JP2003149093A - Liquid dispensing apparatus and method therefor - Google Patents

Abstract

PROBLEM TO BE SOLVED: To prevent valuable samples from being wasted by suppressing the suction remaining quantity to a very small quantity inside a sample container. SOLUTION: This liquid dispensing apparatus 10 comprises an opening 50 for sucking and discharging the sample 54 at its tip and is provided with a channel member 35 for holding the sample 54 inside, a piezoelectric element 36 for generating discharge pressure for discharging the sample 54 in the channel member, and the sample container 21 for holding the sample to be supplied for inside the channel member. Since a recessed part 53 of the sample container 21 is provided with a conic shape in which its cross-sectional area is reduced toward its bottom, and a nozzle 41 of the channel member 35 is provided with both a conic shape in which its outer cross-sectional area is reduced toward its tip and a shape insertable to the deepest part 57 of the sample container 21; the suction remaining quantity in the recessed part 53 after the opening 50 of the tip of the channel member 35 is inserted to the deepest part of the recessed part 53, and the sample is sucked becomes a very small quantity according to the minimum cross-sectional area of the deepest part 57 of the recessed part 53.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a liquid dispensing apparatus for dispensing a minute amount of a liquid such as a reagent or a chemical solution, and a liquid dispensing method for dispensing a minute amount of a liquid such as a reagent or a chemical solution. is there.

[0002]

2. Description of the Related Art As a liquid dispensing device for dispensing a minute amount of liquid, there are, for example, blood analyzers, testing devices for genetic tests, drug discovery tests and the like. In these inspection devices, it is desired to minimize the minimum discharge amount of the liquid discharge system in order to reduce the running cost and improve the throughput. As a conventional technique for ejecting a liquid in such an inspection device, there is, for example, one described in Japanese Patent Application Laid-Open No. 10-114394. The above publication discloses a microfluidic processing device equipped with a microdispenser to which a piezoelectric converter is applied,
This microfluidic treatment device is capable of forming droplets of discontinuous and substantially reproducible size of less than 1 nanoliter. The schematic configuration will be described below with reference to FIG.

A microfluidic treatment apparatus 210 shown in FIG. 6 includes a micro dispenser 216 using a piezoelectric transducer attached to a glass capillary tube, and a micro dispenser 21.
6 is filled with the transfer fluid 224, and the micro dispenser 2
16 withdrawing the transfer fluid 224 from the system fluid 220
Positive displacement pump 212 for controlling the pressure of the pump and cleaning the microdispenser 216 between transfers,
A piezoresistive pressure sensor 214 that measures the pressure of the system fluid 220 and emits a corresponding electrical signal. The pressure signal measured by the piezoresistive pressure sensor 214 is used to check and measure the volume of transfer fluid 224 dispensed, as well as the microdispenser 2
Used to make 16 automated adjustments and diagnostics.

As shown in FIG. 7, the micro dispenser 216 includes a glass capillary tube 262 and a glass capillary tube 262.
And a piezoelectric ceramic tube 260 coupled to the. The piezoelectric ceramic tube 260 includes an inner electrode 2 for receiving an analog voltage pulse for contracting the piezoelectric ceramic tube.
66 and an outer electrode 268. When discharging the liquid, an analog voltage pulse is sent to the piezoelectric ceramics tube 260 to cause the piezoelectric ceramics tube 260 to contract,
This contraction deforms the glass capillary tube 262. Due to the deformation of the glass capillary tube 262, the transfer fluid 224
A pressure wave is formed which travels through the nozzle and reaches the nozzle 263 of the micro dispenser, and one droplet of the transfer fluid is ejected at an extremely high acceleration in the nozzle 263. This prior art is configured to eject, for example, 5 picoliter droplets.

The transfer fluid sucked as a sample in the above-mentioned microfluidic treatment apparatus 210 is a general-purpose sample container 25 called a microtiter plate as shown in the sectional view of FIG.
It is dispensed to 0 and supplied. In the above conventional technique, the nozzle portion of the glass capillary tube 262 in the micro dispenser 216 is infiltrated into the sample to perform suction.

As described above, as the conventional sample container 250 for supplying the sample to the micro dispenser, a recessed part 251 for accommodating the sample is generally a molded product having a cylinder or a prism having an axis in the vertical direction. Target. On the other hand, as the nozzle 263 of the micro dispenser 216 for sucking the sample, an outer shape of the tip end portion thereof is often conical as shown in FIG. 7 is used.

