JP2006112928A - Electrophoretic apparatus - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To arrange a plurality of capillary ends with high precision in a terminal detecting system. <P>SOLUTION: In the terminal detecting system, the reference surface provided to a holding member for holding a plurality of the capillary ends is used to be aligned with a detection optical system. A plurality of the capillary ends can be aligned with the detection optical system with high precision by aligning the reference surface with the detection optical system. By this arrangement, a plurality of the capillary ends can be arranged with high precision and electrophoretic analysis of high precision can be achieved. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a technique for separating and analyzing nucleic acids, proteins and the like by electrophoresis, for example, a capillary electrophoresis apparatus.

  2. Description of the Related Art In recent years, a capillary array type electrophoresis apparatus has been proposed that measures a number of capillaries filled with a gel in order to increase the speed and throughput when determining the base sequence of DNA.

  For example, Japanese Patent Laid-Open No. 10-19846 discloses a capillary electrophoresis apparatus that has a capillary pre-filled with a gel and a buffer tank provided at the lower end of the capillary, and performs fluorescence detection from the lower end of the capillary. It is disclosed. The end detection method for detecting fluorescence emitted from the end of the capillary that propagates through the capillary is also disclosed in JP 2000-506606, JP 2001-519913, and JP 2002-520616. Has been.

  Japanese Laid-Open Patent Publication No. Hei 5 discloses an electrophoretic apparatus in which a capillary head that bundles a plurality of capillary ends is fastened by a ferrule and connected to an electrophoretic medium filling mechanism. The electrophoresis medium is filled into the capillary from the end of the capillary by the gel filling syringe.

JP-A-10-19846 Special Table 2000-506606 JP-T-2001-519913 Japanese translation of PCT publication No. 2002-520616

  As a result of extensive studies by the inventor of the present invention on the method of connecting a plurality of capillary ends and the migration medium filling mechanism in the end detection method, the present inventor has found the following problem.

  When connecting a plurality of capillary ends to a migration medium filling mechanism using a ferrule, there is a possibility that the plurality of capillary ends may slightly move from a desired mounting position when tightening with the ferrule. In addition, since the force for tightening the ferrule varies, there is a possibility that the reproducibility of the attachment positions of the plurality of capillary ends cannot be ensured. If the end of the capillary that emits fluorescence cannot be precisely placed with respect to the light receiving optical system that detects fluorescence, the fluorescence cannot be detected with high accuracy, and the analysis accuracy may deteriorate.

  An object of the present invention relates to arranging a plurality of capillary ends with high accuracy in a terminal detection system.

  The present invention relates to alignment with a detection optical system using a reference surface provided on a holding member that holds a plurality of capillary ends in a terminal detection system. By aligning the reference surface with the detection optical system, the ends of the plurality of capillaries can be aligned with the detection optical system with high accuracy.

  The present invention also relates to individually connecting a detection optical system and a migration medium filling mechanism to a holding member that holds a plurality of capillary ends in a terminal detection system. Since a plurality of capillary ends can be directly aligned with the detection optical system, highly accurate alignment is possible.

  The present invention also relates to the fact that the migration medium filling mechanism and the detection optical system are independent in the end detection method. Substantially independently of the electrophoresis medium filling mechanism, the plurality of capillary ends and the light receiving optical system can be aligned, and one of the error factors in the alignment can be removed.

  According to the present invention, a plurality of capillary ends can be arranged with high accuracy, and high-accuracy electrophoretic analysis can be realized.

  The above and other novel features and benefits of the present invention will be described below with reference to the drawings. However, the drawings are for explanation only, and do not limit the scope of the present invention.

  FIG. 1 shows a schematic perspective view of the electrophoresis apparatus. FIG. 2 is a schematic perspective view of the capillary head. FIG. 3 shows a schematic sectional view in the vicinity of the polymer filling block. FIG. 4 shows a schematic flow diagram of the analysis procedure. The outline of the electrophoresis apparatus will be described below with reference to these drawings.

