US20040163962A1 - Electrophoresis analysis apparatus and sample vessel used therefor - Google Patents
Electrophoresis analysis apparatus and sample vessel used therefor Download PDFInfo
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- US20040163962A1 US20040163962A1 US10/786,053 US78605304A US2004163962A1 US 20040163962 A1 US20040163962 A1 US 20040163962A1 US 78605304 A US78605304 A US 78605304A US 2004163962 A1 US2004163962 A1 US 2004163962A1
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- sample
- analysis apparatus
- electrophoresis analysis
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/416—Systems
- G01N27/447—Systems using electrophoresis
- G01N27/44704—Details; Accessories
- G01N27/44743—Introducing samples
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/416—Systems
- G01N27/447—Systems using electrophoresis
- G01N27/44756—Apparatus specially adapted therefor
- G01N27/44782—Apparatus specially adapted therefor of a plurality of samples
Definitions
- the present invention relates to an electrophoresis analysis apparatus and a sample vessel used therefor, and particularly to an electrophoresis analysis apparatus suitably used for a DNA sequencer (DNA base sequence analyzer) for analyzing biochemical samples such as a DNA (Deoxyribonucleic acid) using a plurality of capillaries or micropassages as migration separation media, and a sample vessel used therefor.
- DNA sequencer DNA base sequence analyzer
- biochemical samples such as a DNA (Deoxyribonucleic acid) using a plurality of capillaries or micropassages as migration separation media
- a DNA analysis technology based on electrophoresis particularly, a DNA sequencer (DNA base sequence analyzer) has been widely available. With the raised need for analysis, the necessity of improving the analysis throughput has been increased.
- One method of increasing the analysis throughput is to integrate electrophoresis media.
- a thin gel layer formed between two flat glass plates has been conventionally used as electrophoresis separation media.
- a multi-capillary method using a plurality of capillaries each having a fine inside diameter has been proposed, for example, in Nature, Vol. 361 (1993), Kanbara, PP. 565-566, the specifications of U.S. Pat. Nos. 5,277,780, 5,366,608, and 5,274,240, Japanese Patent Laid-open No. Hei 5-72177, and PCT international publication for patent application No. Hei 7-503322.
- Such a method makes it possible to increase the degree of integration by making use of the fine inside diameters of the capillaries and to simultaneously analyze a large number of samples.
- one-ends of an electrode and a capillary are first inserted in a sample contained in a sample vessel, followed by applying a voltage across the capillary to electrically migrate the sample into the capillary; and then the one-ends of the electrode and the capillary are inserted in a buffer solution in a buffer bath, followed by applying a voltage across the capillary to separate the sample by electrophoresis.
- the amount of a sample generally used for a DNA sequencer is merely 5 ⁇ l because it is difficult to prepare a large amount of a sample and also a reagent to be used is expensive.
- the sample in an amount of 5 ⁇ l is put in a sample vessel having an inner diameter of 2 mm, the liquid level becomes only about 1.5 mm. It is very difficult to individually insert several tens of electrodes and capillaries in the above small-sized sample vessels.
- An object of the present invention is to provide a multi-capillary type electrophoresis analysis apparatus capable of making easy works for analysis and a sample vessel used therefor.
- an electrophoresis analysis apparatus having a plurality of migration passages and a detector for optically detecting a plurality of sample components separated by electrophoresis, including: a sample vessel for containing a plurality of samples to be introduced in the migration passages, at least part of a portion, of the sample vessel, to be in contact with these samples being made from a conductive material; wherein the samples are introduced in the migration passages by applying a voltage to the migration passages via the conductive material forming part of the sample vessels.
- the sample vessel preferably includes a plate portion having a plurality of openings and a metal base portion fixed on a bottom portion of the plate portion.
- FIG. 1 is a perspective view showing the entire configuration of an electrophoresis analysis apparatus according to one embodiment of the present invention
- FIG. 2 is a plan view of sample vessels used for the electrophoresis analysis apparatus according to one embodiment of the present invention
- FIG. 3 is a sectional view taken on line A-A of FIG. 2;
- FIG. 4 is a plan view of second sample vessels used for the electrophoresis analysis apparatus according to one embodiment of the present invention.
- FIG. 6 is a sectional view of a fourth sample vessel used for the electrophoresis analysis apparatus according to one embodiment of the present invention.
- FIG. 7 is a sectional view of a fifth sample vessel used for the electrophoresis analysis apparatus according to one embodiment of the present invention.
- FIG. 8 is a sectional view of a sixth sample vessel used for the electrophoresis analysis apparatus according to one embodiment of the present invention.
- FIG. 9 is a sectional view of a seventh sample vessel used for the electrophoresis analysis apparatus according to one embodiment of the present invention.
- FIG. 10 is a plan view of an electrode portion of eighth sample vessels used for the electrophoresis analysis apparatus according to one embodiment of the present invention.
- FIG. 11 is a plan view of an electrode portion of ninth sample vessels used for the electrophoresis analysis apparatus according to one embodiment of the present invention.
- FIG. 1 there will be described the entire configuration of the electrophoresis analysis apparatus according to one embodiment of the present invention.
- FIG. 1 is a perspective view showing the entire configuration of the electrophoresis analysis apparatus according to the embodiment of the present invention.
- a migration buffer bath 12 containing a buffer (electrolyte) is disposed on a moving mechanism 10 .
- a platinum electrode 13 is stretchingly mounted in the migration buffer bath 12 in such a manner as to be in contact with the buffer.
- On the moving mechanism 10 are also disposed three sample trays 100 A, 100 B and 100 C via a sample tray holder 14 .
- the sample tray 100 A includes 48 pieces of sample vessels.
- the sample tray 100 A is removably fixed on the sample tray holder 14 with set screws S 1 and S 2 .
- the bottom portion of the sample tray 100 A is made from a conductive metal such as a stainless steel, and is electrically conductive to the sample tray holder 14 which is made from a conductive metal such as a stainless steel.
- each of the sample trays 100 B and 100 C includes 48 pieces of sample vessels and has a bottom portion which is electrically conductive to the sample tray holder 14 .
- the moving mechanism 10 is vertically movable in the Z-axis direction along vertical slide guides 18 Z using a vertically moving motor 16 Z.
- the moving mechanism 10 is also longitudinally movable in the X-axis direction along longitudinal slide guides 18 ⁇ using a longitudinally moving motor 16 X.
- the motors 16 Z and 16 X are controlled by a controller 80 .
- a transparent cover 19 made from polyvinyl chloride or polyacrylate or polymethacrylate resin is disposed in such a manner as to cover the three sample trays 100 A, 100 B and 100 C for suppressing evaporation of samples held in the sample vessels and preventing contamination of the sample vessels with external dust.
- the electrophoresis analysis apparatus includes 48 pieces of capillaries 20 disposed in parallel, each of which is filled with a gel matrix for separation.
- the lower end sides of the capillaries 20 are fixed by capillary retaining plate 22 , and the lower ends of the capillaries 20 are inserted in the buffer in the migration buffer bath 12 .
- the upper end sides of the capillaries 20 are fixed by a capillary retaining plate 24 , and the upper ends of the capillaries 20 are fixedly connected to a coupler 26 .
- the coupler 26 is connected to an electrode plug 32 on the earth side, and the electrode plug 32 is in turn connected to an earth electrode of a high voltage power supply 30 .
- the sample tray holder 14 is connected to an electrode plug 34 on the high voltage side, and the platinum electrode 13 in the buffer bath 12 is connected to an electrode plug 36 on the high voltage side.
- the electrode plugs 34 and 36 are connected to a high voltage ( ⁇ ) electrode of the high voltage power supply 30 .
- the coupler 26 is connected to a sheath flow cell 40 , into which a sheath liquid 44 held in a sheath liquid tank 42 is introduced by the gravity. Samples, which are separated by migration in the capillaries 20 and flow out of migration terminals of the capillaries 20 , are carried to the upper side with the sample components in the capillaries left as separated.
- a light component having a specific wavelength to be detected is selected from the fluorescent light by a filter 64 and is focused through an image-forming lens 66 at an optical sensor 68 such as a two-dimensional CCD sensor.
- a signal detected by the optical sensor 68 is fed to a signal processor 70 , being processed to identify the kind of the terminal base on the basis of the wavelength of the fluorescent light, and the base sequence of the nucleic acid sample is analyzed on the basis of the measured signal.
- a drain adaptor 46 is mounted on the upper end of the sheath flow cell 40 .
- the sample which has flowed from the capillary 20 into the sheath flow cell 40 , is discharged as a wastage into a drain bottle 49 through a drain tube 47 .
