JP2007107916A - Device for filling separation buffer liquid into microchip and microchip processor equipped therewith - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To make it easy to suck a separation buffer liquid from reservoirs. <P>SOLUTION: Suction nozzles 22-1 to 22-3 are pressed against bottom parts of the reservoirs 53-1 to 53-3 by a spring 106. When further turning a ball screw 126, a plunger holding member 114 pushes a plunger 112 to cause air to be supplied from an air supply port 18. The separation buffer liquid in the reservoir 53-4 is thereby pressed into a flow path. The buffer liquid flowing over out of the flow path into the reservoirs 53-1 to 53-3 is sucked by the suction nozzles 22-1 to 22-3, respectively, and removed. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a microchip processing apparatus for performing analysis such as a microchip electrophoresis method and micro liquid chromatography in fields such as chemistry and life science, and for filling a microchip with a separation buffer solution in such a microchip processing apparatus. This relates to the device.

In microchip electrophoresis, a sample such as DNA, RNA, or protein introduced into one end of a separation main channel is electrophoresed in the direction of the other end of the channel by a voltage applied across the channel. Separate and detect.
In microchip electrophoresis, a device that automatically uses a single microchip having one electrophoresis flow path to automatically fill a buffer solution, dispense a sample, perform electrophoresis, and detect separated sample components. It has been developed (see Patent Document 1).

  In order to increase the operating rate of analysis, an electrophoresis apparatus having a plurality of flow paths has also been proposed. One of the devices is equipped with 12 channels, and after manually filling the separation buffer solution and dispensing the sample, electrophoresis is performed sequentially from the 12 channels to obtain data. (See Non-Patent Document 1).

  Other apparatuses have twelve flow paths using capillaries, and automatically perform separation buffer solution filling, sample dispensing, electrophoretic separation, and data acquisition (see Non-Patent Document 2).

In micro liquid chromatography, a microchip is provided with a liquid feed channel including a separation column as a main channel, and a sample introduced to one end of the separation column is moved toward the other end of the separation column. Separate and analyze (see Non-Patent Document 3).
JP-A-10-246721 “Bunseki”, No. 5, 267-270 (2002) Electrophoresis 20003, 24, 93-95 Anal. Chem., 70, 3790 (1998)

  A microchip having a reservoir opened on the surface at each end of the flow path is used. When the microchip is mounted on the microchip processing apparatus, the microchip is held so that the reservoir is on the upper surface. At that time, when the separation buffer solution is filled in the flow channel or when the separation buffer solution in the microchip flow channel after the analysis is exchanged, the separation buffer solution is supplied to one reservoir by the separation buffer solution filling device. The separation buffer solution is pushed into the flow path by pressing the air supply port onto the reservoir to supply air, and the separation buffer solution overflowing from the other reservoir is sucked from the suction nozzle.

At this time, since the mechanism for pressing the air supply port onto the reservoir and the drive mechanism for supplying air are usually different mechanisms, the apparatus tends to be large.
Therefore, a first object of the present invention is to provide a small and inexpensive separation buffer liquid filling device by simplifying a mechanism for supplying air by pressing an air supply port onto a reservoir.

In addition, it is not preferable that the separation buffer solution to be sucked and discharged from the reservoir by the suction nozzle remains in the reservoir. Particularly, when the microchip is repeatedly used, the previous analysis sample is contaminated and the analysis accuracy is lowered.
Accordingly, a second object of the present invention is to provide a separation buffer solution filling device that facilitates aspiration of a separation buffer solution to be discharged from a reservoir when filling the separation buffer solution into the flow path of the microchip.
A third object of the present invention is to provide a microchip processing apparatus using such a separation buffer liquid filling apparatus.

  In order to achieve the first object, the separation buffer liquid filling device of the present invention is provided on the surface of each end portion of a flow path including at least a separation main flow path in which the analysis is performed while the solution moves into the plate member. Provided with an air supply port that is pressed against the microchip arranged so that the open reservoir is on the upper surface of the reservoir at one end of the flow channel, into which the separation buffer solution is injected, while maintaining airtightness. A separation buffer liquid filling device that supplies air from the air supply port to fill the flow path with the separation buffer liquid, wherein the air supply port is an opening of a tip of an air cylinder, and a seal portion is provided in the opening. The air cylinder is pressed against the reservoir by the seal portion, and the air cylinder moves the air cylinder in the vertical direction and operates the plunger. The slider moving / driving mechanism is capable of sliding the air cylinder holding member that holds the air cylinder, the plunger holding member that holds the plunger above the air cylinder holding member, and the air cylinder holding member and the plunger holding member. A guide supported by the air cylinder, an elastic member disposed between the air cylinder holding member and the plunger holding member, a drive mechanism for moving the plunger holding member in the vertical direction, and a top dead center of the plunger holding member. A stopper, and the elastic member pushes the air cylinder holding member with the elastic member until the air supply port comes into contact with the microchip in the descending process of the plunger holding member accompanying the operation of the drive mechanism. After the air supply port comes into contact with the microchip And it is characterized in that it is configured to press the plunger to supply air from the air supply port.

  In order to achieve the second object, the separation buffer liquid filling device of the present invention is provided on the surface of each end portion of the flow path including at least a separation main flow path in which the analysis is performed while the solution moves into the plate member. For the microchip arranged so that the open reservoir is on the upper surface, the flow path is filled with the separation buffer liquid, and the separation buffer liquid is injected into the reservoir at one end of the flow path of the microchip. The air supply port that is pressed airtight on the top and the other remaining reservoirs are inserted from above, and flows when air is blown from the air supply port and the separation buffer solution is pushed into the flow path. A suction nozzle for sucking the separation buffer liquid overflowing from the passage into the reservoir, and these suction nozzles are slidably supported by a nozzle holding member that moves in the vertical direction and are energized. By being biased downward by the step, and is characterized in that the energized state by the biasing means when pressed against the bottom of the reservoir.

  Among the reservoirs, the sample supply reservoir may remove the separation buffer solution or be washed separately from other reservoirs. In order to cope with such an aspect, in a preferred embodiment, in the state before the suction nozzle is inserted into the reservoir, the suction nozzle that is inserted into the sample supply reservoir projects downward from the nozzle holding member. The length is set to be longer than the length of the liquid existing in the reservoir into which the other suction nozzles are inserted, compared to the length of the other suction nozzles projecting downward from the nozzle holding member. Yes.

  In a further preferred form, the outer diameter of the tip of the suction nozzle is smaller than the dimension of the bottom of the reservoir into which they are inserted, and when the suction nozzle sucks liquid from the reservoir, the tip of the suction nozzle is at the bottom side wall of the reservoir It can be pressed against the part.

  In a further preferred form, the air supply port is an opening at the tip of an air cylinder, and a seal portion is provided in the opening, and the air supply port is pressed against the reservoir while maintaining airtightness.

