FR2517064A1 - - Google Patents

Abstract

THE INVENTION RELATES TO CHEMICAL ANALYSIS TECHNIQUES. A SAMPLE INTRODUCTION DEVICE INCLUDES IN PARTICULAR A SAMPLING CIRCUIT 2, 1, 3 AND A CARRIER CURRENT CIRCUIT 4, 1, 5 WHICH HAVE IN COMMON A VOLUMETRIC DUCT 1 WHICH COMMUNICATES PERMANENTLY WITH THE TWO CIRCUITS. BY A DETERMINED COMBINATION OF HYDROSTATIC AND HYDRODYNAMIC FORCES, THE DEVICE ALLOWS TO CREATE IN THE VOLUMETRIC DUCT A WELL-DEFINED SAMPLE ZONE, AND THEN TO TRANSPORT THIS ZONE IN A CONTINUOUS CIRCULATION ANALYZER OF THE CONSISTENT 6 ANALYZER WITH A CONTINUOUS CIRCULATION QUI CONSTITUTION OF THE 6 ANALYZER OF SOLUTION SAMPLE. APPLICATION TO MEDICAL ANALYSIS.

Description

17064

  the present invention relates to a method for introducing

  sample production by which a volume of a sample area

  The liquid sample, which must be introduced into a non-segmented liquid carrying stream, can be defined on the basis of a determined combination of hydrostatic and hydrodynamic forces, this well-defined sample area then being transported to an analyzer. in circulation, in which a substance present in the sample solution, which may possibly result from the course of one or more chemical reactions, may be quantitatively evaluated in a circulating sensor configuration O Analysis by means of the Analysis technique by injection into a current (see for example US Pat. Nos. 4,022,575 and 4,224,033) requires that a sample solution be

  to be analyzed is introduced into a non-segmental carrier

  in the form of a well-defined sample area of which

  the volume and the geometrical form are strictly reproduc-

  Conventional sample introduction techniques can be divided into three groups which are based on the following principles: (1) Direct injection of a precisely measured sample solution quatity into a carrier stream (see for example US Pat. 4,022,575);

  (2) Introduction of a quantity of exchange solution

  accurately measured by means of a valve (see, for example, US Pat. No. 4,224,033); and

  (3) Intercalation of a quantity of sample solution

  accurately measured by means of a device

  magnetic valves (see for example US Patent 4,177,677).

  In the sample introduction process

  first, the sample solution is injected by means of a syringe provided with a hypodermic needle which passes through the wall of the duct in which the carrier stream is propelled, but this method of introduction is not always sufficiently reproducible and , it does not lend itself

  not easily to automation In the introductory procedure

  corresponding to group (2), the most common use is

  Sliding or rotating valves with bores

  whose volume is precisely defined (or who can also

  have external sample loops so

  to accept larger sample volumes) and in the

  which sample bores can be brought in

  in a position in which these bores, with the sample solution, are part of the circuit of the carrier solution, so that the samples can be transported by the carrier current The use of such valves is

  motivated by the fact that it gives very reproduc-

  tibles and can be easily automated

  reside in the high cost of valves that must be

  very precisely, and in the mechanical wear of moving parts which must remain watertight, even after

  thousands of injections In the process of introduction corre-

  group (3), several (at least four) magnetic valves-which can be opened and closed-are used

  a certain sequence and at predetermined intervals of time

  This method of introduction is also easy to automate, but it obviously requires electronic timer circuits. Its biggest drawback however is the fact that the elastic elements on

  which the open / closed magnetic valves act

  can eventually wear out and deform under the effect of the repeated localized pressure exerted by the wedge-shaped shutter of the magnetic valves Thus, at the end of a

  some time, the valves may not open or close

  completely, which leads to a malfunction of

  slowly increasing and can be extremely

difficult to identify.

  The common feature of the three sample introduction methods mentioned above consists of

  in that the measured volume of sample solution to be introduced

  is defined by the volume of an enclosure in the solid state

  of (bore, loop length, etc.) which is closed hermetically

  immediately before the introduction of the sampling area.

  measured in the carrier current (indeed, in the

  1, the measured volume of liquid sample corresponds to the volume trapped under the plunger of the syringe

  hypodermic; in process 2, the liquid contained in

  the closed chamber is represented by the volume of sample liquid that is enclosed within the bore or

  of the sample loop of a sliding valve or

  when the valve is switched from the sampling position to the introduction position; and in the introduction process 3, the closed chamber and the measured volume it contains correspond to the volume that

  magnetic valves trap in a tube or

  duit of given length and diameter).