- a flow controller composed of an orifice and a plurality of capillaries for controlling the flow rate of the sample by making constant the passage resistance of the drain tube 47 .
- Samples to be analyzed are previously poured in specific amounts into 48 pieces of the sample vessels of each of the sample trays 100 A, 100 B and 100 C.
- the sample trays 100 A, 100 B and 100 C in which the samples are contained are fixed on the sample tray holder 14 with the set screws S 1 and S 2 .
- the controller 80 drives the vertically moving motor 16 Z to move down the moving mechanism 10 in the Z1 direction.
- the downward movement of the moving mechanism 10 is stopped at a position where the lower ends of the capillaries 20 are sufficiently separated from the buffer bath 12 .
- the controller 80 drives the longitudinally moving motor 16 X to move the moving mechanism 10 in the X1 direction.
- the controller 80 drives the vertically moving motor 16 Z to move down the moving mechanism 10 in the Z1 direction.
- the downward movement of the moving mechanism 10 is stopped at a position where the lower ends of the capillaries 20 are sufficiently separated from the sample trays 100 A.
- the controller 80 drives the longitudinally moving motor 16 X to move the moving mechanism 10 in the X2 direction.
- the movement of the moving mechanism 10 is stopped at a position where the buffer bath 12 is located directly under the capillaries 20 .
- the controller 80 also drives the vertically moving motor 16 Z to move up the moving mechanism 10 in the Z2 direction.
- the upward movement of the moving mechanism 10 is stopped at a position where the leading ends of the capillaries 20 are inserted in the buffer in the buffer bath 12 .
- the positioning in the vertical movement and the longitudinal movement of the moving mechanism 10 is performed using a position detecting mechanism such as a switch provided in the moving mechanism 10 .
- the samples in the sample trays 100 B and 100 C are introduced in the capillaries 20 in the same procedure as described above, to be thus separated by electrophoresis.
- the method of optically detecting the sample separated by electrophoresis is not limited to fluorescent light detection but may be absorbance detection.
- a sample tray 100 is formed into a rectangular shape in a plan view, in which 48 pieces of circular sample vessels 100 - 1 , 100 - 2 , . . . , 100 - 48 are aligned.
- the sample tray 100 includes an upper sample plate 102 and a metal base 104 fixed on the backface of the sample plate 102 .
- the sample plate 102 is made from a transparent polyacrylate or polymethacrylate resin, and has 48 pieces of circular openings for forming the sample vessels 100 - 1 , 100 - 2 , . . . , 100 - 48 .
- the sample plate 102 may be made from a transparent plastic material such as polyvinyl chloride or polycarbonate.
- sample plate 102 is made from a transparent material, it is possible to easily, visually confirm samples contained in the sample vessels 100 - 1 , 100 - 2 , . . . , 100 - 48 and the states of the capillaries inserted in the samples.
- the sample plate 102 is fixed on the metal base 104 with eight screws.
- the metal base 104 is made from a stainless steel as a conductive material.
- the metal base 104 forms part of wall surfaces of the sample vessels 100 - 1 , 100 - 2 , . . . , 100 - 48 , and is used as an electrode common to samples contained in the sample vessels 100 - 1 , . . . , 100 - 2 , 100 - 48 . Since the metal base 104 forms part of the sample vessels, it is possible to eliminate the necessity of inserting electrodes in the samples as in the conventional apparatus. It is experimentally confirmed that the metal base 104 made from even a stainless steel which is a widely available material exhibits a sufficient durability.
- the electrophoresis analysis apparatus using the metal base 104 made from a stainless steel is allowed to be continuously used for a period of sixth months or more only by periodically washing the sample tray 100 .
- the conventional electrophoresis analysis apparatus is expensive because of use of a noble metal such platinum as an electrode material; however, in the electrophoresis analysis apparatus of the present invention, the use of a stainless steel as an electrode material advantageously reduces the cost of the sample vessels.
- Both end portions of the metal base 104 have circular holes 104 A, and as described with reference to shown in FIG. 1, the sample tray 100 is fixed on the metal made sample tray holder with the set screws passing through the circular holes 104 A.
- the means for fixing the sample tray 100 on the sample tray holder is not limited to the set screws but may be plate springs or the like.
- the metal base 104 there may be used an insulating substrate on which a metal foil is stuck or a metal film is formed by vapor-deposition or sputtering. At this time, the metal foil or metal film forms part of the wall surfaces of the sample vessels, and it functions as a common electrode when it is made electrically conductive to the samples contained in the sample vessels.
- a packing is inserted between the sample plate 102 and the metal base 104 for preventing leakage of samples in the sample vessels.
- a length L 1 of the sample plate 102 is set at 160 mm.
- a distance L 2 from the center of the sample vessel 100 - 1 formed in the sample plate 102 to the center of the sample vessel 100 - 48 formed in the sample plate 102 is set at 141 mm. That is to say, a pitch P between the adjacent sample vessels is set at 3 mm. While the cross-sectional shape of the sample vessel will be described with reference to FIG. 3, an opening diameter of the uppermost portion of the sample vessel is set at ⁇ 2.8 mm.
- the pitch P between the adjacent sample vessels is set at a value obtained by dividing a pitch (9 mm) between adjacent holes formed in a microtiter plate by an integer number.
- the microtiter plate is generally used for preparation of samples.
- the pitch between adjacent pipets used for pipetting samples from the microtiter plate is equal to the pitch between the adjacent holes of the microtiter plate. If the pitch P between the adjacent sample vessels is, as described above, set at the value obtained by dividing the pitch (9 mm) between the adjacent holes of the microtiter plate by an integer number (for example 3 as shown in FIG.
- the samples can be pipetted from the microtiter plate into the sample vessels using the existing pipets.
- samples are poured in every fourth sample vessel, that is, in the order of the sample vessels 100 - 1 , 100 - 4 , . . . , 100 - 46 .
- samples are poured in every fourth sample vessel, that is, in the order of the sample vessels 100 - 2 , 100 - 5 , . . . , 100 - 47 .
- samples are poured in every fourth sample vessel, that is, in the order of the sample vessels 100 - 3 , 100 - 6 , . . . , 100 - 48 .
- the samples can be poured in the sample vessels using the existing pipets.
- the pitch P between the adjacent sample vessels which is set at the value obtained by dividing the pitch (9 mm) between the adjacent holes of the microtiter plate, may be generally in a range of 1 ⁇ 2 to 1 ⁇ 4 of the pitch (9 mm) between the adjacent holes of the microtiter plate in consideration of the poured amount of the sample and the dimension of the sample vessel.
- FIG. 3 is an enlarged sectional view taken on line A-A of FIG. 2.
- the sample plate 102 is fixed on the metal base 104 with the set screws as described with reference to FIG. 2.
- a groove is formed in the lower surface portion of the sample plate 102 , and a packing 106 is previously inserted in the groove for preventing leakage of liquid from a space between the sample plate 102 and the metal base 104 .
- the packing 106 is made from silicon rubber.
- the cross-section of the sample plate 102 has a stepped portion 102 B, a taper portion 102 C, and a cylindrical portion 102 D.
- the stepped portion 102 B is formed into an elliptic shape as shown in FIG. 2, and it has a width W of 6 mm.
- a height H of the sample plate 102 is 7 mm
- a height H 1 of the stepped portion 102 B is 1.5 mm.
- the taper portion 102 C is formed into a cone shape having a taper angle ⁇ of 24.4°.
- An opening diameter R 1 of the taper portion 102 C on the upper end side is ⁇ 2.8 mm, and an opening diameter R 2 of the taper portion 102 C on the lower end side is ⁇ 1.2 mm.
- the taper portion 102 C allows easy insertion of a pipet or capillary in the sample vessel, and specifically, the taper portion 102 C allows the leading end of the pipet or capillary to be easily bottomed.
- a height H 2 of the taper portion 102 C is set at 3.7 mm.
- the cylindrical portion 102 D has an opening diameter R 2 of ⁇ 1.2 mm and a height H 3 of 1 mm. Assuming that the poured amount of a sample is 5 ⁇ l, the sample is contained substantially in the cylindrical portion 102 D.
- each metal pin 108 is previously press-fitted in the metal base 104 .
- the number of the metal pins 108 is the same as that of the sample vessels, that is, 48 pieces in this embodiment.
- the metal pin 108 is made from the same material as that of the metal base 104 , that is, a stainless steel.
- the leading end of the metal pin 108 has a projecting portion 108 A having a diameter R 3 of ⁇ 0.8 mm.
