US3624223A

US3624223A - Blood type indicator

Info

Publication number: US3624223A
Application number: US419128A
Authority: US
Inventors: William J Smythe
Original assignee: Technicon Instruments Corp
Current assignee: Bayer Corp
Priority date: 1964-12-17
Filing date: 1964-12-17
Publication date: 1971-11-30
Anticipated expiration: 1988-11-30
Also published as: FR1458038A; BE673875A; CH457708A; JPS527274B1; GB1122674A; JPS5413798B1; SE333647B; DE1673115A1; DE1673115B2; BE674875A; DE1673115C3

Abstract

A system for testing a plurality of samples for a characteristic, such as the blood group typing of blood samples, includes supplying the samples seriatim as a flowing stream, adding a reagent which will provide an agglutination-type reaction with samples having a predetermined characteristic, continuously concentrating any agglutinated-type material in each sample into a predetermined stratum and continuously separating this stratum from the remainder stratum, and continuously disposing one of these strata on the surface of a continuously advancing medium. The surface of the medium may be examined for the presence of agglutinated-type material. Each sample may be divided into quotients and each treated with a different reagent, and the resulting strata may be disposed on the same medium. In any event, the reaction occurs in the flowing stream, and the results are disposed on the medium for examination and storage.

Description

United States Patent [72] inventor William J. Smythe Rye, N.Y. [21] Appl. No. 419,128 [22] Filed Dec. 17, 1964 [4S] Patented Nov. 30, 1971 [73] Assignee Technicon Instruments Corporation Chauncey, N.Y. The portion of the term of the patent subsequent to July 31, 1984, has been disclairned.

[54] BLOOD TYPE INDICATOR 12 Claims, 5 Drawing Figs.

[52] US. Cl. 424/11, 23/230, 23/253, 210/65, 424/12, 424/13 [51] Int. Cl G01n 31/02 [50] Field of Search 167/845; 23/253, 259, 230; 424/1 1, 12, 13

[56] References Cited UNITED STATES PATENTS 2,770,572 11/1956 Eldon 167/84.5

Primary Examiner- Albert T. Meyers Assistant ExaminerNorman A. Drezin Attorney- Harry Cohen ABSTRACT: A system for testing a plurality of samples for a characteristic, such as the blood group typing of blood samples, includes supplying the samples seriatim as a flowing stream, adding a reagent which will provide an agglutinationtype reaction with samples having a predetermined characteristic, continuously concentrating any agglutinated-type material in each sample into a predetermined stratum and continuously separating this stratum from the remainder stratum, and continuously disposing one of these strata on the surface of a continuously advancing medium. The surface of the medium may be examined for the presence of agglutinated-type material. Each sample may be divided into quotients and each treated with a different reagent, and the result ing strata may be .disposed on the same medium. In any event, the reaction occurs in the flowing stream, and the results are disposed on the medium for examination and storage.

BLOOD TYPE INDICATOR This invention relates to the automatic identification, analysis and documentation of substances.

A major problem in many analytic procedures involves insuring that the results of an analysis of each of a plurality of samples is correlated with the sample which was analyzed, and having the physical results available for subsequent reexamination and determination.

A prime example of this problem is found in the operation of a blood bank. Customarily, a supply of blood is drawn from a plurality of donors. A sample of each of the drawn blood is analyzed for blood type. The blood type determination is correlated with the respective supply of drawn blood. A sample of blood is also drawn from a patient requiring blood, and this sample is analyzed for blood type. This blood type determination is correlated with the patient. Subsequently, a supply of blood is selected which is of the same type as that possessed by the patient, and is administered to him. If blood of an incorrect type is given to the patient, the result may be fatal.

An additional problem is that much of the equipment for performing automatic analysis is relatively expensive. A customary technique in automatic analysis is to first react the sample to provide a color, the optical density of which is correlated to the proportion of the constituent in the sample which is to be determined. Then the optical density is measured by passing the sample through a flow cell and optical bench, and the results are printed by a recorder.