  The electrophoresis apparatus in the present embodiment (hereinafter referred to as “this apparatus”) uses a plurality of capillaries filled with an electrophoresis medium, introduces a sample into each capillary, and separates and analyzes the sample components in the sample. To do. For example, a base sequence can be analyzed by simultaneously analyzing a plurality of samples containing DNA. The basic configuration of this apparatus is a capillary array, an irradiation optical unit, a detection optical unit, an autosampler unit, an electrophoresis medium filling unit, a power supply unit, and a temperature control unit.

  The capillary array 101 is a detachable exchange member composed of a plurality of capillaries 102, and is exchanged for a new one when the quality deteriorates due to a predetermined number of analyzes and the separation performance decreases. When the measurement technique is changed, the length of the capillaries 102 can be adjusted by exchanging the capillaries 102 with capillaries 102 having different lengths. The capillary array 101 includes a sample introduction unit 104 that introduces a sample into the capillary 102, an irradiation unit 103 that irradiates the separated sample with excitation light, and a capillary head 107 that bundles a plurality of capillaries.

  The capillary 102 is a thin tube having an inner diameter of several tens to several hundreds of microns and an outer diameter of several hundreds of microns, and the surface is coated to improve the strength. The electrophoresis path is formed by filling the inside of the capillary 102 with the electrophoresis medium. By applying a voltage to both ends of the electrophoresis path, the sample can be electrophoretically separated.

  In this embodiment, a quartz pipe whose outer surface is coated with fluorine is used so that light generated in the capillary 102 propagates through the inside. In the irradiation unit 103 slightly away from the sample introduction unit 104, the fluorine coating is removed in order to efficiently irradiate the sample in the capillary 102 with the laser beam 122. A plurality of capillaries 102 are bundled to form a capillary array 101. The number of capillaries 102 is, for example, 384, 192, 96, and 8. If necessary, the capillary 102 may be coated with polyimide.

  The sample introduction unit 104 has the sample introduction end 105 of the capillary 102 arranged in alignment with the well of the sample container 147, and can introduce a plurality of samples held in each well into the migration path.

  In this embodiment, the sample introduction end 105 is formed by inserting the tip of the capillary 102 into the hollow electrode 106, and the sample introduction end 105 is arranged in 24 rows and 16 columns to constitute the sample introduction portion 104. At the sample introduction end 105, the tip of the capillary 102 protrudes slightly from the hollow electrode 106. The hollow electrode 106 composed of a stainless steel pipe is electrically connected to a high voltage power source 162. By immersing the sample introduction end 105 in the sample and applying a voltage, the sample can be electrophoresed and introduced into the capillary. The sample introduction method is not limited to electrophoresis, and the sample may be introduced into the electrophoresis path by pressure or dispensing.

  The irradiation unit 103 is a portion that irradiates the electrophoresis medium filled in the capillary 102 with the laser light 122 that is excitation light, and can irradiate the sample component that has been electrophoretically separated with excitation light. The phosphor labeled on the sample component emits light having a wavelength depending on the sample component.

  In the present embodiment, a plurality of capillaries 102 are divided into a plurality of groups, and a plurality of capillaries 102 are arranged on a plurality of glass substrates to form several capillary arrays. In addition, the number of sets of capillary arrays is one set, two sets, three sets, four sets, and the like. On each glass substrate, the capillaries 102 are arranged substantially parallel to each other and substantially parallel to the glass substrate. In addition, the removed portions of the fluorine film in each capillary 102 are arranged in a straight line. Here, the fact that the capillaries 102 are substantially parallel to each other and parallel to the glass substrate means that the degree of parallelism is within a precision error. The plurality of laser beams 122 irradiated from both sides of each glass substrate by the irradiation optical unit propagate through the polyimide film removal portions in the plurality of capillaries 102, respectively, and excite the sample in each capillary 102 at the same time.