[0007]

Generally, a liquid used as a sample for blood analysis, genetic test, drug discovery test, etc. is often very valuable. For example, regarding a DNA solution which is a sample for producing a DNA chip. Are required to be quantitatively controlled in units of microliter. However, in the prior art, since the concave portion of the sample container and the nozzle have a shape that is not related to each other, the opening at the tip of the nozzle and the concave portion of the sample container during suction, such as when the outer diameter of the nozzle is larger than the inner diameter of the concave portion. In some cases, the bottom surface of the sample cannot sufficiently approach due to the interference between the members, and in that case, a sample that cannot be aspirated remains in the concave portion of the sample container. The amount of the remaining sample increases or decreases according to the distance that the opening at the tip of the nozzle and the bottom of the recess of the sample container can approach. Even if the tip of the nozzle and the bottom of the recess are sufficiently close to each other, most of the conventional sample containers having a cylindrical or prismatic recess have a flat bottom, so that the sample is very small. It remains in the sample container so as to cover the entire bottom surface even though it has a large depth. Therefore, it is necessary to increase the amount dispensed into the sample container in advance in anticipation of these residual amounts. Then, the sample remaining as described above is extremely difficult to reuse in order to realize a highly accurate inspection from the viewpoint of controlling the concentration of the discharged liquid and preventing contamination. Therefore,
This residual sample will be discarded and valuable sample will be wasted.

Further, in the above-mentioned conventional micro dispenser 216, due to its ejection principle, the sample liquid to be sucked into the glass capillary tube 262 is sufficiently filled with the liquid column of the sample at the joint portion with the piezoelectric ceramic tube 260. Need quantity. The reason is that when the amount of suction is small and a layer of air, that is, a compressible fluid exists in the contracting region of the glass capillary 262, most of the contraction energy of the glass capillary 262 is consumed for compressive deformation of the air layer. This is because the pressure wave that travels through the transfer fluid 224 and reaches the nozzle 263 of the micro dispenser 216 is reduced, and it becomes difficult to discharge a desired amount of droplets. For this reason, it is necessary to suck a considerably large amount of the sample with respect to an extremely small amount of discharge, so that the undischarged sample remains. It is extremely difficult to recover and reuse the residual sample, as in the case of the residual amount in the sample container.

As described above, in the conventional liquid dispensing device,
It is necessary to aspirate more sample than necessary for the discharge amount,
Moreover, it is necessary to supply more than necessary sample into the sample container for the suction amount. Then, the sample having the suction remaining amount and the discharge remaining amount must be discarded, so that the valuable sample is wasted and the cost is increased.

The first object of the present invention is to provide a liquid dispensing device capable of suppressing the residual suction amount in the sample container to a very small amount.
The purpose of. A second object of the present invention is to provide a liquid dispensing method capable of minimizing the amount of discharge remaining in the liquid holding member.

[0011]

In order to achieve the first object, the first invention according to claim 1 has an opening at the tip for sucking and discharging the sample, and the sample is internally provided. A liquid holding unit that holds a liquid holding member, a driving member that generates a discharge pressure for discharging the sample held in the liquid holding member, and a sample container that holds the sample to be supplied into the liquid holding member. In the pouring device, the sample container includes a recess for holding a sample, and the recess has a shape in which a cross-sectional area decreases toward the bottom, and the liquid holding member has an outer cross-sectional area toward the tip. Is reduced, and the shape is such that it can be inserted into the deepest part of the sample container.

According to the first aspect of the invention, when the sample is sucked, the tip of the flow path member is inserted into the recess of the sample container holding the liquid,
The opening in the tip is brought close to the bottom (the deepest part) of the recess to suck the liquid in the recess. At that time, the recess has a shape in which the cross-sectional area decreases toward the bottom, and the liquid holding member has a shape in which the outer cross-sectional area decreases toward the tip, and the deepest part of the sample container. Since it has a shape that can be inserted up to, the amount of suction remaining in the recess after inserting the opening at the tip of the liquid holding member to the deepest part of the recess and sucking the liquid is the recess of the sample container. It depends on the minimum cross-sectional area of the deepest part of. Therefore, it is possible to reduce the amount of suction remaining in the concave portion of the sample container to a small amount, reduce the amount of discarded sample, and suppress the waste of valuable sample.

