JPS58117458A - Sample introducing method and continuous flow type analyzer - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to partitioning of an unpartitioned liquid carrier stream based on a controlled combination of hydrostatic and hydrodynamic forces. Regarding the sample introduction method for introducing a liquid sample zone, this zone or liquid sample zone is then sent to a flow-through analyzer, in which the seven or more chemical The present invention relates to the sample introduction method described above, which comprises quantitatively evaluating chemical species present in the sample solution (sometimes produced as a result of reaction Q) in a flow-through detector.

Analysis by flow injection analysis method (Fem) K [for example, U.S. Patent No. ρJ J, j? No. 1 and No. 411. ．． 2 Koji,
In the OJ J issue], the sample solution to be analyzed is
The sample area must be introduced into the undivided carrier stream, and the volume and shape of the sample area must be strictly reproducible. . Conventional sample introduction methods can be divided into groups based on the following principles: +11 Methods in which a precisely metered amount of sample solution is introduced directly into the carrier stream (e.g., as described in U.S. Pat. !r); (2) a method of precisely metering a large amount of sample solution and introducing it through a valve (see, e.g., U.S. Pat. A method of introducing the solution by means of a solenoid valve device (e.g. U.S. Pat. No. 777.A
(See No. 77).

In the first mentioned sample introduction method (1) above, the carrier flow is driven by a nine-syringe with a needle penetrating the conduit wall? /pull solution is injected, but this method of introduction is not always sufficiently reproducible, nor is it easy to automate this method of introduction. (2
The method of introduction described in ) uses a nine-slide valve or Using rotary valves, the sample hole is partially opened at the point where the sample solution is introduced into part of the circuit of the middle solution, whereby the sample is transported by the carrier flow, and the use of these valves is highly reproducible. It is the most universal because it produces certain results biomedically and can be easily automated.

The disadvantages of this method are that the valves must be very precisely machined, which makes them expensive, and that the moving parts must remain leak-tight even after injecting the sample thousands of times, making the movement of the valves more expensive. The mechanical wear of the parts is large.

In the case of the introduction method described in (3) above, several (at least three) solenoid valves are used which are opened and closed in a certain order and at predetermined time intervals. Although this method of implementation is also easily automated, it clearly requires auxiliary electronic timing circuitry. However, the most serious drawback of this method is that the elastic member that mechanically opens and closes on the solenoid valve eventually wears out, and the solenoid valve exerts repeated localized pressure on the structure, causing the elastic member to wear out. Deformation occurs, and as time passes, the valve completely opens and closes, resulting in a gradual increase in failures that make it extremely difficult to determine what is wrong. The feature is that the metered volume of sample solution introduced is determined by the volume of the solid container (pore size, loop length, etc.), which container introduces the metered sample area into the carrier stream. It must be sealed liquid-tight immediately before
That is, in introduction method I, the measured volume of the liquid is accommodated under the plunger of the syringe and corresponds to the large volume, and in introduction method -, the liquid in the closed container is measured by a sliding valve or by a rotary valve. enclosed within the hole or sample loop and represented by the volume of sample liquid, at the same time the valve is switched from the sampling position to the introduction position, and in (3) the introduction a closed vessel and a large volume metered into it. 9 tubes of a given length and diameter are accommodated within the conduit (corresponding to the volume of 9 solenoid valves).

SUMMARY OF THE INVENTION In this invention it has been demonstrated that the volume of a liquid sample area introduced into a carrier stream can be equally well defined based on a controlled combination of hydrostatic and hydrodynamic forces. According to the invention, therefore, the container used for metering the volume of the sample area is permanently connected to and is in continuous communication with both the sampling circuit and the carrier flow circuit, i.e., the vessel used for metering the volume of the sample zone is The container is the common part of both conduits. The obvious advantages of such sample introduction systems are their simple construction and the absence of any moving parts, which makes hydrodynamic sample introduction systems not only extremely reliable, but in fact completely It requires no maintenance and is therefore long lasting.

