Electrophoresis apparatus

Abstract

The electrophoresis apparatus disclosed herein is characterized by comprising: a capillary filled with a migration medium; a buffer container containing a buffer solution; a storage section for storing a sample container containing a sample; at least one automatic sampler for transporting the sample container and the buffer container respectively; and a control section for controlling the drive of the automatic sampler, the control section driving the automatic sampler to perform the following control: while the buffer container is positioned at a capillary position where one end of the capillary is located, transporting the sample container from the storage section to a standby position near the capillary position; and while the buffer container is transported from the capillary position to the standby position, transporting the sample container from the standby position to the capillary position.

Description

Technical Field

[0001] This disclosure relates to an electrophoresis apparatus. Background Technology

[0002] Capillary electrophoresis is widely used as a technique for separating and analyzing biological samples, such as deoxyribonucleic acid (DNA). Typically, capillary electrophoresis apparatus includes a sample holder and a stage for transporting the sample to the capillary.

[0003] Patent Document 1, entitled "A Multichannel Capillary Electrophoresis System and Control Console Based on Ultraviolet Absorption with Improved Sample Processing and Control Method for Sample Analysis," discloses the following technology: "The XZ stage moves the sample from a user-accessible drawer to the capillary array for analysis. Through a computer program, the user can add capillary electrophoresis jobs corresponding to the analysis of the sample column or plate to the queue without stopping or interrupting the ongoing processing" (see the abstract of this document).

[0004] Patent Document 2, with the subject matter of "preventing sample deterioration and performing efficient analysis in an electrophoresis apparatus," discloses the following technology: "an electrophoresis analysis unit that analyzes a sample housed in a sample plate by electrophoresis, a cryogenic storage tank capable of holding multiple sample plates, a standby device for temporarily storing the sample plates in the cryogenic storage tank before transferring them to the electrophoresis analysis unit, and a transport device for transporting the sample plates. When the sample plates are analyzed in the electrophoresis analysis unit, other sample plates are stored in the standby device" (see the abstract of this document and technical solution 1).

[0005] Existing technical documents

[0006] Patent documents

[0007] Patent Document 1: Japanese Patent Application Publication No. 2019-35753

[0008] Patent Document 2: Japanese Patent No. 4377764 Summary of the Invention

[0009] The problem that the invention aims to solve

[0010] However, although the electrophoresis apparatuses described in Patent Documents 1 and 2 both have the function of changing unused samples and changing the sample processing order during electrophoresis, the transport time of the transport system is long because there is only one transport platform, and the overall processing of the apparatus requires time.

[0011] Therefore, this disclosure provides a technique for changing sample containers during electrophoresis in an electrophoresis apparatus and shortening the electrophoresis processing time.

[0012] Methods for solving problems

[0013] To address the aforementioned issues, the electrophoresis apparatus of this disclosure is characterized by comprising: a capillary filled with a migratory medium; a buffer container containing a buffer solution; a storage section for storing a sample container containing a sample; at least one automatic sampler for transporting the sample container and the buffer container respectively; and a control section for controlling the drive of the automatic sampler, the control section driving the automatic sampler to perform the following control: while the buffer container is positioned at a capillary position where one end of the capillary is located, transporting the sample container from the storage section to a standby position near the capillary position; and while the buffer container is transported from the capillary position to the standby position, transporting the sample container from the standby position to the capillary position.

[0014] Further features relating to this disclosure will become clear from the description and accompanying drawings. Furthermore, this disclosure is implemented through elements and combinations of elements, as well as through the detailed description that follows and the appended scope of the claimed patent protection.

[0015] The description in this specification is merely a typical example and does not limit the scope of the patent protection sought or the application of this disclosure in any sense.

[0016] Invention Effects

[0017] According to the technology disclosed herein, it is possible to change the sample container during electrophoresis and to shorten the electrophoresis processing time.

[0018] Other issues, structures, and effects not mentioned above become clear through the following description of implementation methods. Attached Figure Description

[0019] Figure 1 This is a schematic diagram of the electrophoresis apparatus according to the first embodiment.

[0020] Figure 2 This is a schematic diagram showing the state of the sample container being moved to the reading position of the barcode reader.

[0021] Figure 3 This is a schematic diagram representing the driving area of ​​the automatic sampler.

[0022] Figure 4A This is a side view of the moving stage of the automatic sampler.

[0023] Figure 4B This is a front view of the moving stage of the automatic sampler.

[0024] Figure 5A This is a top view of the storage department.

[0025] Figure 5B yes Figure 5A View A is a side view of the storage area.

[0026] Figure 6 It is a flowchart representing a series of actions in an electrophoresis apparatus.

[0027] Figure 7 This is a flowchart that outlines the electrophoresis process.

[0028] Figure 8 This is a flowchart illustrating the transport of sample containers and buffer containers when there is only one drive system.

[0029] Figure 9 This is a flowchart illustrating the transfer actions of the automatic sampler and the automatic buffer sampler to the sample container and the buffer container.

[0030] Figure 10 This is a flowchart illustrating the actions taken when reading sample information.

[0031] Figure 11 This is a timing diagram showing the transport actions of the sample container and buffer container in the modified example.

[0032] Figure 12 This is a schematic diagram showing a portion of the structure of the electrophoresis apparatus according to the second embodiment.

[0033] Figure 13 This is a flowchart illustrating the transport operation of the sample container and buffer container in the second embodiment. Detailed Implementation

[0034] In other words, the electrophoresis apparatus of this disclosure is characterized by having at least one automatic sampler that replaces the conventional transfer table, and also having other structures that are effective in reducing the transfer time of the transfer system. Based on this feature, it is expected that the transfer time of the transfer system will be reduced, thereby reducing the overall processing time of the apparatus.

[0035] As for the above-mentioned "other structures", the following three structures are generally considered: (I) a structure that has a part that replaces the conventional transfer table; (II) a structure that also has an information reading unit that reads the sample information recorded in the sample container and a sample container transfer control system associated with the information reading unit; and (III) a structure involving a combination of the above (I) and the above (II).

