Source: https://patents.google.com/patent/US6383356B1/en
Timestamp: 2019-09-19 23:45:41
Document Index: 241607532

Matched Legal Cases: ['art 9', 'art 9', 'art 1', 'art 45', 'art 1', 'art 9', 'art 9', 'art 9', 'art 9', 'art 9', 'art 45', 'art 9', 'art 9', 'art 9', 'art 9', 'art 49', 'art 49', 'art 49']

US6383356B1 - Capillary electrophoretic apparatus - Google Patents
US6383356B1
US6383356B1 US09/448,139 US44813999A US6383356B1 US 6383356 B1 US6383356 B1 US 6383356B1 US 44813999 A US44813999 A US 44813999A US 6383356 B1 US6383356 B1 US 6383356B1
US09/448,139
1998-11-30 Priority to JP10-338898 priority
1999-11-24 Application filed by Japan Science and Technology Agency filed Critical Japan Science and Technology Agency
2000-02-15 Assigned to SHIMADZU CORPORATION, INSTITUTE OF PHYSICAL AND CHEMICAL RESEARCH, THE reassignment SHIMADZU CORPORATION ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: HAYASHIZAKI, YOSHIHIDE, NAKAMURA, SHIN
2001-08-09 Assigned to JAPAN SCIENCE AND TECHNOLOGY CORPORATION reassignment JAPAN SCIENCE AND TECHNOLOGY CORPORATION ASSIGNMENT OF ONE THIRD INTEREST (SEE DOCUMENTS FOR DETAILS) Assignors: INSTITUTE OF PHYSICAL AND CHEMICAL RESEARCH, THE, SHIMADZU CORPORATION
2002-05-07 Publication of US6383356B1 publication Critical patent/US6383356B1/en
A drain joint of a pump block is opened, a piston (19 a) is pushed while a piston (13 a) is fixed, for charging a passage between a Luer-Lok joint (17) and an intersection part as well as a passage between the intersection part and the drain joint with a buffer. Thereafter the piston (13 a) is pushed while the piston (19 a) is fixed, to charge a passage (7 a) with a polymer. Then, the drain joint is closed, the piston (13 a) is pushed and the piston (19 a) is pulled in response to the amount of pushing, for charging the passage between the intersection point and the Luer-Lok joint (17) with the polymer. Thereafter, the piston (13 a) is pushed while the piston (19 a) is fixed, to charge a capillary column with the polymer.
In the capillary electrophoretic apparatus according to this aspect, after the drain port is opened, a piston of the buffer syringe is pushed while a piston of the polymer syringe is fixed, thereby air in the passage between the buffer syringe and the drain port is discharged through the drain port and the passage is charged with the buffer. Then, the piston of the buffer syringe is fixed and the piston of the polymer syringe is pushed while the drain port is kept open, thereby the buffer in the passage between the polymer syringe and the drain port is discharged through the drain port, and the passage is charged with the polymer. After the drain port is sealed, the piston of the polymer syringe is pushed and the piston of the buffer syringe is pulled in response to the amount of pushing, thereby the passage between the polymer syringe and the buffer syringe is charged with the polymer. Thereafter, the piston of the polymer syringe is pushed while the buffer syringe is fixed, thereby the passage between the polymer syringe and the capillary column as well as the capillary column are charged with the polymer.
FIG. 3 is a schematic front elevation view showing an exemplary syringe piston driving linear actuator of the embodiment; and
FIG. 4 is a schematic front elevation view showing another embodiment of the present invention.
FIG. 1 is a schematic front elevation view showing a capillary electrophoretic apparatus according to an embodiment of the present invention.
Numeral 1 denotes a capillary column having an outer diameter of 200 to 300 μm and an inner diameter of 50 to 150 μm, which is made of fused silica. One end 1 a of the capillary column 1 is connected to a pump block 5 through a capillary joint 3. The pump block 5 is provided therein with two passages 7 a and 7 b of 1 to 3 mm in diameter, which are connected with each other at an intersection part 9.
A polymer syringe 13 charged with a polymer is connected to one end of the passage 7 a through a Luer-Lok joint 11. The other end of the passage 7 a is sealed with a switchable drain joint 15.
