JP2007263869A - Liquid container - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a liquid container accessible by a pipette, simple in replenishment work. <P>SOLUTION: This liquid container 61 comprises a main tank 71, a replenishment tank 72, and a connection part 73 for connecting the main tank 71 to the replenishment tank 72. A storage tank 74 for storing the liquid is formed in the main tank 71, and a pipette accesses the storage tank 74 from the upside. The replenishment tank 72 comprises a bottle 86 for storing the liquid, and a cap part 87 for covering a mouth 86a of the bottle 86. The cap part 87 includes a taking-out port 89 for taking out the liquid to the outside and a valve mechanism 91 for opening/closing the taking-out port 89. When the replenishment tank 72 is mounted on the connection part 73, the valve mechanism 91 opens the taking-out port 89, and the liquid in the bottle 86 is replenished into the storage tank 74. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a liquid container for storing a liquid sucked by a pipette.

  2. Description of the Related Art Measuring apparatuses that optically measure the reaction of a sample are known in order to measure interactions between biochemical substances such as proteins and DNA, and to screen for drugs. As one of such measuring apparatuses, there is a measuring apparatus (hereinafter referred to as an SPR measuring apparatus) using a surface plasmon resonance phenomenon (refer to Patent Document 1). The surface plasmon is a density wave of free electrons generated by collective vibration of free electrons in a metal and traveling along the surface of the metal.

  In the SPR measurement device, for example, a transparent dielectric block (hereinafter referred to as a prism) is used, and the surface of the metal film formed on the prism is used as a sensor surface while reacting a sample on the sensor surface. The metal film is irradiated from the back side of the sensor surface through the prism so as to satisfy the total reflection condition, and the reflected light is measured.

  Of the light irradiated to the metal film so as to satisfy the total reflection condition, a small amount of light called an evanescent wave passes through the metal film without being reflected and oozes out to the sensor surface side. At this time, if the frequency of the evanescent wave coincides with the frequency of the surface plasmon, SPR is generated and the intensity of the reflected light is greatly attenuated. In addition, the incident angle (resonance angle) of light at which this attenuation occurs varies depending on the refractive index on the metal film. That is, the SPR measurement device measures the reaction state of the sample on the sensor surface by capturing the reflected light from the metal film and detecting the resonance angle.

  In experiments and research in the field of biochemistry, proteins, DNA, drugs and the like are used as ligands and analytes. For example, when screening for drugs, biological substances such as proteins are used as ligands, and a plurality of types of drugs serving as analytes are brought into contact with the sensor surface to examine their interaction. When measuring the interaction between the analyte and the ligand, the ligand is fixed on the sensor surface, and then the analyte solution is fed to the sensor surface on which the ligand is fixed. Then, contact the analyte with the ligand and examine their reaction status.

  The ligand fixing process is a process in which a ligand solution is fed to a linker film formed in advance on the sensor surface to fix the ligand to the linker film. In the ligand immobilization treatment, before the ligand solution is sent to the linker membrane, the activation solution is sent to the linker membrane to facilitate the binding of the ligand. After the activation treatment is performed in this way, the cleaning liquid is fed to clean the linker film. Thereafter, the ligand solution is fed to the linker film, and the ligand in the solution is fixed to the linker film. Thereafter, the cleaning liquid is again fed to clean the linker film. After such a ligand fixing process is performed, the measurement process is performed.

Thus, in order to perform the measurement, it is necessary to send various liquids to the sensor surface in addition to the sample solution such as the analyte and the ligand. As a method for sending liquid to such a sensor surface, there is a method using piping (tube) connected to a pump, a valve or the like. In this method, in order to prevent contamination, piping is performed for each type of liquid. The pipe must be cleaned each time the liquid is divided or the liquid flowing through the pipe is replaced. Since such a cleaning operation takes time and effort, there is a problem that the processing efficiency of the fixing process and the measurement process is lowered.
JP 2001-330560 A

  Therefore, a method has been studied in which a liquid is accommodated in a well plate in which a plurality of well-shaped ridges are arranged, and this liquid is sucked with a pipette and fed to the sensor surface. If a plurality of well plates are prepared for each type of liquid, contamination can be prevented without performing a complicated cleaning operation if only the pipette tip at the tip of the pipette is replaced. However, since the well plate has a small liquid storage capacity, the number of times of replenishment increases when a large amount of liquid is used. The replenishment of the liquid to the well plate is performed, for example, by pouring the replenishment liquid from the bottle into the well plate. However, since such a replenishment operation is time-consuming, a countermeasure for preventing a decrease in processing efficiency due to this is desired. It had been.

  An object of the present invention is to provide a liquid container that can be accessed by a pipette and can be easily refilled.

  The liquid container of the present invention has a main body in which a storage tank for storing the liquid is formed in a liquid container for storing the liquid sucked by the pipette, and the pipette is accessible from an upper opening of the storage tank. A cap portion provided with a main tank, a bottle for storing the liquid to be replenished in the storage tank, a takeout port for taking out the liquid in the bottle to the outside, and a valve mechanism for opening and closing the takeout port And a connecting portion for connecting the main tank and the replenishing tank to each other in a posture in which the cap portion is directed downward. And

  It is preferable that the valve mechanism is engaged with the connecting portion to open and close the take-out port in conjunction with an attaching / detaching operation of the replenishing tank to the connecting portion.