[0036] The structure described above (I) is characterized by having two separate parts, replacing the conventional transfer table. Since at least one of the two separate transfer table parts needs to be movable, two methods can be considered: (1) both of the two parts are movable, and (2) one of the two parts is fixed while the other is movable. Both (1) and (2) are within the scope of this disclosure. (1) will be referred to as the "first embodiment," and (2) as the "second embodiment." Hereinafter, each embodiment will be described in detail with reference to the accompanying drawings. In particular, the two movable transfer table parts of (1) will be described in the "first embodiment" as an "automatic sampler for samples" and an "automatic sampler for buffer solutions," respectively. Furthermore, the fixed transfer table part and the movable transfer table part of (2) will be described in the "second embodiment" as a "fixed part" and an "automatic sampler," respectively.

[0037] The structures described above (II) and (III) are variations of the "First Embodiment" and will be described together in the description of the "First Embodiment".

[0038] [First Implementation Method]

[0039] <Example of the structure of an electrophoresis apparatus>

[0040] Figure 1 This is a schematic diagram of the electrophoresis apparatus 101 according to the first embodiment. The electrophoresis apparatus 101 includes a capillary electrophoresis unit 102, an irradiation detection unit 103, a pump mechanism 104, an automatic sampler mechanism 105, a signal processing unit 150, and a control unit 160.

[0041] The capillary electrophoresis section 102 includes a loading head 106, a cathode electrode 107, a capillary array 108, a barcode reader 128, a constant temperature bath 109, and a high-voltage power supply 110.

[0042] The capillary array 108 consists of multiple capillaries, with a loading head 106 fixed on the cathode side and a capillary head 111 fixed on the anode side. The capillaries are, for example, glass tubes with an inner diameter of tens of μm and an outer diameter of hundreds of μm, coated with polyimide resin. However, in the detection section 112 of the irradiation detection unit 103, the coating is removed by leakage of light from inside the capillary to the outside.

[0043] The loading head 106 is fixed to the constant temperature bath 109, and a cathode electrode 107 is provided on the loading head 106. Each capillary protrudes from the front end of the cathode electrode 107 through the cathode electrode 107. A high-voltage power supply 110 is connected to the cathode electrode 107 and applies voltage to the cathode electrode 107.

[0044] The thermostatic bath 109 maintains a constant temperature for the capillary array 108 during swimming.

[0045] The irradiation detection unit 103 optically detects samples (e.g., biological samples) separated by an electrophoresis medium. The irradiation detection unit 103 includes a detection section 112, a light source 113, and an optical detector 114. The detection section 112 reads the optical information of the sample flowing within the capillary. The light source 113 can be, for example, a liquid laser, a gas laser, a semiconductor laser, or even an LED. Excitation light is irradiated from the light source 113 onto the detection section 112, thereby releasing light with a wavelength dependent on the sample. The released light is detected by the optical detector 114. The optical detector 114 includes, for example, a CCD sensor, a photodiode, or a light sensor, and outputs the light detection signal to a signal processing unit 150. The signal processing unit 150 includes an analog-to-digital converter (not shown), which converts the detection signal into a digital signal upon receiving it from the optical detector 114 and outputs it to a control unit 160.

[0046] Pump mechanism 104 injects electrophoresis medium into the capillary and the energized path. Pump mechanism 104 includes capillary head 111, block 115, pump 116, check valve 117, needle valve 118, polymer container 119, buffer container 120, and anode electrode 121.

[0047] Capillary head 111 bundles multiple capillaries together and has a protrusion for insertion into block 115. Polymer container 119 contains the polymer that serves as the electrophoresis medium. For example, a polyacrylamide-based separation gel can be used as the polymer. Driven by pump 116, the polymer is injected into the flow path within block 115, thus injecting it into the capillaries. Buffer container 120 contains a buffer solution for electrophoresis, in which anode electrode 121 is immersed.

[0048] The automatic sampler mechanism 105 includes an automatic sampler 123 for samples, an automatic sampler 124 for buffer solutions, and a storage section 126.

[0049] The automatic sampler 123 for samples and the automatic sampler 124 for buffer solutions each have a stage, three stepper motors for moving the stage in three axes, and a linear guide. A sample container 122 is placed on the stage of the automatic sampler 123, and the sample container 122 is transported by moving the stage in three axes. The stage of the automatic sampler 123 has an electrically driven clamp 127 that holds the sample container 122. The sample container 122 is secured to the stage by the electrically driven clamp 127. The sample container 122 may be, for example, a perforated plate with multiple holes. Although not shown in the figure, a barcode indicating information (sample information) about the sample contained in the sample container 122 is printed on the outer wall of the sample container 122.

[0050] A reagent container 125 is placed on the moving stage of the automated buffer sampler 124, and the reagent container 125 is transported by moving the moving stage in three axes. The reagent container 125 contains a buffer solution 129 for containing the buffer solution used for swirling, a cleaning tank 130 for containing cleaning solution for cleaning the capillary, and a waste tank 131 for discarding excess solution; all of these are placed on the same moving stage. Although not shown in the figure, an electric clamp 127 can also be installed in the automated buffer sampler 124.

[0051] In this specification, the position of the sample container 122 or reagent container 125, where the cathode end (cathode 107) of the capillary array 108 is located directly below the loading head 106 and inside the sample container 122 or reagent container 125, is sometimes referred to as the "capillary position". Figure 1 The diagram shows the buffer container 129 in the capillary position, with the cathode electrode 107 immersed in the buffer solution. The automatic sampler 123 and the automatic buffer sampler 124 move the stage, thereby enabling the sample container 122, the buffer container 129, the washing tank 130, or the waste tank 131 to be moved to the capillary position.

[0052] The storage compartment 126 is a location within the electrophoresis apparatus 101 where the sample container 122 is stored, for example, below the capillary position. The storage compartment 126 is, for example, a pull-out device that can be pulled out from the electrophoresis apparatus 101 in a generally horizontal direction. The user can access the storage compartment 126 from outside the electrophoresis apparatus 101 to retrieve and insert the sample container 122. Figure 1 In the example shown, the storage section 126 holds only the sample container 122, but it may also hold both the sample container 122 and the reagent container 125. A reflective light blocker 132 (sensor) is provided in the storage section 126 to detect when the sample container 122 is placed.

