JP2828711B2 - Method and apparatus for supplying sample liquid - Google Patents

Description

Description: BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel and improved sampling device and method capable of automated sampling from closed and open tubes used for sample analysis.

2. Description of the Prior Art A number of closed tube samplers are known in the prior art, and in particular in this case Coulter's "S
−PLUS VI ”in Coulter, Hialeah, Florida, USA
A closed tube sampler included in hematology instruments, such as those marketed by Electronics, and a trademark "Doub
Le Helix under Cort in Northbrook, Illinois, USA
Although closed tube samplers included in hematology instruments, such as those marketed by ex Research, are known, both of these prior art closed tube samplers are simple selector valve devices and sampler configurations. Provides a variety of applications for the immediate selection of automatic switching between closed and open tube sampling through the use of substantially the same sample feeder without the need for external changes in the sample supply and sampling between samples Provides morphology and simplicity of operation using substantially the same flow path for instrument rinsing, or accurately determined and easily reproducible samples with repeated sampling from the same closed sample tube Regarding ensuring a consistent supply of quantitation and reducing the amount of sample remaining to levels below clinical utility Providing a sample analysis accuracy greatly improved with respect to conditions minimized, not be capable to or the operation constituted by novel sampler of the method of the present invention will be appreciated.

Also, various open tube samplers are particularly known in the prior art, and in this case, in particular, U.S. Patent Nos. 3,719,086, 3,756,459, and 3,759,663.
Nos. 3,912,452 and 4,065,973 are known, but any of these prior art open tube samplers are for sampling closed tubes from open tubes. To provide a variety of applications for the immediate selection of switching to, to provide the simplicity of the form of using substantially the same flow path for sample delivery and sampler rinsing between samples, or for closure and The novel sampler of the present invention comprises a need for a novel sampler of the present invention that provides significantly improved sample analysis accuracy with respect to the unconditional minimization of sample residual volume to a level below clinical utility for open-bore tube sampling. It will be understood that it can not be operated or operated.

OBJECTS OF THE INVENTION Accordingly, it is an object of the present invention to provide a novel and improved sample that allows for automated sampling from both closed and open sample tubes without external changes in sampler configuration. It is an object of the present invention to provide a sampling device and a method.

It is another object of the present invention to provide such a novel and improved sampling device and method of relatively simple construction and operation.

It is another object of the present invention to provide a novel and improved sample collection device and method as described above that can ensure consistent and easily reproducible sample quantitation associated with closed tube sampling.

It is another object of the present invention to provide a novel and improved sample collection as described above that is operable to further maximize the accuracy of sample analysis results by minimizing sample residual levels below clinical utility. Device and method.

It is another object of the present invention to provide a novel and improved analyzer and method.

It is another object of the present invention to provide a novel and improved sample collection device and method for use especially in automated hematology instruments.

BRIEF DESCRIPTION OF THE DRAWINGS The foregoing and other important objects and advantages of the invention will be apparent from the following detailed description when read in conjunction with the accompanying drawings. In the drawings, FIG. 1 is shown in operable relationship with a sample analyzer, and shows a novel and improved configuration in which some components are typically constructed and operable in accordance with the teachings of the present invention, with some components shown in cross-section. Figure 2 is a schematic view of the sampler, Figure 2 is a cross-sectional view of the closed tube sampler of Figure 1 under different operating conditions, Figure 3 is a view of the open tube sampler of Figure 1 under different operating conditions. FIG. 4 is a cross-sectional view of the sample valve of FIG. 1 under different operating conditions; FIG. 5 is a cross-sectional view of the open tube sampler and selector valve of FIG. 1 under different operating conditions; FIG. 7 is a cross-sectional view of the reagent valve and the metering pump of the analyzer of FIG. 1 under different operating conditions. FIG. 7 is a sectional view of FIG.
FIG. 8 is a cross-sectional view of the closed tube sampler of FIG. 8, FIG. 8 is a cross-sectional view of the closed tube sampler of FIG. 7 under different operating conditions, FIG. 9 is a closed tube of FIG. 1 and FIG. A closed tube structurally very similar to the sampler; a cross-sectional view of the sampler at different operating conditions; and FIG. 10 a cross-sectional view of the closed tube of FIG. 9 at different operating conditions. is there.

DETAILED DESCRIPTION OF THE INVENTION In FIGS. 1 and 2 of the drawings, a novel and improved sampler typically constructed and operable in accordance with the teachings of the present invention is indicated generally by 10 and generally 12 It consists of a closed tube sampler as indicated at and an open tube sampler as indicated generally at. Sample supply and sampler rinsing
e) The device is generally designated 16 and the sample valve is generally 2
0, sample supply and sampler 12 or open tube sampler 14 for sample supply
Is selectively coupled to the sample valve 18 and is operable to provide for subsequent rinsing of the sample valve and associated sampler.

The automated sample analyzer is shown schematically at 22 and is shown in operable relationship with the sampler 10 for automated analysis of the sample supplied from the sample valve 18.

The controller is shown schematically at 24 and is operable to control the operation of the illustrated sampler and sample analyzer components as described in further detail below.

