Collection device

Abstract

The invention relates to an acquisition device (1), comprising: an electrode nozzle (2); a nozzle movement mechanism that moves the electrode nozzle (2) in the longitudinal direction; a dispensing tip (3) attached to the electrode nozzle (2); positive and negative electrodes (5a, 5b) attached to the electrode nozzle (2) and extending along the dispensing tip (3); a current detection unit (7) that detects the value of current flowing between the positive and negative electrodes (5a, 5b); a sample container for accommodating a sample solution; and a control unit that controls the nozzle movement mechanism. The control unit drives the nozzle movement mechanism to move the electrode nozzle (2) and the dispensing tip (3) in the longitudinal direction, determines the position of the predetermined component layer on the basis of a change in the current value, and drives the electrode nozzle (2) to collect the predetermined component layer.

Description

Technical Field

[0001] The present invention relates to a collecting device for collecting a predetermined component layer from a sample such as whole blood after centrifugation. Background Art

[0002] The whole blood is separated into a plurality of component layers by centrifuging the sample container containing the whole blood at about 1500 rpm. During the centrifugation, the whole blood is diluted and an anticoagulant (sodium citrate, etc.) is added.

[0003] like Figure 6 As shown, in the sample container 10, the multiple component layers are, from the top, an upper layer A, a centrifugal separation agent layer B containing an anticoagulant, etc., and an erythrocyte layer C. The upper layer A is composed of a serum / plasma layer A1 on the upper side and a buffy coat layer A2 on the lower side. The serum / plasma layer A1 is a mixed solution layer of cancer cells, exosomes, proteins, etc. The buffy coat layer A2 is an immune cell solution layer.

[0004] Patent document 1 describes a blood component separation device that separates blood components after centrifugation. It also describes that the blood component separation device presses a mother bag into which whole blood after centrifugation is added, senses the interface of components coming out of the upper part, and transports each component to a different sub-bag. It also describes that the interface is sensed by an optical sensor.

[0005] Prior art literature

[0006] Patent Literature

[0007] Patent Document 1: Japanese Patent Application Publication No. 2003-135591. Summary of the invention

[0008] Problem that the invention aims to solve

[0009] Since the blood component separation device of Patent Document 1 presses and conveys a container such as a mother bag, the interfaces of the plurality of blood component layers tend to become uneven, and accurate separation may not be possible. In addition, since each blood component layer is separated sequentially from the upper layer, it takes time to separate or collect a specific blood component layer.

[0010] Therefore, an object of the present invention is to provide a collecting device that collects a predetermined component layer from a sample such as whole blood after centrifugation by identifying the position of the component layer.

[0011] Solutions for solving problems

[0012] Various aspects of the present invention are exemplified below.

[0013] [Method 1]

[0014] A collecting device for collecting a predetermined component layer from a sample solution after centrifugation, comprising:

[0015] Electrode nozzle;

[0016] A nozzle moving mechanism that moves the electrode nozzle in a longitudinal direction;

[0017] A dispensing gun head, which is installed on the electrode nozzle;

[0018] A positive electrode and a negative electrode, which are mounted on the electrode nozzle and extend along the dispensing gun head;

[0019] a current detection unit that detects a current value flowing between the positive electrode and the negative electrode in the sample solution;

[0020] a sample container containing the sample solution; and

[0021] a control unit that controls the nozzle moving mechanism,

[0022] The control unit drives the nozzle moving mechanism to move the electrode nozzle in the longitudinal direction, determines the position of the predetermined component layer according to the change in the current value, and drives the electrode nozzle to collect the predetermined component layer.

[0023] [Method 2]

[0024] According to the collection device described in method 1,

[0025] The positive electrode and the negative electrode each have an exposed conductive surface at a lower end portion thereof, and are arranged on the side of the lower end portion of the dispensing gun tip in the sample container.

[0026] [Method 3]

[0027] According to the collection device described in method 2,

[0028] The lower ends of the positive electrode and the negative electrode are respectively arranged at substantially the same height as the lower end of the dispensing gun tip (for example, within a range of ±1 mm).

[0029] [Method 4]

[0030] According to the collection device described in method 1,

[0031] The sample container is formed of a light-transmitting material.