  It will be demonstrated in the invention that the volume of the liquid sample zone, which must be introduced into a

  current, can also be defined on the basis of

  of a given combination of hydrostatic and hydrodynamic forces Thus, in the invention, the chamber used to measure the volume of the sample area can be

  therefore communicate permanently with the sample circuit-

  as with the carrier current circuit, and open continuously towards these circuits, that is to say that it can consist of a part of common conduit for both

  The obvious advantage of such an introductory device

  The simplicity of the structure and the total absence of moving parts mean that the sample hydrodynamic device is not only extremely reliable, but also, in fact,

  completely maintenance-free, and therefore very durable.

  The invention will be better understood when reading the-

  following detailed description of embodiments

  and with reference to the accompanying drawings in which: FIGS. 1A, 1B, 1C and 1D show the elements of various embodiments of the device; and Figures 2A, 2B and 2C are photographic reproductions of recorder signals obtained in a

  series of spectrophotometric measurements made with the

positive analysis of the invention.

  FIG. 1, which shows that the device comprises the following elements: (a) a sample introduction enclosure 1 consisting of a given length of conduit (for example of tube) of small inside diameter (the inside diameter

  is typically 0.5 mm and the typical length

  range is 5 to 100 cm, depending on the volume of

  sample introduction to be introduced); (b) liquid propulsion means 2, 3, 4 and (for example peristaltic pumps), which partially serve the sampling circuit, by the simultaneous operation of the elements 2 and 3, and which partially serve the circuit carrier current by the simultaneous operation of elements 4 and 5; and (c) a sequencer device for respectively controlling the liquid propulsion means 2, 3 and 4, so that the latter can be stopped cu misen mareh I It is essential that the liquids flow in the directions indicated by the arrows in the figure, and that the liquid propulsion devices used are

  so that the columns of liquid present in each cir-

  cooked individually, except the one in the cooking part

  which are common to both circuits, are kept completely immobile when the liquid propulsion devices (pumps) belonging to each individual circuit are not in operation. In addition, it is necessary that the

  volumetric pumping rates at the inlet and outlet of the.

  sampling circuit have a ratio as close to the unit as possible, which requires that the pumping means 2 and 3 operate exactly with the same volumetric pumping rate This can however be achieved very easily, for example by using a peristaltic pump

  two-way with two identical pumping tubes.

  The pumping of the liquid at the inlet and the outlet for the cir-

  baked power supply, served by

  pumping 4 and 5, must meet the exact requirements of

  During the sampling cycle, the sampling solution

  9 is sucked from a source 8 to control (it could be for example a reactor in which a chemical reaction takes place which must be controlled, or

  a pipe carrying a given solution, or possibly

  an artery of the blood system), by means of the

  2 and 3, until the volumetric duct

  1 is thoroughly purged and filled with the sample solution over its entire length Throughout the sampling cycle, pumping devices 4 and 5 are

  kept at rest and, consequently, the columns of

  quide located to the left of the duct 1 pocket the input of the sample solution in the carrier current circuit Once the sampling cycle has been completed, the pumps 2 and 3 are stopped while the pumps 4 and 5 are set

  in operation, which introduces a well-defined sample area.

  finished (i.e. corresponding to the length of the conduit 1) in the circulation analysis device 6, in which possibly a chemical reaction occurs, followed by the detection of the introduced sample.

  2 and 3 are now stopped, that is to say that the colonists

  Fluid numbers located to the right of the duct 1 are now fixed, only the quantity of the sample solution that was initially present in the duct 1 can be transported

  in the analyzer device 6, by means of the solution

  7 which is sucked from the tank 8 Thus,

  In this second cycle, the carrier solution is the only one

  fluid in motion in the device, and the pumps

  pes 4 and 5 are kept running until the tota

  the dispersed sample area has crossed the

  positive analyzer 6, which is indicated, on a recorder connected to the detector, in that the recorded signal returns to the baseline and thus indicates that the cycle of the carrier solution is completed can then stop the pumps 4 and 5 while pumps 2 and 3 can be restarted to start a new measurement cycle O Since the sampling and transport cycles can be fully completed in one minute or less, the device is well suited for such applications. that control

  continuous industrial processes or medical applications.

  such as monitoring patients -in critical conditions. In the application described above, the solution

  sample is intermittently introduced into the

  However, it is also possible to use

  the device shown to perform a continuous measurement on a given sample stream, while the principle of hydrodynamic sample introduction is now used to verify the calibration of the flow analyzer that is being used, simply by introducing intermittency a reference solution of the substance that is continuously-controlled We can say that the r Ales

  of the sample stream and the carrier stream were reversed.

