US3435684A - Method and apparatus for the dilution and division of a stream of samples for continuous analysis - Google Patents

Method and apparatus for the dilution and division of a stream of samples for continuous analysis Download PDF

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Publication number
US3435684A
US3435684A US672055A US3435684DA US3435684A US 3435684 A US3435684 A US 3435684A US 672055 A US672055 A US 672055A US 3435684D A US3435684D A US 3435684DA US 3435684 A US3435684 A US 3435684A
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Prior art keywords
stream
sample
samples
coupled
quotient
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US672055A
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English (en)
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William J Smythe
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Technicon Corp
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Technicon Corp
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00Sampling; Preparing specimens for investigation
    • G01N1/28Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/38Diluting, dispersing or mixing samples
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/08Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00Chemistry: analytical and immunological testing
    • Y10T436/11Automated chemical analysis
    • Y10T436/117497Automated chemical analysis with a continuously flowing sample or carrier stream
    • Y10T436/118339Automated chemical analysis with a continuously flowing sample or carrier stream with formation of a segmented stream

Definitions

  • a system for prediluting a flowing stream of samples and for dividing the diluted stream into a plurality of quotient streams includes a peristaltic type pump coupled to an olf-take tube for aspirating samples, from respective containers, interspersed with relatively large gas segments.
  • a valved pump tube periodically adds relatively small gas segments to a separate stream of diluent and this segmentized diluent stream is added to the sample stream and is mixed therewith.
  • Each of the relatively small gas segments is withdrawn and the debubbled, mixed, sum stream is divided into a plurality of quotient streams, each having a portion of each sample and each relatively large gas segment.
  • This invention relates to the automatic, continuous analysis of a flowing stream of liquids, and, more particularly, to a system for continuously dividing the initial sample stream into a plurality of quotient streams, some of which are diluted.
  • the principle of this invention is comprised in a system for uniformly diluting a flowing stream of sequential liquid samples in which successive liquid samples are spaced apart by a gas segment, and for dividing this diluting stream into a plurality of quotient streams.
  • the system includes means for transmitting through a conduit an initial stream of sequential liquid samples, each spaced from the succeeding sample by a relatively large gas segment; means for continuously adding relatively small, spaced apart gas segments, which are just large enough to occlude the conduit, to a stream of diluent and adding this combined stream to the initial stream; means for intramixing the liquid segments in the stream of sample plus diluent; means for continuously removing a portion of the mixed stream at a volumetric rate just great enough to remove each of the relatively small gas segments while leaving at least enough of each of the relatively large gas segments to occlude the conduit; and means for dividing the remaining portion of the stream into a plurality of quotient streams for analysis, each quotient stream containing a portion of the relatively large gas segment adequate to occlude the conduit.
  • FIGURE 1 is a diagram of a flow system embodying this invention.
  • FIGURE 2 is a perspective view of a detail of the flow system.
  • FIGURE 1 includes a sample supply apparatus 10, such as is shown in US. Patent No. 3,230,776 supra, having a carrier 12 supporting a plurality of containers 14 for liquid samples, a container 16 for a wash liquid, and an oif-take tube 18 which has an inlet which is inserted sequentially into each of said sample containers, and between successive containers is inserted into the wash container 16.
  • the outlet end of the off-take tube 18 is coupled by a conduit 20 to a junction 22 having an inlet 24 and five outlets 26, 28, 30, 32 and 34.
  • Pump tubes 36, 38, 40 and 42 are respectively connected to the outlets 26, 28, 30 and 32. These pump tubes are disposed in a peristaltic type pump P, such as is shown in US. Patent No.
  • 3,306,229 which includes a platen and a plurality of rollers for progressively advancing fluids through the pump tubes.
  • This pump also has an air bar 44 for occluding one or more pump tubes and for intermittently and periodically releasing such pump tubes, providing a valving function.
  • the outlet 34 is conected to one end of a pump tube 46, whose other end is coupled to one inlet 48 of a junction 50 having an additional inlet 52 and an outlet 54.
  • a pump tube 56 has its inlet end coupled to a source of relatively inert gas G, such as the atmosphere, and its outlet coupled to an inlet 58 of a junction 60 having another inlet 62 and an outlet 64.
  • the pump tube 56 is so disposed in the pump as to be occluded by the air bar 44.
  • a pump tube 66 has its inlet end coupled to a source of diluent D, such as water, and its outlet coupled to the inlet 62.
  • the outlet 64 is coupled by a conduit 67 to the inlet 52.
  • the outlet 54 is coupled to the inlet of a mixing coil 68 whose outlet is coupled by a conduit 69 to the inlet 70 of a junction 72.
  • the junction 72 has two outlets 74 and 76.
  • a pump tube 78 has its inlet end coupled to the outlet 74.
