JP7626987B2 - Cell transfer device and cell transfer method - Google Patents

Description

The present invention relates to a cell transfer device for transferring cells and a cell transfer method using the cell transfer device.

Technology for transferring cells collected from living organisms has been attracting attention in various fields such as medicine and beauty. One example of a cell transfer technology is used in the technique of purifying cells that contribute to the formation of hair follicles and transplanting the cells intradermally.

In recent years, various studies have been conducted on cells capable of forming hair follicles (see, for example, Patent Documents 1 to 4). The technique of transplanting hair follicle primordia formed from the interaction between epithelial cells and mesenchymal cells enables successful regeneration of hair.

International Publication No. 2017/073625 International Publication No. 2012/108069 JP 2008-29331 A International Publication No. 2019/064653

Technology for transferring cells from a culture environment, processing environment, etc. to the next environment has a significant impact on the survival rate and activity level of the cells. Being able to grasp the status of the object containing the cells, such as its position and speed, during the transfer process increases the accuracy of determining whether the transfer of the object is being performed normally, and ultimately makes it possible to prevent a decrease in survival rate and activity level caused by the transfer. In particular, in hair regeneration in which hair follicle primordia are transferred one by one, being able to grasp the status of the hair follicle primordia during the transfer process can promote good regeneration and lead to the widespread use of the technology.

The object of the present invention is to provide a cell transfer device and a cell transfer method that make it possible to grasp the condition of an object containing cells during the transfer process.

The cell transfer device for solving the above problem is a cell transfer device that transfers an object including a cell, and includes a passageway that guides the object along a path, a first sensor that detects the presence or absence of the object at a first position on the path, and a second sensor that detects the presence or absence of the object at a second position on the path.

The cell transfer method for solving the above problem is a cell transfer method for transferring an object containing cells, and includes passing the object through a passage that guides the object onto a path, detecting the presence or absence of the object at a first position on the path through which the object passes, and detecting the presence or absence of the object at a second position on the path.

According to each of the above configurations, the presence or absence of an object at a first position and the presence or absence of an object at a second position on the path of the object are detected by separate sensors. This makes it possible to grasp the movement of the object from the first position to the second position, or the movement of the object from the second position to the first position. Furthermore, it is possible to grasp that an object that has reached the first position has not reached the second position, or that an object that has reached the second position has not reached the first position. In other words, it is possible to grasp during the process of transporting the object whether it has moved smoothly along the path.

In the above cell transfer device, the passage may be a needle-shaped body for placing the object in a living body, and the first sensor and the second sensor may be disposed in the needle-shaped body.
According to the above configuration, since two sensors are arranged on the needle-shaped body for placing the object in the living body, it is possible to know whether the object has moved smoothly through the needle-shaped body before placing the object in the living body. This makes it possible to change the placement method or stop the placement itself based on the condition of the object during the transfer process. As a result, it is possible to suppress the variation in the action of the cells after placement caused by the transfer.

In the cell transfer device, the passage may be a needle-shaped body for placing the object in a living body, and at least one of the first sensor and the second sensor may be positioned radially outside the needle-shaped body.

According to the above configuration, two sensors are disposed on the outside of the needle-shaped body for placing the target object in the living body, so that a design specialized for the placement of the target object can be applied to the needle-shaped body.
In the above cell transfer device, the target object may include a hair follicle primordium, and the distance between the first position and the second position may be greater than the target object.

According to the above configuration, it is possible to grasp with higher accuracy that the hair follicle primordium has moved from the first position to the second position, and that the hair follicle primordium has moved from the second position to the first position. Furthermore, it is possible to grasp with higher accuracy that the hair follicle primordium that has reached the first position has not reached the second position, and that the hair follicle primordium that has reached the second position has not reached the first position.

In the above cell transfer device, the target object may include a hair follicle primordium, and the distance between the first position and the second position may be smaller than the target object.
According to the above configuration, when an object moves along a path, the second sensor starts to detect the presence of the object while the first sensor detects the presence of the object. Alternatively, the first sensor starts to detect the presence of the object while the second sensor detects the object. On the other hand, when a foreign object such as dust or dirt smaller than the object moves along a path, the second sensor starts to detect the presence of the foreign object after the first sensor has finished detecting the presence of the foreign object. Alternatively, the first sensor starts to detect the presence of the foreign object after the second sensor has finished detecting the presence of the foreign object. Therefore, it is possible to know whether or not a foreign object is mixed in the path of the object.

In the above cell transfer device, the passage, the first sensor, and the second sensor may be a single unit, the device may include a plurality of such units, and the device may further include a pressure application unit that simultaneously applies pressure to the inside of each passage.

With the above configuration, multiple passages simultaneously suck in objects, or multiple passages simultaneously push out objects, making it possible to simultaneously grasp the condition of objects during the transfer process and improve transfer efficiency.

In the cell transfer device, at least one of the first sensor and the second sensor may detect the presence or absence of the object along a circumferential direction of the passage.
According to the above configuration, at least one of the sensors detects an object in the circumferential direction of the passage, so that it is possible to suppress oversight of the object being detected.

In the above cell transfer device, at least one of the first sensor and the second sensor may detect the presence or absence of the object on a spiral extending in the extension direction of the path.
According to the above configuration, at least one of the sensors detects an object within a spiral range, making it possible to prevent the object from being missed when it is detected.

The cell transfer device may further include an insertion member having a holding end, which is a tip for holding the object, and the insertion member may be configured to be movable inside the passage along the extension direction of the passage while holding the object at the holding end.

According to the above configuration, the movement of the object is guided in the extension direction of the passage, so that variation in the direction in which the object moves and variation in the state of the object can be suppressed.
The cell transfer device may further include an estimation unit that estimates a state of the object using a detection result of the first sensor and a detection result of the second sensor.

With the above configuration, the condition of the object is estimated based on the detection results of each sensor, which reduces the load required to process the detection results and makes it easier to grasp the condition of the object as it moves.

The cell transfer device and cell transfer method of the present invention make it possible to grasp the condition of the target object during the transfer process.

FIG. 1 is a block diagram showing a device configuration of a first embodiment of a cell transfer device. 5A to 5C are operational diagrams showing a cell transfer process in the first embodiment of the cell transfer device. 5A to 5C are operational diagrams showing a cell transfer process in the first embodiment of the cell transfer device. 5A to 5C are operational diagrams showing a cell transfer process in the first embodiment of the cell transfer device. FIG. 13 is a block diagram showing the configuration of a cell transfer device according to a second embodiment. 10A to 10C are operational diagrams showing a cell transfer process in the second embodiment of the cell transfer device. 10A to 10C are operational diagrams showing a cell transfer process in the second embodiment of the cell transfer device. FIG. 11 is a cross-sectional view showing a sensor configuration in a first modified example. FIG. 11 is a cross-sectional view showing a sensor configuration in a second modified example. FIG. 13 is a cross-sectional view showing a sensor configuration in a third modified example. FIG. 13 is a cross-sectional view showing a sensor configuration in a fourth modified example. FIG. 13 is a block diagram showing the configuration of a cell transfer device in a fifth modified example. FIG. 13 is a block diagram showing the configuration of a cell transfer device in a sixth modified example.

First Embodiment
A first embodiment of a cell transfer device and a cell transfer method will be described below with reference to Figures 1 to 4. First, the configuration of an object containing cells will be described, then the configuration of a cell transfer device will be described, and finally the cell transfer method will be described.

The cell transfer device transfers an object containing cells from a first environment to a second environment different from the first environment. The first environment and the second environment may be a cell preservation environment and an internal environment of the cell transfer device, an internal environment of the cell transfer device and a cell culture environment, a cell culture environment and an internal environment of the cell transfer device, or an internal environment of the cell transfer device and a cell processing environment. The first environment and the second environment may be a cell processing environment and an internal environment of the cell transfer device, or an internal environment of the cell transfer device and a living body tissue. The living body tissue may be at least one of the intradermal space, the subcutaneous space, and an organ of the living body. The term "living body" includes not only the body of an organism, but also an artificial living body model that imitates the body or tissue. The transfer by the cell transfer device is used for at least one of the steps of cell preservation, cell seeding, cell culture, and cell transplantation.

[Object]
The subject may include a single cell or a cell group consisting of a plurality of cells. The cells contained in the subject may be undifferentiated cells, cells in which differentiation has been completed, or cells with stem cell properties. The cell group contained in the subject may be an aggregate of a plurality of aggregated cells, an aggregate of a plurality of cells bonded by intercellular junctions, or may be composed of a plurality of dispersed cells. The cell group contained in the subject may be composed of undifferentiated cells and differentiated cells, or may include cells with stem cell properties.

The cell group contained in the subject may be a spheroid cell mass, an anlage, tissue, organ, organoid, or mini-organ. The cell group may affect tissue formation by being placed in the transplant destination. The cell group may include cells with stem cell properties.