- the projecting portion 108 A of the metal pin 108 slightly projects into the cylindrical portion 102 D of the sample plate 102 . With this configuration, the sample is certainly brought in electric-contact with the metal pin 108 and the metal base 104 used as an electrode.
- bubbles caused when a sample is poured in the sample vessel using a pipet possibly adhere on a wall surface of the sample vessel. If the bubbles adhere on the lowermost portion of the sample vessel and the capillary is inserted in the bubbles, the sample cannot be introduced into the capillary. To cope with such an inconvenience, the projecting portion 108 A is provided in such a manner as to project into the cylindrical portion 102 D. In this case, even if bubbles adhere on the bottom of the sample vessel, since the capillary is only inserted to the leading end of the projecting portion 108 A, the sample can be introduced into the capillary by reducing the effect of the bubbles.
- the opening diameter R 1 of the upper end of the taper portion 102 C which forms part of the sample vessel is set at ⁇ 7 mm or less depending on the poured amount of a sample. In particular, if the poured amount of a sample is small, the opening diameter R 1 is set at ⁇ 3 mm or less, for example, ⁇ 2.8 mm as described above. If the poured amount of a sample is smaller than that described above, the opening diameter R 1 may be set at ⁇ 2 mm or less.
- the sample tray 100 has a large number (48 pieces) of the sample vessels, since the conductive metal base and metal pins form part of the sample vessels and are taken as a common electrode, the necessity of inserting electrodes in the sample vessels as in the conventional apparatus can be eliminated. As a result, since only the capillaries may be inserted in the sample vessels, the preparation for analysis can be facilitated.
- the capillaries of the multi-capillary type can be easily inserted in the sample vessels only by moving the sample tray 100 upward using the moving mechanism 10 .
- the electrophoresis analysis can be automated using the electrophoresis analysis apparatus having the configuration shown in FIG. 1.
- FIG. 4 is a plan view of the second sample vessels used for the electrophoresis analysis apparatus according to one embodiment of the present invention.
- a sample tray 100 ′ in this embodiment is different from the sample tray 100 shown in FIG. 2 in that sample vessels 100 - 1 , 100 - 2 , . . . , 100 - 48 are arranged in a staggered pattern.
- the cross-sectional shape of the sample vessel is the same as described with reference to FIG. 3.
- the sample tray 100 ′ has a rectangular shape in a plan view, in which 48 pieces of the circular sample vessels 100 - 1 , 100 - 2 , . . . , 100 - 48 are arranged in a staggered pattern.
- the sample tray 100 ′ has an upper sample plate 102 ′ and a metal base 104 fixed on the backface of the sample plate 102 ′.
- the sample plate 102 ′ is made from a transparent acrylic resin, and has 48 pieces of circular openings for forming the sample vessels 100 - 1 , 100 - 2 , . . . , 100 - 48 .
- the sample plate 102 ′ is fixed on the metal base 104 with eight screws.
- the metal base 104 is made from a stainless steel as a conductive material.
- the metal base 104 forms part of wall surfaces of the sample vessels 100 - 1 , 100 - 2 , . . . , 100 - 48 , and is used as an electrode common to samples contained in the sample vessels 100 - 1 , . . . , 100 - 2 , 100 - 48 . Since the metal base forms part of the sample vessels, it is possible to eliminate the necessity of inserting electrodes in samples as in the conventional apparatus.
- Both end portions of the metal base 104 have circular holes 104 A.
- the sample tray 100 ′ is fixed on a metal made sample tray holder with set screws.
- a packing is inserted between the sample plate 102 ′ and the metal base 104 for preventing leakage of samples in the sample vessels.
- a length L 3 of the sample plate 102 ′ is set at 128 mm.
- a distance L 4 from the center of the sample vessel 100 - 1 formed in the sample plate 102 ′ to the center of the sample vessel 100 - 48 formed in the sample plate 102 ′ is set at 106 mm.
- a pitch P between the adjacent sample vessels is set at 3 mm.
- the length of the sample tray 100 ′ can be shortened, to thereby miniaturize the electrophoresis analysis apparatus, particularly, the moving mechanism.
- FIG. 5 is a plan view of the third sample vessels used for the electrophoresis analysis apparatus according to one embodiment of the present invention.
- a sample tray 100 ′′ in this embodiment is different from the sample tray 100 or 100 ′ shown in FIG. 2 or 4 in that 4 n pieces of sample vessels 100 - 11 , 100 - 12 , . . . , 100 - 21 , . . . , 100 - 31 , . . . , 100 - 41 , . . . , 100 - 4 n are arranged in four rows.
- the cross-sectional shape of the sample vessel is the same as described with reference to FIG. 3.
- the sample tray 100 ′′ has a rectangular shape in a plan view, in which 4 n pieces of the circular sample vessels 100 - 11 , 100 - 12 , . . . , 100 - 21 , . . . , 100 - 31 , . . . , 100 - 41 , . . . , 100 - 4 n are arranged in a matrix pattern of four rows (n pieces for each row).
- the sample tray 100 ′′ has an upper sample plate 102 ′′ and a metal base 104 fixed on the backface of the sample plate 102 ′′.
- the sample plate 102 ′′ is made from a transparent acrylic resin, and has 4 n pieces of circular openings for forming the sample vessels 100 - 11 , . . . , 100 - 4 n.
- the sample plate 102 ′′ is fixed on the metal base 104 with screws.
- the metal base 104 is made from a stainless steel as a conductive material.
- the metal base 104 forms part of wall surfaces of the sample vessels 100 - 11 , 100 - 4 n , and is used as an electrode common to samples contained in the sample vessels 100 - 11 , . . . , 100 - 4 n . Since the metal base forms part of the sample vessels, it is possible to eliminate the necessity of inserting electrodes in samples as in the conventional apparatus.
- the sample tray 100 ′′ is fixed on a metal made sample tray holder with set screws. As described with reference to FIG. 3, a packing is inserted between the sample plate 102 ′′ and the metal base 104 for preventing leakage of samples in the sample vessels.
- a pitch P between the adjacent sample vessels is set at a value obtained by dividing a pitch (9 mm) between adjacent holes of the microtiter plate by an integer number.
- the length of the sample tray 100 ′′ can be shortened, to thereby miniaturize the electrophoresis analysis apparatus, particularly, the moving mechanism.
- FIG. 6 is a sectional view of the fourth sample vessel used for the electrophoresis analysis apparatus according to one embodiment of the present invention.
- the planar shape of a sample tray in which a plurality of the sample vessels are arranged is the same as that shown in FIG. 2, 4 or 5 .
- a sample tray 100 A in this embodiment includes a sample plate 102 E composed of a transparent plate made from an acrylic resin, an insulating base 104 B, a packing 106 made from silicon rubber, and metal pins 108 made from a conductive material such as a stainless steel.
- the sample plate 102 E has a taper portion functioning as a sample vessel. That is to say, a sample is contained in the taper portion of the sample plate 102 E.
- the metal pin 108 is brought in electric-contact with a sample and functions as an electrode. Since a plurality of the sample vessels are formed in the sample tray 100 A, the metal pins 108 of the same number as that of the sample vessels are provided in such a manner as to be electrically connected to the metal made sample tray holder shown in FIG. 1.
- the sample plate 102 E is fixed on a base 104 B with screws.
- a groove is formed in a lower surface portion of the sample plate 102 E, and a packing 106 is previously inserted in the groove for preventing leakage of liquid from a space between the sample plate 102 E and the base 104 B.
- FIG. 7 is a sectional view of the fifth sample vessel used for the electrophoresis analysis apparatus according to one embodiment of the present invention.
- planar shape of a sample tray in which a plurality of the sample vessels are arranged is the same as that shown in FIG. 2, 4 or 5 .
- a sample tray 100 B in this embodiment includes a metal made sample plate 102 F, an insulating base 104 C, and a packing 106 made from silicon rubber.
- the sample plate 102 F is formed with a taper portion functioning as a sample vessel. That is to say, a sample is contained in the taper portion of the sample plate 102 F. Further, the sample plate 102 F made from a conductive material has a function as an electrode.
- the sample plate 102 F is fixed on the base 104 C with screws.
- a groove is formed in an upper surface portion of the base 104 C, and a packing 106 is previously inserted in the groove for preventing leakage of liquid from a space between the sample plate 102 F and the base 104 C.
- FIG. 8 is a sectional view of the sixth sample vessel used for the electrophoresis analysis apparatus according to one embodiment of the present invention.