In many cases, however, the accurate proportions of the constituent are not required, an indication as to whether the constituent is present or not will suffice. Such a situation occurs in blood typing. Customarily the blood is typed by separating the red cells from the serum by centrifuging the whole blood, and reacting the cells with suitable antibody and/or reacting the serum with suitable antigens in red cells. A positive reaction will be indicated by an agglutination of the cells. This agglutination may be manually observed, or may be automatically determined as taught in U.S. Pat. No. 3,334,018, issued to William J. Smythe on Aug. l, 1967. In that patent the agglutinated cells are automatically removed from the reacted sample, and then the residue of the sample is hemolyzed to produce a red color whose optical density is responsive to the red cells remaining in the sample. If there was a positive reaction, the red cells originally present will have agglutinated and been removed, and the sample will be relatively colorless. If there was not any reaction, the red cells will not have agglutinated and been removed, and upon hemolysis will provide a red color. The result derived is a yes or no with respect to agglutination.

It is, therefore, an object of this invention to provide an apparatus utilizing relatively inexpensive output equipment which will provide a yes or no result with respect to the presence of a constituent in a sample.

It is another object of this invention to provide an apparatus which will relatively permanently store the physical result of the analysis, so that it may be reexamined and redetermined.

A feature of this invention is the provision of an automatic analysis apparatus having a means for reacting each of a plurality of samples seriatim, and a means for receiving and permanently storing a reaction product from each sample.

These and other objects, features and advantages will become apparent by reference to the following description of the invention considered in conjunction with the accompanying drawings in which:

FIG. 1 is a diagrammatic elevational view of a reaction circuit for either a red cell or a serum sample;

FIG. 2 is a diagrammatic plan view of an eight-channel system for reacting a sample and for disposing the reaction products on an absorptive paper roll; I

F IG. 3 is a diagrammatic elevational view of a modification of the embodiment of FIG. 1;

FIG. 4 is a diagrammatic perspective view of a modification of the embodiment of FIG. 2.

FIG. 5 is a diagrammatic perspective view of a second modification of the embodiment of FIG. 2.

In FIGS. 1 and 2, each sample of whole blood is drawn into a vial or sample container 10 and is centrifuged to separate the red cells from the serum, the red cells accumulating in the lower portion of the vial. Each of the vials is disposed in a sampling apparatus 12 which includes a rotating support member 14 and a pair of offtake tubes 16 and 18. The sampling apparatus is advantageously of the type shown in U.S. Pat. No. 3,252,330, issued to Nelson G. Kling on May 24, 1966. The takeofi tubes are automatically inserted into each vial 10, as each vial is serially presented to the tubes, and withdrawn therefrom. The tube 16 is longer than the tube 18 so that the tube 16 will draw off red cells, and the tube 18 will draw off serum, from each via].

The offtake tubes 16 and 18 are coupled to a plurality of reaction channels, the tube 16 being coupled to four

channels

20, 22, 24 and 26, and the tube 18 being coupled to four

channels

28, 30, 32 and 34. Each of these channels is similar and will be described with respect to FIG. 1. A peristaltic proportioning pump 36 engages four resiliently

compressible pump tubes

38, 40, 42 and 44. The tube 38 is coupled to the sample source which will be either offtake tube 16 or 18. The tube 40 is coupled to a source, not shown, of a suitable reagent, which for channel 20 will be serum type A antibodies, for channel 22 will be serum type B antibodies, for channel 24 will be serum type D (RH-l) antibodies, for channel 26 will be a control of saline solution; for channel 28 will be red cells with type A antigens, for channel 30 will be red cells with type B antigens, for channel 32 will be red cells of type 0, and for channel 34 will be a control of saline solution. The tube 42 is coupled to a source of air, not shown; and the tube 44 is coupled to a source of saline solution, not shown. The pump is advantageously of the type shown in the U.S. Pat. No. 2,935,028, issued on May 3, 1960, to Andres Ferrari, Jr. and .lack lsreeli.

The

tubes

38 and 40 are intercoupled at a junction 46, the outlet of which is coupled to the tube 42 at a junction 48. The pump causes the takeoff tubes to draw off a predetermined volume of sample into the system, which is spaced from the volume of the succeeding sample by a predetermined volume of air. A predetermined portion of each sample is passed into the respective sample tube 38, and to this a predetermined volume of the respective reagent is concurrently added by the tube 40. A predetermined volume of air is concurrently added by the tube 42. The outlet of the junction 48 is coupled to a mixing coil 50, wherein the three volumes are intermixed. The outlet of the mixing coil is coupled to a reaction coil 52, wherein the agglutination reaction, if any, proceeds to completion. Successive samples leaving the outlet of the reaction coil are still spaced apart by a volume of air, which was initially provided by the takeoff tube. Within each sample, the red cells may be agglutinated if the reaction was positive, or not agglutinated, if the reaction was negative. The tube 44 feeds a continuous supply of saline solution, to a pulse chamber 54 which has a trapped head of air 56, therein.