  This can be seen by looking at Figure 1A on

  that the pumps 2 and 5, operating simultaneously and with identical volumetric pumping rates, now aspire continuously the solution 9 to control, and

  this solution is propelled towards the analyzer 6 by the con-

  During this procedure, pumps 4 and 3 are

  and the columns of liquid belonging to this cir-

  cooked, with the exception of the volume present in the

  which is common to both circuits, that is to say the

  When the analyzer is to be adjusted or recalibrated, the pumps 2 and 5 are stopped and the pumps 4 and 3, which pump both with identical volumetric pumping rates, are operated. volumetric duct 1 with a solution

  reference 7 from tank 8, and when the pumps

  4 and 3 are stopped while the pumps 2 and 5 are restarted, the reference solution zone of which a determined quantity has been introduced into the duct 1, is transported by the sample solution 9 in the analyzer 6. in which it gives rise to a signal which, in relation to the permanently recorded sample signal, can be used to adjust or recalibrate the flow analyzer O If the available sample material volume is limited and / or if the sampling cycle is to be kept short, as is often the case when larger series of discrete samples are analyzed, the hydrodynamic sample introduction device can be modified and further simplified, such as Figure 1B shows the sample solution 9 is sucked from a

  sample container 11, placed for example on a

  sampling device or a sample tray, and the suction is carried out by a conduit 12 which is also -

  short that it is possible in practice The sample solution

  lon is then directed to the conduit 1, being sucked due to the start of the pumping device 3, and the sampling cycle is limited to the time necessary to completely purge the volumetric duct 1 and for

  fill it with sample solution 9 As in the example

  first described, pumps 4 and 5 are maintained at

  stop during the sampling cycle and redesigns

  when the content of conduit 1 must be entered between

  in the flow analyzer 6, and at this point the

  pump 3 is stopped It should be emphasized that in the absence

  this of the control pump (pump 2 in Figure 1 A), the volumetric pumping rates of the pumps 4 and 5 must be exactly the same because (a) if the pump 4 pumps faster than the pump 5, the difference between the volumetric flow rates of the carrier current 7 has the effect of directing to the container 11 the excess part of the

  carrier current from the reservoir 8, which dilutes the

  sample before the next sampling cycle; or (b) if the pump 4 pumps more slowly than the pump 5, a part of the sample material 11 is sucked up even during the cycle of the carrier current, which produces in the recorder an erroneous signal, recorded in the form of an elevation of the signal from the baseline However, the

  possibility of achieving a satisfactory balance and

  reproducibility is demonstrated in Figures 2A,

  2 B and 2 C, which are photographic reproductions of

  recorded in a series of spectral measurements.

  trophotometric, recorded by the analysis device 6 equipped with a circulation cell which is placed in a

  spectrophotometer connected to a tape recorder

  pier, so as to allow continuous control of the

  absorbing power (abs) of the carrier current, which is by itself

  Even colorless Thus, by injecting into the device a solution of dye as sample solution 9 (in this case aqueous solutions of bromothymol blue (BTB), the color of which can be recorded by photometry, at 620 nm have been used. ), the sample can be recorded as it passes through the analyzer device 6 under the

  shape of a peak whose height is proportional to the

  present color intensity, which is itself proportional

  on the one hand to the saturation of the color of the sample introduced into the duct 1 and, on the other hand, to the volume of sample introduced into the duct 1.

  fixed sample volume (fixed volume of line 1), the

  peak is directly proportional to the saturation of the color in the sample solution 9 o In Figure 2 A, we first see a series of 15 introductions

  samples in which a volume of sample

  25 mm 3 (i.e., conduit 1 consists of a 12.5 cm tube, 0.5 mm internal diameter), and five different sample solutions of BTB were introduced,

  gradually increasing concentration, with three

  successive troductions for each concentration

  trimmed these solutions from a basic aqueous solution of BTB, by dilutionssuccessives with water, the volumetric ratios of the base solution and water in the five solutions being respectively 1: 4, 2: 3, 3: 2, 4: 1 and: 0. The same experiment was then repeated, but this time introducing fractions of 50 mm 3 of solutions

  dye (FIG. 2B), that is to say that the duct 1

  was 25 cm of tube 0.5 mm inside diameter.