  • the outlet 76 is coupled to a plurality of serially connected junctions 80, 82, 84, 86, 88, 90, 92, and 94, each having an outlet coupled to a respective one of a plurality of pump tubes 98, 100, 102, 104, 106, 108, 110 and 112.
  • Each of these tubes 98, 100, 102, 104, 106, 108, 110 and 112 is coupled to an inlet of a respective junction 116, 118, 120, 122, 124, 126, 128 and 130.
  • each of the pump tubes 36, 38, 40 and 42 is coupled to an inlet of a respective junction 134, 136, 138 and 140.
  • junc tions 134, 136, 138 and 140 respectively form parts of analysis manifolds, for the determination of respective constituents, which do require predilution of the sample, according to this invention, for example, albumin, total protein, chloride, carbon dioxide, sodium, potassium, glucose, and blood-urea-nitrogen.
  • the off-take tube is disposed in a sample container 14 and withdraws sample liquid at a predetermined rate, such as 2 ml./sec. After an interval of time the off-take tube is withdrawn and, advantageously, disposed in a container of wash liquid, such as water. During the time of travel between containers the off-take tube aspirates a volume of air, such as 0.17 ml. After an interval of time the off-take tube is withdrawn and disposed into the next sample container, aspirating a similar volume of air. Thus, successive samples are separated by at least a large bubble of air, if the wash liquid is omitted, and by two bubbles and a wash liquid segment, if the wash liquid is included.
  • a predetermined rate such as 2 ml./sec.
  • a portion of this initial flowing stream of sample segments, air bubbles, and wash segments from the off-take tube is divided oil at each of the outlets 26, 28, 30 and 32 to form four respective quotient streams.
  • Each of these quotients withdraws a portion of the volume of the large air bubble, which may total a loss of 0.07 ml., leaving an air bubble between segments of 0.1 ml. flowing through the pump tube 46 to the junction 50.
  • the air bar 44 periodically releases small volumes of air, such as 0.008 ml. 30 times a minute into the stream of diluent flowing through the pump tube 66 to the junction 60. These small volumes of air are adequate to occlude the conduit 66, and to occlude the conduit of the mixing coil 68 after addition to the sample stream at the junction 50.
  • These small bubbles serve to compartmentalize the segments of sample and added thereto diluent, and insure uniform mixing of this sum stream, as taught in U.S. Patent No. 3,306,229, supra.
  • the junction 72 has an inlet arm and a lower outlet arm which are relatively horizontal and an upper outlet arm which is upwardly directed, and has a volume A at the intersection of the arms which is greater than the volume of the smaller air bubbles, such as .01 ml.
  • the sample stream has been uniformly diluted.
  • a portion of the diluted stream is now removed at each of the subsequent junctions 80 et seq. to provide quotient sample streams.
  • Each of these junctions has a relatively small volume, similar to junction 72, such as .01 ml.
  • wash liquid segment will provide a visual indication of the demarcation between segments of successive samples.
  • a method of preparation for analysis of a plurality of liquid samples with respect to a number of different constituents present in each sample comprising:
  • said relatively small gas segments are uniformly, in-
  • a method according to claim 1 further including:
  • a method according to claim 1 wherein the division of said sum stream into a plurality of quotient streams includes a portion of each diluted sample segment and a porton of each relatively large gas se ment for each quotient stream.
  • Apparatus for the preparation for analysis of a plurality of liquid samples with respect to a number of different constituents present in each sample comprising:
  • supply means coupled to a junction for transmitting the samples sequentially through the junction, each sample being spaced from the preceding sample by a relatively large gas segment, to form an initial stream of sequential samples;
  • additional supply means coupled to the junction for continuously adding to said initial stream a stream of diluent and uniformily spaced apart relatively small gas segments to form a sum stream; mixing means coupled to said junction for continuously intramixing said sum stream of sample and diluent;
  • debubbling means coupled to and downstream of said mixing means having a capacity adequate for withdrawing each of said relatively small gas segments from said intramixed sum stream, yet inadequate for withdrawing most of each of said relatively large gas segments;
  • dividing means coupled to and downstream of said debubbling means for dividing said intramixed, debubbled sum streams into a plurality of quotient streams, each quotient stream including a portion of each diluted sample segment and a portion of each relatively large gas segment.
  • said supply means includes a plurality of sample containers
  • an off-take means having an off-take tube which is coupled to said pump means and insertable sequentially in each of said sample containers;
  • said off-take tube aspirates sample when disposed in a sample container and aspirates air When withdrawn from the sample containers.
  • said supply means further includes a wash liquid container into which said off-take tube is inserted between insertions in successive sample containers;
  • said initial stream includes sequences of sample liquid, a relatively large air segment, wash liquid, and a relatively large air segment.
  • said mixing means comprises a helical coil having a horizontal axis.
  • said debubbling means comprises a junction having a substantially horizontal inlet and outlet and an additional, upwardly directed outlet which is coupled to a pump means, and a volume contained between said inlet and outlets at least equal to said predetermined volume of said relatively small gas segments.