According to a second aspect of the present invention, the concave portion of the sample container has a shape in which the cross-sectional area continuously decreases toward the bottom, and the liquid holding member has a continuous external cross-sectional area toward the tip. It is characterized in that the shape is such that it can be inserted to the deepest part of the sample container.

In the second invention, the concave portion of the sample container has a shape in which the cross-sectional area continuously decreases toward the bottom, and the liquid holding member has a shape in which the outer cross-sectional area continuously decreases toward the tip. There is, and since it is a shape that can be inserted to the deepest part of the sample container, the shape of the concave portion of the sample container and the tip of the liquid holding member can be a conical shape or a pyramidal shape, The work of molding the recess and the tip of the liquid holding member is facilitated.

The third aspect of the present invention is characterized in that the shape of the recess of the sample container and the shape of the tip of the liquid holding member are substantially similar.

In the third aspect of the invention, since the shape of the recess of the sample container and the shape of the tip of the liquid holding member are substantially similar, the tip of the liquid holding member is inserted to the deepest part of the sample container. It is possible to minimize the amount of suction remaining in the recess when the liquid is sucked.

In order to achieve the second object, the invention as set forth in claim 4
A fourth aspect of the present invention is a liquid dispensing method for ejecting a small amount of a sample held in a flow path in a liquid holding member from a tip opening of the liquid holding member, wherein a predetermined liquid is flown in the liquid holding member. A filling step of filling the passage, an air suction step of sucking air from the tip opening of the liquid holding member, an auxiliary liquid suction step of sucking auxiliary liquid from the tip opening of the liquid holding member, and a tip of the liquid holding member. It is characterized in that a sample suction step of sucking a sample from the opening is sequentially performed.

According to the fourth aspect of the invention, after sucking air from the tip opening of the liquid holding member whose inside is filled with the predetermined liquid, the auxiliary liquid is sucked from the tip opening of the liquid holding member, and then the above-mentioned Since the sample is sucked from the tip opening of the liquid holding member, a liquid column in which a predetermined liquid layer, an air layer, an auxiliary liquid layer, and a sample layer are sequentially laminated is formed in the liquid holding member. At this time, some diffusion proceeds at the interface between the auxiliary liquid and the sample liquid, but since the time interval from sample suction to sample discharge is generally short, the amount of auxiliary liquid diffused in anticipation. By setting the suction amount of the sample to be slightly larger than the desired ejection amount, it is possible to eject the sample of the desired ejection amount using the portion of the sample layer that is not affected by the diffusion of the auxiliary liquid. it can. in this case,
Since ejection energy (ejection speed) corresponding to the liquid column composed of the sample layer and the auxiliary liquid layer can be obtained, it is possible to substitute the auxiliary fluid for the portion of the sample which is the ejection remaining amount in the above-mentioned conventional technique. Become. Therefore, it is possible to minimize the residual amount of the sample discharged from the liquid holding member, reduce the amount of the sample to be discarded, and suppress the waste of the sample.

[0019]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. FIG. 1 is a diagram showing a schematic configuration of a liquid dispensing apparatus according to a first embodiment of the present invention, and FIG.
3 is a diagram illustrating a drive voltage waveform applied to the piezoelectric element of the ejection head in the liquid dispensing apparatus of the embodiment, and FIG.
(A)-(e) is a figure for demonstrating the discharge operation of the discharge head of 1st Embodiment, and FIG. 4 is the total suction amount and liquid of the sample and auxiliary liquid in the liquid dispensing apparatus of 1st Embodiment. It is a figure which shows the relationship with the discharge speed of a droplet.

The liquid dispensing apparatus 10 of this embodiment includes the liquid discharge head 20 shown in FIG. The liquid discharge head 20 is supported by a movable transport member (not shown), and is transported by this movable transport member, so that the sample container 21, the cleaning tank 22, the auxiliary liquid tank 58, and the movable stage 23.
A moving arrangement is provided above each of the upper reaction vessels 24.

An upper portion of the liquid discharge head 20 is constructed as a syringe piston pump 25, and a pipe 28 that branches rightward in the drawing in a flow path 27 of the syringe 26.
An electromagnetic valve 29, a water feed pump 30, and a liquid supply tank 31 are sequentially connected to the. The piston 32 provided at the upper end of the syringe piston pump 25 is configured to reciprocate in the direction indicated by an arrow 33 (the vertical direction in the drawing) by a linear reciprocating mechanism including a stepping motor, a gear rack pinion, etc., not shown. There is. The liquid ejection head 20 and the liquid supply tank 31 are installed at substantially the same height.