[0032] The collection device also has an optical sensing unit for optically sensing the component layer in the sample container.

[0033] [Method 5]

[0034] According to the collection device described in method 4,

[0035] The optical sensing section includes: a light receiving section that receives light in the sample container; and an optical sensing section moving mechanism that moves the light receiving section in a longitudinal direction.

[0036] [Method 6]

[0037] According to the collection device described in method 5,

[0038] The control unit drives the optical sensing unit moving mechanism to move the light receiving unit in a longitudinal direction, and determines a position of a predetermined component layer based on a change in intensity or absorbance of light received by the light receiving unit.

[0039] [Method 7]

[0040] According to the collection device described in method 4,

[0041] The optical sensing unit includes a light irradiation unit that irradiates light into the sample container.

[0042] [Method 8]

[0043] The collection device according to method 1 comprises:

[0044] a sample container rack for accommodating the sample container; and a sample container rack moving mechanism for moving the sample container rack in a horizontal direction.

[0045] [Method 9]

[0046] The collection device according to method 8, wherein:

[0047] When the control unit determines the position of the predetermined component layer, the control unit moves the sample container rack moving mechanism in the horizontal direction and suctions the predetermined component layer with the electrode nozzle.

[0048] [Method 10]

[0049] The collection device according to method 9, wherein:

[0050] The sample container rack moving mechanism includes a first moving mechanism that moves the sample container rack in a first horizontal direction and a second moving mechanism that moves the sample container rack and the first moving mechanism in a second horizontal direction.

[0051] [Method 11]

[0052] An extraction device, comprising a plurality of the collection devices described in Embodiment 1, for extracting a target substance contained in a predetermined component layer after centrifugal separation from a sample, wherein the extraction device comprises:

[0053] Multiple collection devices;

[0054] a plurality of shaking containers for containing a predetermined component layer and extracting the target substance;

[0055] A plurality of cartridges are provided for extracting nucleic acid from the target substance.

[0056] Effects of the Invention

[0057] The collecting device of the present invention can identify the position of a predetermined component layer from a sample such as whole blood after centrifugation and collect the component layer. BRIEF DESCRIPTION OF THE DRAWINGS

[0058] Figure 1 This is a longitudinal section showing a collecting device according to an embodiment of the present invention.

[0059] Figure 2 It is shown Figure 1 Schematic diagram of the usage status of the collection device.

[0060] Figure 3 yes Figure 2 A lateral cross-sectional view of an optical sensing portion.

[0061] Figure 4 It is shown Figure 1 Block diagram of the acquisition device.

[0062] Figure 5 This is a plan view showing a bio-related substance extraction device according to an embodiment of the present invention.

[0063] Figure 6 It is a side view showing a sample container into which components of whole blood after centrifugation are added. DETAILED DESCRIPTION

[0064] With reference to the accompanying drawings, embodiments of the collection device and the extraction device of the present invention are described. In each figure, the same reference numerals are given to common parts and the description is omitted as appropriate. In addition, this embodiment is described by taking the case of collecting a specified component layer (buffy coat) after centrifugation from whole blood as an example, but the present invention is not limited to this and can also be applied to the case of collecting any component layer that can be centrifuged from a biological-related substance solution.

[0065] Reference Figures 1 to 4 , the collection device 1 according to the embodiment of the present invention is described. Figure 1As shown, the collection device 1 is composed of an electrode nozzle 2 capable of sucking and discharging a solution, a dispensing gun head 3 installed on the electrode nozzle 2, a positive electrode 5a installed on the electrode nozzle 2 and extending along the dispensing gun head 3, a negative electrode 5b installed on the electrode nozzle 2 and extending along the dispensing gun head 3, a positive terminal portion 6a electrically connected to the upper end of the positive electrode 5a, a negative terminal portion 6b electrically connected to the upper end of the negative electrode 5b, and a current detection portion 7 electrically connected to the positive terminal portion 6a and the negative terminal portion 6b respectively via wiring.

