JPH1068735A - Pipetter - Google Patents

Abstract

PROBLEM TO BE SOLVED: To gather a sample even from a slope, by attaching a cover to a pipetter needle module comprising plural pipetter needle comprising a hydrophobic filter at an upper part and an opening at a lower part, and adjusting the pressure in a space between the cover and the hydrophobic filter. SOLUTION: A number of pipetter needles 2 having internal spaces, are formed on a pipetter needle module 1, an opening 3 for absorbing and exhausting the liquid, is formed at a lower part of the pipetter needle 2, and an upper part of the same is closed by a hydrophobic filter 4 through which the water in not penetrated but the gas is permeated. A cover 5 is attached to an upper face of the pipetter needle module 1, a space is formed between the cover 5 and the hydrophobic filter 4, and a nozzle 6 is formed on the center of the cover 5, to form a pipetter head 8. The decompression or the pressurization of the space in the pipetter head is 8 performed by a pressure adjusting device through the nozzle 6. When the space is depressed, and the sample liquid is absorbed into each pipetter needle 2, the penetration of the sample liquid into the space is prevented by the hydrophobic filter. Accordingly, a specific amount of sample liquid can be absorbed and held in each pipetter needle 2 at all times, even when it is placed on the slope.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a dispenser for collecting a predetermined amount of a liquid sample with a dispenser having a large number of pipettes (dispensing needles) and then dispensing a predetermined amount to a plurality of containers at the same time.
In particular, it relates to a dispenser useful for measurement and diagnosis of substances related to microorganisms, immunity, and the like.

[0002]

2. Description of the Related Art A dispenser capable of easily injecting a fixed amount at a time into a container consisting of 96 wells, such as a microtiter plate, is useful because it can be processed in a large amount in EIA, bacterial testing, and the like. It is something. As such a dispenser, for example, USP
5,348,606 and JP-A-63-159765 are known.

The conventional dispenser has a number of dispensing needles for aspirating and dispensing liquid, and the internal space of the dispensing needle communicates with each other in the upper space of the dispenser. ,
The liquid is sucked and dispensed by negative or pressurizing the upper space. As a method of using the dispenser, a number of dispensing needles of the dispenser are immersed in a tray containing the liquid, and the liquid is suctioned into a conical space in the dispensing needle by a negative pressure, and the liquid is dispensed. Hold an amount of liquid, then
The dispenser is moved to a number of wells to be dispensed, such as a microtiter, or a number of containers to be dispensed are moved to the dispenser, and the liquid held inside the dispensing needle of the dispenser is dispensed. Was injected under pressure. In particular, the technique described in each of the above publications aims to accurately hold a liquid sample in each space of a dispensing needle having a plurality of spaces.
According to the publication, the liquid sample is overfilled in the dispensing needle by forming a negative pressure in the upper space of the dispenser to form a convex meniscus, and then the liquid sample held in the cavity is formed. The amount is evenly controlled.

In such a dispenser, if each dispensing needle of the dispenser is set to be horizontal and the liquid in the tray is sucked, any dispensing needle can be placed in any dispensing needle by the principle of a U-shaped tube. A certain amount of liquid is held, and then it has the effect of dispensing a certain amount of liquid.Adjustment of the amount of liquid sucked into the dispensing needle is achieved by reducing the pressure in the dispensing needle to a negative pressure using a piston or the like. It was adjusted so that the amount of liquid to be sucked was constant.

[0005]

However, when performing a liquid dispensing operation, it is difficult to obtain an accurate horizontal place because of limitations and it is difficult. There is a problem that the amount of the liquid to be sucked varies, and an accurate amount cannot be dispensed. In addition, since the sampling described in the publication is based on suction of the liquid sample by negative pressure, if the sucked liquid sample is added and filled in the dispenser, there is a possibility of contaminating the upper space of the dispenser, Once the dispenser used for sampling was applied to the sampling of another liquid sample, there was a contamination problem.

Accordingly, the present invention provides a dispenser that does not require the sampling location to be horizontal and that can sample and dispense an accurate amount, and is made of low cost materials. It is an object to provide a dispenser which can be used.

