 26B.

Here, the inflow port 26A and the outflow port 26B of the second flow path member 14 are provided at positions that do not overlap with the inflow port 20A and the outflow port 20B of the first flow path member 12 in a plan view. On the other hand, the flow path portion 26C of the second flow path member 14 is provided at a position where it overlaps with the flow path portion 20C of the first flow path member 12 in a plan view.
In other words, the plan view indicates a view of the flow path device 10 of the present invention when viewed from a direction orthogonal to the main surface of the first flow path member 12. Further, the main surface indicates the maximum surface of a sheet-like material, a plate-like material, a film-like material, or the like.

Further, the first flow path member 12 has a through hole 28A that penetrates the first flow path member 12 in the thickness direction and has a lower end communicating with the inflow port 26A and the outflow port 26B of the second flow path member 14. 28B is formed.
Further, a recess 29 is provided on the outer peripheral surface (side surface) of the flow path unit 16 (first flow path member 12 and second flow path member 14) at a position where a spacer 46 described later is arranged.

<Porous membrane>
A porous membrane 30 is arranged between the facing surfaces 12A and 14A of the first flow path member 12 and the second flow path member 14. The porous membrane 30 is made of a polymer material as an example, and is particularly preferably made of a hydrophobic polymer material that is soluble in a hydrophobic organic solvent. The hydrophobic organic solvent is a liquid having a solubility in water at 25 ° C. of 10 (g / 100 g water) or less.

Polymer materials include polystyrene, polyacrylate, polymethacrylate, polyacrylamide, polymethacrylicamide, polyvinyl chloride, polyvinylidene chloride, vinylidene fluoride, polyhexafluoropropene, polyvinylether, polyvinylcarbazole, vinylacetate, and polytetra. Fluoroethylene, polyester (eg, polyethylene terephthalate, polyethylene naphthalate, polyethylene succinate, polybutylene succinate, polylactic acid, and poly-3-hydroxybutyrate, etc.), polylactone (eg, polycaprolactone, etc.), polyamide, and polyimide. (Eg, nylon, polyamic acid, etc.), polyurethane, polyurea, polybutadiene, polycarbonate, polyaromatics, polysulfone, polyethersulfone, polysiloxane derivatives, and cellulose acylates (eg, triacetyl cellulose, cellulose acetate propio). Nate, cellulose acetate butyrate, etc.) and the like.

These polymer materials may be homopolymers, copolymers, polymer blends, polymer alloys and the like, if necessary, from the viewpoints of solubility in solvents, optical properties, electrical properties, film strength, elasticity and the like. May be good. In addition, these polymer materials may be used alone or in combination of two or more. The material of the porous membrane 30 is not limited to the polymer material, and various materials can be selected from the viewpoint of cell adhesion and the like.

The upper surface 30A and the lower surface 30B of the porous membrane 30 have a size that substantially covers the flow path portion 20C and the flow path portion 26C of the first flow path 18 and the second flow path 24.
The porous membrane 30 is provided so as to cover the first flow path 18 and the second flow path 24. As a result, the porous membrane 30 separates the first flow path 18 and the second flow path 24.

Specifically, the upper surface 30A of the porous membrane 30, that is, the main surface facing the first flow path member 12, defines the first flow path 18 together with the recess 20 of the first flow path member 12.
Further, the lower surface 30B of the porous membrane 30, that is, the main surface facing the second flow path member 14, defines the second flow path 24 together with the through hole 26 of the second flow path member 14.

As shown in FIGS. 6 and 7, the porous membrane 30 is formed with a plurality of through holes 32 penetrating the porous membrane 30 in the thickness direction, and the upper surface 30A and the lower surface of the porous membrane 30 are formed. 30B is provided with an opening 32A of the through hole 32, respectively. Further, as shown in FIG. 6, the opening 32A has a circular shape in a plan view. The openings 32A are provided apart from each other, and a flat portion 34 extends between the adjacent openings 32A. The opening 32A is not limited to a circular shape, but may be a polygonal shape, an elliptical shape, an indefinite shape, or the like.

The plurality of openings 32A are regularly arranged. In the present invention, as an example, the openings 32A are arranged in a honeycomb shape.
The honeycomb-like arrangement is an arrangement in which a parallel hexagon (preferably a regular hexagon) or a shape close to the parallel hexagon is used as a unit, and the center of the opening 32A is located at the apex of these figures and the intersection of the diagonal lines. Here, the "center of the opening" means the center of the opening 32A in a plan view.

The arrangement of the openings 32A is not limited to the honeycomb shape, and may be a grid shape or a face-centered lattice shape. The grid-like arrangement is an arrangement in which a parallelogram (including a square, a rectangle, and a rhombus, preferably a square) or a shape close to the parallelogram is used as a unit, and the center of the opening is located at the apex of these figures. The face-centered lattice arrangement is a unit of a parallelogram (including a square, a rectangle, and a rhombus, preferably a square) or a shape close to the parallelogram, and the center of the opening is at the apex of these figures and the intersection of the diagonal lines. It is a positioned arrangement.
The arrangement of the openings 32A is preferably honeycomb-shaped in that the aperture ratio shown below can be easily achieved.