The lower part of the liquid discharge head 20 is constructed as a detachable nozzle unit 34, and mainly comprises
The flow path member 35 and the piezoelectric element 36 functioning as a drive unit for driving the flow path member 35 are included. Piezoelectric element 3
One end (upper end in the drawing) of 6 in the displacement direction is a fixed end joint 3 that can be fitted into a mounting hole 37 formed in the lower end of the syringe 26.
8 is fixed to the lower end portion of the piezoelectric element 36, and the other end (lower end in the drawing) of the piezoelectric element 36 in the displacement direction is fixed to a free end joint 39 having a screw portion formed on the lower inner circumference.

The flow channel member 35 has a hollow cylindrical flow channel 40 for holding the liquid therein, and a nozzle 41 having an inner diameter substantially matching the flow channel 40 and having a tapered tip.
It is composed of a channel 40 having a threaded portion on the outer periphery of the upper part and a channel joint 42 that continuously connects the inner surface of the nozzle 41, and functions as a liquid holding member for holding a liquid such as a sample therein. The free end joint 39 and the flow passage joint 42 can be easily coupled and separated by the screw portion 43. The nozzle unit 34 is assembled using an assembly jig (not shown) so that the coaxiality of each member can be obtained in a state where the free end joint 39 and the flow path joint 42 are coupled. Further, the V groove 44 is provided on the outer periphery of the fitting portion of the fixed end joint 38.
And the nozzle unit 34 is attached to the syringe 26.
When the nozzle unit 34 is mounted on the syringe 26, the nozzle unit 34 can be simply and sufficiently pressured by tightening the retaining screw 45 having a spherical tip on the slope above the V groove 44 in a state where both are fitted. Can be fixed to.

Further, a concave portion 46 having a predetermined inner diameter and depth is formed on the end surface of the fixed end joint 38.
In the present embodiment, one or a plurality of O-rings 47 fitted to the outer periphery of the flow path 40 are axially compressed and deformed in the recess 46 using the fixing pressure of the nozzle unit 34, so that the syringe 26 A sealed flow path communicating with the flow path member 35 is ensured. Also, the recess 4
The inner diameter of 6 is sufficiently large so as not to restrict the outer diameter of the O-ring 47 that expands when the O-ring 47 is deformed.

The nozzle 41 has a taper portion 48 formed on the tip end side and a straight portion 49 whose inner diameter substantially matches that of the flow passage.
And communicates with the external atmosphere at the opening 50 at the tip of the nozzle. The approximate dimensions of the straight portion 49 are an inner diameter of 0.5 to 3 mm, an outer diameter of 1.5 to 6 mm, and a length of 3 to 60 m.
m, and in the present embodiment, an inner diameter of 1.5 mm,
The outer diameter is 2.5 mm and the length is 10 mm. Further, the angle of the tapered portion 48 is 5 to 20 ° on the inner side and 25 to 45 ° on the outer side.
In this embodiment, the inside is 10 ° and the outside is 3
It is formed at 0 °. Further, when the opening 50 has a dimension of 70 to 100 μm, it may have a straight portion 59 having a length of 70 to 200 μm leading to the inside of the tapered portion. In the present embodiment, the opening diameter is 75 μm and the straight portion is It is set to 120 μm.

Since each joint and joint provided between the piezoelectric element 36 and the flow path member 35 are formed as a rigid body, the flow path member 35 can be displaced in the vertical direction in the figure by the displacement of the piezoelectric element 36. Has become. Each of the electrodes 36a and 36b formed on the piezoelectric element 36 has a lead wire 5
A voltage having a desired waveform is applied from a drive circuit (not shown) via 2 (a flexible substrate may be used instead). Further, in order to prevent dust in the air from adhering to the vicinity of the opening 50 due to the charging of the liquid discharge head 20, ionization air can be blown from a blower (not shown) to remove static electricity.

The liquid supply tank 31 is operated by the solenoid valve 29 and the water supply pump 30 to perform clean cleaning water (for example, pure water) whose quality is controlled, an aqueous solution of a surfactant, and an alkali such as an aqueous solution of sodium hypochlorite. The solution can be supplied at a predetermined timing and pressure.