[0007]

In order to solve the above-mentioned problems, a dispenser according to the present invention has an internal space, a lower portion having an opening through which liquid can be sucked and discharged, and an upper portion containing water. A dispensing needle module having a plurality of dispensing needles that are closed by a hydrophobic filter that is impermeable but permeable to gas, and a hydrophobic filter attached to the dispensing needle module and the dispensing needle. It is characterized by comprising a cover forming a space, and a pressure adjusting device attached to the cover and capable of adjusting the pressure of the space in the cover to reduced pressure or increased pressure.

The cost can be reduced by using polyethylene or sterilized paper for the hydrophobic filter. In particular, when the material of the hydrophobic filter is made of polyethylene, it can be easily bonded by heat fusion and an adhesive, and the expansion and contraction of the material is small. Therefore, there are remarkable advantages such as excellent workability during industrial production and low production loss. Such properties of polyethylene are excellent properties not found in Teflon, vinyl chloride, polyvinylidene, and the like, which are known as hydrophobic resins.

The pressure adjusting device preferably employs a system in which the pressure is increased by pushing out the gas accompanying the movement of the piston, and the pressure is reduced by the suction of the gas accompanying the movement of the piston. Further, since the pressure adjusting device is detachably attached to the cover, it is easy to clean the dispensing needle module and the cover.

A specific feature of the pressure adjusting device in the dispenser of the present invention is that a first piston connected to a press button in the same cylinder, and a second piston divided from the first piston The two pistons are separated when the springs biased on the respective pistons are relaxed, and the first piston pushes the second piston by the pressing of the push button, and the piston shaft of the second piston is pressed. Is formed by a stopper, and when the pressing is released in the state of the first stage, the first piston separates from the second piston due to relaxation of a spring, and at this time, spreads in the cylinder. A second stage in which a reduced pressure state is generated by the space is formed, and by releasing the stopper in the state of the second stage, the spring of the second piston is relaxed and the second piston is moved to the second stage. Narrows the space inside the cylinder by approaching the piston, characterized in that it is configured that the third stage of the pressure state is produced is formed.

The dispenser of the present invention is convenient to use because it is portable and manual.

[0012]

DESCRIPTION OF THE PREFERRED EMBODIMENTS FIG. 1 is a front sectional view of a dispensing needle module 1 which is one of the components of the dispenser of the present invention, FIG. 2 is a side sectional view thereof, and FIG. FIG. FIG. 4 is an enlarged sectional view of a part of the dispensing needle module 1. 1 to 4, a dispensing needle module 1 is formed with a plurality of dispensing needles 2 having a large number of substantially conical internal spaces at equal intervals. The lower end of the dispensing needle 2 has an opening 3 through which liquid can be sucked and discharged, and the upper part of the dispensing needle 2 is closed by a hydrophobic filter 4 that is impermeable to water but permeable to gas. The hydrophobic filter 4 is a sheet or sterilized paper having continuous air holes made of polyethylene. When the air holes have a hole diameter of 0.45 μm or less, they have a property of being impermeable to water but permeable to gas. . Each dispensing needle 2 holds a liquid in the internal space by applying a negative pressure through the hydrophobic filter 4, and discharges the held liquid by releasing or pressurizing the negative pressure. Can be.

FIG. 5 is a front sectional view of a cover 5 which is one of the components of the dispenser of the present invention, FIG. 6 is a side sectional view thereof, and FIG. 7 is a top view thereof. The cover 5 is attached to the upper surface of the dispensing needle module, and a space can be formed by the hydrophobic filter, and the fixing portion between the dispensing needle module and the cover 5 is formed at the peripheral edge of each member. At an appropriate position, preferably in the center of the cover 5, a nozzle 6 serving as a gas transfer port for decompressing or pressurizing a space formed in the cover 5 is formed. The nozzle 6
May have a protruding shape on the outside, or may have a structure depressed on the inside. It is desirable to provide a rib 7 for reinforcing the cover 5 at an appropriate position on the cover 5.

FIG. 8 shows a dispensing head 8 formed by dispensing the dispensing needle module 1 and the cover 5 at their peripheral edges. Appropriate fixing means such as heat fusion or adhesion with an adhesive can be employed for the fixing.