In a more preferred form, the air cylinder moving / driving mechanism for moving the air cylinder up and down and operating the plunger includes an air cylinder holding member that holds the air cylinder and a plunger that holds the plunger above the air cylinder holding member. A holding member, a guide for slidably supporting the air cylinder holding member and the plunger holding member, an elastic member disposed between the air cylinder holding member and the plunger holding member, and a drive for moving the plunger holding member in the vertical direction A mechanism and a stopper for defining the top dead center of the plunger holding member, and the elastic member is in the process of lowering the plunger holding member accompanying the operation of the drive mechanism until the air supply port contacts the microchip. The air cylinder holding member is pushed by the elastic member. Lowered Te, after the air supply opening comes into contact with the microchip is configured to supply air from the air supply port by pushing the plunger.
In a more preferred form, the air cylinder holding member is integrated with the nozzle holding member.

  A microchip processing apparatus to which the present invention is applied is not particularly limited, but a preferable example is a microchip including at least a separation main channel for performing analysis while a solution moves inside a plate-like member. A holding unit for holding, a separation buffer liquid filling device for filling the flow path of the microchip with the separation buffer liquid, and a sample or reagent container inserted from above to inhale a sample or reagent and held by the holding unit A micro provided with at least a dispensing probe for injecting into a predetermined position of the microchip, and a dispensing probe driving mechanism for moving the dispensing probe between predetermined positions of the microchip, the sample container, and the reagent container The chip processing apparatus uses the separation buffer liquid filling apparatus of the present invention as the separation buffer liquid filling apparatus.

  In a preferred example of such a microchip processing apparatus, the holding unit holds the microchip so that the number of main flow paths is plural, and a control unit is provided to control the pretreatment process and the analysis process in the main flow path. The dispensing probe is commonly used in a plurality of main flow paths, and performs a pretreatment process prior to the analysis process in the main flow paths, and the control unit performs the following after the pretreatment process in one main flow path is completed. The pretreatment process is performed independently for each main flow path so as to shift to the pretreatment process of the main flow path, and the analysis process is controlled to be performed in parallel on the plurality of main flow paths after the pretreatment process is completed. .

  In the separation buffer liquid filling apparatus, if the air supply port for supplying air for pushing the separation buffer liquid into the flow path is an opening at the tip of the air cylinder, it is not necessary to separately provide an air supply means, so that the apparatus becomes small.

  In addition, as an air cylinder moving / driving mechanism that moves the air cylinder up and down and actuates the plunger, the air cylinder holding member and the plunger holding member are slidably supported by the guide, and the air cylinder holding member and the plunger holding are supported. An elastic member is disposed between the members, and the air cylinder holding member is pushed down by the elastic member until the air supply port contacts the microchip. After the air supply port contacts the microchip, the plunger is pressed to If air is supplied from the supply port, the movement of the air cylinder in the vertical direction and the drive of the plunger can be realized with a single drive source. The filling device is small and inexpensive.

  In the separation buffer liquid filling device, the suction nozzle that sucks the separation buffer liquid that has been pushed into the flow channel and overflowed from the other reservoir is slidably supported by the nozzle holding member that moves in the vertical direction, and is energized. If the means is urged downward and pressed against the bottom of the reservoir, the separation buffer solution to be discharged can be sucked without remaining from the reservoir.

  Of the suction nozzles, the length of the suction nozzle inserted into the sample supply reservoir protrudes downward from the nozzle holding member, and the length of the other suction nozzles protrudes downward from the nozzle holding member. If the liquid is longer than the depth of the liquid existing in the reservoir in which the nozzle is inserted, only the liquid in the sample supply reservoir can be sucked, so the separation buffer liquid in only the sample supply reservoir is removed. Or can be cleaned.

  If the tip of the suction nozzle is pressed against the bottom side wall of the reservoir when the suction nozzle sucks the liquid from the reservoir, the liquid remaining around the bottom of the reservoir can be sucked. As a result, when the microchip is repeatedly used, contamination (carry over) due to the previous measurement sample is reduced. In addition, the amount of water for washing the reservoir can be reduced, and the washing time can be shortened, leading to a reduction in analysis time.

If the air cylinder holding member and the nozzle holding member are integrated, the separation buffer liquid filling device becomes smaller and less expensive.
If the separation buffer solution filling device of the present invention is mounted on the microchip processing device, unnecessary separation buffer solution and washing water can be easily discharged from the reservoir, so that the analysis accuracy can be improved.

FIG. 1 is a block diagram schematically showing a part related to a control unit in an embodiment in which the present invention is applied to a microchip electrophoresis apparatus.
Reference numeral 2 denotes a dispensing unit which includes a dispensing probe driving mechanism provided with a dispensing probe. The dispensing probe of the dispensing unit 2 sucks the separation buffer solution or sample by the syringe pump 4 and injects it into one end of the electrophoresis channel of the microchip, and is provided in common for the plurality of electrophoresis channels. ing. Reference numeral 16 denotes a separation buffer liquid filling device that fills the electrophoresis flow path by air pressure with the separation buffer liquid injected into one end of the electrophoresis flow path, and discharges unnecessary separation buffer liquid by the suction pump unit 23. The filling device 16 is also provided in common for a plurality of electrophoresis channels to be processed. Reference numeral 26 denotes a high voltage power supply unit for electrophoresis that applies a voltage for electrophoresis independently to each of the electrophoresis channels. Reference numeral 31 denotes a fluorescence measurement unit as an example of a detection unit that detects a sample component separated in the electrophoresis channel. Reference numeral 38 denotes a control unit. When the separation buffer solution filling and sample injection into one electrophoresis channel are completed, the operation of the dispensing unit 2 is shifted to the separation buffer solution filling and sample injection into the next electrophoresis channel. And the operation of the high voltage power supply unit for electrophoresis 26 is controlled so as to cause electrophoresis by applying an electrophoresis voltage in the electrophoresis channel after the sample injection is completed, and the detection operation by the fluorescence measuring unit 31 is controlled. Is. Reference numeral 40 denotes a personal computer as an external control device for instructing the operation of the microchip electrophoretic device and for taking in and processing data obtained by the fluorescence measurement unit 31.

  FIG. 2 schematically shows a main part of a microchip electrophoresis apparatus according to an embodiment. Four microchips 5-1 to 5-4 are held by a holding portion (not shown). As will be described later in detail, each of the microchips 5-1 to 5-4 is formed with one electrophoresis channel for processing one sample.

  In order to dispense the separation buffer solution and the sample into the microchips 5-1 to 5-4, the dispensing unit 2 includes a syringe pump 4 that performs suction and discharge, and a dispensing probe 8 that includes a dispensing nozzle. And a container 10 for the cleaning liquid, and the dispensing probe 8 and the container 10 for the cleaning liquid are connected to the syringe pump 4 via the three-way electromagnetic valve 6. The separation buffer solution and the sample are respectively accommodated in holes on the microtiter plate 12 and are dispensed into the microchips 5-1 to 5-4 by the dispensing unit 2. The separation buffer solution may be stored in a dedicated container and placed near the microtiter plate 12. Reference numeral 14 denotes a cleaning unit for cleaning the dispensing probe 8, and the cleaning liquid overflows.

