JP3818187B2 - Capillary array device - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a capillary array electrophoresis apparatus for separating and analyzing a sample such as DNA or protein, a capillary array incorporated in the electrophoresis apparatus, and a method for manufacturing the capillary array.
[0002]
[Prior art]
A technique is well known in which a capillary array apparatus is configured by combining a plurality of capillaries, and an electrophoresis medium and a sample to be analyzed or separated are supplied and migrated to each capillary, and the target sample is used for separation and analysis. ing. In addition, a technique for supplying a sample such as DNA or protein labeled with a fluorescent substance to a capillary is disclosed in US Pat. Nos. 5,366,608, 5,529,679, 5,516,409, 5,730,850, 5,790,727, 5,582,705, and 5,439,578. No. 5,274,240. From the viewpoint of separation and analysis throughput, the use of a multicapillary has many advantages over electrophoresis using a slab gel. Japanese Unexamined Patent Publication No. 9-96623 discloses a capillary array electrophoresis apparatus.
[0003]
FIG. 2 is an explanatory diagram of the capillary array device. Each capillary 1 has an outer diameter of 0.1 to 0.7 mm, an inner diameter of 0.02 to 0.5 mm, and the outer cover is coated with a polyimide resin. The capillaries themselves are quartz pipes, and a plurality of capillaries (generally several to several tens) are arranged to constitute a capillary array apparatus. The capillary array device includes a load header 4 for taking a sample into a capillary by electrophoresis from a sample container containing a fluorescently labeled DNA sample, a separator 16 for arranging a plurality of capillaries, and a capillary in order of sample numbers of the load header 4 1 includes a detection unit (window unit) 5 for arranging and fixing 1 and a capillary head 17 in which a plurality of capillaries are bundled and bonded together. The load header 4 is provided with a hollow electrode 20 for applying an electrophoresis voltage to the capillary. The detection unit (window unit) 5 includes an opening for irradiating light to a plurality of aligned capillaries and an opening for taking out light emitted from the capillaries. It is sufficient that the detection unit 5 according to the present invention has a function capable of holding in parallel a plurality of capillary laser beam irradiation units (portions where the laser beam for generating fluorescence from the sample passes through the capillary). .
[0004]
FIG. 3 is a schematic view showing an electrophoresis system. In the capillary array apparatus shown in FIG. 2, the hollow electrode 20 protruding from the load header 4 and the sample injection end of the capillary 1 are immersed in a sample tray 3 containing a plurality of sample containers 2 containing fluorescently labeled DNA samples. The capillary head 17 at the other end is attached to the buffer solution container 14 containing the buffer solution 13 in a pressure-resistant and airtight manner. A high voltage of about 15 kV is applied to the buffer solution container 14 and the load header 4 from the high voltage power supply 15, and the sample in the sample container is electrophoresed by the buffer solution placed in the capillary from the buffer solution container to separate the sample.
[0005]
The laser light source 6 irradiates the detection unit (window unit) 5 with excitation light by an excitation optical system including a mirror 7, a beam splitter 8, a condenser lens 9, and the like. Fluorescence 10 that is signal light emitted from a sample migrating in the capillary by excitation light irradiation is detected by a CCD camera 12 via a detection lens system 11. The detected signal is arithmetically processed by the signal processing arithmetic unit 21.
[0006]
The electrophoresis system in the illustrated example irradiates laser light from both sides of the capillary array device containing the DNA or protein to be electrophoresed, and condenses the laser light by the lens action of the capillary, thereby exciting all the capillaries. , And fluorescence from each capillary is detected by a detection optical system.
[0007]
The purpose of the load header 4 is a sample container side hollow electrode 20 for applying a high voltage between the sample and the buffer container 14 in addition to sampling the sample. FIG. 4 is a diagram showing the structure of a conventional load header. Each of the 16 capillaries 1 is inserted into a hollow electrode 20 made of a thin pipe made of stainless steel (hereinafter referred to as SUS), and the tip on the sample side is slightly smaller than the hollow electrode. And is fixed with an epoxy adhesive 27. As shown in FIG. 5, the 16 hollow electrodes 20 are aligned and set with strict tolerance together with the connection plate 23 in the soldering machine 22 and are joined to the connection plate 23 with the solder 24. The reason for using the SUS pipe electrode is that the sample and reagent to be separated and analyzed are corrosive.
[0008]
The joined hollow electrode 20 and the connection plate 23 are assembled in a plastic holder 25, and the lid 26 is ultrasonically joined to the holder 25 and fixed. Thereafter, the holder 25 and the hollow electrode 20 are bonded from the outside with an adhesive 27 to be airtight and fixed, and the load header is completed. The capillary 1 is sealed to the lid 26 with an adhesive 27 so as not to come off and prevent high voltage leakage. A part of the connection plate 23 is bent by 90 ° so that a high voltage contact (not shown) can be connected from an opening provided in the holder 25.
[0009]
The capillary array device is a consumable item that is discarded because desired characteristics cannot be obtained if it is used several tens of times.
[0010]
[Problems to be solved by the invention]
The conventional load header described above has the following problems.
(1) There are many operations such as bonding and joining at the time of assembling the load header, and it takes time to manufacture and the cost is high.
(2) Work such as bonding and joining is easily affected by the skill, work conditions and environment of the worker, and is unreliable.
(3) Since a strong acid flux is used in the soldering operation between the connection plate and the SUS electrode, it becomes an ionic impurity, which impairs electrophoresis. Therefore, high quality cleaning is required for the inside and outside of the thin electrode.