[0053] The barcode reader 128 (information reading unit) reads the barcode recorded on the sample container 122, which is moved from the storage unit 126 to the reading position by the automatic sampler 123, and outputs a reading signal to the control unit 160. The control unit 160 obtains sample information by processing the signal from the barcode reader 128. Furthermore, the method for reading sample information is not limited to using barcodes; for example, RFID or QR codes (registered trademarks) can also be used. Alternatively, text indicating sample information can be added to the sample container 122, and a camera can be used instead of the barcode reader 128 to capture an image of the sample container 122; the control unit 160 then obtains the sample information from the image data.

[0054] The control unit 160 is, for example, a computer device such as a personal computer, smartphone, or tablet terminal, that controls the various parts of the electrophoresis apparatus 101. Furthermore, the control unit 160, for example, uses a processor to process the light detection signal (digital signal) from the signal processing unit 150 and the reading signal from the barcode reader 128, as described above. The control unit 160 only needs to be able to communicate with the various parts of the electrophoresis apparatus 101; the connection to the various parts of the electrophoresis apparatus 101 can be a wired connection or a wireless connection. Although not shown in the figures, the control unit 160 includes an input device for user input of instructions and electrophoresis conditions, a GUI display screen, and a display device for analysis results.

[0055] Figure 2 This is a schematic diagram showing the state of sample container 122 being moved to the reading position of barcode reader 128. (See diagram below.) Figure 2 As shown, the automatic sampler 123 picks up one sample container 122 from the storage section 126 and places it on the moving stage 1231. The moving stage 1231 is then driven to move the sample container 122 to the reading position of the barcode reader 128. Furthermore, in this specification, the "reading position" of the barcode reader 128 refers to the position where light 1281 emanating from the barcode reader 128 is incident, and the reflected light from the barcode on the sample container 122 is incident on the barcode reader 128, allowing for the uninterrupted reading of sample information.

[0056] like Figure 2 As shown, the barcode reader 128 is built into the electrophoresis apparatus 101 and the reading position is located above the storage section 126. Thus, the automatic sampler 123 can directly transport the sample container 122 picked up from the storage section 126 to the reading position and read the sample information.

[0057] Furthermore, in this embodiment, which includes both an automatic sampler 123 for samples and an automatic sampler 124 for buffer solutions as an automatic sampler, the barcode reader 128 (information reading unit) and the structure associated with it have been described. However, the barcode reader 128 (information reading unit) and the structure associated with it as described in this disclosure are also effective in a structure that includes an automatic sampler 123 for samples but does not include an automatic sampler 124 for buffer solutions. That is, the electrophoresis apparatus described below also falls within the scope of this disclosure. This electrophoresis apparatus is characterized by comprising: a capillary filled with a swimming medium; a storage section for storing a sample container containing a sample; an automatic sampler for transporting the sample container; an information reading section for reading information of the sample recorded in the sample container; and a control section for controlling the drive of the automatic sampler, which drives the automatic sampler to transport the sample container from the storage section to the reading position of the information reading section. Based on this structure, especially in a structure that has an automatic sampler 123 for samples but not an automatic sampler 124 for buffer solutions, it is also expected that the transport time of the transport system can be shortened, thereby reducing the overall processing time of the device.

[0058] Figure 3 This is a schematic diagram showing the drive area of ​​the automatic sampler mechanism 105. (See diagram below.) Figure 3 As shown, the drive region 201 of the automatic sampler 123 and the drive region 202 of the automatic buffer sampler 124 are independent and do not interfere with each other, except for the position where the negative end of the capillary is inserted into each container. This prevents contact and collision between the automatic sampler 123 and the automatic buffer sampler 124.

[0059] Figure 4A This is a side view of the moving stage 1231 of the automatic sampler 123. Figure 4B This is a front view of the moving stage 1231 of the automatic sampler 123. The moving stage 1231 of the automatic sampler 123 includes an electric clamp 127, a stage 301, a positioning pin 303, a solenoid 304, and a spring 305. Figure 4A The image shows a sample container 122, with a positioning hole 306 on the bottom surface for the positioning pin 303 to engage. Figure 4A The device is equipped with two pairs of locating pins 303 and locating holes 306, but the number is not limited to these.

[0060] By providing positioning pins 303 and positioning holes 306, the sample container 122 can be fixed in a fixed position each time it is fixed on the stage 301. As a result, the capillary can be reliably inserted into the hole 302 containing the sample.

[0061] Solenoid 304 controls the opening and closing of the electric clamp 127. When current flows through solenoid 304, solenoid 304 is driven, and electric clamp 127 opens. When current stops flowing through solenoid 304, electric clamp 127 closes due to the elastic force of spring 305. When sample container 122 is placed on stage 301, electric clamp 127 is in the open state; after sample container 122 is placed on stage 301, electric clamp 127 is in the closed state, thereby holding sample container 122.

[0062] Figure 5A This is a top view of storage unit 126. Figure 5B yes Figure 5A View A is a side view of storage unit 126. (Example) Figure 5A As shown in 5B, the storage section 126 has a base 1261, a storage section 1262, and an interlocking mechanism 1263.

[0063] The storage section is provided with a handle 1264 for the user to open and close the storage section 126. The user can use the handle 1264 to pull the storage section 126 out of or back into the electrophoresis device 101. In this way, the storage section 126 is in a shape that is easily accessible to the user.

[0064] exist Figure 5A In this example, there are four locations for storing sample containers 122 in the storage section 1262, but the number of sample containers 122 stored is not limited to four. A reflective light interruptor 132 is provided at each location of the sample containers 122. The reflective light interruptor 132 detects the presence of sample containers 122, and is not detected if no sample container 122 is present. The detection signal from the reflective light interruptor 132 is output to the control section 160. This allows it to be determined at which position of the sample container 122 is located in the storage section 126.

