JPH0534328A - Method for washing channel of auto-sampler - Google Patents

Abstract

PURPOSE:To obtain a method for washing a channel of an auto sampler which can wash the outside surface of a needle and the inside of the channel where a sample liquid flows etc., positively. CONSTITUTION:A needle 37 is inserted into a washing liquid 44. At this time, since the outer surface of the needle directly contacts a second washing liquid, the outer surface can be washed. Then, a three-way valve 34 is switched and second and third ports b and c are connected. Then, by pulling a piston 35a of a metering cylinder 35, a specified amount of second washing liquid is taken into a sample liquid intake pipe 23 through a needle. Then, by moving the needle into a washing port 39 and at the same time pressing the piston, the second washing liquid which is taken in is discharged outside by the needle, thus enabling an internal channel to be washed.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an improvement of a method used for an HPLC autosampler for cleaning a flow path through which a sample solution flows.

[0002]

2. Description of the Related Art FIG. 4 shows an example of the configuration of a conventional measuring device for an auto sampler. The operation principle will be briefly described with reference to FIG. First, the six-way valve 1 having the six ports A to F is for switching between the sample introduction route and the sample derivation route, and one of the flow paths shown by the solid line and the broken line is selected. Be electrically conducted. The sample suction tube 2 is moved downward with the flow path indicated by the solid line being made conductive, and the needle 3 provided at the tip thereof is inserted into the sample solution 5 filled in the sample bottle 4. Then, the piston of the measuring syringe 6 is pulled, and a predetermined amount of the sample liquid 5 is sucked from the needle 3.

Next, the flow path of the hexagonal valve 1 is switched to the state shown by the broken line. In this state, the piston of the measuring syringe 6 is pushed to inject the sample solution into the sample loop 7 by a predetermined amount.

After that, the flow path of the six-way valve 1 is switched again to the state shown by the original solid line. Then, the eluent 10 in the storage tank 9 delivers the sample in the sample loop to the column 11 by the pump 8. The sample is separated into each component in the column 11 and detected by the detector 12.

When one measurement is completed, the inside of each flow path is cleaned in preparation for the next measurement. Here, first, the inside of the flow path through which the eluent 10 has passed when the sample solution 5 is extruded is washed with the eluent 10. However, the eluent 10
The passage through which the eluent 10 does not pass, that is, the needle 3 and the sample liquid suction pipe 2 are not washed. Therefore, conventionally, the flow path of the three-way valve 13 is switched to the state shown by the broken line, and in this state, the piston of the measuring syringe 6 is pulled to wash the cleaning liquid 1 filled in the cleaning liquid storage tank 14 in the measuring syringe 6.
After inhaling 5, the flow path of the three-way valve 13 is switched to restore the original solid line state. Then, by pushing the piston, the cleaning liquid 15 in the measuring syringe 6 is supplied to the needle 3 side through the sample liquid suction pipe 2 and discharged from the needle 3 to the outside. That is, the cleaning liquid 15 is caused to flow in the direction opposite to the above-described suction of the sample liquid. As a result, the sample liquid injection tube 2
In addition, the inside of the needle 3 and the like is washed.

[0006]

However, the above-mentioned conventional cleaning method has the following problems. That is, since the tip of the needle 3 is inserted into the sample solution 5 when the sample solution is sucked, the sample solution 5 is also attached to the outer surface of the needle 3. Therefore, it is necessary to wash the sample solution 5 as well. However, in the conventional cleaning method, the cleaning liquid 15 is passed through the inside of the sample liquid suction pipe 2, and the main purpose is exclusively to clean the internal flow passage,
The outer surface of the needle 3 cannot be washed sufficiently.

When the sample solution 5 is a biological sample, particularly serum or urine, the proteins and lipids in the sample solution 5 form Teflon (registered trademark) which forms each flow path of the sample solution suction tube 2 and the like. ) Is adsorbed on. Then, in order to remove the adsorbed proteins and the like, washing with various alkalis, acids and organic solvents is required. However, since the conventional apparatus described above has only the single cleaning liquid storage tank 14, only one type of cleaning liquid 15 can be supplied to the needle 3 side during cleaning. Therefore, depending on the type of sample liquid 5 to be measured,
Since one of the above-mentioned three types of cleaning liquid having the highest cleaning effect was selected and used, there is a possibility that a sufficient cleaning effect cannot be exhibited. That is, if an alkaline cleaning liquid is used, the substances dropped by the acidic or organic solvent cleaning liquid may not be removed and may remain attached to the inner wall surface of the flow path.

The present invention has been made in view of the above background, and an object of the present invention is to accurately wash the outer surface of the needle, the internal flow path through which the sample solution flows, and the like to ensure accurate measurement. An object of the present invention is to provide a method for cleaning a flow path of an autosampler that can be performed and that suppresses the occurrence of contamination.

