Search Images Maps Play YouTube News Gmail Drive More »
Sign in
Screen reader users: click this link for accessible mode. Accessible mode has the same essential features but works better with your reader.

Patents

  1. Advanced Patent Search
Publication numberUS3826615 A
Publication typeGrant
Publication dateJul 30, 1974
Filing dateJun 9, 1972
Priority dateJun 9, 1972
Also published asCA974378A1, DE2329348A1, DE2329348B2
Publication numberUS 3826615 A, US 3826615A, US-A-3826615, US3826615 A, US3826615A
InventorsBellinger S, Dannewitz R, Diebler H, Smythe W
Original AssigneeTechnicon Instr
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Fluid system for inclusion in a total automated fluid system of a sample analyzer
US 3826615 A
Abstract  available in
Images(2)
Previous page
Next page
Claims  available in
Description  (OCR text may contain errors)

1* Km .J. ETAL FLUID SYSTEM FOR INCLUSION IN A TOTAL AUTOMATED FLUID SYSTEM OF A SAMPLE ANALYZER 2 Sliwets-Slmet 1 Filed June 9, 1972 3,826,615 FLUID SYSTEM FOR INCLUSION IN A TOTAL AUTOMATED FLUID SYSTEM OF A SAMPLE ANALYZER William .T. Smythe, Tarrytown, and S. Lawrence Bellinger,

Lake lLuzerne, N.Y., Herman G. Diebler, North Haledon, NJL, and Robert Dannewitz, Yonkers, NY, assignors to Technieon Instruments Corporation, Tarrytown, NY.

Filed June 9, 1972, Ser. No. 261,481 Int. Cl. G011] 1/18, 33/16 U.S. Cl. 23-230 R 18 Claims ABSTRACT OF THE DISCLOSURE A fluid system for inclusion in an automated fluid system for analyzing a series of liquid samples flowing seria tim, the first-mentioned system serving to dilute each sample for subsequent division into a large number of parts. Each diluted part is intended for flow to one of a large number of different subcombinations of the total system. In each of the subcombinations the diluted sample part may receive a special treatment, such as mixing with a particular reagent or reagents under controlled temperature conditions for example, prior to analysis of that sample portion as by photometry for example. Each diluted sample part may be subjected to a different test or analysis. There is involved in the first-mentioned system the same and equal dilution treatment of each sample as the series. Also involved in the first-mentioned system is the effective inhibition of cross contamination of samples from the point of introduction of the samples into the dilution system to the point, after division of the samples as aforesaid, where the samples flow into the respective ones of the aforesaid analysis subeombinations.

BACKGROUND OF THE INVENTION (1) Field of the Invention This invention relates to a system, in automated liquid analysis apparatus of the type wherein a series of samples flow seriatim and a large number of different tests are performed on each sample, for the dilution of the samples and for the distribution of each diluted sample between a large number of units respectively performing the aforesaid tests.

(2) Prior Art Apparatus for the continuous analysis of fluids are well known. Such an apparatus is disclosed in Skeggs US. Pat. 2,797,149, issued June 25, 1957. Skeggs US. Pat. 2,879,- 141, issued Mar. 24, 1959 discloses analysis apparatus of an automated type in which samples are fed in a flowing stream by means of a take-off device which aspirates liquid from each of a plurality of sample containers which are sequentially presented thereto by a sampler assembly. Such apparatus is commonly employed for the analysis of various fluids. Skeggs et al. US. Pat. 3,241,432, issued Mar. 22, 1966 discloses automated apparatus for sequentially performing multiple quantitative analyses on different portions of a single sample of a series of such samples, each analysis being for a different specific sample constituent. As shown and described in the last-mentioned patent by way of example, such automated analysis apparatus may include for analysis purposes a colorimeter for analysis of certain portions of a sample and/or a spectral flame photometer for analysis of one or more other sample portions. However, other conventional photometric analysis devices or ion-selective electrodes, for example, may be used for analysis purposes in similar automated sample analysis apparatus.

In accordance with the analysis procedures illustrated "United States Patent 3826,6 Patented July 30, 1974 ice and described in the aforementioned Skeggs et al. US. Patent, the liquid samples of a series flowing seriatim to anal ysis are separated from one another by immiscible fluid segments such as an inert gas, very often air. As shown and described for example, in that patent, it is also common to flow in such systems segments of Wash solution intermediate successive liquid samples flowing to analysis. These wash solution segments are isolated from the neighboring sample segments by immiscible fluid segments, as pointed out in the aforementioned Skeggs US. patent, the immiscible fluid segments such as air perform a scrubbing action on the tubing, in which the samples flow one after another, and very effectively inhibit cross-contamination between the samples. Such scrubbing is commonly known in the industry as wash between samples. The wash is facilitated by the aforementioned segments of wash solution. The exact degree of facilitation of the wash by the use of the aforementioned wash solution segments is not presently fully known. On the other hand, it is known that the aforesaid scrubbing action or wash of the immiscible fluid segments such as gas is, in and by itself, a very significant factor in preventing cross-contamination of samples flowing in a series, such as contamination by one sample or sample portion by a preceding liquid sample portion.