  The capillary head 107 holds a plurality of capillaries in a bundle and can be attached to and detached from the apparatus main body. As shown in FIG. 2, the capillary head 107 of the present embodiment holds the end portions 108 of the capillaries so as to form a matrix. A part of the fluorescence generated from the sample component in the irradiation unit 103 is totally reflected on the inner surface of the capillary 102 and propagates through the capillary 102, is emitted from the terminal unit 108, and is detected by the detection optical unit. Further, the capillary head 107 can be connected to the polymer filling block 152 in a pressure-resistant and airtight manner. Then, a new electrophoresis medium can be filled into the capillary 102 from the end portion 108 by the electrophoresis medium filling unit. Note that the termination units 108 may be arranged in a matrix of 96 rows and 4 columns, 64 rows and 6 columns, or 48 rows and 8 columns as needed, or may be simply converged into one.

  The irradiation optical unit is a mechanism that irradiates the irradiation unit 103 of the capillary array 101 with laser light 122 that is excitation light. The irradiation optical unit of this embodiment includes a laser light source 112, a beam splitter A124, a mirror A125, a beam splitter B126, a mirror B127, and a condenser lens 128.

  The laser light source 112 can oscillate laser light that is excitation light for exciting sample components. The beam splitter A124 and the mirror A125 divide the laser beam 122 into two parts so that the capillary array of the irradiation unit 103 can be irradiated from both sides. The plurality of beam splitters B 126, the plurality of mirrors B 127, and the condenser lens 128 adjust the plurality of laser beams 122 and irradiate the irradiation unit 103 with the laser beams 122. Laser light 122 applied to each capillary array propagates to adjacent capillaries 102 one after another.

As the laser light source 112, a liquid laser, a gas laser, or a semiconductor laser can be used as appropriate, and an LED may be substituted if necessary. For example, an argon ion laser is a multiline that oscillates a laser 122 with wavelengths of 488 nm and 514.5 nm and an output of 100 mW. In addition to a multiline, a single line may be used, or two or more types of laser light sources may be combined. Further, the wavelength of the laser beam 122 may be 532 nm or 633 nm as appropriate. Further, the laser beam 122 may be irradiated only from one side of the capillary array, or the laser beam 122 may be irradiated in a time division manner.

  The detection optical unit 131 is a mechanism for detecting light emitted from the sample component. As shown in FIG. 3, the detection optical unit 131 of this embodiment includes a first camera lens 118, an optical prism 134, a second camera lens 135, and a two-dimensional detector 136.

  The end face of the capillary head 107 having the end portion 108 is filled with the electrophoresis medium and disposed so as to face the detection window 132 made of non-fluorescent quartz glass through the polymer flow path 154. The light emitted from the end portion 108 passes through the migration medium in the polymer flow path 154, is radiated from the detection window 132, enters the first camera lens 133, and becomes a parallel light flux. The parallel light flux is wavelength-dispersed by the optical prism 134 and imaged on the two-dimensional detector 136 which is a CCD camera by the second camera lens 135. Then, the signal from the CCD camera is processed by a computer to analyze the sample.

  Instead of the optical prism 134, the wavelength dispersion means may be configured by appropriately combining diffraction gratings and filters. The two-dimensional detector 136 may be configured by appropriately combining a one-dimensional detector, a photomultiplier, a photodiode, and the like and an optical mechanism.

  The autosampler unit is a mechanism that transports and holds each container used for electrophoretic analysis including the sample container 147 to a predetermined position such as directly below the sample introduction unit 104. The autosampler unit of the present embodiment transports the sample container 147, the buffer container 144, the cleaning container 145, and the waste liquid container 146 by the robot arm 142 having the claws 143.

  The robot arm 142 includes a claw 143 for fixing each container thereon, and can move three-dimensionally. As a result, each container stored in a predetermined place can be transported directly below the sample introduction unit 104, held at that place for a predetermined time, and returned to the predetermined place.

The buffer container 144 is a container that holds a buffer solution that immerses the sample introduction end 105. During the electrophoresis analysis, the buffer container 144 is transported directly below the sample introduction unit 104 so that the buffer solution immerses the sample introduction end 105. Further, during the standby state of the apparatus, the sample is transported in the same manner as in the electrophoresis analysis, and the sample introduction end 105 is immersed in a buffer solution to prevent the electrophoresis medium in the capillary 102 from being dried.

