Biological sample processing apparatus

Abstract

To reduce the risk of contamination during processing of a biological sample.SOLUTION: A biological sample processing apparatus according to an embodiment includes a holder. The holder detachably holds a liquid supplier. The liquid supplier includes storage means that stores a liquid used for processing a biological sample and ejection means that pushes the liquid out from inside the storage means to eject the liquid directly to an ejection destination.SELECTED DRAWING: Figure 3

Description

[Technical field]

[0001] The embodiments disclosed in the specification and drawings relate to a biological sample processing device. [Background technology]

[0002] Biological sample processing devices that process biological samples include cell processing devices and automatic culture devices. Conventional cell processing devices are equipped with a storage unit that stores (reserves) reagents and cell suspensions, and commercially available reagent bottles or reagent bags are attached to the storage unit. The storage unit is connected to a container to which the reagents and cell suspensions are supplied via a flow path such as a tube. In such biological sample processing devices, because liquids such as reagents are supplied via the flow path, residues of the reagents and the like may adhere to the inner walls of the flow path, creating a risk of contamination. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] International Publication No. 2016 / 133209 Summary of the Invention [Problem to be solved by the invention]

[0004] One of the problems that the embodiments disclosed in this specification and the drawings aim to solve is to reduce the risk of contamination during processing of biological samples. However, the problems that the embodiments disclosed in this specification and the drawings aim to solve are not limited to the above problem. Problems corresponding to the effects of each configuration shown in the embodiments described below can also be positioned as other problems. [Means for solving the problem]

[0005] The biological sample processing apparatus according to the embodiment includes a holding unit that detachably holds a liquid supply unit. The liquid supply unit includes a storage unit that stores a liquid used in processing the biological sample, and a discharge unit that pushes the liquid out of the storage unit and directly discharges it to a discharge destination. [Brief description of the drawings]

[0006] [Figure 1] FIG. 1 is a diagram showing the configuration of a biological sample processing apparatus according to a first embodiment. [Diagram 2] FIG. 2 is a diagram showing an example of the configuration of the blood cell separation mechanism according to the first embodiment. [Diagram 3] FIG. 3 is a diagram illustrating an example of the configuration of a liquid supply unit according to the first embodiment. [Figure 4] FIG. 4 is a diagram illustrating an example of the configuration of a liquid supply unit according to the first embodiment. [Diagram 5] FIG. 5 is a diagram illustrating an example of the configuration of a liquid supply unit according to the first embodiment. [Figure 6] FIG. 6 is a flowchart illustrating the procedure of the blood cell separation process according to the first embodiment. [Figure 7] FIG. 7 is a flow chart illustrating the procedure of the blood cell separation process by the biological sample processing apparatus according to the first embodiment. [Figure 8] FIG. 8 is a flow chart illustrating the procedure of the waste treatment by the biological sample processing apparatus according to the first embodiment. [Figure 9] FIG. 9 is a diagram showing the state of the blood cell separation mechanism at the start of the blood cell separation process. [Figure 10] FIG. 10 is a diagram showing the operation of the blood cell separation mechanism in step S202 of FIG. [Figure 11] FIG. 11 is a diagram showing the operation of the blood cell separation mechanism in step S203 of FIG. [Figure 12] FIG. 12 is a diagram showing the operation of the blood cell separation mechanism in step S204 of FIG. [Figure 13] FIG. 13 is a diagram showing the operation of the blood cell separation mechanism in step S206 of FIG. [Figure 14] FIG. 14 is a diagram showing the operation of the blood cell separation mechanism in step S105 of FIG. [Figure 15]FIG. 15 is a diagram showing the configuration of a biological sample processing apparatus according to the second embodiment. [Figure 16] FIG. 16 is a diagram illustrating an example of the configuration of a factor introduction mechanism according to the second embodiment. [Figure 17] FIG. 17 is a flowchart illustrating the procedure of the factor introduction step according to the second embodiment. [Figure 18] FIG. 18 is a flow chart illustrating the procedure of the factor introduction process performed by the biological sample processing apparatus according to the second embodiment. [Figure 19] FIG. 19 is a diagram showing the state of the factor introduction mechanism at the start of the factor introduction process. [Figure 20] FIG. 20 is a diagram showing the operation of the factor introduction mechanism in step S502 of FIG. [Figure 21] FIG. 21 is a diagram showing the operation of the factor introduction mechanism in step S503 of FIG. [Figure 22] FIG. 22 is a diagram showing the operation of the factor introduction mechanism in step S504 of FIG. [Diagram 23] FIG. 23 is a diagram showing the operation of the factor introduction mechanism in step S505 of FIG. [Figure 24] FIG. 24 is a diagram showing an example of the configuration of a liquid supply unit according to a first modified example. [Diagram 25] FIG. 25 is a diagram showing an example of the configuration of a liquid supply unit according to the second modified example. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0007] Hereinafter, an embodiment of the biological sample processing apparatus will be described in detail with reference to the drawings. The biological sample processing apparatus is an apparatus that automatically processes biological samples such as blood and peripheral blood mononuclear cells (hereinafter referred to as PBMCs). The biological sample processing is, for example, processing of cells to create induced pluripotent stem cells (hereinafter referred to as iPS cells). The biological sample processing is, for example, separation of blood cells in blood and introduction of factors into PBMCs. The biological sample processing apparatus includes a cartridge-type liquid supply unit that contains liquid used in processing the biological sample and can directly discharge the contained liquid such as a reagent. The liquid supply unit is detachably attached. In the following description, components having substantially the same functions and configurations are given the same reference numerals, and repeated description will be given only when necessary.

[0008] (First embodiment) Fig. 1 is a block diagram showing an example of the configuration of a biological sample processing apparatus 1 according to a first embodiment. The biological sample processing apparatus 1 of this embodiment is a blood cell separation apparatus that automatically separates blood cells required for creating iPS cells from blood. As shown in Fig. 1, the biological sample processing apparatus 1 includes a blood cell separation mechanism 2, an input interface 6, an output interface 5, a memory circuit 3, and a control circuit 7. The control circuit may be rephrased as a processing circuit.

[0009] The blood cell separation mechanism 2 separates blood cells necessary for producing iPS cells from blood. The detailed configuration of the blood cell separation mechanism 2 will be described later.

[0010] The memory circuit 3 stores programs executed by the control circuit 7, various data used in the processing of the control circuit 7, and the like. As the programs, for example, programs that are installed in advance in a computer from a network or a non-transient computer-readable storage medium and cause the computer to realize each function of the control circuit 7 are used. Note that the various data handled in this specification are typically digital data. The memory circuit 3 is an example of a storage means.

[0011] The communication interface 4 is an interface for performing data communication with external devices via a network.

[0012] The output interface 5 is connected to the control circuit 7 and outputs a signal supplied from the control circuit 7. The output interface 5 is realized by, for example, a display circuit, a printed circuit, and an audio device. The display circuit includes, for example, a CRT display, a liquid crystal display, an organic EL display, an LED display, and a plasma display. The display circuit may also be a processing circuit that converts data representing a display object into a video signal and outputs the video signal to the outside. The printed circuit includes, for example, a printer. The printed circuit may also be an output circuit that outputs data representing a print object to the outside. The audio device includes, for example, a speaker. The audio device may also be an output circuit that outputs an audio signal to the outside.

[0013] The input interface 6 receives various operations from, for example, an operator. The input interface 6 is realized by, for example, a mouse, a keyboard, and a touchpad where instructions are input by touching the operation surface. The input interface 6 is connected to the control circuit 7, converts the operation instructions input by the operator into electrical signals, and outputs the electrical signals to the control circuit 7. The input interface 6 is not limited to one equipped with physical operation parts such as a mouse and a keyboard. For example, the input interface 6 may be a processing circuit that receives an electrical signal corresponding to an operation instruction input from an external input device provided separately from the biological sample processing apparatus 1 and outputs the electrical signal to the control circuit 7.

[0014] The control circuit 7 is a processor that functions as the core of the biological sample processing apparatus 1. The control circuit 7 executes a system control function 71 by executing a program read from the storage circuit 3. The control circuit 7 uses the system control function 71 to comprehensively control each part in the biological sample processing apparatus 1. For example, in the system control function 71, the control circuit 7 controls the blood cell separation mechanism 2 so as to perform a blood cell separation process described below. The control circuit 7 that realizes the system control function 71 is an example of a control unit.