The present invention comprises a sampling circuit and a carrier flow circuit, and a volumetric conduit that is constantly connected to both circuits and simultaneously opened to both axillary circuits for trout, is shared by both circuits. The circuit separates the sample solution and the undivided carrier flow solution to create a clearly defined undivided sample/pull area in the volumetric conduit by a controlled combination of hydrostatic and hydrodynamic forces. After being fed and discharged in a time-divided manner to create an undivided sample area in the volume 111 conduit, the temple area is transported by an undivided Yalla flow through a carrier flow circuit to a continuous flow analyzer equipped with a detector. The sample introduction method consists of several steps.

The invention also provides continuous flow analysis of separately separated samples using undivided carrier streams! ! wherein the apparatus comprises a sampling circuit and a carrier flow circuit, and a volumetric conduit permanently connected to and simultaneously open to both circuits is shared by both said circuits. and both circuits connect the sample solution and the undivided carrier to create a clearly defined undivided sample area within the spinning volume metering conduit by a controlled combination of hydrostatic and hydrodynamic forces. The flow solution is supplied and discharged in a definite time-divided manner to create an undivided sample area in the volumetric conduit, and the sample area is then passed through the carrier flow circuit by the undivided medium flow to a large continuous flow system equipped with a detector. a sampling circuit and a carrier flow circuit for transporting to an analytical device; an electronic device for controlling the duration and sequence of the operating cycles of a mechanical device controlling the movement of liquid within the cough device; and conduits within said device. a flow-through analyzer and a flow-through detector arranged to receive a carrier stream containing a sample solution; There are also Temple's continuous flow analyzers that use carrier streams to separate the separations.

This invention has a long history in which an IIR flow type analyzer and a flow type detector are installed in a sampling circuit, and a standard bath liquid is used to
! AWl flow-through analyzer and fIt flow-through detector Sample solution passes through the sampling circuit except for intermittent periods during which it is being corrected and readjusted. ! Continuously monitors the composition of a liquid stream consisting of a standard solution & a sample stream which is transported in the form of a clearly demarcated area by the sample stream passing through the detector for this purpose. It also relates to a device for.

The invention will be explained in more detail with reference to the figures.

FIG. 1A illustrates the elements of the introduction device of the invention: (ω Sample introduction volume @ 1 m) A narrow inner diameter conduit such as a tube (depending on the volume of sample solution introduced, typical inner diameter & , smm, with a typical length of 1
00CIa); (b) Liquid propulsion device @
J * 4' and j; This number is, for example, a shift pump,
partially activating the sampling circuit by simultaneous operation of C and 3, and partially activating the carrier flow circuit by simultaneously operating D and S; lc) liquid propulsion group C, J, L and S respectively; Timing devices for controlling liquid propulsion groups; these also stop liquid propulsion groups to control these propulsion groups! Make it move (go). Transporting the liquid in the direction indicated by the arrow on the $17A diagram;
and the column of liquid present in each individual circuit, other than the liquid present in the conduit section common to both circuits, is completely stationary when the liquid propulsion device (bonder) belonging to each individual circuit is not in operation. It is essential that the liquid propulsion system works as it should. Furthermore, it is necessary that the liquid volume transport rate introduced into the sampling circuit and discharged from the sampling circuit force 1 be as close as possible to 1, which means that pump groups 1 and 3 operate with exactly the same liquid volume transport efficiency. It is necessary to. However, this does not mean that 41 e.g. two-channels with - identical transport pipes
Fif; is very easily achieved by using a pump. The same conditions apply for determining the liquid genie and discharge for the medium flow operated by the pumping devices S and S. During the sampling cycle, the sample solution is transferred to the source 10 to be monitored (this may be, for example, a reactor in which a chemical reaction to be controlled takes place, a pipe conveying a given solution, or a blood vessel). The volumetric conduit l is removed by pump devices K and J from the sample solution (which may be 100 to 100 mm) and is thoroughly flushed with the sample solution and filled along its length with the sample solution. During the whole sampling cycle the pumps and S are kept stopped, so that lf
A column of liquid to the left of / blocks the sample solution from entering the carrier flow circuit. After the sampling cycle is completed, pumps q and 3 are stopped and pumps q and 3 are turned on, thus filling the well-defined sample area (
A sample area (that is, corresponding to the length of the conduit l) is introduced into a flow-through analysis device 6, in which a chemical reaction takes place in the case of the introduced sample and the result is detected. Since bombs and 3 are now at rest, i.e. the liquid column to the right of conduit l is now stationary, only the amount of sample solution originally present in conduit/is drawn from reservoir g. can be transported into the analytical device 6 by means of a carrier solution 2 . Thus the carrier solution is this #! The only movement (liquid flow) flowing through the cococycle, and the entire dispersed sample area ends up passing through the analyzer 6 (this is a self-recorded signal returning to the baseline,
i.e. displayed on the recording needle connected to the detector by a signal reporting that the carrier solution cycle is complete)
The driver's license will be maintained until. Pump stop and 3 are then stopped, while pump stop and 3 are restarted to start a new measurement cycle. Since the sampling cycle and the carrier flow cycle are completed in total within one minute, the device is suitable for continuous microscopy in industrial operations, for example, or for the management of critical patient care.