  The dispensing unit 2 connects the three-way electromagnetic valve 6 in the direction in which the dispensing probe 8 and the syringe pump 4 are connected, and sucks the separation buffer solution or the sample into the dispensing probe 8, and the microchip 5- It discharges to one of the electrophoresis flow paths of 1-5-4. When washing the dispensing probe 8, the three-way solenoid valve 6 is switched to a direction in which the syringe pump 4 and the washing liquid container 10 are connected, and the washing liquid is sucked into the syringe pump 4, and then the dispensing probe 8 is washed in the washing section 14. Then, the three-way solenoid valve 6 is switched to the side where the syringe pump 4 and the dispensing probe 8 are connected, and washing is performed by discharging the washing liquid from the inside of the dispensing probe 8.

  Separation buffers for the four microchips 5-1 to 5-4 are used to fill the flow path with the separation buffer solution dispensed in the reservoir at one end of the electrophoresis flow paths of the microchips 5-1 to 5-4. A liquid filling device 16 is provided in common. The separation buffer solution filling device 16 presses the air supply port 18 onto the reservoir at one end of the electrophoresis flow path of any one of the microchips 5-1 to 5-4 while keeping the air tight, and inserts the suction nozzle 22 into the other reservoir. Then, air is blown from the air supply port 18 to push the separation buffer solution into the electrophoresis flow path, and the separation buffer solution overflowing from the other reservoir is sucked from the nozzle 22 by the suction pump and discharged to the outside.

  In order to apply the voltage for electrophoresis independently to the electrophoresis channel of each of the microchips 5-1 to 5-4, the high-voltage power supply for electrophoresis 26 (26 -1 to 26-4) are provided.

  A fluorescence measuring unit 31 for detecting the sample components electrophoretically separated in the separation channels 55 of the microchips 5-1 to 5-4 is provided for each of the microchips 5-1 to 5-4. The LEDs (light emitting diodes) 30-1 to 30-4 that irradiate a part of the electrophoresis channel and the sample components that move through the electrophoresis channel are excited by the excitation light from the LEDs 30-1 to 30-4. Optical fibers 32-1 to 32-4 that receive the generated fluorescence, and a filter 34 that removes excitation light components from the fluorescence from the optical fibers 32-1 to 32-4 and transmits only the fluorescence components. And a photomultiplier tube 36 for receiving fluorescence. By causing the LEDs 30-1 to 30-4 to emit light at different times, the fluorescence from the four microchips 5-1 to 5-4 can be identified and detected by one photomultiplier tube 36. The excitation light source is not limited to the LED, and an LD (laser diode) may be used.

  3 and 4 show an example of the microchip in this embodiment. The microchip in the present invention refers to such an electrophoresis apparatus in which an electrophoresis channel is formed in a substrate, and is not necessarily limited to a small size.

  As shown in FIG. 3, the microchip 5 is composed of a pair of transparent substrates (quartz glass or other glass substrate or resin substrate) 51, 52, and on the surface of one substrate 52, as shown in (B). The electrophoresis capillary grooves 54 and 55 intersecting each other are formed, and the reservoir 53 is provided as a through hole in the other substrate 51 at a position corresponding to the end of the grooves 54 and 55 as shown in FIG. Both substrates 51 and 52 are overlapped and joined as shown in FIG. 4C, and capillary grooves 54 and 55 are separated into a separation channel 55 for electrophoresis separation of the sample and a sample for introducing the sample into the separation channel. Let it be an introduction channel 54.

  The microchip 5 is basically the one shown in FIG. 3, but in order to facilitate handling, the electrode terminal for applying a voltage is previously formed on the chip as shown in FIG. Is used. FIG. 4 is a plan view of the microchip 5. The four reservoirs 53 are also ports for applying a voltage to the flow paths 54 and 55. Ports # 1 and # 2 are ports located at both ends of the sample introduction channel 54, and ports # 3 and # 4 are ports located at both ends of the separation channel 55. In order to apply a voltage to each port, electrode patterns 61 to 64 formed on the surface of the chip 5 are formed so as to extend from the respective ports to the side end portions of the microchip 5. 26-1 to 26-4.

  FIG. 5 schematically shows a connection state between the air supply port 18 and the microchip 5 in the buffer filling / discharging unit 16. An O-ring 20 is provided at the tip of the air supply port 18, and the air supply port 18 is pressed against one reservoir of the microchip 5, so that the air supply port is directed to the electrophoresis channel of the microchip 5. 18 can be attached in a secret manner, and air can be pressurized from the air supply port 18 and sent out into the flow path. A nozzle 22 is inserted into the other reservoir, and an unnecessary separation buffer solution overflowing from the flow path is sucked and discharged.

  FIG. 6 shows the operation in one embodiment in detail. Here, a microchip in which one electrophoresis channel is formed is used. Therefore, in this case, the process transfer from one microchip to the next microchip is synonymous with the process transfer from one electrophoresis channel to the next electrophoresis channel.

(A) shows the operation of the embodiment in which the pre-processing step and the electrophoresis / photometry step are sequentially performed by four microchips partially in parallel.
Each process is set in time, the pretreatment process is set to 40 seconds, the electrophoresis / photometry process is set to 120 seconds, and one cycle for one microchip is 160 seconds.

  When the pretreatment process for one microchip is completed, the process proceeds to the pretreatment process for the next microchip without waiting for the completion of the electrophoresis / photometry process in the microchip. That is, when the pretreatment process at the first microchip is completed, electrophoresis is started, photometry is started, and the pretreatment process at the second microchip is started. When the pre-processing step with the second microchip is completed, electrophoresis in the second microchip is started, photometry is started, and the pre-processing step with the third microchip is started. In this way, the pretreatment process is sequentially performed for each microchip, and separately from the microchip after the pretreatment process, electrophoresis and photometry are started sequentially, and as a result, multiple electrophoresis and photometry are performed. Executed in parallel on a microchip. When the pre-processing step is performed up to the fourth microchip, the analysis is finished in the first microchip, and therefore the same process is repeated using the first microchip again.

  In the electrophoresis step, a voltage is applied to guide the sample from the sample introduction channel to the crossing position with the separation channel, and then electrophoretic separation is performed by applying a voltage in the separation channel. At the same time, light is emitted from the LED at the detection position, and fluorescence measurement is started.

The pretreatment process is shown in detail in (B).
The numerical value at the top represents time (seconds). The “microchip” column shows the contents of processing in one microchip. The “dispensing part” column indicates the suction and discharge operations of the separation buffer solution and the sample from the dispensing probe 8 performed by the syringe pump 4.

  In the column of “Separation Buffer Liquid Filling Device”, an operation of performing a filling operation for pushing the separation buffer liquid dispensed to the microchip into the flow path and a suction process for sucking and discharging the overflowing separation buffer liquid using a suction pump. Show.