The cell group contained in the object is placed intradermally, subcutaneously, or in an organ, thereby exerting a desired effect. For example, the cell group contained in the object is placed intradermally or subcutaneously and contributes to hair growth or hair development. For example, the cell group contained in the object is placed in a skin area and exerts a cosmetic effect such as eliminating wrinkles in the skin or improving the moisturizing state. An example of the cell group contained in the object may have the ability to function as a hair follicle organ, the ability to differentiate into a hair follicle organ, the ability to induce or promote the formation of a hair follicle organ, or the ability to induce or promote the formation of hair in a hair follicle. The cell group contained in the object may include cells that contribute to the control of hair color, such as pigment cells or stem cells that differentiate into pigment cells, and may include vascular cells.

A more specific example of the cell group contained in the object may be a primitive organ primordium. The organ primordium may include mesenchymal cells and epithelial cells. The organ primordium may be a hair follicle primordium that differentiates into a hair follicle organ, a liver primordium, a kidney primordium, a pancreatic primordium, primordium cells of the nervous system, and primordium cells of the vascular system. The object containing the organ primordium may include, for example, a nuclear material, a guide wire, and impurities to assist the shape and performance of the primordium, depending on the method of forming the organ primordium.

The hair follicle primordium contained in the subject may be formed by co-culturing mesenchymal cells derived from mesenchymal tissue such as the hair papilla and epithelial cells derived from epithelial tissue located in the bulge region or the base of the hair bulb under specified conditions. The mesenchymal cells and epithelial cells may be derived from the hair follicle organ, an organ different from the hair follicle organ, or pluripotent stem cells.

The cell group contained in the subject may be a single structure or two or more structures. When the cell group contained in the subject is two or more structures, it becomes possible to mimic the environment that exists in a living body for a specific cell group, and to control the appropriate cell density and culture medium conditions for expressing biological functions, as well as the environment in which signaling substances exist.

The object may contain a protective liquid. The protective liquid may be any liquid that does not inhibit cell survival, and may be a liquid that has little effect on the living body when injected into the living body. The protective liquid may be a liquid that protects the skin, such as physiological saline, petrolatum, or lotion, or a mixture of these liquids. The protective liquid may contain an additive component such as a nutrient component. The protective liquid may be a culture medium for culturing cells, or a liquid that has been replaced from the culture medium. The object may be a liquid body containing the protective liquid, a gel-like body, a low-viscosity fluid, or a high-viscosity fluid.

[Cell transfer device]
1, the cell transfer device includes a passage 11, a first sensor 21, and a second sensor 22. The passage 11 guides a target object CM including cells along a path. The first sensor 21 detects the presence or absence of the target object CM at a first position on the path. The second sensor 22 detects the presence or absence of the target object CM at a second position on the path different from the first position.

The path of the object CM is a predetermined path that the object CM follows during its transport. The passage 11 defines at least a portion of the path of the object CM. The first position is a position on the path of the object CM that is a predetermined position. The second position is a position on the path of the object CM that is different from the first position and is a predetermined position. Note that FIG. 1 shows an example in which the position of the first sensor 21 is the first position, the position of the second sensor 22 is the second position, and the first position and the second position are aligned along the direction in which the passage 11 extends.

[aisle]
The passage 11 may be a cylindrical body having a space therein through which the target object CM passes, or may be a needle-shaped body having a space therein through which the target object CM passes. The material constituting the passage 11 may be metal or resin.

The size of the opening 12 of the passage 11 and the inner diameter of the passage 11, which is the space through which the target object CM passes, are selected appropriately according to the requirements of the cell transfer device. Note that FIG. 1 shows an example in which a cylindrical passage 11 has an elliptical ring-shaped opening 12 that is formed by cutting the passage 11 along a cutting plane that intersects with the extension direction of the passage 11.

The larger the opening 12 of the passage 11, the easier it is to accommodate the object CM inside the passage 11. The larger the inner diameter of the passage 11, the more it is possible to reduce friction between the passage 11 and the object CM, thereby minimizing the impact on cell viability and cell activity. On the other hand, the smaller the opening 12 of the passage 11, the more accurately it is possible to adjust the number of objects CM that enter the passage 11. The smaller the inner diameter of the passage 11, the narrower the path of the object CM, making it easier to identify the position of the object CM.

When the passage 11 is a needle-shaped body, the thinner the tip of the needle-shaped body, the smaller the scar caused by the puncture with the needle-shaped body and the less bleeding and pain it can cause. On the other hand, the thicker the tip of the needle-shaped body, the easier it is to form a space through which the target object CM can pass.

The object CM that enters the passage 11 from the opening 12 moves with the flow of the protective liquid, but the closer the position where the object CM is to be held is to the opening 12, the less contact there is between the object CM and the passage 11, and the less stress the object CM receives. Also, the smoother the inside of the passage 11 is, the less stress the object CM receives due to contact between the object CM and the passage 11.

The needle-shaped body may have a portion that enters the inside of a living body. The needle-shaped body is suitable for transferring a target object CM to the inside of a living body. The inside of the living body into which the needle-shaped body enters may be intradermally or subcutaneously. The length of the needle-shaped body in the direction in which it extends may be 200 μm or more and 6 mm or less.

The number of needle-shaped bodies provided in the cell transfer device may be one or two or more. When the cell transfer device has multiple needle-shaped bodies, the multiple needle-shaped bodies may be arranged regularly like the lattice points of a geometric lattice, or may be arranged irregularly. When the cell transfer device has multiple needle-shaped bodies, the multiple needle-shaped bodies may be supported by a single support, or may be supported by two or more supports. When the cell transfer device has multiple needle-shaped bodies, each needle-shaped body may simultaneously draw in the target object CM, or each needle-shaped body may simultaneously push out the target object CM. The fact that the drawing in and pushing out of each needle-shaped body proceeds simultaneously increases the efficiency required for cell transfer. It also makes it possible to prevent the target object from drying out during transfer.

When the cell group contained in the object CM contributes to hair growth or hair growth, the arrangement of the cell group at the destination is determined according to the arrangement of the multiple needle-shaped bodies. That is, the arrangement of the hair by transplantation of the cell group is determined according to the arrangement of the multiple needle-shaped bodies. When the cell group contained in the object CM is a hair follicle primordium, the density of the needle-shaped bodies per unit area is preferably 1 piece/cm2 ^{or more} and 400 pieces/cm2 ^or less, and more preferably 20 pieces/ ^cm2 or more and 100 pieces/ ^cm2 or less. If the density of the needle-shaped bodies is 1 piece/ ^cm2 or more, fine hair regeneration is possible one by one. If the density of the needle-shaped bodies is 400 pieces/cm2 ^or less, the nutrients required for hair regeneration are easily distributed to each cell group.

[sensor]
The first sensor 21 detects whether or not an object CM is present at a first position on the path. The second sensor 22 detects whether or not an object CM is present at a second position on the path. Each of the sensors 21 and 22 is disposed in the passage 11.

In the extension direction of the passage 11, the distance between the upper end of the opening 12 of the passage 11 and the first position is a first distance LA. In the extension direction of the passage 11, the distance between the first position and the second position is a second distance LB. Note that the upper end of the opening 12 of the passage 11 is the portion of the opening 12 where the object CM begins to be exposed to the outside of the passage 11 when the object CM is pushed out of the opening 12.

The first distance LA is determined according to the condition of the object CM to be grasped. For example, when grasping whether the object CM has been drawn into the opening 12 of the passage 11 as the condition of the object CM, the first distance LA may be equal to or less than the diameter of the object CM, or equal to or less than the length of the object CM in the long axis direction of the object CM, or equal to or less than the radius of the object CM, or equal to or less than half the length of the object CM in the long axis direction of the object CM. For example, when grasping whether the object CM is clogged in the opening 12 of the passage 11 as the condition of the object CM, the first distance LA may be equal to or less than the radius of the object CM, or may be 0 mm.

The second distance LB is determined according to the status of the object CM to be grasped. For example, when grasping the status of the object CM as whether or not the object CM is accommodated between the first position and the second position, the second distance LB may be greater than the diameter of the object CM, or greater than the length of the object CM in the long axis direction of the object CM. For example, when grasping the speed of the object CM as the status of the object CM, the second distance LB may be greater than the diameter of the object CM, or greater than the length of the object CM in the long axis direction of the object CM.

When the object CM includes a hair follicle primordium, the length of the object CM in the long axis direction of the object CM is, for example, 1500 μm or less. When determining whether the object CM including the hair follicle primordium is contained between the first position and the second position as the state of the object CM, the second distance LB is greater than 1500 μm. This makes it possible to determine with higher accuracy that the hair follicle primordium has moved from the first position to the second position, and that the hair follicle primordium has moved from the second position to the first position. Furthermore, it can be determined with higher accuracy that a hair follicle primordium that has reached the first position has not reached the second position, and that a hair follicle primordium that has reached the second position has not reached the first position.

