Sample processing apparatus, sample processing system, and cartridge

Abstract

To detect an inclination of a cartridge, the cartridge being configured to internally perform processing on a cell.SOLUTION: A sample processing apparatus according to the present embodiment includes an apparatus body. In the apparatus body, a cartridge for internally performing processing on a cell is installed, and the apparatus body controls liquid feeding in the cartridge and / or adjusts an environment in the cartridge. The apparatus body includes a detector configured to detect an inclination of the cartridge with respect to a horizontal plane and / or the apparatus body.SELECTED DRAWING: Figure 5

Description

[Technical field]

[0001] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The embodiments disclosed in the specification and drawings relate to sample processing devices, sample processing systems, and cartridges. [Background technology]

[0002] Conventionally, the production of induced pluripotent stem cells (hereinafter referred to as iPS cells) has been performed manually by skilled workers in facilities such as safety cabinets. Facilities such as safety cabinets are expensive, and the labor costs of workers are also required, so the production of iPS cells is very expensive. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] International Publication No. 2016 / 172350 Summary of the Invention [Problem to be solved by the invention]

[0004] As a method for reducing the cost of producing iPS cells, for example, a cartridge including a flow path for processing a cell suspension may be set in a device having a liquid transfer function to perform a liquid transfer process. However, the present inventors have found that if the cartridge is tilted, the filter for collecting target cells and / or the culture vessel in the cartridge may also be tilted, making it impossible to properly process the cell suspension.

[0005] One of the problems to be solved by the embodiments disclosed in this specification and the drawings is to detect the inclination of a cartridge for performing cell processing inside the cartridge. However, the problems to be solved by the embodiments disclosed in this specification and the drawings are not limited to the above problem. Problems corresponding to the effects of each configuration shown in the embodiments described later can also be positioned as other problems. [Means for solving the problem]

[0006] The sample processing device according to the embodiment includes an apparatus body. The apparatus body is provided with a cartridge for performing cell processing therein, and controls liquid delivery within the cartridge and / or adjusts the environment within the cartridge. The apparatus body has a detection unit that detects the inclination of the cartridge relative to a horizontal plane and / or the apparatus body. [Brief description of the drawings]

[0007] [Figure 1] FIG. 1 is a diagram showing an example of the appearance of a sample processing system according to an embodiment. [Diagram 2] FIG. 2 is a diagram showing an example of the configuration of a sample processing apparatus according to an embodiment. [Diagram 3] FIG. 3 is a diagram showing an example of an internal configuration of the cartridge as viewed from the X direction in the embodiment. [Figure 4] FIG. 4 is a diagram showing an example of an external appearance of the cartridge in the embodiment. [Diagram 5] FIG. 5 is a diagram showing an example of the positional relationship between a level and a reading device that reads the level in the embodiment. [Figure 6] FIG. 6 is a diagram showing an example of a movement MDM of the cartridge by the transport device in the embodiment. [Figure 7] FIG. 7 is a flowchart showing an example of a procedure of a cartridge inclination detection process in the embodiment. [Figure 8] FIG. 8 is a diagram showing an example of the positional relationship between a level and a reading device 631 that reads the level according to a first modified example of the embodiment. [Figure 9]FIG. 9 is a diagram showing an example of a positional relationship between a contact device and a cartridge according to a second modified example of the embodiment. [Figure 10] 10 is a diagram showing an example of a positional relationship between an arm and a cartridge in two positions according to a third modified example of the embodiment. FIG. [Figure 11] FIG. 11 is a diagram showing an example of a positional relationship between a plurality of sensors and a cartridge according to a fourth modified example of the embodiment. [Figure 12] FIG. 12 is a flowchart showing an example of a procedure of a cartridge inclination detection process according to a fourth modified example of the embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0008] The sample processing device, sample processing system, and cartridge will be described below with reference to the drawings. In the following embodiments, parts with the same reference numerals perform the same operations, and duplicated descriptions will be omitted as appropriate. In addition, the contents described in one embodiment are, in principle, also applicable to modified examples, application examples, and the like.

[0009] (Embodiment) Fig. 1 is a diagram showing an example of the external appearance of a sample processing system 1 according to this embodiment. As shown in Fig. 1, the sample processing system 1 includes a cartridge 3 and a sample processing device 5. The cartridge 3 is inserted into the sample processing device 5 by an operator (user) OP. Before inserting the cartridge 3 into the sample processing device 5, the operator OP fills the cartridge 3 with a sample and a reagent in advance.

[0010] Fig. 2 is a diagram showing an example of the configuration of sample processing device 5. As shown in Fig. 2, sample processing device 5 has an input interface 51, an output interface 53, a memory 55, a transport device 57, a cooling device 59, a valve drive device 61, a liquid delivery device 63, an incubator 65, and a processing circuit 67. A cartridge 3 for internally performing cell processing is installed in the device body of sample processing device 5. As a result, the device body controls the delivery of liquid within the cartridge and / or adjusts the environment within the cartridge.

[0011] The cartridge 3 will be described below with reference to Fig. 3 and Fig. 4. Fig. 3 is a diagram showing an example of the internal configuration of the cartridge 3 as viewed from the X direction. Fig. 4 is a diagram showing an example of the external appearance of the cartridge 3. The cartridge 3 internally processes cells, which are a sample. Specifically, the cartridge 3 processes the cells through various operations by the sample processing device 5.

[0012] 3, the cartridge 3 includes, for example, a sample container, a reagent container, a plurality of storage containers 30, a filter 31 for collecting target cells, a waste liquid container 32, a spiral channel 33, a tapered container 34, an expansion culture container 35, an infection container 36, a pre-culture container 37, a culture container 38 for cell culture, a heat insulating material 39, a plurality of tubes 40, and a plurality of valves 41. Also, as shown in FIG. 4, a level 45 is attached to the cartridge 3.

[0013] In the cartridge 3, a sample container and a reagent container are arranged on the rear side of the multiple storage containers 30 shown in FIG. 3. The sample container holds the sample to be aspirated. The sample is, for example, human blood. In this case, the sample container corresponds to a blood pack. Note that the sample is not limited to blood, and may be other turbid liquids. The reagent container holds the reagent to be aspirated. When the sample processing device 5 produces induced pluripotent stem cells (hereinafter referred to as iPS (induced pluripotent stem cell) cells), the reagent is, for example, a reagent necessary for producing iPS cells. Since known reagents can be applied as the reagent necessary for producing iPS cells, a description thereof will be omitted.