[0011]
According to the present invention, a load header of a capillary array device that takes a sample into a capillary array device and applies a high voltage for electrophoresis can be manufactured at low cost and can be manufactured in a clean manner. The purpose is to have a certain structure.
[0012]
[Means for Solving the Problems]
In one aspect of the present invention, the object is achieved by making the electrical connection method between the plurality of electrodes provided on the load header of the capillary array device and the connection plate a spring contact without using solder. In addition, in order to reduce the bonding work, the plastic holder and electrode are formed by an integral mold to improve reliability. Furthermore, in order to increase the reliability of the contact portion, the contact portion is covered with an adhesive or a conductive adhesive, and the contact portion is shielded from the atmosphere so that an oxide film having a large electric resistance is not generated on the contact portion surface. .
[0013]
That is, the capillary array device according to the present invention includes a plurality of capillaries, openings for illuminating the plurality of capillaries aligned and held in the middle of the length direction, and light emitted from the capillaries. In a capillary array apparatus including a window unit including an opening for extraction, a load header that holds a plurality of capillaries and electrodes at a sample injection end, and a capillary head that holds a plurality of capillaries in a bundle at the other end. The load header includes a holder, a plurality of hollow electrodes fixed to the holder, and a conductive connection plate in spring contact with the outer surface of the hollow electrode, and the plurality of capillaries each pass through the corresponding hollow electrode and the tip thereof It is exposed from the hollow electrode.
[0014]
The hollow electrode and the connection plate are preferably made of austenitic stainless steel such as SUS304 or SUS316 having high corrosion resistance.
[0015]
The connecting plate and the hollow electrode are preferably electrically connected at the outer surface of the hollow electrode and the edge of the connecting plate to increase the contact surface pressure.
[0016]
Further, it is preferable that the connection plate is brought into spring contact with the outer surface of the hollow electrode by a plurality of claw-shaped springs provided symmetrically around each hollow electrode.
[0017]
It is preferable to set the inscribed circles of the plurality of claw-shaped springs of the connection plate to be smaller than the outer diameter of the hollow electrode (preferably about 70 to 85%) and insert the connection plate from the upper end of the hollow electrode for assembly.
[0018]
The contact surface pressure between the outer surface of the hollow electrode and the claw-shaped spring of the connection plate is preferably 5 to 10 MPa.
[0019]
The material of the connection plate can be a metal, a conductive rubber plate, a conductive plastic, or the like.
[0020]
The hollow electrode is preferably molded integrally with the holder.
[0021]
Moreover, you may make it interrupt | block the spring contact part of a connection board and a hollow electrode from air | atmosphere. Specifically, it can be shielded from the atmosphere by applying an adhesive to the spring contact portion. The adhesive may be a conductive adhesive. The conductive material of the conductive adhesive is preferably nickel particles. The adhesive is preferably an epoxy adhesive.
[0022]
Another aspect of the present invention is a capillary array electrophoresis in which a conductive connection plate that is electrically connected to a plurality of hollow electrodes immersed in a sample simultaneously with the sample injection end of the capillary is in close contact with the hollow electrode by its volume elasticity. An apparatus and a capillary array. Preferably, the hollow electrode is fixed through a hole formed in a connection plate having a high elasticity. Thereby, both can be fixed by inserting a hollow electrode in a connection board, and since a contact surface of a hollow electrode and a connection board is crimped | bonded, a contact resistance value can be made small.
[0023]
Another aspect of the present invention is a method of creating a load header by disposing a connecting plate having elasticity between a holder to which a plurality of hollow electrodes are fixed and a lid, and sandwiching the holder and the lid. Thereby, a hollow electrode and a connection board are electrically connected, a holder and a lid can be joined and a load header can be created. Preferably, when the load header is completed, the load header is designed so that the holder and the lid compress the connection plate in the vicinity of the hollow electrode and the connection plate. Thereby, the crimping | compression-bonding force of a hollow electrode and a connection board can be enlarged more.
[0024]
Embodiments of the present invention will be described below with reference to the drawings.
[Embodiment 1]
FIG. 6 shows an example of a load header structure in which the hollow electrode and the connection plate are electrically connected by the tightening force of the spring. 6 (a) is a front sectional view of the load header, FIG. 6 (b) is a top view with the lid removed, and FIG. 6 (c) is a side sectional view.
[0025]
FIG. 7 is a diagram showing the shape of a connection plate incorporated in the load header shown in FIG. 7A is a top view of the connection plate, FIG. 7B is a front view, and FIG. 7C is a side view.
[0026]
As can be seen from FIG. 6, 16 hollow electrodes 20 are accurately bonded and fixed to the holder 25 in two rows with an adhesive 27, and the connection plate 23 shown in FIG. 7 is pushed between the two rows of hollow electrodes. ing. The width w of the connecting plate 23 is made approximately 10% wider than the inner method between the two rows of hollow electrodes 20, and a spring force is generated between the hollow electrode 20 and the contact portion 28 whose ends are bent in a U-shape. Surface pressure can be obtained. After the connection plate 23 is pushed between the two rows of hollow electrodes 20 fixed to the holder 25, the lid 26 is joined, the capillary 1 is inserted into the hollow electrode 20 from the capillary guide hole 29 provided in the lid 26, and the load header is inserted. assemble. The load header structure which does not use solder by the above is obtained.
[0027]
However, this structure has been found to have the following problems.
(1) When the hollow electrode 20 is bent outward by the spring force of the connection plate 23 and the lid 26 is joined, the capillary guide hole 29 provided in the lid and the hollow electrode are misaligned, and the capillary cannot pass through the hollow electrode. is there.
(2) The contact surface pressure varies due to variations in the internal method between the two rows of hollow electrodes 20, and the contact resistance changes greatly in a humidity test or a vibration test.
