Electrophoresis device with integrated pretreatment

Abstract

An electrophoresis device with integrated pretreatment according to the present disclosure comprises: a pretreatment unit that performs a pretreatment on a biological sample to prepare it for electrophoresis; and an optical system that irradiates the sample separated by electrophoresis in a capillary with light and detects the light from the sample. The electrophoresis device with integrated pretreatment further comprises: a first main body and a second main body; and a coupling element that couples the first main body and the second main body. At least one of the first main body and the second main body has an installation surface on which a detachable unit is installed.The coupling element couples the first main body and the second main body in such a way that one of the first main body and the second main body is movable relative to the other, thus enabling the overall size of the electrophoresis device with integrated pretreatment to be variable.

Description

Technical field

[0001] The present disclosure relates to an electrophoresis device with integrated pretreatment. State of the art

[0002] Applications using nucleic acid analysis have been implemented in fields such as forensics, immigration control, and counterterrorism. For example, in the field of forensics, STR analysis has been put into practice. STR analysis analyzes short tandem repeat sequences (STR sequences) in specific regions of the genome. The fact that the lengths of STR sequences are unique to each individual allows for DNA analysis for purposes such as personal identification and paternity testing.

[0003] The procedure for STR analysis is, for example, as follows. First, nucleic acid (typically DNA), which serves as a template, is extracted from a test sample, such as a biological specimen or a sample of a biologically derived material. The extracted template DNA is then amplified by polymerase chain reaction (PCR) and subsequently denatured from double-stranded DNA to single-stranded DNA by formamide treatment or by heating and rapid cooling. For DNA amplification, multiplex PCR amplification is performed using 13 types of primer sets for each DNA sample. During DNA amplification, the amplified DNA fragments are labeled. The solution resulting from this DNA amplification and labeling process serves as the analytical sample (see patent reference 1).

[0004] If the steps for preparing the analytical sample from the above-mentioned test sample are defined as the pretreatment process, the electrophoresis process includes separating the labeled DNA fragments by electrophoresis and detecting and analyzing the electrophoretic patterns of the resulting separated DNA fragments.

[0005] Previously, the separation and detection of DNA fragments using DNA sequencers and similar devices was actively automated. However, the pretreatment process was generally performed manually by specialists. In recent years, efforts have been made to automate this pretreatment process, so that many genetic analyses, including STR analysis, are now performed not only in limited facilities and by specialists, but also by multiple personnel.

[0006] Patent Literature 2 discloses an electrophoresis device integrated into the pretreatment process, which performs a pretreatment process and an electrophoresis process sequentially. The electrophoresis device integrated into the pretreatment according to Patent Literature 2 includes a sample cartridge for extracting and amplifying DNA from a sample and a capillary cartridge equipped with capillaries for performing electrophoresis. When the user places the sample cartridge, containing a sample, into the electrophoresis device integrated into the pretreatment, the device automatically performs the processes from pretreatment to electrophoresis. Such an electrophoresis device integrated into the pretreatment requires no specialized knowledge for its use and is easy to operate, even by users unfamiliar with DNA analysis.Patent literature 3 to 5 will be described later. List of patent literature Patent Literature 1: US Patent No. 6531282 Patent literature 2: US Publication No. 2016 / 0116439 Patent literature 3: Japanese publication no. 2016-0101166 Patent literature 4: Japanese publication no. Hei7(1995)-83900 Patent literature 5: Japanese publication no. Hei10(1998)-282055 Summary of the invention: Technical problem

[0007] Electrophoresis devices integrated into the pretreatment process, which perform all steps from pretreatment to electrophoresis, are primarily used in criminal investigations. In these investigations, the device is operated by a user without specialized knowledge of DNA analysis. The user also transports the device to the crime scene, collects samples there, and loads them into the device. Therefore, ease of use and portability are crucial features of the device.

[0008] In the electrophoresis device integrated into the pretreatment according to patent literature 2, the only consumables are a capillary cartridge containing the reagents and capillaries, and a sample cartridge into which the samples are loaded. This eliminates the need for users to install multiple consumables in multiple locations, resulting in very simple operation. However, the cartridge itself is large, and the device features a configuration for mounting the cartridge within the device. Therefore, space must be provided within the device to accommodate the cartridge. This can hinder the miniaturization of the device, which is important for portability. Furthermore, when transporting the device in a non-temperature-controlled transport vehicle, the cartridge containing the reagents must be removed.Even in this case, the configuration described in patent literature 2 does not reduce the space available for accommodating the cartridge within the device, and therefore the device's volume remains unchanged, requiring additional space in the transport vehicle. Furthermore, removing the cartridge exposes the interior of the device, potentially allowing dust or similar contaminants to enter.

[0009] Accordingly, the present disclosure provides an electrophoresis device with integrated pretreatment that can be miniaturized and further reduced in size during transport. Solution to the problem

[0010] To address the aforementioned problems, an electrophoresis device with integrated pretreatment according to the present disclosure comprises a pretreatment unit that performs a pretreatment on a biological sample to prepare it for electrophoresis, and an optical system that irradiates the sample separated by electrophoresis in a capillary with light and detects the light from the sample. The electrophoresis device with integrated pretreatment further comprises: a first main body and a second main body; and a coupling element that couples the first main body and the second main body. At least one of the first main body and the second main body has an installation surface on which a detachable unit is installed.The coupling element couples the first main body and the second main body in such a way that one of the first main body and the second main body is movable relative to the other, thus enabling the overall size of the electrophoresis device with integrated pretreatment to be variable.