In the aforementioned Skeggs et al. patent, the fluid system of the sample analyzer includes provision for the distribution of a portion of each sample, flowing as from a sampler cup, directly to one sample analysis channel or cartridge for a specific test, after treatment by reagents and subsequent to dialysis. In other words, this sample portions is not prediluted before passage to the last-mentioned test cartridge. Other portions of that sample are prediluted prior to distribution to respective ones of the analytical cartridges. Such predilution enables each sample to be divided into a greater number of parts for different tests.

Injectors for injecting at a suitable interval a measured volume of an immiscible fluid (for stream segmentation) such as gas into a liquid stream, as in automated analysis of the aforementioned type, are well known. One such injector is illustrated and described in Kassel US. Pat. 3,654,959, issued Apr. 11, 1972. Another such injector is illustrated and described in Hrdina US. Pat. 3,524,366, issued Aug. 18, 1970. This last-mentioned injector is of the type that creates a pulsation in the liquid flow concurrently with the injection into the liquid stream of a volume of an immiscible fluid such as air to segment the liquid stream. In the last-mentioned injector, fluid, which is withdrawn at the time of injection of the air segment, is subsequently replaced in the fluid line. Also, the aforementioned Hrdina patent teaches such injection into a liquid stream while creating in the last-mentioned stream a deliberate pulsation resulting in a zero or negative pressure as aforesaid at the time of the air injection, followed by a positive pulsation as the fluid is readmitted into the fluid line through the apparatus. This practice, while suitable for some analysis techniques, is not suitable for all analysis techniques, especially in those wherein it is desired to avoid pulsation in the fluid line which might interfere with such functions as the precise proportioning of a liquid sample portion with a precise volume of reagent or diluent added to that sample portion upstream of the air injector, under certain circumstances. This is one of many examples wherein in liquid sample analysis of the automated type such as described above, pulsations in a fluid line are undesirable.

It is now desirable to provide for a substantially greater number of analytical tests on a single sample than those illustrated and described in the aforementioned Skeggs et al. patent. For various reasons, it is also desirable to use in such an analyzer a smaller amount of each sample.

One such reason is that the source of the sample may be very limited, such as blood taken from a new-born infant for analysis. Another such reason is that it is desirable to employ in such an analyzer analytical equipment of extreme sensitivity to more precisely measure a constituent of a sample. Such highly sensitive analytical equipment often requires, for handling of samples, substantial dilution treatment prior to analysis. However, in the performance of some analytical tests in some cartridges such predilution may not be employed.

SUMMARY OF THE INVENTION One object is to provide a fluid system for inclusion in a total automated fluid system for analyzing a series of samples flowing seriatim, the first-mentioned system serving to dilute each sample for subsequent division into a large number of parts. Each diluted part is intended for flow to one of a large number of different subcombinations of the total system. In each of the subcombinations the diluted sample part may receive a special treatment, such as mixing with a particular reagent or reagents under controlled temperature conditions for example, prior to analysis of that sample portion as by photometry, for example. Each diluted sample part may be subjected to a different test or analysis.

Another object is to provide in the first-mentioned system the same and equal dilution treatment of each sample of the series. Also involved in the first-mentioned system is the effective inhibition of cross-contamination of samples from the point of introduction of the samples into the dilution system to the point, after the division of the samples as aforesaid, where the samples flow into the respective ones of the aforementioned analysis subcombinations.

A further object is to provide in such a dilution system for the immersion of a sample probe into a sample source such as a cup, for example, in such manner that the sample in the cup, which may be one of a series of cups holding different samples, is pecked for flow through the probe before reimmersion of the probe into the same sample cup for a longer period of time during which last-mentioned period considerably more sample flows through the probe than during the aforementioned pecking of the sample. Each peck may result in only a relatively small portion of sample flow in the probe. Prior to immersions of the probe as aforesaid into the sample cup, aid is flowed through the open free end of the probe, and this produces gas segments or air bubbles segmenting or dividing each sample into a number of liquid segments. This air flow into the probe also produces in addition air bubbles which serve as a barrier in a conventional way between successive samples during intervals in which the probe exists from the sample cup for the last time and is immersed for the first time in the samples of the next following sample cup. Also during this interval the sample probe may be immersed in a wash solution in a suitable container one or more times which results in the How in the probe of an equivalent number of wash solution segments each of which wash solution segments is separated from the neighboring liquid segments by gas segments, according to conventional practice.

The invention further contemplates the junction with the fluid stream flowing from the sample probe of a stream of reagent or diluent which last-mentioned stream is itself segmented by immiscible fluid segments such as gas which may be termed immisicible fluid segments of addition. These gas segments of addition serve several useful purposes. One significant purpose of these gas segments of addition is to facilitate the mixing of each sample with the reagent or diluent as the stream flows subsequently through a mixer of the type which will not destroy the segmentation pattern of the stream and may be a coil for example.

The immiscible fluid segments flowing in the tubular conduit of the probe serves to scrub and cleanse the tubular wall structure of the conduit and prevent cross-contamination between samples and segments of each sample. The immiscible fluid segments of addition, which join the stream downstream from the sample probe tube, have a similar scrubbing action, and similarly effectively tend to prevent cross-contamination between successive samples and cross-contamination between segments of the same sample. Subsequent to the aforementioned mixing of the sample with the reagent or diluent, which dilution may be in the order of six to one and in which samplediluent stream the flow rate is considerably higher than the flow rate in the probe tube, the gas is substantially entirely removed from the stream. The gas is removed by a debubbler.