FIG. 9 is a top view showing the sample liquid tray 9 for supplying the sample liquid to the dispensing needle module 1, and shows a depression corresponding to a position corresponding to the tip of each dispensing needle of the dispensing needle module. The recess 10 is configured to be able to be filled with a sample liquid. FIG. 10 is a front sectional view of the sample liquid tray 9. The depressions 10 provided in the sample liquid tray 9 may be all open so as to be filled with the same sample liquid, and may be divided into two equal sections (for example, for BP),
Partitions are provided at arbitrary positions such as an equal section (for example, for ID) and an uneven section (for example, for combo), and each section is filled with different types of sample liquids so that the sample liquids do not mix. It may be.

A dispensing head 8 comprising a dispensing needle module 1 and a cover 5 of the dispenser of the present invention, or a sample liquid tray 9
Materials that can be used in the manufacture of
Any material such as glass, ceramics and metal can be used, and a rigid material suitable for repeated use is preferable.

FIG. 11 shows a pressure adjusting device 20 for reducing or increasing the pressure of the space formed in the dispensing head 8 by the piston 21, and shows the most basic type. When a depressurized state or a pressurized state is formed in the dispensing head 8 using the pressure adjusting device 20, the gas port 26 at the tip of the pressure adjusting device 20 is directly connected to the nozzle 6 of the dispensing head 8. Or, they are indirectly engaged. A position indicated by an arrow A in the pressure adjusting device 20 in FIG.
4, the piston 21 is locked, and the spring 22 is compressed and elastic energy is stored. The piston 21 and the cylinder 25 are slidably and airtightly maintained by an O-ring 201. When the depressurizing operation is performed by the pressure adjusting device 20 in FIG. 11, the stopper 24 is released, and the spring 22 relaxes, so that the piston 21 retreats to the position shown by the arrow B, and the inside of the cylinder 25 becomes negative pressure. Therefore, the space in the cover 5 is depressurized through the gas inlet / outlet 26 provided in the cylinder 25, and the dispensing head 8 immersed in the sample liquid in the sample liquid tray 9.
The sample liquid is filled and held in each dispensing needle 2. When the pressurizing operation is performed, by pressing the solution dispensing button 23, the piston 21 advances to the arrow C, and the inside of the cylinder 25 is pressurized, and therefore, the sample held in the dispensing needle 2 Liquid is released.

FIGS. 12, 13 and 14 show a pressure adjusting device 30 of another embodiment different from that of FIG. When forming a depressurized state or a pressurized state of the space in the dispensing head 8 using the pressure adjusting device 30, the gas port 36 at the tip of the pressure adjusting device 30 is connected to the nozzle 6 of the dispensing head 8. Directly or indirectly. FIG. 12 shows a state of the pressure adjusting device 30 when the stopper 34 is released, and shows a state in which the pressurizing operation is completed. At this time, the spring 321 loaded on the first piston 311 and the second piston 312
Of the first piston 311 and the second piston 312
And the space formed between the cylinder 35 is minimized and a pressurized state is formed. Therefore, the gas passage 38 passing through the second piston 312 and the piston shaft 39 passes through the gas inlet / outlet 36 and the nozzle 6 of the cover 5. The space in the cover 5 is in a pressurized state. By the transition to the pressurized state, the sample liquid held in each dispensing needle 2 is discharged.

Each of the dispensing needles 2 of the dispensing head 8 is immersed in the sample liquid in the sample tray 9 filled with the sample liquid to suck a predetermined amount of the sample liquid into the space inside the dispensing needle 2. Performs a decompression operation with the pressure adjusting device 30. By pressing the solution dispensing button 33 in advance as shown in FIG.
The tip of the first piston 311 presses the second piston 312, and the stopper 34 fits into the stopper hole 37 provided in the piston shaft 39. At this time, since the solution dispensing button 33 is in a pressed state, the spring 3 of the first piston 311
21 is compressed and the spring 322 of the second piston 312
Is also compressed. Next, when the pressing of the solution dispensing button 33 is stopped, as shown in FIG.
Of the second piston 312 continues to be compressed since the first shaft 311 rises due to the relaxation of the spring 321 of the second piston 311, but the piston shaft 39 remains locked by the stopper 37. At this time, the first piston 31
The space formed between the first O-ring 301, the O-ring 302 of the second piston 312, and the cylinder 35 expands and is in a decompressed state, so that the gas inlet / outlet is provided through the gas passage 38 passing through the second piston 312 and the piston shaft 39. The space in the cover 5 is decompressed via 36. Then
The gas inlet / outlet 36 is directly or indirectly engaged with the nozzle 6 of the cover 5, and the solution dispensing head 8 is immersed in the sample solution in the sample solution tray 9 while the solution dispensing button 33 is pressed down. The pressing of the button 33 is returned to the initial state. As a result, the space formed between the O-ring 301 of the first piston 311 and the second piston 312 and the cylinder 35 is depressurized, and as a result, the gas inlet / outlet port passes through the gas passage 38 passing through the second piston 312 and the piston shaft 39. The space in the cover 5 is reduced in pressure through the nozzle 36 of the cover 5 and the nozzle 36. Under this reduced pressure state, the sample liquid is filled and held in each dispensing needle 2.