[0011] Further features relating to the disclosure are clarified with reference to the content of this description and the accompanying drawings. In addition, aspects of the present disclosure are achieved and implemented by the elements and various combinations of elements as set forth in the following detailed description and the accompanying claims. The description in this document is for illustrative purposes only and is not intended to limit the scope of the claims or applications of the present disclosure in any way. Advantageous effects of the invention

[0012] The electrophoresis device with integrated pretreatment according to the present disclosure can be miniaturized and can be further reduced in size during transport. Other problems, configurations and advantages besides those mentioned above will become clear from the description of the embodiments below. Brief description of the drawings Fig. Figure 1 illustrates a front view (left) and a side view (right) of the overall configuration of an electrophoretic device with integrated pretreatment according to a first embodiment. Fig. Figure 2 illustrates the configuration of a capillary cartridge. Fig. Figure 3 is an enlarged view of the area defined by the dotted circle A in Fig. 2 is included. Fig. Figure 4 illustrates a top view (left) and a side view (right) of the electrophoretic device with integrated pretreatment. Fig. Figure 5A shows side views to illustrate the shape of the electrophoretic device with integrated pretreatment when closing an interface unit. Fig. Figure 5B is a cross-sectional view of the electrophoretic device with integrated pretreatment. Fig. 5C is an enlarged view of the area defined by the dotted circle in Fig. Included is 5B, which illustrates the boundary between a main body and the interface unit. Fig. 5D is an enlarged view to illustrate a different structure of the boundary between the main body and the interface unit. Fig. Figure 6 illustrates a top view (left) and a side view (right) of an electrophoretic device with integrated pretreatment according to a second embodiment. Fig. Figure 7 shows side views of the interface unit with and without a capillary cartridge mounted on it. Fig. Figure 8 is a side view of an electrophoretic device with integrated pretreatment according to a third embodiment. Fig. Figure 9 is a side view of an electrophoretic device with integrated pretreatment according to a fourth embodiment.] Fig. Figure 10 illustrates a front view (left) and a side view (right) of an electrophoretic device with integrated pretreatment according to a fifth embodiment. Fig. Figure 11 is a side view of an electrophoretic device with integrated pretreatment according to a sixth embodiment. Fig. Figure 12 is a side view of an electrophoretic device with integrated pretreatment according to a seventh embodiment. Description of the embodiments

[0013] The following describes embodiments according to the present disclosure with reference to the drawings. It should be noted that although the drawings illustrate specific embodiments based on the principles of the present disclosure, they are intended to aid in understanding the present disclosure and in no way to restrict its interpretation. First embodiment<Konfigurationsbeispiel für Elektrophoresevorrichtung mit integrierter Vorbehandlung>

[0014] Fig. Figure 1 illustrates a front view (left) and a side view (right) of the overall configuration of an electrophoresis device 1 with integrated pretreatment according to a first embodiment. The side view of Fig. Figure 1 illustrates the internal and external components of the electrophoresis device 1 with integrated pretreatment. The following description refers to the area shown in the front view of... Fig. Figure 1 illustrates the front surface, and the direction in which this surface points can be referred to as the forward direction. The electrophoresis device 1 with integrated pretreatment is configured to perform nucleic acid analysis, including STR analysis.

[0015] A capillary cartridge 101 and a sample cartridge 102, which are consumables, are detachably attached to the electrophoresis device 1 with integrated pretreatment. The capillary cartridge 101 has one or more capillaries, reagents used during pretreatment, reagents used during electrophoresis, and the like. The sample cartridge 102 is loaded with biological samples, such as cells collected from a human, and the cells are pretreated. The capillary cartridge 101 and the sample cartridge 102 are consumables and are housed during transport in a case that is different from the transport case of the electrophoresis device 1 with integrated pretreatment.

[0016] As seen in the right side view of Fig. As shown in Figure 1, the electrophoresis device 1 with integrated pretreatment comprises a high-voltage power supply 103, an optical system 104, a high-pressure pump 105, a pretreatment unit 106, a PC 107, a touch panel 108, an interface unit 109 (second main body), a hinge 110 (coupling element), and a main body 111 (first main body). The high-voltage power supply 103 applies a high voltage to the capillary during electrophoresis. The optical system 104 irradiates the sample in the capillary with excitation light and detects fluorescence emitted by the sample. The high-pressure pump 105 is driven when an electrophoresis medium is injected into the capillary. The pretreatment unit 106 supplies reagent to the sample cartridge 102 and sets the temperature. The PC 107 controls each component of the electrophoresis device 1 with integrated pretreatment.The touch panel 108 is operated by the user during the use of the electrophoresis device 1 with integrated pretreatment. Instructions entered by the user via the touch panel 108 are sent to the PC 107.

[0017] The interface unit 109 is coupled to the main body 111 by the hinge 110 and can be opened and closed like a door. Fig. Figure 1 illustrates the interface unit 109 in an open state, projecting forward from the front surface of the main body 111. The interface unit 109 is opened during use of the electrophoresis device 1 with integrated pretreatment, and the capillary cartridge 101 is placed on its upper surface. The interface unit 109 serves to connect the capillary cartridge 101 electrically, fluidically, and optically. The coupling between the interface unit 109 and the main body 111 is described in detail later.

[0018] When the interface unit 109 is in the open state, the lower surface of the interface unit 109 and the lower surface of the main body 111 can be provided with legs.