  The storage tank preferably has a substantially V-shaped longitudinal section. Moreover, it is preferable that the said main-body part and a connection part are integrally formed.

  It is preferable that the main body portion and the connecting portion are made of metal. Furthermore, it is preferable that at least a part of the cap portion is made of metal.

  The main tank includes a cover that covers the upper opening, and the cover is preferably formed with an insertion port through which the tip of the pipette is inserted. Furthermore, the cover is preferably made of metal.

  An evaporation preventing sheet that is disposed between the cover and the main body portion and blocks the insertion hole from the inside of the cover to prevent evaporation of the liquid is provided, and this evaporation preventing sheet is formed of an elastic material. In addition, it is preferable that a notch into which the pipette can be inserted is formed at a position corresponding to the insertion port.

  It is preferable that a sealing sheet that is disposed between the cover and the main body and seals a gap between the cover and the main body in a watertight manner is provided.

  It is preferable that the valve mechanism is engaged with the connecting portion to open and close the take-out port in conjunction with an attaching / detaching operation of the replenishing tank to the connecting portion.

  The cap portion has a cap body in which the take-out port is formed, and the valve mechanism is inserted into the cap body with one end projecting toward the outside of the cap body and slides in the vertical direction. And a valve that opens and closes the outlet in response to sliding of the shaft, and a spring that biases the shaft so that the valve closes the outlet, and the cap body is attached to the connecting portion When this is done, it is preferable that the valve opens the outlet when the one end and the connecting portion come into contact with each other and the shaft slides against the bias of the spring.

  According to the present invention, it has a main body part in which a storage tank for storing liquid is formed, and contains a main tank accessible to the pipette from an upper opening of the storage tank, and the liquid to be replenished to the storage tank. And a replenishing tank formed with a cap portion provided with a valve mechanism for opening and closing the discharge port, and a posture with the cap portion facing downward The replenishing tank is detachably attached to the mounting portion, and is composed of a connecting portion that connects the main tank and the replenishing tank. Therefore, a liquid that can be accessed by a pipette and is easy to replenish. A container can be provided.

  As shown in FIG. 1, the measurement method using SPR is roughly divided into three steps: a fixing step, a measurement processing step (data reading step), and a data analysis step. The SPR measuring device includes a fixing machine 10 that performs a fixing process, a measuring machine 11 that performs a measuring process, and a data analyzer that analyzes data obtained by the measuring machine 11.

  The measurement is performed using the sensor unit 12. The sensor unit 12 has a metal film 13 having one surface serving as a sensor surface 13a on which SPR occurs, a prism 14 bonded to a light incident surface 13b on the back surface of the sensor surface 13a, and the sensor surface 13a. And a flow path member 41 having a flow path 16 through which a ligand and an analyte are fed.

  As the metal film 13, for example, gold is used, and the film thickness is, for example, 50 nm. This film thickness is appropriately selected according to the material of the metal film, the emission wavelength of the irradiated light, and the like. The prism 14 is a transparent dielectric having the metal film 13 formed on the upper surface thereof, and condenses the light irradiated so as to satisfy the total reflection condition toward the light incident surface 13b. The flow path 16 is a liquid feeding pipe formed by penetrating the flow path member 41 in a substantially U shape, and a pair of inlets and outlets serving as an inlet for injecting liquid and an outlet for discharging the liquid are provided at both ends. 16a and 16b are provided.

  The bottom of the channel 16 is an open groove, and this open part is covered and sealed with the sensor surface 13a. A sensor cell 17 is constituted by the flow path 16 and the sensor surface 13a. As will be described later, the sensor unit 12 includes a plurality of such sensor cells 17 (see FIG. 2).

  The fixing step is a step of fixing the ligand to the sensor surface 13a. The fixing process is performed by setting the sensor unit 12 to the fixing machine 10. The fixing machine 10 is provided with a pipette pair 19 including a pair of pipettes 19a and 19b. In the pipette pair 19, the pipettes 19a and 19b are inserted into the entrances 16a and 16b, respectively. Each of the pipettes 19a and 19b has a function of injecting liquid into the flow channel 16 and sucking out from the flow channel 16, and when one of them performs the injection operation, the other performs the suction operation. So that they work together. Using this pipette pair 19, a ligand solution 21 in which a ligand is dissolved in a solvent is injected from the entrance / exit 16a.

  A linker film 22 that binds to the ligand is formed at substantially the center of the sensor surface 13a. The linker film 22 is formed in advance at the manufacturing stage of the sensor unit 12. Since the linker film 22 serves as a fixing group for fixing the ligand, it is appropriately selected according to the type of ligand to be fixed.