Immediately downstream of the debubbler, a sequence of bubbles is injected through an air conduit into the stream flowing in the conduit of the sample-diluent by an intermittently driven pump, which is a part of an air injector. The invention contemplates the introduction into the debubbled sample-diluent stream of gas bubbles by the last-mentioned air injector system to create a segmentation pattern immediately downstream of the debubbler which segmentation pattern includes a plurality of immiscible fluid segments associated with each sample, some of which gas or air segments serve as barriers between plural liquid segments of each sample. The last-mentioned gas segments also serve to scrub the tubular Wall structure of the conduit in which the stream flows, and in a very real sense the last-mentioned gas segments replace those previously in the stream though they may equal a smaller number in the stream associated with each sample than those previously associated with each sample. These gas segments introduced by the aforementioned air injector are of substantially larger volume than those gas segments previously described. As previously indicated they are introduced after the aforementioned debubbling of the stream to isolate sample segments and provide optimum scrubbing action as well as meeting the volumetric requirements for re-sampling.

The invention further contemplates, that at the time the last-mentioned large air bubbles are introduced into the stream by the air injector, that a volume of fluid be removed from the stream, the purpose of which, among other things, is to prevent a surge in the fluid stream which surge might prejudice the aforementioned metering of the diluent with the sample. The amount of fluid which is removed by the air injector apparatus in the last-mentioned manner may be proportional or equal to the volume of air injected into the stream by the air injector to create each new gas segment in the stream. The volumetric rate of air injection, being proportional or equal to the rate of fluid removal, also contributes to the minimization of surges in the system. The periodicity of the injection by the aforementioned air injector of a gas segment into the stream is controlled in accordance with the flow of each sample to the point where the stream is debubbled as aforesaid upstream of the air injector. The periodicity of the air injector introduction of each gas segment associated with each sample, previously treated in the aforementioned manner, is also controlled. It is to be understood from the foregoing that the timing or periodicity of the removal of a fluid in communication with the sample-reagent stream by the air injector assembly is also dependent on the periodicity of the air injector introduction of gas segments into the fluid stream. As previously indicated, the air injector includes as a part thereof a conduit joined to the samplediluent stream conduit through the debubbler and the fluid is removed by the air injector apparatus by a negative pressure induced in that conduit which is to convey away at intervals portions of the aforementioned fluid. The fluid removed by the air injector apparatus may be almost entirely gaseous in content, and in the presently contemplated form of the invention this is the case.

It is a feature of the invention that, downstream of the aforementioned debubbler, the stream segmented by the air injector continues its flow at a relatively high velocity to a riser, for example, from which riser the samplediluent stream is resampled respectively by branch conduits off the riser for tests in a large number of analytical cartridges. A portion of each sample segment flows into each resampling or branch line from the riser together with a portion of each stream-segmenting gas bubble to thereby continue the segmentation pattern after resampling. The invention further contemplates an improved manifold which includes many of the aforementioned fluid conduits.

BRIEF DESCRIPTION OF THE DRAWINGS In the drawings:

FIG. 1 is a diagrammatic view of a fluid system for inclusion in a total fluid system of a sampler analyzer, embodying the invention;

FIG. 2 is a front elevational view in somewhat diagrammatic form illustrating the manifold utilized in the fluid system of FIG. 1;

FIG. 3 is a diagrammatic view illustrating the flow pattern in a portion of the fluid system of FIG. 1;

FIG. 4 is a diagrammatic view illustrating the flow pattern in another portion of the fluid system of FIG. 1; and

FIG. 5 is a diagrammatic view illustrating the flow pattern in still another portion of the system of FIG. 1.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS In the drawings and with particular reference to FIG. 1 there is indicated generally at a sample source. The source 10 may take the form of a sampler such as illustrated in De Jong US. Pat. 3,134,263, issued May 26, 1964, and include a turntable 12. The sampler includes a probe 14 for immersion in successive sample cups in circular array on the turntable and containing a series of different samples which by way of illustration and not by way of limitation may be blood samples. Each sample cup of the series may be indexed on angular movement of the table 12 with the probe 14. One such sample cup is indicated at 18 and the next following cup at 20. The sampler also includes a wash receptacle 22 containing a wash solution in which the probe 14 is immersed between successive samples and which wash solution is aspirated by the probe 14 on immersion of the probe in the wash solution. The probe 14 may be immersed as many times in the wash solution as found desirable, and the probe may be immersed periodically in standard solutions not shown suitably supported in the sampler. When the probe 14 leaves the sample liquid or the wash solution or standard air is aspirated into the then open end of the probe and this air flow forms in a conventional way immiscible fluid segments in the stream flowing in the probe 14 on reimmersion of the probe 14 into a liquid, thus producing a segmented liquid stream, all liquid segments of which are bounded by immiscible fluid segments of a gas such as air. The probe 14 is provided with a movable support 16 which enables the probe to move between successive samples and to the wash solution between successive samples and also to any standards employed as previously indicated. The sampler may be under the control of a computer not shown which computer serves, among other functions, to control the movements of the probe 14.