The closed tube sampler 12 includes a closed sample tube holding assembly 26 that includes upper and lower relatively movable plates 28,30. The upper plate 28 includes a generally cylindrical sample tube insertion guide 32 having an upright open end for guiding and supporting a tube 34 holding an inverted closed sample, as shown. Typical applications of the sampler 10 of the present invention include sample tubes
34 is a trademark of Vacutai-Dickinson, Inc. of East Rutherford, NJ, USA, for example.
ner "can take the form of something marketed under
It includes a whole blood sample 36 drawn directly from the patient's arm and held therein as shown by a stopper 38 of a suitably inert self-sealing material, such as a suitable rubber. Tube 34 is manually inserted and supported by a tube insertion guide, as will be understood and understood by those skilled in the art.
32 or can be mechanically inserted therein by a suitable tube insertion device (not shown).

A sampling needle assembly 40 covered with a sheath including a sampling needle 41 is fixedly attached by a threaded support collar 42 in an internally threaded inner hole 44 of the lower plate 30 as shown in the figure. And the aligned inner hole 46 of the upper plate 28
To extend through and leave room for mutual movement to establish a liquid tight seal therebetween. The inner bore 48 is connected to the inner bore 46 via a vacuum line 50 and communicates with a suitable vacuum source (not shown), but the small-diameter vent 52 connects the inner bore 46 to the atmosphere. The bore 46 and thus the sampling needle 41 are slightly off-centered or eccentric with respect to the tube insertion guide 32 and thus the tube stopper 38 for purposes which will become apparent hereinafter.

The closure tube holding assembly drive is generally indicated at 54 and is fixedly mounted on the top plate 28 in a suitable manner, for example, by spot welding as shown at 57, and comprises a double acting piston.
60 reciprocates internally by pressurized fluid from a source 62 such as is applied to the opposite side of piston 60 via lines 66, 68 and 70 via a four-way valve as shown at 64. The four-way valve 64 is preferably operated by an electrically controllable device, for example an electric motor as shown schematically at 65, so that it is rotatable between the valve positions of FIGS. 1 and 2. . The piston rod 72 extends downward from the piston 60 through the sealing device 73 and the inner hole 74 of the upper plate 28 as shown in the drawing, and passes through the stepped inner hole 78 of the lower plate 30 to form the piston rod 72. It is fixed to the lower plate 30 by a mounting screw 76 extending to an inner hole 80 provided with a screw on the bottom surface.

Because the closed sample and tube holding assembly 26 is configured as described above, the piston through valve 64 and lines 66 and 70
When the upper and lower plates 28, 30 are in the abutting or "closed" position of FIG. 1 with the supply of pressurized liquid from source 62 to cylinder 56 below 60, sampling needle assembly 40 is effectively The stopper 38 is pierced and extends so as to be in fluid communication with the sample 36 in the closed tube 34 supported by the guide 32. Conversely, the upper and lower plates are separated or "opened" in FIG. 2 by the supply of pressurized fluid from source 62 to cylinder 56 above piston 60 via valve 64 and lines 66, 68. Once moved into position, the sampling needle assembly 40 is withdrawn from the stopper 38 and exposed to a vacuum through the plate bore 48 and in the upper plate bore 46.

A flexible sample supply line 82 made of a suitably inert, preferably transparent material, such as tetrafluoroethylene resin (Teflon), connects the sheathed sampling needle 40 to the selector valve via a sampling needle connector 83. Connected to 20.
The open tube sampler 14 is to be withdrawn by suctioning a predetermined sample portion with a probe,
1. Includes a withdrawal probe 84 that extends as shown into a sample 86 held in an upright, open sample tube 88 positioned relatively as shown in FIG. tube
The 88 is inserted into the probe 84 by hand or by a suitable tube providing device (not shown), as is well known and understood by those skilled in the art. In a typical application of the sampler 10 of the present invention, the tube 88 is "Vacu
The sample 86 may again be a whole blood sample, as drawn directly from the patient's arm.

A generally cylindrical probe cleaning sleeve is indicated by 90 and has a stepped hole including an enlarged hole portion 94 through which the probe 84 has the freedom to move with respect to each other as shown.
Including 92. A substantially fluid tight seal is formed between the probe 84 and the upper portion of the bore 92. The cleaning sleeve 90 further includes spaced-apart rinsing solution and vacuum bores 97, 98 extending generally transversely to communicate with the enlarged bore portion 94 of the sleeve as shown. The bore 97 may be operable to supply a pressurized rinsing solution from its source 102 to the upper end of the bore portion 94 via a flexible conduit 100, and the bore 98 may be a suitable not shown Operable to connect the lower end of the bore portion 94 via the flexible conduit 104 for escape to a vacuum source.

The cleaning sleeve drive is schematically illustrated by 96,
As shown in the figure, it is operatively connected to a washing sleeve 90, which connects the open sample from the position shown in FIG.
The tube 88 is driven between the positions simultaneously with the removal of the process. The drive 96 is, for example, an electrically controllable fluid pressure motor that forms the drive for the closed tube holding assembly.
54, in which case the piston rod of the motor causes the cleaning sleeve 90 to reciprocate between the cleaning sleeve positions of FIGS. 1 and 3 of the cleaning sleeve.

For example, a valve having the form of a suitable pinch valve is schematically illustrated
As shown at 105 and 107, and as shown, they are operatively associated with a flexible rinsing line 100 and a vacuum line 104, respectively, to control the flow of fluid therein. Valves 105, 107 are electrically controllable devices, for example 10
It is preferably operated by a solenoid as shown schematically at 9,111.