[0015] The term "processor" used in the above description means a circuit such as a central processing unit (CPU), a graphics processing unit (GPU), an application specific integrated circuit (ASIC), a programmable logic device (e.g., a simple programmable logic device (SPLD), a complex programmable logic device (CPLD), and a field programmable gate array (FPGA)). For example, when the processor is a CPU, the processor realizes a function by reading and executing a program stored in the memory circuit 3. On the other hand, when the processor is an ASIC, instead of storing a program in the memory circuit 3, the function is directly incorporated as a logic circuit in the circuit of the processor. Note that each processor in this embodiment is not limited to being configured as a single circuit for each processor, and may be configured as one processor by combining multiple independent circuits to realize the function. Furthermore, the multiple components in FIG. 1 may be integrated into one processor to realize the function. The above description of the "processor" is the same for each of the following embodiments and modifications.

[0016] In this embodiment, each function is described as being realized by a single processor, but is not limited to this. For example, a control circuit may be configured by combining multiple independent processors, and each processor may execute a program to realize each function. The system control function 71 may be called a system control circuit, or may be implemented as an individual hardware circuit. The above description of each function executed by the control circuit 7 is the same for each of the following embodiments and modified examples. The control circuit 7 may include a storage area that stores at least a portion of the data stored in the storage circuit 3. The control circuit 7 may be called a control unit or a processing circuit.

[0017] Next, the configuration of the blood cell separation mechanism 2 will be described in detail. Fig. 2 is a diagram showing an example of the configuration of the blood cell separation mechanism 2 shown in Fig. 1. As shown in Fig. 2, the blood cell separation mechanism 2 includes a housing 201, a blood bag 202, a mixing container 203, a first holding section 204, a second holding section 205, a first pump 206, a first filter 207, a waste liquid container 208, a third holding section 209, a conveyor 210, a reagent cartridge 211, a fourth holding section 212, a second pump 213, a first collection container 214, a fifth holding section 215, a sixth holding section 216, a third pump 217, a flow path 218, a second collection container 219, a seventh holding section 220, an eighth holding section 221, a fourth pump 222, a second filter 223, a third collection container 224, a ninth holding section 225, and a UV irradiation section 226. The blood cell separation mechanism 2 also includes a drive mechanism. The drive mechanism operates each of the above-mentioned components of the blood cell separation mechanism 2 under the control of the control circuit 7. The drive mechanism is realized by, for example, a robot arm, a pump, a gear, a belt conveyor, etc. As the first pump 206, the second pump 213, the third pump 217, and the fourth pump 222, for example, a syringe pump is used. As various containers such as the mixing container 203, the waste liquid container 208, the first collection container 214, the second collection container 219, and the third collection container 224, for example, a well plate, a flask, a dish, or a bag is used.

[0018] The housing 201 is an exterior of the blood cell separation mechanism 2. The blood bag 202 is attached to the outside of the housing 201. Components other than the blood bag 202 (mixing container 203, UV irradiation unit 226, etc.) are provided inside the housing 201. The blood bag 202 may be provided inside the housing 201.

[0019] The blood bag 202 is a container capable of accommodating blood, which is a biological sample. The blood bag 202 may accommodate only an amount of blood used for one blood cell separation, or may accommodate an amount of blood for multiple times. The blood bag 202 has, for example, a sealability capable of suppressing or preventing the blood from being exposed to the outside air. The blood bag 202 is connected to a driving mechanism such as a pump, and supplies blood to a blood flow path 2021.

[0020] Blood is a cell fluid that contains blood cells necessary for the production of iPS cells. The blood cells necessary for the production of iPS cells are cells that are the subject of reprogramming by inductive factors, such as mononuclear cells such as CD34 cells and white blood cells containing CD34 cells.

[0021] The mixing container 203 is a container for mixing blood with phosphate buffered saline (hereinafter referred to as PBS) to prepare a mixture of blood and PBS. The mixing container 203 has, for example, a sealability capable of suppressing or preventing the mixture from being exposed to the outside air. The mixing container 203 contains a single dose of PBS in advance. The single dose is, for example, the amount used at one time to mix with blood.

[0022] The first holding section 204 is a holding mechanism that holds the mixing container 203. The mixing container 203 is attached to the first holding section 204 by an operator. When attached to the first holding section 204, the mixing container 203 is connected to the blood bag 202 via the blood flow path 2021. Blood is supplied to the mixing container 203 from the blood bag 202 via the blood flow path 2021. The other end of the blood flow path 2021 is connected to the blood bag 202. Therefore, the mixing container 203 is connected to the blood bag 202 via the blood flow path 2021. Blood is supplied to the mixing container 203 from the blood bag 202 via the blood flow path 2021, and a mixture of blood and PBS is generated in the mixing container 203. The mixing container 203 is transported from the first holding section 204 to the second holding section 205 by a robot arm.

[0023] The second holding section 205 is a holding mechanism that holds the mixing container 203 transferred from the first holding section 204. The second holding section 205 is disposed between the first pump 206 and the first filter 207.

[0024] The first pump 206 is connected to the mixing container 203 held by the second holding portion 205. The first pump 206 is, for example, a syringe pump. The first pump 206 extends downward under the control of the control circuit 7, and discharges the mixed liquid contained in the mixing container 203 to the first filter 207.

[0025] The first filter 207 is used to capture necessary blood cells contained in the mixed liquid and separate the necessary blood cells from the blood. The first filter 207 removes unnecessary cells such as red blood cells and platelets from the blood and extracts necessary cells such as white blood cells.

[0026] First filter 207 has openings smaller than the particle size of white blood cells and larger than the particle size of red blood cells, platelets, etc. Therefore, when blood passes through first filter 207, first filter 207 allows unnecessary cells such as red blood cells and platelets to pass through and captures necessary cells such as white blood cells.

[0027] The first filter 207 has a first end 2071 and a second end 2072. The first end 2071 is located at one end of the first filter 207, and the second end 2072 is located at the end opposite to the first end 2071. The first filter 207 is disposed directly below the second holder 205 with the first end 2071 located at the upper side and the second end 2072 located at the lower side. The robot arm rotates the first filter 207 that has captured the necessary cells 180 degrees to turn it upside down, and moves it directly below the fourth holder 212. In this state, the second end 2072 is located at the upper side, and the first end 2071 is located at the lower side.

[0028] The waste liquid container 208 is a container for collecting, as waste liquid, the mixed liquid that has passed through the first filter 207. The waste liquid container 208 has, for example, a sealable property that can suppress or prevent the mixed liquid from being exposed to the outside air.

[0029] The third holding unit 209 is a holding mechanism that holds the waste liquid container 208. The third holding unit 209 is located directly below the first filter 207. The third holding unit 209 is realized by a conveyor 210. The conveyor 210 is a belt conveyor that transports the waste liquid container 208 and the third collection container 224. For example, the waste liquid container 208 is transported to a waste liquid collection unit (not shown).

[0030] The reagent cartridge 211 is a cartridge-type container capable of storing PBS. The reagent cartridge 211 is an example of a liquid supply unit in this embodiment. The reagent cartridge 211 stores a single use amount of PBS in advance. The single use amount is, for example, an amount used once to collect cells captured by the first filter 207. The reagent cartridge 211 may store multiple uses of PBS. The reagent cartridge 211 may be called a collection liquid cartridge. A detailed configuration of the reagent cartridge 211 will be described later.

[0031] The fourth holding section 212 is a holding mechanism that holds the reagent cartridge 211. The fourth holding section 212 is an example of a holding section that holds a liquid supply section. The operator attaches the reagent cartridge 211 to the fourth holding section 212. The fourth holding section 212 is disposed directly below the second pump 213. The first filter 207, which is upside down, is disposed directly below the fourth holding section 212. In the fourth holding section 212, the reagent cartridge 211 is directly connected to the first filter 207. The reagent cartridge 211 discharges PBS directly to the first filter 207 by driving the second pump 213. The first filter 207 is an example of a discharge destination to which the liquid is discharged from the liquid supply section. The used reagent cartridge 211 is transported from the fourth holding section 212 to the UV irradiation section 226 by the robot arm.

[0032] The second pump 213 is connected to the reagent cartridge 211 held in the fourth holding section 212. The second pump 213 is, for example, a syringe pump. The second pump 213 extends downward under the control of the control circuit 7, and discharges the PBS contained in the reagent cartridge 211 to the first filter 207. The second pump 213 is an example of a drive section.