The detection of the presence or absence of the object CM by the first sensor 21 may be detection by contact between the first sensor 21 located at the first position and the object CM located at the first position. The detection of the presence or absence of the object CM by the first sensor 21 may be detection by non-contact between the first sensor 21 located at a position different from the first position and the object CM located at the first position.

The detection of the presence or absence of the object CM by the second sensor 22 may be detection by contact between the second sensor 22 located at the second position and the object CM located at the second position. The detection of the presence or absence of the object CM by the second sensor 22 may be detection by non-contact between the second sensor 22 located at a position different from the second position and the object CM located at the second position.

The detection of contact at the first position may be detection of a change in a state quantity due to contact with the object CM at the first position, or may be detection of maintenance of a state quantity due to contact with the object CM at the first position. The detection of contact at the second position may be detection of a change in a state quantity due to contact with the object CM at the second position, or may be detection of maintenance of a state quantity due to contact with the object CM at the second position.

The non-contact detection at the first position may be detection of a change in a state quantity due to the presence of the object CM at the first position, or detection of the maintenance of a state quantity due to the presence of the object CM at the first position. The subject of the non-contact detection at the first position may be the state quantity at the first position, or may be the state quantity at a position other than the first position on the path. The position other than the first position is a position different from the position that is the subject of detection by the second sensor 22, and may be upstream of the first position on the path, may be downstream of the first position, or may be a position at which a state quantity based on the presence of the object CM at the first position is detected.

The non-contact detection at the second position may be detection of a change in a state quantity due to the presence of the object CM at the second position, or detection of the maintenance of a state quantity due to the presence of the object CM at the second position. The subject of the non-contact detection at the second position may be the state quantity at the second position, or may be the state quantity at a position other than the second position on the path. The position other than the second position is a position different from the position that is the subject of detection by the first sensor 21, and may be upstream of the second position on the path, may be downstream of the second position, or may be a position at which a state quantity based on the presence of the object CM at the first position is detected.

The change in the state quantity detected by the first sensor 21 or the maintenance of the state quantity may be caused by any of the following: the arrival of the object CM at the first position, the presence of the object CM at the first position, and the departure of the object CM at the first position. The change in the state quantity detected by the second sensor 22 or the maintenance of the state quantity may be caused by any of the following: the arrival of the object CM at the second position, the presence of the object CM at the second position, and the departure of the object CM at the second position.

The state quantity may be (i) an electrical state quantity such as current, voltage, capacitance, electrical resistance, frequency, inductance, etc., or (ii) a magnetic state quantity such as electromotive force, magnetic field strength, eddy current, etc. The state quantity may be (iii) a wave-dynamic state quantity such as the presence or absence of vibration, frequency, amplitude, phase, propagation speed, etc. The state quantity may be (iv) a thermal state quantity such as electromotive force that changes according to temperature and temperature difference, or an optical state quantity such as transmittance, reflectance, spectral distribution, etc. The state quantity may be a physical quantity resulting from the structure of the object CM, or a physical quantity resulting from the physical properties of the object CM. The state quantity may be a physical quantity resulting from the energy of the object CM, or a physical quantity resulting from energy applied to the object CM from the outside.

(i) The electrical state quantity may be electrical resistance measured using a two-terminal method, a four-terminal method, or the like. The sensor that detects the electrical resistance has two or more terminals for measuring the state quantity. The electrical resistance when the object CM is located between the terminals and the electrical resistance when the object CM is not located between the terminals have mutually different values. The sensor that detects the electrical resistance may detect that the object CM is present between the terminals based on measuring the electrical resistance when the object CM is located between the terminals. The sensor that detects the electrical resistance may use different materials for the materials constituting each terminal in order to reduce noise and increase measurement accuracy and durability.

The electrical state quantity may be capacitance measured using opposing electrodes. The capacitance when the object CM is located between the electrodes and the capacitance when the object CM is not located between the terminals show different values. The sensor that detects capacitance may detect the presence of the object CM between the electrodes based on measuring the capacitance when the object CM is located between the electrodes. Also, a signal at the resonant frequency when the object CM is located between the electrodes and the signal when the object CM is not located between the electrodes show different amplification factors. The sensor that detects the amplification factor may detect the presence of the object CM between the electrodes based on measuring the amplification factor when the object CM is located between the electrodes.

(ii) The magnetic state quantity may be an electromotive force generated when the object CM moves in a magnetic field, a magnetic field strength when the object CM moves in a magnetic field, or an eddy current generated when the object CM moves in a magnetic field. When the object CM moves in a magnetic field, if the flow rate of the object CM is small, the measured electromotive force is also small, and if the flow rate of the object CM is large, the measured electromotive force is also large. When a fluid such as a preservative moves in a magnetic field, if the flow rate is small due to the presence of the object CM, the measured electromotive force is also small, and if the flow rate is large due to the presence of the object CM, the measured electromotive force is also large. The sensor that detects the electromotive force may detect that the object CM is in the magnetic field based on the electromotive force being equal to or greater than a predetermined value. Also, when the object CM moves in a magnetic field, the electromotive force changes irregularly as noise due to the passage of the object CM. The sensor that detects the electromotive force may detect that the object CM is in the magnetic field based on the irregular change in the electromotive force.

(iii) The wave-dynamic state quantity may be the propagation speed of ultrasonic waves between the transmitting unit and the receiving unit, or the presence or absence of micro-vibrations detected by a piezoelectric element. The propagation speed of ultrasonic waves along the direction in which the fluid flows is higher than the propagation speed along the opposite direction to the direction in which the fluid flows. The sensor that detects the propagation speed may include a transmitting unit and a receiving unit. The sensor that detects the propagation speed may detect that the object CM is present between the transmitting unit and the receiving unit based on the detection of the propagation speed when the object CM flows at the detection position. The sensor that detects the presence or absence of micro-vibrations may include a piezoelectric element for detecting micro-vibrations, or may include a diaphragm or thin film for detecting micro-vibrations. The sensor that detects the presence or absence of micro-vibrations may detect that the object CM is present in the vicinity of the piezoelectric element based on the detection of micro-vibrations when the object CM flows.

(iv) The thermal state quantity may be the temperature of the terminal where heat is exchanged between the object CM and the one terminal, or may be an electromotive force generated according to the temperature difference between the two terminals. The amount of heat exchanged between the object CM and the one terminal and the amount of heat exchanged between a fluid such as a preservative solution and the one terminal have mutually different magnitudes. A sensor that detects temperature may detect that the object CM is present at the terminal position based on the detection of the temperature when the object CM is in contact with the one terminal. A sensor that detects the temperature difference between the two terminals may detect that the object CM is present between the terminals based on the detection of the temperature difference when the object CM is in contact with the terminals.

The detection result SG1 output by the first sensor 21 is data indicating whether or not an object CM is present at the first position, and may be data with a time index at the time of detection, or may be data including a state quantity measured by the first sensor 21, or a change in the state quantity. The detection result SG2 output by the second sensor 22 is data indicating whether or not an object CM is present at the second position, and may be data with a time index at the time of detection, or may be data including a state quantity measured by the second sensor 22, or a change in the state quantity.

[Situation Estimation]
The cell transfer device may include a control device 31 and a pressure application unit 41. The control device 31 may include an estimation unit 32 and a memory unit 33.

The estimation unit 32 estimates the status of the object CM using the detection result SG1 of the first sensor 21 and the detection result SG2 of the second sensor 22. The control device 31 outputs the estimation result D3 by the estimation unit 32. The estimation unit 32 may estimate the status of the object CM by a logical operation using the detection result SG1 of the first sensor 21 and the detection result SG2 of the second sensor 22.

The estimation unit 32 may apply the detection result SG1 of the first sensor 21 and the detection result SG2 of the second sensor 22 to the reference data stored in the memory unit 33 to estimate the status of the target object CM.

The estimation unit 32 may also count the number of times the presence of the object CM is detected in the detection results SG1 of the first sensor 21 during the period in which the object CM is pulled into the passage 11, and estimate the status of the object CM using the counting results. The estimation unit 32 may count the number of times the presence of the object CM is detected in the detection results SG1 of the first sensor 21 during the period in which the object CM is pushed out, and estimate the status of the object CM using the counting results.

The estimation unit 32 may also count the number of times the presence of the object CM is detected in the detection results SG2 of the second sensor 22 during the period in which the object CM is pulled into the passage 11, and estimate the status of the object CM using the counting results. The estimation unit 32 may count the number of times the presence of the object CM is detected in the detection results SG2 of the second sensor 22 during the period in which the object CM is pushed out, and estimate the status of the object CM using the counting results.

As a result, the status of the object CM is estimated based on the detection results SG1 and SG2 of the sensors 21 and 22. This reduces the load required to process the detection results SG1 and SG2, and makes it easier to grasp the status of the object CM during its movement.