[0019] Fig. Figure 2 illustrates the configuration of the capillary cartridge 101. Fig. Figure 2 illustrates the arrangement of each component when the capillary cartridge 101 is viewed from above. The capillary cartridge 101 has one or more capillaries 201, a heating device 202, an irradiation detection unit 203, a fiber optic connection section 204, a cathode block 205, an anode block 206, an electrophoresis medium section 207, a waste liquid section 208, an electrophoresis reagent section 209, a pretreatment reagent section 210, a waste liquid section 211, an electrical interface 212, a high-voltage interface 213, a sample connection section 214, a coupling 215, a positioning hole 216, and a pump 217.

[0020] The heating device 202 sets the temperature of the capillary 201. The irradiation detection unit 203 is configured to irradiate the capillary 201 with excitation light and detect fluorescence emitted by the sample in the capillary 201. The fiber optic connection section 204 optically connects the capillary 201, the irradiation detection unit 203, and the optical system 104. The fiber optic connection section 204 bundles fiber optic cables to introduce excitation light from the optical system 104 to the irradiation detection unit 203 and to guide fluorescence from the capillary 201 to the optical system 104. The cathode block 205 injects the sample into the capillary 201. The anode block 206 fills the capillary 201 with the electrophoresis medium. The electrophoresis medium section 207 contains the electrophoresis medium for electrophoresis. The waste liquid section 208 collects waste liquid from the electrophoresis medium.The electrophoresis reagent section 209 contains reagents and the like intended for use in electrophoresis. The pretreatment reagent section 210 contains reagents intended for pretreatment. The waste liquid section 211 contains waste liquid and the like. The electrical interface 212 supplies a voltage to the heating device 202 and the like. The high-voltage interface 213 applies the voltage output by the high-voltage power supply 103 to the capillary 201. The sample connection section 214 supplies the pretreated sample to the cathode block 205. The coupling 215 supplies the reagent from the pretreatment reagent section 210 to the pretreatment unit 106. The positioning hole 216 is used to align the capillary cartridge 101 with the interface unit 109 when the capillary cartridge 101 is installed.Pump 217 is driven when the reagent is introduced from the electrophoresis reagent section 209 into the cathode block 205. It should be noted that the fiber optic connection section 204, the electrical interface 212, the high-voltage interface 213, the sample connection section 214, and the coupling 215 are exposed at a connection surface (the bottom surface of the capillary cartridge 101) on the capillary cartridge 101, which is connected to the interface unit 109.

[0021] Fig. Figure 3 is an enlarged view of the area defined by the dotted circle A in Fig. Figure 2 is included, which illustrates the details of the anode block 206. The anode block 206 has a capillary anode end 301, a valve 302, a pump 303, an electrophoresis medium connection section 304, a waste liquid connection section 305, and a hole 306. The capillaries 201 are bundled together at the capillary anode end 301. The valve 302 seals the flow channel. The pump 303 is driven when the capillaries 201 are filled with the electrophoresis medium. The electrophoresis medium connection section 304 is connected to the electrophoresis medium section 207. The waste liquid connection section 305 is connected to the waste liquid section 208. The hole 306 is provided in the connection surface of the capillary cartridge 101 with the interface unit 109. The hole 306 allows an anode actuator, which will be described later, access to the valve 302 and the piston of the pump 303.

[0022] Fig. Figure 4 illustrates a top view (left) and a side view (right) of the electrophoretic device 1 with integrated pretreatment. Fig. 4 illustrates the in Fig. Figure 1 describes an electrophoretic device 1 with integrated pretreatment, wherein the capillary cartridge 101 has been removed. The main body 111 of the electrophoretic device 1 with integrated pretreatment has a projection 410 that extends forward from the front surface. Hinges 110 are provided on both side faces of the projection 410. The interface unit 109 has an approximately U-shape in plan view and is provided to surround the front and side faces of the projection 410. The interface unit 109 and the projection 410 are coupled by the hinges 110.

[0023] The projection 410 is provided with a positioning pin 401, a body-side fiber optic connection section 402, a body-side sample connection section 403, a body-side reagent connection section 404, and an anode actuator 405. The positioning pin 401 fits into the positioning hole 216 of the capillary cartridge 101. By fitting the positioning pin 401 into the positioning hole 216, the capillary cartridge 101 can be installed in the electrophoresis device 1 with integrated pretreatment with high reproducibility. The body-side fiber optic connection section 402 is connected to the fiber optic connection section 204 of the capillary cartridge 101. The body-side sample connection section 403 is connected to the sample connection section 214 of the capillary cartridge 101.The sample connection section 403 on the body side delivers the sample, which has been pretreated in the pretreatment unit 106, to the capillary cartridge 101. The reagent connection section 404 on the body side is connected to the coupling 215 of the capillary cartridge 101. The reagent connection section 404 on the body side delivers the reagent contained in the pretreatment reagent section 210 of the capillary cartridge 101 to the pretreatment unit 106. The anode actuator 405 controls the opening and closing processes of the pump 303 and the valve 302 of the capillary cartridge 101.

[0024] The interface unit 109 comprises a latch 406, a power supply unit 407, a high-voltage application unit 408, and a magnetic switch 409. When the capillary cartridge 101 is placed on the interface unit 109, the latch 406 engages with a step (not shown) or the like provided on the side of the capillary cartridge 101. This secures the capillary cartridge 101 in place. The power supply unit 407 provides power to the electrical interface 212 of the capillary cartridge 101. The high-voltage application unit 408 applies a high voltage to the cathode end of the capillary 101 via the high-voltage interface 213 of the capillary cartridge 101. The magnetic switch 409 conducts a weak current when the capillary cartridge 101 is installed. This allows the PC 107 to confirm whether the capillary cartridge 101 is installed or not.