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  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
US672055A 1967-10-02 1967-10-02 Method and apparatus for the dilution and division of a stream of samples for continuous analysis Expired - Lifetime US3435684A (en)

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US67205567A 1967-10-02 1967-10-02

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US3435684A true US3435684A (en) 1969-04-01

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US (1) US3435684A (xx)
BE (1) BE721005A (xx)
CH (1) CH498388A (xx)
DE (1) DE1801096A1 (xx)
FR (1) FR1602114A (xx)
GB (1) GB1226584A (xx)
SE (1) SE357443B (xx)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3848633A (en) * 1971-10-22 1974-11-19 Damon Corp Precise fluid-dividing apparatus
US3921439A (en) * 1973-08-27 1975-11-25 Technicon Instr Method and apparatus for selectively removing immiscible fluid segments from a fluid sample stream
US4212845A (en) * 1977-07-06 1980-07-15 The Rank Organisation Limited Analytical apparatus
US4224033A (en) * 1977-02-16 1980-09-23 Bifok Ab Programmable, continuous flow analyzer
US4798803A (en) * 1985-07-10 1989-01-17 The Dow Chemical Company Method for titration flow injection analysis
US5019515A (en) * 1986-04-18 1991-05-28 Ciba-Geigy Corporation Method of controlling and optimizing industrial processes for the manufacture of textile finishing and improving agents via flow injection analysis

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE8201448L (sv) * 1982-03-09 1983-09-10 Walle Roald Franch Forfarande och anordning for transmission av mindre provvetskevolymer
DE3615973A1 (de) * 1985-08-28 1987-11-19 Siegfried Dipl Phys Stiller Methode zur kontinuierlichen messung der haemoglobinkonzentration im extrakorporalen kreislauf
US6261847B1 (en) * 1998-07-10 2001-07-17 Bayer Corporation Sample dilution module with offset mixing chamber

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3020130A (en) * 1959-08-06 1962-02-06 Technicon Instr Digestion apparatus and method
US3109713A (en) * 1959-07-22 1963-11-05 Technicon Instr Liquid analysis apparatus with closed flow cell
US3134263A (en) * 1961-10-20 1964-05-26 Technicon Instr Sample-supply device for automatic analysis apparatus
US3241432A (en) * 1962-01-23 1966-03-22 Technicon Instr Method and apparatus for sequentially performing analyses on a plurality of fluid samples

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3109713A (en) * 1959-07-22 1963-11-05 Technicon Instr Liquid analysis apparatus with closed flow cell
US3020130A (en) * 1959-08-06 1962-02-06 Technicon Instr Digestion apparatus and method
US3134263A (en) * 1961-10-20 1964-05-26 Technicon Instr Sample-supply device for automatic analysis apparatus
US3241432A (en) * 1962-01-23 1966-03-22 Technicon Instr Method and apparatus for sequentially performing analyses on a plurality of fluid samples

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3848633A (en) * 1971-10-22 1974-11-19 Damon Corp Precise fluid-dividing apparatus
US3921439A (en) * 1973-08-27 1975-11-25 Technicon Instr Method and apparatus for selectively removing immiscible fluid segments from a fluid sample stream
US4224033A (en) * 1977-02-16 1980-09-23 Bifok Ab Programmable, continuous flow analyzer
US4212845A (en) * 1977-07-06 1980-07-15 The Rank Organisation Limited Analytical apparatus
US4798803A (en) * 1985-07-10 1989-01-17 The Dow Chemical Company Method for titration flow injection analysis
US5019515A (en) * 1986-04-18 1991-05-28 Ciba-Geigy Corporation Method of controlling and optimizing industrial processes for the manufacture of textile finishing and improving agents via flow injection analysis

Also Published As

Publication number Publication date
DE1801096A1 (de) 1969-08-07
SE357443B (xx) 1973-06-25
FR1602114A (xx) 1970-10-12
CH498388A (fr) 1970-10-31
DE1801096B2 (xx) 1978-06-15
GB1226584A (xx) 1971-03-31
DE1801096C3 (xx) 1979-02-15
BE721005A (xx) 1969-03-18

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