In the porous membrane 30, the coefficient of variation of the opening diameter of the opening 32A is preferably 10% or less, and the smaller it is, the more preferable. The smaller the coefficient of variation of the opening diameter, the more uniformly the red blood cells and the like can pass through the plurality of through holes 32 of the porous membrane 30.
Further, the aperture ratio (porosity) of the porous membrane 30 is preferably 50% or more. By setting the aperture ratio to 50% or more, it is possible to suppress the inhibition of the movement of erythrocytes and the like by the porous membrane 30. If the porosity is too large, the strength of the porous membrane 30 is insufficient with respect to the required strength, so the porosity is preferably 95% or less.
Here, the "aperture ratio" means that the unit volume of the porous membrane 30 is V1 when it is assumed that the main surface of the porous membrane 30 is smooth, that is, when it is assumed that there is no opening 32A. When the sum of the volumes of the through hole 32 and the communication hole 36 provided around the area is V2 and the units of V1 and V2 are the same, the ratio of V2 to V1 is shown as a percentage.

As shown in FIG. 7, the through hole 32 of the porous membrane 30 has a spherical shape in which the upper end and the lower end of the sphere are cut off. Further, the through holes 32 adjacent to each other are communicated with each other by the communication holes 36 inside the porous membrane 30.

It is preferable that one through hole 32 communicates with all the adjacent through holes 32. When the openings 32A of the plurality of through holes 32 are arranged in a honeycomb shape as in the present invention, one through hole 32 communicates with six adjacent through holes 32 by six communication holes 36, respectively. Is preferable.
The through hole 32 may have a barrel shape, a cylindrical shape, a polygonal column shape, or the like, and the communication hole 36 may be a tubular void connecting adjacent through holes 32 to each other.

Examples of the method for producing the porous film 30 in which the through hole 32 is formed include a nanoprint method, a dew condensation method, an etching method, a sandblast method, and a press molding method.
The nanoprint method is a method of producing a through hole 32 by pouring a material constituting the porous film 30 into a mold having an uneven shape or pressing the mold against the material constituting the porous film 30. be. The dew condensation method is a method in which the surface of a material constituting the porous film 30 is dewed to form a through hole 32 using a water droplet as a mold.

The dew condensation method can reduce the film thickness of the porous film 30 as compared with other methods, increase the porosity and the opening ratio of the opening 32A, and communicate with the inside of the porous film 30. It is possible to provide a hole 36. Therefore, in the present invention, the porous film 30 is manufactured by the dew condensation method.
Details of the dew condensation method are described in, for example, Japanese Patent No. 4945281, Japanese Patent No. 5422230, Japanese Patent Application Laid-Open No. 2011-74140, Japanese Patent No. 5405374, and the like.

In the flow path device 10 of the present invention, the porous membrane is not limited to those having such through holes, and is known as a porous membrane such as a non-woven fabric and a membrane in which voids are formed three-dimensionally. Various (porous materials) are available.

In the flow path device 10 of the present invention, the region in which cells on at least the main surface of the porous membrane 30 are seeded is fibronectin, collagen (for example, type I collagen, type IV collagen, type V collagen, etc.), laminin, etc. , Vitronectin, gelatin, pearlcan, nidogen, proteoglycan, osteopontin, tenascin, nephronectin, basement membrane matrix, and collagen is preferably coated with at least one selected from the group.
By coating the porous membrane 30 with these materials, it is possible to enhance the adhesion of cells.

Further, when the flow path device 10 of the present invention is used as an organ simulation device (organ model) or the like, a cell layer constituting the organ to be simulated may be provided on the main surface of the porous membrane 30.
By having the cell layer on the main surface of the porous membrane 30, it is possible to make the inside of the first flow path 18 and the inside of the second flow path 24 close to the inside of the organ to be simulated.
That is, the flow path device of the present invention may be a cell culture device for culturing cells, or may perform measurements for evaluating cells having a cell layer and / or a drug solution. It may be a flow path device for measurement.

Examples of the cells provided on the main surface of the porous membrane 30 include parenchymal cells (eg, hepatic parenchymal cells, pancreatic parenchymal cells, etc.), stromal cells (eg, peridermal cells), and muscle cells (eg, smooth muscle cells). , Myocardial cells, skeletal muscle cells, etc.), fibroblasts, nerve cells, endothelial cells (eg, vascular endothelial cells, lymphatic endothelial cells, etc.), epithelial cells (eg, alveolar epithelial cells, oral epithelial cells, bile ducts, etc.) Epithelial cells, intestinal epithelial cells, pancreatic duct epithelial cells, renal epithelial cells, tubule epithelial cells, and placenta epithelial cells, etc., and cells that differentiate into any of these (eg, precursor cells, mesenchymal stem cells, and pluripotent). Sexual stem cells, etc.) are exemplified.

Examples of pluripotent stem cells include embryonic stem cells (ES cells), artificial pluripotent stem cells (iPS cells), embryonic germ cells (EG cells), and embryos. Embryonal carcinoma cells (EC cells), multipotent adult progenitor cells (MAP cells), adult pluripotent stem cells (APS cells), and Muse cells (multi- lineage differentiating stress enduring cell); etc.

As the cells, cells having a gene mutation and / or cells derived from a patient may be used for the purpose of reproducing the pathological condition.

The cell layer provided on the main surface of the porous membrane 30 may be provided with the same cell layer on both sides, or may be provided with different cell layers one by one.
As an example, by providing a vascular endothelial cell layer on one surface of the porous membrane 30 and providing a smooth muscle cell layer on the other surface of the porous membrane 30, a flow path device 10 serving as a blood vessel wall model can be obtained.