According to the introduction method described above, the sample solution is #
Four people are taken in succession. However, continuous measurement of a given sample flow is also possible using the device described here. In this case, the hydrodynamic sample introduction principle is used to calibrate the used flow-through analyzer by simply introducing intermittently a standard solution of the species to be continuously monitored. . In other words, in this case, the roles of the sample flow and the carrier flow are reversed. This can be explained by FIG. 1A, in which Bombco and j are simultaneously and at the same volumetric transport rate continuously suctioning the bath liquid 9 to be monitored and propelling it through conduit l to analyzer B. During this operation, stop pump-tei and 3,
The columnar liquid area present in this circuit (with the exception of the volume present in the part of the conduit common to both circuits, ie in conduit l) remains stationary. Analyzer #IIk
Alternatively, when making the correction, the pump stop and the pump 5 are stopped and the pump stop and the pump 3 are operated at the same volume transport speed. This operation fills the volume conduit 111 with the standard solution from the reservoir l, and when the pump stop 3 is stopped and the pump holder 3 is restarted, the standard solution area metered into the conduit 1 is filled with the standard solution from the reservoir l. The flow analyzer is connected to the sample signal transported by the solution into the analyzer 6 and continuously recorded.
or generate a signal that can be used to recalibrate.

If there is a limit to the amount of sample material available or the sampling cycle has to be shortened, or both, as often occurs when a series of separate samples are analyzed, The hydrodynamic sample introduction system can be modified and further simplified as shown in Figure 1B, in which the sample solution 9 is placed in a sample container or sample tray, for example The conduit is drawn out from // by the operation of pump 3 /
U (which is made as short as possible in practice) into conduit l, and this sampling cycle is limited to last until volumetric conduit l is completely washed and saturated with sample solution. . What is the pump number and 5 as in the first example listed? Pumps q and S are kept at a standstill during the 7-ring cycle, and pumps q and S are restarted only when the liquid contained in conduit 1 is transferred into the flow-through analyzer (at which point pump J is stopped). be done. Control pump (#!/A
It must be emphasized that in the absence of the bombco in When transporting a solution, carrier l
The difference in the volumetric transport rate of E7 will force a corresponding fraction of the carrier flow from reservoir g into the tip, thus diluting the sample material before the next sampling cycle, or ( 1)) Pump-tei is a pump! This is because at slower transport speeds, the sample material // magenta is aspirated even during the carrier cycle and recorded as an increased base signal on the recorder, causing a false signal on the recorder. However, the method of this invention achieves a satisfactory balance and maintains reproducibility.
This is proven by the I-B diagram and Figure 10. These figures are photographic reproductions of the Ki's silver needle signals obtained as a series of spectrophotometer measurements recorded by an analyzer equipped with a self-recording spectrophotometer and a flow cell. The absorbance of the carrier stream (which itself is colorless) can be continuously monitored. In this way, a dye solution, e.g.
) (the color of this BTB can be recorded as photometer measurements at AJOnrn) was injected into the system. This sample is recorded as a peak during its passage through the analyzer 6, the height of which peak is proportional to the color intensity of the dye present, and the color of the sample introduced into the conduit 1 (
(dye) and proportional to the volume of sample metered in conduit l. That is, for a constant sample volume (constant volume of conduit 1), the peak height is directly proportional to the concentration of color (dye) in the sample solution. The first part of Figure 15 shows 75 l replicate samples (the volume of the sample solution is j 1141 ).