[0028]
FIG. 1 shows an example of a suitable load header that solves the above problems. 1A is a cross-sectional view of the load header, FIG. 1B is a side cross-sectional view, FIG. 1C is a top view showing the main part of the connecting plate, and FIG. 1D is FIG. It is a dd sectional view of).
[0029]
The holder 25 and the austenitic hollow electrode 20 for the electrode were injection molded, and the hollow electrode 20 was integrally molded into the holder 25 and incorporated. Thereby, the bonding operation between the holder 25 and the hollow electrode 20 can be omitted. In the injection mold, a hole into which a hollow electrode is inserted is processed in an upper mold and a lower mold of a mold for manufacturing a holder, and resin is press-fitted and integrally molded in a state where the hollow electrode is set in the mold. In this case, if the electrode surface is dirty, the hollow electrode can be easily removed from the holder. Therefore, it is important to clean the electrode to be used. The injection pressure of the resin is 40 to 60 MPa, and the mold temperature varies depending on the type of resin used. The hollow electrode 20 and the holder 25 manufactured in this way have good dimensional accuracy. In the conventional method, the bending of the electrode is repaired after bonding. However, the integrally molded product does not require repair, and the cost reduction effect is even greater.
[0030]
In addition, as shown in FIG. 1C, the connection plate 23 has a plurality of claws 30 arranged symmetrically around each electrode to form a contact portion so that no force for bending the hollow electrode 20 is generated. The material of the connection plate 23 is the same austenitic SUS plate as that of the hollow electrode 20 in order to increase the spring force and increase the corrosion resistance.
[0031]
The method for attaching the connection plate will be described in detail below. The connection plate 23 is placed on a holder 25 in which the hollow electrodes 20 are integrally molded, and the inner diameters of the 16 hollow electrodes 20 are aligned with the cores of the contact portions.
[0032]
FIG. 8 is an enlarged view of the upper surface of the contact portion at this time, that is, an enlarged view of a portion A in FIG. A circle indicated by an alternate long and short dash line in FIG. 8 is an inscribed circle 31 of the four claws 30. The inscribed circle of the claw 30 is made about 20% smaller than the outer diameter of the hollow electrode 20 so that the spring property after incorporation is obtained.
[0033]
FIG. 9 is an enlarged side view of a contact portion between the hollow electrode 20 and the connection plate 23, that is, an enlarged view of a portion B in FIG.
[0034]
The connecting plate 23 is pushed in the direction of the arrow, and the pawl 30 is assembled while the claw 30 rubs the outer peripheral surface of the hollow electrode. At this time, the passive film on both surfaces is broken to form a metal-to-metal connection. The connecting plate 23 is made by stamping in the direction of the arrow in FIG. 9, and the cross section of the claw portion 30 has an edge on the lower side so that the contact surface pressure is increased as can be seen from the drawing. Although the number of the claws 30 depends on the size of the contact portion and the processing method, 3 to 6 is appropriate. The contact pressure at this time is 5 to 10 MPa, and if it exceeds this, the hollow electrode 20 is deformed, and the capillary 1 cannot enter the hollow electrode 20. A contact resistance of 0.05Ω to several Ω was obtained, and it was confirmed that there was almost no change even in environmental tests such as corrosive gas tests and humidity tests. In FIG. 8, the tip of the nail is a right angle, but it was confirmed that there is no difference in contact resistance even if there is a roundness of about 0.2R practically.
[0035]
The contact surface pressure P between the side surface of the hollow electrode 20 and the claw 30 of the connecting plate 23 is obtained by the following equation, where F is the force with which the claw 30 pushes the hollow electrode 20 and S is the contact area.
[0036]
P = F / S
Here, the contact area S is 0.5 to 1.0 × 10. ^-Four cm ² When the force F is a stress analysis of the relationship between the bending angle of the nail 30 and the force, the material of the nail 30 is a 0.2 mm thick plate made of stainless steel and the nail 30 is bent so that θ is 12 to 15 degrees. When the length and the diameter of the hollow electrode were selected, 45 to 65 grams as F were obtained as shown in FIG. The contact pressure P at this time is 4.4 to 12.7 MPa, and the inner number may be 5 to 10 MPa.
[0037]
Another material of the connection plate 23 may be a non-metallic material such as conductive rubber or conductive plastic. In this case, the contact portion shape may be a circle or a polygon. Further, it is practical that the contact resistance is designed to allow several Ω to several tens of kΩ.
[0038]
FIG. 11 is a diagram illustrating an example of the connection plate 23 manufactured using conductive rubber. Conductive rubber is a rubber material with a thickness of 0.5 to 1.0 mm mixed with carbon powder or metal powder to give conductivity, and is about 1/4 to 3/4 of the outer diameter of the hollow electrode. A hole in the claw portion is formed so as to form an inscribed circle of the above, and the hollow electrode 20 is pushed in as indicated by an arrow. Even when the upper part of the hollow electrode is flare-shaped and the diameter of the opening is 20 to 30% larger than the diameter of the cylindrical part, since the rubber has a great restoring force, the effect of holding the connection plate as with the spring can be obtained. The split groove 33 provided in the claw portion is provided so that the connection plate can be easily inserted. As the rubber agent, NR, NBR or EPDM rubber is preferable. Further, if the hardness is 70 or more in order to increase the elasticity of rubber, a large contact pressure can be obtained.