[0009]

In order to achieve the above object, in the method for cleaning the flow path of the autosampler according to the present invention, a needle provided at the tip of the sample liquid suction tube is inserted into the cleaning liquid to remove the sample. The cleaning liquid is sucked into the sample liquid suction pipe through the needle by substantially the same operation as the liquid suction, and then the cleaning liquid is circulated in the direction opposite to the suction direction to discharge the cleaning liquid to the outside from the needle. I did it.

Further, preferably, a plurality of different cleaning liquids are prepared, the needles are sequentially inserted into the plurality of cleaning liquids, and the cleaning liquids are sucked and discharged.

[0011]

By inserting the needle directly into the cleaning liquid, the outer surface of the needle comes into contact with the cleaning liquid, and the sample liquid adhering to the outer surface at the time of measurement is cleaned. Then, in this state, the cleaning liquid is sucked into the sample liquid suction pipe through the needle, and then the sucked cleaning liquid is caused to flow backward and discharged to the outside, whereby the internal flow path of the sample liquid suction pipe is cleaned.

Since this cleaning liquid can be sucked in by the same work as the sample liquid suction step in the normal measurement, no special mechanism is required. For example, the needles are sequentially placed in different kinds of cleaning liquid. By inserting, it is possible to clean the flow path by using plural kinds of cleaning liquids.

[0013]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT A preferred embodiment of a method for cleaning a flow path of an autosampler according to the present invention will be described in detail below with reference to the accompanying drawings. FIG. 1 shows an example of an apparatus suitable for implementing the first embodiment of the present invention. As shown in the figure, the basic configuration of the measurement system is substantially the same as the conventional configuration described above.
That is, by appropriately switching the six-way valve 20, the sample solution 22 in the sample bottle 21 is temporarily stored in the sample loop 24 via the sample solution suction pipe 23, and then the eluent 27 in the storage tank 26 is removed by the pump 25. By supplying to the sample loop 24 side, the sample liquid 2 once stored
2 is supplied to the column 28 and thus to the detector 29.

Then, the lower end suction port 3 of the cleaning liquid suction pipe 33 is placed in the cleaning liquid storage tank 32 filled with the first cleaning liquid 30.
3a is inserted and arranged, and the other end of the cleaning liquid suction pipe 33 is connected to the first port a of the three-way valve 34. On the other hand, the second port b of the three-way valve 34 is connected to the measuring syringe 35, and as shown by the broken line in the figure,
The measuring syringe 3 with the second ports a and b communicating with each other
By pulling the piston 35a of No. 5, the first cleaning liquid 3
0 is sucked into the measuring syringe 35.

Further, the third port c of the three-way valve 34 is connected to the port F of the six-way valve 20 via the sample liquid suction pipe 36, and the suction of the sample liquid 22 and the sample liquid suction pipe are performed as in the conventional case. This contributes to the cleaning of the inner flow path of the needle 37 attached to the tip of the sample liquid suction tube 36.

Furthermore, on the sample bottle 21 side, that is, on the needle 37 side, a bottomed cylindrical cleaning port 39 for receiving the first cleaning liquid 30 discharged from the needle 37 is provided. In this example, a drain port 39a is provided at the bottom of the cleaning port 39, one end of the drain pipe 40 is connected to the drain port 39a, and the other end of the drain pipe 40 is connected to the cleaning liquid reservoir tank 41. The cleaning liquid storage tank 41 is connected to the vacuum pump 42.

Further, a washing bottle 45 filled with the second washing liquid 44 is provided near the sample bottle 21. The second cleaning liquid 44 may be the same as the above-mentioned first cleaning liquid 30 or may have different components, and is arbitrarily set as necessary. Further, although one washing bottle 45 is provided in this example, a plurality of washing bottles 45 may be provided.
A sample bottle (sample bottle) may be used as a washing bottle similarly to the sample solution.

A flow path cleaning method according to the first embodiment of the present invention will be described using the apparatus having the above-mentioned configuration. Now, it is assumed that the normal measurement of the sample liquid 22 is completed. Then, the needle 37 is moved in a predetermined direction, and the tip of the needle 37 is inserted and arranged in the cleaning port 39. The three-way valve 34 is connected to the first port a and the second port a as shown by the broken line in the figure.
After establishing a state of communication with port b of
A predetermined amount of the first cleaning liquid 30 is sucked into the measuring syringe 35 by pulling the piston 35a of No. 5 by a predetermined amount.