The outlet of the probe 14 is coupled to a pump tube 24 at the inlet end thereof which pump tube 24 may be of the compressible type coacting with peristaltic pump 26 to aspirate fluids from the probe 14. The pump 26 may be of the type illustrated and described in co-pending Kling U.S. patent application Ser. No. 71,773, filed Sept. 14, 1970. It is well known that in the use of such peristaltic pumps there is some degree of pulsation in the fluid flow therethrough and that when a compression member, not

shown, of the pump engages compressible tube such as the tube 24 a back-pressure is momentarily developed. Such back-pressure would interfere with the uniformity of the flow of gas into the probe when the probe is exposed to the ambient atmosphere, having left the liquid, and because uniformity of aspiration volumes of air into the probe 14 is highly advantageous for proportioning purposes there is a control connection, not shown, between the pump 26 and the sampler 10 or between the pump 26 and the unit controlling the operation of the sampler such as the aforementioned non-illustrated computer. This control assures that no back-pressure will be created in the probe 14 when the probe has left a liquid and the open end of the probe is exposed to the ambient atmosphere for gas flow thereinto.

The outlet of the compressible pump tube 24 is connected to the inlet end of conduit 28. A compressible pump tube 30 similar to the pump tube 24 is provided having an inlet end for aspirating a reagent or diluent from a source, not shown. As shown in FIG. 1 a tube 32 is provided having an inlet end connected to a non-illustrated source of air under pressure. An accumulator indicated generally at 34 is interposed intermediate the ends of the air line 32 which accumulator may be of the type illustrated and described in Kassel US. Pat. 3,654,959, issued Apr. 11, 1972. The function of the accumulator 34 is to release at controlled intervals precise volumes of air to flow to one leg of T connection 36 to which the outlet end of the compressible tube 30 is connected, so that these volumes of air released by the accumulator 34 at a pressure more than that in the pump tube 39 form gas segments in the diluent stream exiting from the remaining leg of the T connection 36, the segmentation being very precise and uniform. If desired, the gas supplied to the condiut 32 may be an inert gas other than air.

As shown in FIGS. 1 and 2 the last-mentioned outlet of the T connection 36 is in communication with one leg of T connection 38. Another leg of the T connection 38 is coupled to the outlet end of sample conduit 28. The remaining leg of the T connection 33 provides for the outflow of the combined sample and diluent streams to the inlet end of a conduit 39 in which is interposed a static mixer 40 which may be of the coil type. The mixing of the sample and the diluent in the segmented stream flowing in the conduit 39 takes place in the mixer 40 and the outlet end of the conduit 39 is connected to a fitting 42 through an arm 44 as shown in FIGS. 1 and 2. Another arm 46 of the fitting 42 is coupled to the inlet end of a conduit 47 for the flow therethrough of the sample-diluent stream segmented in a manner differently from the segmentation pattern of the stream entering the arm 44 through the tube 39. The fitting 42 has an arm 48 the function of which is that of debubbling the stream previously segmented in the aforementioned manner, that is, by the air segments admitted to the system through the probe 14 and the air or gas segments admitted to the system through the accumulator-controlled air or gas line 32. The fitting 42 is provided immediately downstream from the exit port provided by the arm 48 with a port 50 shown in FIG. 1 as constituted by another arm of the fitting 42. The port 50 is an air injection port for the pe riodic admission through the port 50 into the samplediluent stream of periodic pulses of gas or air which form immiscible fluid segments in the: sample-diluent stream which exits from the arm 46 as aforesaid into the inlet end of conduit 47.

Conduit 56 has an inlet end thereof (FIGS. 1 and 2) coupled to debubbler arm 48 of fitting '42, and the outlet end of conduit 56 is coupled to one arm of T fitting 58. Another arm of the T fitting 58 is coupled to the inlet end of conduit 60. The remaining arm of the T fitting 58, the arm opposite the first-mentioned arm thereof, is coupled to the inlet end of conduit 62. The outlet end of conduit 62 is connected to pump 63. Pump 63 is operated continuously during the operation of the fluid 7 system. The outlet of pump 63 is coupled to the inlet end of conduit 64. The outlet end of conduit 64 is connected to one arm of a T fitting 66 one function of which T fitting is to convey fluid in line 64 to waste as will appear more fully hereinafter.

The volumetric rate of flow in the conduit 56 connected to arm 48 is substantially less than the volumetric rate of flow in the arms 44 and 46 conveying the samplediluent stream to the conduit 4-7 previously described.

Aforementioned conduit 60 has a compressible portion coacting with a compression member, not shown, of a peristaltic pump 61 which pump 61, when in operation, pumps fluid through the line 60, receiving this fluid from the T fitting 58, to the outlet of conduit 60 connected to aforementioned T fitting 66 having the aforementioned discharge to waste. This waste is conveyed in conduit 72 having an inlet end connected to a corresponding arm of T fitting 66 and having an outlet end directed to a drain or to a suitable waste receptacle not shown. Aforementioned conduit 52, having an outlet end discharging to air injection port 50, also has a compressible portion coacting with a compression member, not shown, of pump 61. The inlet end of conduit 52 may be disposed in a source of a suitable inert gas or left exposed to the ambient atmosphere for flow therethrough of gas delivered to the injection port 50 through the conduit 52 when the pump 61 is in operation.

Pump 61 is operated preferably at non-uniform intervals, but at controlled intervals, through a suitable control unit 63a of a conventional design. The pump 61 is operated in the aforementioned manner on command from the sampler 10. A cable 65 has one end thereof connected to an outlet terminal of the sampler and the other end thereof connected to an input terminal of the control unit 63. A cable 67 has one end thereof connected to an output terminal of the control unit 63 and the other end thereof connected to an input terminal of the pump 61.