[0039]
FIG. 12 is a diagram showing an example of the connection plate 23 made using a conductive plastic. A conductive plastic having a thickness of about 0.1 mm is generally used. The material may be polyacetylene, plastic mixed with metal powder, metal plating film or metal vapor deposition film, and the figure shows an example in which a plurality of contact claws 30 are provided inside the circular hole. Electrical connection is possible not only by circular holes but also by cutting.
[0040]
As described above, when the connection plate 23 is made of a non-metallic material such as conductive rubber or conductive plastic, stable characteristics can be obtained with little plastic deformation even when the deformation of the claws is large. In addition, there is an advantage that it can be manufactured by inexpensive die cutting.
[0041]
When the capillary array device is used in a harsher environment or transportation conditions, or when a contact surface pressure appropriate for the structure cannot be obtained, the interface between the hollow electrode 20 and the SUS contact portion of the claw 30 of the connection plate 23 is not suitable. It is desirable to shield the contact from oxidizing atmosphere and moisture so that no dynamic film is formed. Thereby, the contact resistance can be stably maintained.
[0042]
Specifically, as shown in FIG. 13, the adhesive 27 is applied to the interface between the hollow electrode 20 and the SUS contact portion of the claw 30 of the connection plate 23 and cured, and the contact portion is shielded from oxidizing air and moisture. To do. Thereby, generation | occurrence | production of a passive film and the increase of a passive film can be prevented, and the stable contact resistance is maintained. Further, since the contact portion is fixed by the adhesive 27, the effect is doubled. In general, the adhesive is an insulator, but a conductive adhesive 27 in which conductive particles are mixed with the adhesive may be used for security. As the conductive particles, nickel is preferable. As the adhesive, an epoxy adhesive that is inexpensive, has high strength, and has good water resistance is optimal.
[Embodiment 2]
The present embodiment is a load header in which a hollow electrode penetrates an elastic connection plate and the hollow electrode is pressure-bonded to the connection plate by the volume elastic force of the connection plate, and a manufacturing method thereof. Hereinafter, the present embodiment will be described with reference to FIGS.
[0043]
The load header of a present Example is shown to Fig.14 (a)-(d). (A) shows a cross-sectional view, (b) shows a side cross-sectional view, (c) shows a connecting plate, and (d) shows a detailed view of A in FIG. 14 (a).
[0044]
The load header includes 96 hollow electrodes 20, a connection plate 23 joined to the 96 hollow electrodes and connected to a high voltage contact of an electrophoresis apparatus for applying a high voltage to the hollow electrodes, 20 is arranged in a matrix of 8 × 12, and is composed of a plastic holder 25 including a connection plate therein, and a lid 26 that is ultrasonically bonded to the holder 25 and fixed to the hollow electrode 20. A high-voltage terminal plug 101 for applying a voltage and a concave guide 102 for fitting and connecting the load header to the electrophoresis apparatus are provided.
[0045]
When the load header is attached to the electrophoresis apparatus body, the guide 102 is fitted and connected to the convex rail of the electrophoresis apparatus body. Further, a high voltage contact of an electrophoresis device is inserted into the high voltage terminal plug 101 so that a high voltage for electrophoresis can be applied to the hollow electrode 20. Here, the high voltage terminal plug 101 is an opening formed in the holder 25, and the tag 133 formed on the connection plate 23 is exposed to the outside of the load header.
[0046]
The 96 capillaries 1 are each inserted into a hollow electrode 20 made of a thin stainless steel pipe, and the sample-side tip slightly protrudes from the hollow electrode and is fixed with an epoxy adhesive 27. The reason for using the SUS pipe hollow electrode is that the sample and reagent to be separated and analyzed are corrosive.
[0047]
The connection plate 23 is a plate-shaped member as shown in FIG. 14C, and through holes (insertion positions) 131 for penetrating the hollow electrode 20 are formed in an 8 × 12 matrix, and the holder 25 is provided with a hole 130 for fitting the guide pin 128 and the holder 25 and the connecting plate 23, and a tag 133 connected to the high voltage contact. The material of the connection plate is a member having elasticity and conductivity, and preferably conductive rubber.
[0048]
As shown in FIG. 14 (d), the hollow electrode 20 passes through a hole (insertion position) 131 provided in the elastic connection plate 23, and the hollow electrode 20 pushes the hole 131 to expand the connection member. They are connected by elastic force. More specifically, the outer surface of the hollow electrode 20 and the inner surface of the hole (insertion position) 131 of the connection plate are in close contact with each other, and the degree of coupling is increased by the elastic force (volume elastic force) of the connection plate 23. For this reason, the contact resistance value between the hollow electrode and the connection plate is reduced, and the contact resistivity between each hollow electrode 20 and the connection plate is uniform, so that the separation performance for each capillary can be ensured to be constant. Also, soldering between each hollow electrode and the connection plate is not necessary.
[0049]
The hollow electrode and the holder are fixed by inserting the hollow electrode into a hole formed in the holder that is larger than the outer shape of the hollow electrode, and filling the gap 27 with the adhesive 27. When the adhesive reaches from the upper surface of the holder to the lower surface on the opposite side, the gap is surely closed by the adhesive. In general, it is difficult to remove the liquid that has entered the narrow gap due to the capillary phenomenon, and the sample that has entered the narrow gap causes contamination, but in this example there is no gap between the holder and the hollow electrode. Contamination can be avoided.
[0050]
FIGS. 15A and 15B show the force applied to the hollow electrode by the bulk elastic force of the connection plate. As shown to Fig.15 (a), a hollow electrode is hold | maintained by being clamped by the volume elastic force (F1, F2) of the connecting plate which opposes. In particular, when the entire outer surface of the hollow electrode is in contact with the connection plate, the hollow electrode is subjected to elastic force from all directions, so that the hollow electrode can be returned to its original state regardless of which direction the load is applied to the hollow electrode. A restoring force is generated. In particular, when one cross section of the hollow electrode is a circle, the restoring force (elastic force) is evenly applied from all directions, so that the restoring property is increased.