  In the immobilization process, before injecting the ligand solution 21, as a pretreatment, first, the immobilization buffer solution is sent to the linker film 22 to wet the linker film 22, and then the ligand is transferred to the linker film 22. In order to facilitate bonding, the linker film 22 is activated. For example, in the amine coupling method, carboxymethyl dextran is used as the linker film 22, and the amino group in the ligand is directly covalently bonded to the dextran. As the activation liquid in this case, a mixed liquid of N ′-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) is used. After this activation process, the flow path 16 is washed by the fixing buffer.

  As the buffer for fixation and the solvent (diluent) of the ligand solution 21, for example, various buffer solutions (buffer solutions), physiological salt solutions represented by physiological saline, and pure water are used. . The type of each of these liquids, the pH value, the type of mixture, its concentration, etc. are appropriately determined according to the type of ligand. For example, when a biological substance is used as a ligand, physiological saline whose pH is adjusted to near neutral is often used. However, in the amine coupling method, the linker film 22 is negatively (negatively) charged by carboxymethyl dextran. Therefore, the protein is positively (positively) charged so as to be easily bonded to the linker film 22. In some cases, a phosphate buffer solution (PBS: Phosphatic-Buffered, Saline) having a strong buffering action containing a high concentration of phosphate may be used.

  After such activation treatment and cleaning, the ligand solution 21 is injected into the sensor cell 17. When the ligand solution 21 is injected into the flow path 16, the ligand 21 a diffusing in the solution gradually approaches the linker film 22 and binds. In this way, the ligand 21a is fixed to the sensor surface 13a. The immobilization usually takes about one hour, and during this time, the sensor unit 12 is stored in a state where the environmental conditions including the temperature are set to predetermined conditions. The ligand solution 21 in the channel 16 may be allowed to stand while the immobilization proceeds, but the ligand solution 21 in the channel 16 is preferably stirred and flowed. By doing so, the binding between the ligand and the linker film 22 is promoted, and the amount of the ligand immobilized can be increased.

  When the immobilization of the ligand 21a on the sensor surface 13a is completed, the ligand solution 21 is discharged from the flow path 16. The ligand solution 21 is sucked and discharged by the pipette 19b. After the immobilization, the sensor surface 13a is subjected to a cleaning process by injecting a cleaning liquid into the channel 16. After this washing, if necessary, a blocking liquid is injected into the flow path 16 to perform a blocking process for inactivating the reactive group to which no ligand is bound in the linker film 22. As the blocking liquid, for example, ethanolamine-hydrochloride is used. After this blocking process, the channel 16 is washed again. Thereafter, the drying prevention liquid is injected into the flow path 16, and the sensor unit 12 is stored until the measurement with the sensor surface 13 a immersed in the drying prevention liquid.

  The measurement process is performed with the sensor unit 12 set on the measuring machine 11. The measuring machine 11 is also provided with a pipette pair 26 similar to the pipette pair 19 of the fixing machine 10. By the pipette pair 26, various liquids are injected into the flow path 16 from the inlet / outlet port 16a. In the measurement process, first, a measurement buffer is injected into the flow path 16. Thereafter, an analyte solution 27 in which the analyte is dissolved in a solvent is injected, and then the measurement buffer is injected again. Note that the flow path 16 may be once cleaned before the measurement buffer is first injected. Data reading is started immediately after the measurement buffer is first injected in order to detect a reference signal level, and is performed after the analyte solution 27 is injected and until the measurement buffer is injected again. . As a result, it is possible to measure the SPR signal from detection of the reference level (baseline), reaction state of the analyte and ligand (binding state), and desorption of the combined analyte and ligand by injection of the measurement buffer.

  As the buffer for measurement and the solvent (diluent) of the analyte solution 27, for example, various buffer solutions (buffer solutions), physiological salt solutions represented by physiological saline, and pure water are used. The The type of each of these liquids, the pH value, the type of mixture, its concentration, etc. are appropriately determined according to the type of ligand.

  The measurement unit 31 includes an illumination unit 32 and a detector 33. As described above, the reaction state between the ligand and the analyte appears as a change in the resonance angle (the incident angle of the light applied to the light incident surface). Therefore, the illumination unit 32 irradiates the light incident surface 13b with light having various incident angles that satisfy the total reflection condition. The illumination unit 32 includes, for example, a light source 34 and an optical system 36 including a condensing lens, a diffuser plate, and a polarizing plate. The arrangement position and the installation angle satisfy the total reflection condition in terms of the incident angle of illumination light. To be adjusted.

  As the light source 34, for example, a light emitting element such as an LED (Light Emitting Diode), an LD (Laser Diode), or an SLD (Super Luminescent Diode) is used. One such light emitting element is used, and light is emitted from this single light source toward one sensor cell. When measuring a plurality of sensor cells at the same time, the light from a single light source may be dispersed and irradiated to the plurality of sensor cells, or one light emitting element may be assigned to each sensor cell. A plurality of light emitting elements may be used side by side. The diffusion plate diffuses light from the light source 34 and suppresses unevenness in the amount of light in the light emitting surface. The polarizing plate allows only p-polarized light that causes SPR to pass through. In addition, when using LD, when the direction of polarization of the light itself emitted from the light source is uniform, the polarizing plate is unnecessary. In addition, even when a light source with uniform polarization is used, if the direction of polarization becomes uneven by passing through the diffusion plate, the direction of polarization is aligned using a polarizing plate. The light thus diffused and polarized is condensed by the condenser lens and irradiated onto the prism 14. As a result, it is possible to cause the light incident surface 13b to enter the light rays having various incident angles without variation in light intensity.