<Holding plate>
As shown in FIGS. 4 and 5, the flow path device 10 has a holding plate 38A on the upper side (first flow path member 12 side) as a holding member for holding the flow path unit 16 in a compressed state in the thickness direction. It has a holding plate 38B on the lower side (second flow path member 14 side).
The holding plate 38A and the holding plate 38B are separated from the flow path unit 16 at both ends of the flow path unit 16 in the thickness direction, that is, on the upper side of the first flow path member 12 and on the lower side of the second flow path member 14. It is provided and has a size that covers the entire upper surface of the first flow path member 12 and the entire lower surface of the second flow path member 14.

It is preferable that both the holding plate 38A and the holding plate 38B are made of a hard and transparent polymer material.
Therefore, examples of the constituent materials of the holding plate 38A and the holding plate 38B include cycloolefin polymers, acrylics, polycarbonates, polystyrenes, polyethylene terephthalates, and the like. Further, the holding plate 38A and the holding plate 38B are preferably harder than the above-mentioned first flow path member 12 and the second flow path member 14, and further preferably have a rubber hardness of 80 degrees or more, 90 degrees. It is more preferable that the degree is higher than the degree.

As shown in FIG. 5, a plurality of (8 in the present invention) bolt holes 40 penetrating in the thickness direction are formed at positions of the holding plate 38A and the holding plate 38B corresponding to each other. Further, the holding plate 38A provided on the upper side of the first flow path member 12 has through holes 42A, 42B, which communicate with the through holes 22A, 22B, 28A, and 28B of the first flow path member 12, respectively. 44A and 44B are formed.

A tube (not shown) is connected to the through holes 42A, 42B, 44A, and 44B, respectively, and a solution, a cell suspension, or the like is passed through the tube to the first flow path 18 and the second flow path 24, respectively. It flows in, and the solution, cell suspension, and the like flow out from the first flow path 18 and the second flow path 24.

On the outside of the recess 29 of the flow path unit 16 between the pair of holding plates 38, a plurality of spacers 46 (eight in the illustrated example) that define the spacing between the holding plates 38 are provided. The spacer 46 is a cylindrical member having an inner diameter substantially the same as the inner diameter of the bolt hole 40, and is arranged at a position corresponding to the bolt hole 40.

As shown in FIGS. 8 and 9, the pair of holding plates 38 are joined together by a bolt hole 40 and a plurality of bolts 50 inserted through the spacer 46 and fixed with nuts 48. At this time, the first flow path member 12 and the second flow path member 14 are compressed and held by the pair of holding plates 38 with the porous film 30 sandwiched between them.

<Transparent electrode>
In the flow path device 10 of the present invention, the second transparent electrode 62 is arranged on the holding plate 38B that abuts on the second flow path 24 so as to cover the entire surface of the contact surface with the second flow path member 14. As described above, the second flow path 24 is formed by the holding plate 38B abutting on the lower surface of the second flow path member 14 to close the lower surface of the through hole 26. Therefore, the lower surface side of the second flow path 24 is the second transparent electrode 62, that is, the second transparent electrode 62 is in contact with the second transparent electrode 62.
Further, as described above, the first flow path member 12 has a recess 20 defining the first flow path 18 on the lower surface thereof. The first flow path member 12 has a first transparent electrode 60 on the lower surface thereof, covering the entire surface including the recess 20. That is, the first transparent electrode 60 is in contact with the first flow path 18.
In the flow path device 10, the first transparent electrode 60 in contact with the first flow path 18 and the second transparent electrode 62 in contact with the second flow path 24 form a pair of transparent electrodes (electrode pair). There is.

The flow path device 10 of the present invention has such a first transparent electrode 60 and a second transparent electrode 62, which makes it possible to perform optical measurement and electrical measurement at the same time.

As mentioned above, since the human body is complicated, one kind of measurement is not enough to accurately evaluate cells and the like using a flow path device, and multiple kinds of measurements are performed at the same time, so-called multi. It is preferable to perform validation.
As an example of the measurement using the flow path device, as conceptually shown in FIG. 10, a large molecule with a fluorescent label is flowed through the first flow path 18 or the second flow path 24 and excited from the light source 70. An example is an evaluation of the permeability of a film, which is obtained by irradiating light and measuring fluorescence with an optical sensor 72.
Further, a liquid is flowed through the first flow path 18 and / or the second flow path 24, and the cell layer or the like formed on the porous membrane 30 is imaged with an image pickup camera 74 (transmission electron microscope, fluorescence microscope, etc.) or the like. By (visualization), the structure of the cell layer or the like is also evaluated.
Further, by connecting an electric sensor 76 to the first transparent electrode 60 and the second transparent electrode 62 and measuring electrical characteristics such as potential difference, resistance, and short circuit current, fluid, ions, etc. that have passed through the membrane can be measured. It is also evaluated for the transport function and the formation of barriers.

However, in the conventional flow path device, when an electrode is formed corresponding to the first flow path and the second flow path in order to measure the electrical characteristics of the cell layer formed on the porous membrane, the electrode is usually formed. Since the electrode is made of metal, the electrode acts as a light-shielding member, and it is not possible to properly perform optical measurement and evaluation such as measurement of fluorescence and imaging of a cell layer.
Therefore, in the conventional flow path device, the electrical measurement and the optical measurement cannot be performed at the same time.