[0033] First collection container 214 is a container for collecting PBS containing cells collected from first filter 207. First collection container 214 has, for example, a sealable property capable of suppressing or preventing the mixed liquid from being exposed to the outside air.

[0034] Fifth holding unit 215 is a holding mechanism that holds first collection container 214. Fifth holding unit 215 is disposed directly below first filter 207 that is turned upside down. First collection container 214 is transported from fifth holding unit 215 to sixth holding unit 216 by a robot arm.

[0035] The sixth holding unit 216 is a holding mechanism that holds the first collection container 214 transferred from the fifth holding unit 215. The sixth holding unit 216 is disposed between the third pump 217 and the flow path 218.

[0036] The third pump 217 is connected to the first collection container 214 held by the sixth holding portion 216. The third pump 217 is, for example, a syringe pump. The third pump 217 extends downward under the control of the control circuit 7, and discharges the collection liquid contained in the first collection container 214 into the flow path 218.

[0037] PBMCs are generated by the passage of the recovery liquid containing white blood cells through channel 218. Channel 218 is, for example, a microchannel device for generating PBMCs. Channel 218 is disposed directly below sixth holder 216.

[0038] Second collection container 219 is a container for collecting PBMCs generated in flow channel 218. Second collection container 219 is disposed directly below flow channel 218. Second collection container 219 has, for example, airtightness to suppress or prevent the mixed liquid from being exposed to the outside air.

[0039] Seventh holding unit 220 is a holding mechanism that holds second collection container 219. Seventh holding unit 220 is disposed directly below flow path 218. Second collection container 219 is transported from seventh holding unit 220 to eighth holding unit 221 by a robot arm.

[0040] The eighth holding unit 221 is a holding mechanism that holds the second collection container 219 transferred from the seventh holding unit 220. The eighth holding unit 221 is disposed between the fourth pump 222 and the second filter 223.

[0041] The fourth pump 222 is connected to the second collection container 219 held in the eighth holding portion 221. The fourth pump 222 is, for example, a syringe pump. The fourth pump 222 extends downward under the control of the control circuit 7, and discharges the PBMCs contained in the second collection container 219 into the second filter 223.

[0042] The second filter 223 is a filter for performing a predetermined filtering process on the PBMC. The second filter 223 is disposed immediately below the eighth holding unit 221.

[0043] The third collection container 224 is a culture container containing a culture medium. The third collection container 224 collects PBMCs that have passed through the second filter 223. The third collection container 224 has, for example, airtightness to suppress or prevent the mixed liquid from being exposed to the outside air. The third collection container 224 contains in advance a culture medium for establishing iPS cells. For example, cytokines or StemSpan from Veritas Corporation can be used as the culture medium.

[0044] The ninth holder 225 is a holding mechanism that holds the third collection container 224. The ninth holder 225 is located directly below the second filter 223. The ninth holder 225 is realized by the conveyor 210. The conveyor 210 transports the third collection container 224 to an outlet (not shown). The operator removes the third collection container 224 from the outlet, thereby removing the culture container containing the medium from the blood cell separation mechanism 2, and performs the culture process subsequent to the blood cell separation process.

[0045] The UV irradiation unit 226 stores used reagent cartridges 211 and irradiates the used reagent cartridges 211 with ultraviolet (UV) rays. The UV irradiation unit 226 is provided with an irradiator that irradiates ultraviolet (UV) rays, and irradiates the used reagent cartridge 211 with ultraviolet rays for a fixed period of time. When irradiation of ultraviolet rays ends, the reagent cartridge 211 is removed from an outlet (not shown), discharged to the outside, and discarded. The UV irradiation unit 226 is an example of a waste treatment unit that treats waste generated by processing biological samples.

[0046] The small flow paths and filters provided in the blood cell separation mechanism 2 may be configured to be removable. For example, the first filter 207, the flow path 218, and the second filter 223 may be arbitrarily made removable, and these may be replaced with filters and flow paths having desired functions. The removable first filter 207, the flow path 218, and the second filter 223 are examples of removable processing means used in processing biological samples.

[0047] Next, an example of the configuration of the reagent cartridge 211, which is the reagent cartridge of this embodiment, will be described. 3 is a diagram showing an example of the configuration of the reagent cartridge 211. As shown in FIG.

[0048] The storage unit 2111 is a reagent bag that stores PBS, which is a reagent. The storage unit 2111 has, for example, airtightness so as to suppress or prevent the PBS from being exposed to the outside air. The storage unit 2111 is an example of a storage means that stores a liquid used in processing a biological sample. The fourth holding unit 212 is, for example, fixed at a predetermined position inside the housing 201. The fourth holding unit 212 supports the storage unit 2111. The exterior of the storage unit 2111 is formed in a shape that can be detachably attached to the fourth holding unit 212. The fourth holding unit 212 has, for example, a fitting hole into which the storage unit 2111 can be fitted from the lower side or the side.

[0049] The piston portion 2112 is provided inside the storage portion 2111 and is attached to the second pump 213. The discharge portion 2113 is an outlet provided at the bottom of the storage portion 2111. The discharge portion 2113 is an outlet provided at the bottom end of the storage portion 2111, and is directly connected to the first filter 207. The piston portion 2112 moves by driving the second pump 213. When the piston portion 2112 is pushed in by driving the second pump 213, the PBS stored in the storage portion 2111 is directly discharged from the discharge portion 2113 to the first filter 207. The piston portion 2112 and the discharge portion 2113 are an example of a discharge means for pushing out the liquid from the storage means and discharging it directly to the discharge destination. Also, the second pump 213 is an example of a drive unit for discharging the liquid from the discharge means.

[0050] The blood cell separation mechanism 2 includes a mix-up prevention means for preventing the mix-up of the reagent cartridge 211. In this embodiment, the fourth holding section 212 is formed so that only the corresponding liquid supply section can be attached, and the storage section 2111 of the reagent cartridge 211 is formed in a shape that can be attached only to the fourth holding section 212. Specifically, the fourth holding section 212 is formed in a shape that can be attached only to the reagent cartridge 211. For example, the reagent cartridge 211 is shaped so that it can be attached to the fourth holding section 212 but cannot be attached to the attachment section of the blood bag 202, and the blood bag 202 is shaped so that it can be attached to the attachment section of the blood bag 202 but cannot be attached to the fourth holding section 212, thereby preventing mix-up. The fourth holding section 212 and the reagent cartridge 211 formed in this manner are examples of mix-up prevention means.

[0051] 4 and 5 are diagrams showing an example of a reagent cartridge 211 having a mix-up prevention function. For example, as shown in FIG. 4, the fourth holding section 212 may be formed in a shape having a rectangular mating hole, and the outer shape of the reagent cartridge 211 may be formed in a rectangular shape that fits into the mating hole. Also, as shown in FIG. 5, the fourth holding section 212 may be formed in a shape having a circular mating hole, and the outer shape of the reagent cartridge 211 may be formed in a circular shape that fits into the mating hole. Also, the outer shape of the reagent cartridge 211 may be formed in a rectangular shape, and the outer shape of the blood bag 202 may be formed in a circular shape. Also, the outer shape of the reagent cartridge 211 may be formed in a circular shape, and the outer shape of the blood bag 202 may be formed in a rectangular shape.

[0052] Next, the operation of the biological sample processing apparatus 1 of this embodiment will be described. FIG. 6 is a flow chart showing an example of the procedure of a blood cell separation process performed by an operator using the biological sample processing apparatus 1. The blood cell separation process is a process of separating blood cells necessary for creating iPS cells, such as white blood cells, from the blood of a subject. FIG. 7 is a flow chart showing an example of the procedure of a blood cell separation process, which will be described later, performed in step S104 of FIG. 6. FIG. 8 is a flow chart showing an example of the procedure of a disposal process, which will be described later, performed in step S106 of FIG. 6. Note that the procedure of each process described below is merely an example, and each process can be appropriately changed as much as possible. In addition, steps can be omitted, replaced, and added to the procedure described below as appropriate depending on the embodiment. The above description of the procedure of each process is the same for each of the following embodiments and modified examples.

[0053] (Blood cell separation process) (Step S101) First, the operator installs a pump unit including a first pump 206, a second pump 213, a third pump 217, and a fourth pump 222 at a predetermined position inside the housing 201 of the blood cell separation mechanism 2. The pump unit may be called a nozzle unit.