[0025] The interface unit 109 and the projection 410 form an installation surface for the capillary cartridge 101. Therefore, when the interface unit 109 is open, the installation surface for the capillary cartridge 101 (the upper surface of the interface unit 109 and the upper surface of the projection 410) is designed to be flush. However, the upper surfaces of the interface unit 109 and the upper surfaces of the projection 410 do not all need to be at the same height, and it is acceptable for only a portion of them to be aligned vertically.

[0026] When installing the capillary cartridge 101, the positioning pin 401 mentioned above is inserted into the positioning hole 216. This connects the corresponding connection sections of the interface unit 109 and the capillary cartridge 101 with high precision, and the capillary cartridge 101 is further secured by the latch 406. It should be noted that instead of using the latch 406, the capillary cartridge 101 can be secured to the installation surface by using a magnet or similar device. The fixing components for the capillary cartridge 101 are not limited to latches and magnets.

[0027] In the present embodiment, the positioning pin 401 is arranged on the main body 111 (projection 410), which is a non-moving section, and furthermore, flow channel components (body-side sample connection section 403, body-side reagent connection section 404, and anode actuator 405) are installed on the same surface as the surface on which the positioning pin 401 is installed. This enables a precise connection between the flow channel components (sample connection section 214, coupling 215, and anode block 206) on the side of the capillary cartridge 101 and the flow channel components (body-side sample connection section 403, body-side reagent connection section 404, and anode actuator 405) on the side of the electrophoresis device 1 with integrated pretreatment.Meanwhile, the electrical components on the side of the electrophoresis device 1 with integrated pretreatment (power supply unit 407, high-voltage application unit 408, magnetic switch 409), which are connected to the capillary cartridge 101, are arranged on the interface unit 109, which is a movable section. This is because, compared to the flow channel components described above, the connection of the electrical components does not require high positioning accuracy, and rattling that occurs in the hinges 110 when the interface unit 109 is opened can be tolerated. Furthermore, the risk of liquid reaching the electrical components, even if liquid, such as reagents, leaks from the flow channel components, is reduced because the installation area for the flow channel components and the installation area for the electrical components are surfaces of different elements. <Betrieb der Elektrophoresevorrichtung mit integrierter Vorbehandlung>

[0028] The mechanism from the pretreatment process to the electrophoresis process of the electrophoresis device 1 with integrated pretreatment is described below. First, the user removes the electrophoresis device 1 with integrated pretreatment from the transport case. Then, the user opens the interface unit 109 and places the capillary cartridge 101 on the upper surface of the interface unit 109. When the capillary cartridge 101 is placed, the PC 107 detects that the capillary cartridge 101 has been installed based on the current flowing from the magnetic switch 409. The PC 107 drives a pump (not shown) or the like to draw the reagent from the pretreatment reagent section 210 into the capillary cartridge 101 and fill the flow channel in the device with the reagent. Furthermore, the PC 107 drives the anode actuator 405 to operate the valve 302 and the pump 303.Thus, the electrophoresis medium is supplied from the electrophoresis medium section 207 in the capillary cartridge 101 to the anode block 206 via the electrophoresis medium connection section 304. The electrophoresis medium is then introduced into the capillary 201 via the capillary anode end 301. Additionally, the PC 107 operates the pump 217 to introduce the reagent from the electrophoresis reagent section 209 into the cathode block 205. At this point, the temperature of the capillary 201 is set by the heating device 202. The above is the preparatory operation of the electrophoresis device 1 with integrated pretreatment prior to analysis.

[0029] The analysis flow is described next. The user collects biological samples such as oral cells, bloodstains, and fingerprints using a swab. After collection, the user seals the swab in the sample cartridge 102 and mounts the sample cartridge 102 onto the electrophoresis device 1 with integrated pretreatment. When the user selects a desired application using the touch panel 108 or similar, the electrophoresis device 1 with integrated pretreatment starts the analysis process. All subsequent processes are performed automatically by the electrophoresis device 1 with integrated pretreatment.The pretreatment unit 106 of the electrophoresis device 1 with integrated pretreatment uses the reagent enclosed in the sample cartridge 102 and the reagent in the pretreatment reagent section 210 of the capillary cartridge 101 to lysis cells in the sample cartridge 102 and to perform elution, purification, amplification, and the like of DNA. DNA bases are labeled with a fluorescent dye. Pretreating the biological sample in this way prepares it for capillary electrophoresis. The PC 107 operates a pump (not shown) to deliver the sample, containing the ultimately amplified DNA, from the pretreatment unit 106 to the cathode block 205 in the sample cartridge 102. Afterwards, the PC 107 operates the high-voltage power supply 103 to apply a negative high voltage to the cathode block 205 via the high-voltage interface 213.A voltage is then applied between a ground electrode (not shown) in the anode block 206 and the cathode block 205. Since the DNA carries a negative charge, it migrates through the capillary 201 towards the anode block 206 during electrophoresis. The irradiation detection unit 203 emits laser light (excitation light) from a laser (not shown) and irradiates the capillary 201 via a fiber optic cable. As a result, the DNA migrating through the capillary 201 during electrophoresis emits fluorescence. The fluorescence is introduced via the fiber optic cable into the optical system 104 and detected. The PC 107 analyzes the DNA base sequence by processing the detected fluorescence signal. The above is the analysis flow for the electrophoresis device 1 with integrated pretreatment. <Nach Verwendung der Elektrophoresevorrichtung mit integrierter Vorbehandlung>