On the other hand, in the flow path device 10 of the present invention, a pair of first transparent electrodes 60 and second transparent electrodes 62 are provided so as to sandwich the first flow path 18 and the second flow path 24.
Since the flow path device 10 of the present invention is a transparent electrode even if a pair of electrodes is provided so as to sandwich the first flow path 18 and the second flow path 24, the electrodes are fluorescent and optical such as imaging of a cell layer. It does not interfere with the standard measurement method. Therefore, according to the flow path device 10 of the present invention, the measurement of fluorescence using the light source 70 and the optical sensor 72 as shown in FIG. 10, the imaging of the cell layer or the like using the image pickup camera 74 or the like, and the electric sensor 76 are performed. It is possible to perform optical measurement and electrical measurement at the same time, such as measurement of the resistance to be used.
Further, since the transparent electrode is used, even if the electrode is a planar electrode, it does not interfere with the optical measurement. Therefore, stable electrical measurement can be performed with electrodes having a sufficient area. Furthermore, it is also possible to extract the electrical properties of the surface of the cell layer formed on the porous membrane 30 as an electrical signal.

In the flow path device 10 of the present invention, the first transparent electrode 60 and the second transparent electrode 62 are conductive and transparent electrodes.
In the present invention, having conductivity means that the sheet resistance value is 0.1 to 10,000 Ω / □ (Ω / sq (Ohms per Square)), and includes a layer generally called an electric resistance layer. When a general-purpose power supply is used, it is preferable that the sheet resistance value is low, specifically, 300Ω / □ or less is preferable, 200Ω / □ or less is more preferable, and 100Ω / □ or less is further preferable. In the present invention, the sheet resistance value (surface resistivity) may be measured in accordance with JIS (Japanese Industrial Standards) K 7194.
Further, in the present invention, being transparent means that the transmittance is 60 to 99.99%. The transmittance of the transparent electrode is preferably 75% or more, more preferably 80% or more, still more preferably 90% or more. In the present invention, the total light transmittance [%] may be measured in accordance with JIS K 7631-1.

In the flow path device 10 of the present invention, the materials of the first transparent electrode 60 and the second transparent electrode 62 are not limited, and are used as transparent electrodes in various electronic devices (electronic devices, electronic elements). However, various types are available.
Specifically, the materials contained in the first transparent electrode 60 and the second transparent electrode 62 include metal oxides (Indium Tin Oxide: ITO, etc.), carbon nanotubes (Carbon Nanotube: CNT, and Carbon Nanobud: CNB, etc.). ), Graphene, polymer conductors (polyacetylene, polypyrrole, polyphenol, polyaniline, and PEDOT / PSS (polyethylenedioxythiophene / polystyrene sulfonic acid), etc.), metal nanowires (silver nanowires, copper nanowires, etc.), and , Metal mesh (silver mesh, copper mesh, etc.) and the like. The transparent electrode of the metal mesh is preferably formed by dispersing conductive fine particles such as silver and copper in a matrix, rather than being formed only of metal, from the viewpoint of heat shrinkage.

The transparent electrode made of these materials may be formed by a known method depending on the material.
For example, in the case of a transparent electrode containing carbon nanotubes, a paint made by dispersing carbon nanotubes is prepared, and the prepared paint is applied to a portion forming the transparent electrode such as the lower surface of the first flow path member 12 and dried. Then, a transparent electrode may be formed by a coating method in which heat treatment is further performed if necessary.
In the case of a transparent electrode containing carbon nanobuds, direct dry printing described on page 1012 of SID (Society for Information Display) 2015 DIGEST is also performed on a portion forming the transparent electrode such as the lower surface of the first flow path member 12. A transparent electrode may be formed by the (DDP: Direct Dry Printing) method.
Further, in the case of a transparent electrode containing silver nanowires, the portion forming the transparent electrode, such as the lower surface of the first flow path member 12, is described in Example 1 of US Patent Application Publication No. 2013/0341074. A transparent electrode may be formed by such a method.

Here, in the flow path device 10 of the present invention, the first flow path member 12 on which the first transparent electrode 60 is formed and the holding plate 38B on which the second transparent electrode 62 is formed are both made of a polymer material. It is preferable to be done.
Considering this point, the materials constituting the first transparent electrode 60 and the second transparent electrode 62 include a vapor deposition method (vapor deposition method) such as plasma CVD (Chemical Vapor Deposition), sputtering, and vacuum deposition. ), But a material that can be formed by a coating method is preferable, and carbon nanotubes are preferably exemplified. Further, in the flow path device 10 of the present invention, as described above, observation of fluorescence can be used, but the metal material such as a metal oxide absorbs excitation light and / or fluorescence. Some materials emit light. In this respect as well, carbon nanotubes that do not absorb excitation light and / or fluorescence are preferable as materials for transparent electrodes.

As will be described later, in the flow path device of the present invention, the transparent electrode is not limited to the configuration formed on the entire lower surface of the first flow path member 12 and the entire surface of the holding plate 38B as in the present invention.

Also, transparent electrodes are available in a variety of shapes and sizes. Therefore, the transparent electrode may be linear or planar, but for the above reasons, it is preferable that at least one transparent electrode, preferably both transparent electrodes, are planar electrodes. This enables stable electrical measurement with electrodes of sufficient area.
In the present invention, the planar electrode refers to an electrode having an area larger than the area of the region where the first flow path 18 and the second flow path 24 are separated by the porous membrane 30.
More preferably, the shape and size of at least one transparent electrode, preferably both transparent electrodes, include the porous membrane 30 when viewed from a direction orthogonal to the main surface of the first flow path member 12. Is preferable. When viewed from a direction orthogonal to the main surface of the first flow path member 12, that is, it is the same as the above-mentioned plan view. In particular, the transparent electrode that abuts on the porous membrane 30 such as the first transparent electrode 60 has such a configuration, so that the electrical properties of the surface such as the cell layer formed on the porous membrane 30 can be taken out. Is possible and preferable.