The sample supply and sampler rinsing device 16 includes a pressure equalizing chamber 108 connected via a flexible conduit 110 as shown to communicate via a suitable vacuum source not shown. An electrically operable conductive detector is shown schematically at 112 and includes interconnected flow paths 114, 116, 117 extending therethrough as shown. A flexible conduit 118 connects the conductive detector passage 116 to the balancing chamber 108 and the flexible conduit 12
0 is the rinse liquid supply source 102 pressurized in the conductive detector flow path 117
Connect to As is well known and understood by those skilled in the art,
The conductivity detector 112 detects the presence of the sample liquid in the passages 114, 117 based on the resulting change in conductivity,
It may also be operative to generate and output an electrical signal indicative thereof.

Valves in the form of pinch valves, shown schematically at 122, 124, 126, each have a flexible conduit 110, 1 as shown in the figure.
18, 120 and operatively associated therewith to control the fluid flow therethrough. The valves 122, 124, 126 are preferably operated by electrically controllable devices, for example, solenoids schematically shown at 123, 125, 127.

The sample valve 18 is stationary and has a substantially cylindrical outer valve body portion 129 having an inner hole 130 formed therein, and is arranged substantially fluid-tight in the inner hole 130 as shown in FIG. On 13
An operatively connected electrically operated drive which preferably has the form of a motor as shown at 3 provides a substantially cylindrical interior rotatable between the positions of FIGS. 1 and 4. In the form of a sluice valve 128 composed of the valve body 131 of FIG. Inner valve body 131 includes spaced sample fluid loops or passages 132, 134, 136, 1 formed as shown.
38, but the outer valve body 129
When the sample valve is in its position as shown in FIG. 1, it forms a continuous sample fluid passage extending from the outer valve body passage 139, 140 through the sample valve. , Exactly the inner valve body 132, 134, 136, 1
It consists of spaced sample fluid loops or passages 142, 144, 146 that can be precisely aligned with 38.

Further included in the valve body portion 129 outside the gate valve 128,
Spaced fluid passage pairs 150 and 152, 154 and 156,
158 and 160, and 162, 164, each of which has an inner valve body 131 driven by a drive motor 133 to form four individual sample fluid passages through the valve as shown in FIG. With the tube closed or open tube sampler 1
2, 14 or with the sample and sampler rinsing liquid supply 16 can be precisely aligned without being in circulation.

Flexible conduit 170 connects outer valve body passage 139 to flow passage 114 of conductivity detector 112.

The selector valve 20 comprises a three-way valve, shown schematically at 172, connected to the passage 140 of the gate valve 128 by a flexible conduit 174 as shown. The three-way valve is operated by an operatively connected electrically operated drive, for example in the form of a motor as schematically shown at 176, in FIGS.
It is rotatable between the positions shown in FIG. 5 and FIG. This three way valve
When 172 is in the position of FIG. 1, the closed tube sampler 10 is operatively connected therein to the gate valve 128 via lines 82 and 174 while the open tube sampler 14 is open. It will be apparent that is effectively isolated or isolated from the sample supply circuit of the sampling device 10. Conversely, with the three-way valve 172 in the position of FIG. 5, the open tube sampler 14 has a line therein.
Although operatively connected to gate valve 128 via 106, 174, it will be apparent that closed tube sampler 12 is effectively shut off or isolated from the sample supply circuit of sampler 10.

With the inner valve body 131 pivoted by the drive motor 133 to the position of FIG. 4, it is operable as described above to form four discrete sample loops 132, 134, 136, 138. For use with the sample valve 18 in the form of a gate valve 128, there are four individual but four sample analyzers 22 operatively associated with the gate valve based on one of the sample analysis channels for each of the sample loops. It will be apparent to one of skill in the art that it advantageously includes an automated sample analysis channel that can be operated simultaneously. Overall 175
One of each of these sample analysis channels, as shown at, is typically shown schematically in FIG. 1 but in somewhat more detail, while the remaining three such sample analysis channels are all gate valves. It is shown in block diagram form at 179, 177, 179 in operative relation to 128.

As shown schematically in FIG. 1, the automated sample analysis channel 175 comprises a reagent supply 180, a reagent light pump 182, a three-way reagent valve 184, and a sample / reagent reaction analysis chamber 186. The reagent lightweight pump 182 includes a piston 188 that can be reciprocated in a cylinder 189 by an electric motor 190. A flexible line 192 connects the reagent supply 180 to the reagent valve 184, while the flexible lines 194 and 196 separate the reagent valve 184 and the sample / reagent reaction and analysis chamber 186 from the passage of the isolation valve 128.
158, 160 so that the gate valve 128
When in the position shown, the sample analyzer channel 175 is operatively connected to the gate valve loop 136. The flexible conduit 197 is
The reagent light pump 183 is connected to the three-way valve 184,
An electrically controllable drive, preferably in the form of a motor as shown at 198, comprises a reagent valve 184 as shown.
Operatively connected to the reagent light pump 182 to the source 180
Or to connect to the sluice valve 128 to be operable to pivot between the positions of FIGS.
In addition, the automated sample analysis channel 175 has a light source 200, such as a laser, for example, and a reaction, such as, respectively, operatively associated with the sample / reagent reaction analysis chamber 186 and retained therein in a manner well known to those skilled in the art. Photosensitive detector 202 operable to automatically analyze the extracted sample
And a sample analyzer in the form of.