The Operation of the pump 61 is such that when the pump 61 is operative to inject air through the conduit 52 and the air injection port 50 into the sample-diluent stream, the pump 61 is also operative to withdraw fluid at a proportional or the same volumetric rate through the conduit 60 connected to fitting 58, through which fitting 58 the fluid debubbled through the debubbler arm 48 connected to the conduit 56 flows to enter the conduit 62 as shown in FIGS. 1 and 2. The fluid flowing in conduit 56 may include a small amount of liquid. If desired, a pump of a type other than the peristaltic type may be utilized in place of the pump 61, and it will be obvious from the foregoing that, if desired, rather than utilizing a single pump coacting with conduits 52 and 60, each of the last-mentioned conduits may be acted upon by a separate pump. The pump 61 with its associated parts is herein referred to as an air injector. Of course, it is recognized that this air injector also has a fluid removal function.

As previously indicated the air segments injected into the sample-diluent stream by the air injector 61 are of substantial size and of a size or volume substantially larger than the air segments in the probe tube 24 and the air segments of addition flowing in conduit 39. Also as previously indicated, pulsations in the sample-diluent stream in both the aforementioned conduits 39 and 47 at the time of the injection of each air segment by the air injector 61 are effectively inhibited by the aforementioned fluid withdrawal function of the air injector 61.

The segmented sample-diluent stream issuing from the fitting 42 into the inlet end of the conduit 47 and through the outlet end of this conduit is appropriately resampled in any convenient manner so that the segmented samplediluent stream serves a greater number of analytical cartridges each performing a different test as aforesaid.

In the form illustrated by way of example and not by limitation, the outlet of the conduit 47 is coupled to the inlet end of a riser or substantially vertically arranged conduit 74 to which are coupled (FIG. 1) the inlet ends of resampling conduits 76 in staggered relation as illustrated in the last-mentioned view. A plurality of pumps 78, are provided one interposed in each resampling conduit 76. The pumps 78 convey fluid into respective resampling lines 76 toward the respective outlet ends of the resampling conduit 76.

The manifold of FIG. 2 is shown in the attitude in which it may be suitably secured as by fasteners, not shown, to a panel on which a great number of other, different manifolds are also secured in an analytical chemistry module, all of which other manifolds may be served by the dilution manifold of FIG. 2 and which other manifolds perform different analytical tests on each segmented sample.

Nipple-equipped fitting 51 is secured on the block of manifold 29 in any suitable manner and this fitting S1 is connected with various fluid conduits as shown in FIG. 2. Nipple-equipped fitting 70 may be of any conventional construction and it too is secured to the block of manifold 29 in fluid flow connection with the various conduits shown in FIGS. 1 and 2.

As previously indicated, a large number of analytical cartridges are provided for performing different tests on the same sample, only a few of these cartridges being shown and being indicated at 80. Each cartridge 80 is associated with a respective one of the resampling conduits 76, each resampling conduit 76 having its outlet end connected to the inlet end of the respective cartridge. As previously indicated the segmentation of the sample-diluent stream flowing in conduit 47 is maintained as each aliquot of this stream is delivered to a respective one of the cartridges 80.

The manner of performing the particular analyses in the cartridges 80 need not be described here. Certain of the analyses may be in accordance with the disclosure of the aforementioned Skeggs et al. patent. Other analyses may be performed by direct potentiometric measurements as described and illustrated in Ast et al. US. patent application Ser. No. 242,556, filed Apr. 10, 1972 and co-pending with this application. The results of the analyses may be suitably processed for suitable display in a manner not shown. The upper limit of the analytical cartridges which may be served by a single predilution manifold such as that shown in FIGS. 1 and 2 is not presently known but it is known that the number is in excess of 20.

In FIGS. 3, 4 and 5 the flow or segmentation patterns of the stream flowing from the probe 14 and to which other streams are joined as aforesaid is shown respectively in conduit 24, conduit 39 and conduit 47. It should be noted that the aforementioned fitting 42 appears in both FIG. 4 and in FIG. 5.

Referring now to FIG. 3, as previously indicated the illustrated system provides for the immersion of the sample probe 14 into a sample source such as the cup 18 in such manner that the sample in the cup, which may be one of a series of cups holding different samples, is peeked for flow through the probe before reimmersion of the probe into the same sample cup for a longer period of time during which more sample flows through the probe than during the aforementioned pecking of the sample. Each peck may result in only a relatively small portion of sample flow in the probe. Prior to immersion of the probe as aforesaid into the sample cup, air is flowed through the open free end of the probe, on these exits of the probe from liquid and exposure to ambient atmos phere, producing gas segments or air bubbles segmenting the stream or dividing each sample into a number of liquid segments. This air flow into the probe also produces, in addition, air bubbles which serve as a barrier in a conventional Way between successive samples during the interval in which the probe exits from the sample cup for the last time and is immersed for the first time in the sample of the next following sample cup 20. Also during this interval the sample probe may be immersed in a wash solution in the container 22 one or more times which results in the flow in the probe of an equivalent number of wash solution segments each of which wash solution segments is separated from the neighboring liquid segments by gas segments. For the sake of convenience the segments of the leading sample are designated S1, the segments of the following sample S2 and the first segment of the next following sample as at S3. The air or gas segments are designated A and the wash solution segments W.