<Method of manufacturing flow path device>
When producing the flow path device 10 of the present invention, first, a porous membrane 30 to which sterile paper is attached to the main surface is prepared. Then, the sterile paper on the lower surface 30B of the porous membrane 30 is peeled off with tweezers, and as shown in FIG. 11, the porous membrane 30 is placed on the second flow path member 14 on which the through hole 26 is formed, and the porous membrane 30 is placed. The tweezers 30 and the second flow path member 14 are joined.

Next, the sterilized paper on the upper surface 30A of the porous membrane 30 is peeled off with tweezers, and while checking with a microscope, the positions of the first flow path member 12 on which the first transparent electrode 60 is formed and the second flow path member 14 As shown in FIG. 12, the first flow path member 12 in which the recess 20 is formed is laminated on the porous membrane 30. As a result, the first flow path 18 is defined by the recess 20 of the first flow path member 12 and the porous membrane 30. Further, the first flow path 18 comes into contact with the first transparent electrode 60 formed on the first flow path member 12.

Next, as shown in FIG. 13, the holding plate 38A is placed on the upper surface of the first flow path member 12 while aligning the positions of the through holes 22A and 22B and the 42A and 42B.
After that, the flow path unit 16 is turned over, and the holding plate 38B on which the second transparent electrode 62 is formed is placed on the lower surface of the second flow path member 14. As a result, the second flow path 24 is defined by the through hole 26 of the second flow path member 14, the porous film 30, and the holding plate 38A. Further, the second flow path 24 comes into contact with the second transparent electrode 62 formed on the holding plate 38B.

Finally, as shown in FIG. 14, the flow path device 10 is manufactured by arranging the spacer 46 around the flow path unit 16 and tightening the holding plate 38A and the holding plate 38B with the bolt 50 and the nut 48. do.
The above-mentioned manufacturing process is an example, and the order may change. Further, other steps may be added to the above steps.

<Other embodiments>
Although one embodiment of the flow path device of the present invention has been described above, the present invention is not limited to this embodiment, and the present invention is not limited to this embodiment, and is not limited to the above-described configuration, as long as it does not deviate from the gist of the present invention. It can be modified in various ways.

For example, the transparent electrode corresponding to the first flow path 18 may be arranged only on the entire wall surface of the first flow path 18 (recess 20) instead of the entire lower surface of the first flow path member 12 including the recess 20. Alternatively, it may be arranged only on the upper surface of the first flow path 18, or may be arranged only on the side surface of the first flow path 18.
Similarly, the transparent electrode corresponding to the second flow path 24 may be arranged not on the entire surface of the holding plate 38B but only on the portion of the holding plate 38B corresponding to the second flow path 24, or the second flow path may be arranged. It may be arranged only on the side surface of 24 (through hole 26).

Further, in the present invention, the transparent electrode may not be in contact with the first flow path 18 and the second flow path 24.
For example, the transparent electrode corresponding to the first flow path 18 is arranged on the upper surface of the first flow path member 12 (the surface opposite to the porous membrane 30), and the transparent electrode corresponding to the second flow path 24 is held on the holding plate 38B. At least one of the transparent electrode corresponding to the first flow path 18 and the transparent electrode corresponding to the second flow path 24, such as being arranged on the lower surface (the surface opposite to the porous membrane 30), is separated from the flow path. May be placed.
By providing the transparent electrode at a distance from the first flow path 18 and / or the second flow path 24, impedance and dielectric constant can be measured.

That is, in the flow path device of the present invention, if a pair of transparent electrodes are provided so as to sandwich the first flow path 18 and the second flow path 24 (at least a part thereof), various positions are provided. It can be arranged by shape.

Further, in the flow path device 10 of the present invention, the porous film 30 is arranged between the first flow path member 12 and the second flow path member 14, and the laminated body is sandwiched between the holding plate 38A and the holding plate 38B. However, the present invention is not limited to this configuration.
For example, the flow path described in Patent Document 1 using a second flow path member having a recess having a bottom instead of the through hole 26 defining the second flow path 24 without using a holding plate. Like the device (organ mimicking device having a microchannel), the flow path device may be configured by the first flow path member, the porous membrane, and the second flow path member.
Further, as the first flow path member, a first flow path member having a through hole defining the first flow path is used instead of the concave portion defining the first flow path, and the through hole is closed by the holding plate. It may be configured to be. In this case, the transparent electrode corresponding to the first flow path may be provided on the lower surface of the first flow path member (the surface on the porous membrane side), or may be provided on the main surface of the holding plate.

The flow path device used as the cell culture device in the present invention has been described in detail above, but the present invention is not limited to the above-mentioned examples, and various improvements and changes are made without departing from the gist of the present invention. Of course, you can go.

Hereinafter, a specific example of the channel device used as the cell culture device in the present invention will be described in more detail. However, the scope of the present invention should not be construed as being limited by the specific examples shown below.