Next, when performing the pressurizing operation, the stopper 3
By releasing 4 and returning to the state shown in FIG.
As described above, the O-ring 301 of the first piston 311
Further, the space formed between the O-ring 302 of the second piston 312 and the cylinder 35 is minimized, and a pressurized state is established.
A range indicated by a double-headed arrow in FIG. 14 indicates a suction stroke, and a range indicated by a double-headed arrow indicates a discharge stroke.

In the dispenser of the present invention, the dispensing head 8
Even if the sample solution is sucked into each dispensing needle 2
Since the upper portion of the dispensing needle 2 is closed by the hydrophobic filter 4, the sample liquid does not enter the space of the dispensing head 8. Therefore, even if the sample liquid tray 9 is not placed strictly horizontally, as long as each dispensing needle 2 is filled in the sample liquid filled in the sample liquid tray 9, the dispensing head 8
By merely reducing the pressure, the sample liquid sucked into the dispensing needle 2 is regulated by the hydrophobic filter 4 above the dispensing needle 2,
A constant amount of the sample solution is always sucked and held in the dispensing needle 2. Further, the sample liquid does not contaminate the inside of the cover 5 of the dispensing head 8.

[Experimental Example] The following experiment was conducted on the inclination of the sample liquid tray in the dispensing operation. FIG. 15 shows a sample liquid tray 9 filled with sterilized water placed on an inclined table 101 whose angle can be adjusted. The sterilized water in the sample liquid tray 9 is supplied to the dispenser of the present invention and a comparative example. Water is aspirated and held on each dispensing needle using a dispenser dedicated to a Linox system (Dade: MicroScan system), and then transferred to a dedicated microplate placed on the same inclined table 101. Dispensed. The total weight of the microplates of the two dispensed systems was measured, and then the sterilized water in the wells was removed by suction one well at a time, and the weight measurement was repeated to calculate the dispensed volume of each well. The results are shown in Table 1 below.
The values in the table indicate the average dispensed volume per well (unit: microliter).

[0023]

[Table 1]

According to Table 1, in the dispenser of the present invention, the inclination of the tilting table has no effect on the dispensed amount, whereas in the comparative system (Linox system), the inclination is only 1 degree. The dispensed amount is extremely small in the right column (the 12th column: the column at the highest position). Further, when the angle was further tilted to about 2 degrees, it was confirmed that the dispensed amount was significantly reduced in all the wells in the comparative system. At this time, undispensed sterile water remained in the dispensing head. From the above experiments, it can be seen that the dispenser of the present invention is excellent in that it always has a constant dispensing accuracy without being affected by the slight inclination of the sample liquid tray.

[0025]

According to the dispenser of the present invention, an accurate amount can be sampled and dispensed even if the sampling place is not kept horizontal, and the upper part of the dispensing needle is closed by a hydrophobic filter. As a result, the sample solution does not contaminate the inside of the cover of the dispensing head. In addition, since the hydrophobic filter can be made of polyethylene, the dispenser of the present invention is low in cost, and has excellent heat-sealing properties, excellent adhesive property, and small expansion and contraction of the material. Workability is improved, and production loss is reduced.

[Brief description of the drawings]

FIG. 1 is a front sectional view of a dispensing needle module which is one of the components of the dispenser of the present invention.

FIG. 2 is a side sectional view of a dispensing needle module which is one of the components of the dispenser of the present invention.

