JPH0134344B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an improvement in an autosampler that eliminates waste in sample collection.

Conventionally, an autosampler has been equipped with fixed members 75 and 76 each having two channels 71, 72 and 73, 74, and a rotating member having a metering through hole 77 with a predetermined volume, as shown in FIG. A large number of sample storage tanks 2 are arranged on the circumference of the rotary table 79 using a two-channel two-way switching valve consisting of a rotary table 79.
The table is intermittently rotated by a drive device, and samples are sequentially pipetted into pipettes 81 by a pressure reducing device 80.
From tube 82, flow path 73, metering through hole 7
7, pressure reducing device 80 via flow path 71 and tube 83
, and then the intermediate rotating member 7
8 to connect the metering through hole 77 to the metering pump 84.
The communication hole 7 communicates with the flow path leading from the reaction tube 85
A device for introducing a sample separated into a reaction tube 85 into a reaction tube 85 (see, for example, Japanese Patent Laid-Open Nos. 49-39483, 49-39484, and 49-39487) is known.

However, in this type of autosampler, the inside of the flow path from the pipette 81 to the flow path 73 and the flow path 71 are
This has the major disadvantage that the sample in the flow path from the decompression device 80 to the decompression device 80 is completely wasted, and it is difficult to collect expensive and valuable sample liquids, from children for whom it is difficult to collect blood, or from seriously ill patients from whom only a small amount of blood can be collected. This method has the problem that it cannot be used when the sample is extremely small, such as blood sample.

As a result of various studies to solve these problems, the present inventor succeeded in developing a new autosampler that does not waste samples at all, and has previously filed a patent application (Japanese Patent Application No. 54-167584). Unexamined Japanese Patent Publication 1986
-90260], 55-146340 [Unexamined Japanese Patent Publication No. 57-70426])
However, as a result of further intensive research, compared to the invention for which a patent was applied for earlier, the operating process was simplified, the accuracy of analysis was dramatically improved, and the components of the device were reduced to the minimum necessary. succeeded in developing an autosampler.

In each of the inventions for which patent applications were previously filed, first, there is a sample suction process in which a fixed amount of sample is sucked and collected from the tip of a suction nozzle, and then a sample transfer process in which a switching valve body is switched to temporarily discharge and transfer the sample to a sample holding tube. The process is complicated, as it consists of a sample introduction step in which the switching valve body is switched and the transferred sample is introduced into the reaction system (separation column).

In addition, in each of the above steps, the sample remains confined within the elongated channel and moves back and forth within the channel while one or both end surfaces are in contact with the eluent. When trying to quantitatively analyze individual components in a sample using liquid chromatography, the separation of the components becomes slightly worse. , there arises the disadvantage that the analytical accuracy is also slightly lowered.

Furthermore, as shown in FIG. 10, the sample 5 collected by suction in the suction nozzle 6 by retreating the eluent 20 is transferred to the inside of the sample holding tube 3 as shown in FIG. First, extrude all the eluent (broken line area), then push out a part of the eluent (dotted chain line area), and then
and the tip opening of the suction nozzle 6 so that the sample does not remain in the space, and
As shown in Figure 10, the sample in the suction nozzle is transferred to the sample holding tube without losing the last drop, such as preventing spillage of the diffusion region e that occurs near the contact surface between the sample 5 and the eluent 20. There are problems that require consideration.

Furthermore, since the capacity of the diffusion area e in FIG. 10 changes depending on the type of sample, it is necessary to know the capacity of the diffusion area e in advance in the sample transfer process. Skill is required when setting operating conditions.

Furthermore, a flow path, a piston cylinder, and a pressure reducing device are required for the sample transfer process, and the number of communication holes in the flow path switching valve body is also difficult to manufacture, making the overall structure of the device extremely difficult. However, there are problems in that it is complicated and increases manufacturing cost.

The present invention is an epoch-making invention that solves all the inconveniences and problems of the inventions for which patent applications were previously filed, and the gist thereof is as set forth in the claims of the patent application.

The present invention will be explained in detail below.