[0054] (Step S102) Next, the operator places the blood bag 202, and places the reagent cartridge 211 in the fourth holding section 212. At this time, since the reagent cartridge 211 and the fourth holding section 212 are provided with the above-mentioned mix-up prevention function, the operator can attach the blood bag 202 and the reagent cartridge 211 in the correct positions without mixing them up.

[0055] (Step S103) Next, the operator operates the input interface 6 to start the operation of the biological sample processing apparatus 1.

[0056] (Step S104) When the operation of the biological sample processing apparatus 1 starts, the biological sample processing apparatus 1 executes a blood cell separation process under the control of the control circuit 7. In the blood cell separation process, the blood cell separation mechanism 2 automatically executes an operation of separating blood cells from blood under the control of the control circuit 7.

[0057] Here, the blood cell separation process performed by the biological sample processing apparatus 1 will be described in detail. 7 is a flow chart showing an example of a processing procedure of blood cell separation processing executed by the biological sample processing apparatus 1. Each processing described below is executed by driving mechanisms such as the robot arm and the conveyor 210 under the control of the control circuit 7, but the description thereof will be omitted.

[0058] (Blood cell separation process) 9 is a diagram showing the internal state of the blood cell separation mechanism 2 at the start of blood cell separation processing. As shown in FIG. 9, at the start of blood cell separation processing, the blood bag 202 is attached to the outside of the housing 201, and the reagent cartridge 211 is attached to the fourth holding section 212. In addition, the mixing container 203 containing PBS is attached to the first holding section 204. The first filter 207 is placed directly below the second holding section 205, the waste liquid container 208 is placed in the third holding section 209, the first collection container 214 is placed in the fifth holding section 215, the second collection container 219 is placed in the seventh holding section 220, and the third collection container 224 containing the culture medium is placed in the ninth holding section 225.

[0059] (Step S201) When the blood cell separation process starts, first, the blood cell separation mechanism 2 supplies blood from the blood bag 202 to the mixing container 203, and generates a mixture of blood and PBS in the mixing container 203.

[0060] (Step S202) 10, the mixing container 203 moves from the first holding section 204 to the second holding section 205. Thereafter, the mixed liquid contained in the mixing container 203 is discharged to the first filter 207 by driving the first pump 206, and filtering is performed by the first filter 207. In the filtering process, white blood cells contained in the blood are captured by the first filter 207. The mixed liquid that has passed through the first filter 207 is collected as a waste liquid in a waste liquid container 208 installed in the third holding section 209.

[0061] (Step S203) 11, the first filter 207 rotates upside down and moves between the fourth holding section 212 and the fifth holding section 215. The waste liquid container 208 is transported to a waste liquid recovery section (not shown) by the conveyor 210. Thereafter, the second pump 213 is driven to discharge one dose of PBS contained in the reagent cartridge 211 into the upside-down first filter 207, and a filter process is performed by the first filter 207. In the filter process, the white blood cells captured by the first filter 207 are collected into the first collection container 214 together with the PBS.

[0062] (Step S204) 12, first collection container 214 moves from fifth holding portion 215 to sixth holding portion 216. Thereafter, third pump 217 is driven to discharge the collection liquid contained in first collection container 214 into flow path 218.

[0063] (Step S205) Next, the recovery liquid passes through flow channel 218 to generate PBMCs, and the PBMCs that have passed through flow channel 218 are recovered in second recovery container 219.

[0064] (Step S206) 13, second collection container 219 moves from seventh holding section 220 to eighth holding section 221. Thereafter, fourth pump 222 is driven to discharge the PBMCs contained in second collection container 219 into second filter 223, and filtering is performed by second filter 223. In filtering, for example, any process is performed on the PBMCs.

[0065] Thus, in the blood cell separation process in step S104, PBMCs necessary for processing iPS cells are obtained by a series of processes from step S201 to step S206. When the blood cell separation process is completed, the operator simultaneously performs the processes of step S105 and step S106 in FIG.

[0066] (Step S105) The operator operates the biological sample processing apparatus 1 to inject the PBMCs that have passed through the second filter 223 into the third collection container 224 containing the culture medium. After that, the operator transports the third collection container 224 from the ninth holder 225 to the removal port, as shown in Fig. 14, and the blood cell separation process is completed.

[0067] Thereafter, the operator removes the third collection container 224 from the biological sample processing apparatus 1, and performs the culture step using the third collection container 224 removed from the biological sample processing apparatus 1.

[0068] (Step S106) At the same time as step S105, the operator executes disposal processing by the biological sample processing apparatus 1. The disposal processing is a process for sterilizing the used reagent cartridge in order to safely dispose of the used reagent cartridge.

[0069] 8 is a flow chart showing an example of a procedure for disposal processing executed by the biological sample processing apparatus 1. Each process described below is executed by driving each driving mechanism of the blood cell separation mechanism 2 under the control of the control circuit 7, but the description thereof will be omitted.

[0070] (Disposal) (Step S301) In the disposal process, first, the used reagent cartridge 211 from which the PBS has been discharged is moved from the fourth holder 212 to the UV irradiation section 226 as shown in FIG.

[0071] (Step S302) Next, an irradiator provided in the UV irradiating section 226 irradiates the used reagent cartridge 211 with ultraviolet (UV) rays for a certain period of time, and the used reagent cartridge 211 is sterilized.

[0072] (Step S303) When the irradiation of ultraviolet (UV) rays is completed, the sterilized reagent cartridge 211 is discharged to the outside and discarded.

[0073] The effects of the biological sample processing apparatus 1 according to this embodiment will be described below.

[0074] The biological sample processing apparatus 1 of this embodiment includes a fourth holding section 212 that detachably holds a reagent cartridge 211. The reagent cartridge 211 is an example of a liquid supply section. The fourth holding section 212 is an example of a holding section that detachably holds a liquid supply section. The reagent cartridge 211 includes a storage section 2111, a piston section 2112, and a discharge section 2113. The storage section 2111 stores PBS as a reagent. The PBS is an example of a reagent for creating iPS cells. The biological sample processing apparatus 1 includes a second pump 213 as a drive section for driving the discharge means. The second pump 213 is, for example, a syringe pump. The discharge section 2113 is directly connected to the first filter 207, and the piston section 2112 and the discharge section 2113 push out the PBS from inside the storage section 2111 and directly discharge the PBS to the first filter 207. The first filter 207 is an example of a discharge destination.

[0075] With the above configuration, the biological sample processing apparatus 1 of this embodiment uses the reagent cartridge 211 having a storage means and a discharge means, and thus it is possible to directly inject PBS from the reagent cartridge 211 into the first filter 207 without providing a flow path connecting a storage section for storing PBS to a discharge destination. This reduces the risk of contamination due to the adhesion of reagent residues to the inner wall of the flow path. It also eliminates the need for liquid transfer losses due to the adhesion of reagent residues to the inner wall of the flow path, and the need to prepare an extra amount of reagent to take into account liquid transfer losses.

[0076] In addition, in conventional processing devices, multiple doses of reagent are stored in a storage unit such as a reservoir, and the required amount of reagent is aspirated from the storage unit each time cells are processed. In such devices, in order to reliably aspirate the required amount of reagent, it is necessary to store an amount of reagent in the reservoir taking into consideration the excess amount. Also, while the reagent is stored in the reservoir, the time during which the reagent is exposed to the outside air increases, which may increase the risk of contamination. On the other hand, in this embodiment, the reagent cartridge 211 is previously filled with an amount of PBS to be used in one blood cell separation process. By using a cartridge type in which the reagent is sealed in advance, it is no longer necessary to aspirate the reagent, and it is possible to prevent the reagent from scattering during aspirating. In addition, since the storage unit is not reused as in the case of storing multiple doses of reagent, the time during which the reagent is exposed to the outside air can be shortened, and the risk of microbial contamination and deterioration due to long-term use can be reduced. In other words, by using a single-use system in which only the amount required to be used up in one use is stored, the risk of contamination can be reduced. In addition, since each component such as the reagent storage unit can be made smaller, the distance between the reagent ejection unit and the ejection destination can be reduced, and scattering of the reagent during ejection can be suppressed. Note that the reagent cartridge 211 may contain enough reagent for multiple uses.