- the planar shape of a sample tray in which a plurality of the sample vessels are arranged is the same as that shown in FIG. 2, 4 or 5 .
- a sample tray 100 C in this embodiment includes an insulating sample plate 102 G, an insulating base 104 D, a packing 106 A made from silicon rubber, and a metal seat 109 .
- the sample plate 102 G has a taper portion functioning as a sample vessel. That is to say, a sample is contained in the taper portion of the sample plate 102 G.
- the sample plate 102 G is fixed on the base 104 D with screws.
- the metal seat 109 and the packing 106 A made from silicon rubber are held between the sample plate 102 G and the base 104 D.
- the metal seat 109 is brought in contact with a sample and functions as an electrode.
- the packing 106 A prevents leakage of liquid from a space between the sample plate 102 G and the base 104 D.
- FIG. 9 is a sectional view of the seventh sample vessel used for the electrophoresis analysis apparatus according to one embodiment of the present invention.
- the planar shape of a sample tray in which a plurality of the sample vessels are arranged is the same as that shown in FIG. 2, 4 or 5 .
- a sample tray 100 D in this embodiment includes an insulating sample plate 102 H, an insulating base 104 C, a packing 106 B made from silicon rubber, and a metal wire 109 A.
- the sample plate 102 H has a taper portion functioning as a sample vessel. That is to say, a sample is contained in the taper portion of the sample plate 102 H.
- the sample plate 102 H is fixed on the base 104 C with screws.
- the metal wire 109 A and the packing 106 B made from silicon rubber are held between the sample plate 102 H and the base 104 C.
- the metal wire 109 A is brought in contact with a sample and functions as an electrode.
- the packing 106 B prevents leakage of liquid from a space between the sample plate 102 H and the base 104 C.
- FIG. 10 is a plan view of an electrode portion of the eighth sample vessel used for the electrophoresis analysis apparatus according to one embodiment of the present invention.
- the planar shape of a sample tray in which a plurality of the sample vessels are arranged is the same as that shown in FIG. 2, 4 or 5 .
- the cross-sectional structure is also the same as that shown in, for example, in FIG. 8.
- a metal film is formed on an insulating base 104 C by vapor-deposition, and electrode patterns 109 B are formed by selective etching.
- the electrode patterns 109 B are connected to a high voltage power supply via a connector 110 .
- FIG. 11 is a plan view of an electrode portion of the ninth sample vessel used for the electrophoresis analysis apparatus according to one embodiment of the present invention.
- metal made projections 104 F 1 and 104 F 2 are integrally formed on a base 104 F made from a metal such as a stainless steel. Insulating rings 103 A and 103 B are inserted around the projections 104 F 1 and 104 F 2 respectively, to form sample vessels.
- the base 104 F functions as an electrode for each sample vessel.
- a conductive rubber or conductive organic material may be used in place of a metal.
- part of the sample tray is made from a conductive material; however, the entire sample tray may be made from a metal.
- the capillaries of the multi-capillary type can be easily inserted in the sample vessels only by moving the sample tray upward using a moving mechanism.
- the electrophoresis analysis can be automated using the electrophoresis analysis apparatus of the present invention.
Abstract
A multi-capillary type electrophoresis analysis apparatus has a sample tray for containing a plurality of samples, wherein part of the sample tray is made from a conductive material. Samples are introduced by applying a high voltage from a high voltage power supply between the sample tray and a coupler in a state in which one-ends of the capillaries are inserted in the samples contained in the sample tray. The apparatus eliminates the necessity of individually inserting electrodes in a plurality of samples contained in the sample tray, thereby making easy works for analysis.
Description
- The present invention relates to an electrophoresis analysis apparatus and a sample vessel used therefor, and particularly to an electrophoresis analysis apparatus suitably used for a DNA sequencer (DNA base sequence analyzer) for analyzing biochemical samples such as a DNA (Deoxyribonucleic acid) using a plurality of capillaries or micropassages as migration separation media, and a sample vessel used therefor.
- A DNA analysis technology based on electrophoresis, particularly, a DNA sequencer (DNA base sequence analyzer) has been widely available. With the raised need for analysis, the necessity of improving the analysis throughput has been increased. One method of increasing the analysis throughput is to integrate electrophoresis media.
- A thin gel layer formed between two flat glass plates has been conventionally used as electrophoresis separation media. On the other hand, a multi-capillary method using a plurality of capillaries each having a fine inside diameter has been proposed, for example, in Nature, Vol. 361 (1993), Kanbara, PP. 565-566, the specifications of U.S. Pat. Nos. 5,277,780, 5,366,608, and 5,274,240, Japanese Patent Laid-open No. Hei 5-72177, and PCT international publication for patent application No. Hei 7-503322. Such a method makes it possible to increase the degree of integration by making use of the fine inside diameters of the capillaries and to simultaneously analyze a large number of samples. In this method, further, since the cross section of migration passages becomes smaller than that of the conventional flat glass plates, a current caused by electrophoresis becomes smaller to thereby suppress generation of a Joule heat. As a result, by applying a higher electrophoresis voltage, a sample can be migrated at a higher speed. Accordingly, a number of samples can be simultaneously separated and analyzed at a high speed.
- As a second method, a multi-capillary method of making use of fine grooves formed in a surface portion of a glass plate as migration passages has been proposed, for example, in the specification of U.S. Pat. No. 5,192,412 and Japanese Patent Laid-open No. Hei 5-93711. Even in this method, a number of samples can be simultaneously separated and analyzed at a high speed.
- In the above-described multi-capillary method, one-ends of an electrode and a capillary are first inserted in a sample contained in a sample vessel, followed by applying a voltage across the capillary to electrically migrate the sample into the capillary; and then the one-ends of the electrode and the capillary are inserted in a buffer solution in a buffer bath, followed by applying a voltage across the capillary to separate the sample by electrophoresis.
- In the case where the number of samples to be simultaneously analyzed is several pieces, since the number of electrodes/capillaries is the same as that of the samples, it does not take a labor so much to insert the electrodes and capillaries in sample vessels and a buffer bath.
- However, in the case where several tens of samples are simultaneously analyzed to improve the analysis throughput, it is difficult to insert electrodes and capillaries in sample vessels and a buffer bath. To be more specific, the amount of a sample generally used for a DNA sequencer is merely 5 μl because it is difficult to prepare a large amount of a sample and also a reagent to be used is expensive. In the case where the sample in an amount of 5 μl is put in a sample vessel having an inner diameter of 2 mm, the liquid level becomes only about 1.5 mm. It is very difficult to individually insert several tens of electrodes and capillaries in the above small-sized sample vessels.
- An object of the present invention is to provide a multi-capillary type electrophoresis analysis apparatus capable of making easy works for analysis and a sample vessel used therefor.
- According to the present invention, there is provided an electrophoresis analysis apparatus having a plurality of migration passages and a detector for optically detecting a plurality of sample components separated by electrophoresis, including: a sample vessel for containing a plurality of samples to be introduced in the migration passages, at least part of a portion, of the sample vessel, to be in contact with these samples being made from a conductive material; wherein the samples are introduced in the migration passages by applying a voltage to the migration passages via the conductive material forming part of the sample vessels. With this configuration, since part of the sample vessel can be used as an electrode and thereby insertion of electrodes in samples can be eliminated, it is possible to make easy works for analysis.
- The sample vessel preferably includes a plate portion having a plurality of openings and a metal base portion fixed on a bottom portion of the plate portion.
- In the drawings:
- FIG. 1 is a perspective view showing the entire configuration of an electrophoresis analysis apparatus according to one embodiment of the present invention;
- FIG. 2 is a plan view of sample vessels used for the electrophoresis analysis apparatus according to one embodiment of the present invention;
- FIG. 3 is a sectional view taken on line A-A of FIG. 2;
- FIG. 4 is a plan view of second sample vessels used for the electrophoresis analysis apparatus according to one embodiment of the present invention;
- FIG. 5 is a sectional view of third sample vessels used for the electrophoresis analysis apparatus according to one embodiment of the present invention;
- FIG. 6 is a sectional view of a fourth sample vessel used for the electrophoresis analysis apparatus according to one embodiment of the present invention;
- FIG. 7 is a sectional view of a fifth sample vessel used for the electrophoresis analysis apparatus according to one embodiment of the present invention;
- FIG. 8 is a sectional view of a sixth sample vessel used for the electrophoresis analysis apparatus according to one embodiment of the present invention;
- FIG. 9 is a sectional view of a seventh sample vessel used for the electrophoresis analysis apparatus according to one embodiment of the present invention;
- FIG. 10 is a plan view of an electrode portion of eighth sample vessels used for the electrophoresis analysis apparatus according to one embodiment of the present invention; and
- FIG. 11 is a plan view of an electrode portion of ninth sample vessels used for the electrophoresis analysis apparatus according to one embodiment of the present invention.