[0014] The plurality of storage containers 30 stores, for example, physiological saline. As the physiological saline, for example, PBS (phosphate-buffered saline) may be used. The storage containers 30 store a sample aspirated from a sample container by a liquid delivery device 63 described later. Among the plurality of storage containers 30, a storage container other than the storage container in which the sample is stored stores a sample aspirated from a reagent container by the liquid delivery device 63. In the other storage containers among the plurality of storage containers 30, residue remaining on the filter 31 is collected and stored by backwashing the filter 31. In this case, the other storage containers 30 may be referred to as collection containers.

[0015] The filter 31 filters out particles in the sample, which is a suspension. For example, the filter 31 collects target cells for cell culture carried out in the culture vessel 38. The target cells, which are particles, are, for example, red blood cells, white blood cells, etc. The waste liquid vessel 32 is, for example, a vessel for collecting the suspension after filtering by the filter 31. Descriptions of the spiral flow channel 33, the tapered vessel 34, the expansion culture vessel 35, the infection vessel 36, and the pre-culture vessel 37 will be omitted.

[0016] In the culture vessel 38, a sample and a reagent are mixed. The culture vessel 38 may be called a mixing vessel in which a sample and a reagent are mixed. For example, in the culture vessel 38, a sample that has been subjected to various processes and a reagent are mixed. The culture vessel 38 is a vessel used for cell culture. The contents in the culture vessel 38 (target cells for cell culture) are cultured by an incubator 65 described below.

[0017] 3, a heat insulator 39 is disposed between the tapered container 34 and the expansion culture container 35. The heat insulator 39 keeps the temperature, etc., of the culture container 38 and the expansion culture container 35 in the cartridge 3 inserted into the incubator 65, for example, constant.

[0018] 3, the multiple tubes 40 respectively connect, for example, the sample container, the reagent container, the multiple storage containers 30, the filter 31, the waste liquid container 32, the spiral channel 33, the tapered container 34, the expansion culture container 35, the infection container 36, the pre-culture container 37, the culture container 38, etc. The channel formed by the multiple tubes 40 is realized as a closed system (hereinafter referred to as a closed system channel) as shown in FIG.

[0019] The multiple valves 41 are provided in the multiple tubes 40. In other words, the multiple tubes 40 are each provided with the multiple valves 41. Each of the multiple valves 41 uses a magnet or a magnetic body with the tube 40 as an opening / closing member. Each of the multiple valves 41 switches the flow path in the closed flow path via a cover (wall) of the cartridge 3 parallel to the YZ plane by a valve drive device 61 described below under the control of a control function 673 of the processing circuit 67.

[0020] As shown in FIG. 4, the cartridge 3 includes a level gauge 45. The level gauge 45 is attached to a housing constituting the exterior of the cartridge 3, for example, so that the bottom or top surface of the cartridge 3 indicates a horizontal plane. The level gauge 45 measures the horizontal state of the cartridge 3. The horizontal state is, for example, a numerical value reflecting the degree of horizontality of the cartridge 3, the gradient of the cartridge 3, the position of the bubble in the bubble tube of the level gauge 45, etc. As a known level gauge 45 can be applied, a description thereof will be omitted. Note that a goniometer that detects the inclination of the cartridge 3 with respect to the horizontal plane may be used as the level gauge 45. The attachment position of the level gauge 45 is not limited to that shown in FIG. 4, and it can be set at any position on the top surface of the cartridge 3.

[0021] The configuration of the sample processing device 5 will now be described with reference to FIGS.

[0022] The input interface 51 accepts various input operations from an operator OP who operates the sample processing device 5, converts the accepted input operations into electrical signals, and outputs them to the processing circuit 67. For example, the input interface 51 accepts selection instructions, various conditions, etc. from the operator. As the input interface 51, for example, a mouse, a keyboard, a trackball, a switch, a button, a joystick, a touch pad, a touch panel display, etc. can be used as appropriate.

[0023] In this embodiment, the input interface 51 is not limited to one having physical operation parts such as a mouse, keyboard, trackball, switch, button, joystick, touchpad, and touch panel display. For example, an example of the input interface 51 includes an electrical signal processing circuit that receives an electrical signal corresponding to an input operation from an external input device provided separately from the device and outputs the electrical signal to the processing circuit 67. The input interface 51 may also be configured as a tablet terminal or the like capable of wireless communication with the sample processing device 5 main body.

[0024] The output interface 53 has, for example, a communication interface and a display. The output interface 53 may further have a speaker that outputs audio to the operator OP. The communication interface performs data communication, for example, between the sample processing device 5 and a network. The communication standard between the communication interface and the network may be any standard.

[0025] The display displays various types of information. For example, the display outputs a GUI (Graphical User Interface) for receiving various operations from a user. For example, a liquid crystal display (LCD), a cathode ray tube (CRT) display, an organic electroluminescence display (OLED), a plasma display, or any other display can be used as appropriate. The display may be a desktop type, or may be configured as a tablet terminal or the like capable of wireless communication with the sample processing device 5.

[0026] The memory 55 is a storage device such as an HDD (Hard disk Drive), an SSD (Solid State Drive), or an integrated circuit storage device that stores various information. The memory 13 may be a drive device that reads and writes various information between the memory 55 and a portable storage medium such as a CD (Compact Disc), a DVD (Digital Versatile Disc), or a flash memory, or a semiconductor memory element such as a RAM (Random Access Memory), in addition to an HDD or SSD.

[0027] The memory 55 stores various programs related to the execution of, for example, an information acquisition function 671, a control function 673, a detection function 675, etc. The memory 55 stores information related to sample processing (hereinafter referred to as sample processing information) acquired from the input interface 51, etc. by the information acquisition function 671. The sample processing information is information related to sample processing, such as the amount of sample aspirated from a sample container, the amount of reagent aspirated from a reagent container, and the placement time at which the culture container (mixing container) 38 is placed in the incubator 65. The memory 55 stores the tilt of the cartridge 3 detected by the detection function 675.