<Manufacturing of flow path device>
The flow path device 10 as shown in FIG. 1 was manufactured by the method described above.
The first flow path member 12 and the second flow path member 14 were made of PDMS, and the holding plate 38A and the holding plate 38B were made of cycloolefin polymer. Both the first flow path 18 (recessed portion 20) and the second flow path 24 (through hole 26) have a width of 300 μm and a depth of 300 μm.
Further, the lower surface of the first flow path member 12 (the surface on which the recess 20 is formed) and the upper surface of the holding plate 38B (the surface on the first flow path member 12 side) contain carbon nanotubes according to a coating method. A 0.5 μm first transparent electrode 60 and a second transparent electrode 62 were formed. When a similar transparent electrode was produced and confirmed by the above method, both the first transparent electrode 60 and the second transparent electrode 62 had a sheet resistance value of 300 Ω / □ or less and a transmittance of 80% or more. rice field.

As the porous film 30, a polycarbonate film having 32 through holes arranged in a honeycomb shape was prepared. The surface of the porous membrane 30 was coated with collagen. Then, the porous membrane 30 was sandwiched between sterile papers.

The sterile paper on one side of the porous membrane 30 was peeled off with tweezers. Next, the porous membrane 30 was set on the second flow path member 14 with the sterilized paper peeled side down (see FIG. 11).
Further, ethanol was immersed in the porous membrane 30 using a cotton swab to join the porous membrane 30 and the second flow path member 14.

The sterile paper on the other side of the porous membrane 30 was peeled off with tweezers. Next, the first flow path member 12 and the second flow path member 14 were aligned with each other, and the first flow path member 12 was laminated on the porous membrane 30 (see FIG. 12).

Next, the holding plate 38A was placed on the upper surface of the first flow path member 12 by aligning the through holes 22A and the through holes 22B with the through holes 42A and the through holes 42B. Further, the laminated body was turned over and the holding plate 38B was arranged on the lower surface of the second flow path member 14 (see FIG. 13).
Further, a spacer 46 was arranged around the flow path unit 16, and the holding plate 38A and the holding plate 38B were tightened with bolts 50 and nuts 48 to fabricate the flow path device 10 (see FIG. 14).

<Cell culture in channel device>
A suspension (3 × 10 ^-6 cells / mL (liter)) of bone marrow-derived mesenchymal stem cells (manufactured by Lonza) was prepared. 200 μL of the prepared suspension was injected into the second channel 24 of the channel device 10.

The flow path device 10 was inverted and allowed to stand in a CO ₂ incubator at 37 ° C. for 3 hours, then the medium was flowed at a rate of 0.7 μL / min and cultured overnight.

Next, a suspension (1 × 10 ^-6 cells / mL) of iPS cell-derived vascular endothelial cells (iCell EC, manufactured by CDI) stained with CellTracker Orange (manufactured by Thermo Fischer) was prepared.
200 μL of the prepared suspension was injected into the first channel 18 of the channel device 10.

<Measurement of cells>
The distribution of stained iPS cell-derived vascular endothelial cells injected into the first channel 18 was observed using an inverted fluorescence microscope (IX83, manufactured by Olympus).
Next, a fluorescently labeled dextran (D1830 manufactured by Thermo Fischer) was injected into the first flow path 18, and the distribution of the fluorescently labeled dextran injected into the first flow path 18 was observed using an inverted fluorescence microscope, and the fluorescently labeled dextran was observed. Leakage to the second flow path 24 was evaluated.
At the same time, a photodetector (photomultiplier tube H11902-20 manufactured by Hamamatsu Photonics Co., Ltd.) is used to detect the amount of light transmitted through the second flow path 24, and the amount of fluorescently labeled dextran leaking to the second flow path 24. Was measured.

Next, Phenol Red (manufactured by Tokyo Chemical Industry Co., Ltd.) is injected into the first flow path 18 and transmitted through the second flow path 24 using a photodetector (manufactured by Sorabo Co., Ltd., differential amplification photodetector PDB210A / M). The amount of incoming light was detected, and the amount of Phenol Red leaking to the second flow path 24 was measured. At this time, since the molecular weights of the fluorescently labeled dextran and Phenol Red are different, if there is a defect in the cell structure, the size of the defect can be quantitatively evaluated by comparing the leakage amount of each.

Using OCT (Optical Coherence Tomography, see Patent No. 6184905), the three-dimensional structure of cells in the first flow path 18 and the second flow path 24, the composition of the cell layer, and the thickness of the cell layer were measured. ..
At the same time, wiring is attached to the first transparent electrode 60 formed in the first flow path 18 and the second transparent electrode 62 formed in the holding plate 38B, and electricity inside the first flow path 18 and the second flow path 24 is supplied. The state of the internal structure was monitored by measuring the resistance (manufactured by HIOKI, digital multimeter DT4282). A high electric resistance value indicates that the cells are densely arranged, and a low electric resistance value indicates that a gap is formed between the cells, and the state of the cell structure is quantitatively evaluated by the electric resistance value. be able to.

As described above, using the flow path device used in the present invention, cells are subjected to multi-validation by combining optical observation with an inverted fluorescence microscope, light detection of a plurality of tracers, OCT, and electrical measurement. Structure and defect size can be evaluated non-destructively and non-invasively.
On the other hand, in any one of these measurements alone, the original "gap" of the defect structure and the "defect (abnormal part where cells are not properly present)" are distinguished. It is difficult to quantify the size of each.
That is, the channel device used as the cell culture device in the present invention is very effective for the analysis of the organ model (biological chip) by multi-validation. Therefore, it is extremely effective as a cell culture device used in the management method and management system of the cell culture device according to the present invention.