Referring again to FIG. 3, when the probe 14 leaves the wash solution in the receptacle 22 and the open free end thereof is exposed to the ambient atmosphere gas flows into the probe forming gas segment 85 trailing the slug of wash solution in the probe tube 24. The probe 14 then peeks sample 1 drawing into the probe tube sample slug 90 followed by an air segment 85. The probe then peeks sample ll for the second time resulting in liquid slug 92 in the probe tube 24 followed by an air segment 85. The probe 14 is then reimmersed in sample 1 over a considerable interval of time, say on the order of 12 or 13 seconds before emerging from sample 1 for the last time, which results in the formation of a long liquid slug 94 and an air segment 85 following it. The last-mentioned air slug is followed by a slug of wash solution from receptacle 22.

As previously indicated the aforementioned sample peeks may be greater or smaller in number and the duration of such peeks may be controlled as well as the duration of the much longer dwell time of the probe in the sample after the last peck. The number of immersions of the probe in the wash solution between samples may also be greater than the single immersion illustrated and described. The movement of the probe 14 may be dictated by the aforementioned non-illustrated computer. Sample fiow in conduit 24 may be at the rate of approximately 440 mL/min. The total sampling time of the probe for any one sample may be approximately 18 seconds.

Diluent may be caused to flow by pressure differential into the inlet of conduit 30 at a flow rate of approximately 2100 ml./min. to be joined to the sample stream at the fitting 36 of FIGS. 1 and 2. Air or gas from the aforementioned non-illustrated source flowing into the inlet end of conduit 32 for control by accumulator 34 (FIG. 1) may be admitted to the combined sample-diluent stream at a rate of approximately 90 bubbles a minute. Waste in conduit flows at a rate of approximately 610 mL/min. The outflow from the predilution manifold of FIG. 2 through conduit 47 to distribution conduit 74 (FIG. 1) is approximately 2020 mL/min. As previously indicated the intervals of injection of these air bubbles from the accumulator 34 is closely phased with the movements of the sample probe 14, and also as previously indicated the volumetric rate of flow of air into the probe 14 is very carefully regulated so that air or gas bubbles in conduit 24 are of uniform size.

The larger internal diameter of the conduit 39 receiving the sample-diluent stream with air segments of addition from conduit 32 forms a liquid segment and gas segment pattern shown in FIG. 4. There may be approximately twenty-seven gas segments of addition associated with each sample which occlude conduit 39. As the internal diameter of the conduit 39 shown in FIG. 4 is larger than the internal diameter of the conduit 24 the air segments produced through the probe 14 and indicated at 85 are not of suflicient size to occlude the internal diameter of the conduit 39. As will be seen in FIG. 4 one liquid segment flowing in conduit 39 is a combination of a segment of sample 1 and some wash solution.

Referring to FIGS. 4 and 5, all the gas segments in the stream are removed from the stream through debubbler arm 48 of FIGS. 1 and 2. Referring now to FIG. 5, immediately downstream in the sample-diluent stream from the debubbler arm 42 air injector port 50 (FIG. 1) of fitting 42 injects pulses of air through the action of the injector 61 under the control of controller 63a connected to the pump 61 and the sampler by cables 67 and 65 indirectly under the control of the sampler probe. The first of these gas segments from port 50) associated with sample 2, for example is injected into the last liquid segment of sample 1. The bubbles or gas segments injected by the air injector 61 occlude conduit 47, and are considerably larger for the above-described subsequent resampling from conduit 74. This first large bubble prevents the forward contaminating flow in the stream of sample 2 which would contaminate sample 1, and it will be noted that this large air bubble and the next following one generated by the air injector 61 bracket a portion of sample 1, the wash solution W and a portion of sample 2. Obviously this particular liquid segment designated 98 in FIG. 5 is not uscful for analysis purposes because of the aforementioned combination of samples 1 and 2 and the wash solution. In other words, it is a contaminated liquid segment.

The next two following air bubbles injected by air injector 61 are at relatively short intervals as indicated in FIG. 5 and following the second of the last-mentioned air bubbles there is a long segment of sample 2 which is essentially free from any contamination and is useful for analysis purposes. This long segment is designated 104 and the preceding liquid segment of sample 2 is designated 102. The segment of sample 2 preceding the segment 102 is designated 100. Following the last-mentioned series of bubbles injected by the air injector 61 the cycle is repeated with reference to sample 3. As previously indicated, at the time the larger air or gas segments are introduced by the air injector into the liquid stream, fluid is withdrawn for the aforementioned purpose by the injector 61 through conduit 60 joined to conduit 56 of FIG. 1.

It will be clearly understood from the foregoing that the previously stated objectives of the fluid system of the invention are achieved. In accordance with the invention, only aproximately .227 ml. of each sample of a series is required for the analysis system which may have different analytical cartridges in excess of 20 in number, each cartridge performing a different test on the same sample. The sample requirement of the analytical equipment that evolved from the aforementioned Skeggs et al. patent apparatus require approximately 2 ml. of each sample, and the number of tests or different analyses performed on each sample were considerably fewer in number than the number of different tests possible with the use of the fluid system of the invention. In addition, the equipment that evolved from the aforementioned Skeggs et al. patent might run between approximately 60 and samples per hour, whereas the analytical system in which the fluid system of the invention is incorporated may handle in excess of different samples per hour.