[0066] The surfaces of the positive electrode 5a and the negative electrode 5b are covered with an insulating layer. A positive lower end portion 5a1 which is not covered with an insulating layer and exposes a conductive surface is provided at the lower end of the positive electrode 5a. A negative lower end portion 5b1 which is not covered with an insulating layer and exposes a conductive surface is provided at the lower end of the negative electrode 5b. The positive lower end portion 5a1 and the negative lower end portion 5b1 are arranged on the side of the lower end portion 3a of the dispensing gun head 3. More preferably, the positive lower end portion 5a1 and the negative lower end portion 5b1 are arranged at substantially the same height as the lower end portion (opening) 3a of the dispensing gun head 3 (for example, within a range of ±1 mm).

[0067] like Figure 2 and 3 As shown, the collection device 1 has an optical sensing unit 8 disposed on the outer side of the sample container 10. The sample container 10 is formed of a light-transmitting material (plastic, glass, etc.). The optical sensing unit 8 is composed of a light irradiation unit (light-emitting element such as LED) 8a for irradiating light to the sample container 10, a light receiving unit (light receiving element such as photodiode) 8b for receiving light from the light irradiation unit 8a after passing through the sample container 10, a recess 8d for storing a part of the sample container 10, an optical sensing unit housing 8e for housing the light irradiation unit 8a and the light receiving unit 8b, and an optical sensing unit moving mechanism 8c for moving the optical sensing unit housing 8e in the longitudinal direction along the sample container 10. As the optical sensing unit moving mechanism 8c, for example, a rack gear and its driving motor can be used.

[0068] like Figure 3 As shown in the figure, by providing the light irradiation surface of the light irradiation part 8a and the light receiving surface of the light receiving part 8b in the concave part 8d, the influence of the ambient light can be reduced. In addition, by arranging the light irradiation direction of the light irradiation part 8a and the light receiving direction of the light receiving part 8b in a cross manner, it is possible to avoid that the strong light of the light irradiation part 8a directly enters the light receiving part 8b. In addition, it is also possible to replace the light irradiation part 8a and the light receiving part 8b with an imaging element such as a CCD, so as to determine the position of the specified component layer according to the difference in the color of each component layer.

[0069] In addition, if Figure 2As shown, the collection device 1 has a sample container rack 12 for accommodating sample containers 10, and a sample container rack moving mechanism 12a for moving the sample container rack 12 in a horizontal direction. The sample container rack moving mechanism 12a is preferably composed of a first moving mechanism 12a1 for moving the sample container rack 12 in a first horizontal direction (x direction), and a second moving mechanism 12a2 for moving the sample container rack 12 and the first moving mechanism 12a1 in a second horizontal direction (y direction). The first moving mechanism and the second moving mechanism may be, for example, a conveyor belt and a driving motor thereof.

[0070] Figure 4 1 is a block diagram of the collection device 1. The control unit 9 of the collection device 1 is connected to the current detection unit 7, the electrode nozzle moving mechanism 4, the cylinder driving mechanism 11 that drives the cylinder body of the electrode nozzle 2, the sample container rack moving mechanism 12a, the light irradiation unit 8a, the light receiving unit 8b, and the optical sensing unit moving mechanism 8c. The control unit 9 receives the current value flowing in the solution in the sample container 10 detected by the current detection unit 7. The control unit 9 controls the operation of the electrode nozzle moving mechanism 4, the cylinder driving mechanism 11, and the sample container rack moving mechanism 12a. As for the optical sensing unit 8, the control unit 9 causes light to be irradiated from the light irradiation unit 8a, receives a light receiving signal from the light receiving unit 8b, and controls the operation of the optical sensing unit moving mechanism 8c.

[0071] The collection operation of the collection device 1 of this embodiment is described. Figure 6 As shown in FIG. 1 , a sample container 10 containing whole blood is separated into component layers A1 to C using a centrifugal separator. Figure 2 As shown in the figure, in the state where the sample container 10 having these component layers A1 to C is accommodated in the sample container rack 12, the control unit 9 drives the electrode nozzle moving mechanism 4 to make the electrode nozzle 2 with the dispensing gun head 3 attached thereto descend at a fixed speed into the sample container 10. During this descending action, a voltage is applied between the positive lower end 5a1 and the negative lower end 5b1, and the current value flowing through each layer is detected by the current detection unit 7. Since the current value of each layer is different due to the difference in the composition of each layer, the control unit 9 can sense the interface of each layer through the change in the current value output by the current detection unit 7.