A buffer syringe 19 charged with a buffer is connected to one end of the passage 7 b through a Luer-Lok joint 17. The capillary column 1 is connected to the other end of the passage 7 b through the capillary joint 3. As shown in FIG. 2, a pressure sensor 21 measuring the pressure in the passage 7 b is provided on the passage 7 b between the intersection part 9 and the Luer-Lok joint 17. FIG. 2 is a sectional view taken along the line Z—Z in FIG. 1.
An electrode 33 consisting of a platinum wire is embedded in a piston 19 a of the buffer syringe 19 so that its forward end is in contact with the buffer in the buffer syringe 19.
Syringe piston driving linear actuators 13 b and 19 b drive a piston 13 a of the polymer syringe 13 and the piston 19 a of the buffer syringe 19 respectively.
FIG. 3 is a front elevation view showing an example of the syringe piston driving linear actuator 13 b for the polymer syringe 13. The syringe piston driving linear actuator 19 b for the buffer syringe 19 is identical in structure to the syringe piston driving linear actuator 13 b.
One end of a coupling member 23 is fixed to the piston 13 a, and the other end thereof is slidably supported on a guide 25 set in parallel with the sliding direction of the piston 13 a. A female screw 27 engaging with a rod screw 31 driven by a stepping motor 29 is fixed to the coupling member 23. The stepping motor 29 rotates the rod screw 31, so that the coupling member 23 slides along the guide 25 and the piston 13 a also slides.
Referring again to FIG. 1, the other end 1 b of the capillary column 1 is dipped in purified water 37 a stored in a container set on a tray 35 with an electrode 39 consisting of a platinum wire. Other containers on the tray 35 store a buffer 37 b and a sample 37 c respectively. The tray 35 is vertically and horizontally movable along arrows by a tray driving mechanism (not shown), so that the other end 1 b of the capillary column 1 is dipped in the purified water 37 a, the buffer 37 b or the sample 37 c as needed.
The electrodes 33 and 39 are connected to an electrophoresis high voltage power source 41 for serving as an anode and a cathode respectively and applying a high voltage to the both ends 1 a and 1 b of the capillary column 1 in sample introduction and electrophoresis.
A detection light source 43 such as an Ar laser unit applying light to a part to be detected 1 c of the capillary column 1 and a detector 47 detecting light from the part 1 c through a condensing and spectroscopic part 45 are arranged in the vicinity of the part 1 c as a detection part.
The Luer-Lok joint 11 connects the polymer syringe 13 charged with the polymer to the passage 7 a of the pump block 5, and the piston 13 a is fixed to the syringe piston driving linear actuator 13 b. The Luer-Lok joint 17 connects the buffer syringe 19 charged with the buffer to the passage 7 b of the pump block 5, and the piston 19 a is fixed to the syringe piston driving linear actuator 19 b. The containers storing the purified water 37 a, the buffer 37 b and the sample 37 c are arranged on the tray 35 respectively. The capillary joint 3 connects the one end 1 a of the capillary column 1 to the passage 7 b of the pump block 5 for mounting the capillary column 1. The tray 35 is moved to dip the other end 1 b of the capillary column 1 and the electrode 39 into the purified water 37 a.
After the drain joint 15 is opened, the piston 19 a is pushed while the piston 13 a is fixed, thereby the passage 7 b between the Luer-Lok joint 17 and the intersection part 9 and the passage 7 a between the intersection part 9 and the drain joint 15 are charged with the buffer. Then, the piston 13 a is pushed while the piston 19 a is fixed, thereby the passage 7 a is charged with the polymer and the buffer charged in the passage 7 a between the intersection part 9 and the drain joint 15 is discharged through the drain joint 15.
When the passages 7 a and 7 b are charged with the polymer and the buffer, the capillary joint 3 is opened through the capillary column 1 while the inner diameter of the capillary column 1 is small and hence passage resistance is developed to guide the polymer and the buffer only to the drain joint 15.
After the drain joint 15 is closed, the syringe piston driving linear actuators 13 b and 19 b are synchronously driven at the same speed for pushing the piston 13 a, pulling the piston 19 a, and charging the passage 7 b between the intersection part 9 and the Luer-Lok joint 17 with the polymer.
Then, the piston 19 a is fixed and the piston 13 a is pushed for charging the capillary column 1 with the polymer through the intersection part 9 and the capillary joint 3. At this time, the pressure sensor 21 monitors the pressure in the passage 7 b, so that various problems such as clogging of the capillary column 1 can be detected in an early stage.