  The cleaning container 145 is a container that holds a cleaning liquid for cleaning the sample introduction end 105, and is transported directly below the sample introduction unit 104 after loading of the electrophoresis medium, preliminary migration, and sample introduction. By immersing the sample introduction end 105 in the cleaning liquid in the cleaning container, the sample introduction end 105 can be cleaned and contamination can be avoided.

  The waste liquid container 146 is a container for holding a used electrophoresis medium, and receives the used electrophoresis medium that is transported directly below the sample introduction unit 104 when filling the electrophoresis medium and discharged from the sample introduction end 105 when filling the electrophoresis medium. .

The sample container 147 is a container that holds a plurality of trace samples, and is transported immediately below the sample introduction unit 104 when the sample is introduced. In this embodiment, a sample container 147 is configured by placing a septa, which is a resin sheet, on a sample plate having 24 rows and 16 columns of wells capable of holding a sample of several tens of μl, and sandwiching it with a holder and a clip. ing. The sample is, for example, a solution that is fluorescently labeled so as to identify four types of nucleoside base molecules and contains a large number of nucleic acids having an appropriate length (size). The septa usually have a sealed through hole at a position corresponding to the well, and the sample introduction end 105 and the sample can be contacted at the time of sample introduction while preventing the sample in the well from evaporating. Moreover, a protective film can be stuck on the upper surface of the septa to prevent sample evaporation. In addition, the holder and the clip sandwich a sample plate and a septa between them, and are integrated to form a sample container 147 that can be transported by the robot arm 142.

  The electrophoresis medium filling unit shown in FIGS. 1 and 3 is a mechanism for filling the capillary 102 with a polymer as the electrophoresis medium. The electrophoresis medium filling unit of this embodiment includes a polymer filling block 152, a syringe 153, a tube 155, and an electromagnetic valve 156, and can automatically fill the capillary 102 with a new electrophoresis medium before starting analysis.

The polymer filling block 152 has a polymer flow path 154 and a detection window 132, is connected to the syringe 153 and the tube 155, and the capillary head 110 can be attached and detached. The capillary head 110 is mounted on the polymer filling block 152 while maintaining pressure and air tightness. The terminal portion 108 of the capillary head 107 is disposed so as to face the detection window 132, and a region sandwiched between the capillary head 106 and the detection window 132 forms a part of the polymer flow path 154. The polymer flow path 154 communicates with a syringe 153 filled with a migration medium and a tube 155 provided with an electromagnetic valve 156. The other end of the tube 155 is immersed in a buffer solution held in the anode buffer container 163.

  When filling the capillary 102 with the electrophoresis medium, the waste liquid container 146 is disposed immediately below the sample introduction unit 104, the electromagnetic valve 156 is closed, and the plunger of the syringe 153 is pushed. As a result, the electrophoresis medium in the syringe 153 flows into the capillary 102 from the terminal end portion 108 via the polymer channel 154. Further, the used electrophoresis medium in the capillary 102 is discharged from the sample introduction end 105 and received by the waste liquid container 146.

  The power supply unit is a mechanism that applies a voltage to the migration path composed of the migration medium in the capillary 102, and can electrophorese the sample. The power supply unit of this embodiment includes a high voltage power supply 162 that is electrically connected to the hollow electrode 106 and the anode electrode 164 and can generate a high voltage of around 15 kV.

  At the time of sample introduction, the inside of the capillary 102, the polymer channel 154 and the tube 155 is filled with the electrophoresis medium, the sample introduction end 105 is immersed in the sample held in the well of the sample container 147, and the electromagnetic valve 156 is opened. As a result, an energization path comprising the hollow electrode 106, the sample in the well, the capillary 102, the polymer flow path 154, the tube 155, the buffer solution in the anode buffer container 163, and the anode electrode 164 is formed. Then, a pulse voltage is applied to this energization path with the hollow electrode 106 as a negative potential and the anode electrode 164 as a positive potential. As a result, a negatively charged sample component, such as DNA, present in the well is introduced from the sample introduction end 105 into the migration path.