As the sample container 21, for example, 8 places × 1
A transparent resin molded product having a total of 96 recesses 53 arranged in two rows is used. This sample container 21
Can hold (store) the sample 54 inside the recess 53 when installed horizontally. The recess 53 has a cylindrical shape in its opening 55 and a conical shape in its bottom 56. The inner diameter of the cylinder is the outer diameter of the nozzle +
The conical taper angle may be 30 to 50 °, which is slightly larger than the outer angle of the tapered portion 48 of the nozzle 41. In the present embodiment, the inner diameter of the cylindrical portion is The outer diameter of the nozzle is +1.5 mm, and the taper angle of the conical shape is 40 °.

In the sample container 21, a single or a plurality of types of sample liquids (for example, DNA solution) are dispensed into the sample container 21 by a fixed amount, so that the liquid dispensing apparatus of the present embodiment can be used. With the sample container 21 installed,
By driving the liquid ejection head 20 (or the movable stage 23), the nozzle 41 can be made to penetrate into each of the predetermined recesses. At that time, the nozzle 41 and the recess 5
By controlling the relative positional relationship with the nozzle 41.
It is possible to safely approach the deepest part 57 of the recess 53 while preventing the tip of the contact part from contacting the wall surface of the sample container 21. Further, in order to suppress changes in the concentration of the sample held in the sample container 21 due to drying, a cover mechanism (not shown) that can seal the upper surface of the sample container 21 is provided, and the liquid dispensing apparatus 10 has an installation atmosphere of the sample container 21. An air conditioning mechanism (not shown) that appropriately holds the temperature and humidity of the above shall be provided.

In the cleaning tank 22, clean cleaning water (for example, pure water) whose quality is controlled, an aqueous solution of a surfactant, and an alkaline solution such as an aqueous solution of sodium hypochlorite are predetermined by a supply device (not shown). It is possible to supply up to the water level. In addition, ultrasonic waves are applied to the cleaning tank 22 by a driving device (not shown). Also,
The auxiliary liquid tank 58 is quality-controlled and is relatively unlikely to diffuse into the sample (in other words, the diffusion speed is relatively slow), and a clean liquid is supplied as an auxiliary liquid by a supply device (not shown) and held therein. Keep it. For example, when a DNA solution is used as a sample, ultrapure water is used as an auxiliary liquid,
Freon etc. shall be used. Since each of the cleaning tank 22 and the auxiliary liquid tank 58 has an upper opening,
By driving the liquid ejection head 20, the nozzle 41 can be safely infiltrated into the liquid to be held.

The shape of the concave portion 53 of the sample container 21 and the shape of the tip of the nozzle 41 are not limited to the conical shape as described above, and the concave portion 53 has a shape whose cross-sectional area decreases toward the bottom ( It is preferable that the nozzle 41 has a shape in which the cross-sectional area continuously decreases toward the bottom portion, and the nozzle 41 has a shape in which the external cross-sectional area decreases toward the tip (preferably the external cross-sectional area continuously decreases toward the tip). The shape of the sample container 21 can be inserted into the deepest part 57 of the sample container 21. As such a shape, in addition to the conical shape, a triangular pyramid shape,
A polygonal pyramid shape such as a quadrangular pyramid shape can be used. Further, the shape of the concave portion 53 of the sample container 21 and the nozzle unit 34
It is preferable that the shape of the tip of the nozzle 41 is substantially similar to the above because it will minimize the amount of suction that will be described later. Further, both the shape of the concave portion of the sample container and the shape of the tip of the nozzle are spherical as shown in FIG. 5, or the combination of the concave portion of the sample container which is spherical and the nozzle whose tip is conical. You may use. When the combination shown in FIG. 5 is used, the curvature of the tip of the nozzle is set to be equal to or less than the curvature of the sample container.

Next, various operations of the liquid dispensing apparatus of this embodiment will be described. First, for the cleaning operation, the liquid ejection head 20 is moved above the cleaning tank 22, and then the tip portion is immersed in the cleaning tank 22. Next, the solenoid valve 29
By driving the water pump 30 after opening the
The cleaning water in the liquid supply tank 31 is sent to the liquid ejection head 20. As a result, the inner peripheral surface of the flow path 27 and the inner peripheral surface of the flow path member 35 are cleaned with cleaning water. At the same time, cleaning water is supplied to the cleaning tank 22 to clean the outer circumference of the nozzle 41. During this cleaning, ultrasonic cleaning is applied to the cleaning tank 22 to promote cleaning. While the washing water is being sent to the flow passage 27, the piston 32 of the syringe piston pump 25 is moved to the midpoint, and then the electromagnetic valve 29 is closed to move the flow passage 27 to the flow passage 27 as shown in FIG. Fill with cleaning water 71.