FIGS. 1 and 2 are perspective views of a pair of switching valve bodies A and B used in the autosampler of the present invention, respectively, and FIG. 3 is a schematic explanatory diagram of an autosampler showing an embodiment of the present invention. 5 is an enlarged partial vertical sectional view of the main part of FIG. 3, FIG. 5 is an enlarged explanatory view of the measuring cylinder 9, and FIG. Move the switching valve body A to the left by 1/6 (60 degrees) from the state shown in Figure 3 above.
The figure obtained by rotating the cylinder, Figure 7, is an explanatory diagram of the state of the measuring cylinder 9. Figure a shows the state immediately before starting the sample aspiration operation, with a small amount of eluent in the upper part of the cylinder. FIG. 8 is a diagram showing the sample transfer process of the present invention, and FIG. 9 is a diagram showing the sample transfer process of the present invention for which a patent application was previously applied. 10 is a diagram showing that the sample 5 is sucked and collected by the retreat of the eluent 20 in the suction nozzle 6, and a diffusion region e is generated accordingly, and FIG. 11 is a diagram showing a conventional autosampler. FIG.

A pair of switching valve bodies A and B are in liquid-tight contact with each other in a state where the protrusion a and the supplementary hole b are complemented, and are driven by, for example, an air cylinder drive method using a solenoid valve or a motor drive by a Geneva mechanism. (None of the driving methods are shown for simplicity of drawing) so that they can slide relatively liquid-tightly. In this case, switching valve body B
may be slid by a corresponding distance between a communication hole 21 and a communication hole 22, which will be described later, or alternatively, instead of switching valve body B, switching valve body A may be relatively slid in the opposite direction by the same distance. The same effect can be achieved even if the

One of the switching valve bodies has one communication hole 1 and flow channels C, D at the center of the protrusion a as shown in FIGS. 1, 3, and 6 at the contact surface with the other switching valve body B. It opens on the circumference centered on . These passages may take the form of holes drilled inside the switching valve body A, or may take the form of surface grooves provided on the surface of the switching valve body A.

As shown in FIGS. 4 and 8, a suction nozzle 6 is fitted into the communication hole 1 so as to be able to move forward and backward, and a packing member is inserted between the inner peripheral wall of the communication hole 1 and the outer peripheral wall of the suction nozzle 6. 7 is interposed so that the inside of the communication hole 1 is held liquid-tight with respect to the outside, and communicates with one end of the sample holding tube 3, as is clear from FIGS. 3 and 6.

Further, six communicating holes 21 to 26 are opened in the other switching valve body B at the contact surface with the switching valve body A. These holes are positioned at equal intervals on a circumference having the same radius as the communication hole 1 and the flow paths C and D, centered on the center of the supplementary hole b in the recess as shown in FIGS. 3 and 6. It is being The communication hole 21 is formed so that the suction nozzle 6 can be inserted thereinto, the communication hole 22 communicates with a reaction system 17 such as a column via the tube 16, and the communication hole 23 communicates with the tube 1.
The communication hole 24 communicates with the reagent liquid storage tank 57 through the metering pump 11 provided at
communicates with the suction nozzle 6 via the sample holding tube 3, the communication hole 25 communicates with the measuring cylinder 9 via the tube 90, and the communication hole 26 communicates with the sample liquid storage tank 57 via the tube 91. It's communicating.

As shown in FIG. 3 in detail, the suction nozzle 6 includes a motor 34, a cam 35 rotated by the motor, a crank 36 connected to the peripheral edge of the cam, and a reciprocating rod 37 connected to the crank.
The holding arm 38 of the drive device 18, which is composed of a holding arm 38 fixed to the reciprocating rod and a guide frame 39 for the reciprocating rod, is attached to the upper part of the reciprocating rod and held.

As shown in detail in FIG. 5, the measuring cylinder 9 includes a motor 40, a cam 41 rotated by the motor, a crank 42 connected to the peripheral edge of the cam, and a reciprocating rod 43 connected to the crank.
A piston holding plate 44 in contact with the reciprocating rod, a piston 45 fixed to the holding plate, a cylinder 46 in which the piston fits liquid-tightly, and a piston interposed between the cylinder 46 and the piston holding plate 44. Elastic body 47 such as a push spring and the piston holding plate 4
4, and a stopper 48 such as a control screw for controlling the return position of the piston 4. By screwing the control screw and its knob 19, the amount of movement of the piston can be arbitrarily changed, and the sample can be sucked into the suction nozzle 6. Accurately determine the amount of 5.