That is, the conduit l has an inner diameter o, s mm, a length l, jc
The absorbance when s is introduced is shown. These/j
Samples gradually increase in concentration of BTB! It consists of 11 sample solutions of BTB with different concentrations, and each sample with the same concentration consists of 3 samples. These sample solutions were prepared by sequentially diluting the stock solution of BTB aqueous solution with water, and the volume ratio of stock solution to water in the five solutions was /:4 (3.3:3, 4t:/). and s:o
Met.

The same experiment was then repeated, but this time introducing 5 Opl of dye IL wave (IaB diagram, i.e. conduit l).
is the inner diameter 0. It was made into a tube with a length of 16 cm. As can be seen from the -Am and 1sλB diagrams, this series of experiments proves that the hydrodynamic sample introduction method provides excellent reproducibility. No. C
The last series of sample introduction methods shown in the figure shows the absorbance of 13 samples introduced over a period of 23 minutes. The same tick t BTB sample solution so pit was introduced. This experiment not only shows excellent reproducibility of the measurements, but also shows that the method has a high degree of stability over time.

Still another embodiment of the hydrodynamic sample introduction method (introduction device) will be described with reference to FIG. 1C. The sample solution transport device (pump) group is connected to the syringe/3 containing the sample solution 9
It was replaced with a piston device like this. This syringe/3 is used to introduce the sample solution through the sample circuit into the volumetric conduit/(its length and internal diameter define the volume of the sample area). Thus, only one solution propelling device, such as a hydraulic pump, is required, and these pumps are started after the sample circuit and conduit l are filled with sample solution. The sample area is then introduced into the carrier stream and further into the analyzer 6. The prerequisites for this embodiment to achieve satisfactory performance are that the piston in the injection gtJ remains in a constant position during the operation of the carrier flow cycle, and that the bomber and! The transport speed within is the same. The advantage of this embodiment is that the experimental setup is simple and that it is possible to handle a small volume of the sample from a sample source, such as a sick patient, and introduce it into the analytical device under air exclusion. If the syringe is operated manually, the disadvantage is that it requires skilled handling.

It should be emphasized that the above-mentioned variants of the invention do not change the basic idea of the invention. Such modifications include (a) solution propeller groups that work in pairs and supply the sample solution to the sample solution circuit (e.g. the pair of bo/pco and 3 in the tlilA diagram) and/or to the carrier fIt circuit; An open-close valve for one of the solution propeller groups of a solution propeller group (e.g. pump pair 1 and 3 in Figure 1A) that supplies solution (when in the open position the corresponding solution propeller is in operation). and when in the closed position, the corresponding solution propulsion device is in the stopped condition], by adding another flow propulsion device (e.g. 741 and tS in FIG. The device adds an additional flow to the analyzer 6 and causes the liquid to flow out (provided that the transport rate is such that exactly the same volume of liquid leaves the volumetric conduit 1 from the opposite end of the volumetric conduit 1). This means that the suction speed of device S is equal to that of device U,
The value must be equal to the net sum of the transport speeds of /U and /j.