  As shown in FIGS. 2A and 2B, these two series of experiments demonstrate the excellent reproducibility afforded by the hydrodynamic introduction process.

  The last series of sample introduction

  1, shown in FIG. 2C, comprises 23 samples introduced over a period of 23 minutes (the associated recorder operating at a slower paper feed speed than in the experiments of FIGS.

  and 2 B), and each time 50 mm 3 of the same

  sample dilution of BTB diluted in 4: 1 ratio addition

  the fact that this experience shows an excellent reproduc-

  tibility of the measurement, the device has a very high degree of stability over time.

  We will now consider Figure 1 C to describe

  another embodiment of the system of introduction

  Hydrodynamic Sample Drainage The pumping device

  of sample solution is replaced by a pis-

  such as a syringe 13, containing the sample solution

  9, which is used for the introduction of the sample solution

  lon, by the sample circuit, in the volumetric duct

  1, whose length and cross-sectional area

  the volume of the sample area. Thus, just two solution propulsion elements, 4, 5, as per

  example a two-way peristaltic pump

  pump after the sample circuit and

  duit 1 were filled with the sample solution, which introduces the sample area into the current conduit

  carrier and then in the analyzer 6 A precondition for

  necessary for this embodiment to work

  satisfactory is that the piston of the device 13 is now

  in a fixed position during the operating period of the carrier current cycle, and that the pumping rates in channels 4 and 5 are identical. The advantage of this technique lies in the simplicity of the experimental setup; and in the ability to handle small volumes

  anaerobic samples, from a source that gives

  sample, such as a patient, up to

  troduction in the analytical device A disadvantage

  possible lies in the need for an experienced manipulation of

  if the syringe is operated manually.

  It should be emphasized that the modifications of the invention described above do not affect its basic principle. Such modifications may include:

  (a) the replacement of one of the propulsion

  solution, operating in pairs and serving the sample solution circuit (such as pair 2, 3 on the

  Figure 1A) and / or the carrier current circuit (such as

  4, 5 in FIG. 1A), by an opening-closing valve

  re which is in the open position when the corresponding solution propulsion means are active, and which is in the closed position when the corresponding solution propulsion means are inactive;

  (b) the addition to the device of additional means

  (14, 15 in Figure 1 D) by which we can add

  additional currents to the analysis device 6, or extracting additional currents from this device, provided that the flow rates are balanced so that the

  propulsion means 4 introduce into the volumetric duct.

  1 a quantity of liquid exactly equal to that coming out of this conduit at the opposite end, which imposes that the suction speed of the means 5 is exactly equal to the resultant sum of the flow rates of the means 4, 14 and 15 alternatively, the pumping device 5 may be replaced by an open-close valve, with the modifications described in paragraph (a);

  (c) the addition of one or more

  metric 1, 1 ', 1 ", etc., which can be placed in series in the sampling circuit so that each individual volumetric duct is served by a separate carrier current, for the purpose of carrying out analyzes in a number of of analyzers 6, 6 ', 6 ", etc., arranged in parallel, the only necessary condition consisting in the hydrodynamic and hydrostatic equilibrium as well as in an appropriate time sequence for the operating cycles of the sample and carrier circuits ; (d) the possibility of replacing for a short

  duration the hydrostatic control by a hydrodynamic control

  Thus, for example, in the embodiment shown in FIG.

  can be seen in Figure 1A, we can continue to pump the

  sample 9 using the means of propulsion of

  synchronized sample output 2, 3, even after the propulsion means 4, 5 of the power line circuit have

  have been actuated, so that the carrier current 7 is also

  The volume of the sample solution can thus be increased in relation to the volume that can contain the conduit 1 when the solutions are stopped.

  of the sample volume introduced depends on the length of time

  the duration during which the functional cycle of the sampling circuit and the functional cycle of the carrier current circuit overlap each other, as well as

  respective pumping rates of the propulsion means of

  2, 3, 4 and 5 The advantage of this technique, which is characterized by the fact that the hydrostatic control in the sampling circuit and the volumetric duct 1 is replaced, for a definite time, by a hydrodynamic control, is that it opens up possibilities

  flexibility to vary the volume of the

  sample introduced by means of the electronic order

  tronic repetitive start / stop intervals which

  kill the operational cycles of the respective circuits.