Next, the liquid discharge head 20 is raised above the cleaning tank 22, and ionized air is blown from a blower (not shown) there to remove electricity and remove dust from the liquid discharge head 20. Next, by moving the piston 32 upward by a predetermined amount, a predetermined amount of air is sucked into the flow path member 35 from the opening 50. By sucking the air, an air layer 72 is formed below the wash water layer 71 in the flow path 27 as shown in FIG.

Thereafter, the liquid discharge head 20 is attached to the auxiliary liquid tank 5
8 of the liquid ejecting head 20 to the auxiliary liquid supplied and held in the auxiliary liquid tank 58.
Soak part 1. Then, the piston 32 is moved upward by a predetermined amount to suck the auxiliary liquid into the flow path member 35. At that time, the wash water layer 71 and the auxiliary liquid layer 73 in the flow path member 35 are separated by the air layer 72 as shown in FIG. Then, after sucking a predetermined amount of the auxiliary liquid 73, the liquid ejection head 20 is raised above the auxiliary liquid tank 22.

Thereafter, the liquid discharge head 20 is attached to the sample container 2
1 to a predetermined position above the liquid ejection head 2 in the sample dispensed and held in the recess 53 of the sample container 21.
The portion of the nozzle 41 of No. 0 is immersed, and is made as close to the deepest portion 57 as possible so that the opening 50 at the nozzle tip does not collide with the deepest portion 57 of the concave portion 53. In this state, the sample 32 is sucked into the flow path member 35 by moving the piston 32 upward by a predetermined amount.

By suctioning the sample 54, the flow path member 35
Since the auxiliary liquid layer 73 and the sample layer 74 are in contact with each other inside, the mutual diffusion starts at the interface 75 between them. Therefore, in the present embodiment, a region of the sample layer 74 that may be affected by mutual diffusion with the auxiliary liquid layer 73 within a predetermined ejection required time is analyzed in advance, and the region is converted into a volume. The total amount obtained by adding the volume conversion amount to the desired discharge amount is set as the actual suction amount of the sample. On the other hand, on the side of the sample container 21, by holding (storing) a sample having an appropriate liquid amount (for example, a liquid amount slightly larger than the actual suction amount), the sample liquid level is set to the nozzle when the suction of the sample is completed. It is located slightly above the tip surface of 41. In this case, the sample remaining without being sucked is accumulated in the deepest portion 57 of the recess 53 of the sample container 21 (that is, the portion in the vicinity of the apex of the conical shape), and therefore has a very small volume.

After the suction of the sample in the amount corresponding to the above setting is completed, the liquid discharge head 20 is raised above the sample container 21. After that, the liquid ejection head 20 is moved to above the reaction container 24, and a desired amount of the sample is promptly ejected to a predetermined position of the reaction container 24 in a spot shape.

Next, the liquid discharging operation of the liquid dispensing apparatus of this embodiment will be described with reference to FIGS. 2 and 3. When the driving voltage E as shown in FIG. 2 is applied, the voltage E = before the instant t1 when the application of the voltage is started (t <t1).
Since it is E0, the liquid ejection head 20 is stopped.
The position of the tip of the liquid ejection head 20 at this time is shown in FIG.
Let it be A shown in (a). As the voltage E gradually rises between t1 <t <t2, the liquid ejection head 20 moves to the position shown in FIG.
As shown in, it is displaced downward gently. If such a displacement continues, a displacement corresponding to the voltage E1 occurs in the piezoelectric element 32 immediately before the instant t2 when the drive voltage E reaches the maximum value E1, so that the liquid ejection is performed as shown in FIG. The tip of the head 20 descends to a position B in the figure.