Although various embodiments and examples of the cell culture device management method and the cell culture device management system according to the present invention have been described in detail above, the present invention describes these embodiments and embodiments. Of course, the present invention is not limited to the example, and various improvements or changes may be made without departing from the gist of the present invention.

It can be suitably used in various fields such as life science research, drug discovery, drug development, and safety testing, as well as chemical and biological tests.

10 Flow path device 12 1st flow path member 12A, 14A Opposing surface 14 2nd flow path member 16 Flow path unit 18 1st flow path 20 Recess 20A, 26A Inlet 20B, 26B Outlet 20C, 26C Flow path 22A, 22B, 28A, 28B Through hole 24 Second flow path 26 Through hole 29 Recess 30 Porous membrane 30A Top surface 30B Bottom surface 32 Through hole 32A Opening 34 Flat part 36 Communication hole 38, 38A, 38B Holding plate 40 Bolt hole 42A, 42B, 44A, 44B Through hole 46 Spacer 48 Nut 50 Bolt 60 1st transparent electrode 62 2nd transparent electrode 70 Light source 72 Optical sensor 74 Imaging camera 76 Electric sensor 80 Cell culture device management system 82 Manufacturer's factory 84 Cell culture unit 86 Cell culture device 88 Transport vehicle 90 User equipment 92 Drug test unit 94 Data server 96 1st controller 98 Manufacturing equipment 100 1st condition controller 102 1st measurement unit 104 1st memory unit 106 2nd controller 106
108 2nd condition controller 110 2nd measurement unit 112 2nd memory unit 114 3rd controller 116 3rd condition controller 118 3rd measurement unit 120 3rd memory unit

Claims (25)