  In the “microchip” column, the first separation buffer solution suction (B suction) is a step of sucking and discharging the separation buffer solution used in the previous analysis. In the next “W4B dispensing” step, the separation buffer solution is dispensed to the fourth reservoir, and in the next “filling / suctioning” step, pressurized air is supplied from the separation buffer solution filling device to electrically discharge the separation buffer solution. The channel is washed with a new separation buffer solution by pushing into the electrophoresis channel and sucking and discharging unnecessary separation buffer solution from other reservoirs.

  In order to wash the first reservoir in the next “W1B dispensing” step, a new separation buffer solution is dispensed into the first reservoir, and in the next “filling / suctioning” step, the separation buffer solution filling device is the fourth. Pressurized air is supplied to the reservoir and the separation buffer solution is pushed into the electrophoresis channel, and unnecessary separation buffer solution is sucked and discharged from the other reservoirs to fill the separation buffer solution into the channel. Thereafter, the separation buffer solution is also dispensed from the second, third, and fourth reservoirs in the next “W2, 3, 4 buffer dispensing” step. This completes the filling of the separation buffer solution into the electrophoresis channel.

  Next, in order to dispense the sample, the sample is sucked into the dispensing probe of the dispensing unit, and the sample is discharged into the first reservoir by the “W1S dispensing” process, thereby dispensing the sample. After the sample is dispensed, the dispensing probe of the dispensing unit is cleaned, and then prepared for inhalation of the separation buffer solution for the next sample. This completes the pretreatment process in the electrophoresis channel of the microchip.

  The microchip of the embodiment employs a cross-injection type electrophoresis channel, but the present invention is not limited to this, and a microchip having only a separation channel may be used.

  In addition, although the microchip of the example uses one microchip provided with only one electrophoresis channel, a plurality of electrophoresis channels may be formed on one microchip, In that case, the present invention may be applied in units of electrophoresis channels.

Although the thing which measures fluorescence is used as a detection part, besides measuring fluorescence, a light absorbency can also be measured and the detection method using chemiluminescence or bioluminescence can also be used.
For the detection unit, even if each microchip does not irradiate excitation light independently, a photometric system commonly used for all microchips is prepared, and the optical system is used as the detection position for all microchips. It may be of a type that scans so as to move between.

Next, the dispensing unit 2 will be described in detail.
As shown in an enlarged view in FIG. 7, the dispensing probe 8 is hollow and has a needle at its tip, and sucks and discharges liquid from the hole at the tip. The dispensing probe 8 is shared by the sample and the reagent (in this embodiment, a separation buffer solution). FIG. 7 shows a state where the tip of the dispensing probe 8 is inserted into the sample container 90. As shown in FIG. 7, the sample container 90 is attached to the microchip processing apparatus in a state where the upper opening is closed with a sealing material 90 a such as a septum that can be penetrated by the needle of the dispensing probe 8. On the other hand, the reagent container containing the separation buffer solution is mounted on the microchip processing apparatus with the outer lid removed and the upper opening opened. At the time of sample dispensing operation, the needle of the dispensing probe 8 penetrates the sealing material 90a and is inserted into the sample container 90 to inhale the sample. At the time of reagent dispensing, the needle of the dispensing probe 8 The reagent is sucked by being inserted into the opened reagent container.

  The dispensing probe 8 has a groove 8b on its side surface. The groove 8b has a width and a depth of, for example, 50 μm to 0.6 mm. The position of the groove 8b is that when the tip of the dispensing probe 8 is inserted into the sample container 90 and the sample is inhaled, the inside of the sample container 90 and the atmosphere It is a position that communicates, that is, a position that penetrates the sealing material 90a. Thereby, even if the sample in the container 90 is inhaled by the dispensing probe 8, the atmosphere flows into the container 90 through the groove 8b, so that the negative pressure in the container 90 can be prevented. The liquid can be sucked well.

  The dispensing probe 8 is made of metal, and is a capacitance type liquid level sensor by detecting the capacitance at the tip. The capacitance at the tip of the dispensing probe 8 changes when it is inserted into the sample container or reagent container and comes into contact with the liquid in the container, thereby detecting the liquid level. As shown by reference numeral 92 in FIG. 1, the liquid level sensor is connected to the control unit 38 and the capacitance level is constantly monitored to detect the liquid level position in the sample container or the reagent container. The

Based on the output of the liquid level sensor, the control unit 38 calculates the residual liquid amount in the sample container or the reagent container, and displays the personal computer (PC) 40 as the residual liquid amount display unit as shown in FIG. To do. (Figure 8 does not appear to be displayed. Please correct the text.)

When the remaining liquid amount based on the output of the liquid level sensor is insufficient before the analysis is started, the control unit 38 may notify the fact by using the personal computer 40 as an alarm means.
When the remaining liquid amount based on the output of the liquid level sensor is insufficient, the control unit 38 may notify the personal computer 40 as an alarm means each time.

  In FIG. 9, among the dispensing probe driving mechanisms in the dispensing unit 2, the dispensing probe 8 is driven in the Z direction (vertical direction), and when the dispensing probe 8 is pulled out from the sample container 90, the sample container 90. An example is shown in which a pressing lever 86 as a pressing mechanism having a horizontal pressing member 86b that biases downward so as not to float is provided at the lower end.

  The holding lever 86 is slidably attached to a probe holder 80 that holds the dispensing probe 8 and moves in the vertical direction, and serves as an urging means for urging the holding lever 86 downward with respect to the probe holder 80. And a stopper 86a for restricting the pressing member 86b from moving further downward than the stop position at the lower end of the dispensing probe 8 (the position in the state of FIG. 9A) with respect to the probe holder 80. It has. The stopper 86a is fixed to the pressing lever 86 on the upper side of the probe holder 80, and abuts against the upper surface of the probe holder 80, thereby restricting the pressing lever 86 from moving further downward. The spring 87 is a tension spring and is placed between the upper end of the holding lever 86 and the probe holder 80 on the upper side of the probe holder 80.

The holding lever 86 and the dispensing probe 8 are driven by a uniaxial drive system that moves the probe holder 80 in the vertical direction. Explaining this mechanism in more detail, the drive unit 70 for driving the dispensing probe 8 is fixed to a drive mechanism (not shown) for moving the drive unit 70 in the X and Y directions in the horizontal plane. The fixed shaft 72 is provided. A vertical linear guide 82 is fixed to the fixed shaft 72, and the probe holder 80 is guided by the linear guide 82 and supported so as to be slidable in the vertical direction. A ball screw 76 is screwed into the probe holder 80, and the vertical movement of the probe holder 80 is driven by the rotation of the ball screw 76. Further, a stepping motor is attached to the fixed shaft 72 as the driving motor 74, and the rotation shaft of the driving motor 74 and the ball screw 76 are connected by the timing belt 78, so that the rotation of the driving motor 74 is rotated by the ball screw 76. Is transmitted to.
The operation of sucking the sample with the dispensing probe 8 by the dispensing unit of FIG. 9 will be described.

(Standby state)
The position shown in FIG. 9A is a standby position. In the standby position, the probe holder 80 is raised to the uppermost position, and the stopper 86a of the pressing lever 86 comes into contact with the upper surface of the probe holder 80 so as to be in contact with the probe holder 80. Thus, the holding lever 86 is in the lowest position. In this standby state, the pressing member 86 b at the lower end of the pressing lever 86 is located below the tip of the dispensing probe 8.