When the inner valve body 131 is pivoted to its position in FIG. 4, the flexible conduits 204 and 206, 208 and 210, 212 and 214 respectively cause the sample analyzer channel 179, Gate valve sample loop 13 for 177 and 178
4, 132, 138, and it will be apparent that each sample analyzer channel 179, 177, 178 can take any form that can be shared with automated sample analysis.

The controller 24 is illustrated, for example, by a power supply (not shown) for electrical control, i.e., start, stop, sequence and time, and control of the sampler and sample analyzer components as shown in FIG. In the form of a suitable programmable microprocessor device operable as follows.

From the closed tube sampler 12 to the sample analyzer 22, first the sample tube insertion / support guide 32
To operate the sampler 10 of the present invention, which supplies a sample without using the tube 34, the controller 24 opens the pinch valve 124, closes the pinch valves 122, 126, 105, 107, and the gate valve 128, It will be appreciated that the three-way valve 172 and the four-way valve 64 are biased to be positioned as shown in FIG. This operation effectively disconnects the open tube sampler 14 from the sampler 10 and removes the tube holding assembly.
26 is placed in its "closed" position of FIG. 1 to assure ambient atmospheric pressure in the balancing chamber 108 via the open and exposed tip of the sampling needle 41 via associated connected conduits and fluid passages. I do. At the same time, controller 24 drives reagent valve 184 to its position in FIG. 6 and drives reagent metering pump piston 188 down to bottom dead center as shown to draw reagent from Actuating to aspirate via 192, the cylinder 189 of the pump is filled with this reagent.

Then, the closed sample with the stopper 38 firmly in place
The tube 34 is manually inserted into the sample / tube insertion guide 32 and pressed down until the stopper comes in contact with the upper surface of the plate 28 and stands still. As a result, the needle 41 is stuck into the hermetic plug 38 and is extended so as to be in a state of communication with the sample 36 as shown in the figure. In such a condition, a vacuum created above the sample 36 in the closed tube 34 from the balancing chamber 108 to the needle 41, as would otherwise occur with repeated aspiration of the sample from the same closed sample tube. The required amount of ambient atmospheric pressure air flow inwardly over the sample 36 of the closure tube 34 through the open end of the closure tube 34 will effectively be removed, and the nature of the character discussed herein within the closure tube 34. The consequence of the formation of a vacuum is that the formation and inclusion of microbubbles in the sample as aspirated by a concomitant reduction in the total volume of the sample obtained for analysis, as well as a significant and simultaneously unacceptable loss of sample analysis accuracy It will be appreciated by those skilled in the art that The problem of the formation of microbubbles in the aspirated sample is that
A tapering amount, e.g., 100 microliters of sample, is aspirated to supply to the sample analyzer, and the accuracy of the sample analysis result is the availability in each instance of an exactly known sample volume for analysis, in this example Of particular interest in today's sample analyzers, where each sample volume is strictly anticipated as held in gate valve loops 132, 134, 136, 138, as described below. Also,
In those situations where the closure tube 34 is constituted by a "Vacutainer" and results in significantly less than the optimal amount of blood sample obtained for analysis as a result of a short "aspiration" from the patient, as described above, It will be apparent to those skilled in the art that the application of ambient atmospheric pressure on the sample 36 proves indispensable as a practical matter in allowing satisfactory sample aspiration.

According to the pressure balance as described above between the balancing chamber 108 and the closed sample tube 34, which occurs almost simultaneously with the actual entry of the sampling needle into the closed tube, the controller 24 operates to open the pinch valve 122, Connect the associated vacuum source to sampling needle 41 via line 110 such that sample 36 is aspirated from closure tube 34 via needle 41, connector 83, line 82, valve 172 and line 174, Connected gate valve passages and loops 140, 138,
146, 136, 144, 134, 142, 132, 139 flow into and fill it, and from there flow into conduit 114 of conductive detector 112 via line 170. Thus the conductivity detector
Simultaneously with the arrival and detection of the leading edge of the sample aspirated into the 112, and thus the arrival and detection of the leading edge of the sample aspirated into the conductive detector 112, the detector is connected to the controller 24. Operate to signal pinch valve 12
4 is closed to aspirate the sample from the closure tube 34.

The controller 24 then pivots the body 131 inside the sluice valve 128 to the position of FIG. 4, whereby the four individual, precisely volumetrically determined sluice valves 128 The loops 136, 134, 132, 138 each operate to effectively partition a sample-filled flow path to the sample volume held therein, which loops then each have a valve passage.
Via 158,160 and lines 194,196, valve passages 154,156 and lines 204,206, valve passages 152,150 and lines 208,210, and valve passages 164,162 and lines 212,214, It is placed in flow communication with the sample analyzer channels 175, 179, 177, 178.

In sample analysis by the sample analyzer channel 175, the controller 24 then returns the reagent valve 184 to its position in FIG.
Actuating to drive 188 to top dead center and pumping the accurately metered amount of reagent via line 184 to line 194, the sample contained in gate valve loop 136 is passed to line 194, valve passage
158, loop 136, insert into the reagent flow path formed by valve passage 160 and line 196, and allow the resulting sample / reagent solution to be subsequently energized by controller 24 of light energy source 200 and detector 202. The resulting complete sample / reagent mixing and reaction is filled into the reaction analysis chamber 186 for reaction and automated sample analysis. Controller 24 then returns reagent valve 184 to its position in FIG. 6 for refilling with reagent from supply 180 of reagent lightweight pump 182 as described above.