In the factory, at least one cell culture device for culturing living cells is manufactured, the living cells are seeded in the cell culture device to start culturing, and the culture state of the living cells being cultured is measured. 1 Collect measurement data continuously and
In the factory, the cell culture device in which the living cells are being cultured is loaded into a transport vehicle as it is or kept at a low temperature.
In the transport vehicle, the temperature of the living cells and the cell culture device is controlled to culture the living cells and / or measure the state of the living cells maintained at the low temperature state . 2 While continuously collecting measurement data, the cell culture device is transported from the factory to the user of the cell culture device.
In the user, the cell culture device is received from the transport vehicle, the living cells in the culture are left as they are, the living cells in the low temperature state, and the cell culture device are returned to the culture state, and then the cells are described. When culturing a living cell, measuring the culture state, continuously collecting the third measurement data, and using the living cell matured to a usable state, the living cell is used.
From the start of culturing the living cells in the factory to the use of the mature living cells by the user, the first measurement data showing the culture state of the living cells, the third measurement data, and the above. A method for managing a cell culture device for managing the cell culture device for culturing the living cells by continuously recording and centrally managing the second measurement data indicating the state of the living cells.
The cell culture device is
A first flow path member having a first flow path and
A second flow path member having a second flow path and
A porous membrane provided between the first flow path member and the second flow path member, which covers and separates the first flow path and the second flow path,
A first transparent electrode provided in contact with the first flow path and facing the porous membrane,
It has a second transparent electrode that is in contact with the second flow path and is provided so as to face the porous membrane.
The first flow path is formed between the first flow path member and the porous membrane, and is formed.
The second flow path is a method for managing a cell culture device formed between the second transparent electrode, the second flow path member, and the porous membrane. From the first measurement data, the second measurement data, and the third measurement data that are continuously recorded and centrally managed, it is determined that the living cells have matured to a usable state. The method for managing a cell culture device according to claim 1, wherein the user is notified of the timing of use. From the first measurement data, the second measurement data, and the third measurement data, which are continuously recorded and centrally managed, to mature the living cells to a state in which the living cells can be used by the user. The method for managing a cell culture device according to claim 1 or 2, wherein the culture conditions of the cell culture device are obtained, and the cell culture device is controlled under the obtained culture conditions. The cell culture device according to any one of claims 1 to 3, wherein the first measurement data, the second measurement data, and the third measurement data are recorded in a data server installed at one point. Management method. The first measurement data is collected by the first controller installed in the factory and is collected.
The first controller is
The collected first measurement data is transmitted to the server, and the collected data is transmitted to the server.
From the collected first measurement data, the first culture conditions of the cell culture device for culturing the living cells were obtained.
The method for managing a cell culture device according to claim 4, wherein the cell culture device is controlled under the obtained first culture conditions. The second measurement data is collected by the second controller installed in the transport vehicle, and is collected.
The second controller transmits the collected second measurement data to the server.
From the received first measurement data and the second measurement data, the server obtains the second culture condition of the cell culture device for culturing the living cells in the transport vehicle during transportation, and obtains the second culture condition. 2 The culture conditions are transmitted to the second controller, and the culture conditions are transmitted to the second controller.
The method for managing a cell culture device according to claim 4 or 5, wherein the second controller controls the cell culture device being transported in the transport vehicle to the second culture conditions. The third measurement data is collected in the third controller installed by the user, and is collected.
The third controller transmits the collected third measurement data to the server.
The server is a third of the cell culture device for maturing the living cells from the received first measurement data, the second measurement data, and the third measurement data to a state in which the living cells can be used by the user. The culture conditions are obtained, and the third culture conditions are transmitted to the third controller.
The method for managing a cell culture device according to any one of claims 4 to 6, wherein the third controller controls the cell culture device to the third culture condition in the user. In order to collect the first measurement data, the second measurement data, and the third measurement data, the living body maintained in the culture state of the living cells being cultured in the cell culture device or in the low temperature state. The method for managing a cell culture device according to any one of claims 1 to 7, wherein the state of cells is continuously measured electrically and optically. The management of the cell culture device according to any one of claims 1 to 8, wherein in the factory, a shipping inspection is performed to inspect that the culture state of the living cells is appropriate before being transported by the transport vehicle. Method. The method for managing a cell culture device according to any one of claims 1 to 9, wherein the first transparent electrode and the second transparent electrode are planar electrodes. The first flow path member, or the first flow path member and the second flow path member are made of a polymer material.
The method for managing a cell culture device according to any one of claims 1 to 10, wherein the first transparent electrode and the second transparent electrode are carbon nanotubes. Claims 1 to 11 receive the cell culture device in which the living cells are being cultured in the transport vehicle from the factory, control the temperatures of the living cells and the cell culture device, and continue culturing the living cells. The method for managing a cell culture device according to any one of the above items. The method for managing a cell culture device according to any one of claims 1 to 11 , wherein the low temperature state includes a state in which the living cells and the cell culture device are frozen and the living cells are frozen. The method for managing a cell culture device according to claim 13 , wherein the living cells and the cell culture device are frozen in the factory, and the living cells are in a frozen state. The method for managing a cell culture device according to claim 13 , wherein the living cells and the cell culture device are frozen in the transport vehicle, and the living cells are in a frozen state. The invention according to any one of claims 13 to 15 , wherein when the user receives the cell culture device and the living cells in a frozen state from the transport vehicle, the cells are thawed by the user. How to manage cell culture devices. The method for managing a cell culture device according to any one of claims 13 to 15 , wherein the cell culture device in a frozen state and the living cells are thawed in the transport vehicle. A cell culture unit in which at least one cell culture device for culturing a living cell is arranged, a first condition controller for controlling the culture conditions of the living cells seeded and cultured in the cell culture device, and the cell culture device. A factory equipped with a measurement unit for measuring the culture state of living cells and a first controller having a first memory unit for collecting first measurement data measured by the measurement unit.
A cell culture unit including the cell culture device for culturing the living cells, a second condition controller for controlling the conditions of the living cells of the cell culture device, and a second condition for measuring the state of the living cells of the cell culture device. The cell culture unit is provided with two measurement units and a second controller having a second memory unit for collecting the second measurement data measured by the second measurement unit, from the factory to the user of the cell culture device. The transport vehicle to transport and
The cell culture unit provided with the cell culture device for culturing the living cells and maturing them to a usable state, a third condition controller for controlling the culture conditions of the living cells of the cell culture device, and the cell culture device. User-side equipment including a third measurement unit for measuring the culture state of living cells and a third controller having a third memory unit for collecting the third measurement data measured by the third measurement unit.
The first measurement data collected at the factory is received from the first controller, the second measurement data collected by the transport vehicle is received from the second controller, and the user side is received from the third controller. The living body that has received the third measurement data collected by the equipment and has matured the first measurement data, the second measurement data, and the third measurement data indicating the state of the living cell to a usable state. A data server that manages the cell culture device that continuously records and centrally manages cells until they are used, and cultivates the living cells.
Is a management system for cell culture devices with
The cell culture device is
A first flow path member having a first flow path and
A second flow path member having a second flow path and
A porous membrane provided between the first flow path member and the second flow path member, which covers and separates the first flow path and the second flow path,
A first transparent electrode provided in contact with the first flow path and facing the porous membrane,
It has a second transparent electrode that is in contact with the second flow path and is provided so as to face the porous membrane.
The first flow path is formed between the first flow path member and the porous membrane, and is formed.
The second flow path is a management system for a cell culture device formed between the second transparent electrode, the second flow path member, and the porous membrane . The cell culture device management system according to claim 18 , wherein the factory further has a manufacturing facility for manufacturing the at least one cell culture device. In the transport vehicle, the living cells are continuously cultured in the cell culture device of the cell culture unit.
The condition of the second condition controller is a culture condition for culturing the living cell by controlling the temperature of the living cell and the cell culture device in the transport vehicle.
The state of the living cell measured by the second measuring unit is the state of culturing the living cell.
Claim 18 or claim 18 , wherein the data server continuously records and centrally manages the first measurement data, the second measurement data, and the third measurement data indicating the culture state of the living cell culture. 19. The cell culture device management system according to 19. The cell culture device management system according to claim 18 or 19 , wherein the factory further has a freezing unit that freezes the living cells and the cell culture device to bring the living cells to a low temperature state. The cell culture device according to any one of claims 18 to 21 , further comprising a freezing unit that freezes the living cells and the cell culture device to bring the living cells to a low temperature state. Management system. The cell culture device management system according to claim 21 , wherein the low temperature state includes a state in which the living cells and the cell culture device are frozen and the living cells are frozen. The cell culture device management system according to claim 23 , wherein the user-side equipment further includes the cell culture device in a frozen state and a thawing unit for thawing the living cells. The management system for a cell culture device according to claim 23 , wherein the transport vehicle further includes the cell culture device in a frozen state and a thawing unit for thawing the living cells.

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