  Also, during the electrophoresis analysis, unlike the sample introduction, the sample introduction end 105 is immersed in a buffer solution held in the buffer container 144. As a result, a current path including the hollow electrode 106, the buffer solution in the buffer container 144, the capillary 102, the polymer channel 154, the tube 155, the buffer solution in the anode buffer container 163, and the anode electrode 164 is formed. Then, unlike the sample introduction, a high voltage of around 15 kV is applied. As a result, an electric field is generated in the direction from the irradiation unit 103 to the sample introduction unit 104, and the negatively charged sample component introduced into the migration path is electrophoresed in the direction of the irradiation unit 103.

  The temperature control unit is a mechanism for controlling the temperature of the migration path that affects the migration speed of the sample components. The temperature control unit in the present embodiment houses the capillary 102 in a thermostat (not shown). Then, the air maintained at a constant temperature by a temperature control mechanism such as Peltier is circulated in the thermostatic chamber by a blowing mechanism such as a fan, and the capillary 102 is maintained at a predetermined temperature.

  Hereinafter, the basic procedure of electrophoretic analysis will be described mainly with reference to FIG.

  The basic procedure of electrophoretic analysis can be broadly divided into pre-preparation 201, electrophoresis medium filling 203, preliminary electrophoresis 204, sample introduction 205, and electrophoresis analysis 206. The operator of this apparatus sets a sample and a reagent in this apparatus as a preliminary preparation before starting analysis (201). More specifically, first, the buffer container 144 and the anode buffer container 163 are filled with a buffer solution that forms part of the current path. The buffer solution is, for example, an electrolyte solution that is commercially available for electrophoresis from various companies.

  In addition, a sample to be analyzed is dispensed into the well of the sample container 147. The sample is, for example, a DNA PCR product. In addition, a cleaning solution for cleaning the sample introduction unit 104 is dispensed into the cleaning container 145. The cleaning solution is pure water, for example. In addition, a separation medium for electrophoresis of the sample is injected into the syringe 153. The electrophoresis medium is, for example, a polyacrylamide separation gel commercially available for electrophoresis from various companies. Furthermore, when the deterioration of the capillary 102 is expected or when the length of the capillary 102 is changed, the capillary array 101 is replaced. Then, after the preliminary preparation is completed, the operator operates the apparatus and starts analysis (202). The electrophoresis medium filling 203 is a procedure for filling the capillary 102 with a new electrophoresis medium and forming an electrophoresis path.

  In the loading of the loading medium 203 in the present embodiment, first, the waste solution 146 is carried directly under the sample introduction unit 104 by the autosampler unit so that the used migration medium discharged from the sample introduction end 105 can be received (211). ). Then, the syringe 153 is driven to fill the capillary 102 with a new electrophoresis medium, and the used electrophoresis medium is discarded (212). Finally, the sample introduction end 105 is immersed in the cleaning solution in the cleaning container 145, and the sample introduction end 105 soiled with the electrophoresis medium is washed (213). The preliminary electrophoresis 204 is a procedure for applying a predetermined voltage to the electrophoresis medium so that the electrophoresis medium is in a state suitable for electrophoresis. In the preliminary electrophoresis 204 in the present embodiment, first, the sample introduction end 105 is immersed in the buffer solution in the buffer container 144 by the autosampler unit to form a current path (214). Then, a voltage of about several to several tens of kilovolts is applied to the electrophoresis medium for several to several tens of minutes by the power supply unit to bring the electrophoresis medium into a state suitable for electrophoresis (215). Finally, the sample introduction end 105 is immersed in the washing solution in the washing container 145, and the sample introduction end 105 soiled with the buffer solution is washed (216). The sample introduction 205 is a procedure for introducing sample components into the migration path.

  In the sample introduction 205 in the present embodiment, first, the sample introduction end 105 is immersed in the sample held in the well of the sample container 147 by the autosampler unit. As a result, an energization path is formed, and a sample component can be introduced into the migration path (217). Then, a pulse voltage is applied to the energization path by the power supply unit, and the sample component is introduced into the migration path (218). Finally, the sample introduction end 105 is immersed in the cleaning solution in the cleaning container 145, and the sample introduction end 105 contaminated with the sample is washed (219). The migration analysis 206 is a procedure for separating and analyzing each sample component contained in a sample by electrophoresis. In the electrophoretic analysis 206 in the present embodiment, first, the sample introduction end 105 is immersed in the buffer solution in the buffer container 144 by the autosampler unit to form a current path (220).