Next, the flow path of the three-way valve 34 is switched to bring the second port b and the third port c into communication with each other. In this state, by pushing the piston 35a of the measuring syringe 35, the first syringe sucked into the measuring syringe 35
The cleaning liquid 30 is discharged from the lower end of the needle 37 into the cleaning port 39 through the sample liquid suction pipe 36, the ports A and F of the hexagonal valve 20, and the needle 37. As a result, each inner channel is cleaned. Further, in this example, while the first cleaning liquid 30 is being discharged from the needle 37, the vacuum pump 42 is operated to suck the first cleaning liquid 30, and the first cleaning liquid 30 discharged into the cleaning port 39 is constantly drained 39a. , A cleaning liquid reservoir tank 42 through the drain pipe 40
The used first cleaning liquid 30 is prevented from accumulating in the cleaning port 39 to prevent the used cleaning liquid from re-adhering to the outer surface of the needle 37, but it is not always necessary to operate the cleaning liquid. Absent.

When the normal cleaning of the flow path is completed in this way, the process proceeds to the cleaning step according to the present invention. That is, first, as shown in FIG. 2 (A), the needle 37 is inserted into the second cleaning liquid 44 (the same material as the first cleaning liquid 30 in this example) filled in the cleaning bottle 45, and the three-way valve is inserted. As shown by the solid line in FIG. 1, the second and third ports b and c are in communication with each other. Measuring syringe 3 in this state
By pulling the piston 35 a of No. 5, a predetermined amount of the second cleaning liquid 44 is sucked into the sample liquid suction pipe 23.

Then, the second cleaning liquid 44 of the needle 37
The outer surface of the needle 37 becomes the second
The cleaning liquid 44 is touched and the sample liquid attached to the outer surface thereof is cleaned. In addition, preferably, before aspirating the second cleaning liquid 44, more specifically, before the needle 37 is inserted into the second cleaning liquid 44, the piston 35a of the measuring syringe 35 is pulled to suck a small amount of air. Let me keep it.

Next, the needle 37 is moved upward, its lower end is separated from the liquid surface of the second cleaning liquid 44, and in this state, the piston 35a of the measuring syringe 35 is further pulled to suck in a small amount of air (see the same figure ( See B)). Then, the needle 37 is moved to be positioned inside the cleaning port 39. In this state, the piston 35 of the measuring syringe 35
By pressing a, the second cleaning liquid 44 once sucked is discharged from the needle 39 toward the discharge port 39 (see (C) in the figure), and the cleaning of the inner channel is completed. Then, the discharged second cleaning liquid 44 is the same as the first cleaning liquid 3 described above.
Like 0, it is discharged to the outside.

When the cleaning is completed, the vacuum pump 42 is stopped and the needle 37 is raised to be separated from the cleaning port 39. As described above, in this example, the used cleaning liquids 30, 4 are used in the cleaning port 39.
Since No. 4 is not stored, the cleaning liquid does not reattach to the outer surface of the needle 37 when the needle 37 moves upward.

If necessary, the cleaning process by suction from the needle 37 may be repeated a plurality of times. In such a case, the cleaning effect is further enhanced. In addition, like the present embodiment, when used in combination with a normal cleaning process, the cleaning process by suction from the needle 37 according to the present invention may be performed at regular intervals or randomly without performing each measurement. You can Further, in the above embodiment, the cleaning according to the present invention is performed after the normal cleaning, but the order may be reversed.

Further, the operation timing of the vacuum pump 42 is the same as in the above-described embodiment, that is, the cleaning liquids 30, 44.
Need not be performed before jetting from the needle, all washing steps for the needle 37 are completed, and the needle 3
7 is operated before moving upward, and the washing port 39
It suffices if the cleaning liquid in the inside can be discharged, but preferably, the used cleaning liquid is collected in the cleaning port 39 and the needle 27
The vacuum pump 42 is operated before the used cleaning liquid comes into contact with the lower end of the vacuum pump 42.

FIG. 3 shows the essential parts of the working process of the second embodiment of the present invention. Also in this example, the steps of inserting the needle 37 into the second cleaning liquid 44 and sucking it, then moving the needle 37 up and then sucking a small amount of air are the same as in the first embodiment. The state inside the sample liquid suction pipe 23 and the six-way valve 20 after sucking the air is shown in FIG. 3 (A). That is, the second cleaning liquid 44 shown in black is located up to the central portion of the sample liquid suction pipe 23 that connects the port F of the six-way valve 20 and the measuring syringe 35. The reference numeral 47 in the figure is the air sucked before the second cleaning liquid 44 is sucked.

In this state, the piston 35a of the measuring syringe 35 is pushed by a predetermined amount. This pushing amount is smaller than the pulling amount in the previous step. Then, as shown in FIG. 3B, the second cleaning liquid 44 is pushed back by a predetermined amount. However, although not shown, the second cleaning liquid 4 is also in this state.
The second cleaning liquid 44 does not leak from the tip of the needle 37 due to the air sucked after the suction of No. 4 described above.