A sample analyzer channel 179, 177, 178, which may be of the same or a different form than the analysis channel 175, obtains each sample volume from the gate valve 134, 132, 138;
Controller to react and analyze (if necessary)
Operated simultaneously by 24.

The controller 24 then returns the gate valve 128 to its position in FIG. 1, thereby re-establishing a continuous flow path therethrough and pivoting the four-way valve 64 to its position in FIG. This activates the fluid motor 54 to drive the closed sample tube holding assembly 26 to its "open" position in FIG. Thus, the tip of the sampling needle 41 is retracted into the inner hole 46 of the upper plate 28, thereby exposing the needle to the vacuum through the now uncovered vacuum hole 48 and the conduit 50.

The sample from the open tip of the needle 41 to the sluice valve 128 to minimize contamination of the subsequent sample by residual sample, e.g., residues of the previous sample and to maximize the analytical accuracy of the subsequent sample. A particularly thorough rinsing and cleaning of the retained flow path is achieved via a pinch valve via the controller 24.
Starting with the re-opening of 124, the sampling needle 41 is reconnected to the associated vacuum source, thereby causing the needle 41, connector
83, line 82, three-way valve 172, line 174, gate valve passage and sample loop 140, 138, 146, 136, 144, 134, 14
2, 132, 139, line 170, and a large amount of sample remaining in the conductive detector passage 114 are aspirated and discharged through the conductive detector passage 116, line 118, balancing chamber 108, and line 110, respectively. I do. Of course, the atmosphere required by such aspiration to evacuate the remaining sample is provided by vents 52 in the top plate 28 of the closed sample tube holding assembly 26. The controller 24 then operates to close the pinch valve 124 and open the pinch valve 126, thereby providing the source 1
From 02, the conduit 120, the conductive detector passages 117, 11 respectively
4, line 170, the above-mentioned connected gate valve passage and loop, line 174, three-way valve 172, line 82, connector 83 and covered sampling needle 40, the inner hole 46, the vacuum hole 48
A strong flow of the pressurized rinsing solution is produced so as to discharge through line 50 and line 50. As a result, such a strong backflow of the rinsing solution in the entire sample supply path from the tip of the sampling needle 41 to the sluice valve 128 results in a particularly effective and thorough rinsing and washing, and likewise the opening of the rinsing solution. As it flows from the tip of the sampled needle 41 down and all the way down the way to the vacuum hole 48, it results in a particularly thorough rinsing and cleaning of the exposed outer surface of the tip of the needle 41.

The controller 24 then closes the pinch valve 126 again and reopens the pinch valve 127, thereby shutting off the pressurized rinsing liquid supply and draining the rinsing liquid via line 110, causing a problem with sample supply. The entire path of the sample and the exposed outer surface of the tip of the sampling needle are then effectively dried with air. in this way,
All relevant sampler and valve components are substantially clean and dry, and sample residue in subsequent samples is reduced to a minimum that is not completely clinically problematic; The result is that the accuracy of the analysis is maximized.

The closed sample tube 34 is manually removed from the sample tube insertion guide 32 of the closed sample tube holding assembly 26 at or before the completion of the rinsing and drying operation.

At the completion of the rinsing and drying operations, the controller closes the pinch valve 122 again and returns the four-way valve 64 to its position in FIG. 1, thereby again validating the ambient atmospheric pressure in the balancing chamber 108, and The closed sample tube holding assembly 26 is returned to its "closed" position in FIG. 1 in preparation for repeating the closed sample tube sampling and analysis cycle as described in.

The sampling needle 41 is the sample / tube insertion guide 32
The closure tube, which is placed slightly eccentrically to the needle 41, punctures the closure 38 exactly at the same location, thereby unduly weakening the closure and creating an unacceptable leak at the point where the needle pierces the closure. The expected probability of subsequent reintroduction of tube 34 to sampler 12 is reduced.

When using the sampler 10 of the present invention to supply a sample from the open tube sampler 14 to the sample analyzer 22 for analysis, an open sample holding the sample so that the withdrawal probe 84 is immersed in the sample 86 When the tube 88 is placed as shown in FIG. 1 and the cleaning sleeve 90 is placed as shown in FIG.
Will close the pinch valves 105, 126, 107, open the pinch valves 124, 122 and place the three-way valve 172 as in FIG. 5 and the sluice valve 128 as in FIG. This effectively isolates the closed tube sampler 12 from the sampler 10, thereby removing each from the open sample tube 88, the open end of the probe 84, the line 106, the three-way valve 172, the line 174, Aspiration and flow will occur under the action of the associated vacuum source of sample 86 via the coupled passage and loop of sluice valve 128 and conduit 170 to passage 114 of conductive detector 112,
Therefore, the gate valve sample loop 138, 136, 134, 1
The result is a filling with 32 samples. at the same time,
The controller 24 will activate the sample analyzer channel 175 to fill the reagent light pump 182 with reagent as described above.

Upon detection of the leading edge of the sample 86 in the conductive detector passage 114, the detector provides a signal to the controller 24 to close the pinch valve 124, thereby further removing the sample from the open sample tube 88. Is stopped, and the gate valve 128 is rotated to that position in FIG. The sample analyzer channels 175, 179, 177, 178 are then operated by the controller 24, all as described in detail above for the operation of the closed tube sampler 12, the gate valve loops 136, 132, 134, 138. From each sample, react (in any case, if necessary), and automatically analyze, and open sample tube 88 is removed from sampler 12 and the open sample
The tube 88 is taken out of alignment with the take-out probe 84.