  The detector 33 receives the light reflected by the light incident surface 13b and outputs an electrical signal having a level corresponding to the light intensity. Since light rays are incident on the light incident surface 13b at various angles, the light rays are reflected on the light incident surface 13b at various reflection angles according to respective incident angles. The detector 33 receives light beams having these various reflection angles. When the analyte is fed onto the sensor surface 13a, the refractive index changes according to the reaction state between the analyte and the ligand, the resonance angle changes, and the reflection angle at which the light intensity attenuates also changes.

  The detector 33 uses, for example, a CCD area sensor or a photodiode array, receives reflected light reflected at various reflection angles on the light incident surface 13b, photoelectrically converts them, and outputs them as SPR signals. The reaction state between the ligand and the analyte appears as a transition of the attenuation position of the reflected light in the light receiving surface. For example, the refractive index on the sensor surface 13a is different before and after the analyte comes into contact with the ligand, and therefore the resonance angle at which SPR occurs and the corresponding reflection angle are different. When the analyte comes into contact with the ligand and starts to react, the resonance angle of the reflected light starts to change accordingly, and the attenuation position of the reflected light in the light receiving surface starts to move. An SPR signal representing the reaction situation obtained in this way is output to the data analyzer 91. In the data analysis step, the SPR signal obtained by the measuring instrument 11 is analyzed to analyze the characteristics of the analyte.

  For the sake of convenience, in FIG. 1, the direction of the incident light beam on the light incident surface 13 b and the reflected light beam reflected there is the flow direction of the liquid in the flow channel 16 so that the configuration of the measurement unit 31 becomes clear. Although the illumination unit 32 and the detector 33 are arranged so as to be parallel to each other, actually, the direction of the incident light beam and the reflected light beam is irradiated in a direction orthogonal to the flow direction. An illumination unit 32 and a detector 33 are arranged. Of course, the measurement unit 31 may be arranged and measured as shown in FIG.

  FIG. 2 is an exploded perspective view of the sensor unit 12. The sensor unit 12 has a long shape, and a plurality (for example, six) of the sensor cells 17 are arranged along the longitudinal direction. Six channels 16 are formed on the channel member 14, and linker films 22 are formed on the metal film 13 of the prism 14 at positions corresponding to the channels 16. The holding member 42 engages with the prism 14 to hold the flow path member 41 with the prism 14. Engaging claws 14 a that engage with the engaging portions 42 a of the holding member 42 are provided on both side surfaces of the prism 14 in the longitudinal direction. By these engagements, the bottom surface 41a of the flow path member 41 and the top surface of the prism 14 are integrated in a pressed state.

  In the upper part of the holding member 42, a receiving port 42 b into which the tip of the pipette (19 a, 19 b, 26 a, 26 b) enters is formed at a position corresponding to the inlet / outlet 16 a, 16 b of each channel 16. The receiving port 42b has a funnel shape so that the liquid discharged from the pipette is guided to each inlet / outlet port 16a. When the holding member 42 sandwiches the channel member 41 and engages with the prism 14, the lower surface of the receiving port 42b is joined to the inlets 16a and 16b, and the receiving port 42b and the channel 16 are connected.

  As shown in FIG. 3, a mounting space 51 for mounting the plurality of sensor units 12 is secured on the housing base 50 that is a base of the fixed machine 4. The sensor unit 12 is subjected to a fixing process while being placed in the placement space 51.

  The sensor unit 12 is placed in the placement space 51 while being housed in the holder 52. The holder 52 can store a plurality of sensor units 12 (eight in this example).

  In the mounting space 51, for example, ten holders 52 can be arranged side by side, and pedestals 53 corresponding to the number of the holders 52 are provided. Each pedestal 53 is formed with a positioning boss for positioning the holder 52.

  The fixing machine 10 is provided with a pipette head 54 in which six pairs of pipettes 19 are connected in accordance with the number of flow paths 16 of the sensor unit 12. The pipette head 54 simultaneously accesses the six flow paths 16 of the sensor unit 12 on the placement space 51 to inject and discharge liquid. The fixed machine 4 is provided with a controller (not shown). The suction and discharge operations of the pipette head 74 are controlled by this controller, and the suction amount, discharge amount, timing, and the like are determined for each pipette pair 19.

  Further, the pipette head 54 can operate one pipette 19a of each pipette pair 19 independently of the other pipette 19b. As will be described later, when the liquid is sucked from the liquid container, In this case, only the suction side pipette 19a accesses the liquid container to perform suction.