  Then, a high voltage of about 15 kV is applied to the energization path by the power supply unit to generate an electric field in the migration path (221). Due to the generated electric field, each sample component in the migration path moves to the irradiation unit 103 at a speed depending on the property of each sample component. That is, the sample components are separated by the difference in moving speed. And it detects in order from the sample component which reached the irradiation part 103. For example, when the sample includes a large number of DNAs having different base lengths, a difference occurs in the moving speed depending on the base length, and the irradiation unit 103 is reached in order from the DNA having the shorter base length. If a fluorescent substance depending on the terminal base sequence is attached to each DNA, the terminal base sequence can be detected in the order of arrival at the irradiation unit 103.

When the planned data is taken, the voltage application is stopped and the electrophoresis analysis is finished (213).

  The above is a series of analysis procedures. When further analysis is performed, the analysis procedure is advanced from the loading of the migration medium 203.

  FIG. 5 is a detailed perspective view of the capillary head in the present embodiment. FIG. 6 is a detailed sectional view of the capillary head in the present embodiment. Hereinafter, the details of the capillary head in this embodiment will be described with reference to FIGS.

  The capillary head 501 includes a capillary end plane 502 in which a plurality of capillary ends are arranged in a matrix of 64 rows and 6 columns, and a flange portion 504 including a capillary head reference plane 503 parallel thereto. The capillary head 501 is made of a resin such as PEEK. Each capillary is fixed by an adhesive. The capillary end plane 502 and the capillary head reference surface 503 are formed by inserting each capillary into a resin-made capillary head component, fixing it with an adhesive, and then cutting it with a diamond cutter. The capillary end plane 502 and the capillary head reference plane 503 are the same polishing surface, and the capillary end plane 502 and the capillary head reference plane 503 are parallel to each other. The capillary end plane 502 and the capillary head reference surface 503 may be separated from each other by a predetermined distance. The capillary head includes, for example, two polymer filling block mounting screws 505 and two detection optical system mounting screws 506. The polymer filling block 507 is connected to the capillary head 501 so as to cover the capillary end plane 502 and is fixed by two polymer filling block mounting screws 505. The capillary head 501 and the polymer filling block 507 are in close contact with each other by a sealing material such as an O-ring or resin packing. A polymer filling block 507 can fill the capillary with the polymer. Further, the capillary head 501 to which the polymer filling block 507 is attached can be moved independently of the detection optical system. The capillary head 501 is easy to handle, and the positional relationship between the polymer filling block 501 and the detection optical system 508 does not affect the measurement of the capillary end plane by the detection optical system 508.

  The capillary head 501 and the detection optical system 508 are fixed by a detection optical system mounting screw 506 with the flange reference surface 510 provided in the flange 509 of the detection optical system aligned with the capillary head reference surface 503. The flange 509 of the detection optical system is, for example, a substantially cylindrical metal member that fixes the first camera lens, the optical prism, the second camera lens, and the two-dimensional detector. A flange reference surface 510 is provided at a location corresponding to the end surface of the cylinder, and a positioning pin 511 exists on the flange reference surface 510. The flange reference surface 510 is inclined at a predetermined angle with respect to the optical axis of the detection optical system. By tilting the capillary end plane 502 at a predetermined angle with respect to the optical axis of the detection optical system, chromatic aberration caused by the wavelength dispersion means is reduced. It is corrected. If necessary, the flange reference surface 510 may be perpendicular to the optical axis of the detection optical system so that the optical axis of the detection optical system is perpendicular to the capillary end plane 502. The flange reference surface 510 provided on the flange 509 of the capillary detection optical system and the mounting reference surface of the first camera lens are dimensioned with high precision by machining, and the focus of the detection optical system is on the flange reference surface. Exists. Thereby, by joining the capillary head reference surface 503 and the flange reference surface 510, the capillary end plane 502 can be arranged with high accuracy at the focal position of the detection optical system. The positioning pin 511 is fitted in a recess 512 provided in the capillary head, and prevents the capillary end plane 502 from rotating with respect to the optical axis of the detection optical system. The central axis of the capillary end plane 502 and the optical axis of the detection optical system coincide with each other with high accuracy, and the capillary end plane 502 and the rotation angle of the wavelength dispersion means such as a prism are aligned with high accuracy.