Following the acquisition of the sample volume by the sample analyzer 22, the controller 24 operates the pivot valve 128 to pivot to its position in FIG. 1, thereby re-establishing a continuous flow path therein. Then, open the pinch valve 124 again,
Take-out probe 84, conduit 106, selector valve 17 respectively
2, line 174, and the majority of the sample 86 remaining in the passages and loops of the gate valve reconnected, to line 170, detector passages 114, 116 and lines 118, chamber 108, and line 110.
Suction to exhaust through. At the same time, the controller
24 operates to open pinch valves 105, 107, thereby forcing pressurized rinsing fluid from source 102 through line 100 and cleaning sleeve bore 94 at the top of cleaning sleeve bore 94. The rinsing solution thus introduced is surrounded by the outer surface of the withdrawal probe 84 and forced into contact therewith.
Discharge via 98 and line 104. At this time, the controller 24 also operates to bias the cleaning sleeve drive motor 96 to drive the cleaning sleeve so operated from the position of FIG. 1 to the position of FIG. Remove the cleaning sleeve and rinse it completely by traversing it over substantially the entire outer surface of probe 84,
The remaining amount of sample 86 will be taken from now on.

When the cleaning sleeve 90 reaches its position in FIG. 3, the vacuum present at the distal end of the withdrawal probe 84 causes the rinsing liquid to flow from the rinsing liquid hole 97 of the cleaning sleeve with the surrounding air in the proper necessary mixing. As described above, it acts to aspirate to the open end of the probe so as to flow following the remaining sample for discharge through channel 110. As will be appreciated by those skilled in the art, such a mixed flow of air and rinsing liquid in the form of air bubbles is provided by the withdrawal probe 84, line 106, selector valve 1
72, sample from the inside of the associated connected passages and loops of line 104 and gate valve 128
It has a particularly effective cleaning action, especially with regard to the particularly complete removal of the 86 residues.

The controller 24 then operates to close the pinch valves 105, 124 and open the pinch valves 126, thereby shutting off the supply of rinsing liquid to the cleaning sleeve 90, and
Detector passages 117, 114, line 170, associated connected passages and loops of gate valve 128, line 174, selector valve 17
2. Begin supplying rinse fluid to the withdrawal probe 84 via line 106 and withdrawal probe 84, thereby providing a more complete and effective wash of the remaining sample 86 with the direction of the internal sample flow and Conversely, the rinse is reversed. As the backwashing rinse exits the tip of the probe 84, the rinse will simply pass through the sleeve vacuum holes 98 and line.
It is aspirated to drain through 104, thereby preventing the overflow of contaminated rinsing liquid at the operating location of sampler 10. Of particular importance with respect to backwashing the probe when the sample in question consists of a whole blood sample is the remarkable effectiveness of removing fibrinogen or fibrin from clotted blood which is otherwise difficult to remove.

At the end of the backwash of the probe 84 and the sample supply device as described above, the controller 24 closes the pinch valve 126,
Actuating to open the pinch valve 124 to aspirate the probe 84, the associated connected passage of the sluice valve 128 and the rinsing liquid remaining in the loop, the line 170, the detector passage 114, respectively.
Discharge via line 116, line 118, chamber 108 and line 110, whereby they are again effectively rinsed in the direction of the sample stream with the rinse solution, and particularly thorough cleaning with the rinse solution and sample 86 residues. Complete. Of course, as previously described, ambient air is drawn into the probe as the remaining rinse is drawn from the withdrawal probe 84 to air dry the probe and all other associated sampler components. Drain and complete the wash. At the same time, the controller 24
Actuates the cleaning sleeve drive motor 96 to return the cleaning sleeve 90 to its position in FIG. 1, thereby effectively drying the probe with the flow of air around the probe to the sleeve vacuum hole 98 and removing the outer surface of the probe. Complete on the line.

Upon completion of the above process, the controller 24 closes the pinch valves 122 and 107 again, and removes the removal probe 84 as described above.
The provision of the open tube sampler 14 for successive working cycles as described above is provided simultaneously with the provision of the open tube containing another sample to the sampler.

Although the closed tube sampler 12 of the present invention has been typically described so far as can be used with a generally vertical position of the sampling needle 41 below the closed tube 34 holding the sample, the closed tube sampler 12 has been described. Harvester 12
It will also be appreciated that the sampling needle 41 can be used in a different orientation than necessarily "down" of the closure tube 34 holding the sample.

In particular, FIGS. 7 and 8 show that the sampling needle 41 is slightly inclined with respect to the horizontal as shown in FIG.
At an angle and of course holding the sample 34
Also shown is a typical use of the closed tube sampler 12 in a position aligned with the sampling needle by a closed tube insertion / support guide 32. FIG.
As described in detail above with respect to FIG.
FIG. 8 shows the closed tube sampler 12 in a "closed" position, in which a sampling needle 41 pierces the tube stopper 38 and enters the stopper to aspirate the sample 36 therefrom, while FIG. Closed tube sampling in the "open" position, as shown and described in detail above with respect to FIG. 2, in which the sample has been aspirated and the sampling needle is withdrawn from the closed tube stopper 38 and fully rinsed. The container 12 is shown.