Note that 57 is a reagent solution storage tank such as a selected eluent.

The outline of the configuration has been described above, but the details will become clear through the explanation of the operating functions below.

The reaction system 17 is used as an analytical column, and the reagent liquid storage tank 5
7 as an eluent storage tank as shown in FIG.
During this period, the switching valve body A is rotated to a position where it communicates between the flow path D and the communication holes 24-25, and a third valve body is placed between the measuring cylinder 9 and the sample storage tank 2.
As shown by the dashed line in the figure, the measuring cylinder 9, the tube 90, the communication hole 25, the flow path D, the communication hole 24,
A flow path consisting of the sample holding tube 3 and the suction nozzle 6 is completed, and the inside of the flow path is filled with an eluent.

Next, in this state, the motor 34 of the drive device 18 of the suction nozzle 6 is driven to drive the cam 35,
The suction nozzle 6 is lowered via the crank 36, the reciprocating rod 37, and the holding arm 38, and its tip is immersed into the sample 5 in the sample storage tank 2. See Figure 4.

Next, as shown in FIG.
2. The piston 45 is lowered via the reciprocating rod 43 and the piston holding plate 44, and a predetermined amount of the sample 5 is placed inside the flow path from the suction nozzle 6 to the tube 3, as shown by the broken line in FIG. Inhale and hold the amount. The fixed amount at this time is determined by screwing the knob 19 of the stopper 48 and moving the stopper forward or backward to control the return position of the piston 45.

Next, the motor 34 of the drive device 18 of the suction nozzle 6 is driven, and the suction nozzle 6 is
is raised to a position where its tip opening does not impede rotation of the switching valve body A (see FIG. 8).

Next, the switching valve body A is rotated to the left in the drawing by a distance corresponding to the communication holes (21, 22).

It will be understood that the state shown in FIG. 6 is obtained by this rotation.

In the state shown in FIG. 6, the eluent storage tank 57
and column 17, as shown by the two-dot chain line,
From the eluent storage tank 57 to the pump 11 and tube 1
0, the communication hole 23, the flow path C, the communication hole 24, the sample holding tube 3, the suction nozzle 6, the communication hole 22, and the flow path leading to the column 17 via the tube 16 is completed.

Therefore, when the pump 11 is operated, the eluent flows through the channel, pushes out the sample held in the suction nozzle 6 and the sample holding tube 3, and is introduced into the column 17, where analysis is performed. It will be done. The sample can be introduced into the column using the eluent as shown in FIG. This is because the communication hole 1 is held completely liquid-tight with respect to the outside of the switching valve body A, and the eluent that was held as shown by the dashed line in FIG. As shown by the line, the entire amount of sample 5 held was transferred to the 8th sample.
It is introduced into the column 17 as shown in the figure.

On the other hand, in FIG. 6, there is a space between the measuring cylinder 9 and the eluent storage tank 57, as shown by the three-dot chain line.
Measuring cylinder 9 to tube 90, communication hole 2
5. It will be understood that the flow path leading to the eluent storage tank 57 via the flow path D, the communication hole 26, and the tube 91 has been completed.

Therefore, move the piston of the metering cylinder 9 in the ejection direction, and once move the piston to its top dead center (the most extreme part).
When the metering cylinder 9 reaches C and is stopped, the measuring cylinder 9 becomes C in FIG. 7, and the flow path from the cylinder 9 to the eluent storage tank 57 can be filled with the eluent. In this way, it is ready for the next step of inhaling the sample.

In addition, in the sample inhalation process, C in Figure 7
As shown in , when the suction movement of the piston 45 is started from the top dead center of the piston, the motor 40
Play "backlash" in the connecting part from to the piston 45
Therefore, the driving energy of the motor 40 is not immediately transmitted to the piston 45, so that it may not be possible to accurately and reproducibly collect a sample.