The memory unit 33 stores reference data used by the estimation unit 32 for estimation. The reference data is data for deriving the status of the target object CM from the detection results SG1, SG2 of each sensor 21, 22. The reference data may be data that associates the detection results SG1, SG2 of each sensor 21, 22 with the status of the target object CM, or may be a calculation model that receives SG1, SG2 of each sensor 21, 22 as input and outputs the status of the target object CM.

The reference data may be the first distance LA or the second distance LB, or a predetermined time used for the estimation. The reference data may be the cross-sectional area of the passage 11, the force that draws the object CM into the passage 11, or the contact area between the object CM and the passage 11 estimated from the size of the object CM. The reference data may be the force that pushes the object CM out of the passage 11, or the volume of fluid measured by an external device when the object CM is pushed out of the passage 11.

The status of the object CM is the appearance of the object CM due to transportation, derived using the detection result SG1 of the first sensor 21 and the detection result SG2 of the second sensor 22. The status of the object CM may be (A) the status of the movement of the object CM on the route, (B) the status of the load received by the object CM on the route, or (C) the status of the shape of the object CM on the route.

(A) The movement status of the object CM may be (A1) that the object CM is between a first position and a second position. The movement status of the object CM may be (A2) that the object CM is located farther from the opening 12 than the second position, or (A3) that the object CM is located even closer to the opening 12 than the first position. In addition, the movement status of the object CM may be (A4) that the object CM is clogged in the passage 11.

(A1) The presence of the object CM between the first position and the second position may mean that the object CM has passed the first position and not reached the second position, or that the object CM has passed the second position and not reached the first position. The presence of the object CM between the first position and the second position may be detected based on the first sensor 21 detecting the presence of the object CM when the object CM is pulled in and then not detecting the presence of the object CM by the second sensor 22. The presence of the object CM between the first position and the second position may be detected based on the second sensor 22 detecting the presence of the object CM when the object CM is pushed out and then not detecting the presence of the object CM by the first sensor 21.

(A2) The object CM being located farther from the opening 12 than the second position may be detected when the object CM passes through the first position and then the second position. The object CM being located farther from the opening 12 than the second position may be detected when the object CM is pulled in and its presence is detected by the first sensor 21 and then the second sensor 22.

(A3) The object CM being located closer to the opening 12 than the first position may be detected when the object CM passes through the second position and then passes through the first position. The object CM being located closer to the opening 12 than the first position may be detected when the object CM is pushed out and its presence is detected by the second sensor 22 and then the first sensor 21.

(A4) The object CM being stuck in the passage 11 may mean that the object CM is stuck in the opening 12 of the passage 11, or that the object CM is stuck between the first position and the second position, or that the object CM is stuck in a position farther from the opening 12 than the second position.

The fact that the object CM is stuck in the opening 12 of the passage 11 may be detected based on the fact that the first sensor 21 does not detect the presence and the second sensor 22 does not detect the presence when a predetermined time has elapsed since the start of the retraction of the object CM. The fact that the object CM is stuck between the first position and the second position may be detected based on the fact that the first sensor 21 detects the presence and the second sensor 22 does not detect the presence when a predetermined time has elapsed since the start of the retraction of the object CM. The fact that the object CM is stuck between the first position and the second position may be detected based on the fact that the second sensor 22 detects the presence and the first sensor 21 does not detect the presence when a predetermined time has elapsed since the start of the extrusion of the object CM. The fact that the object CM is stuck in a position farther from the opening 12 than the second position may be detected based on the fact that the first sensor 21 does not detect the presence and the second sensor 22 does not detect the presence when a predetermined time has elapsed since the start of the extrusion of the object CM.

(B) The load condition of the object CM may be (B1) the speed of the object CM, or (B2) the resistance force that the object CM experiences in the liquid. The load condition of the object CM may be (B3) the friction force that the object CM experiences from the passage 11, or (B4) the state of the cells estimated from the speed, resistance force, friction force, etc. of the object CM. The state of the cells is a normal state and an abnormal state. Abnormal states include cell death, division, differentiation induction, dormancy, cytokine production, and expression of a specific gene.

(B1) The velocity of the object CM may be calculated by calculating the period between the time when the object CM was at the first position and the time when the object CM was at the second position, and dividing the second distance LB, which is the distance between the first position and the second position, by the period. The velocity of the object CM may be calculated by calculating the period from the start of the extrusion of the object CM to the time when the object CM reaches the second position, and calculating the fluid flow rate from the volume of fluid flowing through the passage 11 during that period, the cross-sectional area of the passage 11, and the period.

(B2) The resistance force acting on the object CM may be calculated using the size of the object CM and the difference between the flow velocity of the fluid described above and the velocity of the object CM (B1).
(B3) The frictional force applied to the object CM may be calculated using a force pulling the object CM into the passage 11, a contact area between the object CM and the passage 11 estimated from the size of the object CM, and (B1) the speed of the object CM. The frictional force applied to the object CM may be calculated using a force pushing the object CM out of the passage 11, a contact area between the object CM and the passage 11 estimated from the size of the object CM, and (B1) the speed of the object CM.

(C) The shape status of the object CM may be (C1) that the object CM has not been cleaved or decomposed, (C2) that the object CM has been cleaved or decomposed, or (C3) that a part of the object CM remains inside the passage 11. The shape status of the object CM may be (C4) that the object CM has not been deformed, or (C5) that the object CM has been deformed, or that the size of the object CM exceeds a predetermined size.

(C1) The fact that the target object CM has not been cleaved or decomposed may be detected based on the fact that the first sensor 21 or the second sensor 22 detects the presence of the target object CM once during the period from the start of the drawing of one target object CM to the end of the drawing. The fact that the target object CM has not been cleaved or decomposed may be detected based on the fact that the first sensor 21 detects the presence of the target object CM once and the second sensor 22 detects the presence of the target object CM once during the period from the start of the drawing of one target object CM to the end of the drawing.

Furthermore, the fact that the target object CM has not been torn apart or decomposed may be detected based on the fact that the first sensor 21 or the second sensor 22 detects the presence of the target object CM once during the period from the start of extrusion of one target object CM to the end of extrusion. Furthermore, the fact that the target object CM has not been torn apart or decomposed may be detected based on the fact that the second sensor 22 detects the presence of the target object CM once and the first sensor 21 detects the presence of the target object CM once during the period from the start of extrusion of one target object CM to the end of extrusion.

(C2) The fact that the target object CM has been cleaved or decomposed may be detected based on the first sensor 21 or the second sensor 22 detecting the presence of the target object CM two or more times during the period from the start of the drawing of one target object CM to the end of the drawing. The fact that the target object CM has been cleaved or decomposed may also be detected based on the first sensor 21 or the second sensor 22 detecting the presence of the target object CM two or more times during the period from the start of the extrusion of one target object CM to the end of the extrusion.

(C3) The fact that a part of the object CM remains inside the passage 11 may be detected based on the fact that the first sensor 21 detects the presence of the object CM once and the second sensor 22 detects the presence of the object CM twice or more during the period from the start to the end of the extrusion of one object CM.

(C4) The fact that the object CM is not deformed may mean that the object CM is not extending in the direction in which the passage 11 extends. The fact that the object CM is not extending may be detected based on the fact that the second distance LB is greater than the length of the object CM in the longitudinal direction and the detection period of the object CM by the first sensor 21 and the detection period of the object CM by the second sensor 22 do not overlap.

(C5) The deformation of the object CM may mean that the object CM is elongated in the direction in which the passage 11 extends. The size of the object CM exceeding a predetermined size may mean that the size of the object CM in the direction in which the passage 11 extends is greater than the second distance LB. The extension of the object CM may be detected based on the fact that the length of the object CM in the major axis direction is greater than the second distance LB, thereby causing the detection period of the object CM by the first sensor 21 and the detection period of the object CM by the second sensor 22 to overlap.

The pressure application unit 41 is connected to the base end 13, which is the end of the passage 11 opposite the opening 12. The pressure application unit 41 applies suction pressure to the inside of the passage 11 to draw the object CM into the passage 11. The pressure application unit 41 may also apply discharge pressure to the inside of the passage 11. The suction pressure applied by the pressure application unit 41 attracts the object CM to the opening 12, which is the tip of the passage 11. The discharge pressure applied by the pressure application unit 41 pushes the object CM out of the opening 12.

The control device 31 may input a command SG4 to the pressure application unit 41. The command SG4 causes the pressure application unit 41 to start and end the retraction. The command SG4 causes the pressure application unit 41 to start and end the extrusion. Upon receiving the command SG4 from the control device 31, the pressure application unit 41 quantitatively draws the fluid present around the target object CM into the passage 11. Upon receiving the command SG4 from the control device 31, the pressure application unit 41 quantitatively pushes out the fluid present around the target object CM from the passage 11.