Then, immediately after the instant t2, the drive voltage E instantaneously decreases to E0.
With the sudden decrease of the drive voltage, the drive voltage is abruptly displaced upward as shown in FIG. With this upward displacement, an inertial force acts on the liquid column composed of the sample layer 74 and the auxiliary liquid layer 73 in the flow path member 35, so that the liquid column simultaneously and instantaneously moves downward in the drawing. With the movement of the sample layer 74 and the auxiliary liquid layer 73, the taper portion 7 in the nozzle 41 is moved.
Since the pressure at the tip of 6 (see FIG. 3A) rises, as shown in FIG. 3E, the surface tension in the opening 50 is broken and a part of the sample layer 74 is discharged to the outside as a droplet. Will be. At that time, the amount of the sample discharged is determined by the nozzle 4
1 is determined by the taper angle of the taper portion 76, the diameter of the opening 50, the drive voltage waveform, and the like, and the range is about 0.01 nL to 0.3 μL, but in this embodiment, the sample discharge amount is 0.5 nL. Is set to. Needless to say, the sample ejected within the predetermined ejection time is not affected by the mutual diffusion with the auxiliary liquid, and the sample having a desired concentration and purity is ejected.

In the above, the suction amount of the auxiliary liquid 73 is
The total amount with the suction amount of the sample 54 forming the sample layer 74 is set to be an appropriate amount for obtaining the inertial force that acts when the droplets are ejected. Specifically, since the total suction amount of the sample 54 and the auxiliary liquid 73 and the discharge speed of the liquid droplets have the relationship shown in FIG. 4, the total suction amount needs to be v or more in the figure. At this time, the actual suction amount of the sample 54 is determined as the liquid amount obtained by adding the desired discharge amount and the amount in consideration of the influence of the mutual diffusion with the auxiliary liquid, as described above, and therefore the total suction amount is calculated from the total suction amount. The remaining amount after subtracting the actual suction amount of 54 is the suction amount of the auxiliary liquid 73. In addition to the cleaning water 71, the auxiliary liquid 73 and the auxiliary liquid 73 are provided in the flow path member 35 after the desired discharge amount of the sample is discharged.
The sample 54 that is affected by the diffusion of the auxiliary liquid 73 and a small amount of the sample 54 that is not affected by the diffusion of the auxiliary liquid 73 remain.

After the sample is discharged, the liquid discharge head 20 is moved to the cleaning tank 22 again, and then the cleaning water is fed into the flow path member 35 so that the sample 5 remaining inside the cleaning liquid is flown.
4 and the auxiliary liquid 73 are discharged, and the nozzle 41
Clean the outer peripheral surface and the tip surface of the. After that, a desired amount of sample is repeatedly discharged into the reaction container 24 by repeating the above-described steps from the cleaning step to the discharging step.

According to the liquid dispensing apparatus of this embodiment, the concave portion 53 of the sample container 21 has a shape in which the cross-sectional area decreases toward the bottom, and the external cross-sectional area decreases toward the tip of the flow path member 35. Has a shape that
Since it has a shape that can be inserted to the deepest part of the sample container,
The amount of suction remaining in the recess after inserting the opening 50 at the tip of the flow path member 35 to the deepest part of the recess 53 and sucking the sample depends on the minimum cross-sectional area of the deepest part 57 of the recess 53.
Therefore, it is possible to reduce the amount of suction remaining in the concave portion of the sample container to a small amount, reduce the amount of discarded sample, and suppress the waste of valuable sample.

Further, according to the liquid dispensing apparatus of this embodiment, the concave portion 53 of the sample container 21 has a conical shape whose cross-sectional area continuously decreases toward the bottom, and the flow path member 35 is formed. Since the conical shape has a shape in which the outer cross-sectional area continuously decreases toward the tip, the work of molding the recess 53 of the sample container 21 and the tip of the flow path member 35 becomes easy. Further, since the shape of the concave portion 53 of the sample container 21 and the shape of the tip of the flow path member 35 are substantially similar to each other, the tip of the nozzle 41 of the flow path member 35 is inserted to the deepest portion 57 of the sample container 21 to sample the sample. The amount of suction of the sample in the recess 53 when sucked can be minimized.