In such a case, after the piston of the metering cylinder 9 has reached the top dead center, move it further in the suction direction and stop midway to achieve the state shown in a in Fig. 7, and in this state proceed to the sample suction process. Good. In this state, the driving energy of the motor 40 is immediately transmitted to the piston 45, so that the sample can be sucked and collected accurately and with good reproducibility.

When performing the above operation, as shown in FIG.
and respective switches 65 for detecting bottom dead center.
and 66, so that the piston can rotate while temporarily stopping at each of the above points in sequence. That is, as shown in FIG.
The cam 4 controls switches 65 and 66 to temporarily stop the reciprocating movement of the piston at an appropriate point from the top dead center to the bottom dead center, and when the piston reaches the bottom dead center.
1, and a protrusion 67 that acts on the switch is provided on the cam, and as shown in FIG. Then, move the protrusion 67 from the switch 65 to the position 66, as shown in FIG. In the flow path leading to the pipe 3,
A sample having the same volume as the eluent sucked and held in the cylinder 46 is accurately collected by suction.

Next, in the state shown in FIG. 6, the motor 40 is driven again to rotate the cam 41, and the protrusion 67 shown in FIG.
The piston is moved from the switch 66 to the position 65 (the piston passes the top dead center on the way) and brought to the state a in Fig. 7, and then stopped until the state shown in Fig. 3 is reached.
Just wait.

Next, from the state shown in FIG. 6, the switching valve body A is rotated rightward in the drawing by a distance corresponding to the communication holes 21 and 22. It will be understood that by this rotation, the original state shown in FIG. 3 is obtained.

On the other hand, a new sample storage tank is transported directly below the switching valve body B by a belt conveyor or the like (not shown).

Next, the motor 34 of the suction nozzle drive device 18 is driven to lower the suction nozzle 6 via the cam 35, crank 36, reciprocating rod 37, and holding arm 38, and immerse its tip into the new sample storage tank 2.

Next, the above-mentioned operation is repeated, and samples can be successively collected from new sample storage tanks 2 accurately without wasting a single drop, and added to a reaction system such as a column.

The rotation operation of the switching valve body A or B, the operation operation of the drive device of the suction nozzle 6, the operation operation of the metering cylinder 9, the operation operation of the pump 11, and the transportation operation of the sample storage tank 2, etc. described above are performed using, for example, a cam timer. This can be carried out completely automatically using conventional sequence control equipment using known devices.

As described above, the present invention rotates two cylindrical switching valve bodies in liquid-tight contact with each other to collect a sample.
We have described an example of a device that performs the introduction operation, but instead of the cylindrical switching valve mentioned above, plate-shaped (sliding) switching valves as shown in Fig. 2 are used in a straight line while in fluid-tight contact with each other. It goes without saying that exactly the same effects can be obtained even if the parts are slid back and forth.

According to the present invention, like an autosampler using a conventional two-channel two-way switching valve, the sample can be sampled in the flow path from the pipette to the metering through hole and in the flow path beyond the metering through hole. It goes without saying that waste can be completely eliminated, and the sample transfer process of the prior patented invention, which consists of a sample inhalation process, a sample transfer process, and a sample introduction process, can be omitted, so the sample flow in this process can be reduced. Diffusion within the sample can be prevented, the individual components of the sample can be separated very well, and the accuracy of analysis can be dramatically improved.

In addition, the flow path (tube) required for the sample transfer process, sample holding tube, piston cylinder,
The pressure reducing device and its connecting members are no longer required, and the number of communication holes provided in the switching valve element can be reduced, making it easier to manufacture and simplifying the overall structure of the autosampler device. It has extremely great industrial effects.