[0077] In addition, in the conventional processing device, when a plurality of commercially available reagent bags or reagent bottles are used, there is a risk of mixing up the reagents because the appearances of the reagent bags and reagent bottles are similar. On the other hand, the present embodiment is provided with a mix-up prevention means for preventing the mix-up of the reagent cartridge 211. As shown in Figs. 4 and 5, the fourth holding section 212 is formed in a unique shape that can only be attached to the corresponding liquid supply section (reagent cartridge 211), and the reagent cartridge 211 is formed in a unique shape that can only be attached to the corresponding holding section (fourth holding section 212), so that a reagent other than the reagent cartridge 211 cannot be attached to the fourth holding section 212. In this way, by making the shape of the reagent cartridge and the shape of the attachment section a unique combination for each process, it is possible to prevent the attachment of the reagent to the wrong process, prevent the mix-up of the reagent or cell suspension, and reduce the risk of contamination of the reagent or cell suspension. The mix-up prevention means may be called a suppression means for suppressing the attachment of the liquid supply section to an incompatible holding section.

[0078] Other means may be used as a mix-up prevention means. For example, an identification code for identifying the type and amount of the reagent may be provided on the outer surface of the storage section 2111 of the reagent cartridge 211. The identification code may be, for example, a barcode, a symbol, or a reagent name. In this case, a reading means capable of reading the identification code is provided near the fourth holding section 212. The reading means is, for example, a camera or a barcode reader, and is installed at a position where the identification code of the reagent cartridge 211 can be read. The control circuit 7 obtains the reading result of the identification code from the reading means, and determines whether or not the correct reagent cartridge 211 is attached based on the reading result of the identification code. For example, if the read identification code corresponds to the blood bag 202 or another reagent bag, the control circuit 7 determines that an incorrect reagent has been attached to the fourth holding section 212, and warns the operator.

[0079] Furthermore, the operator may be able to arbitrarily set a combination of the fourth holding part 212 and the correct reagent to be attached to the fourth holding part 212. For example, the operator may be able to set in advance the type of correct reagent cartridge to be attached to the fourth holding part 212 and its identification code according to the amount of reagent to be used.

[0080] Also, the operator may be able to determine for himself whether or not the correct reagent cartridge 211 is attached. In this case, for example, as a means for preventing mix-up, an identification marker for identifying the corresponding relationship between the reagent cartridge 211 and the fourth holding section 212 is provided on each of the reagent cartridge 211 and the fourth holding section 212. The identification marker is, for example, a mark of a specific color or shape. For example, by attaching marks of the same color and shape to the reagent cartridge 211 and the fourth holding section 212, the operator can determine for himself whether or not the correct reagent is attached in the correct position.

[0081] The biological sample processing apparatus 1 also includes a transport means for transporting the product generated during the processing step. In this embodiment, the transport means includes a conveyor 210 for moving the third collection container 224 containing PBMCs from the ninth holding unit 225, and when the PBMCs are contained in the third collection container 224, the conveyor 210 can automatically transport the third collection container 224. In the conventional processing apparatus, every time a final product is generated in the biological sample processing step, the operator needs to take out the final product and then process the next biological sample. On the other hand, according to the biological sample processing apparatus 1 of this embodiment, by using the transport means to move the final product, the blood cell separation step can be performed continuously without the operator having to collect the third collection container 224 every time one blood cell separation step is completed. In other words, the biological sample processing apparatus 1 can perform continuous processing of biological samples. In this way, the biological sample processing apparatus 1 can perform continuous production of PBMCs, and therefore the production amount of PBMCs per batch can be increased. Furthermore, the production volume can be adjusted by adjusting the transport speed of the conveyor 210 during continuous production according to the desired yield.

[0082] A unit operation in which one blood cell separation step is carried out in one operation may be performed, and the operator may arbitrarily set switching between the unit operation and the continuous operation.

[0083] The blood cell separation mechanism 2 also includes a UV irradiation unit 226 as a waste treatment unit for treating waste generated by processing the biological sample. The UV irradiation unit 226 can sterilize the used reagent cartridge 211 by irradiating it with ultraviolet (UV) rays. This allows the used reagent to be safely disposed of.

[0084] Second Embodiment A second embodiment will be described. This embodiment is a modification of the configuration of the first embodiment as follows. Descriptions of the same configuration, operation, and effects as those of the first embodiment will be omitted. The biological sample processing device 1 of this embodiment is a factor introduction device that automatically introduces factors into peripheral blood mononuclear cells (hereinafter referred to as PBMCs) after expansion culture in the production of iPS cells.

[0085] Fig. 15 is a block diagram showing a configuration example of a biological sample processing apparatus 1 according to a second embodiment. As shown in Fig. 15, the biological sample processing apparatus 1 of this embodiment includes a factor introduction mechanism 8 instead of a blood cell separation mechanism 2. The factor introduction mechanism 8 introduces a factor into PBMCs after expansion culture. PBMCs are an example of a biological sample.

[0086] FIG. 16 is a diagram showing an example of the configuration of the factor introduction mechanism 8 shown in FIG. 15. As shown in FIG. 16, the factor introduction mechanism 8 includes a housing 801, a first reagent cartridge 802, a first holding section 803, a first pump 804, a PBMC container 805, a second holding section 806, a third holding section 807, a second pump 808, a first filter 809, a first collection container 810, a fourth holding section 811, a conveyor 812, an infection section 813, a fifth holding section 814, a third pump 815, a second filter 816, a second collection container 817, a sixth holding section 818, a second reagent cartridge 819, a seventh holding section 820, a fourth pump 821, an eighth holding section 822, and a UV irradiation section 823. The factor introduction mechanism 8 also includes a drive mechanism. The drive mechanism operates each of the above-mentioned components of the factor introduction mechanism 8 under the control of the control circuit 7. The driving mechanism is realized by, for example, a robot arm, a pump, a gear, a belt conveyor, etc. For example, the driving mechanism operates each pump and moves each component to an arbitrary position using a robot arm according to the control of the control circuit 7. For example, syringe pumps are used as the first pump 804, the second pump 808, the third pump 815, and the fourth pump 821. For example, well plates, flasks, dishes, and bags are used as various containers such as the PBMC container 805, the first collection container 810, and the second collection container 817.

[0087] The housing 801 is the exterior of the factor introduction mechanism 8 .

[0088] The first reagent cartridge 802 is a cartridge-type container capable of accommodating a stealth RNA vector (hereinafter referred to as SRV). The first reagent cartridge 802 is an example of a liquid supply unit in this embodiment. The first reagent cartridge 802 accommodates an amount of SRV for one use in advance. The amount for one use is, for example, the amount used in one factor introduction step. Note that the first reagent cartridge 802 may accommodate an amount of SRV for multiple uses. The first reagent cartridge 802 may be called a factor cartridge. The configuration of the first reagent cartridge 802 is similar to that of the reagent cartridge 211 in FIG. 3, and therefore description thereof will be omitted. SRV is an example of a factor.

[0089] The first holding unit 803 is a holding mechanism that holds the first reagent cartridge 802. The first holding unit 803 is an example of a holding unit that holds a liquid supply unit. The first reagent cartridge 802 is attached to the first holding unit 803 by an operator. The first holding unit 803 is disposed directly below the first pump 804. The second holding unit 806 is disposed directly below the first holding unit 803.

[0090] The first pump 804 is connected to the first reagent cartridge 802 held in the first holding unit 803. The first pump 804 is, for example, a syringe pump. The first pump 804 extends downward under the control of the control circuit 7, and discharges the SRV contained in the first reagent cartridge 802 into the PBMC container 805 held in the second holding unit 806. The first pump 804 is an example of a drive unit.

[0091] The PBMC container 805 is a container capable of containing PBMCs after expansion culture. The PBMCs after expansion culture are supplied, for example, from a culture device that performs a culture step. The PBMC container 805 has a sealability capable of suppressing or preventing the mixed liquid from being exposed to the outside air. A predetermined amount of PBMCs is contained in the PBMC container 805 in advance.

[0092] Second holding unit 806 is a holding mechanism that holds PBMC container 805. An operator attaches PBMC container 805 to second holding unit 806. Second holding unit 806 is disposed directly below first holding unit 803.

[0093] The first reagent cartridge 802 discharges SRV directly into the PBMC container 805 by driving the first pump 804. The PBMC container 805 is an example of a destination to which liquid is discharged from a liquid supply unit. When the SRV is discharged into the PBMC container 805, the SRV is introduced into the PBMCs in the PBMC container 805. The PBMC container 805 is then transported from the second holding unit 806 to the third holding unit 807 by the robot arm. The used first reagent cartridge 802 is transported from the first holding unit 803 to the UV irradiation unit 823 by the robot arm.