  The example of the present invention has been described above, but the present invention is not limited to the above-described example, and various modifications can be made by those skilled in the art within the scope of the invention described in the claims. Will be understood.

The schematic perspective view of an electrophoresis apparatus. The schematic perspective view of a capillary head. The schematic sectional drawing of the polymer filling block vicinity. Schematic flow chart of analysis procedure. The detailed perspective view of a capillary head. The detailed sectional view of a capillary head.

Explanation of symbols

DESCRIPTION OF SYMBOLS 101 ... Capillary array, 102 ... Capillary, 103 ... Irradiation part, 104 ... Sample introduction part, 105 ... Sample introduction end, 106 ... Hollow electrode, 107,501 ... Capillary head, 108 ... End part, 112 ... Laser light source, 121 ... Irradiation optical unit 122... Laser beam 124... Beam splitter A 125. Mirror A 126 126 beam splitter B 127 mirror B 131 131 detection unit 132 detection window 133 first camera lens 134 ... optical prism, 135 ... second camera lens, 136 ... two-dimensional detector, 141 ... autosampler unit, 142 ... robot arm, 143 ... claw, 144 ... buffer container, 145 ... cleaning container, 146 ... waste liquid container, 147 ... Sample container 151... Migration medium filling unit 152 507. 153 ... Syringe, 154 ... Polymer flow path, 155 ... Tube, 156 ... Solenoid valve, 161 ... Power supply unit, 162 ... High voltage power supply, 163 ... Anode buffer container, 164 ... Anode electrode, 502 ... Capillary end plane, 503 ... Capillary head reference surface, 504. Flange, 505. Polymer filling block mounting screw, 506. Detection optical system mounting screw, 508. Detection optical system, 509. Detection optical system flange, 510. …Positioning pin.

Claims (24)