- Hereinafter, preferred embodiments in which the present invention is applied to an electrophoresis analysis apparatus and sample vessels used therefor will be described with reference to FIGS.1 to 11.
- Referring first to FIG. 1, there will be described the entire configuration of the electrophoresis analysis apparatus according to one embodiment of the present invention.
- FIG. 1 is a perspective view showing the entire configuration of the electrophoresis analysis apparatus according to the embodiment of the present invention.
- First, the entire configuration will be described below.
- A
migration buffer bath 12 containing a buffer (electrolyte) is disposed on amoving mechanism 10. Aplatinum electrode 13 is stretchingly mounted in themigration buffer bath 12 in such a manner as to be in contact with the buffer. On themoving mechanism 10 are also disposed threesample trays sample tray holder 14. As will be described later with reference to FIG. 2, thesample tray 100A includes 48 pieces of sample vessels. Thesample tray 100A is removably fixed on thesample tray holder 14 with set screws S1 and S2. The bottom portion of thesample tray 100A is made from a conductive metal such as a stainless steel, and is electrically conductive to thesample tray holder 14 which is made from a conductive metal such as a stainless steel. Similarly, each of thesample trays sample tray holder 14. - The
moving mechanism 10 is vertically movable in the Z-axis direction alongvertical slide guides 18Z using a vertically movingmotor 16Z. Themoving mechanism 10 is also longitudinally movable in the X-axis direction along longitudinal slide guides 18×using a longitudinally movingmotor 16X. Themotors controller 80. Atransparent cover 19 made from polyvinyl chloride or polyacrylate or polymethacrylate resin is disposed in such a manner as to cover the threesample trays - The electrophoresis analysis apparatus includes 48 pieces of
capillaries 20 disposed in parallel, each of which is filled with a gel matrix for separation. The lower end sides of thecapillaries 20 are fixed bycapillary retaining plate 22, and the lower ends of thecapillaries 20 are inserted in the buffer in themigration buffer bath 12. The upper end sides of thecapillaries 20 are fixed by acapillary retaining plate 24, and the upper ends of thecapillaries 20 are fixedly connected to acoupler 26. - The
coupler 26 is connected to anelectrode plug 32 on the earth side, and theelectrode plug 32 is in turn connected to an earth electrode of a highvoltage power supply 30. Thesample tray holder 14 is connected to anelectrode plug 34 on the high voltage side, and theplatinum electrode 13 in thebuffer bath 12 is connected to anelectrode plug 36 on the high voltage side. Theelectrode plugs voltage power supply 30. - The
coupler 26 is connected to asheath flow cell 40, into which asheath liquid 44 held in a sheathliquid tank 42 is introduced by the gravity. Samples, which are separated by migration in thecapillaries 20 and flow out of migration terminals of thecapillaries 20, are carried to the upper side with the sample components in the capillaries left as separated. - Laser light emitted from a
laser 50 is collimated into parallel light beams by alens 52, and thesheath flow cell 40 is irradiated with the laser beams from its side surface (in the Y-direction in the drawing), to excite the separated sample in thesheath flow cell 40. Ashutter 54 is provided between thelaser 50 and thelens 52 for selectively exciting the sample. Fluorescent light generated by laser irradiation is taken out along the X-axis direction perpendicular to the Y-axis direction, and converged through acondenser lens 62. Then, a light component having a specific wavelength to be detected is selected from the fluorescent light by afilter 64 and is focused through an image-forminglens 66 at anoptical sensor 68 such as a two-dimensional CCD sensor. A signal detected by theoptical sensor 68 is fed to asignal processor 70, being processed to identify the kind of the terminal base on the basis of the wavelength of the fluorescent light, and the base sequence of the nucleic acid sample is analyzed on the basis of the measured signal. - In determination of the base sequence of a DNA (Deoxyribonucleic Acid), measurement is generally performed for four kinds of wavelengths. Fluorescent dyes are previously combined in the reaction operation so that each maximum wavelength corresponds to the kind of a terminal base of a DNA fragment.
- A
drain adaptor 46 is mounted on the upper end of thesheath flow cell 40. The sample, which has flowed from the capillary 20 into thesheath flow cell 40, is discharged as a wastage into adrain bottle 49 through adrain tube 47. In the course of thedrain tube 47 is provided a flow controller composed of an orifice and a plurality of capillaries for controlling the flow rate of the sample by making constant the passage resistance of thedrain tube 47. - The entire operation of the electrophoresis analysis apparatus in this embodiment will be described below.
- Samples to be analyzed are previously poured in specific amounts into 48 pieces of the sample vessels of each of the
sample trays sample trays sample tray holder 14 with the set screws S1 and S2. Thecontroller 80 drives the vertically movingmotor 16Z to move down the movingmechanism 10 in the Z1 direction. The downward movement of the movingmechanism 10 is stopped at a position where the lower ends of thecapillaries 20 are sufficiently separated from thebuffer bath 12. Then, thecontroller 80 drives thelongitudinally moving motor 16X to move the movingmechanism 10 in the X1 direction. The movement of the movingmechanism 10 is stopped at a position where thesample tray 100A is located directly under thecapillaries 20. Thecontroller 80 also drives the vertically movingmotor 16Z to move up the movingmechanism 10 in the Z2 direction. The upward movement of the movingmechanism 10 is stopped at a position where the leading ends of thecapillaries 20 are to be inserted in the samples in the sample vessels of thesample tray 100A. The positioning in the vertical movement and the longitudinal movement of the movingmechanism 10 is performed by a position detecting mechanism such as a switch provided in the movingmechanism 10. - By applying a high voltage from the high
voltage power supply 30 between thesample tray 100A and thecoupler 26 in a state in which the lower ends of thecapillaries 20 are inserted in the samples, the samples in the sample vessels are introduced into thecapillaries 20. - The
controller 80 drives the vertically movingmotor 16Z to move down the movingmechanism 10 in the Z1 direction. The downward movement of the movingmechanism 10 is stopped at a position where the lower ends of thecapillaries 20 are sufficiently separated from thesample trays 100A. Then, thecontroller 80 drives thelongitudinally moving motor 16X to move the movingmechanism 10 in the X2 direction. The movement of the movingmechanism 10 is stopped at a position where thebuffer bath 12 is located directly under thecapillaries 20. Thecontroller 80 also drives the vertically movingmotor 16Z to move up the movingmechanism 10 in the Z2 direction. The upward movement of the movingmechanism 10 is stopped at a position where the leading ends of thecapillaries 20 are inserted in the buffer in thebuffer bath 12. The positioning in the vertical movement and the longitudinal movement of the movingmechanism 10 is performed using a position detecting mechanism such as a switch provided in the movingmechanism 10. - By applying a high voltage from the high
voltage power supply 30 between theplatinum electrode 13 and thecoupler 26 in a state in which the lower ends of thecapillaries 20 are inserted in the buffer, the samples introduced in thecapillaries 20 are separated by electrophoresis. - After the analysis of the samples in the
sample tray 100A is completed, the samples in thesample trays capillaries 20 in the same procedure as described above, to be thus separated by electrophoresis. - It takes about two hours to analyze one sample, and therefore, by provision of the three
sample trays sample tray holder 14 as shown in FIG. 1, it becomes possible to carry out automatic analysis for about six hours. The number of the sample trays is not limited to three pieces but may be four pieces or more. - The method of optically detecting the sample separated by electrophoresis is not limited to fluorescent light detection but may be absorbance detection.
- The configuration of a sample vessel used in the electrophoresis analysis apparatus of the present invention will be described with reference to FIGS. 2 and 3.
- FIG. 2 is a plan view of sample vessels used for the electrophoresis analysis apparatus according to one embodiment of the present invention, and FIG. 3 is a sectional view taken on line A-A of FIG. 2.