(Descent for sample inhalation)
FIG. 9B shows a state when the dispensing probe 8 is lowered. The rotation of the driving motor 74 is transmitted to the ball screw 76 via the timing belt 78, and the probe holder 80 is lowered by the rotation of the ball screw 76. Since the dispensing probe 8 is fixed to the probe holder 80, the dispensing probe 8 is lowered together with the probe holder 80, and the holding lever 86 is urged downward with respect to the probe holder 80 by the spring 87. It descends with the holder 80. When the pressing member 86b at the lower end of the pressing lever 86 contacts the upper surface of the sample container 90, the lowering of the pressing lever 86 stops.

(Sample inhalation)
The probe holder 80 continues to descend from the state of FIG. Since the holding member 86b at the lower end of the holding lever 86 is in contact with the sample container, the holding lever 86 cannot be lowered any further. The holding lever 86 slides with respect to the probe holder 80 as the probe holder 80 is lowered. Only the probe holder 80 continues to descend and the spring 87 extends. The dispensing probe 8 is lowered together with the probe holder 80, and the tip of the dispensing probe 8 passes through the shield material 90 a of the sample container 90 and is inserted into the sample container 90. Since the tip of the dispensing probe 8 is a liquid level sensor, when the liquid level sensor detects the liquid level in the sample container 90, the drive motor 74 is driven when it enters the sample by a predetermined depth. It stops and the descent of the probe holder 80 is stopped. The state is the state shown in FIG. 9C, and a predetermined amount of the sample is sucked by the dispensing probe 8 in this state.

  Next, the drive motor 74 rotates in the reverse direction, and the probe holder 80 starts to rise. As the probe holder 80 is raised, the dispensing probe 8 starts to rise and is pulled out from the sample container 90. At this time, since the holding lever 86 is urged downward with respect to the probe holder 80 by the spring 87, even if the probe holder 80 starts to rise, the holding lever 86 remains in the position of FIG. As a result, when the dispensing probe 8 is pulled out from the sealing material 90a of the sample container 90, a force is exerted on the sample container 90 by the friction between the dispensing probe 8 and the sealing material 90a. Since the member 86b is fixed at the position shown in FIG. 9C, the sample container 90 is prevented from being lifted.

When the probe holder 80 is raised to the position shown in FIG. 9B, the stopper 86a attached to the holding lever 86 comes into contact with the upper surface of the probe holder 80, and when the probe holder 80 is further raised thereafter, the holding lever 86 is It rises with the probe holder 80. When the probe holder 80 is raised to the position shown in FIG. 9A, the sample suction operation is completed.
Thereafter, the entire drive unit 70 is moved to a predetermined position of the microchip, and the dispensing probe 8 is inserted into a predetermined reservoir of the microchip to inject a sample.

  The dispensing probe 8 is used not only for sample dispensing but also for reagent dispensing. The reagent is a separation buffer solution in this embodiment, but the same applies when other reagents are used. A reagent container having a larger size than the sample container is used to accommodate a reagent that is repeatedly dispensed to the microchip, and the reagent container is mounted on the microchip processing apparatus with the lid of the opening portion removed. The dispensing probe 8 is assumed to be inserted into the reagent container with the lid removed. The lid of the reagent container is harder than the sealing material 90a of the sample container 90, such as metal, and if the reagent container is attached to the microchip processing apparatus with the lid of the reagent container attached, the dispensing probe 8 The tip of the tube may be pressed against the lid of the reagent container and damaged. As an embodiment for preventing such a situation, FIG. 10 shows a device provided with means for detecting that the dispensing probe 8 has hit the lid of the reagent container.

  The drive unit 70a shown in FIG. 10 is different from the drive unit 70 of FIG. 9 in the mechanism for holding the dispensing probe 8 with respect to the probe holder 80, and that the tip of the dispensing probe 8 has hit the lid. It differs from that of FIG. 9 in that a sensor for detection is provided.

  10, the dispensing probe 8 is slidably held with respect to the probe holder 80. The probe holder 80 is integrally provided with an L-shaped spring pressing portion 80a extending upward. The dispensing probe 8 is slidably supported through the probe holder 80 and the spring holding portion 80a, and a compression spring 84 is inserted into the lower surface of the spring holding portion 80a so that the dispensing probe 8 is attached to the probe holder 80. It is energizing downward.

  In order to detect that the dispensing probe 8 is displaced with respect to the probe holder 80, the dispensing probe 8 is provided with a protruding piece 8 a on the upper side of the probe holder 80. The probe holder 80 is provided with a position sensor 88 such as a photo sensor in order to detect the protruding piece 8a. The positions of the protruding piece 8a and the position sensor 88 are determined so that the position sensor 88 is turned on when the dispensing probe 8 is displaced upward with respect to the probe holder 80 by a predetermined amount.

An operation for detecting that the tip of the dispensing probe 8 has hit the lid of the reagent container in the embodiment of FIG. 10 will be described.
The reagent container 91 should be attached with the lid 91a removed, but it is assumed that the reagent container 91 is accidentally attached to the microchip processing apparatus with the lid 91a still attached.

  FIG. 10A shows a standby state, from which the probe holder 80 is lowered as described in FIG. 9, and the pressing member 86b at the lower end of the pressing lever 86 is the reagent as shown in FIG. 10B. When it comes into contact with the upper surface of the container 91, the lowering of the holding lever 86 stops, but the tip of the dispensing probe 8 comes into contact with the lid 91 a of the reagent container 91 as the probe holder 80 continues to descend.

  Thereafter, the probe holder 80 continues to descend, but since the tip of the dispensing probe 8 cannot penetrate the lid 91a, the dispensing probe 8 stops and the probe holder 80 slides relative to the dispensing probe 8. And continue to descend further. Since the position sensor 88 is fixed to the probe holder 80, the position sensor 88 descends together with the probe holder 80, and when the position sensor 88 reaches the position of the projecting piece 8a as shown in FIG. It turns on and the tip of the dispensing probe 8 is in contact with a hard object, but it is detected. In this state, the descent of the probe holder 80 is stopped, and the dispensing operation is stopped.

  In this microchip processing apparatus, the processing procedure when the microchip is repeatedly used is shown in FIGS. 11 to 14, and will be described with reference to the flowchart of FIG. Reference numerals (A to U) in the flowchart of FIG. 15 mean the reference numerals of the steps in FIGS. In this process, the microchip used in the previous analysis is washed, the flow path is filled with the separation buffer solution, and the current flows normally through the flow channel with each reservoir filled with the separation buffer solution. This is a series of steps in which an electrophoresis test is performed and then a sample is dispensed to start electrophoresis, and the dispensing probe and the suction nozzle are washed.