A plurality of capillaries capable of being filled with an electrophoresis medium;
A power source for electrophoresis of the sample in the electrophoresis medium;
An excitation optical system for irradiating the separated sample with excitation light;
A detection optical system for detecting fluorescence from a sample emitted from a plurality of capillary ends;
An electrophoresis medium filling mechanism for filling the capillary with the electrophoresis medium from a plurality of capillary ends;
An electrophoresis apparatus comprising:
Multiple capillary ends are held by the capillary head,
The capillary head includes a capillary head reference plane parallel to a plane formed by a plurality of capillary ends,
An electrophoretic apparatus for joining the capillary head reference surface to a detection optical system reference surface provided in a detection optical system. The electrophoresis apparatus according to claim 1,
An electrophoresis apparatus characterized in that the focal point of the detection optical system is on a plane on which the reference plane of the detection optical system exists. The electrophoresis apparatus according to claim 1,
The detection optical system includes a lens and a two-dimensional detector, and the lens and the two-dimensional detector are held by a detection optical system flange provided with a detection optical system reference surface. apparatus. The electrophoresis apparatus according to claim 1,
The electrophoresis apparatus characterized in that the plurality of capillary ends are not on the capillary head reference surface, and the plurality of capillary ends do not contact the detection optical system reference surface. The electrophoresis apparatus according to claim 1,
An electrophoretic device, wherein a plane constituted by a plurality of capillary ends and a capillary head reference plane are on the same plane. The electrophoresis apparatus according to claim 1,
An electrophoretic device, wherein the detection optical system includes an anti-rotation member that prevents rotation of a plurality of capillary ends with respect to the optical axis of the detection optical system. The electrophoresis apparatus according to claim 1,
An electrophoresis apparatus, wherein a detection optical system and an electrophoresis medium filling mechanism are individually connected to a capillary head. The electrophoresis apparatus according to claim 1,
An electrophoretic apparatus, wherein the electrophoretic medium filling mechanism is movable with respect to the detection optical system. A plurality of capillaries capable of being filled with an electrophoresis medium;
A power source for electrophoresis of the sample in the electrophoresis medium;
An excitation optical system for irradiating the separated sample with excitation light;
A detection optical system for detecting fluorescence from a sample emitted from a plurality of capillary ends;
An electrophoresis medium filling mechanism for filling the capillary with the electrophoresis medium from a plurality of capillary ends;
An electrophoresis apparatus comprising:
An electrophoresis apparatus in which a detection optical system and an electrophoresis medium filling mechanism are individually connected to a capillary head. The electrophoresis apparatus according to claim 9, wherein
Multiple capillary ends are held by the capillary head,
The capillary head includes a capillary head reference plane parallel to a plane formed by a plurality of capillary ends,
An electrophoresis apparatus characterized in that the capillary head reference surface is joined to a detection optical system reference surface provided in a detection optical system. The electrophoresis apparatus according to claim 9, wherein
An electrophoresis apparatus characterized in that the capillary head reference surface is joined to a detection optical system reference surface provided in a detection optical system. The electrophoresis apparatus according to claim 9, wherein
An electrophoresis apparatus characterized in that the focal point of the detection optical system is on a plane on which the reference plane of the detection optical system exists. The electrophoresis apparatus according to claim 9, wherein
The detection optical system includes a lens and a two-dimensional detector, and the lens and the two-dimensional detector are held by a detection optical system flange provided with a detection optical system reference surface. apparatus. The electrophoresis apparatus according to claim 9, wherein
The electrophoresis apparatus characterized in that the plurality of capillary ends are not on the capillary head reference surface, and the plurality of capillary ends do not contact the detection optical system reference surface. The electrophoresis apparatus according to claim 9, wherein
An electrophoretic device, wherein a plane constituted by a plurality of capillary ends and a capillary head reference plane are on the same plane. The electrophoresis apparatus according to claim 9, wherein
An electrophoretic device, wherein the detection optical system includes an anti-rotation member that prevents rotation of a plurality of capillary ends with respect to the optical axis of the detection optical system. The electrophoresis apparatus according to claim 9, wherein
An electrophoresis apparatus, wherein a detection optical system and an electrophoresis medium filling mechanism are individually connected to a capillary head. A plurality of capillaries capable of being filled with an electrophoresis medium;
A power source for electrophoresis of the sample in the electrophoresis medium;
An excitation optical system for irradiating the separated sample with excitation light;
A detection optical system for detecting fluorescence from a sample emitted from a plurality of capillary ends;
An electrophoresis medium filling mechanism for filling the capillary with the electrophoresis medium from a plurality of capillary ends;
An electrophoresis apparatus comprising:
The electrophoresis medium filling mechanism is movable with respect to the detection optical system. The electrophoretic device according to claim 18, wherein
Multiple capillary ends are held by the capillary head,
The capillary head includes a capillary head reference plane parallel to a plane formed by a plurality of capillary ends,
An electrophoresis apparatus characterized in that the capillary head reference surface is joined to a detection optical system reference surface provided in a detection optical system. The electrophoretic device according to claim 18, wherein
The detection optical system includes a lens and a two-dimensional detector, and the lens and the two-dimensional detector are held by a detection optical system flange provided with a detection optical system reference surface. apparatus. The electrophoretic device according to claim 18, wherein
The electrophoresis apparatus characterized in that the plurality of capillary ends are not on the capillary head reference surface, and the plurality of capillary ends do not contact the detection optical system reference surface. The electrophoretic device according to claim 18, wherein
An electrophoretic device, wherein a plane constituted by a plurality of capillary ends and a capillary head reference plane are on the same plane. The electrophoretic device according to claim 18, wherein
An electrophoretic device, wherein the detection optical system includes an anti-rotation member that prevents rotation of a plurality of capillary ends with respect to the optical axis of the detection optical system. The electrophoretic device according to claim 18, wherein
An electrophoresis apparatus, wherein a detection optical system and an electrophoresis medium filling mechanism are individually connected to a capillary head.

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