[Cell transfer method]
As an example of a cell transfer method, a method using the above-mentioned cell transfer device will be described below.
A cell transfer method using a cell transfer device includes passing an object CM through a passage 11 that guides the object CM onto a path, detecting the presence or absence of the object CM at a first position on the path through which the object CM passes, and detecting the presence or absence of the object CM at a second position on the path.

As shown in FIG. 2, first, the opening 12 of the passage 11 is placed in a protective liquid containing the object CM. Next, the object CM is drawn into the passage 11 from the opening 12 of the passage 11. The drawing of the object CM may be performed by applying a suction pressure by the pressure application unit 41.

During this time, as shown by the dashed line in FIG. 2, until the object CM reaches the first position, the first sensor 21 outputs the absence of the object CM at the first position as a detection result SG1. The second sensor 22 also outputs the absence of the object CM at the second position as a detection result SG2. The estimation unit 32 estimates the status of the object CM based on the detection results SG1 and SG2. The estimation unit 32 outputs the estimation result D3 to the outside.

The estimation result D3 lets the user of the cell transfer device know that the object CM has not reached the first position. The user of the cell transfer device continues to pull in the object CM based on the fact that the object CM has not reached the first position. On the other hand, the user of the cell transfer device stops pulling in the object CM based on the fact that the condition of the object CM is abnormal, such as when the presence of the object CM is detected at both the first position and the second position, or when the presence of the object CM is detected at the second position.

As shown in FIG. 3, when the object CM reaches the first position, the first sensor 21 outputs the presence of the object CM at the first position as a detection result SG1. The second sensor 22 continues to output the absence of the object CM at the second position as a detection result SG2. The estimation unit 32 estimates the status of the object CM based on the detection results SG1 and SG2. The estimation unit 32 outputs the estimation result D3 to the outside.

The estimation result D3 lets the user of the cell transfer device know that the object CM has reached the first position. The user of the cell transfer device continues to pull in the object CM based on the object CM having reached the first position. On the other hand, the user of the cell transfer device stops pulling in the object CM based on the fact that the condition of the object CM is abnormal, such as when the presence of the object CM is detected at both the first and second positions.

When the object CM passes the first position, the first sensor 21 outputs the absence of the object CM at the first position as a detection result SG1. The second sensor 22 continues to output the absence of the object CM at the second position as a detection result SG2. The estimation unit 32 estimates the status of the object CM based on the detection results SG1 and SG2. The estimation unit 32 outputs the estimation result D3 to the outside.

The estimation result D3 lets the user of the cell transfer device know that the object CM has passed the first position. The user of the cell transfer device continues to pull in the object CM based on the object CM having passed the first position. On the other hand, the user of the cell transfer device stops pulling in the object CM based on the fact that the condition of the object CM is abnormal, such as when the presence of the object CM at the first position continues to be detected for a predetermined period of time or longer, or when the presence of the object CM is detected at both the first position and the second position.

As shown by the dashed line in FIG. 3, when the object CM reaches the second position, the first sensor 21 continues to output the absence of the object CM at the first position as a detection result SG1. The second sensor 22 continues to output the presence of the object CM at the second position as a detection result SG2. Then, when the object CM passes the second position, the first sensor 21 continues to output the absence of the object CM at the first position as a detection result SG1. The second sensor 22 outputs the absence of the object CM at the second position as a detection result SG2. The estimation unit 32 estimates the status of the object CM based on the detection results SG1 and SG2. The estimation unit 32 outputs the estimation result D3 to the outside.

The estimation result D3 informs the user of the cell transfer device that the object CM has passed the second position. The estimation result D3 also informs the user that the movement status, load status, or morphology status of the object CM is normal. The user of the cell transfer device ends the pulling of the object CM based on the fact that the status of the object CM is normal. This completes the transfer of the object CM from the storage environment to the internal environment of the cell transfer device.

On the other hand, the user of the cell transfer device stops the transfer of the object CM based on the abnormality detected in the estimation result D3. Note that the user of the cell transfer device performs an action such as removing the object CM after the attraction of the object CM has stopped and after the transfer of the object CM has stopped.

For example, as shown in FIG. 4, if the object CM becomes caught or clogged in the opening 12 when the object CM is drawn in, the presence of the object CM at the first position continues to be detected for a predetermined period of time or more. If the object CM is transferred while it is caught or clogged in the opening 12, the holding conditions for the object CM are not met, which may result in the object CM falling or the properties of the object CM deteriorating. In this regard, the estimation unit 32 described above estimates that the condition of the object CM is abnormal if the presence of the object CM at the first position continues to be detected for a predetermined period of time or more. As a result, it becomes possible for the user of the cell transfer device to know that the object CM is caught or clogged in the opening 12.

Then, the opening 12 of the passage 11 is placed in another environment, such as inside a living body. The object CM is then pushed toward the opening 12 of the passage 11. The object CM may be pushed out by applying a discharge pressure by the pressure application unit 41.

During this time, until the object CM reaches the second position, the first sensor 21 outputs the absence of the object CM at the first position as a detection result SG1. The second sensor 22 also outputs the absence of the object CM at the second position as a detection result SG2. The estimation unit 32 estimates the status of the object CM based on the detection results SG1 and SG2. The estimation unit 32 outputs the estimation result D3 to the outside.

The estimation result D3 lets the user of the cell transfer device know that the object CM has not reached the second position. The user of the cell transfer device continues pushing the object CM based on the fact that the object CM has not reached the second position. On the other hand, the user of the cell transfer device stops pushing the object CM based on the fact that the condition of the object CM is abnormal, such as when the presence of the object CM is detected at both the first position and the second position, or when the presence of the object CM is detected at the first position.

When the object CM reaches the second position, the first sensor 21 continues to output the absence of the object CM at the first position as a detection result SG1. The second sensor 22 outputs the presence of the object CM at the second position as a detection result SG2. The estimation unit 32 estimates the status of the object CM based on the detection results SG1 and SG2. The estimation unit 32 outputs the estimation result D3 to the outside.

The estimation result D3 lets the user of the cell transfer device know that the object CM has reached the second position. The user of the cell transfer device continues pushing the object CM based on the object CM having reached the second position. On the other hand, the user of the cell transfer device stops pushing the object CM based on the fact that the condition of the object CM is abnormal, such as when the presence of the object CM is detected at both the first position and the second position.

When the object CM passes through the second position, the first sensor 21 outputs the absence of the object CM at the first position as a detection result SG1. The second sensor 22 continues to output the absence of the object CM at the second position as a detection result SG2. The estimation unit 32 estimates the status of the object CM based on the detection results SG1 and SG2. The estimation unit 32 outputs the estimation result D3 to the outside.

The estimation result D3 lets the user of the cell transfer device know that the object CM has passed the second position. The user of the cell transfer device continues pushing the object CM based on the object CM having passed the second position. On the other hand, the user of the cell transfer device stops pushing the object CM based on the fact that the condition of the object CM is abnormal, such as when the presence of the object CM at the second position continues to be detected for a predetermined period of time or more, or when the presence of the object CM is detected at both the first position and the second position.

When the object CM reaches the first position, the first sensor 21 outputs the presence of the object CM at the first position as a detection result SG1. The second sensor 22 continues to output the absence of the object CM at the second position as a detection result SG2. Then, when the object CM passes the first position, the first sensor 21 outputs the absence of the object CM at the first position as a detection result SG1. The second sensor 22 continues to output the absence of the object CM at the second position as a detection result SG2. The estimation unit 32 estimates the status of the object CM based on the detection results SG1 and SG2. The estimation unit 32 outputs the estimation result D3 to the outside.

The inference result D3 informs the user of the cell transfer device that the object CM has passed the first position. The inference result D3 also informs the user that the movement status, load status, or morphology status of the object CM is normal. The user of the cell transfer device stops pushing the object CM based on the fact that the status of the object CM is normal. This completes the transfer from the internal environment of the cell transfer device to the placement environment of the object CM. On the other hand, the user of the cell transfer device takes action such as re-transferring the object CM based on the abnormality detected in the inference result D3.

As described above, according to the first embodiment, the following effects can be obtained.
(1-1) It is possible to grasp the movement of the object CM from the first position to the second position, or the movement of the object CM from the second position to the first position. Furthermore, it is possible to grasp that the object CM that has reached the first position has not reached the second position, or that the object CM that has reached the second position has not reached the first position. In other words, it is possible to grasp whether the object CM has moved smoothly along the path during the transport process of the object CM.

(1-2) Whether the object CM has moved smoothly through the needle-shaped body can be determined before the object CM is placed in the living body. This makes it possible to change the placement method or stop placement altogether based on the state of the object CM during the transfer process. As a result, it is possible to suppress variations in the action of cells after placement that are caused by transfer.