After charging the polymer, the tray 35 is moved to dip the other end 1 b of the capillary column 1 and the electrode 39 into the sample 37 c. The electrophoresis high voltage power source 41 applies a prescribed voltage, for injecting the sample 37 c into the capillary column 1.
Thereafter, the tray 35 is moved to dip the other end 1 b of the capillary column 1 and the electrode 39 into the buffer 37 b. The electrophoresis high voltage power source 41 applies a prescribed voltage for electrophoresing and separating the sample 37 c in the capillary column 1. Separated components successively pass through the part to be detected 1 c, so that the detector 47 detects interaction with the sample 37 c caused by light from the detection light source 43 through the condensing and spectroscopic part 45.
After completing detection of the sample 37 c, the tray 35 is moved to dip the other end 1 b of the capillary column 1 and the electrode 39 into the purified water 37 a, and thereafter the piston 13 a is pushed for discharging the polymer from the capillary column 1 through the other end 1 b thereof, and charging the capillary column 1 with a new polymer thereby preparing for analysis of a next sample.
While the passage 7 b between the intersection part 9 in the pump block 5 and the Luer-Lokjoint 17 is charged with the buffer before the same is charged with the polymer in this embodiment, the buffer charging operation may be omitted, and the passage 7 b between the intersection part 9 and the Luer-Lok joint 17 may be charged with the polymer after charging the passage 7 a with the polymer. In this case, air present in the passage 7 b between the intersection part 9 and the Luer-Lok joint 17 is fed into the buffer syringe 19. Therefore, it is preferable to project the forward end of the electrode 33 from the forward end of the piston 19 a to some extent so that the electrode 33 comes into contact with the buffer also when the air is fed into the syringe 19.
Alternatively, the passage 7 b between the intersection part 9 and the Luer-Lok joint 17 may be previously charged with the polymer so that no air enters the buffer syringe 19.
While the electrode 33 is embedded in the piston 19 a in this embodiment, the part connecting for example the buffer syringe 19 with the Luer-Lok joint 17 may be formed by an electrode, so far as the electrode comes into contact with the buffer.
Furthermore, the pressure sensor 21 may be omitted and an encoder or the like may be provided on the syringe piston driving linear actuator 13 b for monitoring motion of the syringe piston driving linear actuator 13 b or loss of synchronism of the stepping motor 29 thereby monitoring various problems such as clogging of the capillary column 1 during polymer charging.
FIG. 4 is a schematic elevation view showing a structure around a pump block 47 in another embodiment of the present invention.
One end 1 a of a capillary column 1 is connected to one end of a passage 7 c of the pump block 47 through a capillary joint 3. The pump block 47 is provided therein with two passages 7 a and 7 c of 1 to 3 mm in diameter, which are connected with each other at an intersection part 49.
A polymer syringe 13 is connected to one end of the passage 7 a through a Luer-Lok joint 11 while the other end thereof is sealed with a drain joint 15.
A ferrule 51 is provided on the other end of the passage 7 c, and an electrode 53 reaching the intersection part 49 from the ferrule 51 is inserted in the passage 7 c. The ferrule 51 airtightly fixes the electrode 53.
Operations of charging the capillary column 1 with a polymer in the embodiment shown in FIG. 4 shall now be described.
The polymer syringe 13 charged with the polymer is connected to the Luer-Lok joint 11 and a piston 13 a is fixed to a syringe piston driving linear actuator 13 b. The one end 1 a of the capillary column 1 is connected to the capillary joint 3 and the other end thereof is dipped into purified water.
After the drain joint 15 is opened, the piston 13 a is pushed for charging the passage 7 a with the polymer. At this time, the capillary joint 3 is opened through the capillary column 1 while the inner diameter of the capillary column 1 is small and hence passage resistance is developed to guide the polymer only to the drain joint 15.
After the drain joint 15 is closed, the syringe piston driving linear actuator 13 b is driven to push the piston 13 a for charging the capillary column 1 with the polymer through the intersection part 49 and the capillary joint 3. The polymer comes into contact with the electrode 53 in the passage 7 c.
Then, after a sample is separated and analyzed similarly to the embodiment shown in FIG. 1, the syringe piston driving linear actuator 13 b is driven to push the piston 13 a for exchanging the polymer in the capillary column 1 with a new polymer.