[0030] Fig. Figure 5A is a side view to illustrate the shape of the electrophoresis device 1 with integrated pretreatment when the interface unit 109 is closed. The left side of Fig. Figure 5A illustrates interface unit 109 in an open state. The right side of Fig. Figure 5A illustrates the interface unit 109 in a closed state. If the electrophoresis device 1 with integrated pretreatment is not used for a period of time after the analysis, or if the electrophoresis device 1 with integrated pretreatment is transported, the user removes the capillary cartridge 101, as shown in Fig. Figure 5A illustrates this, and rotates the interface unit 109 around the hinges 110. This allows the size of the electrophoresis device 1 with integrated pretreatment to be reduced. In other words, at least one of the maximum values ​​of the length, width, and height of the electrophoresis device 1 with integrated pretreatment is reduced. In the example of Fig. 5A, when the interface unit 109 is closed, reduces the maximum length in the forward-backward direction (the sum of the length of the bottom of the main body 111 and the length of the bottom of the interface unit 109). Therefore, the electrophoresis device 1 with integrated pretreatment can be stored in a space-saving manner. If a transport case is used to transport the electrophoresis device 1 with integrated pretreatment, the size of the transport case itself can also be reduced.

[0031] Fig. Figure 5B is a cross-sectional view of the electrophoresis device 1 with integrated pretreatment. As shown in Fig. As illustrated in Figure 5B, the interface unit 109 is closed to surround the upper surface and side surfaces of the projection 410. In this way, closing the interface unit 109 seals the installation area for the capillary cartridge 101 (the upper surface of the interface unit 109 and the upper surface of the projection 410), thus preventing the ingress of dust, dirt, and the like into the fluid connection flow channel components and the electrical connection components on the interface unit 109.

[0032] In the present embodiment, taking into account the dripping during the opening and closing of the interface unit 109, the fluid connection section is not provided on the interface unit 109, but instead on the projection 410 of the main body 111. Furthermore, since the fluid connection section is arranged vertically below the electrical connection section, fluid does not drip from the fluid connection section onto the electrical connection section when the interface unit 109 is closed. This arrangement of the fluid component and the electrical component can prevent failure of the electrophoresis device 1 with integrated pretreatment.However, if suitable measures are taken to prevent liquid dripping (for example, by using a drip-resistant coupling), components such as fluid connection sections can be provided on the interface unit 109. Even in this case, when the interface unit 109 is closed, the fluid connection section is located below the electrical connection section, thus preventing liquid from adhering to the electrical connection section. By designing the arrangement of the fluid and electrical components as described above, the folded structure of the electrophoresis device 1 with integrated pretreatment can be achieved.

[0033] Fig. 5C is an enlarged view of the area defined by the dotted line in Fig. Figure 5B is included, illustrating the boundary between the main body 111 and the interface unit 109. The main body 111 and the interface unit 109 each have a stepped, spigot-like structure 501 around their entire circumference, forming a structure that can prevent the inflow of air, dirt, dust, and the like from the outside. This prevents dirt, dust, and the like from adhering to the flow channel components provided on the projection 410.

[0034] Fig. Figure 5D is an enlarged view to illustrate a different structure of the boundary between the main body 111 and the interface unit 109. To prevent the ingress of dust and dirt, a seal 502 (sealing element) can be provided on the main body 111, as shown in Fig. 5D illustration. The seal 502 can, for example, be provided on the front surface of the main body 111 around the entire circumference of the interface unit 109. The seal 502 prevents the ingress of dust and dirt more effectively than the pin structure 501. The seal 502 can be made of a material such as rubber or resin.

[0035] It should be noted that in the present embodiment, the capillary cartridge 101 is designated as such because it is equipped with the capillary. However, it is not strictly necessary to use a cartridge equipped with the capillary 201, and the capillary 201 can alternatively be provided on the side of the electrophoretic device 1 with integrated pretreatment. Furthermore, in the present embodiment, a removable unit placed on the interface unit 109 is defined as the capillary cartridge 101. Instead of the capillary cartridge 101, another unit (such as a reagent cartridge) can be configured to be removablely attached to the interface unit 109. <Zusammenfassung der ersten Ausführungsform>

[0036] As described above, the electrophoresis device 1 with integrated pretreatment according to the first embodiment comprises the pretreatment unit 106 for performing a pretreatment on a biological sample (cells) to prepare a sample for electrophoresis, and the optical system 104, which irradiates the sample separated by electrophoresis in the capillary 201 with light and detects the light from the sample. The electrophoresis device 1 with integrated pretreatment comprises: the main body 111 (first main body) and the interface unit 109 (second main body); and the hinge 110 (coupling element) that couples the main body 111 and the interface unit 109. The main body 111 and the interface unit 109 have an installation surface on which the capillary cartridge 101 (removable unit) is placed.The hinge 110 couples the main body 111 and the interface unit 109 such that the interface unit 109 is rotatable relative to the main body 111 (movable relative to the main body 111). By rotating the interface unit 109 to open and close, the overall size of the electrophoresis device 1 with integrated pretreatment is variable. Since the size of the electrophoresis device 1 with integrated pretreatment can be changed, it is possible to improve portability and reduce the transport space required by decreasing its size during transport. Furthermore, since there is no need to provide space within the device to accommodate the capillary cartridge 101, the electrophoresis device 1 with integrated pretreatment itself can be miniaturized, and its size is independent of the size of the capillary cartridge 101.

[0037] When the interface unit 109 is closed to reduce the size of the electrophoresis device 1 with integrated pretreatment, the installation area for the capillary cartridge 101 between the interface unit 109 and the main body 111 is sealed. This protects the installation area for the capillary cartridge 101 from external contamination. Therefore, there is no need to seal the installation area with a blanking plug or similar device. Furthermore, when the interface unit 109 is opened to increase the size of the electrophoresis device 1 with integrated pretreatment, the installation area for the capillary cartridge 101 is exposed, allowing the capillary cartridge 101 to be inserted.