[0072] The sensing of the interface using the optical sensing unit 8 is described. Since the refractive index changes due to the difference in the components in the component layer in the sample container 10, when the optical sensing unit 8 is moved along the sample container 10 and the light receiving unit 8b is used for measurement, the light receiving amount of the light receiving unit 8b changes due to the difference in the component layer when passing through the interface of each layer. By sensing this change, the control unit 9 can sense the position of the specified component layer (the buffy coat A2). By using the light receiving unit 8b to detect the change in light intensity or light receiving amount when passing through the interface between the serum / plasma layer A1 and the buffy coat A2, and the change in light intensity or light receiving amount when passing through the interface between the buffy coat A2 and the centrifugal separation agent layer B, the control unit 9 can determine the longitudinal position of the buffy coat.

[0073] In addition, when the electrode nozzle 2 descends, the control unit 9 also causes the light irradiation unit 8a and the light receiving unit 8b to descend at the same fixed speed as the electrode nozzle 2. During this descent, the light irradiation unit 8a irradiates each layer in the sample container 10 from the side, and the light receiving unit 8b receives the light after passing through each layer from the side. It is preferably configured in a manner that the light irradiation direction and the light receiving direction intersect. By sensing the change in light intensity or absorbance received by the light receiving unit 8b, the longitudinal position of a specified component layer can be determined.

[0074] When the control unit 9 determines the longitudinal position of the specified component layer using the current detection unit 7 and / or the optical sensing unit 8, the control unit 9 makes the lower end 3a of the dispensing gun head 3 fixed in the longitudinal direction so that the lower end 3a is located in the specified component layer. In this fixed state, the sample container rack moving mechanism 12 can be driven to move the lower end 3a of the dispensing gun head 3 in the horizontal direction (x and y directions) within the circle of the cross section of the sample container 10, and the specified component layer (buffy coat) is sucked into the dispensing gun head 3. By moving the electrode nozzle 2, the specified component layer sucked and collected into the dispensing gun head 3 is discharged into the component layer container.

[0075] A bio-related substance extraction device 100 including a plurality of collection devices 1 according to an embodiment of the present invention will be described. Figure 5 The invention relates to an extraction device 100 capable of collecting and extracting components from a plurality of whole bloods in parallel. The extraction device 100 has a horizontal platform 120 for arranging the various parts, and a nozzle unit 101 capable of moving in the y direction on the platform 120. The nozzle unit 101 has a plurality of collection devices 1 (electrode nozzles 2 and electrodes 5a, 5b) arranged in a row along the x direction. The nozzle unit 101 has an electrode nozzle moving mechanism 4 for moving the nozzle unit 101 as a whole in the y direction and the z direction. The extraction device 100 can also have a plurality of dispensing nozzles without electrodes.

[0076] The platform 120 includes a plurality of boxes 102 , a target material container rack 113 for accommodating a plurality of target material containers 13 , a sample container rack 12 for accommodating a plurality of sample containers 10 , a light sensing unit 108 having a plurality of light sensing portions 8 , and a shaking unit 114 having a plurality of shaking containers 14 .

[0077] The plurality of boxes 102 are arranged in a row in the x direction. Each of the plurality of boxes 102 has a plurality of holes arranged in the y direction. Each of the plurality of boxes 102 is used to perform various processes such as extracting and purifying a target substance from a collected component layer using a dispensing nozzle and magnetic particles.

[0078] The plurality of target substance containers 13 are arranged in a row in the x direction in the target substance container rack 113. The plurality of target substance containers 13 contain target substances separated by the shaking container 14, respectively.

[0079] The sample container rack 12 can be moved in the x direction and the y direction using the sample container rack moving mechanism 12a. The light sensing unit 108 is arranged near the sample container rack 12. When the light sensing unit 108 is used, the sample container rack 12 is moved in the y direction using the sample container rack moving mechanism 12a, and the optical sensing parts 8 of the light sensing unit 108 are respectively arranged at positions where the sample containers 10 accommodated in the sample container rack 12 can be measured.

[0080] The shaking unit 114 has a shaking shaft 114a extending in the x direction and a shaft driving mechanism (conveyor belt and motor) to shake the plurality of shaking containers 14 arranged in a row in the x direction as a whole. The shaking unit 114 shakes the shaking container 14 in a more stable condition than the suction and discharge by the electrode nozzle 2.