[0051]
The tag 133 which is a part of the connection plate is bent. This is to simplify the attachment mechanism of the high-voltage contact by making the contact surface of the tag with the high-voltage contact perpendicular to the attachment direction of the load header to the electrophoresis apparatus. Also, the high voltage contact is in direct contact with the tag. This is because the problem of individual differences in the contact resistance value between the conductive members can be avoided as compared with the case where the connection is made indirectly through a conductive member such as metal. In this embodiment, since the hollow electrode is electrically connected to the high voltage contactor only through the connection plate, it is possible to avoid the above-mentioned problem of the difference in contact resistance value between the capillaries as well as between the capillaries. Can be made uniform.
[0052]
Hereinafter, a method for creating a load header according to the present embodiment will be described with reference to FIGS.
[0053]
As shown in FIG. 16 (a), the connection plate is placed on the holder to which the hollow electrode is bonded, and the convex guide pin 128 provided on the holder is aligned with the hole 130 of the connection plate. The center and the center of the insertion position 131 of the connection plate are aligned. Here, the tag 133 at the end of the rubber sheet is inserted by being bent in advance along the shape of the groove 134 of the holder. Further, the hollow electrode is inserted into a hollow electrode insertion hole provided in the guide, and the tip thereof is fixed by a stand 136, and the gap between the hollow electrode and the hollow electrode insertion hole is filled with a resin so as to adhere to the holder. Is done. Thereby, 96 hollow electrode tips can be aligned with high accuracy.
[0054]
Moreover, as shown in FIG.16 (b), the front-end | tip part of a hollow electrode is carrying out the flare shape where an opening becomes small gradually as it leaves | separates from an edge part. Since the opening at the tip is large, it is easy to insert the capillary into the hollow electrode. In particular, 96 capillaries can be easily inserted into the lid and the hollow electrode after the hollow electrode is inserted into the connection plate and the lid is fixed to the holder with ultrasonic waves. This is because the distance between the passage hole of the capillary provided in the lid and the hollow electrode is small, and the opening at the tip of the hollow electrode is larger than the passage hole.
[0055]
Next, as shown in FIG. 17A, the hollow electrode insertion member 135 having a hollow shape and a hole is sequentially covered at 96 insertion positions on the connection plate. Since the connecting plate is pierced with a needle of about φ0.5 mm before insertion, the hollow electrode can be smoothly inserted into a predetermined position. In addition, it is preferable that the through hole before inserting the hollow electrode 20 is closed by the elastic force of the connection plate. This is because the contact pressure between the hollow electrode 20 and the connection plate increases. By pushing the connection plate around the insertion position in the direction of the arrow (longitudinal direction of the hollow electrode), a load is generated around the insertion position of the hollow electrode, and the hollow electrode breaks through the connection plate. As a result, the hollow electrode is in close contact with the connection plate.
[0056]
FIG. 17B shows the shape (c) of the insertion port of the hollow electrode insertion member 135. The insertion port has a donut shape, and its inner diameter is preferably slightly larger than the outer shape of the hollow electrode. This is because if the inner diameter is small, the insertion becomes troublesome and the working efficiency deteriorates. If the inner diameter is large, the connection plate near the hollow electrode is turned over.
[0057]
Also, as shown in FIG. 18, an adhesive 27 is applied to the upper part of the hollow electrode and the connection plate and cured. As the adhesive, an epoxy adhesive that has good strength and water resistance and is inexpensive is optimal. Thereby, since a contact part is interrupted | blocked from oxidizing air | atmosphere and a water | moisture content, generation | occurrence | production and increase of a passive film can be prevented and deterioration of contact resistance can be suppressed. In addition, the contact pressure between the hollow electrode and the connection plate can be increased. In particular, it is possible to prevent performance degradation when the capillary array is transported and stored in a harsh environment, such as when air transported using a cargo compartment of an airplane that is below freezing.
[0058]
If a conductive adhesive mixed with conductive particles is used as the adhesive 27, the contact resistance between the hollow electrode and the connection plate can be further reduced. As the conductive particles, silver, nickel, carbon and the like are suitable.
[0059]
According to this embodiment, since the contact resistance value between the hollow electrode and the connection plate can be reduced, fluctuations in the electrophoresis voltage applied to the sample in the capillary due to the stability of the high voltage power source can be reduced. . Moreover, the contact state of each hollow electrode and the connection plate can be made the same state. Therefore, the separation performance of the electrophoresis apparatus can be improved.
[0060]
Further, the electrical connection between the hollow electrode and the connection plate can be performed very easily.
[Embodiment 3]
The present embodiment is a method in which a work of inserting a hollow electrode into a hole of a connection plate in a load header production process and a work of joining a lid to a holder by an ultrasonic wave are carried out at a time. The contents of the present embodiment will be described below with reference to FIGS. 19A shows a state before ultrasonic bonding, FIG. 19B shows a state after bonding, and FIG. 19C shows details of the vicinity of the hollow electrode after bonding shown in D of FIG. 19B. FIG. 20 shows the production flow.
[0061]
First, 96 hollow electrodes 20 are fixed to the holder 25 in the same manner as in the second embodiment.