  (A) shows the microchip 5. The microchip 5 is the one shown in FIGS. 3 and 4, and is provided so that the separation channel 55 and the sample introduction channel 54 intersect each other, and a reservoir 53 is formed at the end of each channel 54, 55. It is a thing. The reservoirs No. 1 to No. 4 in FIG. 4 are denoted by reference numerals 53-1 to 53-4 here.

  (B) The analysis of the previous sample is completed, and the separation buffer solution remains in the flow path and each reservoir, and the separated sample also remains in the separation buffer solution.

  (C) First, in order to wash the sample injection reservoir 53-1, only the suction nozzle 22-1 is inserted into the reservoir 53-1. The suction nozzle 22-2 and the suction nozzle 22-3 also move up and down simultaneously with the suction nozzle 22-1, but the length of the suction nozzle 22-1 is longer than the other suction nozzles 22-2 and 22-3. Therefore, only the suction nozzle 22-1 is inserted into the reservoir 53-1, and is pressed against the bottom of the reservoir 53-1, but the other suction nozzles 22-2 and 22-3 are respectively Are not inserted into the corresponding reservoirs 53-2 and 53-3. By being sucked from the suction nozzle 22-1 in this state, the separation buffer solution in the reservoir 53-1 is sucked and removed.

(D) Wash water is supplied from the dispensing probe 8 to the reservoir 53-1.
(E) The suction nozzle 22-1 is again inserted into the reservoir 53-1, and the washing water is sucked and discharged.
(F) Washing water is supplied again from the dispensing probe 8 to the reservoir 53-1.

  (G) Next, the suction nozzles 22-1 to 22-3 are inserted into the reservoirs 53-1 to 53-3, respectively. At this time, the three suction nozzles 22-1 to 22-3 are inserted into the respective reservoirs 53-1 to 53-3 and are pressed against each other to come into contact with the bottoms of the respective reservoirs. The liquid is simultaneously sucked and removed from the three suction nozzles 22-1 to 22-3. The dispensing probe 8 is inserted into the rinse port 100 to discharge the entire amount of washing water in the dispensing probe 8 and the inside and outside of the dispensing probe 8 are washed.

  (H) The fourth suction nozzle 22-4 is inserted into the other reservoir 53-4. The suction nozzle 22-4 is provided separately from the three suction nozzles 22-1 to 22-3, and is disposed near a cylinder for an air supply port shown in FIG. . The suction nozzle 22-4 is also pressed against the bottom of the reservoir 53-4. The separation buffer solution in the reservoir 53-4 is sucked and removed from the suction nozzle 22-4. The dispensing probe 8 aspirates the separation buffer solution from the reagent container 91 containing the buffer solution.

(I) The dispensing probe 8 is moved to the reservoir 53-4, and the separation buffer solution is dispensed.
(J) The air supply port 18 is pressed on the reservoir 53-4 while maintaining airtightness, and the cylinder shown in FIG. 15 is driven later to supply air from the reservoir 53-4 to the flow path. Suction nozzles 22-1 to 22-3 are inserted into the other reservoirs 53-1 to 53-3, respectively, and the separation buffer solution overflowing from the flow paths to the respective reservoirs 53-1 to 53-3 is sucked. Removed.

(K) The suction nozzle 22-4 is inserted into the reservoir 53-4, and the separation buffer solution in the reservoir 53-4 is sucked and removed. As a result, the separation buffer solution remains only in the flow path.
(L) to (O) The separation buffer solution is sequentially dispensed to the reservoirs 53-1 to 53-4 by the dispensing probe 8.

(P) An electrode is inserted into each reservoir and a migration test is performed. Here, it is confirmed whether dust or bubbles are mixed in the flow path by detecting the current value between the electrodes. Here, the voltage applied to the flow path may be the same as the electrophoresis voltage for separating the sample, but may be lower than that.
The dispensing probe 8 into which the separation buffer solution has been dispensed is inserted into the rinse port 100, and the entire amount of the separation buffer solution in the dispensing probe 8 is discharged and the inside and outside of the dispensing probe 8 are washed.

  If it is determined in this migration test step that the separation buffer is normally filled into the flow path, the process proceeds to the next step (Q) to inject the sample for analysis. If it is not determined that the buffer is normally filled, the process returns to step (B) to refill the flow path with the separation buffer solution.

  The number of times (N) that allows the refilling of the separation buffer liquid into the flow path is set in advance, and the separation buffer is normally filled into the flow path even if the separation buffer liquid is refilled by that number of times. If it is not determined that the process has been performed, the process returns to step (B) after replacing with another microchip. The number N of allowable refilling of the separation buffer solution is not particularly limited, but 2 or 3 is suitable, for example.

(Q) The suction nozzle 22-1 is inserted only into the sample supply reservoir 53-1, and the separation buffer solution in the reservoir reservoir 53-1 is sucked and removed.
(R) A sample is injected from the dispensing probe 8 into the reservoir 53-1.
(S) An electrode is inserted into each of the reservoirs 53-1 to 53-4, a voltage for introducing a sample is applied, and the sample is guided to the intersection of the flow paths 54 and 55.

(T) The applied voltage is switched to the voltage for electrophoretic separation, and the sample is electrophoresed in the direction of the reservoir 53-4 in the separation channel 55 and separated.
(U) After the analysis is completed, each of the suction nozzles 22-1 to 22-4 is inserted into the phosphorus spool 102, the cleaning liquid is sucked, the inside and outside of the nozzle is cleaned, and the probe 8 is inserted into the rinse port 100 so Washed.

Next, an embodiment of the separation buffer liquid filling device will be described with reference to FIGS.
The three suction nozzles 22-1 to 22-3 are slidably held by the nozzle holding member 104, and the vertical movement range is restricted by the upper and lower stoppers 105 and 107 as shown in an enlarged view in FIG. It is biased downward from the nozzle holding member 104 by the spring 106. These suction nozzles 22-1 to 22-3 can be moved upward against the spring 106 by being pressed against the reservoir.

  As shown in FIG. 16A, in a state before the suction nozzle is inserted into the reservoir, the suction nozzle 22-1 is separated from the nozzle holding member 104 as compared with the other suction nozzles 22-2 and 22-3. The length protruding downward is set longer than the depth of the liquid present in the reservoir. This is because the suction nozzles 22-2 and 22-3 are still in the reservoirs 53-2 and 53 when the tip of the suction nozzle 22-1 protrudes downward and comes into contact with the bottom of the reservoir 53-1. It means that the liquid level in -3 is not reached. When the nozzle holding member 104 moves further downward, any of the suction nozzles 22-1 to 22-3 comes into contact with the bottom surface of the reservoir.

  In this embodiment, the nozzle holding member 104 also serves as an air cylinder holding member, and the cylinder 108 is fixed to the nozzle holding member 104. A seal portion 110 is provided at the opening at the tip of the cylinder 108, and the opening having the seal portion serves as the air supply port 18. The cylinder 108 has a plunger 112 on its upper side, and air is discharged from the cylinder by the vertical movement of the plunger 112. The plunger 112 is fixed to the plunger holding member 114.