Alternatively, the pump device S may be replaced by an open-close valve according to the modifications described in Section 0;
etc. can be arranged in series in a sampling circuit, in which case each individual volumetric conduit can be connected to a number of analyzers arranged in parallel &,! ', 4', etc. to provide separate stream streams for analysis. In this case, what is required is a balance between hydrodynamic and hydrostatic forces and appropriate time sequence timing between the sample 1111gl path and the middle flow circuit; As in the embodiment shown in FIG. 1, it can be replaced by hydrodynamic control, and by synchronizing the sample solution propulsion devices 3 and 3, the Nakayaya circuit flow propulsion device 3 is started to operate. Even, thereby, the carrier solution fIL7
The sample solution stream can continue to be transported even if the sample solution starts to move. In this way, the volume of the sample solution can be increased beyond the volume that can be accommodated in the conduit l while the solution is at rest. The increase in the volume of the sample introduced into the conduit 1 depends on the length of the overlap between the duration of the sampling cycle and the duration of the operating cycle of the carrier flow circuit and on the respective solution transport rate generated by the solution thruster λ5Jtle5. The advantage of this embodiment is that the protostatic control in the sampling circuit and the volumetric conduit is replaced by a hydrodynamic control method during a well-defined period. The single-child control of the repeating stop/operation (STOP/()O) intervals that constitute the opening of the possibility of flexibility for varying the amount of sample solution introduced.

A disadvantage of using this combination of hydrostatic and hydrodynamic control is that the reproducibility of the sample volume introduced is limited by the precise timing of each operating cycle and by the liquid propulsion system.3. Da, S
This depends on the transport and suction speed of the The hydrostatic control of the introduction of the sample area contained within the volumetric conduit I described above is independent of these parameters.

According to this sample introduction method, a sample can be pretreated before analysis in an extremely simple manner. For example, an ion exchanger, a dialyzer or an extraction device can be inserted into the sample tube;
The properties of the sample can be completely changed by such treatment. Very dilute samples can be concentrated, impurities that introduce errors in the analysis can be extracted or adsorbed into the column, or the substance of interest can be adsorbed onto the column and the solution introduced into the analyzer. can.

Although representative embodiments of this invention have been illustrated by several examples, modifications of the structure, materials and components described above may be made without departing from the spirit of this invention and the scope of this invention as defined in the claims. I want you to understand that I am doing my best.

The method and apparatus of the present invention has a simple structure of the sample introduction device and has no moving parts, making the hydrodynamic sample introduction system extremely reliable, maintenance free and long lasting.

Furthermore, as can be seen from FIGS. 18 and 13, excellent reproducibility can be obtained by the fluid sample introduction method.

SUMMARY OF THE INVENTION The present invention comprises a sampling circuit and a carrier flow circuit, one of the circuits sharing a volumetric conduit, the volumetric conduit being permanently connected to both the sampling circuit and the carrier 111 circuit; For a sample introduction device that is simultaneously open, the device creates a well-defined sample area within the volumetric needle volume conduit by a controlled combination of hydrostatic and hydrodynamic forces, and then is transported with extremely high reproducibility into a continuous flow analyzer in which quantitative analysis of the components in the sample solution is carried out.
The present invention relates to a sample introduction device consisting of generating a signal which is carried out optionally even with the aid of a chemical reaction and which is supplied by a Wt-type detector.