(1-3) In the extension direction of the passage 11, the second distance LB is greater than the size of the object CM including the hair follicle primordium. Therefore, it is possible to grasp with greater accuracy that the hair follicle primordium has moved from the first position to the second position, and that the hair follicle primordium has moved from the second position to the first position. Furthermore, it is possible to grasp with greater accuracy that a hair follicle primordium that has reached the first position has not reached the second position, and that a hair follicle primordium that has reached the second position has not reached the first position.

(1-4) The status of the object CM is estimated based on the detection results SG1 and SG2 of the sensors 21 and 22, which reduces the load required to process the detection results SG1 and SG2 and makes it easier to grasp the status of the object CM during its movement.

(1-5) Since the movement status, load status, and shape status of the object CM are estimated, it is possible to grasp in more detail any abnormalities occurring in the status of the object CM. If an abnormality occurs in the movement status, it is possible to take measures to attempt transportation again using the same object CM. On the other hand, if an abnormality occurs in the load status or shape status, it is necessary to replace the object CM itself. With the above configuration, it is also possible to take measures appropriate to the type of abnormality occurring in the object CM.

(1-6) If the first distance LA is equal to or less than the diameter of the object CM or equal to or less than the length of the object CM in the long axis direction of the object CM, it is possible to grasp a situation in which the object CM is stuck or clogged in the opening 12 of the passage 11.

Second Embodiment
A second embodiment of the cell transfer device and cell transfer method will be described below with reference to Figures 5 to 7. First, the configuration of the cell transfer device will be described, and then the cell transfer method using the cell transfer device will be described. The cell transfer device of the second embodiment differs from the cell transfer device of the first embodiment in the size of the second distance LB. Below, differences from the cell transfer device of the first embodiment will be described in detail, and components similar to those of the cell transfer device of the first embodiment will be assigned the same reference numerals and their description will be omitted.

[Cell transfer device]
5, the second distance LB is determined according to the state of the object CM to be grasped. For example, in the case where whether or not a foreign object smaller than the object CM has been drawn into the passage 11 is to be grasped as the state of the object CM, the second distance LB may be smaller than the diameter of the object CM or smaller than the length of the object CM in the long axis direction of the object CM.

The status of the object CM estimated by the estimation unit 32 is information derived using the detection result SG1 of the first sensor 21 and the detection result SG2 of the second sensor 22. The status of the object CM may be (D) the status of foreign matter in the moving environment of the object CM.

(D) The foreign matter mixing situation may be (D1) a foreign matter entering the inside of the passage 11 before the target object CM, or (D2) a foreign matter entering the inside of the passage after the target object CM.
(D1) The entry of a foreign object prior to the target object CM may be detected by first detecting non-detection of a moving object by the first sensor 21 and the second sensor 22 between a period during which the first sensor 21 detects the presence of a moving object and a period during which the second sensor 22 detects the presence of a moving object, and based on this non-detection, the moving object may be detected as a foreign object. Then, based on the overlapping of a period during which the first sensor 21 detects the presence of a moving object and a period during which the second sensor 22 detects the presence of a moving object, the entry of the target object CM after the foreign object may be detected.

(D2) The entry of a foreign object following the object CM may be detected by first recognizing that the period during which the first sensor 21 detects the presence of a moving object overlaps with the period during which the second sensor 22 detects the presence of a moving object, and based on this overlap in the detection periods, the entry of the object CM may be detected. Thereafter, between the period during which the first sensor 21 detects the presence of a moving object and the period during which the second sensor 22 detects the presence of a moving object, non-detection of the moving object by the first sensor 21 and the second sensor 22 may be recognized, and based on this non-detection, the moving object may be detected as a foreign object.

[Cell transfer method]
As an example of a cell transfer method, a method using the above-mentioned cell transfer device will be described below.
A cell transfer method using a cell transfer device includes passing an object CM through a passage 11 that guides the object CM onto a path, detecting the presence or absence of the object CM at a first position on the path through which the object CM passes, and detecting the presence or absence of the object CM at a second position on the path.

As shown in FIG. 6, first, the opening 12 of the passage 11 is placed in a protective liquid containing the object CM. Next, the object CM is drawn into the passage 11 from the opening 12 of the passage 11. The drawing of the object CM may be performed by applying a suction pressure by the pressure application unit 41.

Next, when the object CM reaches the first position, the first sensor 21 outputs the presence of the object CM at the first position as a detection result SG1. The second sensor 22 continues to output the absence of the object CM at the second position as a detection result SG2. The estimation unit 32 estimates the status of the object CM based on the detection results SG1 and SG2. The estimation unit 32 outputs the estimation result D3 to the outside.

Then, before the object CM passes through the first position, the object CM reaches the second position. When the object CM reaches the second position, the second sensor 22 outputs the presence of the object CM at the second position as a detection result SG2. At this time, the first sensor 21 continues to output the presence of the object CM at the first position as a detection result SG1. That is, the period during which the first sensor 21 detects the presence of the object CM and the period during which the second sensor 22 detects the presence of the object CM overlap. The estimation unit 32 estimates the status of the object CM based on the detection results SG1 and SG2. The estimation unit 32 outputs the estimation result D3 to the outside.

The inference result D3 allows the user of the cell transfer device to understand that one object CM is present at the first position and the second position. In other words, the inference result D3 allows the user to understand that the moving object detected by each of the sensors 21 and 22 is the object CM.

When the object CM passes the first position, the first sensor 21 outputs the absence of the object CM at the first position as a detection result SG1. The second sensor 22 outputs the presence of the object CM at the second position as a detection result SG2. Then, when the object CM passes the second position, the first sensor 21 continues to output the absence of the object CM at the first position as a detection result SG1. The second sensor 22 outputs the absence of the object CM at the second position as a detection result SG2. The estimation unit 32 estimates the status of the object CM based on the detection results SG1 and SG2. The estimation unit 32 outputs the estimation result D3 to the outside.

The estimation result D3 informs the user of the cell transfer device that the object CM has passed the second position. The estimation result D3 also informs the user that the movement status, load status, or morphology status of the object CM is normal. The user of the cell transfer device ends the pulling of the object CM based on the fact that the status of the object CM is normal. This completes the transfer of the object CM from the storage environment to the internal environment of the cell transfer device.

On the other hand, as shown in FIG. 7, when the foreign object PC first reaches the first position before the target object CM, the first sensor 21 outputs the presence of a moving object at the first position as a detection result SG1. The second sensor 22 continues to output the absence of a moving object at the second position as a detection result SG2. The estimation unit 32 estimates the status of the target object CM based on the detection results SG1 and SG2. The estimation unit 32 outputs the estimation result D3 to the outside.

Then, the foreign object PC passes through the first position, and thereafter, the foreign object PC reaches the second position. At this time, between the period in which the first sensor 21 detects the presence of a moving object and the period in which the second sensor 22 detects the presence of a moving object, there is a period in which each of the sensors 21, 22 detects the absence of a moving object. The estimation unit 32 estimates the status of the target object CM based on these detection results SG1, SG2. The estimation unit 32 outputs the estimation result D3 to the outside.

Here, if the size of the foreign object PC is smaller than the size of the target object CM, it becomes difficult to confirm the presence of the foreign object PC by other inspections during transportation. In particular, when working in an environment where the user's hands are present, fibrous foreign objects PC smaller than the target object CM often get mixed into the surrounding environment of the target object CM. In a configuration with a single sensor, it becomes difficult to distinguish between such foreign objects PC and the target object CM. In addition, air bubbles caused by the inflow of liquid often occur at the air-liquid interface in the surrounding environment of the target object CM. In a configuration with a single sensor, it becomes difficult to distinguish between such air bubbles and the target object CM.

In this regard, the inference result D3 allows the user of the cell transfer device to understand that the foreign object PC has passed the first position and is now at the second position. In other words, the inference result D3 allows the user to understand that the moving object detected by each of the sensors 21 and 22 is the foreign object PC, and that the foreign object PC entered before the target object CM.

As described above, according to the above embodiment, the following effects can be obtained.
(2-1) The state of detection by the sensors 21, 22 when the target object CM passes through is different from the state of detection by the sensors 21, 22 when the foreign object PC passes through. Therefore, it is possible to grasp that the foreign object PC has entered the passage 11.

(2-2) When a foreign object PC, such as dust or dirt, smaller than the target object CM moves along the path, the second sensor 22 begins to detect the presence of the foreign object PC after the first sensor 21 has finished detecting the presence of the foreign object PC. Alternatively, the first sensor 21 begins to detect the presence of the foreign object PC after the second sensor 22 has finished detecting the presence of the foreign object PC. Therefore, by using the sensors 21 and 22 to grasp the status of the target object CM, it can be grasped whether or not a foreign object PC has been mixed in along the path.

Each of the above embodiments can be modified as follows.
[sensor]
The sensors 21, 22 may be disposed on the inner surface of the passage 11 or on the outer surface of the passage 11. When the sensors 21, 22 are disposed on the inner surface of the passage 11, the inner surface of the passage 11 may have a recess, and the sensors 21, 22 may be embedded in the recess. If the sensors 21, 22 are configured to be embedded in the recess, the movement of the target object CM inside the passage 11 is prevented from being disturbed by the sensors 21, 22.