[0065] Support members 1265 for fixing the position of sample container 122 are provided at each placement location of sample container 122. In addition, a recess 1266 that does not contact a portion of the side of sample container 122 is provided at each placement location of sample container 122, and the recess 1266 serves as a passage when electric clamp 127 is in the open state.

[0066] The interlocking mechanism 1263 includes a metal plate 1267 and a solenoid 1268. The metal plate 1267 has an opening, and the solenoid 1268 has a rod-shaped member 1269 that can be inserted into the opening of the metal plate 1267. When current flows in the solenoid 1268, the rod-shaped member 1269 is inserted into the opening of the metal plate 1267, thus locking the mechanism. Figure 5A (The dotted line). When the current flowing through the solenoid 1268 is interrupted, the rod-shaped component 1269 retracts from the opening of the metal plate 1267, becoming unlocked. Figure 5A (The solid line). The application of current to the solenoid 1268 is controlled by the control unit 160.

[0067] The interlock mechanism 1263 locks the automatic sampler 123 when it is not in the predetermined position, preventing user access. Except during sample injection for electrophoresis and sample information reading (described later), when the automatic sampler 123 is in the predetermined position, the interlock mechanism 1263 unlocks at intervals other than these two processes, allowing user access to the sample. The "predetermined position" of the automatic sampler 123 is, for example, the initial position when the electrophoresis apparatus 101 is started, and can be set near the capillary position.

[0068] By placing the storage section 126 near the capillary position, the transport time can be shortened. In addition, by positioning the storage section 126 above the linear guide of the automatic sampler 123, the size of the electrophoresis apparatus 101 can be reduced.

[0069] <Operation of the electrophoresis apparatus>

[0070] Figure 6 This is a flowchart illustrating a series of actions within the electrophoresis apparatus 101.

[0071] (Step 501)

[0072] The user places the capillary array 108, the polymer container 119 containing the polymer, the buffer container 120 containing the buffer solution on the anode side, the buffer container 129 containing the buffer solution on the cathode side, and the sample container 122 containing the sample at predetermined positions in the electrophoresis apparatus 101. When placing the buffer solution into the container, the solution needs to be placed up to the level of immersing the electrode. In addition, the tip of the tube extending from block 115 on the anode side is also immersed in the buffer solution in the buffer container 120. This is because if electrophoresis is performed without immersing the electrode and tube in the buffer solution, discharge may occur. Furthermore, by ensuring that the water levels of the buffer solution on both the anode and cathode sides are the same, pressure differences caused by height differences can be prevented.

[0073] (Step 502)

[0074] The user turns on the power to the electrophoresis apparatus 101. When the control unit 160 receives a signal indicating that the power to the electrophoresis apparatus 101 is turned on, it drives the pump mechanism 104 to fill the capillary with polymer.

[0075] (Step 503)

[0076] The user confirms that the electrophoresis path is functioning correctly. Specifically, the user checks whether the path is filled with polymer or contains foreign matter such as air bubbles. When replacing the capillary array 108 and polymer container 119, after manually refilling the flow path with polymer using the pump mechanism 104 or a syringe, the user visually inspects for abnormalities such as air bubbles. However, it is difficult to visually identify tiny foreign matter or air bubbles, and sometimes they may be missed. If electrophoresis is performed with foreign matter present, the foreign matter acts as a resistor, posing a risk of preventing normal measurements and causing discharge during electrophoresis. In the case of foreign matter, the control unit 160 removes the foreign matter from the electrophoresis path by any method, such as flowing the buffer solution into the capillary.

[0077] (Step 504)

[0078] The user uses the input device of the control unit 160 to set the conditions for electrophoresis.

[0079] (Step 505)

[0080] The user inputs an instruction to start the electrophoresis process. Upon receiving the instruction to start electrophoresis, the control unit 160 executes the electrophoresis process.

[0081] (Step 506)

[0082] When electrophoresis of one sample or all samples in one sample container 122 is completed, the control unit 160 determines whether there are any samples that need to be processed next. If there are samples that need to be processed, the process returns to step 505 and performs the electrophoresis operation again. If there are no samples that need to be processed, the operation ends.

[0083] <Electrophoresis Methods>

[0084] Figure 7 This is a flowchart summarizing the electrophoresis action in step 505 above.

[0085] (Step 601)

[0086] The control unit 160 drives the pump 116 to fill the block 115 with polymer.

[0087] (Step 602)

[0088] The control unit 160 closes the needle valve 118 and drives the pump 116 to inject polymer into the capillary array 108.

[0089] (Step 603)

[0090] The control unit 160 drives the automatic sampler 123 to place one of the sample containers 122 stored in the storage unit 126 onto the moving stage 1231 and move it to the reading position of the barcode reader 128. The control unit 160 receives the reading signal from the barcode reader 128 and reads the sample information.

[0091] (Step 604)

[0092] The control unit 160 drives the automatic sampler 124 for buffer solution, causing the buffer solution container 129 to retract from the capillary position. Next, it drives the automatic sampler 123 for sample, moving the sample container 122 to the capillary position, immersing the cathode end of the capillary array 108 in the sample within the sample container 122. The control unit 160 drives the high-voltage power supply 110, applying voltage between the cathode electrode 107 and the anode electrode 121, thereby injecting the sample into the capillary array 108.

[0093] (Step 605)

[0094] The control unit 160 drives the automatic sampler 123 to return the sample container 122 to the storage unit 126, and drives the automatic buffer sampler 124 to move the buffer container 129 to the capillary position, immersing the cathode end of the capillary array 108 in the buffer solution within the buffer container 129. Then, the control unit 160 drives the high-voltage power supply 110 to apply a voltage between the cathode electrode 107 and the anode electrode 121, thereby performing electrophoresis.

[0095] In this electrophoresis, the buffer sampler 124 secures the buffer container 129 to the capillary position, but the sample sampler 123 can be activated. Furthermore, the interlocking mechanism 1263 of the storage compartment 126 can be unlocked during electrophoresis. Therefore, the user can open the storage compartment 126 during electrophoresis to replace it with a new sample container 122, and the sample information can be read using the barcode reader 128 by activating the sample sampler 123.