[0081] The extraction device 100 can collect multiple specified component layers from multiple sample containers 10 in parallel using multiple collection devices 1. By moving the collected multiple specified component layers to multiple shaking containers 14 and shaking the multiple shaking containers 14 under conditions that are more stable than the suction and discharge performed by the electrode nozzle 2 or the dispensing nozzle, multiple target substances (specific cancer cells, etc.) bound to magnetic beads with lectins can be separated from the multiple specified component layers using magnets. The multiple target substances are moved to the multiple target substance containers 13 through the multiple electrode nozzles 2 or the dispensing nozzles. Furthermore, the multiple target substances are moved from the multiple target substance containers 13 to the multiple boxes 102. The multiple target substances are purified, nucleic acids are extracted, etc. using the dispensing nozzles, magnetic particles, and external magnets on the multiple boxes 102.

[0082] Description of Reference Numerals

[0083] 1: Collection device;

[0084] 2: Electrode nozzle;

[0085] 3: Dispensing tip;

[0086] 4: Nozzle moving mechanism;

[0087] 5a: positive electrode;

[0088] 5b: negative electrode;

[0089] 7: Current detection unit;

[0090] 8: Optical sensing unit;

[0091] 10: sample container;

[0092] 100: Extraction device.

Claims

1. A collection device for collecting a predetermined component layer from a sample solution after centrifugation, comprising: Electrode nozzle; A nozzle moving mechanism that moves the electrode nozzle in a longitudinal direction; A dispensing gun head, which is installed on the electrode nozzle; A positive electrode and a negative electrode, which are mounted on the electrode nozzle and extend along the dispensing gun head; a current detection unit that detects a current value flowing between the positive electrode and the negative electrode in the sample solution; a sample container, containing the sample solution; as well as a control unit that controls the nozzle moving mechanism, The control unit drives the nozzle moving mechanism to move the electrode nozzle in the longitudinal direction, determines the position of the predetermined component layer according to the change in the current value, and drives the electrode nozzle to collect the predetermined component layer.

2. The collection device according to claim 1, wherein: The positive electrode and the negative electrode each have an exposed conductive surface at a lower end portion thereof, and are arranged on the side of the lower end portion of the dispensing gun tip in the sample container.

3. The collection device according to claim 2, wherein: The lower ends of the positive electrode and the negative electrode are respectively arranged at substantially the same height as the lower end of the dispensing gun tip (for example, within a range of ±1 mm).

4. The collection device according to claim 1, wherein: The sample container is formed of a light-transmitting material. The collection device also has an optical sensing unit for optically sensing the component layer in the sample container.

5. The collection device according to claim 4, wherein: The optical sensing unit has: a light receiving unit that receives light in the sample container; and an optical sensing portion moving mechanism that moves the light receiving portion in a longitudinal direction.

6. The collection device according to claim 5, wherein: The control unit drives the optical sensing unit moving mechanism to move the light receiving unit in a longitudinal direction, and determines a position of a predetermined component layer based on a change in intensity or absorbance of light received by the light receiving unit.

7. The collection device according to claim 4, wherein: The optical sensing unit includes a light irradiation unit that irradiates light into the sample container.

8. The collection device according to claim 1, comprising: a sample container rack for accommodating the sample container; and a sample container rack moving mechanism for moving the sample container rack in a horizontal direction.

9. The collection device according to claim 8, wherein: When the control unit determines the position of the predetermined component layer, the control unit moves the sample container rack moving mechanism in the horizontal direction and suctions the predetermined component layer with the electrode nozzle.

10. The collection device according to claim 9, wherein: The sample container rack moving mechanism includes a first moving mechanism that moves the sample container rack in a first horizontal direction and a second moving mechanism that moves the sample container rack and the first moving mechanism in a second horizontal direction.

11. An extraction device comprising a plurality of the collection devices according to claim 1, for extracting a target substance contained in a predetermined component layer after centrifugal separation from a sample, the extraction device comprising: Multiple collection devices; a plurality of shaking containers for containing a predetermined component layer and extracting the target substance; A plurality of cartridges are provided for extracting nucleic acid from the target substance.

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