The outlet of the chamber is coupled to a junction 58 which is also coupled to the outlet of the reaction coil. The saline solution serves as a diluent. The head of air absorbs any pounding which might occur in the line at the junction due to the serial passage therethrough of volumes of reacted sample and volumes of air. The outlet of the junction 58 is coupled to a second mixing coil 60 wherein the sample and diluent are intermixed. The outlet of the mixing coil may be coupled to a settling coil, not shown here, and thence to a decent junction 62. The agglutinated red cells are denser than the rest of the sample and tend to settle to the bottom of the sample as it progresses to the decant junction. As shown in U.S. Pat. No. 3,334,018 supra, the junction consists of a substantially horizontal conduit 64 having a downwardly extending outlet of relatively small diameter, through which a predetermined fraction of the lower portion of the sample is removed as it passes thereover. This removed fraction contains most of the agglutinated red cells, if any. The remainder of the sample passes out through the horizontally extending outlet 68. The outlet 66 is coupled to a drip tube 70.

The eight drip tubes 70, one for each channel, are disposed over an unwinding length of absorbent paper 72, and drip their respective fractions of sample onto the paper as it is unwound thereunder by suitable means, not shown. The dripping from each tube will either be colorless as straight saline solution 74 is dripped; relatively colorless as unagglutinated blood 76 having a normal distribution of red cells is dripped; or relatively strongly colored as agglutinated blood 78 having a high distribution of red cells is dripped.

The color of each channel may be visually inspected, and the blood type determined from the combinational results. Al tematively, the color may be automatically determined by a densiometer 80 for each channel. Each densiometer consists of a light source 82, a focusing lens 84 which focuses the light onto the dripping passing thereunder, a light detector 86, and a focusing lens 88 which focuses the light reflected from the dripping to the detector. The outputs from the detectors may be fedto a computer, to automaticallydetermine the blood type, as shown in U.S. Pat. No. 3,320,618, issued to Bailin L. Kuch et al. on May l6, 1967.

Alternatively, as shown in FIG. 3, drip tube 90 may be coupled to the second outlet 68 of the decant junction 62, to drip on the paper 72. In such a case the dripping from an unagglutinated sample will be more strongly colored than the dripping from an agglutinated sample. This arrangement, however, is not as sensitive as the arrangement of FIG. I.

A web of nonporous sheet material 100, such as cellulose acetate, as shown in FIG. 4, is advantageously substituted for the roll of absorbent paper 72. The sheet has eight preformed channels therein, each channel being divided alternately into long depressions 102 to receive sample drippings, and short depressions 104 to receive straight saline drippings. The depressions are subsequently covered by a second web of nonporous, light-permeable sheet material 106, such as cellulose acetate, from a supply roll. The two webs are bonded to each other over their absorbing faces by a suitable precoated contact adhesive, or by suitable sealing transducers. Such a laminated storage arrangement permits extended storage of the drippings under refrigeration without decomposition of the red cells.

As shown in FIG. 5, each group of sample drippings is advantageously stamped with an identification number 110, by a stamping mechanism 112. This mechanism consists of a plurality of automatically settable printing wheels and a suitable ink supply mechanism. In this case, the identification number may be a sequential one, or advantageously, may be correlated to the particular donor or vial from which the sample was offtaken. Suitable means for supplying identification numbers for the printing mechanism is shown on the U.S. Pat. application, Ser. No. 39 l ,093, by Jack lsreeli, filed Aug. 2 l 1964, and assigned to the assignee of this application. The laminated webs are advantageously automatically cut by a guillotine l 14, into rectangles each including the eight sample drippings and the identification number, and are stored in the manner of index cards. Should a question subsequently arise, the sample card of interest may be selected and reexamined.

It will be appreciated that on occasion the intensity of the color of the dripping may be ambiguous as to whether agglutination is indicated or not. In such a case, the sample dripping may be microscopically examined, and an accurate determination of the blood type may be made.

The advance of sheet material 100 under the drip tubes 70 is accurately phased with the dispensing of the liquid from the drip tubes so that the depressions I02 are under the tubes when the sample volumes are dripping out, and the depressions 104 are under the tubes when the saline spacing volumes are dripping out. This advance is controlled by a star wheel 116 which engages a plurality of notches 92 in the sheet material to advance the same. The star wheel is rotated by a suitable motor 120 which is controlled by the operation of the offtake tubes 16 and 18. The advance of the absorbent paper 72 may be advantageously controlled by a drive mechanism as shown in U.S. Pat. No. 3,333,826, issued to Gerald Kessler on Aug. 1, I967.

