US 3435684 A
Description (OCR text may contain errors)
7 April 1; 1969 w. J. SMYTHE METHOD AND APPARATUS FOR THE DILUTION AND DIVISION FIG.2
OF A STREAM 0F SAMPLES FOR CONTINUOUS ANALYSIS Filed Oct. 2, 1967 INVENTOR.
WILLIAM J. SMYTHE ATTORNEY METHOD AND APPARATUS FOR THE DILUTION AND DIVISION OF A STREAM OF SAMPLES FOR CONTINUOUS ANALYSIS William J. Smythe, Rye, N.Y., assignor to Technicon Corporation, Ardsley, N.Y., a corporation of New York Filed Oct. 2, 1967, Ser. No. 672,055 Int. Cl. G01n 1/28 US. Cl. 73-423 9 Claims ABSTRACT OF THE DISCLOSURE 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 Each of the relatively small gas segments is withdrawn and the debubbled, mixed, sum stream is divided into a plurality of quotient streams, each having a portion of each sample and each relatively large gas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.
BACKGROUND OF THE INVENTION Field of the invention 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.
Prior art Systems for the automatic, continuous analysis of liquids are well known. Such a system is shown in US. Patent No. 2,797,149, issued to L. T. Skeggs on June 25, 1957. The analysis system is fed sequential samples as a flowing stream by means of an off-take device which aspirates liquid from each of a plurality of sample containers, which are sequentially presented thereto by a sampler assembly, such as is shown in U.S. Patent No. 2,879,141, issued to L. T. Skeggs on Mar. 24, 1959. More recently, systems have become known wherein the initial stream of samples is divided into a plurality of quotient streams, each containing a fractional portion of each sample from the initial stream. Each quotient stream is then analyzed, and the results are recorded in correlation automatically. Such a system is shown in US. Patent No. 3,241,432, issued to L. T. Skeggs et al. on Mar. 22, 1966. The sampler may be as shown in US. Patent No. 3,230,776, issued to I. Isreeli et al. on Jan. 25, 1966, which provides a segment of wash liquid between successive samples.
Much of this analytical work is in the clinical field, and is especially directed to the analysis of blood samples for different constituents thereof. The number of constituents being limited by the number of quotient streams provided. Present commercial systems may provide analyses of 60 samples per hour for 12 constituents of each sample.
I have found that it is advantageous to dilute the initial stream during the division of the stream into the quotient streams. This provides a threefold benefit. Firstly, it ensures that each sample quotient is of conveniently large volume for processing. Secondly, it minimizes the possibility of clogging of the small diameter conduits by the non-liquid material carried in the blood sample.
3,435,684 Patented Apr. 1, 1969 Thirdly, it permits a reduction in the sensitivity of certain colorimetric reactions, so that the optical density thereof is kept within the substantially linear range of the detector-recorder subsystem.
SUMMARY OF THE INVENTION 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.
BRIEF DESCRIPTION OF THE DRAWING FIGURE 1 is a diagram of a flow system embodying this invention; and
FIGURE 2 is a perspective view of a detail of the flow system.
THE PREFERRED EMBODIMENT The embodiment shown in 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. Similarly, each of the pump tubes 36, 38, 40 and 42 is coupled to an inlet of a respective junction 134, 136, 138 and 140.
As shown in U.S. Patent No. 3,241,432, supra, 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 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. Thus the entire volume of these small bubbles is taken off through the upwardly directed outlet arm and the pump tube 78 to waste. However, at this point, 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. so that a portion of the large air bubble (now .09 ml.) is available for each quotient stream. This portion of the air bubble suffices to provide a cleansing action through the pump tubes to the junctions 116 through 130. At these junctions a suitable diluent, and supply of small air bubbles is added to each quotient stream, as taught in U.S. Patent No. 3,241,432, supra.
It will be appreciated, that if necessary, the wash liquid segment, will provide a visual indication of the demarcation between segments of successive samples.
While there has been shown and described a presently preferred embodiment of the invention, it will be understood that the invention may be embodied otherwise than as herein specifically illustrated or described and that in the illustrated embodiment certain changes in the details of construction and in the form and arrangement of parts may be made without departing from the underlying idea or principles of the invention. Accordingly, the invention is not limited to the prior construction shown or described herein.
What is claimed is:
1. 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:
sequentially transmitting said samples through a conduit, each sample being spaced from the preceding sample by a relatively large gas segment, to form an initial stream of sequential samples;
continuously adding to said initial stream a stream of diluent and uniformily spaced apart relatively small gas segments to form a sum stream;
continuously intramixing the sum stream of sample and diluent;
continuously withdrawing said relatively small gas segments but not all of said relatively large gas segments from said sum stream; and
continuously dividing said sum stream into a plurality of quotient sample streams.
2. A method according to claim 1 wherein:
said relatively small gas segments are uniformly, in-
termittently added to a stream of diluent, which is then continuously added to said initial sample stream.
3. A method according to claim 1 further including:
continuously adding to each quotient stream a respective stream of reagent and uniformly spaced apart relatively small gas segments.
4. 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.
5. 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; and
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.
6. Apparatus according to claim 5 wherein:
said supply means includes a plurality of sample containers;
a pump means; and
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;
whereby said off-take tube aspirates sample when disposed in a sample container and aspirates air When withdrawn from the sample containers.
7. Apparatus according to claim 6 wherein:
said supply means further includes a wash liquid container into which said off-take tube is inserted between insertions in successive sample containers;
whereby said initial stream includes sequences of sample liquid, a relatively large air segment, wash liquid, and a relatively large air segment.
8. Apparatus according to claim 5 wherein said mixing means comprises a helical coil having a horizontal axis.
9. Apparatus according to claim 5 wherein said additional supply means provides said relatively small gas segments with a predetermined volume;
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.
References Cited UNITED STATES PATENTS 3,020,130 2/ 1962 Ferrari 23-230 3,109,713 11/1963 Ferrari et a1 23--253 3,134,263 5/1964 De Jong 73423 10 3,241,432 3/1966 Skeggs et a1 23-230 XR LOUIS R. PRINCE, Primary Examiner.
HARRY C. POST, Assistant Examiner.