  The housing base 50 is provided with a head moving mechanism 56 that moves the pipette head 54 in three directions of X, Y, and Z. The head moving mechanism 56 is a known moving mechanism including, for example, a conveyance belt, a pulley, and a motor. The head moving mechanism 56 is an elevating mechanism that moves the pipette head 54 up and down, and the pipette head 54 can be moved in the Y direction together with the elevating mechanism. A Y-direction moving mechanism including a guide rail 58 to be held and an X-direction moving mechanism that holds the guide rail 58 at both ends and moves the pipette head 54 in the X direction together with the guide rail 58. The head moving mechanism 56 is controlled by a controller, and the controller drives the head moving mechanism 56 to control the front / rear / left / right / up / down positions of the pipette head 54.

  Further, in the mounting space 51, a plurality of liquid containers 61 for storing various liquids to be injected into the flow path 16, a pipette tip storage unit 63 for storing pipette tips 62, and a plurality of well-like tubs are arranged in a matrix. The well plate 64 is provided.

  The number of liquid containers 61 is determined according to the type of liquid used, such as a ligand solution, a cleaning solution, a fixing buffer solution, a drying prevention solution, an activation solution, or a blocking solution. When the pipette head 54 injects a liquid into the flow path 16, the liquid container 61 is accessed to suck in a desired liquid, and then moves to the placement space 51 and is injected into each flow path 16.

  The pipette tip 62 stored in the pipette tip storage unit 63 is detachably held by the pipette head 54. Since the pipette tip 62 is in direct contact with the liquid, it is exchanged for each liquid to be used so that different kinds of liquids are not mixed through the pipette tip 62. The pipette head 54 incorporates a mechanism for picking up and releasing the pipette tip 62 so that the pipette tip 62 is automatically replaced. When exchanging the pipette tip 62, the pipette head 54 first releases the used pipette tip 62 at a disposal unit (not shown), and then accesses the pipette tip storage unit 63 to access an unused pipette tip. Pick up 62. This prevents liquid contamination.

  The well plate 64 is used for temporarily storing the liquid sucked up by the pipettes 19a and 19b, or for preparing a mixed liquid by mixing a plurality of types of liquids.

  Further, when the fixing device 10 performs the fixing process, the housing base 50 is covered with the cover, and the inside of the fixing device 4 including the placement space 51 is shielded. The sensor unit 12 is stored in the mounting space 51 for a predetermined time until the ligand immobilization is completed. At this time, the degree of progress of immobilization depends on the temperature. Therefore, the fixing machine 10 keeps the internal temperature at a predetermined temperature by a temperature controller (not shown) while fixing. The set temperature, standing time, and the like are appropriately determined according to the type of ligand to be immobilized.

  As shown in FIG. 4, the liquid container 61 includes a main tank 71 that stores liquid, a replenishment tank 72 that stores liquid to be replenished to the main tank 71, and a connecting portion 73 that connects them. The connecting portion 73 is formed integrally with the main tank 71, and a replenishment tank 72 is detachably attached to the connecting portion 73. In the liquid container 61, the length of the main tank 71 in the longitudinal direction is about 20 centimeters, the diameter of the replenishing tank 72 is about 15 centimeters, and has a larger capacity than the well plate. The size of the liquid container 61 shown in this example is an example, and can be changed as appropriate according to the amount of liquid used.

  The main tank 71 has an elongated shape, and six insertion ports 75 into which the pipette 19a is inserted are formed in the center of the upper surface in the width direction. The insertion openings 75 are arranged in a line at substantially equal intervals in accordance with the arrangement of the pipettes 19a attached to the pipette head 54. The pipette head 54 accesses the main tank 71 in a state where only the suction-side pipette 19a for sucking liquid is lowered from the other pipette 19b, and inserts the six pipettes 19a into the insertion port 75, Aspirate liquid. In this example, there are six insertion openings 75, but the number and arrangement pitch of each insertion opening 75 can be appropriately changed according to the number of pipettes provided in the pipette head 54 and the arrangement pitch.

  As shown in FIG. 5, the main tank 71 includes a main body 76 in which a storage tank 74 is formed, and a cover 77 that covers the upper opening 74 a of the storage tank 74. The cover 77 has a substantially U-shaped cross section, and the insertion port 75 is formed on the upper surface of the cover 77. The tip of the pipette 19 a enters the storage tank 74 through the insertion port 75. A support piece 76a is formed around the upper opening 74a of the main body 76 so as to protrude horizontally and receive and support the cover 77. The cover 77 is fixed to the support piece 76a by a bolt 78, and It is attached to the part 76.

  The main body portion 76 and the connecting portion 73 are integrally formed, and the main body portion 76, the connecting portion 73, and the cover 77 are made of metal. As described above, the temperature of the fixing machine 10 is adjusted in order to keep the temperature of the liquid at an appropriate temperature. By using a metal having high thermal conductivity, the temperature of the liquid in the liquid container 61 can be easily adjusted.