  The nozzle holding member (air cylinder holding member) 104 and the plunger holding member 114 are slidably supported by the linear guide 116, and a coil spring 118 is inserted between the nozzle holding member 104 and the plunger holding member 114. A stopper 120 extending upward from the nozzle holding member 104 is provided, and the stopper 120 defines the top dead center of the plunger holding member 114.

  The separation buffer solution filling device is fixed to the support 122, and the support member 122 is attached to a horizontal moving mechanism, so that the separation buffer solution filling device is movable in the lateral direction. As a mechanism for moving the nozzle holding member 104 and the plunger holding member 114 in the vertical direction, a stepping motor is attached to the support 122 as a drive motor 124, and a ball screw 126 is screwed to the plunger holding member 114. A timing belt 128 is applied between the motor 124 and the ball screw 126, and the rotation of the motor 124 is transmitted to the ball screw 126 via the timing belt 128. The plunger holding member 114 is moved in the vertical direction by the rotation of the ball screw 126. In this embodiment, since the nozzle holding member 104 also serves as an air rinser holding member, the driving of the suction nozzles 22-1 to 22-3 and the movement and driving mechanism of the air cylinder 108 are driven by a single driving motor 124. Can do.

  In FIG. 16, the mode in which the nozzle holding member 104 does not include the suction nozzles 22-1 to 22-3, that is, the mode in which the member 104 simply functions as an air cylinder holding member without performing the function of the nozzle holding member. This is one embodiment of the invention.

  Next, the operation of filling the microchip 5 with the separation buffer solution will be described with reference to FIG. In FIG. 12 (I), after the separation buffer solution is supplied to the reservoir 53-4 in FIG. 12 (I), air is supplied from the air supply port 18 in (J), and the separation buffer solution is pressurized and press-fitted. This corresponds to the process until the separation buffer liquid overflowing from the path is sucked by the suction nozzles 22-1 to 22-3 and discharged.

  (A): FIG. 16A is in a standby state, and the plunger holding member 114 is at the top dead center. In this state, the separation buffer solution has already been supplied to the microchip reservoir 53-4.

  (B): The ball screw 126 rotates to lower the plunger holding member 114, and the nozzle holding member 104 is pushed down via the coil spring 118. As shown in FIG. 16 (B), the seal portion 110 of the cylinder 108 is brought into contact with the reservoir 53-4 in an airtight manner, and at the same time, the three suction nozzles 22-1 to 22-3 are placed in the respective reservoirs. It is inserted and pressed against the bottom of the reservoirs 53-1 to 53-3.

  (C): When the ball screw 126 is further rotated to lower the plunger holding member 114, the nozzle holding member 104 is restricted from further lowering because the lower end of the cylinder 108 is in contact with the microchip 5. As shown in FIG. 16C, when the coil spring 118 contracts, the plunger holding member 114 further moves down from the stopper 120 and pushes the plunger 112 to supply air from the air supply port 18. As a result, the separation buffer solution in the reservoir 53-4 is press-fitted into the flow path, and the separation buffer liquid overflowing from the flow path to the reservoirs 53-1 to 53-3 is sucked into the respective suction nozzles 22-1 to 22-3. Is removed by suction.

  After the separation buffer solution is press-fitted into the flow path in the state of FIG. 16C, the ball screw 126 rotates in the reverse direction and returns to the state of FIG. Thereafter, when the ball screw 126 further rotates in the reverse direction, the plunger holding member 114 comes into contact with the stopper 120, thereby pulling up the nozzle holding member 104 and returning to the standby state shown in FIG.

  In the separation buffer liquid filling device of FIG. 16, when the rotation of the ball screw 126 is stopped when the tip of the suction nozzle 22-1 reaches the bottom surface of the reservoir 53-1, only the suction nozzle 22-1 is inserted into the reservoir 53-1. Then, the other suction nozzles 22-2 and 22-3 are stopped at positions where they do not reach the liquid levels of the respective reservoirs 53-2 and 53-3. This state is a state used in the steps of FIGS. 11 (E) and 13 (Q).

  Although not shown in FIG. 16, the other suction nozzle 22-4 is provided in the vicinity of the cylinder 108 and is moved downward by a spring in the same manner as the other suction nozzles 22-1 to 22-3. It is energized. When the suction nozzle 22-4 is inserted into the reservoir 53-4, since the support body 122 is moved in the horizontal direction, the other suction nozzles 22-1 to 22-3 are respectively associated with the corresponding reservoirs 53-1 to 53-1. It is not inserted into 53-3.

  FIG. 18 shows the liquid in the reservoir when the suction nozzle 22 (22-1 to 22-4) is in contact with a place other than the peripheral portion of the bottom of the reservoir 53 (53-1 to 53-4), for example, the central portion. This shows the state of suction removal.

  The outer diameter of the tip of the suction nozzle 22 is smaller than the dimension of the bottom of the reservoir 53, the tip of the suction nozzle 22 is cut obliquely, and the liquid is sucked from the gap between the reservoir bottom and the tip of the suction nozzle. When the suction nozzle 22 comes into contact with a place other than the side wall portion of the reservoir bottom, for example, the central portion, the liquid 130 remains in a donut shape around the reservoir bottom. In particular, when the reservoir 53 is a sample supply reservoir, if it is not sufficiently washed, it causes a carry-over for the next analysis. For this reason, when the liquid remains around the bottom of the reservoir, the amount of water for washing the reservoir must be increased or the number of times of washing must be increased, resulting in a longer washing time, resulting in a longer overall analysis time.

  Therefore, as a preferred embodiment, as shown in FIG. 19, the suction nozzle 22 is inserted so as to press against the bottom peripheral wall portion of the reservoir 53. By adjusting the position of the suction nozzle 22 in this manner, the liquid can be sucked and removed without leaving the reservoir 53. As a result, the carry-over is reduced and less washing water is required, and the washing time is shortened. As a result, the analysis time can be shortened. Also, the analysis accuracy is improved by reducing the carry-over under the same cleaning conditions.

It is a block diagram which shows roughly the part regarding the control part in the microchip electrophoresis apparatus of an example to which this invention is applied. It is a perspective view which shows roughly the principal part of the microchip electrophoresis apparatus. It is a figure which shows an example of a microchip, (A) and (B) are top views which show the transparent plate-shaped member which comprises a microchip, (C) is a front view of a microchip. It is a top view which shows a specific example of a microchip. It is sectional drawing which shows roughly the connection state of the air supply port at the time of filling the separation buffer liquid in the microchip electrophoresis apparatus, and a microchip. It is a time chart figure which shows operation | movement of the microchip electrophoresis apparatus. It is a schematic front view which shows the dispensing probe in one Example. It is a figure which shows an example of the display screen which displays the residual liquid amount in a reagent container. It is a front view which shows the dispensing probe drive mechanism in one Example, (A) is a standby position, (B) is the descent | fall process for sample inhalation, (C) represents a sample inhalation position, respectively. It is a front view which shows the dispensing probe drive mechanism in another Example, (A) is a stand-by position, (B) is the descent | fall process for reagent inhalation, (C) is the state which detected having contacted the foreign material Represents each. It is a perspective view which shows operation | movement of one Example in order of a process. It is a perspective view which shows operation | movement of the Example in order of a subsequent process. It is a perspective view which shows operation | movement of the Example further in order of a subsequent process. It is a perspective view which shows operation | movement of the Example further in order of a subsequent process. It is a flowchart which shows the process sequence in operation | movement of the Example. It is a front view which shows the separation buffer liquid filling apparatus in one Example, (A) is a standby position, (B) is the state which pressed the air supply port and the suction nozzle against the microchip, (C) is the separation buffer liquid. Each of the steps of press-fitting into the flow path is represented. It is sectional drawing which expands and shows the suction nozzle part in the separation buffer liquid filling apparatus. It is a figure which shows the state which attracts | sucks a liquid from a reservoir with a suction nozzle, (A) is a top view, (B) is sectional drawing. FIG. 6 is a cross-sectional view showing an improved method of sucking liquid from a reservoir by a suction nozzle.