[Brief explanation of the drawing]

Figures 1A to 1D are explanatory diagrams of the method of introducing a sample into the analyzer according to the present invention, and Figures 18 to 13 are samples of varying amounts of bromothymol blue aqueous solutions at different concentrations measured by the analyzer. Figure 10 is a diagram similar to Figures 18 and 13 when a sample injector is used as a syringe. In the figure: Place, ri...carrier solution or standard solution, g...storage tank,! ...Sample solution, 10...(su/pull) source, l
/...Sample tip (sample item '1t)'s' co-conduit, /J--syringe. Fl'6.2C-FIG, 28 FIG 2A
Mocking Ham no same

Claims (1)

[Scope of Claims] l It is equipped with a sampling circuit and a carrier flow circuit, is always connected to both of these circuits, and is connected to both circuits at the same time.
The volume needle volume conduit which is released is connected to both circuits.
In common, both circuits generate a sample solution and an undivided carrier flow to create a well-defined undivided sample area within the volumetric conduit through a controlled combination of hydrostatic and hydrodynamic forces. After supplying and discharging the solution in a well-defined time-shared manner and creating an undivided sample zone in the volumetric conduit, the sample zone is passed through the carrier flow circuit by an undivided carrier flow into a continuous flow analyzer equipped with a detector. The volume metering conduit shared by the sampling circuit and the carrier flow circuit forms a narrow flow path, and the volume of the sinenpule area is determined by the length and cross-sectional area of the conduit. 2. A method as claimed in claim 1, in which a sample solution is contained within said volumetric conduit and then discharged by means of a carrier flow towards a continuous flow analyzer. A column of liquid where the carrier flow circuit is closed at all ends and an undivided column of liquid within the closed carrier flow circuit is within a volumetric area shared by the sampling circuit and the carrier flow circuit. The sampling circuit is kept in operation when the sampling circuit is kept stationary; When the column of liquid within is kept stationary,
3. A method of introducing a sample according to claim 1, wherein the carrier flow circuit is maintained in an operating state mK. Claims 1 to 3, in which the period of sampling circuit operation cycle overlaps with the start of the operating cycle of the carrier flow circuit and introduces a volume of sample solution greater than the volume accommodated within the volume of the volumetric conduit. The sample introduction method according to any of Item 3. Claims 1, 2 and 3, in which several volumetric conduits are connected in series, each volumetric conduit being fed by a separate Φ Yalla flow circuit, each carrier flow circuit being connected to a corresponding continuous flow analyzer. The method for introducing a temple according to any one of paragraphs 1 to 3. In the patent claim, several volumetric metering conduits are connected in series, each volumetric metering conduit receiving supply from a separate sampling circuit, and the total volumetric metering conduit being supplied with carrier flow from a common carrier flow circuit. The method for introducing a sample according to any one of Items 1 to 3 of the scope. t. The sample introduction method according to any one of claims 7 to 9, wherein a sample processing station is arranged in front of the temple introduction device, and the station is equipped with an ion exchange agent, a dialysis device, etc. t. An apparatus for continuous flow analysis of separately separated samples using an undivided carrier flow, the apparatus comprising a sampling circuit and a carrier flow circuit, the apparatus being permanently connected to both circuits and a volumetric conduit simultaneously open to the circuit is shared by both said circuits;
Both circuits are clearly defined by a controlled large combination of hydrostatic and hydrodynamic forces to produce a sample solution and an undivided carrier flow solution in the volumetric conduit to produce nine undivided sample areas within the volumetric conduit. and are supplied and discharged in a well-defined time-shared manner to create an undivided sample area in the volumetric conduit, which is then passed by an undivided carrier flow through a carrier flow circuit to a continuous flow analyzer equipped with a detector. an electronic device for controlling the duration and sequence of operating cycles of a mechanical device that controls the movement of fluid within the axillary device; and a conduit within said device. a flow-through analyzer and a flow-through detector arranged to receive a carrier stream containing a sample solution; Continuous flow analyzer with separate samples separated using a carrier stream. The continuous flow analyzer and flow detector are installed in the sampling circuit, and the sample solution is not sampled except for intermittent periods when the continuous flow analyzer and flow detector are recalibrated and readjusted by the standard solution. Continuously monitor the composition of a liquid stream that is transported continuously through the circuit, and this standard solution is transported in the form of clearly demarcated areas by the sample flow through a detector for this purpose. equipment for