[Brief explanation of drawings]

FIGS. 1 and 2 are perspective views of a pair of switching valve bodies A and B used in the autosampler of the present invention, respectively, and FIG. 3 is a schematic explanatory diagram of an autosampler showing an embodiment of the present invention. 5 is an enlarged partial vertical sectional view of the main part of FIG. 3, FIG. 5 is an enlarged explanatory view of the measuring cylinder 9, and FIG. Move the switching valve body A to the left by 1/6 (60 degrees) from the state shown in Figure 3 above.
The figure obtained by rotation, Figure 7, is an explanatory diagram of the state of the measuring cylinder 9, and the figure a shows the state immediately before starting the sample suction operation, and shows a state in which a small amount of eluent is contained in the upper part of the cylinder. Fig. 8 shows the state at the end of the sample suction operation, Fig. 8 shows the sample transfer process of the present invention, and Fig. 9 shows the sample transfer process of the invention for which a patent application was previously filed. , FIG. 10 is a diagram showing that the sample 5 is collected by suction as the eluent 20 recedes in the suction nozzle 6, and a diffusion portion e is generated accordingly, and FIG. 11 is a diagram showing a conventional autosampler. It is a schematic explanatory diagram. 1...Communication hole, 2...Sample storage tank, 3...
Sample holding tube, 5...Sample, 6...Suction nozzle, 7...Packing member, 9...Measuring cylinder, 10...Tube, 11...Pump, 16
...Tube, 17 ... Reaction system, 18 ... Drive device, 20 ... Eluent, 21-26 ... Communication hole, 4
0... Motor, 41... Cam, 42... Crank, 43... Reciprocating rod, 44... Piston holding plate,
45... Piston, 46... Cylinder, 47...
...Elastic body, 48...Stopper, 57...Reagent solution storage tank, 65-66...Switch, 67...Protrusion, 71-74...Flow path, 75-76...Fixing member, 77...Measuring through hole, 78...rotating member,
79... Rotating table, 80... Decompression device, 81
...Pipette, 82-83...Tube, 84...
...metering pump, 85...reaction tube, 90-91...
Tube, A, B...Switching valve body, a...Protrusion, b
...Complete hole, C, D...channel, e...diffusion area.

Claims (1)

[Claims] 1. It has two switching valve bodies A and B that slide relative to each other while being in liquid-tight contact with each other, and one of the switching valve bodies A has a communication hole 1 and a flow path C. , D are open on the contact surface, and the inside of the communication hole 1 is connected to a suction nozzle 6.
A gasket member 7 is interposed between the inner circumferential wall of the communication hole 1 and the outer circumferential wall of the suction nozzle 6 to hold them liquid-tightly. The body B has six communication holes 21 to 26 open on the contact surface, the communication hole 21 is formed so that the suction nozzle 6 can be inserted therein, and the communication hole 22 is formed through the tube 16 to allow reaction. The communication hole 23 is connected to the reagent liquid storage tank 57 via the tube 10.
The communication hole 24 communicates with the suction nozzle 6 via the sample holding tube 3, the communication hole 25 communicates with the measuring cylinder 9 via a tube 90, and the communication hole 26 communicates with the tube 91. The communication hole 1 communicates with the reagent liquid storage tank 57 through the reagent liquid storage tank 57, and the communication hole 1 is connected to the communication hole 21 by sliding of the switching valve body.
or 22, the flow path C is between the communication holes 22-23 or between the communication holes 23-24, and the flow path D is between the communication holes 24-25 or between the communication holes 2
5 to 26 so as to selectively communicate with each other. 2. The measuring cylinder 9 has a motor 40, a cam 41 rotated by the motor, a crank 42 connected to the peripheral edge of the cam, a reciprocating rod 43 connected to the crank, and a piston holding plate 44 in contact with the reciprocating rod. , the piston 45 fixed to the holding plate, the cylinder 46 into which the piston is fitted in a fluid-tight manner, the elastic body 47 interposed between the cylinder and the piston holding plate 44, and the return position of the piston holding plate. The autosampler according to claim 1, further comprising a control stopper 48. 3 The measuring cylinder 9 is equipped with respective switches 6 for detecting appropriate points from the top dead center to the bottom dead center of the piston 45 of the measuring cylinder and for detecting the bottom dead center.
5 and 66, and when the piston reaches each point in sequence, the piston drive motor 40
Claim 1 that allows for temporary suspension of
Autosampler as described in section.