Further, according to the liquid dispensing apparatus of the present embodiment, before the sample is discharged, the flow channel member 35 is formed with the washing water layer 71, the air layer 72, the auxiliary liquid layer 73 and the sample layer 74. Since the liquid column is formed, the sample layer 7 is formed by using the ejection energy (ejection speed) generated by the liquid column including the auxiliary liquid layer 73 and the sample layer 74 according to the characteristics of FIG.
4 (that is, the auxiliary liquid 7 of the sample layer 74).
3 is a portion that is not affected by the diffusion and corresponds to a desired ejection amount). Therefore, since the auxiliary fluid can replace the sample in the portion where the discharge remaining amount is in the above-mentioned conventional technique, the discharge remaining amount of the sample in the flow path member 35 can be minimized, and the amount of the discarded sample can be reduced. Can be reduced and the waste of the sample can be suppressed.

In the first embodiment described above, the liquid ejecting head that ejects the liquid by reciprocating the flow path member in the ejecting direction is used. However, the present invention is not limited to this. A technique similar to that of the technique, that is, a technique of ejecting a liquid by contracting a cylindrical piezoelectric ceramic in the radial direction and changing the volume of the flow path member may be used.

[Brief description of drawings]

FIG. 1 is a diagram showing a schematic configuration of a liquid dispensing apparatus according to a first embodiment of the present invention.

FIG. 2 is a diagram exemplifying a drive voltage waveform applied to the piezoelectric element of the ejection head in the liquid dispensing apparatus of the first embodiment.

3A to 3E are diagrams for explaining the ejection operation of the ejection head of the first embodiment.

FIG. 4 is a diagram showing a relationship between a total suction amount of a sample and an auxiliary liquid and a droplet discharge speed in the liquid dispensing apparatus of the first embodiment.

FIG. 5 is a diagram showing a modification of the concave shape of the sample container and the tip shape of the nozzle of the flow path member in the liquid dispensing apparatus of the first embodiment.

FIG. 6 is a diagram showing a schematic configuration of a conventional liquid dispensing device.

FIG. 7 is a detailed view of a micro dispenser of a conventional liquid dispensing device.

FIG. 8 is a cross-sectional view showing a concave shape of a sample container of a conventional liquid dispensing device.

[Explanation of symbols]

10 Liquid dispensing device 20 Liquid ejection head 21 Sample container 22 Cleaning tank 23 Movable stage 24 reaction vessels 25 syringe piston pump 26 syringes 27 channels 28 plumbing 29 Solenoid valve 30 water pump 31 Liquid supply tank 32 pistons 34 nozzle unit 35 flow path member 36 Piezoelectric element 36a, 36b electrodes 37 mounting holes 38 Fixed end fitting 39 Free end fitting 40 channels 41 nozzles 42 flow path fitting 43 screw 44 V groove 45 captive screw 46 recess 47 O-ring 48 taper 49 Straight part 50 openings 52 lead wire 53 recess 54 samples 55 opening 56 bottom 57 deepest part 58 Auxiliary liquid tank 59 Straight part 71 Wash water layer 72 Air layer 73 Auxiliary liquid layer 74 Reagent layer 75 Interface 76 taper

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Claims (4)

[Claims] 1. A liquid holding member having an opening for sucking and discharging a sample at its tip and holding the sample therein, and a discharge pressure for discharging the sample held in the liquid holding member. A liquid dispensing apparatus comprising: a driving member for generating the liquid; and a sample container for holding a sample to be supplied into the liquid holding member, wherein the sample container includes a concave portion for holding a sample, and the concave portion is a bottom portion. The cross-sectional area decreases toward the tip, the liquid holding member has a shape in which the external cross-sectional area decreases toward the tip, and a shape that can be inserted to the deepest part of the sample container. Characteristic liquid dispensing device. 2. The concave portion of the sample container has a shape whose cross-sectional area continuously decreases toward the bottom, and the liquid holding member has a shape whose external cross-sectional area continuously decreases toward the tip. The liquid dispensing device according to claim 1, wherein the liquid dispensing device has a shape capable of being inserted to the deepest part of the sample container. 3. The liquid dispensing apparatus according to claim 1, wherein the shape of the recess of the sample container and the shape of the tip of the liquid holding member are substantially similar. 4. A liquid dispensing method for ejecting a minute amount of a sample held in a flow path in a liquid holding member from a tip opening of the liquid holding member, wherein a predetermined liquid is filled in the flow path in the liquid holding member. Filling step, an air suction step of sucking air from the tip opening of the liquid holding member, an auxiliary liquid suction step of sucking auxiliary liquid from the tip opening of the liquid holding member, and a sample from the tip opening of the liquid holding member A liquid dispensing method comprising sequentially performing a sample suction step of sucking.