- A
sample tray 100 is formed into a rectangular shape in a plan view, in which 48 pieces of circular sample vessels 100-1, 100-2, . . . , 100-48 are aligned. Thesample tray 100 includes anupper sample plate 102 and ametal base 104 fixed on the backface of thesample plate 102. Thesample plate 102 is made from a transparent polyacrylate or polymethacrylate resin, and has 48 pieces of circular openings for forming the sample vessels 100-1, 100-2, . . . , 100-48. Thesample plate 102 may be made from a transparent plastic material such as polyvinyl chloride or polycarbonate. Since thesample plate 102 is made from a transparent material, it is possible to easily, visually confirm samples contained in the sample vessels 100-1, 100-2, . . . , 100-48 and the states of the capillaries inserted in the samples. - The
sample plate 102 is fixed on themetal base 104 with eight screws. Themetal base 104 is made from a stainless steel as a conductive material. Themetal base 104 forms part of wall surfaces of the sample vessels 100-1, 100-2, . . . , 100-48, and is used as an electrode common to samples contained in the sample vessels 100-1, . . . , 100-2, 100-48. Since themetal base 104 forms part of the sample vessels, it is possible to eliminate the necessity of inserting electrodes in the samples as in the conventional apparatus. It is experimentally confirmed that themetal base 104 made from even a stainless steel which is a widely available material exhibits a sufficient durability. The electrophoresis analysis apparatus using themetal base 104 made from a stainless steel is allowed to be continuously used for a period of sixth months or more only by periodically washing thesample tray 100. The conventional electrophoresis analysis apparatus is expensive because of use of a noble metal such platinum as an electrode material; however, in the electrophoresis analysis apparatus of the present invention, the use of a stainless steel as an electrode material advantageously reduces the cost of the sample vessels. - Both end portions of the
metal base 104 havecircular holes 104A, and as described with reference to shown in FIG. 1, thesample tray 100 is fixed on the metal made sample tray holder with the set screws passing through thecircular holes 104A. - The means for fixing the
sample tray 100 on the sample tray holder is not limited to the set screws but may be plate springs or the like. - In place of the
metal base 104, there may be used an insulating substrate on which a metal foil is stuck or a metal film is formed by vapor-deposition or sputtering. At this time, the metal foil or metal film forms part of the wall surfaces of the sample vessels, and it functions as a common electrode when it is made electrically conductive to the samples contained in the sample vessels. - As will be described later, a packing is inserted between the
sample plate 102 and themetal base 104 for preventing leakage of samples in the sample vessels. - A length L1 of the
sample plate 102 is set at 160 mm. A distance L2 from the center of the sample vessel 100-1 formed in thesample plate 102 to the center of the sample vessel 100-48 formed in thesample plate 102 is set at 141 mm. That is to say, a pitch P between the adjacent sample vessels is set at 3 mm. While the cross-sectional shape of the sample vessel will be described with reference to FIG. 3, an opening diameter of the uppermost portion of the sample vessel is set at φ 2.8 mm. - The pitch P between the adjacent sample vessels is set at a value obtained by dividing a pitch (9 mm) between adjacent holes formed in a microtiter plate by an integer number. The microtiter plate is generally used for preparation of samples. The pitch between adjacent pipets used for pipetting samples from the microtiter plate is equal to the pitch between the adjacent holes of the microtiter plate. If the pitch P between the adjacent sample vessels is, as described above, set at the value obtained by dividing the pitch (9 mm) between the adjacent holes of the microtiter plate by an integer number (for example 3 as shown in FIG. 2), that is, if the pitch P between the adjacent sample vessels is set at 3 mm, the samples can be pipetted from the microtiter plate into the sample vessels using the existing pipets. To be more specific, at the first pipetting, samples are poured in every fourth sample vessel, that is, in the order of the sample vessels100-1, 100-4, . . . , 100-46. At the second pipetting, after the pipets are shifted only 3 mm, samples are poured in every fourth sample vessel, that is, in the order of the sample vessels 100-2, 100-5, . . . , 100-47. At the third pipetting, after the pipets are shifted only 3 mm, samples are poured in every fourth sample vessel, that is, in the order of the sample vessels 100-3, 100-6, . . . , 100-48. In this way, while the pipetting of the samples is divided into three times, the samples can be poured in the sample vessels using the existing pipets.
- The pitch P between the adjacent sample vessels, which is set at the value obtained by dividing the pitch (9 mm) between the adjacent holes of the microtiter plate, may be generally in a range of ½ to ¼ of the pitch (9 mm) between the adjacent holes of the microtiter plate in consideration of the poured amount of the sample and the dimension of the sample vessel.
- The cross-sectional structure of the
sample tray 100 will be described with reference to FIG. 3 which is an enlarged sectional view taken on line A-A of FIG. 2. - The
sample plate 102 is fixed on themetal base 104 with the set screws as described with reference to FIG. 2. A groove is formed in the lower surface portion of thesample plate 102, and a packing 106 is previously inserted in the groove for preventing leakage of liquid from a space between thesample plate 102 and themetal base 104. The packing 106 is made from silicon rubber. - The cross-section of the
sample plate 102 has a steppedportion 102B, ataper portion 102C, and acylindrical portion 102D. The steppedportion 102B is formed into an elliptic shape as shown in FIG. 2, and it has a width W of 6 mm. When a height H of thesample plate 102 is 7 mm, a height H1 of the steppedportion 102B is 1.5 mm. - The
taper portion 102C is formed into a cone shape having a taper angle θ of 24.4°. An opening diameter R1 of thetaper portion 102C on the upper end side is φ 2.8 mm, and an opening diameter R2 of thetaper portion 102C on the lower end side is φ 1.2 mm. Thetaper portion 102C allows easy insertion of a pipet or capillary in the sample vessel, and specifically, thetaper portion 102C allows the leading end of the pipet or capillary to be easily bottomed. A height H2 of thetaper portion 102C is set at 3.7 mm. - The
cylindrical portion 102D has an opening diameter R2 of φ 1.2 mm and a height H3 of 1 mm. Assuming that the poured amount of a sample is 5 μl, the sample is contained substantially in thecylindrical portion 102D. - On the other hand, each
metal pin 108 is previously press-fitted in themetal base 104. The number of the metal pins 108 is the same as that of the sample vessels, that is, 48 pieces in this embodiment. Themetal pin 108 is made from the same material as that of themetal base 104, that is, a stainless steel. The leading end of themetal pin 108 has a projectingportion 108A having a diameter R3 of φ 0.8 mm. In a state in which thesample plate 102 is fixed on themetal base 104, the projectingportion 108A of themetal pin 108 slightly projects into thecylindrical portion 102D of thesample plate 102. With this configuration, the sample is certainly brought in electric-contact with themetal pin 108 and themetal base 104 used as an electrode. - In general, bubbles caused when a sample is poured in the sample vessel using a pipet possibly adhere on a wall surface of the sample vessel. If the bubbles adhere on the lowermost portion of the sample vessel and the capillary is inserted in the bubbles, the sample cannot be introduced into the capillary. To cope with such an inconvenience, the projecting
portion 108A is provided in such a manner as to project into thecylindrical portion 102D. In this case, even if bubbles adhere on the bottom of the sample vessel, since the capillary is only inserted to the leading end of the projectingportion 108A, the sample can be introduced into the capillary by reducing the effect of the bubbles. - The opening diameter R1 of the upper end of the
taper portion 102C which forms part of the sample vessel is set at φ 7 mm or less depending on the poured amount of a sample. In particular, if the poured amount of a sample is small, the opening diameter R1 is set at φ 3 mm or less, for example, φ 2.8 mm as described above. If the poured amount of a sample is smaller than that described above, the opening diameter R1 may be set atφ 2 mm or less. - As described above, while the
sample tray 100 has a large number (48 pieces) of the sample vessels, since the conductive metal base and metal pins form part of the sample vessels and are taken as a common electrode, the necessity of inserting electrodes in the sample vessels as in the conventional apparatus can be eliminated. As a result, since only the capillaries may be inserted in the sample vessels, the preparation for analysis can be facilitated. - As described with reference to FIG. 1, since 48 pieces of the capillaries arranged in parallel are fixed in position by the
capillary retaining plate 22, the capillaries of the multi-capillary type can be easily inserted in the sample vessels only by moving thesample tray 100 upward using the movingmechanism 10. As a result, the electrophoresis analysis can be automated using the electrophoresis analysis apparatus having the configuration shown in FIG. 1. - The configuration of a second sample vessel used for the electrophoresis analysis apparatus of the present invention will be described with reference to FIG. 4.
- FIG. 4 is a plan view of the second sample vessels used for the electrophoresis analysis apparatus according to one embodiment of the present invention.