While each of the embodiments shown in FIGS. 1 and 4 is applied to a capillary electrophoretic apparatus employing a single capillary column, the present invention is also applicable to a multi-capillary electrophoretic apparatus. When the present invention is applied to a multi-capillary electrophoretic apparatus, the passage in the pump block connected with the capillary column may be branched for providing capillary joints on branched parts of the passage respectively and fixing ends of a plurality of capillary columns to the pump block. Alternatively, ends of a plurality of capillary columns may be collectively inserted in and airtightly fixed to the capillary joint. Thereby, the polymer can be simultaneously injected into the plurality of capillary columns.
1. A capillary electrophoretic apparatus comprising:
a capillary electrophoretic part configured to perform electrophoresis of a sample injected into a capillary column charged with a polymer;
a detection part detecting each component separated in the capillary column on an appropriate position of the capillary column;
a polymer syringe charged with a polymer;
a pump block connecting the polymer syringe with one end of the capillary column through a passage; and
a high voltage power supply device having electrodes provided on the one end and the other end of the capillary column so that the electrode provided on the one end comes into contact with the polymer, for applying an electrophoresis voltage between the both ends of the capillary column with the electrodes.
2. The capillary electrophoretic apparatus in accordance with claim 1, wherein
the pump block comprises a polymer port connected with the polymer syringe, a column port connected with the one end of the capillary column and a passage connecting the polymer port and the column port with each other, and
the electrode on the one end is provided to come into contact with the polymer in the polymer syringe or the pump block.
3. The capillary electrophoretic apparatus in accordance with claim 1, further comprising a buffer syringe charged with a buffer, wherein
the pump block comprises a polymer port connected with the polymer syringe, a buffer port connected with the buffer syringe, a column port connected with the one end of the capillary column and a passage connecting the ports with each other, and
the electrode on the one end is provided to come into contact with the polymer through the buffer.
4. The capillary electrophoretic apparatus in accordance with claim 1, wherein
the pump block comprises an openable drain port connected to the passage.
5. The capillary electrophoretic apparatus in accordance with claim 1, wherein
the pump block comprises a pressure sensor measuring the pressure in the passage.
6. The capillary electrophoretic apparatus in accordance with claim 1, further comprising a tray storing a sample, a buffer and purified water,
the tray being movable for inserting the other end of the capillary column and the electrode on the other end into the sample, the buffer or the purified water.
US09/448,139 1998-11-30 1999-11-24 Capillary electrophoretic apparatus Expired - Fee Related US6383356B1 (en)
JP10-338898 1998-11-30
US6383356B1 true US6383356B1 (en) 2002-05-07
US09/448,139 Expired - Fee Related US6383356B1 (en) 1998-11-30 1999-11-24 Capillary electrophoretic apparatus
US6660148B2 (en) * 2000-02-28 2003-12-09 Hitachi, Ltd. Electrophoretic method and electrophoretic instrument therefor
US20040003994A1 (en) * 2002-01-18 2004-01-08 Tomihiro Shoji Capillary electrophoresis device
US20070278101A1 (en) * 2006-06-05 2007-12-06 Hitachi High-Technologies Corporation Capillary electrophoresis apparatus
JP4681433B2 (en) * 2005-11-29 2011-05-11 株式会社日立ハイテクノロジーズ Capillary electrophoresis apparatus
JP5218017B2 (en) * 2008-12-18 2013-06-26 株式会社島津製作所 Adoption monitoring system and introducing status monitoring method
GB2530446B (en) * 2013-07-08 2018-06-13 Hitachi High Tech Corp Capillary electrophoresis device
JP6098471B2 (en) * 2013-10-22 2017-03-22 株式会社島津製作所 Capillary electrophoresis apparatus
US7081191B2 (en) * 2002-01-18 2006-07-25 Hitachi High-Technologies Corporation Capillary electrophoresis device
US7883613B2 (en) * 2006-06-05 2011-02-08 Hitachi High-Technologies Corporation Capillary electrophoresis apparatus
EP1006356A2 (en) 2000-06-07
CA2383912C (en) 2009-11-10 Automated parallel capillary electrophoresis system with hydrodynamic sample injection
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:HAYASHIZAKI, YOSHIHIDE;NAKAMURA, SHIN;REEL/FRAME:010552/0130
Free format text: ASSIGNMENT OF ONE THIRD INTEREST;ASSIGNORS:SHIMADZU CORPORATION;INSTITUTE OF PHYSICAL AND CHEMICAL RESEARCH, THE;REEL/FRAME:012057/0305