[0094] The third holding unit 807 is a holding mechanism that holds the PBMC container 805 transferred from the second holding unit 806. The third holding unit 807 is disposed between the second pump 808 and the first filter 809.

[0095] The second pump 808 is connected to the PBMC container 805 held in the third holding unit 807. The second pump 808 is, for example, a syringe pump. The second pump 808 discharges the PBMCs contained in the PBMC container 805 into the first filter 809.

[0096] The first filter 809 is a filter for performing a predetermined filtering process on the PBMC into which the SRV has been introduced. The first filter 809 is disposed immediately below the third holding unit 807.

[0097] First collection container 810 is a container for collecting PBMCs that have passed through first filter 809. First collection container 810 has, for example, airtightness so as to suppress or prevent the collection liquid from being exposed to the outside air.

[0098] Fourth holding unit 811 is a holding mechanism that holds first collection Container 810. Fourth holding unit 811 is located directly below first filter 809. Fourth holding unit 811 is realized by conveyor 812. Conveyor 812 is a belt conveyor that transports first collection Container 810 and second collection Container 817. First collection Container 810, which has collected PBMCs that have passed through first filter 809, is transported by conveyor 812 to infection unit 813.

[0099] Infection section 813 is a waiting position for infecting PBMCs in first collection container 810 with SRV. Infection section 813 is disposed, for example, on conveyor 812. First collection container 810 is disposed in infection section 813 until a predetermined time has elapsed. After the predetermined time has elapsed, first collection container 810 is transported to fifth holding section 814 by a robot arm.

[0100] The fifth holding section 814 is a holding mechanism that holds the first collection container 810 transported from the infection section 813. The fifth holding section 814 is disposed between the third pump 815 and the second filter 816.

[0101] The third pump 815 is connected to the first collection container 810 held in the fifth holding section 814. The third pump 815 is, for example, a syringe pump. The third pump 815 causes the first pump 804 to discharge the infected PBMCs contained in the first collection container 810 to the second filter 816.

[0102] Second filter 816 is a filter for performing a predetermined filtering process on the infected PBMCs. Second filter 816 is disposed immediately below fifth holding section 814.

[0103] Second collection container 817 is a container for collecting PBMCs that have passed through second filter 816. Second collection container 817 has, for example, airtightness to suppress or prevent the collection liquid from being exposed to the outside air.

[0104] Sixth holding unit 818 is a holding mechanism that holds second collection container 817. Sixth holding unit 818 is disposed directly below second filter 816. Second collection container 817 is transported from sixth holding unit 818 to eighth holding unit 221 by conveyor 812.

[0105] The second reagent cartridge 819 is a cartridge-type container capable of accommodating a culture medium such as StemSpan. The second reagent cartridge 819 is an example of a liquid supply unit in this embodiment. The second reagent cartridge 819 previously accommodates a single dose of StemSpan. The single dose is, for example, the amount used in one factor introduction step. The second reagent cartridge 819 may accommodate a multiple dose of PBS. The second reagent cartridge 819 may be called a recovery liquid cartridge. The configuration of the second reagent cartridge 819 is similar to that of the reagent cartridge 211 in FIG. 3, and therefore description thereof will be omitted.

[0106] The seventh holding unit 820 is a holding mechanism that holds the second reagent cartridge 819. The seventh holding unit 820 is an example of a holding unit that holds a liquid supply unit. The second reagent cartridge 819 is attached to the seventh holding unit 820 by an operator. The seventh holding unit 820 is disposed between the fourth pump 821 and the eighth holding unit 221.

[0107] The fourth pump 821 is connected to the second reagent cartridge 819 held in the seventh holding unit 820. The fourth pump 821 is, for example, a syringe pump. The fourth pump 821 causes the first pump 804 to discharge the StemSpan contained in the second reagent cartridge 819 into the second collection container 817 held in the eighth holding unit 221. The fourth pump 821 is an example of a drive unit.

[0108] In the seventh holding unit 820, the second reagent cartridge 819 is directly connected to the second collection container 817. The second reagent cartridge 819 directly discharges StemSpan into the second collection container 817 by driving the fourth pump 821. The second collection container 817 is an example of a destination to which liquid is discharged from the liquid supply unit. The second reagent cartridge 819 is transported from the seventh holding unit 820 to the UV irradiation unit 226 by the robot arm.

[0109] Eighth holding unit 822 is a holding mechanism that holds second collection container 817 transported from second holding unit 806. Eighth holding unit 822 is realized by conveyor 812. Second collection container 817 into which StemSpan has been introduced is transported by conveyor 812 to an outlet (not shown). The operator removes second collection container 817 from the outlet, thereby removing the infected PBMCs into which StemSpan has been introduced from factor introduction mechanism 8, and performs the next step in the factor introduction step.

[0110] The UV irradiation unit 823 stores the used first reagent cartridge 802 and second reagent cartridge 819 and irradiates them with ultraviolet (UV) rays. The UV irradiation unit 823 is provided with an irradiator that irradiates ultraviolet (UV) rays, and irradiates the used first reagent cartridge 802 and second reagent cartridge 819 with ultraviolet rays for a fixed period of time. When irradiation of ultraviolet rays is completed, the first reagent cartridge 802 and second reagent cartridge 819 are removed from an outlet (not shown), discharged to the outside, and discarded. The UV irradiation unit 823 is an example of a waste treatment unit that treats waste generated by processing biological samples.

[0111] The small flow paths and filters provided in the factor introduction mechanism 8 may be configured to be removable. For example, the first filter 809 and the second filter 816 may be made removable as desired, and these may be replaced with filters and flow paths having desired functions. The removable first filter 809 and the second filter 816 are examples of removable processing means used in processing biological samples.

[0112] Furthermore, similarly to the first embodiment, the biological sample processing apparatus 1 is provided with mix-up prevention means for preventing mix-up of the first reagent cartridge 802 and the second reagent cartridge 819. For example, as the mix-up prevention means, the first reagent cartridge 802, the first holder 803, the second reagent cartridge 819 and the seventh holder 820 are formed so that only the corresponding reagent cartridges can be attached.

[0113] For example, the first reagent cartridge 802 and the first holder 803 are formed into a shape as shown in the example of Fig. 4, and the second reagent cartridge 819 and the seventh holder 820 are formed into a shape as shown in the example of Fig. 5. In this case, the first reagent cartridge 802 cannot be attached to the seventh holder 820, and can only be attached to the first holder 803. Furthermore, the second reagent cartridge 819 cannot be attached to the first holder 803, and can only be attached to the seventh holder 820.

[0114] Next, the operation of the biological sample processing apparatus 1 of this embodiment will be described. FIG. 17 is a flow chart showing an example of the procedure of a factor introduction step performed by an operator using the biological sample processing apparatus 1 of this embodiment. The factor introduction step is a step of introducing factors such as SRV and StemSpan into PBMCs that have completed the culture step in the production of iPS cells. FIG. 18 is a flow chart showing an example of the procedure of the factor introduction process performed in step S404 of FIG. 17. Note that the procedure in each process described below is merely an example, and each process can be appropriately changed as much as possible. Also, steps can be omitted, replaced, or added to the procedure described below as appropriate depending on the embodiment.

[0115] (Factor introduction process) (Step S401) First, the operator installs a pump unit including a first pump 804, a second pump 808, a third pump 815, and a fourth pump 821 at a predetermined position inside the housing 801 of the factor introduction mechanism 8. The pump unit may be called a nozzle unit.

[0116] (Step S402) Next, the operator places the first reagent cartridge 802, in which an SRV is already housed, in the first holding section 803, and places the second reagent cartridge 819, in which StemSpan is already housed, in the seventh holding section 820. At this time, since the first reagent cartridge 802, first holding section 803, second reagent cartridge 819, and seventh holding section 820 are provided with the above-mentioned mix-up prevention function, the operator can install the first reagent cartridge 802 and the second reagent cartridge 819 in the correct positions without mixing them up. (Step S403) Next, the operator operates the input interface 6 to start the operation of the biological sample processing apparatus 1.