  The advantage of this combined hydrostatic and hydrodynamic control is that the reproducibility of the introduced sample volumes depends on an exact definition of the time characteristics of the operational cycles and the pumping and suction speeds of the propulsion means.

  of liquid 2, 3, 4 and 5 The hydrostatic control of the in-

  troduction of the sample area, described previously,

  in which the zone is contained in the volumetric duct

  that 1, is independent of these parameters O With this sample introduction method, the sample can be pre-treated in a very simple way

  before the analysis It is possible to introduce into the sample

  an ion exchanger, a dialyzer, or an apparatus for ex-

  traction, for example, and the treatment may change completely.

  character of the sample A very large sample

  lute may be concentrated, contaminants likely to falsify the analysis may be extracted or adsorbed in a column, or the substances of interest may be

  adsorbed in a column and the eluted product can be

ge to the analyzer.

  It goes without saying that many modifications can

  can be made to the described device and process and

  represented, without departing from the scope of the invention.

Claims (7)

  1 Sample introduction device, characterized   in that it comprises a sampling circuit (2, 3, 3) and a load current circuit (4, 1, 5), these circuits sharing a volumetric duct (1) which is permanently connected to both circuits and opens simultaneously in   the two circuits, these circuits providing and evacuating,   defined time periods, a sample solution (9) and an unsegmented carrier stream solution (7), for the purpose of creating, by means of a determined combination of hydrostatic and hydrodynamic forces, a non-sample area segmented well defined within the volumetric duct, this sample area being transported by the unsegmented carrier current through the carrier current circuit, in order to bring this zone   sample in a flow-through analysis device   tinue (6) which is equipped with a detector.   2 Sample introduction device according to   claim 1, characterized in that the volumetric duct   metric (1), used in common by the sample circuit-   and the carrier current circuit, is a narrow channel whose length and cross-sectional area determine the   volume of the sample area when the sample solution   lon (9) is introduced initially into the volumetric conduit   before being driven by the carrier current to the   continuous flow analysis device (6).   3 Sample introduction device according to -   any of claims 1 or 2, characterized in that   the carrier current circuit (4, 1, 5) is closed at   all the ends and columns of non-segmented liquid   tees within the closed carrier current circuit are held stationary with the exception of the liquid column portion within the volumetric circuit (1) commonly used by the sampling circuit (2, 1, 3) and the carrier current circuit   (4, 1, 5), when the sampling circuit is in   tioning; and in that the sampling circuit is closed at at least one of its two ends, so that   the columns of liquid that are inside the cir-   baked sampling except the column of liquid that is   found in the volumetric circuit (1), can be   immobile suits losing the powerline circuit is in operation. 4 Sample introduction device according to   any of claims 1 to 3, characterized in that   that the duration of the operational cycle of the sample circuit-   extends beyond the beginning of the operational cycle of the   1 C feedcurrent, in order to introduce a volume of the sample solution (9) larger than that which can   contain the volume of the volumetric duct (1).   Sample introduction device according to   any of claims 1 to 4, characterized in that   that several volumetric ducts are connected in series, each volumetric duct is served by a separate carrier current circuit, and each carrier current circuit is connected to a corresponding continuous circulation analysis device. 6 Sample introduction device according to   any of claims 1 to 4, characterized in that   that several volumetric ducts are connected in series and each volumetric duct is served by a circuit   separate sampling, while all the volumetric ducts   metric are served by a single current circuit common   7 Sample introduction device according to   any of claims 1 to 4, characterized in that   a processing station for the sample (9) is placed before the introducer, and this post includes a   ion exchanger, dialyzer or the like.   8 Apparatus for circulation analysis   continuous discrete samples using a current   non-segmented reactor, characterized in that it comprises: the following sample hydrodynamic introduction device   any one of claims 1 to 7; electronic means   means for controlling the duration and sequence of operational cycles of the mechanical means for controlling the movement of liquids in the apparatus; means (2, 3,   4, 5) for propelling, sucking or stopping   within the ducts and circuits of the appli-   the same; and a circulation analysis device (6) and a circulation detector which are arranged so as to   receive the carrier current containing the sample solution lon (9).   Apparatus for the continuous analysis of the composition of a liquid stream according to the claim   8, characterized in that the circulating analysis device   (6) and the circulation detector are located in the sampling circuit (4, 1, 5) in which the sample solution is transported continuously, except for intermittent periods during which the analysis device continuous circulation and the circulation detector are recalibrated or readjusted by means of a reference solution which is transported for this purpose by the sample stream through the detector, in the form of well-defined areas.