[0028] The transport device 57 moves the cartridge 3 to a position for aspirating and discharging the sample and reagent (hereinafter referred to as the aspirating and discharging position) under the control of the control function 673. The transport device 57 moves the cartridge 3 from the aspirating and discharging position to the incubator 65 by the control function 673. The transport device 57 moves the cartridge 3 from the incubator 65 to the aspirating and discharging position by the control function 673. The transport device 57 moves the cartridge 3 from the sample processing device 5 to the outside of the sample processing device 5 by the control function 673. For example, the transport device 57 is capable of placing the cartridge 3 thereon and transports the cartridge 3 in a horizontal direction. The transport device 57 corresponds to a transport section.

[0029] When the cartridge 3 is inserted into the sample processing device 5, the cooling device 59 cools the cartridge 3 under the control of the control function 673. The cooling device 59 is realized by, for example, a Peltier element. The cooling device 59 cools, for example, one side of the cartridge 3 that is in contact with the cooling device 59 under the control of the control function 673.

[0030] The valve drive device 61 drives the opening and closing of the valve 41 by magnetic interaction with the magnet or magnetic body in the valve 41 under the control of the control function 673. That is, the valve drive device 61 drives the opening and closing of the valve 41 by magnetic interaction from outside the cartridge 3, via the cover of the cartridge 3. Specifically, the valve drive device 61 has a magnet (hereinafter referred to as a first magnet) in the valve 41 or a magnet (hereinafter referred to as a second magnet) that attracts the magnetic body via the cover of the cartridge 3, a movement support mechanism that supports the second magnet so that it can move in the horizontal direction, and a power source that supplies power to the movement support mechanism. The valve drive device 61 corresponds to a valve drive unit.

[0031] The moving support mechanism is realized by, for example, an actuator that supports the second magnet at its tip. The moving support mechanism may be a known actuator such as, for example, a double-acting air cylinder, a single-acting air cylinder, or a hydraulic cylinder. Under the control of the control function 673, the moving support mechanism moves the second magnet closer to the cartridge 3 or moves the second magnet away from the cartridge 3. This moves the first magnet or magnetic body in the valve 41, thereby opening and closing the valve 41.

[0032] The liquid delivery device 63 has a pressure pad (which may be called a pressurizing pad) that can move in the vertical direction (Z direction) and a moving mechanism that can move in the longitudinal direction (Y direction) of the cartridge 3. The liquid delivery device 63 is moved under the control of the control function 673 so that the pressure pad connection part connected to the storage container 30 is located directly below the pressure pad. Next, the liquid delivery device 63 lowers the pressure pad arranged at the tip of the liquid delivery device 63 so as to be in close contact with the pressure pad connection part by the control function 673. Next, the liquid delivery device 63 sucks or pumps air in the pressure chamber through the pressure pad and the pressure pad connection part by the control function 673. As a result, the pressure in the storage container is reduced or increased, and the sample or reagent is sucked or discharged through the tube 40. As a result, the liquid delivery device 63 controls the liquid delivery in the cartridge.

[0033] The liquid delivery device 63 includes a reading device that reads the level. For example, the liquid delivery device 63 is equipped with a reading device near the tip of a pressure pad or the like. The reading device reads, for example, the position of an air bubble in the level by, for example, an optical method. Note that the reading device is not limited to a device that realizes optical reading, and may be realized by, for example, a reader that uses electromagnetic waves, a laser, or the like. As a reading device, a known one can be applied, and therefore a description thereof will be omitted.

[0034] FIG. 5 is a diagram showing an example of the positional relationship between the level 45 and a reading device 631 that reads the level 45. In FIG. 5, the reading device 631 is provided at the tip of an arm 635 that movably supports the pressure pad 633 together with the pressure pad 633. The installation location of the reading device 631 is not limited to the tip of the arm 635 in the liquid delivery device 63, and can be installed at any position close to the cartridge 3 when the cartridge 3 is inserted into the sample processing device 5, such as the end of the incubator 65 or the end of the cooling device 59, as a modified example, as shown in FIG. 5. In the following, for the sake of specificity, the reading device 631 will be described as being installed at the tip of the liquid delivery device 63.

[0035] When the cartridge 3 is set in the sample processing device 5 and an instruction to operate the device is input via the input interface 51, the reader 631 executes a reading operation on the level 45. In the reading operation, for example, first, under the control of the control function 673, the liquid delivery device 63 is moved by the moving mechanism in the liquid delivery device 63 so that the pressure-feeding pad connection part 43 connected to the storage container 30 is located directly below the pressure-feeding pad 633 and the reader 631 is located directly above the level 45 (LDM). Next, when the pressure-feeding pad 633 is lowered (DN) to the pressure-feeding pad connection part 43 by the moving mechanism, the reader 631 reads the horizontal state of the level 45 from the level 45. For example, the reader 631 reads the horizontal state from the level 45 when the distance from the level 45 becomes equal to or less than a predetermined distance. The reader 631 outputs the result (horizontal state) read from the level 45 to the processing circuit 67. The reading device 631 corresponds to a reading unit. Note that the reading device 631 may perform a reading operation even in a case where contact with the cartridge 3 by the operator OP is expected, such as when a reagent or the like is set.

[0036] 5 shows a form in which the liquid delivery device 63 moves relative to the cartridge 3 when reading the level 45, but the cartridge side may be moved by the transport device 57 when reading the level 45. FIG. 6 is a diagram showing an example of movement MDM of the cartridge 3 by the transport device 57. At this time, in the reading operation, the cartridge 3 is moved along the Y direction together with the cooling device 59. Note that both the liquid delivery device 63 and the cartridge 3 may be moved in the reading operation, etc.

[0037] The incubator 65 realizes an environment suitable for culturing in the culture container 38. For example, the incubator 65 realizes a carbon dioxide concentration, an oxygen concentration, a temperature, and a humidity suitable for culturing under the control of the control function 673. In this way, the incubator 65 adjusts the environment inside the cartridge. As the incubator 65, a known incubator can be applied, and therefore a description thereof will be omitted.

[0038] The processing circuitry 67 controls the overall operation of the sample processing device 5 in accordance with the sample processing information output from the input interface 51 or the memory 55. For example, the processing circuitry 67 has, as hardware resources, a processor such as a CPU (Central Processing Unit), MPU (Micro Processing Unit), or GPU (Graphics Processing Unit), and a memory such as a ROM (Read Only Memory) or RAM.