In particular, a sampling needle as shown at 43 in FIG.
Regarding the complete rinsing and cleaning of the exposed outer surface of the tip of 41, in order again to ensure the completeness of such rinsing of the sampling needle, it is formed between the inner bore 46 of the plate 28 and The flow rate of the surrounding air through the vent 52 to the entire surface of the tip of the exposed outer needle of the annular portion and to the vacuum hole 48 penetrating the upper plate is increased by the sampling needle 41 as described above. It will be understood that the flow rate of the backwashing rinsing liquid flowing from the opening end of the sampling needle to the annular portion at the same time as the backwashing is determined to be considerably larger. This is easily achieved in practice due to the very small water basin provided by the bore of the sampling needle 41, which, in a typical application of the method and apparatus of the present invention, is 1/2 mm It may have a small diameter.

According to the above, when the backwash rinse from the pressurized source 102 (FIG. 1) flows out of the open tip of the sampling needle 41, this rinse will be applied to the needle tip / top plate. The instantaneous mixing with a much larger amount of ambient air flowing near the tip of the generally spiral sampling needle in the annulus of the inner bore immediately turns and thereby turns around, a particularly advantageous overall result being the cleaning action. A very effective mixing of the rinsing liquid with the surrounding air in the light forces the sampling needle 41 to flow around the entire exposed tip of the sampling needle 41 at the annulus of the sampling needle tip / upper plate, so that said exposed sampling needle is It will be evident that the tip of the tubing is particularly thoroughly washed and then flows directly out of this via the vacuum hole 48 and the vacuum line 50. Thus, completely minimizing the amount of sample liquid both outside and inside the sampling needle 41 can also be achieved by directing the sampling needle in a direction different from that shown in FIGS. Provided in spite of the fact that

FIGS. 9 and 10 illustrate another exemplary application of the closed tube sampler 12, in which the sampling needle 41, which is again substantially vertically oriented, faces downward, and Rather than below the closure tube 34 holding the sample, which is of course oriented to coincide with the closure sample tube insertion / support guide 32. FIG. 9 shows the closed tube sampler 12 in a "closed" position with respect to the closed tube 34 as described in detail above with respect to FIG. 1, wherein the sampling needle 41 is shown in FIG. Tube stopper
FIG. 10 shows the closed tube in the "open" position as described in detail above with respect to FIG.
Shows the sampler 12, in which the sample has been aspirated and the sampling needle 41 is withdrawn from the closed stopper 38 into the inner hole 46 of the upper plate 28 in the process of complete rinsing. Of course, a closed tube sampler 12 oriented as shown in FIGS.
Requires that the length of the cylinder 56 and the piston rod 72 of the drive motor 54 of the sampling needle 41 and the closure tube holding assembly be increased as shown, thereby reducing the sampling needle 41. It is long enough to reach the sample 36 at the bottom of the closure tube 34, and the actuation stroke of the fluid motor drive 54 is sufficient to move the sampling needle 41 between the positions of FIGS. 9 and 10. Guarantee length.

The closed tube sampler is oriented as shown in FIGS. 9 and 10, and the sampling needle is retracted into the annulus of the needle tip / top plate hole for rinsing as shown in FIG. And the flow rate of the surrounding air to the annular portion through the ventilation hole 52 is changed as described above.
The flow rate of the backwash rinsing liquid from the open end of the needle is also substantially greater than the flow rate of the backwashing rinsing liquid from the open end of the needle. As a result of the change of direction of the rinsing liquid, again when the rinsing liquid thus mixed and the surrounding air are forced to flow all around the distal end of the entire needle of the annular portion, the exposed distal end of the sampling needle 41 is exposed. The whole is very thoroughly washed and then discharged through the vacuum holes 48 and the vacuum lines 50. Thus, despite the fact that the sampling needle 41 in FIGS. 9 and 10 is pointed just opposite to that shown in FIGS. 1 and 2, a complete minimization of the remaining amount of sample liquid is achieved. It will be clear that this is also obtained for both the outside and inside of the sampling needle 41.

From the above, it can be seen that the closed tube sampler 12 provides for a clinically very thorough cleaning of the exposed outside of the sampling needle 41, especially after aspiration of a sample of the closed tube.
It will be apparent that the apparatus and method of the present invention can be operatively directed over the 360 ° obtained in such a position in any manner without sacrificing any character in minimizing the remaining amount of sample liquid.

Of course, such ability to use an effective closed tube sampler in any direction adds significantly to the versatility of the devices and methods of the present invention.

Although described herein as being stationary with respect to the plate 28 of the upper closed tube holding assembly, the tube insertion / support guide 34 is located in a manner well known to those skilled in the art, such as on a turntable. In the form of a plurality of tube insertion / support guides as described above and further indexable to the use position shown for sampling from a closed tube holding a sample as further inserted and supported, It will be clear that you can move freely.

Although described herein as being typical for use in collecting and analyzing blood samples, it is to be understood that the devices and methods of the present invention are not in any way limited to use with samples comprising blood. Will be apparent to those skilled in the art.

Of course, various modifications can be made in the preferred embodiments disclosed herein without departing from the spirit and scope of the invention as defined by the appended claims.