[0117] (Step S404) When the operation of the biological sample processing apparatus 1 starts, the biological sample processing apparatus 1 executes a factor introduction process under the control of the control circuit 7. In the factor introduction process, the factor introduction mechanism 8 automatically executes an operation of introducing a factor into the PBMC under the control of the control circuit 7.

[0118] Here, the factor introduction process executed by the biological sample processing apparatus 1 will be described in detail. 18 is a flow chart showing an example of the procedure of the factor introduction process executed by the biological sample processing apparatus 1. Each process described below is executed by driving mechanisms such as the robot arm and the conveyor 812 under the control of the control circuit 7, but the description thereof will be omitted.

[0119] (Factor introduction process) Fig. 19 is a diagram showing the internal state of the factor introduction mechanism 8 at the start of the factor introduction process. As shown in Fig. 19, at the start of the factor introduction process, a first reagent cartridge 802 is attached to a first holding section 803, and a second reagent cartridge 819 is attached to a seventh holding section 820. In addition, a PBMC container 805 containing PBMCs after the culture step is placed in a second holding section 806. In addition, a first collection container 810 is placed in a fourth holding section 811, and a second collection container 817 is placed in a sixth holding section 818.

[0120] (Step S501) When the factor introduction process starts, as shown in FIG. 19, the first pump 206 is driven to discharge the SRV contained in the first reagent cartridge 802 into the PBMC container 805, and the SRV is introduced into the PBMCs in the PBMC container 805.

[0121] (Step S502) 20 , PBMC container 805 moves from second holding section 806 to third holding section 807. Thereafter, second pump 808 is driven to discharge the SRV-containing PBMCs contained in PBMC container 805 into first filter 809, where they are filtered. The PBMCs that pass through first filter 809 are collected in first collection container 810 placed in fourth holding section 811.

[0122] (Step S503) 21, first collection container 810 is transported to infection section 813. First collection container 810 waits in infection section 813 until a predetermined time has elapsed and the PBMCs are infected with SRV.

[0123] (Step S504) 22, first collection container 810 moves from infection section 813 to fifth holding section 814. Thereafter, third pump 815 is driven to discharge the infected PBMCs contained in first collection container 810 into second filter 816, where they are filtered. The PBMCs that have passed through second filter 816 are collected in second collection container 817 installed in sixth holding section 818.

[0124] (Step S505) 23, second collection container 817 moves from sixth holding section 818 to eighth holding section 822. Thereafter, fourth pump 821 is driven to eject StemSpan contained in second reagent cartridge 819 as culture medium into second collection container 817, and StemSpan is introduced into the infected PBMCs.

[0125] Thus, in the factor introduction process in step S404, a series of processes from step S501 to step S505 introduces SRV into PBMCs required for processing iPS cells, and introduces StemSpan into the infected PBMCs.

[0126] (Step S405) When the factor introduction process in step S404 is completed, the operator transports the second collection container 817 from the eighth holder 822 to the removal port as shown in FIG. 23, and ends the factor introduction step. At the same time, the operator executes a disposal process by the biological sample processing apparatus 1. In the disposal process, similar to the processes in steps S301 to S303 in FIG. 8, ultraviolet rays (UV) are irradiated for a certain period of time onto the used first reagent cartridge 802 that has been moved to the UV irradiation section 823. When the irradiation of ultraviolet rays (UV) is completed, the sterilized first reagent cartridge 802 is discharged to the outside and discarded. Note that the same disposal process as for the first reagent cartridge 802 may also be executed for the used second reagent cartridge 819.

[0127] The effects of the biological sample processing apparatus 1 according to this embodiment will be described below.

[0128] The biological sample processing apparatus 1 of this embodiment includes a first holding unit 803 that detachably holds a first reagent cartridge 802, and a seventh holding unit 820 that detachably holds a second reagent cartridge 819. The first reagent cartridge 802 and the second reagent cartridge 819 are examples of a liquid supply unit. The first holding unit 803 and the seventh holding unit 820 are examples of a holding unit that detachably holds a liquid supply unit.

[0129] The first reagent cartridge 802 includes a storage means for storing SRV as a reagent, and a discharge means for pushing out the SRV from the storage section and discharging the SRV directly into the PBMC container 805. SRV is an example of a reagent for producing iPS cells. The biological sample processing apparatus 1 also includes a first pump 804 as a drive section for driving the discharge means. The first pump 804 is, for example, a syringe pump. The first reagent cartridge 802 is directly connected to the PBMC container 805, and pushes out the SRV from the storage section and discharges the SRV directly into the PBMC container 805. The PBMC container 805, which is a storage container, is an example of a discharge destination.

[0130] The second reagent cartridge 819 also includes a storage means for storing StemSpan as a reagent, and a discharge means for pushing out StemSpan from the storage section and discharging StemSpan directly into the second collection container 817. StemSpan is an example of a reagent for creating iPS cells. The biological sample processing apparatus 1 also includes a fourth pump 821 as a drive section for driving the discharge means. The fourth pump 821 is, for example, a syringe pump. The second reagent cartridge 819 is directly connected to the second collection container 817, and pushes out StemSpan from the storage section and directly discharges StemSpan into the second collection container 817. The second collection container 817, which is a storage container, is an example of a discharge destination.

[0131] With the above configuration, the biological sample processing apparatus 1 of this embodiment uses the first reagent cartridge 802 and the second reagent cartridge 819, each having a storage means and a discharge means, and thus can introduce the reagent directly to the discharge destination without providing a flow path connecting the storage section and the discharge destination. Therefore, the same effects as those of the first embodiment can be obtained. For example, the risk of contamination and liquid transfer loss caused by the adhesion of residues of the reagent or the like to the inner wall of the flow path can be reduced, and it becomes unnecessary to prepare an extra amount of reagent in consideration of liquid transfer loss.

[0132] Furthermore, similarly to the first embodiment, the first reagent cartridge 802 and the second reagent cartridge 819 are single-use cartridges that store only the amount required to be used up in one go, thereby reducing the risk of contamination.

[0133] Also in this embodiment, a mix-up prevention means is provided to prevent the first reagent cartridge 802 and the second reagent cartridge 819 from being mixed up. Therefore, as in the first embodiment, it is possible to prevent the attachment of the reagent to the wrong process, prevent the mix-up of the reagent and the cell suspension, and reduce the risk of mixing (contamination risk) of the reagent and the cell suspension. For example, by forming the first reagent cartridge 802 and the first holding section 803 into unique shapes that can only be attached to each other, and forming the second reagent cartridge 819 and the seventh holding section 820 into unique shapes that can only be attached to each other, it is possible to prevent the first reagent cartridge 802 and the second reagent cartridge 819 from being mixed up. Note that, as in the first embodiment, other means may be used as the mix-up prevention means.

[0134] In addition, since the present embodiment also includes a conveyor 812 as a transport means for transporting products generated during the processing step, it is possible to perform continuous production of PBMCs into which SRV and StemSpan have been introduced, as in the first embodiment. Furthermore, a unit operation in which one factor introduction step is performed in one operation may be performed, and the operator may arbitrarily set switching between unit operation and continuous operation.

[0135] In addition, in this embodiment, the factor introduction mechanism 8 is also equipped with a UV irradiation unit 823 as a waste treatment unit that treats waste generated by processing the biological sample, so that used reagents can be safely disposed of, as in the first embodiment.

[0136] (First Modification) It is also possible to use a reagent cartridge that can separately store two types of reagents to be mixed immediately before the processing step. Fig. 24 is a diagram showing an example of the configuration of a reagent cartridge 91 according to a first modified example. The reagent cartridge 91 is held in a holder 92 and connected to a pump 93.

[0137] The reagent cartridge 91 includes a first storage section 911A and a second storage section 911B. Although not shown, the reagent cartridge 91 also includes a piston section and a discharge section as a discharge means. The first storage section 911A and the second storage section 911B are reagent containers that respectively store different types of reagents. The first storage section 911A stores a liquid A as a reagent, and the first storage section 911B stores a liquid B as a reagent. The first storage section 911A and the second storage section 911B store, for example, two types of reagents that need to be mixed immediately before a biological sample processing step. By driving the pump 93, the reagent is discharged from each of the first storage section 911A and the second storage section 911B to a discharge destination such as a collection container. In the discharge destination container, the reagents discharged from each of the first storage section 911A and the second storage section 911B are mixed. In this way, by using a reagent cartridge 91 that can separately store two types of reagents to be mixed immediately before the processing step and simultaneously eject these reagents, it is possible to mix the reagents without having to prepare separate reagent containers for each reagent or providing flow paths between the reagent containers. Since there is no need to provide flow paths between the reagent containers, it is possible to prevent reagents from remaining in the flow paths. Note that a reagent cartridge that can separately store three or more types of reagents may also be used.