It will be understood from the foregoing that the gas segments introduced into the system shown in FIGS. 1 and 2 through the probe 14 have a highly desirable scrubbing or washing action on the probe and the successively communicating conduits 24 and 28, and very effectively tend to prevent crosscontamination between samples or sample segments flowing seriatimi. It will also be understood that diluent is combined with the sample stream at a high volumetric ratio, and that the diluent is segmented by gas segments of addition which have a scrubbing action on the wall structure of the tubing from the point of introduction of the segmented diluent stream into the sample stream to the point where all the gas segments in the sample-diluent stream are removed in the fitting 42, and hence this section of the tubular wall structure within which the segmented sample-diluent stream flows is maintained in such condition that there is little, if any, likelihood of contamination of one sample with the next following sample or for that matter between sample segments.

The advantages of the gas injector which injects gas into the fitting 42 as aforesaid, which air injector also serves for the removal of fluid permanently from the fluid system, have already been enumerated. The gas segments injected into the system by the air injector in the fitting 42 serve the useful purpose of replacing previous gas segmentation of the sample-diluent stream and provide sufficiently large gas segments to enable resampling of the segmented sample-diluent stream in the distribution manifold to the various analytical cartridges, as from the conduit 74. The large gas segments also scrub the tubing walls and eflectively tend to prevent cross-contamination between sample segments. While not previously mentioned, in a system having such high sampling rates per hour it would be diificult, if not impossible, to introduce these large gas segments into the fluid system through the probe because of the length of time which would be required for the flow into the probe of such large volumes of gas.

While one preferred embodiment of the invention has been illustrated in the drawings and several have been described, it will be apparent, especially to those versed in the art, that the fluid system is susceptible of taking other forms and is susceptible of various changes in details without departing from the principles of the invention.

What is claimed is:

1. An automated fluid sample analyzer, comprising: means for flowing along a first conduit, a stream of sample liquid segmented by a separating fluid immiscible with the sample, means in said conduit for removing a controlled volume of said stream from said conduit comprising a volume of said separating fluid, and a dosage device downstream from said fluid-removing means and con nected to said conduit for introducing a proportional volume of fluid into said stream.

2. Apparatus as defined in claim 1, wherein: said dos age device introduces fluid in the form of plural gaseous segments into said stream.

3. Apparatus as defined in claim 1, wherein: said fluid sample stream comprises plural samples, said separating fluid being gaseous, said means flowing aid plurality of samples comprising probe means for introducing said samples along a second conduit for introduction into said first conduit, said probe means being operative to introduce at least one gaseous segment intermediate adjacent samples and at least one gaseous segment within each sample to be passed along said second conduit, said gaseous segments bening operative to occlude, at least, said conduit.

4. Apparatus as defined in claim 1, wherein: said sample stream comprises plural samples, said flowing means includes probe means and sample supply means for presenting successive sample volumes to said probe means, said probe means being operative to be repeatedly immersed into each sample volume presented thereto.

5. Apparatus as defined in claim 4, wherein: said sample stream comprises plural samples, said sample supply means further includes a wash reservoir, said probe means being immersed into said wash reservoir between immersion in successive sample volumes.

6. Apparatus as defined in claim 5, wherein: said probe means is controlled to be immersed within said wash reservoir between immersions in successive sample volumes and to be repeatedly immersed in each sample volume.

7. An automated fluid sample analyzer for flowing a plurality of liquid samples along a first conduit in sequential fashion as a continuous stream in which adjacent samples are separated from one another by a separating fluid in the form of immiscible fluid segments, comprising: fluid-removing means connected to said conduit for removing said separating fluid from said stream, fluid-introducing means immediately downstream of said fluid-removing means connected to said conduit for introducing into said stream a separating fluid in the form of immiscible fluid segments at controlled and repetitive intervals with reference to the respective samples to prevent intercontamination of liquid sample segments of said stream, the volume of each of the last-mentioned immiscible fluid segments being greater than the volume of the first-mentioned immiscible fluid segments, and resampling means downstream from said fluid introducing means for distribution of said stream to plural analysis conduits.

8. Apparatus as defined in claim 7, further including means for introducing a diluent into said segmented sample stream through a conduit portion in communication with said first conduit.

9. Apparatus as defined in claim 7, further including means for introducing a diluent stream segmented by segments of a separating fluid into said segmented sample stream through a conduit portion in communication with said first conduit, all of said segments of said separating fluid being removed from said sample-diluent stream by said fluid-removing means.

10. Apparatus as defined in claim 9, wherein: said separating fluid is a gas and said fluid-removing means comprises a debubbler.

11. Apparatus as defined in claim 7, wherein: said fluid-removing means includes means for relieving pressure in said sample stream while said fluid-introducing means injects an immiscible fluid segment into said stream.

12. An automated liquid sample analyzer comprising: means for flowing a plurality of liquid samples along a first conduit in sequential fashion as a continuous stream in which adjacent samples are separated from one another by a separating fluid in the form of immiscible fluid segments, fluid-removing means connected to said conduit for removing said separating fluid from said stream, and fluidintroducing means connected to said conduit immediately downstream of said fluid removing means for introducing into said stream a separating fluid in the form of immiscible fluid segments at controlled and repetitive intervals with reference to the respective samples, said fluidintroducing means comprising means to introduce such fluid segments in at least two unequal intervals in each sample, whereby each sample has at least one relatively short liquid segment and a longer liquid segment.