FIG. 3 is a top view of a dispensing needle module which is one of the components of the dispenser of the present invention.

FIG. 4 is an enlarged sectional view of a part of a dispensing needle module which is one of the components of the dispenser of the present invention.

FIG. 5 is a front sectional view of a cover which is one of the components of the dispenser of the present invention.

FIG. 6 is a side sectional view of a cover which is one of the components of the dispenser of the present invention.

FIG. 7 is a top view of a cover which is one of the components of the dispenser of the present invention.

FIG. 8 shows a dispensing head in which a dispensing needle module and a cover in the dispenser of the present invention are fixed to each other at peripheral portions.

FIG. 9 is a top view of a sample liquid tray that can be filled with a sample liquid used in the present invention.

FIG. 10 is a front sectional view of a sample liquid tray which can be filled with a sample liquid used in the present invention.

FIG. 11 is a pressure adjusting device for reducing or increasing the pressure of a space formed by a piston in a dispensing head.

FIG. 12 shows a state in which the stopper of the pressure adjusting device used in the dispenser of the present invention is released, that is, a state in which the pressurizing operation is completed.

FIG. 13 shows a state in which the solution dispensing button of the pressure adjusting device used in the dispenser of the present invention is pressed.

FIG. 14 shows a state in which the pressure of the solution dispensing button of the pressure adjusting device used in the dispenser of the present invention is stopped and the pressure reducing operation is performed.

FIG. 15 shows a state in which a sample liquid tray filled with a sample liquid is placed on an inclined table whose angle can be adjusted in order to examine the effect of the dispensing operation on the inclination.

[Explanation of symbols]

 Reference Signs List 1 dispensing needle module 2 dispensing needle 3 opening 4 hydrophobic filter 5 cover 6 nozzle 7 rib 8 dispensing head 9 sample liquid tray 10 dent 20, 30 pressure adjusting device 21 piston 22 spring 23, 33 solution dispensing button 24, 34 Stopper 25, 35 Cylinder 26, 36 Gas inlet / outlet 37 Stopper hole 38 Gas passage 39 Piston shaft 101 Inclined base 201, 301, 302 O-ring 311 First piston 312 Second piston 321, 322 Spring

 ────────────────────────────────────────────────── ─── Continuing on the front page (72) Inventor Masatoshi Mishina 1075-2 Kita-Namoro, Yuki-city, Ibaraki Pref. Nissui Pharmaceutical Co., Ltd. No. Arakawa Resin Cork Industrial Co., Ltd.

Claims (7)

[Claims] 1. A dispensing needle having an internal space, a lower part having an opening through which liquid can be sucked and discharged, and an upper part closed by a hydrophobic filter which is impermeable to water but permeable to gas. A dispensing needle module having a plurality of dispensing needle modules, a cover attached to the dispensing needle module and forming a space with the hydrophobic filter of the dispensing needle, and a cover attached to the cover and reducing a pressure of a space in the cover. A pressure regulator that can be adjusted to reduced or increased pressure,
A dispenser consisting of 2. The dispenser according to claim 1, wherein said hydrophobic filter is made of polyethylene. 3. The dispenser according to claim 1, wherein the hydrophobic filter is a sterilized paper. 4. The dispenser according to claim 1, wherein the pressure adjusting device is detachably attached to the cover. 5. The dispenser according to claim 1, wherein the pressure adjusting device pressurizes the gas by pushing out the gas with the movement of the piston and reduces the pressure by sucking the gas with the movement of the piston. 6. The pressure regulating device has a first piston connected to a press button in the same cylinder, and a second piston that is divided from the first piston, and both pistons are respectively provided. The first step in which the first piston pushes the second piston by pressing the push button and the piston shaft of the second piston is locked by the stopper When the pressure is released in the state of the first stage, the first piston separates from the second piston due to the relaxation of the spring, and at this time, the decompressed state is generated by the space expanding in the cylinder. A step is formed. By releasing the stopper in the state of the second step, the spring of the second piston relaxes and the second piston approaches the first piston. The dispenser according to claim 1, 4 or 5, wherein a third stage in which a pressure state is generated by reducing a space in the damper is formed. 7. The dispenser according to claim 1, wherein the dispenser is free to carry and is manually operated.