[0138] (Second Modification) Alternatively, a reagent cartridge in which two types of reagents are mixed within the cartridge may be used. Figure 25 is a diagram showing an example of the configuration of a reagent cartridge 94 according to a second modified example. The reagent cartridge 94 is held in a first holding section 95 and connected to a first pump 96.

[0139] The reagent cartridge 94 includes a first cartridge 94A and a second cartridge 94B. The first cartridge 94A and the second cartridge 94B are detachably connected inside the reagent cartridge 94. The first cartridge 94A and the second cartridge 94B are reagent containers that contain different types of reagents. The first cartridge 94A stores liquid A as a reagent, and the second cartridge 94B stores liquid B as a reagent. The first cartridge 94A and the second cartridge 94B store, for example, two types of reagents that need to be mixed at the start of a biological sample processing step.

[0140] The first cartridge 94A and the second cartridge 94B each include a storage means for storing a reagent, and a piston portion and a discharge portion as a discharge means for discharging the reagent from the storage means. Inside the reagent cartridge 91, the discharge portion of the first cartridge 94A is connected to the storage portion of the second cartridge 94B. The first pump 96 is connected to the piston portion of the first cartridge 94A.

[0141] When mixing two reagents immediately before a processing step, first, the reagent A contained in the first cartridge 94A is injected from the discharge portion of the first cartridge 94A into the storage portion of the second cartridge 94B by driving the first pump 96. In the storage portion of the second cartridge 94B, the liquids A and B are mixed.

[0142] When the liquid A and the liquid B are mixed, the second cartridge 94B is removed from the reagent cartridge 94 and moved to the second holding section 98 by a driving mechanism such as a robot arm. In the second holding section 98, the second cartridge 94B is connected to the second pump 99. Then, the second pump 99 is driven to discharge the mixed liquid of the liquid A and the liquid B contained in the second cartridge 94B to a discharge destination such as a collection container. In this way, by using the reagent cartridge 94 that can mix two types of reagents to be mixed immediately before the processing step, it is possible to mix the reagents without preparing separate reagent containers for each reagent or providing a flow path between the reagent containers. Since it is not necessary to provide a flow path between the reagent containers, it is possible to prevent the reagent from remaining in the flow path. It is also possible to use a reagent cartridge that can store three or more types of reagents separately.

[0143] (Examples) In the above embodiment and modified example, the biological sample processing apparatus is described as an apparatus that automatically performs a blood cell separation process and a factor introduction process for creating iPS cells, but the present invention is not limited to this. For example, the biological sample processing apparatus may be a culture apparatus that automatically cultures cells, a dispensing apparatus that automatically dispenses liquid, or a cell processing apparatus that automatically performs various processes on various cells. That is, the biological sample processed by the biological sample processing apparatus may be blood, a blood suspension, or PBMC, or may be a culture solution. In addition, the liquid used in processing the biological sample may be a medium or factor used in cell culture, or a reagent or other liquid used in various cell processes.

[0144] In any of the above cases, by using a cartridge-type liquid supply unit that stores the liquid used in processing the biological sample and can directly discharge the liquid to the discharge destination, the liquid can be supplied to the discharge destination without passing through a flow path, thereby reducing the risk of contamination by the biological sample or liquid. Also, in any of the above cases, by applying a mix-up prevention means to the liquid supply unit or the holder of the liquid supply unit, it is possible to prevent mix-ups of multiple types of liquid used in processing.

[0145] Furthermore, the cartridge-type liquid supply unit may be applied to a container that contains an intermediate product generated during a processing step, not limited to commercially available reagent bags that contain PBS, SRV, StemSpan, etc. For example, the mixing container 203, first collection container 214, and second collection container 219 in the first embodiment, and the PBMC container 805 and first collection container 810 in the second embodiment may be cartridge-type liquid supply units.

[0146] In the above embodiment, an example in which a piston structure driven by a pump is provided as the discharge means provided in the liquid supply unit has been described, but the present invention is not limited to this. For example, the liquid may be automatically discharged to the connected discharge destination by creating a positive pressure inside the storage means. The piston part may also be manually driven by an operator. In this case, a drive unit such as a pump is not required. The storage means may also be formed in a structure that allows the operator to crush it from both sides by hand. In this case, the discharge port and the structure for crushing provided in the storage means correspond to the discharge means, and a drive unit such as a pump is not required.

[0147] According to at least one of the embodiments described above, it is possible to reduce the risk of contamination during processing of a biological sample.

[0148] 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]

[0149] 1. Biological sample processing equipment 2…Blood cell separation mechanism 3…Memory circuit 4. Communication interface 5. Output interface 6…Input interface 7...Control circuit 71...System control function 201…Housing 202...Blood bag 202 2021…Blood flow path 203…Mixing container 203-UV…Mixing container 204, 205, 209, 212, 215, 216, 220, 221, 225...holding part 206, 213, 217, 222…Pumps 207, 223…Filter 208...Waste liquid container 210…Conveyor 211...Reagent cartridge 2111…Storage section 2112…Piston section 2113…Discharge part 214, 219, 224...Collection containers 218...Flow path 226…UV irradiation section 8...Factor introduction mechanism 801…Housing 802, 819...Reagent cartridge 803, 806, 807, 811, 814, 818, 820, 822...holding part 804, 808, 815, 821... Pumps 805...PBMC container 809, 816… Filter 810, 817…Collection container 812...Conveyor 813…Infected part 823...UV irradiation section 91, 94...Reagent cartridge 911A…Storage section 911B…Storage section 92, 95, 98...holding part 93, 96, 99…Pump 94A, 94B... Cartridge

Claims

1. a holding part for detachably holding a liquid supply part including a storage means for storing a liquid used in processing a biological sample and a discharge means for pushing out the liquid from the storage means and discharging it directly to a discharge destination; Biological sample processing equipment.

2. The storage means stores a single dose of the liquid. The biological sample processing device according to claim 1 .

3. The storage means stores the liquid for multiple uses. The biological sample processing device according to claim 1 .

4. Further comprising a drive unit for discharging the liquid from the discharging means. The biological sample processing device according to claim 1 .

5. Further comprising a conveying means for conveying the product produced during the processing step; The biological sample processing device according to claim 1 .

6. The biological sample processing apparatus continuously processes the biological samples. The biological sample processing device according to claim 5.

7. Further comprising a mix-up prevention means for preventing mix-up of the liquid supply unit. The biological sample processing device according to claim 1 .

8. The mix-up prevention means is provided in the storage means and includes an identification code for identifying the liquid and a reading means for reading the identification code. The biological sample processing device according to claim 7.

9. the mix-up prevention means further includes a control unit that determines whether or not a correct liquid supply unit is attached to the holding unit based on a result of reading the identification code. The biological sample processing device according to claim 8.

10. The mix-up prevention means includes the holding portion formed so that only the corresponding liquid supply portion can be attached thereto. The biological sample processing device according to claim 7.

11. the mix-up prevention means includes an identification marker provided in each of the liquid supply unit and the holder for identifying a correspondence between the liquid supply unit and the holder; The biological sample processing device according to claim 7.

12. Further comprising a removable processing means used for the processing of the biological sample. The biological sample processing device according to claim 1 .

13. Further comprising a waste treatment unit for treating waste generated by the processing. The biological sample processing device according to claim 1 .

14. The drive unit is a syringe pump. The biological sample processing device according to claim 4.

15. The discharge means includes a piston portion that moves when the syringe pump is driven. The biological sample processing device according to claim 14.

16. the biological sample is blood for generating induced pluripotent stem cells; The processing includes separating blood cells from blood; The liquid is phosphate buffered saline (PBS); The biological sample processing device according to claim 1 .

17. The biological sample is a peripheral blood mononuclear cell (PBMC) for generating induced pluripotent stem cells; The processing includes introducing a factor into the peripheral blood mononuclear cells; The liquid is the agent. The biological sample processing device according to claim 1 .

18. The liquid is an intermediate product produced during the generation of induced pluripotent stem cells. The biological sample processing device according to claim 1 .

19. The discharge destination is a filter or a container. The biological sample processing device according to claim 1 .

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