[0039] In addition, the processing circuit 67 may be realized by an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), other complex programmable logic devices (CPLDs), simple programmable logic devices (SPLDs), etc.

[0040] The processing circuit 67 has, for example, an information acquisition function 671, a control function 673, and a detection function 675. The information acquisition function 671, the control function 673, and the detection function 675 are stored in the memory 55 in the form of a program executable by a computer. The processing circuit 67 executes the information acquisition function 671, the control function 673, and the detection function 675 by a processor that executes a program deployed in the memory of the processing circuit 67 itself.

[0041] That is, the processing circuit 67 corresponds to a processor that realizes a function corresponding to each program by reading and executing the program from the memory 55. In other words, the processing circuit 67 in a state in which each program is read has a function corresponding to the read program. Note that each function in the information acquisition function 671, the control function 673, and the detection function 675 is not limited to being realized by a single processing circuit. A processing circuit may be configured by combining a plurality of independent processors, and each processor may execute a program to realize each function in the information acquisition function 671, the control function 673, and the detection function 675. The processing circuit 67 that realizes the information acquisition function 671, the control function 673, and the detection function 675 is an example of an information acquisition unit, a control unit, and a detection unit.

[0042] The processing circuit 67 acquires the sample processing information output from the input interface 51 by the information acquisition function 671. The information acquisition function 671 stores the acquired sample processing information in the memory 55.

[0043] The processing circuit 67 controls the entire sample processing device 5 through the control function 673. For example, the control function 673 controls the transport device 57, the cooling device 59, the valve drive device 61, the liquid delivery device 63, and the incubator 65 in accordance with the sample processing information. For example, when the cartridge 3 is inserted into the sample processing device 5, the control function 673 controls at least one of the transport device 57 and the liquid delivery device 63 in accordance with the sample processing information so as to position the cartridge 3 at a position related to the aspirating and discharging of the sample. At this time, the control function 673 controls the cooling device 59 to cool the cartridge 3.

[0044] The processing circuit 67 controls the valve drive device 61 by the control function 673 in accordance with the sample processing information. Specifically, the control function 673 moves the position of the valve drive device 61 relative to the cartridge 3 in accordance with the sample processing information. Next, the control function 673 controls the valve drive device 61 in accordance with the sample processing information to drive the valve 41 provided in the cartridge 3.

[0045] The processing circuit 67 controls the liquid delivery device 63 by the control function 673 in accordance with the sample processing information. For example, the control function 673 controls the movement of the liquid delivery device 63 so that the storage container 30 is located directly under the pressure-feeding pad 633 at the tip of the liquid delivery device 63. Next, the control function 673 controls the liquid delivery device 63 so that the pressure-feeding pad 633 is brought into close contact with a pressure chamber connected to the upper end of the storage container 30. Next, the control function 673 controls the liquid delivery device 63 so that air is sucked or pumped through the pressure-feeding pad 633.

[0046] The processing circuit 67 controls the incubator 65 according to the sample processing information through the control function 673. For example, when a reagent and a sample are delivered to the culture container 38, the control function 673 controls the incubator 65 to realize an environment suitable for culture in the culture container 68. Note that the control of the incubator 65 may be started from the point in time when the cartridge 3 is inserted into the sample processing device 5.

[0047] The processing circuit 67 detects the inclination of the cartridge 3 relative to the horizontal plane and / or the device body of the sample processing device 5 using the detection function 675. For example, the detection function 675 detects the inclination of the cartridge 3 based on the reading result by the reading device 631. Specifically, the detection function 675 determines the inclination of the cartridge 3 based on the reading result of the level 45 (for example, data such as the position of the air bubble in the level 45, and the elevation angle or depression angle by the level 45).

[0048] For example, if the reading result of the level 45 is equal to or less than a predetermined threshold, the detection function 675 detects (determines) that the cartridge 3 is not tilted. Also, if the reading result of the level 45 exceeds a predetermined threshold, the detection function 675 detects (determines) that the cartridge 3 is tilted. Note that other known methods may be used to determine the tilt of the cartridge 3 based on the reading result of the level 45. The detection function 675 outputs the tilt of the cartridge 3 to the output interface 53.

[0049] Above, each component of the sample processing system 1 has been described. Below, the procedure of the control process for detecting the tilt of the cartridge 3 by the sample processing device 5 (hereinafter referred to as the cartridge tilt detection process) will be described. The method for realizing the cartridge tilt detection process may be called the tilt detection method. FIG. 7 is a flowchart showing an example of the procedure of the cartridge tilt detection process. It is assumed that the sample and reagent are set in advance in the cartridge 3 prior to the implementation of the cartridge tilt detection process. It is also assumed that the sample processing information is set in advance prior to the implementation of the cartridge tilt detection process.

[0050] (Cartridge tilt detection process) (Step S701) The processing circuit 67 acquires the sample processing information by the information acquisition function 671. The information acquisition function 671 may acquire the sample processing information from each server device or the like via a network. The information acquisition function 671 stores the acquired sample processing information in the memory 55.

[0051] (Step S702) The cartridge 3 is inserted into the sample processing device 5 by an operation of the operator OP. At this time, the cartridge 3 is supported by the transport device 57.

[0052] (Step S703) The processing circuit 67 controls the transport device 57, the cooling device 59, etc., through a control function 673. In addition, the control function 673 controls the valve drive device 61 in accordance with the sample processing information. Under the control of the control function 673, the valve drive device 61 drives the opening and closing of the valve 41 from outside the cartridge 3 through magnetic interaction with the first magnet or the magnetic body.

[0053] (Step S704) The processing circuit 67 controls the liquid delivery device 63 in accordance with the sample processing information through the control function 673. Under the control of the control function 673, the liquid delivery device 63 aspirates and discharges the sample and / or reagent.

[0054] (Step S705) When the arm 635 is lowered by the control of the liquid delivery device 63 by the control function 673, the reading device 631 reads the horizontal state from the level 45. The reading device 631 outputs the reading result from the level 45 to the processing circuit 67.

[0055] (Step S706) The processing circuit 67 detects the inclination of the cartridge 3 with respect to the horizontal plane and / or the apparatus main body based on the reading result by the detection function 675. The detection function 675 outputs the inclination of the cartridge 3 to the output interface 53.