[0062]
Next, as shown in FIG. 19A, the connection plate 23 and the lid 26 are placed on a holder on which 96 (12 rows and 8 columns) hollow electrodes are accurately fixed with an adhesive. 26 are arranged in the order of 26. At this time, the holes 130 of the connection plate 23 and the alignment grooves 137 provided in the lid 26 are matched with the plurality of guide bosses 138 provided in the holder 25. Thereby, the position shift of the holder 25, the connection board 23, and the lid | cover 26 can be prevented. In this state, the hole of the connection plate is not inserted into the hollow electrode.
[0063]
Then, the lid 26 is loaded with a horn 140 that emits ultrasonic waves. A circumferential rib 139 provided on the lid 26 pushes around the hole 131 of the connection plate 23 to push the hollow electrode 20 into the connection plate 23, and the connection plate 23 moves to a position where it contacts the holder 25.
[0064]
Finally, the annular rib 139 further pushes the periphery of the hole 131 of the connection plate 23 to bring the holder into contact with the lid. Immediately thereafter, as shown in FIG. Are joined together. As described above, 96 hollow electrodes can be passed through the connection plate only by the operation of sandwiching the lid and the holder.
[0065]
FIGS. 21A to 21C show the load header created by the above method. 22A is a partial cross-sectional detail view of the load header, FIG. 22B is a partial cross-sectional side view, and FIG. 21C is a detailed view of E in FIG. 21A. In this embodiment, by setting the rib 139, the holder 25, and the connection plate 23 to predetermined dimensions, a load header in which the rib 139 increases the pressure-bonding force between the hollow electrode and the connection plate 23 can be manufactured. Referring to FIG. 19C, the annular rib 139 compresses the connection plate around the hollow electrode and applies a force (F) in the longitudinal direction of the hollow electrode to the connection plate 23. The connecting plate is compressed. Thereby, since the connecting plate 23 is pushed away from the rib 139, the volume elastic force (F ') applied to the hollow electrode 20 increases. Therefore, the crimping force between the hollow electrode 20 and the connection plate 23 is increased, and the contact resistance can be reduced. Thus, if the load header includes a mechanism for compressing the vicinity of the contact surface between the hollow electrode and the connection plate, the contact resistance value of the contact surface can be reduced.
[0066]
In addition, for example, when the rib 139 is a circular tube, one cross section of the rib is concave, and a hollow electrode exists in a region sandwiched between the compressed portions of the connection plate (the portion of the connection plate compressed by the rib). Then, the volume elastic force that opposes the hollow electrode increases almost evenly, which facilitates the production of the capillary. Here, “near” means a range in which an increase in volume elastic force is recognized due to compression of the connecting plate 23.
[0067]
In the above production method, when the shape of the holder, the connection plate, and the lid satisfies the predetermined conditions, the lid can be smoothly inserted into the holder and the connection plate can be compressed. Hereinafter, the conditional expressions (1) to (4) will be described based on the distances a to f shown in FIGS.
[0068]
Here, the distances a to f are used in the following meaning.
a: Distance from the upper surface of the connection plate before ultrasonic bonding to the upper surface of the connection plate after ultrasonic bonding.
b: Distance from the upper surface of the connection plate before ultrasonic bonding to the lower surface of the connection plate after ultrasonic bonding.
c: Distance from the lower surface of the connecting plate mounting portion after ultrasonic bonding to the tip of the guide boss.
d: The distance between the portions where the holder and the lid face each other in the state before ultrasonic bonding.
e: Distance from the lower surface of the connecting plate mounting portion after ultrasonic bonding to the deepest surface of the groove into which the alignment groove provided on the lid is inserted.
f: Depth of the alignment groove.
t: thickness of the connecting plate.
[Condition (1); ba ≦ t]
This conditional expression indicates the dimensional condition after compression of the connecting plate after final assembly. When this condition is satisfied, the rib 139 after ultrasonic bonding is in contact with the connection plate 23 or compresses the connection plate 23. On the other hand, if this condition is not satisfied, the rib 139 after ultrasonic bonding is separated from the connection plate 23.
[Condition (2); a ≦ d]
This conditional expression indicates a dimensional condition for joining the holder and the lid with ultrasonic waves. When this condition is satisfied, the holder and the lid can be joined. However, if this condition is not satisfied, a gap is generated between the holder and the lid, so that the joining cannot be performed.
[Condition (3); c> a + t]
This conditional expression indicates the dimensional condition for positioning the guide boss with the mating groove. When this condition is satisfied, the guide boss tip protrudes from the connection plate before ultrasonic bonding, so that the guide boss can be coupled to the mating groove, and displacement between the holder and the lid can be prevented.
[Condition (4); c + f> e]
This conditional expression indicates a dimensional condition that determines the length of the guide boss. When this condition is not satisfied, the guide boss and the alignment groove come into contact with each other, so that the holder and the lid cannot be joined.
[0069]
In this embodiment, a convex guide boss 138 is provided on the holder, and a concave alignment groove 137 is provided on the lid. Constitutes a prevention mechanism. However, the configuration of the misalignment prevention mechanism is not limited to this, and an example of a modification is shown with reference to FIGS. 22 (a) and 22 (b).
[0070]
FIG. 22A is a cross-sectional view of a load header having a misalignment prevention mechanism in which an alignment groove having a recessed central portion of the boss is provided in the holder and a guide boss that matches the groove is provided in the lid.
[0071]
The necessary conditions at this time are as follows.
[Condition (1); ba ≦ t]
[Condition (2); a ≦ d]
[Condition (3); g> a + t]
[Condition (4); h + i> j]
FIG. 22B is a cross-sectional view of the load header in which a fitting groove having a shape in which the center portion of the boss is recessed is provided on the lid so as to match the hole of the connection plate. At this time, if the hole diameter of the connecting plate is about 0.5 mm smaller than the mating groove, it will be prevented from coming off.