- A
sample tray 100′ in this embodiment is different from thesample tray 100 shown in FIG. 2 in that sample vessels 100-1, 100-2, . . . , 100-48 are arranged in a staggered pattern. The cross-sectional shape of the sample vessel is the same as described with reference to FIG. 3. - The
sample tray 100′ has a rectangular shape in a plan view, in which 48 pieces of the circular sample vessels 100-1, 100-2, . . . , 100-48 are arranged in a staggered pattern. Thesample tray 100′ has anupper sample plate 102′ and ametal base 104 fixed on the backface of thesample plate 102′. Thesample plate 102′ is made from a transparent acrylic resin, and has 48 pieces of circular openings for forming the sample vessels 100-1, 100-2, . . . , 100-48. - The
sample plate 102′ is fixed on themetal base 104 with eight screws. Themetal base 104 is made from a stainless steel as a conductive material. Themetal base 104 forms part of wall surfaces of the sample vessels 100-1, 100-2, . . . , 100-48, and is used as an electrode common to samples contained in the sample vessels 100-1, . . . , 100-2, 100-48. Since the metal base forms part of the sample vessels, it is possible to eliminate the necessity of inserting electrodes in samples as in the conventional apparatus. - Both end portions of the
metal base 104 havecircular holes 104A. As described with reference to FIG. 1, thesample tray 100′ is fixed on a metal made sample tray holder with set screws. - As described with reference to FIG. 3, a packing is inserted between the
sample plate 102′ and themetal base 104 for preventing leakage of samples in the sample vessels. - A length L3 of the
sample plate 102′ is set at 128 mm. A distance L4 from the center of the sample vessel 100-1 formed in thesample plate 102′ to the center of the sample vessel 100-48 formed in thesample plate 102′ is set at 106 mm. A pitch P between the adjacent sample vessels is set at 3 mm. - By arranging the sample vessels in the
sample tray 100′ in the staggered pattern, the length of thesample tray 100′ can be shortened, to thereby miniaturize the electrophoresis analysis apparatus, particularly, the moving mechanism. - The configuration of a third sample vessel used for the electrophoresis analysis apparatus of the present invention will be described with reference to FIG. 5.
- FIG. 5 is a plan view of the third sample vessels used for the electrophoresis analysis apparatus according to one embodiment of the present invention.
- A
sample tray 100″ in this embodiment is different from thesample tray - The
sample tray 100″ has a rectangular shape in a plan view, in which 4 n pieces of the circular sample vessels 100-11, 100-12, . . . , 100-21, . . . , 100-31, . . . , 100-41, . . . , 100-4 n are arranged in a matrix pattern of four rows (n pieces for each row). Thesample tray 100″ has anupper sample plate 102″ and ametal base 104 fixed on the backface of thesample plate 102″. Thesample plate 102″ is made from a transparent acrylic resin, and has 4 n pieces of circular openings for forming the sample vessels 100-11, . . . , 100-4 n. - The
sample plate 102″ is fixed on themetal base 104 with screws. Themetal base 104 is made from a stainless steel as a conductive material. Themetal base 104 forms part of wall surfaces of the sample vessels 100-11, 100-4 n, and is used as an electrode common to samples contained in the sample vessels 100-11, . . . , 100-4 n. Since the metal base forms part of the sample vessels, it is possible to eliminate the necessity of inserting electrodes in samples as in the conventional apparatus. - The
sample tray 100″ is fixed on a metal made sample tray holder with set screws. As described with reference to FIG. 3, a packing is inserted between thesample plate 102″ and themetal base 104 for preventing leakage of samples in the sample vessels. A pitch P between the adjacent sample vessels is set at a value obtained by dividing a pitch (9 mm) between adjacent holes of the microtiter plate by an integer number. - By arranging a plurality of rows of the sample vessels in the
sample tray 100″, the length of thesample tray 100″ can be shortened, to thereby miniaturize the electrophoresis analysis apparatus, particularly, the moving mechanism. - The cross-sectional structure of a fourth sample vessel used for the electrophoresis analysis apparatus of the present invention will be described with reference to FIG. 6.
- FIG. 6 is a sectional view of the fourth sample vessel used for the electrophoresis analysis apparatus according to one embodiment of the present invention. In addition, the planar shape of a sample tray in which a plurality of the sample vessels are arranged is the same as that shown in FIG. 2, 4 or5.
- A
sample tray 100A in this embodiment includes asample plate 102E composed of a transparent plate made from an acrylic resin, an insulatingbase 104B, a packing 106 made from silicon rubber, andmetal pins 108 made from a conductive material such as a stainless steel. Thesample plate 102E has a taper portion functioning as a sample vessel. That is to say, a sample is contained in the taper portion of thesample plate 102E. Themetal pin 108 is brought in electric-contact with a sample and functions as an electrode. Since a plurality of the sample vessels are formed in thesample tray 100A, the metal pins 108 of the same number as that of the sample vessels are provided in such a manner as to be electrically connected to the metal made sample tray holder shown in FIG. 1. - The
sample plate 102E is fixed on abase 104B with screws. A groove is formed in a lower surface portion of thesample plate 102E, and a packing 106 is previously inserted in the groove for preventing leakage of liquid from a space between thesample plate 102E and thebase 104B. - By independently connecting a plurality of the metal pins108 to a high voltage power supply and also connecting a current detection circuit between each metal pin and the high voltage power supply, it is possible to monitor a current for each sample.
- The cross-sectional structure of a fifth sample vessel used for the electrophoresis analysis apparatus of the present invention will be described with reference to FIG. 7.
- FIG. 7 is a sectional view of the fifth sample vessel used for the electrophoresis analysis apparatus according to one embodiment of the present invention. In addition, the planar shape of a sample tray in which a plurality of the sample vessels are arranged is the same as that shown in FIG. 2, 4 or5.
- A
sample tray 100B in this embodiment includes a metal madesample plate 102F, an insulatingbase 104C, and a packing 106 made from silicon rubber. Thesample plate 102F is formed with a taper portion functioning as a sample vessel. That is to say, a sample is contained in the taper portion of thesample plate 102F. Further, thesample plate 102F made from a conductive material has a function as an electrode. - The
sample plate 102F is fixed on thebase 104C with screws. A groove is formed in an upper surface portion of thebase 104C, and a packing 106 is previously inserted in the groove for preventing leakage of liquid from a space between thesample plate 102F and thebase 104C. - The cross-sectional structure of a sixth sample vessel used for the electrophoresis analysis apparatus of the present invention will be described with reference to FIG. 8.
- FIG. 8 is a sectional view of the sixth sample vessel used for the electrophoresis analysis apparatus according to one embodiment of the present invention. In addition, the planar shape of a sample tray in which a plurality of the sample vessels are arranged is the same as that shown in FIG. 2, 4 or5.
- A
sample tray 100C in this embodiment includes an insulatingsample plate 102G, an insulatingbase 104D, apacking 106A made from silicon rubber, and ametal seat 109. Thesample plate 102G has a taper portion functioning as a sample vessel. That is to say, a sample is contained in the taper portion of thesample plate 102G. - The
sample plate 102G is fixed on thebase 104D with screws. Themetal seat 109 and thepacking 106A made from silicon rubber are held between thesample plate 102G and thebase 104D. Themetal seat 109 is brought in contact with a sample and functions as an electrode. The packing 106A prevents leakage of liquid from a space between thesample plate 102G and thebase 104D. - The cross-sectional structure of a seventh sample vessel used for the electrophoresis analysis apparatus of the present invention will be described with reference to FIG. 9.
- FIG. 9 is a sectional view of the seventh sample vessel used for the electrophoresis analysis apparatus according to one embodiment of the present invention. In addition, the planar shape of a sample tray in which a plurality of the sample vessels are arranged is the same as that shown in FIG. 2, 4 or5.
- A
sample tray 100D in this embodiment includes an insulatingsample plate 102H, an insulatingbase 104C, apacking 106B made from silicon rubber, and ametal wire 109A. Thesample plate 102H has a taper portion functioning as a sample vessel. That is to say, a sample is contained in the taper portion of thesample plate 102H. - The
sample plate 102H is fixed on thebase 104C with screws. Themetal wire 109A and thepacking 106B made from silicon rubber are held between thesample plate 102H and thebase 104C. Themetal wire 109A is brought in contact with a sample and functions as an electrode. The packing 106B prevents leakage of liquid from a space between thesample plate 102H and thebase 104C. - The structure of an electrode portion of an eighth sample vessel used for the electrophoresis analysis apparatus of the present invention will be described with reference to FIG. 10.
- FIG. 10 is a plan view of an electrode portion of the eighth sample vessel used for the electrophoresis analysis apparatus according to one embodiment of the present invention. In addition, the planar shape of a sample tray in which a plurality of the sample vessels are arranged is the same as that shown in FIG. 2, 4 or5. The cross-sectional structure is also the same as that shown in, for example, in FIG. 8.