[0056] (Step S707) If the inclination of the cartridge 3 is detected (Yes in step S707), the process from step S708 onwards is executed. If the inclination of the cartridge 3 is not detected (No in step S707), the cartridge inclination detection process ends. At this time, the output interface 53 may notify the operator OP by a display, microphone, etc. that the inclination of the cartridge 3 has not been detected (for example, the amount of deviation (angle) from horizontal or that the cartridge 3 is horizontal).

[0057] (Step S708) The processing circuit 67 controls the output interface 53 by the control function 673. As a result, the output interface 53 notifies the operator OP of the inclination of the cartridge 3 by a display, a microphone, etc. At this time, various operations by the valve drive device 61, the liquid delivery device 63, etc. are stopped.

[0058] (Step S709) The inclination of cartridge 23 is corrected by operation of operator OP. For example, cartridge 3 is removed from sample processing device 5 in response to an instruction from operator OP via input interface 51. Cartridge 3 is reinserted into sample processing device 5 by operator OP. This completes the correction of the inclination of cartridge 23. Note that the inclination of cartridge 23 may be corrected by operating each of a plurality of actuators (tilt mechanisms) under the control of control function 673. The tilt mechanism is provided, for example, on a stage installed directly above transport device 57 or on transport device 57 itself. The stage adjusts the inclination of cartridge 3 by controlling the tilt mechanism by control function 673.

[0059] The sample processing device 5 according to the embodiment described above is equipped with a cartridge 3 for performing cell processing therein, a device body that controls the delivery of liquid within the cartridge and / or adjusts the environment within the cartridge, and detects the inclination of the cartridge 3 relative to a horizontal plane and / or the device body. The cartridge 3 in the sample processing device 5 according to the embodiment is equipped with a spirit level 45 that reflects the horizontality of the cartridge 3, and the device body of the sample processing device 5 reads the spirit level 45 and detects the inclination of the cartridge 3 based on the reading result of the spirit level 45.

[0060] From these facts, according to the sample processing device 5 of the embodiment, the liquid delivery device 63 is equipped with the reading device 631, and the motion axis of the liquid delivery device 63 in the connection operation between the pressure delivery pad connection part 43 and the pressure delivery pad 633 during liquid delivery can also be used for the reading operation, and the cartridge inclination detection process can be realized without increasing the motion axis related to the reading operation. As a result, according to the sample processing device 5 of the embodiment, the inclination of the cartridge 3 relative to the horizontal plane and / or the device main body can be notified to the operator OP, etc. Therefore, according to the sample processing device 5 of the embodiment, the inclination of the cartridge 3 can be corrected, that is, the cartridge 3 can be maintained in a horizontal state, and a sample such as a cell suspension can be appropriately processed.

[0061] (First Modification) The first modified example of this embodiment is such that a level 45 is provided on the filter 31 and / or the culture vessel 38, the expansion culture vessel 35, or the like in the cartridge 3 via a jig.

[0062] FIG. 8 is a diagram showing an example of the positional relationship between the level 45 and a reading device 631 that reads the level 45 in the first modified example. Although a plurality of level 45 are shown in FIG. 8, one level may be used. As shown in FIG. 8, the filter 31, the culture vessel 38, and the expansion culture vessel 35 are fixed horizontally to the cartridge 3 via a fixture. A jig 47 is connected to the fixture for the filter 31, the culture vessel 38, and the expansion culture vessel 35. The level 45 is disposed, for example, on the upper surface of the cartridge 3 via the jig 47. The cartridge inclination detection process in this modified example is the same as that in the embodiment, and therefore will not be described.

[0063] According to the sample processing device 5 of this modification, the inclination of the culture container 38 or the filter 31 relative to the horizontal plane and / or the device body can be directly detected. Therefore, according to this modification, samples such as cell suspensions can be processed more appropriately. Other effects of this modification are the same as those of the embodiment, so a description thereof will be omitted.

[0064] (Second Modification) In the second modified example of this embodiment, the device body of the sample processing device 5 is provided with a contact part capable of contacting the cartridge 3. In the second modified example, the level in the cartridge 3 is not necessary. The processing circuit 67 detects the inclination of the cartridge 3 based on the contact result when the contact part contacts the cartridge 3 using the detection function 675. For the sake of concrete explanation, the contact part will be described below as a contact device that contacts the cartridge 3 at a variable angle. In this case, the contact device is realized by, for example, a level or a goniometer. In this modified example, the mounting of the level 45 on the cartridge 3 and the reading device 631 are not necessary.

[0065] FIG. 9 is a diagram showing an example of the positional relationship between the contact device 637 and the cartridge 3. As shown in FIG. 9, the contact device 637 is supported on an arm 635 in the liquid delivery device 63 via a vibration suppressor (damper, shock absorber) 639. The vibration suppressor 639 is used to absorb impact and vibration to the contact device 637 and the cartridge 3 when the contact device 637 contacts the cartridge 3. In FIG. 9, the vibration suppressor 639 is represented by, for example, a spring and a cylinder, but a known vibration suppressor can be applied. In addition, the contact device 637 and the vibration suppressor 639 are connected via a ball joint. This allows the contact device 637 to smoothly contact the cartridge 3.

[0066] 9, the location of the contact device 637 is not limited to the tip of the arm 635 of the liquid delivery device 63, and may be any location such as an end of the incubator 65 or an end of the cooling device 59 as a modified example, as long as the contact device 637 can contact the cartridge 3 when the cartridge 3 is inserted into the sample processing device 5. For the sake of concreteness, the contact device 637 will be described below as being installed at the tip of the liquid delivery device 63.

[0067] Under the control of the control function 673, the liquid sending device 63 is moved (LDM) by the movement mechanism in the liquid sending device 63 so that the pressure-feeding pad connection part 43 connected to the storage container 30 is positioned directly below the pressure-feeding pad 633. Next, when the pressure-feeding pad 633 is lowered (DN) to the pressure-feeding pad connection part 43 by the movement mechanism, the contact device 637 contacts the cartridge 3 by the ball joint in a variable angle. At this time, the contact device 637 outputs to the processing circuit 67 the contact result when the contact device 637 contacts the cartridge 3, for example, the inclination of the contact device 637 (the position of the bubble in the bubble tube if the contact device 637 is a level, and angle data if the contact device 637 is a goniometer).