  An evaporation prevention sheet 81 and a sealing sheet 82 are disposed between the main body 76 and the cover 77. The evaporation preventing sheet 81 covers the upper opening 74a and closes the insertion port 75 from the inside of the cover 77 to prevent the liquid in the storage tank 74 from evaporating. The evaporation preventing sheet 81 is formed with a cross-shaped cut 81 a at a position corresponding to each insertion opening 75. The evaporation preventing sheet 81 is formed of an elastic material. When the pipette 19a is inserted from the insertion port 75, the notch 81a is elastically deformed by contacting the tip of the pipette 19a, and the pipette 19a is inserted. When it is pulled out, it returns to its initial shape and closes the insertion port 75. By preventing evaporation of the liquid in the storage tank 74 in this way, fluctuations in the liquid concentration due to evaporation are prevented. Since the concentration fluctuation of the liquid ultimately affects the measurement accuracy in the measurement process, the measurement accuracy can be improved by preventing evaporation of the storage tank 74.

  The sealing sheet 82 is a rubber sheet having an opening corresponding to the upper opening 74a. The sealing sheet 82 seals the gap between the cover 77 and the support piece 76a in a watertight manner, and liquid leaks out of the storage tank 74 to the outside. Do not. Each of the evaporation preventing sheet 81 and the sealing sheet 82 is formed with a hole through which the bolt 78 is inserted, and is sandwiched between the main body 76 and the cover 77.

  As shown in FIG. 6, the storage tank 74 has a substantially V-shaped vertical section with the bottom of the storage tank 74 at the top, and the lateral width is narrowed downward from the upper opening 74a. . For this reason, when the water level falls, the liquid in the storage tank 74 concentrates near the top. The position of the vertex and the insertion port 75 in the width direction correspond to each other. Therefore, when the pipette 19a is inserted into the insertion port 75 substantially vertically, the tip of the pipette 19a reaches the vicinity of the apex. Thereby, even if the liquid in the storage tank 74 becomes small, it collects near the tip of the pipette 19a, so that suction by the pipette 19a is possible. Therefore, the amount (dead volume) that cannot be sucked can be reduced.

  The connecting portion 73 has a cup shape with a circular cross section, and is provided at one end of the main body portion 76. The connection part 73 is connected with the storage tank 74 so that a liquid can distribute | circulate through the replenishment path 83 (refer FIG. 7). An opening is formed in the upper portion of the connecting portion 73, and this opening becomes an attachment portion 84 to which the replenishment tank 72 is attached. The attachment portion 84 receives a part of the replenishing tank 72 therein and supports the replenishing tank 72. The attachment portion 84 is formed with an internal thread that is screwed into the replenishment tank 72 and screwed to the inner peripheral surface thereof, and the replenishment tank 72 is detachably attached to the connecting portion 73 by screwing.

  The replenishing tank 72 includes a substantially cylindrical bottle 86 that contains a replenishing liquid, and a cap portion 87 that is attached to the mouth 86 a of the bottle 86. The bottle 86 is made of, for example, transparent glass so that the remaining amount of liquid can be visually confirmed. The cap portion 87 covers the mouth 86a and has a cap body 88 formed with a take-out port 89 for taking out the liquid in the bottle 86, and a valve mechanism 91 provided in the cap body 88 for opening and closing the take-out port 89. Consists of. On the outer periphery of the distal end portion 88a of the cap body 88, a male screw that is screwed with the female screw of the attachment portion 84 is formed. The replenishing tank 72 is attached to the connecting portion 73 with the cap portion 87 facing downward so that the tip end portion 88a engages with the attaching portion 84.

  As shown in FIG. 7, the take-out port 89 passes through the cap body 88. Since the replenishment tank 72 is attached with the cap portion 87 facing downward, the liquid in the bottle 86 is directed to the take-out port 89 by gravity. When the takeout port 89 is opened by the valve mechanism 91, it flows out to the outside in exchange for the air taken into the bottle 86 from the takeout port 89. The valve mechanism 91 includes a shaft 92 provided on the cap body 88 so as to be slidable in the vertical direction, a valve 93 that opens and closes the extraction port 89 according to the sliding of the shaft 92, and a shaft so that the valve 93 closes the extraction port 89. It becomes a spring 94 for biasing 92.

  The shaft 92 has such a length that one end enters the bottle 86 and the other end protrudes from the cap body 88 to the outside, and the valve 93 is formed at one end of the shaft 92 that enters the bottle 86. . The valve 93 has a disk shape, and has a closed position that covers the end face of the cap body 88 to close the takeout port 89, and an open position that retreats from the closed position by sliding the shaft 92 and opens the takeout port 89. Move between.

  At the other end of the shaft 92, an abutting portion 95 that abuts against the floor surface of the connecting portion 73 when the cap portion 87 is attached to the connecting portion 73 is formed. The contact portion 95 has a larger diameter than the shaft 92. A spring 94 is inserted into the other end of the shaft 92. Both ends of the spring 94 are in contact with the contact portion 95 and the cap body 88, respectively, and the shaft 92 is urged in a direction in which the distance between the contact portion 95 and the cap body 88 is increased. Thereby, the valve 93 is urged to the closed position.

  When the cap portion 87 is attached to the connecting portion 73, the contact portion 95 contacts the floor surface of the connecting portion 73 before the tip end portion 88a and the attaching portion 84 are screwed. When the top end 88 a is screwed by rotating the replenishment tank 72 while resisting the bias of the spring 94, the front end 88 a is pushed into the connecting portion 73. Thereby, since the shaft 92 slides relatively with respect to the cap main body 88 in the direction in which the space between the tip end portion 88a and the contact portion 95 is narrowed, the valve 93 moves to the open position. As a result, the liquid flows out from the outlet 89 to the connecting portion 73 and is sent to the storage tank 74 through the replenishment path 83. When removing the replenishing tank 72 from the connecting portion 73, the valve 93 returns to the closed position by the bias of the spring 94. In this way, the valve 93 is automatically opened and closed in conjunction with the attaching / detaching operation of the replenishing tank 72 to the connecting portion 73.

  As shown in FIG. 8, a notch 97 is formed in the distal end portion 88 a, and the water level h of the storage tank 74 is maintained at a predetermined height by the notch 97. Since the liquid in the bottle 86 flows out from the outlet 89 according to the amount of air flowing into the bottle 86, the bottle 86 passes through the outlet 89 through the outlet 89 while the water level h is lower than the notch 97. Since the atmosphere flows in, the liquid continues to flow out of the bottle 86 in exchange for the atmosphere. Then, when the water level h rises and the notch 97 is blocked, the atmosphere cannot flow into the bottle 86, so that the outflow of liquid stops. When the liquid is sucked from the storage tank 74 by the pipette 19a, the water level h is lowered accordingly, so that the notch 97 is opened and the liquid flows out from the bottle 86 until the notch 97 is closed. Thus, the liquid corresponding to the suction amount of the pipette 19a is replenished from the bottle 86 to the storage tank 74, and the water level h of the storage tank 74 is maintained at a predetermined height.

  The cap portion 87 is made of plastic except for the spring 94, but may be made of metal like the main body portion 76 and the connecting portion 73. This is advantageous because the effect of adjusting the temperature of the liquid can be further enhanced.

  Hereinafter, the operation of the above configuration will be described. When the fixing process is performed, each liquid container 61 is filled with various liquids such as a fixing buffer solution, an activation solution, a ligand solution, a cleaning solution, and a drying prevention solution. Then, the unprocessed sensor unit 12 is accommodated in the holder 52 and set in the fixing machine 10. In the fixing machine 10, a cover (not shown) is attached to the housing base 50 and the fixing process is started. During the fixing process, the temperature in the fixing machine 10 is adjusted and maintained at a predetermined temperature. In the liquid container 61, since the main body 76 and the connecting portion 73 are metallic, the temperature of the liquid in the storage tank 74 is adjusted appropriately. In addition, since the storage tank 74 of the liquid container 61 is covered with the cover 77, the evaporation preventing sheet 81, and the sealing sheet 82, the liquid is prevented from evaporating, so that the concentration fluctuation is small.

  The pipette head 54 accesses each liquid container 61 in a predetermined order and sends the sucked liquid to each sensor unit 12. The pipette head 54 replaces the pipette tip 62 every time the type of liquid to be sucked changes. Thereby, contamination is prevented. Of course, since the liquid is fed by the pipette, the pipe cleaning work and the exchange work for preventing the contamination are not required as in the case of sending the liquid by the pipe.

  The pipette head 54 accesses the liquid container 61, inserts the tip of the pipette 19a into the insertion port 75, and sucks the liquid. When the water level h of the storage tank 74 falls below the notch 97 by this suction, the liquid flows out from the replenishing tank 72 and is replenished to the storage tank 74. Further, by making the storage tank 74 substantially V-shaped, the liquid is stored near the tip of the pipette 19a even when the remaining amount of liquid in the storage tank 74 is low, so the liquid in the storage tank 74 Can be used up to the end.

  When the liquid in the replenishing tank 72 and the storage tank 74 is used up, the replenishing tank 72 is replaced. The empty replenishment tank 72 is removed from the connecting portion 73, and instead, a new replenishing tank 72 full of liquid is attached to the connecting portion 73. Since the replenishment tank 72 is attached by screwing, replacement work is easy. The replenishment tank 72 is attached to the connecting portion 73 with the cap portion 87 facing downward. Until the replenishment tank 72 is attached to the connecting portion 73, the valve 93 is closed by the bias of the spring 94, so that no liquid leaks from the inside of the bottle 86 to the outside.

  When the cap portion 87 is attached to the attachment portion 84, the valve 93 moves to the open position by the contact between the contact portion 95 and the floor surface of the connecting portion 73, and the takeout port 89 is opened. As a result, the liquid flows out from the replenishing tank 72 and is sent to the storage tank 74 through the connecting portion 73 and the replenishing path 83. When the liquid level h reaches the position of the notch 97, the liquid outflow stops.

  Since the storage amount of the liquid container 61 is larger than that of the well plate, a sufficient amount of liquid can be stored by one filling. Therefore, the number of liquid replenishment operations is reduced, and a reduction in the efficiency of the fixing process is suppressed. Moreover, since the replacement work of the replenishment tank 72 is easy, the labor and time required for the replenishment work itself are reduced. Therefore, among various liquids, it is suitable for containing a liquid that is used in a particularly large amount (particularly, a fixing buffer solution or a cleaning solution).