[0096] <Action of the automatic sampler>

[0097] For the above electrophoresis action ( Figure 7 The transport actions of sample container 122 and buffer container 129 performed by the automatic sampler mechanism 105 in the sample sampler 123 are described in detail. The transport actions are mainly divided into (1) reading sample information and (2) replacing the sample container and buffer container at the capillary position during sample injection. (1) Reading sample information is an action in the automatic sampler 123 for sample use, and (2) replacing the sample container and buffer container at the capillary position is a replacement action between the automatic sampler 123 for sample use and the automatic sampler 124 for buffer solution.

[0098] Before describing the transport operation of the two drive systems, sample autosampler 123 and buffer autosampler 124, we will first describe the operation when a single autosampler is used to transport the sample container 122 and buffer container 129 instead of sample autosampler 123 and buffer autosampler 124. In this case, the structure of the autosampler in the electrophoresis apparatus is as follows: [Installation details omitted] Figure 1 The sample autosampler 123 and buffer autosampler 124 are provided, with only one autosampler, on which sample container 122 or reagent container 125 is placed on the moving stage.

[0099] Figure 8 This is a flowchart illustrating the transport operation of sample container 122 and buffer container 129 when there is one automatic sampler. Figure 8 The left figure (steps 701-707) shows the actions taken when reading sample information.

[0100] (Step 701)

[0101] The user replaces the sample container 122 in storage section 126.

[0102] (Step 702)

[0103] After the user places the sample container 122 into the storage unit 126 and finishes, the user closes the storage unit 126. At this time, the reflective light interruptor 132 of the storage unit 126 detects that the sample container 122 has been placed there and outputs a detection signal to the control unit 160.

[0104] (Step 703)

[0105] The control unit 160 determines the location where the sample container 122 is located based on the detection signal from the reflective light interruptor 132, and reads the information of the sample container 122 at that location. Specifically, the control unit 160 drives the automatic sampler to move the buffer solution container 129 located at the capillary position to the storage unit 126.

[0106] (Step 704)

[0107] The control unit 160 drives the automatic sampler to place the sample container 122 in the above-mentioned configuration location onto the moving stage and transport it to the reading position of the barcode reader 128.

[0108] (Step 705)

[0109] The control unit 160 receives the reading signal from the barcode reader 128 and reads the sample information.

[0110] (Step 706)

[0111] The control unit 160 drives the automatic sampler, causing the sample container 122 to return from the reading position of the barcode reader 128 to the storage unit 126.

[0112] (Step 707)

[0113] The control unit 160 drives the automatic sampler to move the buffer container 129 from the storage unit 126 to the capillary position, so that the cathode end of the capillary array 108 is immersed in the buffer solution.

[0114] Figure 8 The right figure (steps 708-715) shows the action during sample injection.

[0115] (Step 708)

[0116] In this step, the buffer container 129 on the autosampler is in the capillary position, which is the state in which the cathode end of the capillary array 108 is inserted into the buffer container 129.

[0117] (Step 709)

[0118] The control unit 160 drives the automatic sampler to move the buffer solution container 129 to the storage unit 126.

[0119] (Step 710)

[0120] The control unit 160 drives the automatic sampler to place the sample container 122 at the designated storage unit 126 position onto the moving stage of the automatic sampler.

[0121] (Step 711)

[0122] The control unit 160 drives the automatic sampler to transport the sample container 122 to the capillary position, immersing the cathode end of the capillary array 108 in the sample.

[0123] (Step 712)

[0124] The control unit 160 drives the high-voltage power supply 110 to apply voltage between the cathode electrode 107 and the anode electrode 121, thereby injecting the sample into the capillary array 108.

[0125] (Step 713)

[0126] After the sample injection is completed, the control unit 160 drives the automatic sampler to return the sample container 122 from the capillary position to the storage unit 126.

[0127] (Step 714)

[0128] The control unit 160 drives the automatic sampler to place the buffer container 129 back onto the moving stage of the automatic sampler.

[0129] (Step 715)

[0130] The control unit 160 drives the automatic sampler to move the buffer container 129 to the capillary position and immerse the cathode end of the capillary array 108 in the buffer solution.

[0131] The above describes an example of returning the buffer container to the capillary position (step 707) after reading the sample information (step 705) and then proceeding to sample injection (step 708 onwards). Alternatively, after reading the sample information (step 705), and with electrophoresis preparation complete, steps 706-710 can be skipped, and the sample container 122 can be directly moved to the capillary position (step 711) and the sample injected (step 712).

[0132] As described in step 701 above, when a sample container is replaced, sample information needs to be read in order to identify which sample container has been replaced and determine the order of subsequent electrophoresis processing. Conventionally, sample information reading is performed externally to the apparatus before the sample container is mounted, or information from all sample containers mounted on the apparatus is read. In contrast, in the method of this embodiment, the sample information reading function, such as the barcode reader 128, is built into the electrophoresis apparatus 101, and only the information of the replaced sample container is read. Furthermore, an automatic sampler can pick up the sample container 122 from the storage unit 126 and move it to the reading position of the barcode reader 128 to read the sample information. Therefore, after the sample container 122 is inserted, the information of the contained sample can be read immediately, thus shortening the overall processing time.

[0133] However, if only one automated sampler (drive system) is used, the buffer container 129 must be returned to the storage unit 126 before the sample container 122 is transferred. After the sample container 122 is transferred, the buffer container 129 is replaced and transferred to the capillary position. The automated sampler transfers the sample container between the capillary position and the storage unit 126 multiple times, requiring processing time. Furthermore, because the automated sampler is used during the transfer of the sample container 122, the cathode of the capillary array 108 is continuously exposed to air during this transfer, potentially degrading analytical performance.

[0134] Therefore, by using the two drive systems, the automatic sampler 123 for samples and the automatic sampler 124 for buffer solutions, the processing time can be further reduced, and the degradation of analytical performance can be prevented.