- In this embodiment, a metal film is formed on an
insulating base 104C by vapor-deposition, andelectrode patterns 109B are formed by selective etching. Theelectrode patterns 109B are connected to a high voltage power supply via aconnector 110. - The structure of a ninth sample vessel used for the electrophoresis analysis apparatus of the present invention will be described with reference to FIG. 11.
- FIG. 11 is a plan view of an electrode portion of the ninth sample vessel used for the electrophoresis analysis apparatus according to one embodiment of the present invention.
- In this embodiment, metal made projections104F1 and 104F2 are integrally formed on a
base 104F made from a metal such as a stainless steel. Insulatingrings - The
base 104F functions as an electrode for each sample vessel. - As the conductive material forming part of the sample vessel, a conductive rubber or conductive organic material may be used in place of a metal.
- In the above description, part of the sample tray is made from a conductive material; however, the entire sample tray may be made from a metal.
- As described above, according to this embodiment, since part of a plurality of the sample vessels provided on a sample tray are made from a conductive material and are taken as a common electrode, the necessity of inserting electrodes in the sample vessels as in the conventional apparatus can be eliminated. As a result, since only the capillaries may be inserted in the sample vessels, the preparation for analysis can be facilitated.
- By arranging a plurality of the capillaries in parallel and fixing them in position by a capillary retaining plate, the capillaries of the multi-capillary type can be easily inserted in the sample vessels only by moving the sample tray upward using a moving mechanism. As a result, the electrophoresis analysis can be automated using the electrophoresis analysis apparatus of the present invention.
- While the preferred embodiments have been described using specific terms, such description is for illustrative purposes only, and it is understood that many changes and variations may be made without departing from the spirit or scope of the following claims.
Claims (16)
1. An electrophoresis analysis apparatus comprising:
a plurality of migration passages;
a sample tray holder capable of removably fixing a sample tray including a plurality of sample vessels for containing samples;
a detector for optically detecting sample components separated by electrophoresis;
a power supply for applying a voltage to the migration passages,
wherein said sample tray comprises an electrode capable of contacting the sample in at least one of said plurality of sample vessels;
wherein a part of the sample tray holder is electrically connected to the power supply; and
wherein said part of the sample tray holder is electrically connected to said electrode in response to fixing the sample tray on the sample tray holder.
2. An electrophoresis analysis apparatus according to claim 1 , wherein the part of the sample vessel is transparent.
3. An electrophoresis analysis apparatus according to claim 1 , wherein the electrode is made of a stainless steel.
4. An electrophoresis analysis apparatus according to claim 1 , and further comprising a current detection circuit to monitor a current for each sample.
5. An electrophoresis analysis apparatus according to claim 1 , wherein the sample tray comprises a plate portion having a plurality of openings and a metal base portion fixed on a bottom portion of the plate portion.
6. An electrophoresis analysis apparatus according to claim 5 , wherein the sample tray further comprises metal pins fixed on the metal base portion, the metal pins having portions projecting in the openings of the plate portion.
7. An electrophoresis analysis apparatus according to claim 1 , wherein the sample tray comprises a metal plate portion having a plurality of openings and a base portion fixed on a bottom portion of the plate portion.
8. An electrophoresis analysis apparatus according to claim 1 , wherein the sample tray comprises a plate portion having a plurality of openings; a base portion fixed on a bottom portion of the plate portion; and a plate or wire made of conductive material, the plate or wire being in contact with samples.
9. An electrophoresis analysis apparatus comprising:
a migration passage;
a sample tray holder capable of removably fixing a sample tray including a sample vessel for containing a sample;
a detector for optically detecting sample components separated by electrophoresis;
a power supply for applying a voltage to the migration passage,
wherein said sample tray comprises an electrode capable of contacting the sample in said sample vessel;
wherein a part of the sample tray holder is electrically connected to the power supply; and
wherein said part of the sample tray holder is electrically connected to said electrode in response to fixing the sample tray on the sample tray holder.
10. An electrophoresis analysis apparatus according to claim 9 , wherein the part of the sample vessel is transparent.
11. An electrophoresis analysis apparatus according to claim 9 , wherein the electrode is made of a stainless steel.
12. An electrophoresis analysis apparatus according to claim 9 , and further comprising a current detection circuit to monitor a current for a sample.
13. An electrophoresis analysis apparatus according to claim 9 , wherein the sample tray comprises a plate portion comprising an opening and a metal base portion fixed on a bottom portion of the plate portion.
14. An electrophoresis analysis apparatus according to claim 13 , wherein the sample tray further comprises a metal pin fixed on the metal base portion, the metal pin comprising a portion projecting in the opening of the plate portion.
15. An electrophoresis analysis apparatus according to claim 9 , wherein the sample tray comprises a metal plate portion comprising an opening and a base portion fixed on a bottom portion of the plate portion.
16. An electrophoresis analysis apparatus according to claim 9 , wherein the sample tray comprises a plate portion comprising an opening; a base portion fixed on a bottom portion of the plate portion; and a plate or wire made of conductive material, the plate or wire being in contact with sample.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/786,053 US20040163962A1 (en) | 1997-08-26 | 2004-02-26 | Electrophoresis analysis apparatus and sample vessel used therefor |
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP22908097A JP3481828B2 (en) | 1997-08-26 | 1997-08-26 | Electrophoresis analyzer, electrophoresis analysis method, and sample container used therefor |
JP9-229080 | 1997-08-26 | ||
US09/132,323 US6325908B1 (en) | 1997-08-26 | 1998-08-11 | Electrophoresis analysis apparatus and sample vessel used therefor |
US09/852,269 US6740219B2 (en) | 1997-08-26 | 2001-05-10 | Electrophoresis analysis apparatus and sample vessel used therefor |
US10/786,053 US20040163962A1 (en) | 1997-08-26 | 2004-02-26 | Electrophoresis analysis apparatus and sample vessel used therefor |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/852,269 Continuation US6740219B2 (en) | 1997-08-26 | 2001-05-10 | Electrophoresis analysis apparatus and sample vessel used therefor |
Publications (1)
Publication Number | Publication Date |
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US20040163962A1 true US20040163962A1 (en) | 2004-08-26 |
Family
ID=16886443
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/132,323 Expired - Lifetime US6325908B1 (en) | 1997-08-26 | 1998-08-11 | Electrophoresis analysis apparatus and sample vessel used therefor |
US09/852,269 Expired - Fee Related US6740219B2 (en) | 1997-08-26 | 2001-05-10 | Electrophoresis analysis apparatus and sample vessel used therefor |
US10/786,053 Abandoned US20040163962A1 (en) | 1997-08-26 | 2004-02-26 | Electrophoresis analysis apparatus and sample vessel used therefor |
Family Applications Before (2)
Application Number | Title | Priority Date | Filing Date |
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US09/132,323 Expired - Lifetime US6325908B1 (en) | 1997-08-26 | 1998-08-11 | Electrophoresis analysis apparatus and sample vessel used therefor |
US09/852,269 Expired - Fee Related US6740219B2 (en) | 1997-08-26 | 2001-05-10 | Electrophoresis analysis apparatus and sample vessel used therefor |
Country Status (2)
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US (3) | US6325908B1 (en) |
JP (1) | JP3481828B2 (en) |
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US9733234B2 (en) | 2002-03-11 | 2017-08-15 | Jp Scientific Limited | Probe for extraction of molecules of interest from a sample |
US8598325B2 (en) | 2002-03-11 | 2013-12-03 | Janusz B. Pawliszyn | Solid-phase microextraction coatings and methods for their preparation |
US7232689B2 (en) | 2002-03-11 | 2007-06-19 | Pawliszyn Janusz B | Calibration procedure for investigating biological systems |
US6833919B2 (en) * | 2002-10-11 | 2004-12-21 | Combisep | Multiplexed, absorbance-based capillary electrophoresis system and method |
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US20080166805A1 (en) | 2005-06-08 | 2008-07-10 | The Regents Of The University Of California | Culturing human cells and tissues in an N-glycolylneuraminic acid-free environment |
US8828209B2 (en) | 2005-06-22 | 2014-09-09 | The Research Foundation For The State University Of New York | Massively parallel 2-dimensional capillary electrophoresis |
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Also Published As
Publication number | Publication date |
---|---|
JP3481828B2 (en) | 2003-12-22 |
US6740219B2 (en) | 2004-05-25 |
JPH1164277A (en) | 1999-03-05 |
US20010027919A1 (en) | 2001-10-11 |
US6325908B1 (en) | 2001-12-04 |
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STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |