JP-7855188-B2 - Cell manufacturing apparatus and system

Inventors

• 伴 一訓
• 木下 聡
• 田邊 剛士
• 平出 亮二

Assignees

• ファナック株式会社
• アイ ピース，インコーポレイテッド

Dates

Publication Date

20260508

Application Date

20200528

Priority Date

20190829

Claims (13)

1. A cell preparation plate equipped with a fluid circuit that integrates multiple functional sites, Multiple closed connectors that connect the fluid circuit to the external space in a closed manner, Equipped with, The fluid circuit comprises the following multiple functional parts: Multiple injection/discharge units capable of injecting multiple types of fluids into the fluid circuit or discharging them outside the fluid circuit via the multiple closed connectors, Multiple fluid reservoirs capable of storing the multiple types of fluids to be injected or discharged, Multiple transfer units capable of transferring each of the multiple types of fluids stored, A cell induction and culture unit that performs cell induction and culture based on the multiple types of fluids stored therein, Equipped with, A cell manufacturing apparatus in which the plurality of fluid reservoirs each store a fluid containing source cells, an inducer reagent, a culture medium for reprogramming or induction, and a fluid containing target cells, respectively.
2. It includes a cell preparation plate equipped with a fluid circuit that integrates multiple functional sites, The fluid circuit comprises the following multiple functional parts: Multiple fluid reservoirs capable of storing multiple types of fluids, Multiple transfer units capable of transferring each of the multiple types of fluids stored, A cell induction and culture unit that performs cell induction and culture based on the multiple types of fluids stored therein, Equipped with, A cell manufacturing apparatus in which the plurality of fluid reservoirs each store a fluid containing source cells, an inducer reagent, a culture medium for reprogramming or induction, and a fluid containing target cells, respectively.
3. The cell manufacturing apparatus according to claim 1 or 2, further comprising a first variable-volume section for storing fluids extruded or drawn out by the aforementioned plurality of fluids.
4. The cell manufacturing apparatus according to claim 3, wherein the first volume-variable section comprises a physically or chemically volume-variable material.
5. The cell manufacturing apparatus according to claim 4, wherein the aforementioned physically variable volume material comprises a flexible bag or a syringe.
6. The cell manufacturing apparatus according to claim 1, wherein each of the multiple fluid reservoirs is positioned between each of the multiple closed connectors and each of the multiple transfer sections.
7. The cell manufacturing apparatus according to claim 1, wherein the plurality of closed connectors are attached to one side of the cell manufacturing plate and are connectable to a fluid container equipped with a plurality of discharge/suction sections.
8. A cell production plate equipped with a fluid circuit integrating multiple functional parts, and a cell production apparatus equipped with multiple closed connectors that connect the fluid circuit to the external space in a closed manner, A fluid container that can be connected to at least one of the plurality of closed connectors, Equipped with, The aforementioned fluid circuit is The system includes multiple injection and discharge sections that can inject multiple types of fluids into the fluid circuit or discharge them outside the fluid circuit via the multiple closed connectors, The aforementioned fluid container is Multiple fluid reservoirs capable of storing multiple types of fluids , A discharge/suction unit that discharges the fluid into the fluid circuit and draws it out from the fluid circuit via at least one of the plurality of closed connectors, Equipped with, The fluid circuit or the fluid container further comprises a plurality of transfer units capable of transferring the stored fluid into the fluid circuit, A cell manufacturing system in which the plurality of fluid reservoirs each store a fluid containing source cells, an inducer reagent, a culture medium for reprogramming or induction, and a fluid containing target cells, respectively.
9. The cell manufacturing system according to claim 8, further comprising a first volume variable section for storing fluid extruded or drawn out by the injected or discharged fluid in the fluid circuit.
10. The cell manufacturing system according to claim 9, wherein the first volume-variable section comprises a physical or chemical volume-variable material.
11. The cell manufacturing system according to any one of claims 8 to 10, wherein the fluid container further comprises a second variable-volume section for storing the fluid drawn out and extruded by the discharged and aspirated fluid.
12. The cell manufacturing system according to claim 11, wherein the second volume-variable section comprises a physical or chemical volume-variable material.
13. The cell manufacturing apparatus according to claim 10 or 12, wherein the physically variable volume material comprises a flexible bag or a syringe.

Description

This invention relates to a cell manufacturing apparatus and system, and more particularly to a cell manufacturing apparatus and system that simplifies the fluid injection and discharge process. Embryonic stem cells (ES cells) are stem cells established from early-stage goblet cells of humans or mice, and possess pluripotency, meaning they can differentiate into all cell types present in the body. Human ES cells are considered useful for cell transplantation in many diseases, including Parkinson's disease, juvenile diabetes, and leukemia. However, ES cell transplantation, like organ transplantation, carries the risk of rejection. Furthermore, there is considerable ethical opposition to the use of ES cells established by destroying human goblet cells. In response, Professor Shinya Yamanaka of Kyoto University succeeded in establishing induced pluripotent stem cells (iPS cells) by introducing four genes: Oct3/4, Klf4, c-Myc, and Sox2, into somatic cells, and was awarded the Nobel Prize in Physiology or Medicine in 2012 (see, for example, Patent Document 1). iPS cells are ideal pluripotent cells that do not cause rejection reactions or ethical problems, and are expected to be used in cell transplantation methods. Induced stem cells, such as iPS cells, are established by introducing inducing factors such as genes into cells, then undergo expanded culture and cryopreservation. However, producing clinical-grade iPS cells (GLP, GMP grade), for example, requires a cleanroom that is kept extremely clean, resulting in high maintenance costs. For industrialization, the challenge has been how to streamline cleanroom operations and reduce costs. Furthermore, while the creation of iPS cells relies heavily on manual labor, there are few technicians capable of producing iPS cells for clinical use. The entire process, from stem cell establishment to storage, is complex. Clinical cell culture requires three steps: verification of the Standard of Process (SOP), operation according to the SOP, and confirmation of whether the SOP was followed. Performing these steps manually is highly unproductive. Cell culture requires 24-hour, daily monitoring, and stem cell storage can last for decades, making it impossible to manage solely through human intervention. Therefore, closed-system cell manufacturing equipment has been developed that eliminates the need for highly cleanrooms and can be operated in normally controlled areas (for example, where at least one of microorganisms and particulate matter is Grade D or higher according to WHO-GMP standards) (see, for example, Patent Document 2). Furthermore, cell manufacturing systems equipped with robots to assist in cell manufacturing have also been developed to automate complex cell manufacturing processes and eliminate the need for human labor. The following documents are known prior art regarding such cell manufacturing equipment. Patent Document 3 discloses a somatic cell manufacturing system that packages a pre-transfer cell delivery channel, a factor introduction device for introducing somatic cell-inducing factors into pre-transfer cells to produce factor-inducing cells, and a cell production device for culturing factor-inducing cells to produce somatic cells, all within a single enclosure. Patent Document 4 discloses a cell culture vessel with a closed system of culture vessels and flow channels, in which the cell culture vessel holds a second vessel eccentrically inside a first vessel, allowing for clear observation of the cell culture growth state. Patent Document 5 discloses a cell culture apparatus in which a culture medium storage means, a cell inoculation means, and a culture vessel are configured in a closed system. The cell culture apparatus reduces the operator's workload by determining the cell culture status from images of cells in the culture vessel and performing culture operations based on this determination. Patent Document 6 discloses a cell culture apparatus comprising a main body having side walls surrounding the volume of a cell culture chamber, a lid covering the cell culture chamber, and a bottom plate positioned at the bottom of the main body, wherein the main body has an integrally formed microfluidic conduit for fluid communication between the inlet/outlet connector and the cell culture chamber. Patent Document 7 discloses a microchip reaction apparatus equipped with a bubble removal means for moving bubbles in the internal space of a microchip to the external space. Patent Document 8 discloses a cell culture apparatus equipped with a vent that allows gas to be discharged from a first culture medium storage chamber and a second culture medium storage chamber, and an air filter is provided in the vent. Patent Document 9 discloses a cell culture apparatus equipped with a channel-integrated plate and a base plate. The channel-integrated plate comprises a channel plate forming channels for the culture medium and a pump section equipped with a group of peristalt