[0135] Figure 9 This is a flowchart illustrating the transport actions of sample container 122 and buffer container 129 performed by automatic sampler 123 and automatic buffer sampler 124. Figure 9 The left figure (steps 801-805) shows the actions taken when reading sample information.

[0136] (Step 801)

[0137] The user replaces the sample container 122 in storage section 126.

[0138] (Step 802)

[0139] After the user places the sample container 122 into the storage unit 126 and finishes, the user closes the storage unit 126. At this time, the reflective light interruptor 132 of the storage unit 126 detects that the sample container 122 has been placed there and outputs a detection signal to the control unit 160.

[0140] (Step 803)

[0141] The control unit 160 determines the location where the sample container 122 is located based on the detection signal from the reflective light interruptor 132, and reads the information of the sample container 122 at that location. Specifically, the control unit 160 drives the automatic sampler 123 to place the sample container 122 at the aforementioned location onto a moving stage and transport it to the reading position of the barcode reader 128.

[0142] (Step 804)

[0143] The control unit 160 receives the reading signal from the barcode reader 128 and reads the sample information.

[0144] (Step 805)

[0145] The control unit 160 drives the automatic sampler 123 to return from the reading position of the barcode reader 128 to the storage unit 126.

[0146] Figure 9 The right figure (steps 806-813) shows the action during sample injection.

[0147] (Step 806)

[0148] In this step, the buffer container 129 on the automatic sampler 124 is in the capillary position, meaning the cathode end of the capillary array 108 is inserted into the buffer container 129.

[0149] (Step 807)

[0150] The control unit 160 drives the automatic sampler 123 to place the sample container 122, which is positioned as described above, onto the moving stage and transport it to the reading position of the barcode reader 128. The control unit 160 receives the reading signal from the barcode reader 128 and reads the sample information. This reading of sample information is to confirm that it is the same as the sample information read in step 804, i.e., that the sample is not erroneous. Next, the control unit 160 drives the automatic sampler 123 to transport the sample container 122 to the standby position directly below the capillary position.

[0151] (Step 808)

[0152] The control unit 160 drives the automatic sampler 124 for the buffer solution, causing the buffer solution container 129 to retract from the capillary position, thereby pulling out the capillary array 108.

[0153] (Step 809)

[0154] The control unit 160 drives the automatic sampler 123 to move the sample container 122 from the standby position to the capillary position.

[0155] (Step 810)

[0156] The control unit 160 drives the high-voltage power supply 110 to apply voltage between the cathode electrode 107 and the anode electrode 121, thereby injecting the sample into the capillary array 108.

[0157] (Step 811)

[0158] The control unit 160 drives the automatic sampler 123 to move the sample container 122 from the capillary position to the standby position.

[0159] (Step 812)

[0160] The control unit 160 drives the automatic sampler 124 for the buffer solution to move the buffer solution container 129 back to the capillary position.

[0161] (Step 813)

[0162] The control unit 160 drives the automatic sampler 123 to return the sample container 122, which is in the standby position, to the storage unit 126.

[0163] Regarding the interlocking mechanism 1263 of the storage section 126, if it is unlocked while the automatic sampler 123 is in operation or processing, the user may put their hand into the drive section and suffer injury. Therefore, the control unit 160 locks the interlocking mechanism 1263 in a locked state so that the storage section 126 cannot be opened when the automatic sampler 123 is not in a predetermined position, and unlocks it in other states.

[0164] Figure 10 This is a flowchart showing the operation of the interlocking mechanism 1263 and the reflective light interruptor 132 when reading sample information (steps 801-805).

[0165] During sample replacement in step 801, the storage unit 126 is locked; therefore, in step 901, the control unit 160 unlocks the interlocking mechanism 1263. In step 902, the user opens the storage unit 126, and in step 903, the sample container 122 is placed in the predetermined placement location. At this time, since there is no sample container 122 in the predetermined placement location, the reflective light interruptor 132 does not detect the sample container 122 in step 904. After placement, the reflective light interruptor 132 detects the sample container 122.

[0166] After configuring the sample container 122, the user closes the storage unit 126 in step 802. Next, in step 803, the automatic sampler 123 removes the sample container 122 from the storage unit 126 and moves it to the reading position. At this time, in step 905, when configuring the sample container 122, the user specifies the configuration location where the reflective light blocker 132 changes from an undetected state to a detected state. In step 906, the automatic sampler 123 retrieves the sample container 122 from the specified configuration location. In step 907, when the sample container 122 is placed in the automatic sampler 123, the control unit 160 confirms that the reflective light blocker 132 changes from a detected state to an undetected state. In step 908, the control unit 160 moves the sample container 122 to the reading position via the automatic sampler 123. Then, steps 804 and 805 are executed.

[0167] <Summary>

[0168] As described above, the electrophoresis apparatus 101 of the first embodiment includes a sample information reading device such as a barcode reader 128 and a storage section 126 for storing sample containers 122. At the location where the sample containers 122 are positioned in the storage section 126, the presence or absence of a sample container 122 is detected by a sensor such as a reflective light blocker 132, and sample information is read only for the replaced sample container 122. Therefore, it is not necessary to read the sample information of all sample containers 122 located in the storage section 126, and only the sample containers 122 for which information needs to be read can be processed. This reduces the processing time of the electrophoresis apparatus 101. Furthermore, it shortens the time limited by the user for operating the electrophoresis apparatus 101.

[0169] Furthermore, in the electrophoresis apparatus 101 of the first embodiment, the automatic sampler mechanism 105 transports the sample container from the storage section to the standby position while the buffer container is positioned in the capillary position, and transports the sample container from the standby position to the capillary position while the buffer container is transported from the capillary position to the standby position. In this way, by waiting in the standby position near the capillary position before the sample container 122 is transported to the capillary position and inserted into the capillary array 108, the time the cathode end of the capillary array 108 is exposed to air can be shortened. As a result, degradation of analytical performance is prevented.