- In addition to the condition of the target object CM, each sensor 21, 22 may detect the properties of the fluid, such as the protective liquid, flowing through the passage 11. Curves or cracks in the passage 11, or foreign matter attached to the inside of the passage 11, change the properties of the fluid flowing through the passage 11. The properties of the fluid may be turbulence in the fluid flow, the electrical properties of the fluid, or the magnetic characteristics of the fluid. The detection results SG1, SG2 of the fluid by each sensor 21, 22 may be used to detect deterioration that may occur in the passage 11.

The cell transfer device may be provided with another first sensor 21 that detects the presence or absence of the object CM at the first position, and may be provided with another second sensor 22 that detects the presence or absence of the object CM at the second position. If multiple sensors are configured to detect the presence or absence of the object CM at the same position, it is possible to improve the detection accuracy of the detection result of the presence or absence of the object CM.

The cell transfer device may further include a third sensor that detects the presence or absence of the object CM at a third position on the path, or may detect the presence or absence of the object CM at four or more positions on the path. If the device is configured to estimate the status of the object CM based on the detection results at three or more positions on the path, it may be possible to improve the estimation accuracy.

- When one sensor has two or more terminals, a voltage may be applied between the terminals to attract foreign objects toward the terminals. With this configuration, it is also possible to distinguish between the target object CM and the foreign object PC inside the passage 11.

It should be noted that one of the modifications relating to the function of the sensor described above may be implemented in combination with another modification different from the modification.
[First Modification]
8, the terminals 21A, 21B constituting the first sensor 21 may be arranged on a spiral along the circumferential surface of the passage 11. The detection range of the first sensor 21 may have an elliptical ring shape arranged on a spiral along the circumferential surface of the passage 11. The first sensor 21 may be arranged on the inner surface of the passage 11 or on the outer surface of the passage 11, as in the respective embodiments.

The terminals 22A and 22B constituting the second sensor 22 may be arranged in a spiral along the circumferential surface of the passage 11. The detection range of the second sensor 22 may have an elliptical ring shape arranged in a spiral along the circumferential surface of the passage 11. The second sensor 22 may be arranged on the inner surface of the passage 11 as in each embodiment, or on the outer surface of the passage 11.

With this configuration, at least one of the sensors 21, 22 detects the object CM in a spiral range along the circumferential surface of the passage 11, so that the presence of the object CM can be detected even if the object CM is unevenly distributed in the circumferential direction of the passage 11.

[Second Modification]
9 , the terminals 21A, 21B constituting the first sensor 21 may be arranged on a ring shape along the circumferential surface of the passage 11. The detection range of the first sensor 21 may have a ring shape along the circumferential surface of the passage 11. The first sensor 21 may be arranged on the inner surface of the passage 11 or on the outer surface of the passage 11, as in the respective embodiments.

The terminals 22A and 22B constituting the second sensor 22 may be arranged on a ring along the circumferential surface of the passage 11. The detection range of the second sensor 22 may have a ring shape along the circumferential surface of the passage 11. The second sensor 22 may be arranged on the inner surface of the passage 11 as in each embodiment, or on the outer surface of the passage 11.

With this configuration, at least one of the sensors 21, 22 detects the object CM around the entire circumference of the passage 11, so that the presence of the object CM can be detected even if the object CM is unevenly distributed around the passage 11.

[Third Modification]
10 , the terminals 21A and 21B constituting the first sensor 21 may be disposed on a straight line along the extension direction of the passage 11. The first sensor 21 may be disposed on the inner surface of the passage 11 or on the outer surface of the passage 11, as in the respective embodiments.

The terminals 22A and 22B constituting the second sensor 22 may be arranged on a straight line along the extension direction of the passage 11. The second sensor 22 may be arranged on the inner surface of the passage 11 as in each embodiment, or on the outer surface of the passage 11.

The terminals 21A and 21B constituting the first sensor 21 and the terminals 22A and 22B constituting the second sensor 22 may be arranged on a straight line along the extension direction of the passage 11, with equal intervals of, for example, about 0.2 mm between them.

With this configuration, the sensors 21 and 22 are regularly arranged along the extension direction of the passage 11, making it easier to design the installation of the sensors 21 and 22 in the passage 11.

[Fourth Modification]
11 , the cell transfer device may include an extrapolation member 15 that supports the sensors 21, 22. The extrapolation member 15 defines a space inside the extrapolation member 15 for inserting and removing the passage 11. The first sensor 21 may be composed of a first transmission unit 21E and a first reception unit 21D. The second sensor 22 may be composed of a second transmission unit 22E and a second reception unit 22D. The transmission units 21E, 22E and the reception units 21D, 22D detect the presence or absence of the object CM from outside the passage 11.

The extrapolation member 15 may support the first transmitting unit 21E and the first receiving unit 21D so that they face each other. The extrapolation member 15 may support the second transmitting unit 22E and the second receiving unit 22D so that they face each other.

According to this configuration, the sensors 21, 22 are arranged radially outward in the passage 11. A design specialized for the arrangement of the object CM can be applied to the passage 11, and a design specialized for detecting the condition of the object CM can be applied to the extrapolation member 15. Furthermore, it is possible to adopt a common extrapolation member 15 for transfers using passages 11 having mutually different lengths.

It should be noted that the above-mentioned variation in sensor arrangement may be combined with the variation in sensor function described above.
[Fifth Modification]
As shown in Fig. 12, the passage 11 of the cell transfer device may include an insertion member 11BL inside the passage 11. The insertion member 11BL includes a holding end 11B, which is a tip for holding the object CM. The insertion member 11BL may separate a space inside the insertion member 11BL through which a fluid such as a protective liquid flows. The space separated by the insertion member 11BL is large enough that the object CM cannot enter. The holding end 11B of the insertion member 11BL may be an annular plane perpendicular to the direction in which the insertion member 11BL extends, or an elliptical annular plane intersecting the direction in which the insertion member 11BL extends.

The insertion member 11BL reciprocates inside the passage 11 along the extension direction of the passage 11. The insertion member 11BL reciprocates between a position where the holding end 11B protrudes from the opening of the passage 11 and a position where the holding end 11B is housed inside the passage 11. The insertion member 11BL reciprocates inside the passage 11 without holding the object CM at the holding end 11B. The insertion member 11BL also reciprocates inside the passage 11 with the object CM held at the holding end 11B.

The passage 11 defines a portion of the path along which the object CM moves. The insertion member 11BL protruding from the passage 11 defines the path along which the insertion member 11BL travels back and forth as a portion of the path along which the object CM moves.

The inside of the insertion member 11BL is connected to the pressure application unit 41. The pressure application unit 41 applies a suction pressure to the inside of the insertion member 11BL. The pressure application unit 41 may apply a discharge pressure to the inside of the insertion member 11BL. The suction pressure applied by the pressure application unit 41 attracts the object CM to the holding end 11B. The discharge pressure applied by the pressure application unit 41 detaches the object from the holding end 11B. The pressure application unit 41 does not have to be connected to the passage 11.

In the cell transfer method, the insertion member 11BL applies suction pressure to the object CM by the pressure application unit 41 at a position where the holding end 11B of the insertion member 11BL protrudes from the opening of the passage 11. The object CM receiving the suction pressure is guided toward the holding end 11B of the insertion member 11BL. The insertion member 11BL provided in the passage 11 guides the object CM along a path determined by the insertion member 11BL.

The insertion member 11BL holds the object CM on the holding end 11B by the action of suction pressure. With the object CM held on the holding end 11B, the insertion member 11BL moves the holding end 11B into the passage 11. As the holding end 11B moves, the insertion member 11BL accommodates the object CM inside the passage 11. As a result, the insertion member 11BL guides the object CM onto the path determined by the insertion member 11BL, and the passage 11 guides the object CM onto the path separated by the passage 11.

During this time, when the object CM passes the first position, the first sensor 21 outputs the presence of the object CM at the first position as a detection result SG1. When the object CM passes the second position, the second sensor 22 outputs the presence of the object CM at the second position as a detection result SG2. The estimation unit 32 estimates the situation of the object CM based on the detection results SG1 and SG2. The estimation unit 32 outputs the estimation result D3 to the outside.

The estimation result D3 lets the user of the cell transfer device know that the condition of the object CM is normal. Based on the fact that the condition of the object CM is normal, the user of the cell transfer device performs an action such as inserting the passage 11 into the living body, and moves the opening 12 of the passage 11 to the next environment. On the other hand, based on the fact that the condition of the object CM is abnormal, the user of the cell transfer device stops the transfer of the object CM.