[0072]
At this time, the conditional expression for smoothly inserting the lid into the holder is as follows.
[0073]
[Condition (1); ba ≦ t]
[Condition (2); a ≦ d]
[Condition (3); k> a + t]
[Condition (4); l + k <e]
Here, g to l shown in FIGS. 22A and 22B are used in the following meaning.
g: Distance from the lower surface of the connecting plate mounting portion after joining with ultrasonic waves to the tip of the alignment groove.
h: The length of the guide boss.
i: Groove depth of the alignment groove.
j: Distance from the deepest surface of the alignment groove to the root of the guide boss.
k: Groove depth of the alignment groove.
l: Distance from the lower surface of the connecting plate mounting portion after ultrasonic bonding to the tip of the guide boss.
t: thickness of the connecting plate.
Although not shown, a concave recess may be provided where the connection plate contacts the hollow electrode or the rib. In this way, at least one of the holder, the connection plate, and the lid prevents the relative movement of these members in the direction perpendicular to the longitudinal direction of the hollow electrode, thereby electrically connecting the hollow electrode and the connection plate. The holder and lid can be joined. In particular, since 96 hollow electrodes and connection plates can be connected in a substantially uniform state, the separation performance of the electrophoresis apparatus can be ensured.
[0074]
According to the present embodiment, it is possible to produce a capillary array having a load header in which the hollow electrode comes into contact with the connection plate by bulk elastic force by sandwiching the holder and the lid. In addition, preferably, a capillary array in which the connection plate around the hollow electrode is compressed can be produced.
[0075]
【The invention's effect】
According to the present invention, it is possible to obtain a capillary array having high resolution, easy manufacture, and high reliability, and an electrophoresis apparatus including the capillary array.
[Brief description of the drawings]
FIG. 1 is a diagram showing an example of a load header according to the present invention.
FIG. 2 is an explanatory diagram of a capillary array device.
FIG. 3 is a schematic diagram showing an electrophoresis system.
FIG. 4 is a diagram showing a structure of a conventional load header.
FIG. 5 illustrates a conventional device.
FIG. 6 is a diagram showing an example of a load header structure in which an electrode and a connection plate are electrically connected by a spring tightening force.
FIG. 7 is a view showing the shape of a connection plate.
FIG. 8 is an enlarged view of the upper surface of the contact portion.
FIG. 9 is a side view of a contact portion between an electrode and a connection plate.
FIG. 10 is a diagram showing the relationship between the bending angle of the nail and the force with which the nail presses the electrode.
FIG. 11 is a view showing an example of a connection plate manufactured using conductive rubber.
FIG. 12 is a diagram showing an example of a connection plate made using a conductive plastic.
FIG. 13 is a diagram showing an example in which a contact portion between a connection plate and an electrode is shielded from the atmosphere.
FIG. 14 is a diagram showing a load header according to the second embodiment.
FIG. 15 is a diagram showing the force exerted by the connection plate on the hollow electrode.
FIG. 16 is a diagram illustrating a load header production method according to the second embodiment;
FIG. 17 is a diagram showing a load header production method according to the second embodiment;
FIG. 18 is a view showing fixing between a hollow electrode and a connection plate by an adhesive.
FIG. 19 is a diagram illustrating a load header production method according to the third embodiment;
FIG. 20 is a flowchart of a load header production method according to the third embodiment;
FIG. 21 is a diagram showing a load header according to the third embodiment.
FIG. 22 is a diagram showing a modification of the load header production method according to the third embodiment;
[Explanation of symbols]
DESCRIPTION OF SYMBOLS 1 ... Capillary, 2 ... Sample container, 3 ... Sample tray, 4 ... Load header, 5 ... Detection part, 6 ... Laser light source, 7 ... Mirror, 8 ... Beam splitter, 9 ... Condensing lens, 10 ... Fluorescence, 11 ... Detection lens system, 12 ... CCD camera, 13 ... buffer solution, 14 ... buffer solution container, 15 ... high voltage power supply, 16 ... separator, 17 ... capillary head, 20 ... hollow electrode, 21 ... signal processing arithmetic unit, 22 ... solder 23 ... connecting plate, 24 ... solder, 25 ... holder, 26 ... lid, 27 ... adhesive, 28 ... contact part, 29 ... capillary guide hole, 30 ... claw, 31 ... inscribed circle, 101 ... high voltage Terminal plug, 102 ... guide, 128 ... guide pin, 129 ... flare shape, 130130 ... connection plate hole, 131 ... insertion position, 132 ... conductive adhesive, 133 ... tag, 134 ... groove in holder, 35 ... hollow electrode insertion employment, 136 ... stand, 137 ... combined groove 138 ... guide boss 139 ... ribs, 140 ... horn.