[0170] Furthermore, by dividing the automatic sampler for transporting the sample container 122 and the buffer container 129 into two separate units—one for transporting the sample container and the other for transporting the reagent container—it is unnecessary to return the buffer container 129 to the storage unit 126, thus shortening the processing time. During electrophoresis, the automatic sampler 124 transports the buffer container 129 to the capillary position and fixes it in place. However, since the automatic sampler 123 can be freely driven, the sample container 122 can be retrieved from the storage unit 126 and transported to the sample information reading position to read the sample information.

[0171] <Modifications of the First Embodiment>

[0172] Figure 9 The method shown is to drive the automatic sampler 123 for samples and the automatic sampler 124 for buffer solutions independently. However, in order to shorten the processing time, the automatic sampler 123 for samples and the automatic sampler 124 for buffer solutions can also be driven simultaneously.

[0173] Figure 11 This is a timing diagram showing the conveying action of sample container 122 and buffer container 129 in the modified example. Figure 11 The upper part indicates Figure 9 The operation of the automatic sampler 123 for samples and the automatic sampler 124 for buffer solution in the right figure (steps 806-813) is shown in the lower section, which illustrates the operation in this modified example. Figure 11 As shown, in Figure 9 In the original example, the automatic sampler 123 for samples and the automatic sampler 124 for buffer solutions are driven alternately. In contrast, in this modified example, the automatic sampler 123 for samples and the automatic sampler 124 for buffer solutions are driven simultaneously during a portion of the operation. As a result, the processing time is shortened.

[0174] [Second Implementation]

[0175] In the first embodiment, an example of an automatic sampler 123 for transporting sample container 122 and an automatic buffer sampler 124 for transporting buffer container 129 was described. In contrast, in the second embodiment, a structure is proposed in which one automatic sampler is provided, and a fixing part capable of fixing the sample container 122 and the buffer container 129 is provided in a standby position near the capillary position.

[0176] <Example of the structure of an electrophoresis apparatus>

[0177] Figure 12 This is a schematic diagram showing a portion of the structure of the electrophoresis apparatus 1001 according to the second embodiment. The electrophoresis apparatus 1001 of this embodiment includes fixing parts 1101 to 1103 and an automatic sampler 223. Other structures are identical to those of the electrophoresis apparatus 101 of the first embodiment, and therefore descriptions are omitted.

[0178] The fixing part 1103 (first fixing part) is positioned directly below the loading head 106, i.e., at the capillary position. Fixing parts 1101 and 1102 (second fixing parts) are positioned adjacent to the fixing part 1103, i.e., in a standby position near the capillary position. The fixing parts 1101 to 1103 have an L-shaped cross-section with opposing components, and can be opened and closed by moving the L-shaped components horizontally. The opening and closing of the fixing parts 1101 to 1103 is controlled by the control unit 160.

[0179] The automatic sampler 223 has a moving stage 2231 that transports sample container 122 and reagent container 125 from storage section 126 to fixed section 1103 at the capillary position and fixed sections 1101 and 1102 near the capillary position. For example, sample container 122 is transported to fixed section 1101 and reagent container 125 is transported to fixed section 1102.

[0180] The storage section 126 is located below the fixing sections 1101 to 1103. The storage section 126 houses the sample container 122 and the reagent container 125.

[0181] <Action of the automatic sampler>

[0182] Figure 13 This is a flowchart illustrating the conveying operation of the sample container 122 and the buffer container 129 in the second embodiment. Furthermore, the overall operation of the electrophoresis apparatus is similar to that in the first embodiment (…). Figure 6 as well as Figure 7 )same.

[0183] (Step 1201)

[0184] The control unit 160 drives the automatic sampler 223 and the fixing unit 1103 to move the buffer container 129 from the storage unit 126 to the fixing unit 1103 at the capillary position and fix it.

[0185] (Step 1202)

[0186] The control unit 160 drives the automatic sampler 223 and the fixing unit 1101 to move the sample container 122 from the storage unit 126 to the fixing unit 1101 and fix it.

[0187] (Step 1203)

[0188] The control unit 160 drives the pump mechanism 104 to fill the capillary with polymer. Then, the control unit 160 drives the fixing unit 1103 to release the fixing of the buffer container 129, drives the automatic sampler 223 and the fixing unit 1102 to move the buffer container 129 from the fixing unit 1103 to the fixing unit 1102 and fix it.

[0189] (Step 1204)

[0190] The control unit 160 drives the automatic sampler 223 and the fixing unit 1101 to release the sample container 122 from the fixing unit 1101, and drives the automatic sampler 223 and the fixing unit 1103 to move the sample container 122 from the fixing unit 1101 to the fixing unit 1103 and fix it. Then, the control unit 160 drives the high-voltage power supply 110 to apply voltage between the cathode electrode 107 and the anode electrode 121, thereby injecting the sample into the capillary array 108.

[0191] (Step 1205)

[0192] The control unit 160 drives the automatic sampler 223 and the fixing unit 1103 to release the sample container 122 from the fixing unit 1103 and to move the sample container 122 from the fixing unit 1103 to the fixing unit 1101 and fix it.

[0193] (Step 1206)

[0194] The control unit 160 drives the automatic sampler 223 and the fixing unit 1102 to release the buffer container 129 from the fixing unit 1102, and drives the automatic sampler 223 and the fixing unit 1103 to move the buffer container 129 from the fixing unit 1102 to the fixing unit 1103 and fix it. Then, the control unit 160 drives the high-voltage power supply 110 to apply a voltage between the cathode electrode 107 and the anode electrode 121, thereby performing electrophoresis.

[0195] (Step 1207)

[0196] During electrophoresis, the control unit 160 drives the automatic sampler 223 and the fixing unit 1101 to release the sample container 122 from the fixing, and the automatic sampler 223 returns the sample container 122 to the storage unit 126.

[0197] In this embodiment, the filling of the polymer into the energized path and the reading of sample information can be performed, for example, between steps 1201 and 1202.