Then, the insertion member 11BL moves again so that the holding end 11B protrudes from the opening 12 of the passage 11. As the insertion member 11BL moves, the insertion member 11BL protrudes the object CM from the opening 12 of the passage 11.

During this time, when the object CM passes the second position, the second sensor 22 outputs the presence of the object CM at the second position as a detection result SG2. When the object CM passes the first position, the first sensor 21 outputs the presence of the object CM at the first position as a detection result SG1. The estimation unit 32 estimates the status of the object CM based on the detection results SG1 and SG2. The estimation unit 32 outputs the estimation result D3 to the outside.

The estimation result D3 lets the user of the cell transfer device know that the condition of the object CM is normal. Based on the fact that the condition of the object CM is normal, the user of the cell transfer device causes the pressure application unit 41 to stop applying suction pressure. Alternatively, the user of the cell transfer device causes the pressure application unit 41 to start applying discharge pressure. As a result, the object CM is detached from the holding end 11B of the insertion member 11BL and placed in the next environment. Note that the user of the cell transfer device stops placing the object CM based on the fact that the condition of the object CM is abnormal.

In this way, the insertion member 11BL guides the movement of the object in the extension direction of the passage 11, thereby suppressing variation in the direction of movement of the object CM and variation in the condition of the object CM. Note that the modification example including the insertion member can also be implemented in combination with the modification example related to the function of the sensor described above or the modification example related to the placement of the sensor.

[Sixth Modification]
In each of the above embodiments, the second sensor 22 may monitor the suction pressure when the fluid is drawn into the passage 11. In the above fifth modified example, the second sensor 22 may monitor the suction pressure when the fluid is drawn into the insertion member 11BL. The second sensor 22 may output the monitored suction pressure to the pressure application unit 41.

In each of the above embodiments, the second sensor 22 may monitor the discharge pressure when the fluid is pushed out of the passage 11. In the above fifth modified example, the second sensor 22 may monitor the discharge pressure when the fluid is pushed out of the insertion member 11BL. The second sensor 22 may output the monitored result of the discharge pressure to the pressure application unit 41.

As shown in FIG. 13, the control device 31 may input a command SG4 to start drawing to the pressure application unit 41. The pressure application unit 41 quantitatively draws the fluid around the target object CM into the passage 11. The pressure application unit 41 may include the suction pressure by the second sensor 22 in the detection result SG2 and continue to output the detection result SG2 to the control device 31. The control device 31 may detect the presence or absence of the target object CM based on the suction pressure included in the detection result SG2. The detection of the presence or absence of the target object CM based on the suction pressure may be a determination result of whether the suction pressure has increased in the negative direction, whether the suction pressure is equal to or greater than a predetermined value in the negative direction, or whether a fluctuation has been observed in the suction pressure.

The control device 31 may input a command SG4 to start the extrusion to the pressure application unit 41. The pressure application unit 41 may include the discharge pressure by the second sensor 22 in the detection result SG2 and continue to output the detection result SG2 to the control device 31. The control device 31 may detect the presence or absence of the object CM based on the discharge pressure included in the detection result SG2. The detection of the presence or absence of the object CM based on the discharge pressure may be a determination result of whether or not the discharge pressure has decreased in a positive direction, whether or not the discharge pressure is equal to or lower than a predetermined value in a positive direction, or whether or not a fluctuation has been observed in the discharge pressure.

The suction pressure for drawing the object CM into the passage 11 is greater in the negative direction than the suction pressure for drawing only fluid into the passage 11. An increase in the suction pressure in the negative direction is an indication that the object CM has just been drawn into the opening of the passage 11. The discharge pressure for pushing only fluid out of the passage 11 is smaller in the positive direction than the discharge pressure for pushing the object CM out of the passage 11. A decrease in the discharge pressure in the positive direction is an indication that the object CM has just been pushed out from the opening of the passage 11.

The pressure application unit 41 may quantitatively draw in the fluid present around the target object CM into the insertion member 11BL. In this case, the pressure application unit 41 may include the suction pressure by the second sensor 22 in the detection result SG2 and continue to output the detection result SG2 to the control device 31. The control device 31 may detect the presence or absence of the target object CM at the holding end 11B of the insertion member 11BL based on the suction pressure included in the detection result SG2. The pressure application unit 41 may also include the discharge pressure by the second sensor 22 in the detection result SG2 and continue to output the detection result SG2 to the control device 31. The control device 31 may detect the presence or absence of the target object CM at the holding end 11B of the insertion member 11BL based on the discharge pressure included in the detection result SG2.

In this way, since it is possible to detect the presence or absence of the object CM outside the passage 11, it is possible to expand the degree of freedom in the configuration for grasping the status of the object CM during the transfer process. Furthermore, it is possible to detect the presence or absence of the object CM without contacting the object CM, and to detect the presence or absence of the object CM without applying energy other than the load required for transfer to the object CM. Therefore, it is possible to reduce the impact on the survival rate and activity level of the cells when grasping the status of the object CM. Note that the modification example in which the second sensor monitors the suction pressure can also be implemented in combination with the modification example related to the sensor function or the modification example related to the sensor arrangement described above, assuming that the second sensor is separately provided.

[unit]
The passage 11, the first sensor 21, and the second sensor 22 may form a single unit. The cell transfer device may include a plurality of units and simultaneously drive separate pressure application units 41 connected to each passage 11, or may drive a single pressure application unit 41 common to each passage 11. In this way, the cell transfer device may simultaneously suck separate objects CM into each passage 11.

In this way, since multiple passages 11 simultaneously suck in the target CM, it is possible to grasp the status of the target CM during the transfer process and improve the transfer efficiency at the same time. In particular, the improvement in transfer efficiency is remarkable in regeneration technology that requires the transfer of multiple hair follicle primordia as separate targets CM. Note that the modification example in which the pressure of each passage 11 is changed simultaneously can also be implemented in combination with at least one of the modification examples related to the sensor function, the modification example related to the sensor arrangement, the modification example including an insertion member, and the modification example in which the suction pressure is monitored, which have been described above.

CM: object; LA: first distance; LB: second distance; 11: passage; 11BL: insertion member; 12: opening; 13: base end; 21: first sensor; 22: second sensor; 31: control device; 32: estimation unit; 33: memory unit; 41: pressure application unit;

Claims (10)

A cell transfer device for transferring an object containing cells, comprising:
A passage for guiding the object along a path;
a first sensor that detects the presence or absence of the object at a first position on the passage based on a change in an optical state quantity caused by the object;
a second sensor that detects the presence or absence of the object at a second position on the passage based on a change in an optical state quantity caused by the object ;
The object includes a cell or a cell group composed of a plurality of cells,
The passage extends along an extension direction,
The first sensor and the second sensor are aligned along the extension direction,
a pressure applying unit that applies a suction pressure to the inside of the passage so as to draw the object into the inside of the passage,
The pressure application unit is configured to be capable of applying the suction pressure to the inside of the passage such that the object passes through the first position and reaches the second position.
Cell transfer device. The passage is a needle-shaped body for placing the object in a living body,
The cell transfer device according to claim 1 , wherein the first sensor and the second sensor are disposed on the needle-shaped body. The passage is a needle-shaped body for placing the object in a living body,
The cell transfer device according to claim 1 , wherein at least one of the first sensor and the second sensor is disposed radially outward of the needle-shaped body. The subject includes a hair follicle primordium,
The cell transfer device according to claim 1 , wherein a distance between the first position and the second position is greater than the distance between the first position and the second position. The subject includes a hair follicle primordium,
The cell transfer device according to claim 1 , wherein a distance between the first position and the second position is smaller than the distance between the first position and the second position. the passageway, the first sensor, and the second sensor are a single unit;
A plurality of the units are provided,
The pressure application unit is configured to be able to simultaneously apply pressure to the inside of each passage.
The cell transfer device according to any one of claims 1 to 5. The cell transfer device according to claim 1 , wherein at least one of the first sensor and the second sensor detects the presence or absence of the object along a circumferential direction of the passage. The cell transfer device according to claim 1 , wherein at least one of the first sensor and the second sensor detects the presence or absence of the object on a spiral extending in the extension direction of the path. The cell transfer device according to claim 1 , further comprising an estimation unit that estimates a state of the object using a detection result of the first sensor and a detection result of the second sensor. A cell transfer method for transferring an object containing cells, comprising the steps of:
a pressure application unit of the cell transfer device passing the object through a passage of the cell transfer device excluding biological tissue;
Detecting the presence or absence of the object at a first position on the path through which the object passes by detecting a change in an optical state quantity caused by the object; and
detecting the presence or absence of the object at a second position on the passage based on a change in an optical state quantity caused by the object ;
The object includes a cell or a cell group composed of a plurality of cells,
The passage extends along an extension direction,
The first position and the second position are aligned along the extension direction,
The pressure application unit is configured to be capable of applying a suction pressure to the inside of the passage such that the object passes through the first position and reaches the second position.
Cell transfer methods.