[0038] Patent documents 3 to 5 disclose technologies for analyzing samples using electrophoresis. Patent document 3 discloses an analysis system enclosed in a case-shaped housing. However, the structure according to patent document 3 differs significantly from the electrophoresis device 1 with integrated pretreatment according to the present embodiment, in which the system itself has a foldable structure. Furthermore, patent document 3 does not describe how the system itself can be miniaturized to fit into a transport case, as is the case with the electrophoresis device 1 with integrated pretreatment.

[0039] Patent documents 4 and 5 disclose electrophoresis devices equipped with a detachable unit. However, the electrophoresis devices according to patent documents 4 and 5 do not have a foldable structure, and there is no description or suggestion of how to fold them or make them compact for transport. Second embodiment

[0040] In the first embodiment, it was described that the electrophoresis device with integrated pretreatment can be miniaturized by rotating the interface unit 109 using the hinges 110. In a second embodiment, an example is described in which the electrophoresis device with integrated pretreatment is miniaturized by linearly moving the interface unit 109. <Konfigurationsbeispiel für Elektrophoresevorrichtung mit integrierter Vorbehandlung>

[0041] Fig. Figure 6 illustrates a top view (left) and a side view (right) of an electrophoresis device 2 with integrated pretreatment according to the second embodiment. The configuration of the electrophoresis device 2 with integrated pretreatment according to the present embodiment is almost the same as that of the first embodiment. However, the main body 111 does not have the projection 410. Instead, the positioning pin 401, the body-side fiber optic connection section 402, the body-side sample connection section 403, the body-side reagent connection section 404, and the anode actuator 405 are provided at the locations corresponding to the projection 410 on the interface unit 109. The arrangement of the fluid components and the electrical components is the same as that of the first embodiment.Furthermore, the interface unit 109 is coupled to the main body 111 by a linear guide component, such as a linear rail 601 (coupling element). This allows the interface unit 109 to move in the forward and backward direction. As shown on the right side of . Fig. As illustrated in Figure 6, a space 602 is provided within the main body 111 to accommodate the interface unit 109.

[0042] Fig. Figure 7 shows side views of the interface unit 109 with and without the capillary cartridge 101 mounted on it. The connection section between the interface unit 109 and the capillary cartridge 101 is similar to that in the first embodiment. When using the electrophoresis device 2 with integrated pretreatment, the user places the capillary cartridge 101 on the upper surface of the interface unit 109. If the capillary cartridge 101 is not mounted, the interface unit 109 is housed in space 602 of the electrophoresis device 2 with integrated pretreatment, thus enabling miniaturization of the electrophoresis device 2 with integrated pretreatment. Furthermore, the fluid connection section and the electrical connection section between the capillary cartridge 101 and the interface unit 109 are housed within the electrophoresis device 2 with integrated pretreatment.This makes it possible to protect the fluid connection section and the electrical connection section from the adhesion of dust and the like. <Zusammenfassung der zweiten Ausführungsform>

[0043] As described above, in the electrophoresis device 2 with integrated pretreatment according to the second embodiment, the interface unit 109 (second main body) and the main body 111 (first main body) are coupled by a linear guide component, and the interface unit 109 is linearly movable. The main body 111 is provided with space 602 for receiving the interface unit 109. The size of the electrophoresis device 2 with integrated pretreatment is variable by either withdrawing the interface unit 109 from space 602 within the main body 111 or by placing the interface unit 109 within space 602. This allows the electrophoresis device 2 with integrated pretreatment to be miniaturized independently of the size of the capillary cartridge 101, as in the first embodiment.By converting the electrophoresis device 2 with integrated pretreatment into a smaller size during transport, portability is improved and the transport space can also be reduced.

[0044] Furthermore, in the second embodiment, the interface unit 109 (second main body) has an installation surface for the capillary cartridge 101 (removable unit). Since both the flow channel components and the electrical components are arranged on the interface unit 109 and the orientation of the installation surface for the capillary cartridge 101 does not change, there is no risk of fluid from the flow channel components reaching the electrical components. Moreover, the electrophoresis device 2 with integrated pretreatment according to the second embodiment is easy to construct. Third embodiment

[0045] In the second embodiment, the interface unit 109 is described as a pull-out type. In a third embodiment, a configuration similar to that of the second embodiment is described, in which the size of the electrophoresis device with integrated pretreatment is variable according to the size of the capillary cartridge 101.

[0046] Fig. Figure 8 is a side view of an electrophoresis device 3 with integrated pretreatment according to the third embodiment. The configuration of the electrophoresis device 3 with integrated pretreatment is almost the same as that of the second embodiment. As shown in Fig. As illustrated in Figure 8, a plurality of grooves 801 are provided in the interface unit 109, and a ball piston 802 is provided on the main body 111. When the interface unit 109 is withdrawn, the ball piston 802 fits into the grooves 801, thus allowing the withdrawal amount of the interface unit 109 to be changed. Although not illustrated in the figure, the plurality of grooves 801 are provided at intervals along the linear direction of movement of the interface unit 109. In the example of Fig. 8 The pull-out amount of the interface unit 109 can be changed in three stages, but this is not limited to that.