  The sensor unit 12 for which the fixing process has been completed is sent to the measuring machine 11 and sequentially subjected to the measurement process. Since the liquid used for the fixing process is contained in the liquid container 61, the concentration fluctuation is small. For this reason, there is no variation in density between the sensor units 12. Therefore, high measurement accuracy can be obtained also in the measurement process.

  In the above embodiment, the valve opens and closes in conjunction with the attachment and detachment operation to the replenishment tank and the connecting portion. However, the opening and closing of the valve does not necessarily have to be interlocked with the attachment and detachment operation. You may make it open and close a valve by providing a member and operating this manually.

  In the above embodiment, the example in which the liquid container of the present invention is used in the fixing process executed as the pre-measurement process has been described. Also good. When used in a measuring machine, for example, a measuring buffer solution, a cleaning solution, an analyte solution, etc. are accommodated.

  Examples of the liquid contained in the liquid container include a fixing buffer solution, a cleaning solution, an activation solution, a ligand solution, an anti-drying solution, a measurement buffer solution, a cleaning solution, and an analyte solution. It may be used to contain liquids or may be used only for certain of these liquids.

  In the above-described embodiment, the example in which the liquid container of the present invention is used as the liquid container for storing the liquid used for the sample reaction measurement using the SPR has been described. Of course, the sample reaction measurement is used for the SPR measurement. The liquid container of the present invention may be applied to other types of reaction measurement. Moreover, you may use the liquid container of this invention for the liquid feeding apparatus which sends liquid to a predetermined place using not only the reaction measurement of a sample but a pipette.

  Moreover, in the said embodiment, although the example which formed the main-body part, the cover, and the connection part with the metal is demonstrated, compared with metals, such as a plastic, if it is not necessary to control the temperature of the liquid to accommodate strictly. In addition, a material having low thermal conductivity may be used.

It is explanatory drawing of a SPR measuring method. It is a disassembled perspective view which shows schematic structure of a sensor unit. It is a block diagram of a fixing machine. It is an external appearance perspective view of a liquid container. It is a disassembled perspective view of a liquid container. It is explanatory drawing which shows the shape of a storage tank. It is explanatory drawing of a cap part and a connection part. It is explanatory drawing of the notch provided in the cap part.

Explanation of symbols

DESCRIPTION OF SYMBOLS 10 Fixing machine 12 Sensor unit 19 Pipette pair 19a, 19b Pipette 54 Pipette head 61 Liquid container 71 Main tank 72 Replenishment tank 73 Connection part 74 Reservoir tank 74a Upper opening 75 Insertion port 86 Bottle 87 Cap part 88 Cap main body 89 Outlet 91 Valve Mechanism 92 Shaft 93 Valve 94 Spring 95 Contact part

Claims (11)

In a liquid container that contains the liquid aspirated by a pipette,
A main tank in which a storage tank for storing the liquid is formed, and a main tank accessible by the pipette from an upper opening of the storage tank;
Replenishment comprising a bottle for storing the liquid to be replenished to the storage tank, and a cap portion provided with a valve mechanism for opening and closing the take-out opening and forming a take-out opening for taking out the liquid in the bottle to the outside A tank,
A liquid container comprising a connecting portion for connecting the main tank and the replenishing tank, wherein an attaching portion to which the replenishing tank is detachably attached is formed with the cap portion facing downward.   The liquid container according to claim 1, wherein the storage tank has a substantially V-shaped longitudinal section.   The liquid container according to claim 1, wherein the main body portion and the connecting portion are integrally formed.   The liquid container according to claim 1, wherein the main body portion and the connecting portion are made of metal.   The liquid container according to claim 1, wherein at least a part of the cap portion is metallic.   The said main tank is provided with the cover which covers the said upper opening, The insertion port in which the front-end | tip of the said pipette is inserted is formed in this cover, The one of Claims 1-5 characterized by the above-mentioned. Liquid container.   The liquid container according to claim 6, wherein the cover is made of metal.   An evaporation preventing sheet that is disposed between the cover and the main body portion and blocks the insertion port from the inside of the cover to prevent evaporation of the liquid is provided, and this evaporation preventing sheet is formed of an elastic material. The liquid container according to claim 6 or 7, wherein a notch through which the pipette can be inserted is formed at a position corresponding to the insertion port.   The liquid according to any one of claims 6 to 8, wherein a sealing sheet is provided between the cover and the main body, and a watertight seal is provided between the cover and the main body. container.   10. The valve mechanism according to claim 1, wherein the valve mechanism opens and closes the take-out port in conjunction with an attaching / detaching operation of the replenishing tank to the connecting portion by engaging with the connecting portion. Liquid container.   The cap portion has a cap body in which the take-out port is formed, and the valve mechanism is inserted into the cap body with one end projecting toward the outside of the cap body and slides in the vertical direction. And a valve that opens and closes the outlet in response to sliding of the shaft, and a spring that biases the shaft so that the valve closes the outlet, and the cap body is attached to the connecting portion 11. The valve opens the take-out port when the one end and the connecting portion come into contact with each other when the shaft slides against the spring bias. Liquid container.

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