Claims (32)

A plurality of capillaries that are filled with a separation medium for separating a sample and have a sample injection end for introducing the sample, and a plurality of laser light irradiation units of the capillaries (laser light for generating fluorescence from the sample is the capillary A load header provided with a conductive connection member that is disposed in parallel with the detection unit that holds the portion in the vicinity of the sample injection end and is electrically connected to the hollow electrode; A capillary array including a capillary head holding the other end,
A capillary array, wherein the conductive connecting member has a contact surface with the hollow electrode, and the contact surface is pressure-bonded by a volume elastic force. The capillary array according to claim 1 , wherein
The capillary array, wherein the conductive connecting member is a conductive rubber. The capillary array according to claim 1 , wherein
The capillary array, wherein the hollow electrode is made of austenitic stainless steel. The capillary array according to claim 1 , wherein
A capillary array characterized in that the cross-sectional shape of the outer surface of the hollow electrode is a circle. The capillary array according to claim 1 , wherein
The capillary array, wherein the load header includes a compression member that compresses the conductive connection member in the vicinity of a contact surface between the hollow electrode and the conductive connection member. The capillary array according to claim 5 , wherein
The capillary array, wherein the hollow electrode exists between a plurality of compressed portions (portions of the conductive member compressed by the compression member). 2. The capillary array according to claim 1 , wherein one end of the hollow electrode has a flare shape. The capillary array according to claim 1 , wherein
A capillary array, wherein the conductive member is in direct contact with a high voltage contact. A plurality of capillaries that are filled with a separation medium for separating a sample and have a sample injection end for introducing the sample, and a plurality of laser light irradiation units of the capillaries (laser light for generating fluorescence from the sample is the capillary A load header provided with a conductive connection member that is disposed in parallel with the detection unit that holds the portion in the vicinity of the sample injection end and is electrically connected to the hollow electrode; An electrophoresis apparatus having a capillary array including a capillary head holding the other end,
An electrophoretic device, wherein the conductive connecting member has a contact surface with the hollow electrode, and a capillary array that presses the contact surface with a volume elastic force. The electrophoresis apparatus according to claim 9, wherein
The electrophoretic device, wherein the conductive connecting member is a conductive rubber. The electrophoresis apparatus according to claim 9, wherein
The electrophoresis apparatus, wherein the hollow electrode is made of austenitic stainless steel. The electrophoresis apparatus according to claim 9, wherein
The electrophoresis apparatus according to claim 1, wherein a cross-sectional shape of an outer surface of the hollow electrode is a circle. The electrophoresis apparatus according to claim 9, wherein
The electrophoretic device, wherein the load header includes a compression member that compresses the conductive connection member in the vicinity of a contact surface between the hollow electrode and the conductive connection member. The electrophoresis apparatus according to claim 13, wherein
The electrophoresis apparatus, wherein the hollow electrode is present between a plurality of compressed portions (portions of the conductive member compressed by the compression member). 10. The electrophoresis apparatus according to claim 9, wherein one end of the hollow electrode has a flare shape. The electrophoresis apparatus according to claim 9, wherein
The electrophoretic device, wherein the conductive member is in direct contact with a high voltage contact. A plurality of capillaries having a sample injection end for introducing a sample;
A detection member that holds a part of the plurality of capillaries irradiated with light;
A sample injection end holding member comprising: a hollow electrode holding the sample injection end; and a conductive connection member electrically connected to the hollow electrode;
A capillary array including a second end holding member that holds the other end of the plurality of capillaries,
The capillary array, wherein the conductive connecting member is made of conductive rubber or conductive plastic. The capillary array according to claim 17,
The capillary array, wherein the hollow electrode is made of austenitic stainless steel. The capillary array according to claim 17,
The capillary array, wherein the conductive connection member is a conductive connection plate. The capillary array according to claim 17,
The capillary array, wherein the conductive connecting member is in contact with an outer surface of the hollow electrode by a plurality of claw-shaped springs provided symmetrically around each hollow electrode. The capillary array according to claim 20,
A capillary array, wherein a contact surface pressure between the outer surface of the hollow electrode and the claw-shaped spring of the conductive connecting member is 5 to 10 MPa. The capillary array according to claim 17,
A capillary array, wherein an adhesive is applied to a contact portion between the hollow electrode and the claw-shaped spring of the conductive connecting member and cured. The capillary array according to claim 17,
The capillary array, wherein the hollow electrode penetrates the conductive connecting member. The capillary array according to claim 23, wherein
A capillary array, wherein a contact surface between the hollow electrode and the conductive connecting member is pressure-bonded by a volume elastic force. A plurality of capillaries having a sample injection end for introducing a sample, a detection member for holding a part of the plurality of capillaries irradiated with light, a hollow electrode for holding the sample injection end, and the hollow electrode A capillary array including a sample injection end holding member including a conductive connection member electrically connected to the other end holding member for holding the other end of the plurality of capillaries;
A power source capable of electrophoresis of the samples in the plurality of capillaries;
An excitation optical system capable of irradiating the detection member with light;
An electrophoresis apparatus including a detection lens system capable of detecting light emitted from a sample,
The electrophoretic device, wherein the conductive connecting member is made of conductive rubber or conductive plastic. The electrophoresis apparatus according to claim 25, wherein
The electrophoresis apparatus, wherein the hollow electrode is made of austenitic stainless steel. The electrophoresis apparatus according to claim 25, wherein
The electrophoretic device, wherein the conductive connecting member is a conductive connecting plate. The electrophoresis apparatus according to claim 25, wherein
The electrophoretic device, wherein the conductive connecting member is in spring contact with an outer surface of the hollow electrode by a plurality of claw-shaped springs provided symmetrically around each hollow electrode. The electrophoresis apparatus according to claim 28, wherein
An electrophoretic device, wherein a contact surface pressure between the outer surface of the hollow electrode and the claw-shaped spring of the conductive connecting member is 5 to 10 MPa. The electrophoresis apparatus according to claim 28, wherein
An electrophoresis apparatus, wherein an adhesive is applied to a contact portion between the hollow electrode and the claw-shaped spring of the conductive connecting member and cured. The electrophoresis apparatus according to claim 25, wherein
The electrophoresis apparatus, wherein the hollow electrode penetrates the conductive connecting member. The electrophoresis apparatus according to claim 31, wherein
An electrophoresis apparatus, wherein a contact surface between the hollow electrode and the conductive connecting member is pressure-bonded by a volume elastic force.

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