[0047] By forming the grooves 801 in the interface unit 109 to match the size of the capillary cartridge 101 to be used, the user can easily change the extension amount of the interface unit 109. This allows the size of the electrophoresis device 2 with integrated pretreatment to be adapted to the size of the capillary cartridge 101. It should be noted that in the present embodiment, other positioning components, such as magnets or leaf springs, can be used instead of the ball piston 802 and the grooves 801, and the configuration is not limited to these. Fourth embodiment

[0048] In the first to third embodiments, the configuration was described in which the interface unit 109 is movable relative to the main body 111. However, the interface unit 109 does not necessarily have to be movable.

[0049] Fig. Figure 9 is a side view of an electrophoresis device 4 with integrated pretreatment according to a fourth embodiment. The configuration of the electrophoresis device 4 with integrated pretreatment is almost the same as that of the electrophoretic device 2 with integrated pretreatment according to the second embodiment, but the main body 111 is movable relative to the interface unit 109. Although not illustrated, a linear guide component, such as a linear rail, couples the upper surface of the interface unit 109 to the lower surface of the main body 111. In this case, the high-pressure pump 105, the optical system 104, and the like can be mounted on the interface unit 109. Some of the components contained in the optical system 104, such as optical fibers and cable harnesses, are delicate, and minimizing the movement of these components can reduce the risk of failure.Furthermore, highly durable components are generally expensive, and by placing sensitive components, such as optical components, in the stationary section, it is possible to use components with relatively short lifespans and low costs. As a result, the manufacturing costs of the electrophoretic device with integrated pretreatment can be reduced. Fifth embodiment

[0050] Fig. Figure 10 illustrates a front view (left) and a side view (right) of an electrophoresis device 5 with integrated pretreatment according to a fifth embodiment. As shown in Fig. As illustrated in Figure 10, the capillary cartridge 101 can be connected to the main body 111 instead of the interface unit 109. In this case, various electrical and fluid components are arranged on the main body 111. As in the first embodiment, because the flow channel components are arranged vertically below the electrical components, fluid does not adhere to the electrical components, even if fluid drips from the flow channel components. In the present embodiment, the interface unit 109 serves as a mounting base for the capillary cartridge 101 and also serves as a cover for the flow channel components and electrical components of the main body 111 when the interface unit 109 is closed. Sixth embodiment

[0051] In the first to fifth embodiments, the electrophoresis device with integrated pretreatment was described, configured such that the capillary cartridge 101 is detachably attached to the interface unit 109 or the main body 111. The unit detachably attached to the electrophoresis device with integrated pretreatment is not limited to the capillary cartridge 101.

[0052] Fig. Figure 11 is a side view of an electrophoresis device with integrated pretreatment 6 according to a sixth embodiment. As in Fig. As shown in Figure 11, the electrophoresis device 6 with integrated pretreatment does not include the touch panel 108, and a tablet connector 1011 can be installed on the interface unit 109 instead of the touch panel 108. In this case, the interface unit 109 is equipped with connection components such as a connector for the tablet connector 1011. Furthermore, the capillary cartridge 101 is placed on the upper surface of the main body 111.

[0053] In the present embodiment, the tablet connector 1011 can be configured to implement the functions of the PC 107. In this case, the PC 107 can be removed from the main body 111, thus making the electrophoresis device with integrated pretreatment more compact. Fig. Figure 11 illustrates the pull-out interface unit 109, but it can also be a foldable interface unit 109 (like the first embodiment). Seventh embodiment

[0054] In the first to sixth embodiments, a configuration was described in which a single detachable unit is installed on the interface unit 109 of the electrophoresis device with integrated pretreatment. As described in a seventh embodiment below, the configuration can be such that a plurality of detachable units can be installed on the interface unit 109.

[0055] Fig. Figure 12 is a side view of an electrophoresis device 7 with integrated pretreatment according to the seventh embodiment. As in Fig. As shown in Figure 12, the tablet connector 1011 and the high-voltage power supply 103 are installed as detachable units on the interface unit 109. The reason for configuring the high-voltage power supply 103 to be detachable is explained below. Connections between the components of an optical system and between the components of a fluid delivery system (such as a high-pressure pump) require both specialized tools and a certain amount of force, and the user may need to be a skilled professional to make the connections. In contrast, the high-voltage power supply 103 only requires an electrical connection to the electrophoresis device 7 with integrated pretreatment, and therefore no special skills are required for installation by the user.By configuring such components to be detachably attached to the electrophoresis device 7 with integrated pretreatment, and removing them from the main body 111, the size of the main body 111 can be reduced.

[0056] It should be noted that in Fig. 12 the number of detachable units is two (the tablet connector 1011 and the high-voltage power supply 103), but there may be three or more units. Eighth embodiment

[0057] The seventh embodiment describes a configuration in which a plurality of detachable units are installed on the single interface unit 109. Alternatively, a plurality of interface units 109 can be provided. For example, the foldable interface unit 109 described in the first embodiment and the pull-out interface unit 109 described in the second embodiment can be combined. The same type of interface unit 109 can also be provided. Additionally, the plurality of interface units 109 need not all be installed in the same location. For example, some can be provided on the front of the main body 111 and others can be provided on the rear of the main body 111.It should be noted that the number of interface units (109) may be the same as the number of removable units, or it may be different.

[0058] The size of each of the numerous interface units 109 can be designed to match the size of the removable unit to be installed. This allows the size of the electrophoresis device with integrated pretreatment to be optimized in use. [Modification]

[0059] The present disclosure is not limited to the embodiments described above and includes various modifications. For example, the embodiments described above have been described in detail to clearly explain the present disclosure, and it is not necessary to include all described configurations. Furthermore, a part of one embodiment can be replaced by the configuration of another embodiment. Additionally, the configuration of another embodiment can be added to the configuration of one embodiment. Moreover, for a part of the configuration of each embodiment, a part of the configuration of another embodiment can be added, deleted, or replaced.