[0198] <Summary>

[0199] As described above, the electrophoresis apparatus 1001 of the second embodiment includes fixing sections 1101-1103 capable of mounting and fixing sample container 122 and buffer container 129 at and near the capillary position, and an automatic sampler 223. The automatic sampler 223 transports the buffer container 129 between the fixing section 1103 (capillary position) and the fixing section 1102 (standby position), and transports the sample container 122 between the storage section 126, the fixing section 1101 (standby position), and the fixing section 1103 (capillary position).

[0200] Therefore, the transport distance of sample container 122 and buffer container 129 is shortened, and it is not necessary to return these containers to storage unit 126 every time, thus suppressing the degradation of electrophoresis performance. When there is only one autosampler and no fixing parts 1101-1103 are provided, the autosampler is used to hold the buffer container 129 at the capillary position during electrophoresis, so the sample container reading operation cannot be performed. In contrast, in this embodiment, the buffer container 129 is fixed by the fixing part 1103 during electrophoresis, so even if there is only one autosampler 223, sample information can be read during electrophoresis in the same way as in the first embodiment.

[0201] Furthermore, in the electrophoresis apparatus 1001 of the second embodiment, the sample container 122 is transported from the storage section 126 to the fixed section 1101 (standby position) by the automatic sampler 223 while the buffer container 129 is positioned in the fixed section 1103 (capillary position). Simultaneously, the sample container 122 is transported from the fixed section 1101 (standby position) to the fixed section 1103 (capillary position) while the buffer container 129 is transported from the fixed section 1103 (capillary position) to the fixed section 1102 (standby position). This way, by waiting in the standby position near the capillary position before the sample container 122 is transported to the capillary position and inserted into the capillary array 108, the time the cathode end of the capillary array 108 is exposed to air can be shortened. As a result, degradation of analytical performance is prevented.

[0202] [Variation Example]

[0203] This disclosure is not limited to the embodiments described above, but includes various modifications. For example, the embodiments described above are those that have been explained in detail for ease of understanding of this disclosure, and do not necessarily require all of the described structures. Furthermore, a portion of an embodiment can be replaced with the structure of another embodiment. Additionally, structures of other embodiments can be added to the structure of a certain embodiment. Furthermore, for a portion of the structure of each embodiment, a portion of the structure of another embodiment can be added, deleted, or replaced.

[0204] Explanation of reference numerals in the attached figures

[0205] 101…Electrophoresis apparatus, 102…Capillary electrophoresis unit, 103…Irradiation detection unit, 104…Pump mechanism, 105…Automatic sampler mechanism, 106…Loading head, 107…Cathode electrode, 108…Capillary array, 109…Thermostatic bath, 110…High voltage power supply, 111…Capillary head, 112…Detection unit, 113…Light source, 114…Optical detector, 115…Block, 116…Pump, 117…Check valve, 118…Needle valve, 119…Polymer container, 120…Buffer container, 121…Anode electrode, 122… …sample container, 123…automatic sampler for samples, 124…automatic sampler for buffer solutions, 125…reagent container, 126…storage section, 127…electric clamp, 128…barcode reader, 129…buffer solution container, 130…washing tank, 131…waste tank, 132…reflective light blocker, 201…drive area of ​​automatic sampler for samples, 202…drive area of ​​automatic sampler for buffer solutions, 301…stage, 302…hole, 303…locating pin, 304…solenoid, 305…spring, 306…locating hole.

Claims

1. An electrophoresis apparatus, characterized in that, The electrophoresis apparatus includes: Capillary tubes, which are filled with a swimming medium; The reagent container includes a buffer solution container containing a buffer solution, a cleaning tank containing a cleaning solution for cleaning capillaries, and a waste liquid tank for discarding excess liquid. Storage department, which stores and contains sample containers; An automated sampler is used to transport the sample container; An automated sampler for buffer solutions, which transports the reagent containers; and The control unit performs the following controls: An automatic sampler for driving the buffer solution is used to transport the buffer solution container between a capillary position and a standby position near the capillary position, wherein the capillary position is the position of the sample container and the reagent container where the cathode end of the capillary array is located inside the sample container or the reagent container. The automatic sampler is driven to move the sample container between the storage section, the standby position, and the capillary position; and The control unit drives the automatic sampler for samples and the automatic sampler for buffer solutions to perform the following control: During the placement of the buffer solution container in the capillary position, the sample container is moved from the storage section to a standby position near the capillary position. as well as When the buffer solution container is moved from the capillary position to the standby position, the sample container is also moved from the standby position to the capillary position. The driving regions of the automatic sampler for the sample and the automatic sampler for the buffer solution are different except for the capillary position. The control unit simultaneously drives the automatic sampler for the sample and the automatic sampler for the buffer solution at predetermined time intervals.

2. The electrophoresis apparatus according to claim 1, characterized in that, The control unit drives the automatic sampler to perform the following control: After the capillary is filled with the migratory medium, the transport of the sample container begins; and After the sample container is moved to the capillary position and the sample is injected into the capillary, but before electrophoresis begins, the sample container is retracted from the capillary position.

3. The electrophoresis apparatus according to claim 1, characterized in that, The control unit performs the following control: when the automatic sampler is not in the predetermined position, the storage unit is locked; when the automatic sampler is in the predetermined position, the storage unit is unlocked.

4. The electrophoresis apparatus according to claim 1, characterized in that, The electrophoresis apparatus also includes an information reading unit. The sample container contains information about the sample. The control unit drives the automatic sampler to move the sample container from the storage unit to the reading position of the information reading unit.

5. The electrophoresis apparatus according to claim 4, characterized in that, The storage section is equipped with a sensor to detect the presence or absence of the sample container. When the sensor detects that the sample container is present, the control unit drives the automatic sampler to move the sample container from the storage unit to the reading position, and reads the information of the sample based on the reading signal of the information reading unit.

6. The electrophoresis apparatus according to claim 5, characterized in that, The storage department stores the sample containers in multiple storage locations. The sensor is located at each of the plurality of storage locations. The control unit drives the automatic sampler to move the sample container from the storage location where the sample container is detected by the sensor to the reading location.

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