Explanation of symbols

2 Dispensing part 4 Syringe pump 5,5-1 to 5-4 Microchip 8 Dispensing probe 8b Groove 16 Separation buffer liquid filling device 22-1 to 22-4 Suction nozzle 26 (26-1 to 26-4) Electricity Electrophoresis high voltage power supply unit 38 Control unit 70, 70a Driving unit 74 Driving motor 76 Ball screw 80 Probe holder 80a Spring pressing unit 82 Linear guide 84 Compression spring 86 Pressing lever 86b Holding member 87 Spring 88 Position sensor 90 Sample container 90a Sealing material 92 Liquid level sensor 104 Nozzle holding member 106 Spring 108 Cylinder 110 Seal part 112 Plunger 114 Plunger holding member 116 Linear guide 118 Coil spring 120 Stopper 124 Drive motor 126 Ball screw

Claims (9)

The microfluidic chip is arranged such that a reservoir opened at the surface of each end portion of the flow path including at least the main flow path for separation in which the analysis is performed while the solution moves inside the plate-like member is placed on the upper surface. An air supply port that keeps airtight pressure on the one where the separation buffer solution is injected in the reservoir at one end of the channel is filled with the separation buffer solution by supplying air from the air supply port. In the separation buffer liquid filling device,
The air supply port is a tip opening of an air cylinder, and a seal portion is provided in the opening, and the seal portion is pressed against the reservoir while keeping airtightness,
The air cylinder moving / driving mechanism for moving the air cylinder in the vertical direction and operating the plunger includes an air cylinder holding member for holding the air cylinder, and a plunger holding for holding the plunger above the air cylinder holding member. A member, a guide for slidably supporting the air cylinder holding member and the plunger holding member, an elastic member disposed between the air cylinder holding member and the plunger holding member, and moving the plunger holding member in the vertical direction A drive mechanism for causing the plunger holding member to have a top dead center,
The elastic member pushes and lowers the air cylinder holding member by the elastic member until the air supply port comes into contact with the microchip in the lowering process of the plunger holding member accompanying the operation of the drive mechanism. The separation buffer liquid filling device is configured to supply air from the air supply port by pushing the plunger after the supply port comes into contact with the microchip. The microfluidic chip is arranged such that a reservoir opened at the surface of each end portion of the flow path including at least the main flow path for separation in which the analysis is performed while the solution moves inside the plate-like member is placed on the upper surface. In the separation buffer liquid filling device for filling the path with the separation buffer liquid,
An air supply port that is pressed airtightly on the one of the reservoirs at one end of the flow path of the microchip where the separation buffer solution is injected, and is inserted into the other remaining reservoirs from above, and the air supply A suction nozzle that sucks the separation buffer liquid overflowing from the flow path into the reservoir when air is blown from the mouth and the separation buffer liquid is pushed into the flow path;
The suction nozzle is slidably supported by a nozzle holding member that moves in the vertical direction, and is urged downward by the urging means, so that when it is pressed against the bottom of the reservoir, the urging means A separation buffer solution filling device, wherein the separation buffer solution filling device is energized. In a state before the suction nozzle is inserted into the reservoir, the length of the suction nozzle that is inserted into the sample supply reservoir among the suction nozzles so as to protrude downward from the nozzle holding member is such that the other suction nozzles 3. The separation buffer according to claim 2, wherein the separation buffer is installed so as to be longer than the length of the liquid existing in the reservoir into which the other suction nozzles are inserted as compared to the length protruding downward from the nozzle holding member. Liquid filling device. The outer diameter of the tip of the suction nozzle is smaller than the size of the bottom of the reservoir into which they are inserted,
4. The separation buffer liquid filling device according to claim 2, wherein when the suction nozzle sucks the liquid from the reservoir, the tip of the suction nozzle is pressed against the bottom side wall of the reservoir. 5. The air supply port according to claim 2, wherein the air supply port is a front end opening of an air cylinder, and a seal portion is provided in the opening, and the air supply port is pressed against the reservoir while maintaining airtightness. Separation buffer liquid filling device. The air cylinder moving / driving mechanism for moving the air cylinder in the vertical direction and operating the plunger is as follows:
An air cylinder holding member for holding the air cylinder;
A plunger holding member for holding the plunger above the air cylinder holding member;
A guide for slidably supporting the air cylinder holding member and the plunger holding member;
An elastic member disposed between the air cylinder holding member and the plunger holding member;
A drive mechanism for moving the plunger holding member in the vertical direction;
A stopper for defining a top dead center of the plunger holding member;
With
The elastic member pushes and lowers the air cylinder holding member by the elastic member until the air supply port comes into contact with the microchip in the lowering process of the plunger holding member accompanying the operation of the drive mechanism. 6. The separation buffer liquid filling device according to claim 5, wherein after the supply port comes into contact with the microchip, the plunger is pushed to supply air from the air supply port. The separation buffer liquid filling apparatus according to claim 6, wherein the air cylinder holding member is integrated with the nozzle holding member. A holding unit for holding a microchip having at least a separation main channel for performing analysis while the solution moves inside the plate-like member, and a separation buffer solution filling device for filling the separation buffer solution in the channel of the microchip A dispensing probe for inserting the sample or reagent into the sample container or reagent container from above and injecting the sample or reagent into a predetermined position of the microchip held by the holding unit; and the dispensing probe for the microchip In a microchip processing apparatus comprising at least a dispensing probe driving mechanism for moving between a predetermined position of a sample container and a reagent container,
A microchip processing apparatus using the separation buffer liquid filling apparatus according to any one of claims 1 to 7. The holding unit holds the microchip so that the number of the main flow paths is plural,
A control unit is provided to control the pretreatment process and the analysis process in the main channel,
The dispensing probe is commonly used in the plurality of main flow paths, and performs a pretreatment process prior to the analysis process in the main flow paths,
The control unit performs the pretreatment process independently for each main flow path so that the process proceeds to the pretreatment process of the next main flow path when the pretreatment process in one main flow path is completed. The microchip processing apparatus according to claim 8, wherein the microchip processing apparatus is controlled so as to perform the analysis process in parallel on the road.

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