By pushing and pulling the piston 35a a predetermined number of times, as shown in FIGS. 3 (A) and 3 (B).
Repeat the state of. As a result, the second cleaning liquid 44 reciprocates in the sample liquid suction tube 23, and the cleaning effect is further enhanced.

After that, the needle 37 is moved to the cleaning port 39 side and the piston 35a is largely pushed to discharge the sucked second cleaning liquid 44. Other configurations and effects are the same as those of the above-described first embodiment, and therefore description thereof will be omitted.

In each of the above-mentioned embodiments, one type of cleaning liquid is sucked through the needle 37, but the present invention is not limited to this, and a plurality of cleaning bottles are prepared, Each cleaning bottle may be filled with a cleaning liquid of a different type, for example, an alkaline solvent, an acidic solvent, or an organic solvent, and the above cleaning operation may be performed on a desired cleaning liquid. With such a configuration, it is possible to reliably perform the cleaning process even on a sample solution such as a biological sample (serum or the like) that cannot be completely cleaned without using a plurality of kinds of cleaning solutions.

When a plurality of types of cleaning liquid, especially two types of cleaning liquid, are required, one of the cleaning liquids is filled in the cleaning liquid storage tank for normal cleaning without preparing a plurality of cleaning bottles as described above. In addition, the same effect can be obtained by filling the other cleaning liquid in the cleaning bottle.

In addition, in each of the above-mentioned embodiments, an example in which the cleaning method of the present invention is carried out in addition to the usual cleaning method has been described, but the cleaning of the flow path and the like is performed only by the cleaning method of the present invention. You may do it. In such a case, the three-way valve and the washing liquid storage tank are not required, and the metering syringe can be directly connected to one port of the six-way valve, and the apparatus for carrying out the method of the present invention can be simplified.

[0033]

As described above, in the flow path cleaning method of the autosampler according to the present invention, since the needle is directly inserted into the cleaning liquid, the outer surface of the needle comes into contact with the cleaning liquid,
This allows the outer surface to be cleaned. Then, in that state, the cleaning liquid is sucked into the sample liquid suction pipe through the needle, and then the sucked cleaning liquid is backflowed and discharged to the outside, so that the internal flow path of the sample liquid suction pipe can be cleaned. . That is, in the present invention, since the cleaning work can be performed in the same work as the step of inhaling the sample solution during the normal measurement, there is no need for a special device / mechanism, and the conventional device can be used as it is. Also plays.

Moreover, for example, by sequentially inserting the needles into different types of cleaning liquids, it is possible to clean the flow channels using a plurality of types of cleaning liquids, and it is possible to more reliably clean the flow channels. Therefore, for example, even after the measurement of the sample liquid, which cannot be completely washed unless a plurality of washing liquids such as serum and urine are used, the washing treatment can be reliably performed. As a result, the proteins and lipids in the serum and urine are not adsorbed to the Teflon (registered trademark) forming each flow path such as the sample liquid suction tube, so that the volume (cross-sectional area) in the flow path is It can be kept constant at all times, and accurate measurement can be performed without the sample liquid to be measured and the sample liquid performed last time being mixed. Furthermore, it is possible to continuously perform measurements on sample liquids that require different cleaning liquids, and work efficiency is improved.

[Brief description of drawings]

FIG. 1 is a configuration diagram showing an example of an apparatus suitable for carrying out a first embodiment of a method for cleaning a flow path of an autosampler according to the present invention.

FIG. 2 is a diagram for explaining the operation of the first embodiment.

FIG. 3 is a diagram showing a main part of a process of a second embodiment of a method for cleaning a flow path of an autosampler according to the present invention.

FIG. 4 is a configuration diagram showing a conventional example.

[Explanation of symbols]

22 Sample liquid 23 Sample liquid suction tube 37 needles 44 Second cleaning liquid (cleaning liquid)

Claims (2)

[Claims] 1. A needle provided at the tip of a sample liquid suction pipe is inserted into the cleaning liquid, and the cleaning liquid is sucked into the cleaning liquid suction pipe through the needle by substantially the same operation as the suction of the sample liquid. A flow path cleaning method for an auto sampler, characterized in that the cleaning liquid is circulated in a direction opposite to the suction direction and the cleaning liquid is discharged from the needle to the outside. 2. The flow path of the autosampler according to claim 1, wherein a plurality of different cleaning liquids are prepared, the needles are sequentially inserted into the plurality of cleaning liquids, and the cleaning liquids are sucked and discharged. Cleaning method.