[0060] In the embodiment described above, the hinge 110 and the linear rail 601 are described as examples of coupling elements between the interface unit 109 and the main body 111. The coupling elements between the interface unit 109 and the main body 111 are not limited to these, and any element can be used as long as it allows the interface unit 109 and the main body 111 to move relative to each other and allows the size of the electrophoresis device with integrated pretreatment to be changed. List of reference symbols 1 to 7 Electrophoresis device with integrated pretreatment 101 capillary cartridge 102 Sample cartridges 103 High-voltage power supply 104 optical system 105 High-pressure pump 106 Pretreatment unit 107 PC 108 Touch Panel 109 Interface unit (second main body) 110 Hinge (coupling element) 111 Main body (first main body) 201 capillaries 202 Heating device 203 Irradiation Detection Unit 204 Fiber optic connection section 205 Cathode block 206 Anode block 207 Electrophoresis medium section 208 Waste liquid section 209 Electrophoresis reagent section 210 Pretreatment reagent section 211 Waste liquid section 212 electrical interface 213 High-voltage interface 214 Sample connection section 215 coupling 216 Positioning hole 217 Pump 301 Capillary anode end 302 Valve 303 Pump 401 Positioning pin 402 body-side fiber optic connection section 403 Body-side sample connection section 404 body-side reagent connection section 405 Anode actuator 406 bars 407 Power Supply Unit 408 High-voltage application unit 409 Magnetic switches 410 lead 501 cone structure 502 Seal 601 linear rail (coupling element) 801 Nut 802 Spherical pistons 1011 Tablet connector QUOTES INCLUDED IN THE DESCRIPTION

[0000] This list of documents cited by the applicant was automatically generated and is included solely for the reader's convenience. The list is not part of the German patent or utility model application. The DPMA accepts no liability for any errors or omissions. Cited patent literature

[0000] US 6531282

[0006] US 2016 / 0116439

[0006] JP 2016-0101166

[0006] JP 83900

[0006] JP 282055

[0006]

Claims

Electrophoresis device with integrated pretreatment comprising: a pretreatment unit that performs a pretreatment on a biological sample to prepare a sample for electrophoresis; and an optical system that irradiates the sample separated by electrophoresis in a capillary with light and detects the light from the sample, wherein the electrophoresis device with integrated pretreatment further comprises: a first main body and a second main body;and a coupling element that couples the first main body and the second main body, wherein at least one of the first main body and the second main body has an installation surface on which a removable unit is installed, and the coupling element couples the first main body and the second main body in such a way that one of the first main body and the second main body is movable relative to the other, so that the overall size of the electrophoresis device with integrated pretreatment is variable. Electrophoresis device with integrated pretreatment according to claim 1, wherein the coupling element couples the first main body and the second main body such that the size of the electrophoresis device with integrated pretreatment without the installed removable unit is smaller than the size of the electrophoresis device with integrated pretreatment with the installed removable unit, and the installation surface between the first main body and the second main body is sealed when the size of the electrophoresis device with integrated pretreatment is reduced, and exposed when the size of the electrophoresis device with integrated pretreatment is increased. Electrophoresis device with integrated pretreatment according to claim 1, further comprising: a positioning component for positioning the removable unit; and a flow channel component for fluid connection with the removable unit, wherein both the positioning component and the flow channel component are arranged on the installation surface of one of the first main body and the second main body. Electrophoresis device with integrated pretreatment according to claim 3, further comprising an electrical component for electrical connection with the removable unit, wherein the electrical component is arranged on a surface that differs from the installation surface on which the positioning component and the flow channel component are arranged. Electrophoresis device with integrated pretreatment according to claim 4, wherein the flow channel component is arranged vertically below the electrical component when the size of the electrophoresis device with integrated pretreatment is reduced. Electrophoresis device with integrated pretreatment according to claim 1, wherein the coupling element has a hinge configured to allow one of the first main body and the second main body to open and close relative to the other. Electrophoresis device with integrated pretreatment according to claim 6, wherein the first main body has a projection extending towards the second main body and having the hinge, and when the second main body rotates about the hinge into an open position relative to the first main body, the projection and the second main body are at least partially at the same height and form the installation surface. Electrophoresis device with integrated pretreatment according to claim 7, wherein when the second main body rotates about the hinge into a closed position relative to the first main body, the installation surface of the projection is surrounded by the second main body. Electrophoresis device with integrated pretreatment according to claim 8, wherein the first main body and the second main body each have a stepped cone structure, and when the second main body is closed, the cone structures are in engagement with each other. Electrophoresis device with integrated pretreatment according to claim 8, wherein one of the first main body and the second main body has a sealing element on a surface facing the other when the second main body is closed. Electrophoresis device with integrated pretreatment according to claim 1, wherein the removable unit comprises at least one capillary, a reagent for use in electrophoresis and a reagent for use in pretreatment. Electrophoresis device with integrated pretreatment according to claim 1, wherein the removable unit comprises an input device for entering operating instructions into the electrophoresis device with integrated pretreatment. Electrophoresis device with integrated pretreatment according to claim 1, wherein the coupling element has a linear guide component configured such that one of the first main body and the second main body is linearly movable relative to the other. Electrophoresis device with integrated pretreatment according to claim 13, wherein the first main body has a space capable of receiving the second main body, and a linear movement of the second main body causes the second main body to be accommodated in the first main body or withdrawn from the first main body.

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