[0068] The processing circuit 67 detects the inclination of the cartridge 3 by the detection function 675 based on the contact result by the contact device 637. For example, the detection function 675 detects the inclination of the cartridge 3 based on the inclination of the contact device 637 when the contact device 637 is brought into contact with the cartridge 3. Specifically, the detection function 675 determines the inclination of the cartridge 3 based on the contact result of the contact device 637 (for example, data such as the position of an air bubble in a spirit level, and the elevation or depression angle measured by a goniometer). The contents of the determination are similar to those in the embodiment, and therefore description thereof will be omitted.

[0069] Except for the processes in steps S705 and S706, the procedure of the cartridge tilt detection process in this modified example is the same as the cartridge tilt detection process shown in Fig. 7. The process in steps S705 and S706 in this modified example will be described below.

[0070] (Step S705) When the arm 635 is lowered by the control of the liquid delivery device 63 by the control function 673, the contact device 637 comes into contact with the cartridge 3. The contact device 637 outputs the contact result to the processing circuit 67.

[0071] (Step S706) The processing circuit 67 detects the inclination of the cartridge 3 with respect to the horizontal plane and / or the device main body based on the contact result by the detection function 675. The detection function 675 outputs the inclination of the cartridge 3 to the output interface 53.

[0072] The device body of the sample processing device 5 according to this modification further includes a contact part capable of contacting the cartridge 3, and detects the inclination of the cartridge 3 based on the contact result when the contact part 637 contacts the cartridge 3. For example, the contact part 637 in the sample processing device 5 according to the second modification contacts the cartridge 3 at a variable angle, and detects the inclination of the cartridge 3 based on the inclination of the contact part 637 when the contact part 637 is brought into contact with the cartridge S. Other effects of this modification are similar to those of the embodiment, so description thereof will be omitted.

[0073] (Third Modification) In the third modified embodiment, the device body of the sample processing device 5 is provided with a contact part that can come into contact with the cartridge 3. In the third modified embodiment, the spirit level 45 is not necessary. The contact part is provided on the pressure feed pad 633. At this time, the processing circuit 67 detects the inclination of the cartridge 3 by the detection function 675 based on the contact result when the contact part comes into contact with the cartridge 3.

[0074] For the sake of specificity, the following description will be given assuming that the contact portion is a contact sensor that descends from each of a plurality of positions on a horizontal plane to contact the cartridge 3. The contact sensor is, for example, a pressure detection type sensor mounted on the pressure-feed pad 633. Note that the contact portion is not limited to a contact sensor, and various known contact sensors can be applied. In addition, the determination of when the contact portion has come into contact with the cartridge 3 is not limited to the response (ON state) of the contact sensor, and may be performed, for example, by a change in the load (change in current) of the motor that processes the arm 635. In this case, the contact sensor is not necessary, and the contact portion corresponds to the pressure-feed pad.

[0075] As an application example of this modification, laser ranging, LiDAR (light detection and ranging), etc. may be performed from multiple positions on the same horizontal plane. At this time, the processing circuit 67 detects the inclination of the cartridge 3 by detecting the distance to the top surface of the cartridge 3 from multiple positions on the horizontal plane using the detection function 675.

[0076] Fig. 10 is a diagram showing an example of the positional relationship between the arm 635 and the cartridge 3 at two positions. The dotted line BL shown in Fig. 10 corresponds to a reference line (horizontal plane) for detecting the inclination of the cartridge 3. As shown in Fig. 10, the pressure-feeding pad 633 is lowered toward the pressure-feeding pad connection part 43 at the two positions.

[0077] Under the control of the control function 673, the liquid sending device 63 is moved (LDM) by the movement mechanism in the liquid sending device 63 so that the pressure-feeding pad connection part 43 is located directly below the pressure-feeding pad 633. Next, when the pressure-feeding pad 633 is lowered (DN) to the pressure-feeding pad connection part 43 by the movement mechanism, the pressure-feeding pad 633 detects contact between the cartridge 3 and the pressure-feeding pad 633 by the contact sensor. As a result, the contact part outputs the time when the pressure-feeding pad 633 contacts the cartridge 3 (hereinafter referred to as the contact time) to the processing circuit 67. The contact time is detected at each of a plurality of positions (two points in FIG. 10 (hereinafter referred to as the first position and the second position)). Hereinafter, the contact time at the first position is referred to as the first time, and the contact time at the second position is referred to as the second time.

[0078] The processing circuit 67 detects the inclination of the cartridge 3 at a plurality of positions based on the length of the contact portion reaching the cartridge 3 by the detection function 675. Specifically, the detection function 675 calculates the distance from the reference line (hereinafter referred to as the first distance) by multiplying the difference between the time when the pressure-feed pad 633 starts descending at the first position (hereinafter referred to as the first descending start time) and the first time by the descending speed of the pressure-feed pad 633. Note that the detection function 675 may calculate the first distance using the output value of a rotary encoder in a motor related to the descending of the pressure-feed pad 633 during the period from the time referred to as the first descending start time to the first time.

[0079] Furthermore, the detection function 675 calculates the distance from the reference line (hereinafter referred to as the second distance) by multiplying the difference between the time when the pressure pad 633 starts descending at the second position (hereinafter referred to as the second descending start time) and the second time by the descending speed of the pressure pad 633. Note that the detection function 675 may calculate the second distance using an output value of a rotary encoder in a motor related to the descent of the pressure pad 633 during the period from the time referred to as the second descending start time to the second time.

[0080] The processing circuit 67 detects (determines) the inclination of the cartridge 3 using the first distance and the second distance by the detection function 675. The contents of the determination are the same as those in the embodiment, and therefore a description thereof will be omitted.

[0081] Except for the processes in steps S705 and S706, the procedure of the cartridge tilt detection process in this modified example is the same as the cartridge tilt detection process shown in Fig. 7. The process in steps S705 and S706 in this modified example will be described below.

[0082] (Step S705) When the arm 635 is lowered to the first position by the control of the liquid delivery device 63 by the control function 673, the pressure-feeding pad 633 comes into contact with the cartridge 3. At this time, the contact portion outputs the first time to the processing circuit 67. Also, when the arm 635 is lowered to the second position by the control of the liquid delivery device 63 by the control function 673, the pressure-feeding pad 633 comes into contact with the cartridge 3. At this time, the contact portion outputs the second time to the processing circuit 67.

[0083] (Step S706) The processing circuit 67 calculates a first distance based on the first descent start time and the first time using the detection function 675. The detection function 675 also calculates a second distance based on the second descent start time and the second time. Next, the detection function 675 detects (determines) the inclination of the cartridge 3 based on the first distance and the second distance. That is, the detection function 675 detects the inclination of the cartridge 3 based on the length until the contact portion reaches the cartridge 3 at multiple positions.

[0084] The contact portion of the sample processing device 5 according to this modification descends from multiple positions on a horizontal plane to contact the cartridge 3, and the sample processing device 5 detects the inclination of the cartridge 3 based on the length of the contact portion at each of the multiple positions until it reaches the cartridge 3. Other effects of this modification are similar to those of the embodiment, so a description thereof will be omitted.

[0085] (Fourth Modification) In the fourth modified embodiment, the conveying device 57 is equipped with a plurality of acquisition units that acquire information regarding the inclination of the cartridge 3 from below the cartridge 3 placed on the conveying device 57, and the inclination of the cartridge 3 is detected based on the output results output from the plurality of acquisition units. In the fourth modified embodiment, the spirit level 45 is not required. The plurality of acquisition units are, for example, a plurality of distance sensors or a plurality of contact sensors. The distance sensor is realized by a known sensor such as laser ranging or LiDAR. Also, the contact sensor can be realized by a known method such as a switch, and therefore a description thereof will be omitted.

[0086] FIG. 11 is a diagram showing an example of the positional relationship between the multiple sensors 571 and the cartridge 3. As shown in FIG. 11, the multiple sensors 571 are arranged in a concave recess that opens vertically upward. The multiple sensors 571 may be arranged directly below a hole provided in the transport device 57. As shown in FIG. 11, the cartridge 3 includes a detection target 573 corresponding to an object to be detected by the multiple sensors 571. The detection target 573 has a shape that fits into, for example, a concave recess or hole provided in the transport device 57. Hereinafter, for the sake of concrete explanation, the multiple sensors 571 are assumed to be two sensors arranged at two positions, respectively, as shown in FIG. 11.

[0087] If the two sensors 571 are distance sensors, the two distance sensors measure the distance from the lower part of the cartridge 3 to the bottom surface of the cartridge 3. The distance sensors output the distance to the processing circuit 67. If the two sensors 571 are contact sensors, the contact sensors determine the presence or absence of contact with the bottom surface (detectable portion 573) of the cartridge 3. Each contact sensor outputs the presence or absence of contact (ON: contact, OFF: non-contact) to the processing circuit 67.

[0088] The processing circuit 67 detects the inclination of the cartridge 3 by the detection function 675 based on the output results output from the multiple acquisition units 571. For example, when the multiple acquisition units 571 are two distance sensors, the detection function 675 judges whether or not the two distances at the two points both exceed a threshold value (hereinafter referred to as the distance threshold value). When the two distances at the two points both exceed the distance threshold value, the detection function 675 detects that the cartridge 3 is floating (hereinafter referred to as a floating error). When either one of the two distances at the two points exceeds the distance threshold value, the detection function 675 detects that the cartridge 3 is tilted (hereinafter referred to as a tilt error). When the two distances at the two points are both equal to or less than the distance threshold value, the detection function 675 detects that the cartridge 3 is in a horizontal state (hereinafter referred to as no abnormality).

[0089] Also, for example, if the multiple acquisition units 571 are two contact sensors, the detection function 675 determines whether or not the cartridge 3 is tilted based on a combination of ON / OFF at two points. If the outputs from the two contact sensors are both OFF (OFF·OFF), the detection function 675 detects a float error. If the outputs from the two contact sensors are ON and OFF (ON·OFF), the detection function 675 detects a tilt error. If the outputs from the two contact sensors are both ON (ON·ON), the detection function 675 detects no abnormality. The detection function 675 outputs a "float error," "tilt error," or "no abnormality" to the output interface 53.

[0090] The cartridge inclination detection process in this modified example will be described with reference to Fig. 12. Fig. 12 is a flowchart showing an example of a procedure for the cartridge inclination detection process in the fourth modified example.

[0091] (Cartridge tilt detection process) (Step S121) The cartridge 3 is inserted into the sample processing device 5 by an operation of the operator OP. At this time, the cartridge 3 is supported by the transport device 57.

[0092] (Step S122) The multiple acquisition units 571 acquire information regarding the inclination of the cartridge 3 for multiple positions on the bottom surface of the cartridge 3. The multiple acquisition units 571 output the information regarding the inclination of the cartridge 3 to the processing circuit 67. When the multiple acquisition units 571 are multiple distance sensors, the multiple distance sensors acquire multiple distances corresponding to the multiple positions as information regarding the inclination of the cartridge 3. When the multiple acquisition units 571 are multiple contact sensors, the multiple contact sensors acquire the presence or absence of contact (ON / OFF) corresponding to the multiple positions as information regarding the inclination of the cartridge 3.

[0093] (Step S123) The processing circuit 67 determines (detects) a “floating error”, a “tilt error”, or “no abnormality” based on the information regarding the tilt of the cartridge S. The detection function 675 outputs the determination result (detection result) to the output interface 53.

[0094] (Step S124) If the state of the cartridge 3 is "normal" (Yes in step S124), the cartridge tilt detection process ends. Next, various processes are executed on the sample (cells) in the cartridge 3. At this time, the output interface 53 may notify the operator OP by a display, microphone, etc. that the tilt of the cartridge 3 has not been detected (for example, "normal"). If the state of the cartridge 3 is not "normal" (No in step S124), the processes from step S125 onwards are executed.

[0095] (Step S125) The processing circuit 67 controls the output interface 53 by the control function 673. As a result, the output interface 53 notifies the operator OP of the determination result such as "floating error" or "tilt error" by a display, a microphone, or the like.

[0096] (Step S126) The attitude of the cartridge 3 corresponding to the determination result such as "floating error" or "tilt error" is corrected by the operation of the operator OP. For example, the cartridge 3 is removed from the sample processing device 5 in response to an instruction from the operator OP via the input interface 51. The cartridge 3 is then reinserted into the sample processing device 5 by the operator OP. This completes the correction of the determination result such as "floating error" or "tilt error".

[0097] The attitude of the cartridge 3 may be corrected by operating each of the multiple actuators (tilt mechanisms) under the control of the control function 673. The tilt mechanism is provided, for example, on a stage installed directly above the transport device 57 or on the transport device 57 itself. The stage adjusts the inclination of the cartridge 3 by controlling the tilt mechanism by the control function 673.

[0098] The transport unit in the sample processing device 5 according to this modification is capable of receiving the cartridge 3 and transports the cartridge 3 horizontally, and is equipped with a plurality of acquisition units 571 that acquire information regarding the inclination of the cartridge 3 with respect to a plurality of positions on the bottom surface of the cartridge 3, and the sample processing device 5 detects the inclination of the cartridge 3 based on the output results output from the plurality of acquisition units 571. The plurality of acquisition units 571 in the sample processing device 5 according to this modification are a plurality of distance sensors or a plurality of contact sensors, and the plurality of distance sensors measure the distance from the lower part of the cartridge 3 to the bottom surface of the cartridge 3, and the plurality of contact sensors determine the presence or absence of contact with the bottom surface of the cartridge 3. The effects of this modification are similar to those of the embodiment, so a description thereof will be omitted.

[0099] When the technical features of this embodiment are realized in a sample processing system 1, the sample processing system 1 includes a cartridge 3 for internally performing processing on cells, and a sample processing device 5 in which the cartridge 3 is installed and which controls the delivery of liquid within the cartridge and / or adjusts the environment within the cartridge, and the sample processing device 5 has a detection unit that detects the inclination of the cartridge 3 relative to the horizontal plane and / or the sample processing device 5. The procedure and effects of the cartridge inclination detection process in the sample processing system 1 are similar to those in the embodiment, and therefore a description thereof will be omitted.

[0100] When the technical features of this embodiment are realized by the cartridge 3, the cartridge 3 has a culture vessel 38 for cell culture and a filter 31 for collecting target cells for cell culture, and is equipped with a cartridge body for performing cell processing inside and a level 45 that reflects the horizontality of the cartridge body, and the culture vessel 38 and the filter 31 are fixed to the housing of the cartridge body. The procedure and effect of the cartridge tilt detection process in the cartridge 3 are similar to those of the embodiment, so a description will be omitted.

[0101] According to at least one of the embodiments and at least one of the modified examples described above, it is possible to detect the inclination of the cartridge 3 in which cell processing is performed.

[0102] Although some embodiments have been described, these embodiments are presented as examples and are not intended to limit the scope of the invention. These embodiments can be implemented in various other forms, and various omissions, substitutions, modifications, and combinations of embodiments can be made without departing from the spirit of the invention. These embodiments and their modifications are included in the scope of the invention and its equivalents as described in the claims, as well as in the scope and spirit of the invention. [Explanation of symbols]

[0103] 1. Sample processing system 3 Cartridge 5. Sample Processing Device 30 Storage Container 31 Filters 32 Waste liquid container 33 Spiral Channel 34 Tapered container 35 Expansion Culture Container 36 Infection Container 37 Pre-culture container 38 Culture container (mixed container) 39 Insulation 40 Tubes 41 Valve 43 Pressure pad connection 45 Level 51 Input Interface 53 Output Interface 55 Memory 57 Transport Equipment 59 Cooling device 61 Valve drive mechanism 63 Liquid delivery device 65 Incubator 67 Processing Circuit 571 Acquisition unit (sensor) 573 Detected part 631 Reading Device 633 Pressure Pad 635 Arm 637 Contact device 639 Vibration damper 671 Information Acquisition Function 673 Control Functions 675 Detection Function

Claims

1. A cartridge for performing cell processing therein is installed, and an apparatus main body is provided that controls the supply of liquid within the cartridge and / or adjusts the environment within the cartridge; the apparatus main body has a detection unit that detects a horizontal plane and / or a tilt of the cartridge relative to the apparatus main body; Sample processing equipment.

2. the cartridge includes a level gauge for measuring a horizontal state of the cartridge, The device body further includes a reading unit that reads the horizontal state from the level, the detection unit detects a tilt of the cartridge based on a reading result by the reading unit; The sample processing device of claim 1 .

3. the apparatus body further includes a contact portion capable of contacting the cartridge, the detection unit detects a tilt of the cartridge based on a contact result when the contact unit contacts the cartridge; The sample processing device of claim 1 .

4. the contact portion is in contact with the cartridge at a variable angle; the detection unit detects the inclination of the cartridge based on the inclination of the contact unit when the contact unit is brought into contact with the cartridge; The sample processing device according to claim 3 .

5. the contact portion descends from a plurality of positions on a horizontal plane to contact the cartridge; the detection unit detects a tilt of the cartridge based on a length until the contact portion reaches the cartridge at the plurality of positions; The sample processing device according to claim 3 .

6. the apparatus main body further includes a transport section capable of mounting the cartridge thereon and transporting the cartridge in a horizontal direction; the transport unit is equipped with a plurality of acquisition units that acquire information regarding the inclination of the cartridge with respect to a plurality of positions on a bottom surface of the cartridge; The detection unit detects a tilt of the cartridge based on output results output from the plurality of acquisition units. The sample processing device of claim 1 .

7. The plurality of acquisition units are a plurality of distance sensors or a plurality of contact sensors, the plurality of distance sensors measure a distance from a lower portion of the cartridge to a bottom surface of the cartridge; the plurality of contact sensors determine whether or not there is contact with a bottom surface of the cartridge; The sample processing device according to claim 6 .

8. The cartridge has a culture vessel for cell culture, The culture vessel is fixed to the cartridge. The sample processing device according to any one of claims 1 to 7.

9. the cartridge has a filter for collecting target cells; The filter is fixed to the cartridge. The sample processing device according to any one of claims 1 to 7.

10. A cartridge for performing a process on cells inside; a sample processing device in which the cartridge is installed and which controls the delivery of liquid within the cartridge and / or adjusts the environment within the cartridge; Equipped with The sample processing device has a detection unit that detects a horizontal plane and / or a tilt of the cartridge relative to the sample processing device. Sample processing system.

11. A cartridge body having a culture vessel for cell culture and a filter for collecting target cells for the cell culture, and for performing a process on the cells therein; a level indicator that reflects the levelness of the cartridge body; Equipped with The culture vessel and the filter are fixed to the housing of the cartridge body. cartridge.

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