13. Apparatus as defined in claim 12, wherein: the volume of an immiscible fluid segment introduced into said stream by said fluid-introducing means is substantially equal to the volume of said stream removed by said fluidremoving means.

14. A method of treating a fluid for analysis, comprising the steps of:

flowing liquid sample along a conduit while segmenting the sample with a separating fluid in the form of immiscible fluid segments;

removing a controlled volume of said stream comprising a volume of said separating fluid; and

downstream introducing a proportional volume of fluid into said stream. 15. A method of treating a fluid for analysis, comprising the steps of:

flowing a plurality of liquid samples along a conduit in sequential fashion as a continuous stream in which adjacent samples are separated from one another by a separating fluid in the form of immiscible fluid segments; removing said separating fluid from said stream; immediately downstream introducing into said stream a separating fluid in the form of immiscible fluid segments at controlled and repetitive intervals with reference to the respective samples to prevent intercontamination of liquid sample segments of said stream, the volume of each of the last-mentioned immiscible fluid segments being greater than the volume of the first-mentioned immiscible fluid segments; and

resampling downstream from said fluid introduction, to distribute said stream to plural analysis conduits.

16. The method as defined in claim 15, further including the step of introducing a diluent into said segmented sample stream prior to said fluid removal.

17. The method as defined in claim 15, further including the step of introducing a gas segmented diluent stream 13 14 into said segmented sample stream prior to said fluid References Cited removal, said separating fluid being a gas. UNI

18. A method for treating a fluid for analysis, compris- TED STATITZS PATENTS ing the steps 3,186,235 1/1965 Ferrari 23--253 X flowing a plurality of liquid samples along a conduit 3,241,432 3/1966 Skeggs 23-453 X in sequential fashion as a continuous stream in which 5 3,435,684 4/1969 Smythe 23253 X adjacent samples are separated from one another by a 3,484,170 12/1969 Smythe X separating fluid in the form of immiscible fluid seg- 3,551,063 12/1970 Smythe i 3- X ments; 3,583,232 6/1971 Isreel et al. 23-259 UX removing said separating fluid from said stream; and 3'600953 8/1971 Israel at immediately downstream introducing into said stream a 10 3,627,495 12/1971 Adler et X separating fluid in the form of immiscible fluid seg- 3,635,680 1/1972 Peoples 23-259 X ments at controlled and repetitive intervals with refer ence to the respective samples, said fluid introduction RONALD SERWIN Pnmary {Bummer comprising introducing such fluid segments in at least r U S C1 X R two unequal intervals in each sample, whereby each R 259 sample has at least one relatively short liquid segment and a longer liquid segment.

Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US3876374 *Mar 22, 1974Apr 8, 1975Technicon InstrMethod and apparatus for automated quantitative fluid analysis
US4015938 *Nov 18, 1975Apr 5, 1977Technicon Instruments CorporationContinuous flow
US4049381 *Mar 23, 1976Sep 20, 1977Technicon Instruments CorporationObtaining a concentration gradient
US4053282 *Feb 26, 1976Oct 11, 1977Hach Chemical CompanyMethod and apparatus for sampling impure water
US4058363 *Feb 25, 1976Nov 15, 1977Silbert Jerome AMethod and apparatus for sterile handling of fluids
US4188466 *Jul 6, 1977Feb 12, 1980I.N.R.A.By enzymatic hydrolysis
US4219530 *Jan 27, 1978Aug 26, 1980Brinkmann Instruments, Inc.Apparatus for analyzing biological specimens
US4331767 *Sep 4, 1979May 25, 1982Fujisawa Pharmaceutical Co., Ltd.Immobilized enzyme column
US4853336 *Feb 2, 1987Aug 1, 1989Technicon Instruments CorporationSingle channel continuous flow system
US5134079 *Mar 27, 1989Jul 28, 1992International Technidyne Corp.Fluid sample collection and delivery system and methods particularly adapted for body fluid sampling
US7860542Dec 21, 2005Dec 28, 2010Optiscan Biomedical CorporationAnalyte detection system with reduced sample volume
US7860543Aug 15, 2006Dec 28, 2010Optiscan Biomedical CorporationAnalyte detection system with reduced sample volume
EP0109278A1 *Nov 11, 1983May 23, 1984TECHNICON INSTRUMENTS CORPORATION (a New York corporation)Single channel continuous flow system
EP0200235A2Nov 11, 1983Nov 5, 1986TECHNICON INSTRUMENTS CORPORATION(a Delaware corporation)Continuous flow method
Classifications
U.S. Classification436/53, 422/82
International ClassificationG01N35/08, G01F13/00, A61B5/00, G01N1/00
Cooperative ClassificationG01N35/08
European ClassificationG01N35/08
Legal Events
DateCodeEventDescription
Jul 5, 1988ASAssignment
Owner name: TECHNICON INSTRUMENTS CORPORATION
Free format text: MERGER;ASSIGNOR:REVGROUP PANTRY MIRROR CORP.;REEL/FRAME:004912/0740
Effective date: 19871231