 ──────────────────────────────────────────────────続 き Continuation of the front page (56) References JP-A-62-110158 (JP, A) JP-A-57-26754 (JP, A) JP-A-51-108888 (JP, A) 500184 (JP, A) US Patent No. 4516437 (US, A) European Publication 220430 (EP, A2)

Claims (4)

(57) [Claims] 1. A sampling needle having an opening for aspirating a sample liquid is inserted into the inside of a closed sample container, and after aspirating the sample liquid, the sampling needle is withdrawn from the closed sample container and the sample liquid is removed from the closed sample container. Disposing the sampling needle and the closed sample container at an angle other than vertical, and withdrawing the sampling needle from the closed sample container and opposing the direction of flow of the sample liquid drawn through the sampling needle, The sampling needle is backwashed by flowing the rinsing liquid through the opening of the sampling needle, the residue of the sucked sample liquid is removed from the inside of the sampling needle, and the rinsing liquid is discharged from the opening of the sampling needle to the outside of the tip of the sampling needle. Rinsing around and removing any residue of the sample liquid therefrom; The step of flowing the liquid around the outside of the sampling needle tip includes flowing ambient air from outside the sampling needle around the entire surface outside the sampling needle tip at a flow rate much higher than the flow rate of the rinsing liquid, and mixing with the rinsing liquid. Of the sample liquid from the opening of the sampling needle to around the entire outer surface of the tip of the sampling needle to remove the residue of the sample liquid from the entire outer surface, and the remaining of the sample liquid from the subsequent sample liquid container to the suction by the sampling needle. The method of claim 1, further comprising the step of: 2. A sample needle having an opening for sucking a sample liquid is inserted into the inside of the closed sample container and the sample liquid is sucked. Then, the sampling needle is withdrawn from the closed sample container and the sample liquid is removed from the closed sample container. A method of dispensing, wherein the sampling needle is positioned above the closed sample container and the sampling needle and the closed sample container are disposed substantially vertically, and the sampling needle is withdrawn from the closed sample container and aspirated through the sampling needle Backwash the sampling needle by passing the rinsing liquid through the sampling needle and out of the opening of the sampling needle in the opposite direction of the flow of the sample liquid;
Removing the aspirated sample liquid residue from the interior of the sampling needle and flowing the rinsing liquid from the opening of the sampling needle around the outside of the sampling needle tip to remove the sample liquid residue therefrom; The step of flowing the rinsing liquid around the outside of the sampling needle tip includes flowing the surrounding air from the outside of the sampling needle around the entire surface of the sampling needle tip at a flow rate much higher than the flow rate of the rinsing liquid, mixing with the rinsing liquid, and rinsing. The flow of the liquid is directed from the opening of the sampling needle to around the entire outer surface of the tip of the sampling needle to remove the residue of the sample liquid from the entire outer surface, and the sample liquid is subsequently sucked from the sample liquid container by the sampling needle. The above method, comprising the step of minimizing residuals. 3. A sampling needle having an opening for aspirating a sample liquid is inserted into a closed sample container at a distal end thereof, and after aspirating the sample liquid, the sampling needle is withdrawn from the closed sample container and the sample liquid is removed from the closed sample container. Means for cooperating with the sampling needle and the closed sample container so as to arrange the sampling needle and the closed sample container at an angle other than the vertical direction, and withdrawing the sampling needle from the closed sample container and aspirating through the sampling needle Backwashing the sampling needle by passing a rinsing liquid through the sampling needle and out of the opening of the sampling needle in the opposite direction of the flow of the sample liquid to be taken;
Means cooperating with the sampling needle to remove the aspirated sample liquid residue from the interior of the sampling needle, and flowing the rinsing liquid from the opening of the sampling needle around the outside of the sampling needle tip to remove the residue of the sample liquid. Means for cooperating with the sampling needle to remove therefrom; means for flowing the rinsing liquid around the outside of the sampling needle tip, rinsing ambient air from outside the sampling needle to the entire surface outside the sampling needle tip. Flow at a flow rate much higher than the flow rate of the liquid, mix with the rinsing liquid, remove the residue of the sample liquid from the entire outer surface by directing the flow of the rinsing liquid from the opening of the sampling needle to around the entire outer surface of the tip of the sampling needle, Means for minimizing residual sample liquid from the subsequent sample liquid container to suction by the sampling needle. Serial devices. 4. A sampling needle having an opening for aspirating a sample liquid is inserted into the inside of the closed sample container, and after aspirating the sample liquid, the sampling needle is withdrawn from the closed sample container, and the sample liquid is removed from the closed sample container. A means for cooperating with the sampling needle and the closed sample container so that the sampling needle is positioned above the closed sample container and the sampling needle and the closed sample container are arranged in a substantially similar vertical orientation, and the closed sample container. Withdrawing the sampling needle from the sample and backwashing the sampling needle by flowing the rinsing liquid through the sampling needle and out of the opening of the sampling needle, in the opposite direction of the flow of the sample liquid being aspirated through the sampling needle;
Means cooperating with the sampling needle to remove the aspirated sample liquid residue from the interior of the sampling needle, and flowing the rinsing liquid from the opening of the sampling needle around the outside of the sampling needle tip to remove the residue of the sample liquid. Means for cooperating with the sampling needle to remove therefrom; means for flowing the rinsing liquid around the outside of the sampling needle tip, rinsing ambient air from outside the sampling needle to the entire surface outside the sampling needle tip. Flow at a flow rate much higher than the flow rate of the liquid, mix with the rinsing liquid, remove the residue of the sample liquid from the entire outer surface by directing the flow of the rinsing liquid from the opening of the sampling needle to around the entire outer surface of the tip of the sampling needle, Means for minimizing residual sample liquid from the subsequent sample liquid container to suction by the sampling needle. Serial devices.