Although the invention has been disclosed in embodiments particularly suitable for blood typing, it will be appreciated that other uses exist whenever it is desired to store a reaction product, e.g. to store a precipitant, for subsequent examination.

While I have shown and described the 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 certain changes in the form and arrangement of parts and in the specific manner of practicing the invention may be made without departing fromthe under lying idea or principles of this invention within the scope of the appended claims. i

What I claim is:

l. A liquid analysis apparatus comprising: reactingmeans for supplying a reagent for an agglutinate-type reaction with a liquid sample of i a certain "type; means for automatically providing a plurality of such liquid samples seriatim'to said reacting means; means coupled to said reacting means for automatically segregatingany'reaction product within each sample; means coupled to said separating means for automatically withdrawing a portion of each sample containing said segregated reaction product seriatim and having an outlet therefor; a web of sheet material in the form of a roll; and means for advancing said web past said withdrawing means outlet; whereby such withdrawn sample portions are deposited on said web seriatim. q

2. A blood-typing apparatus comprising:

reacting means having an inlet and an outlet; means coupled to said reacting means inlet for automatically providing a plurality of blood samples seriatim thereto; means coupled to said reacting means inlet for automatically providing a blood-agglutinating reagent thereto, whereby agglutinated red cells are provided in samples of certain blood in said reacting means; said reacting means including means for automatically segregating such agglutinated red cells within each sample; means having an inlet coupled to said reacting means outlet for automatically withdrawing a portion of each sample containing any such segregated red cells seriatim, and having an outlet therefor; a web of sheet material in the form of a roll; and

1 means for advancing said web past said withdrawing means outlet, whereby such withdrawn portions are deposited on said web seriatim.

3. A method of testing a plurality of liquid samples for a particular type comprising:

transmitting the samples seriatim as a flowing stream of samples in a conduit; treating the samples with a reagent which provides an agglutination-type reaction with samples of the particular type;

separating any agglutinated-type material produced by-any such reaction in each sample in the flowing stream to a first stratum of each sample, whereby the flowing stream of samples has a first stratum, containing at least most of any agglutinated-type material, and a second stratum;

depositing portions of one of said strata on a continuously advancing surface of a web of sheet material in the form of a roll; and

examining the deposits while on said surface for the presence of agglutinated-type material.

4. A method according to claim 3 wherein said separating is accomplished by gravitational settling and said first stratum is the lowermost stratum, and said second stratum contains a uniform share of any nonagglutinated material.

5. A method according to claim 4 wherein said first stratum is the one of said strata from which said portions are deposited on said continuously advancing web surface.

6. A method according to claim 4 wherein portions of said second stratum are deposited on said continuously advancing web surface for examination. 7. A method according to claim 3 wherein each of the samples is divided into a plurality of parts to provide a plurality of flowing streams of said parts;

each of the parts in a stream being mixed with a different reagent which provides an agglutination-type reaction with samples of a particular type;

separating any agglutinated-type material produced in each part in each stream in said first stratum from said second stratum; and

depositing portions of said first strata on a common advancing surface provided by said web.

8. A method according to claim 7 wherein said samples are blood, certain of said parts being red cells, which red cells comprise the material to be agglutinated.

9. A method according to claim 7 wherein said samples are blood, certain of said parts being sera,

the respective reagents being added being red cells, which comprise the material to be agglutinated.

10. A method according to claim 7 further including:

continuously overlaying said surface of the web, after the deposits thereon, with a protective web of sheet material in the form of a roll.

11. Apparatus for testing a plurality of liquid samples for a particular type, comprising:

first means for supplying the samples seriatim as segments in a flowing stream, each sample segment being spacedfrom a succeeding sample segment and compartmentalized by a segment of a fluid immiscible therewith;

second means, coupled to said first means, for supplying to and mixing with the samples in the flowing stream a reagent which provides an agglutination-type reaction with samples of the particular type;

third means, coupled to said second means, separating any agglutinated-type material produced by any such reaction to a first stratum of such segments, whereby the flowing stream of segments has a first stratum containing at least most of any agglutinated-type material, and a second stratum;

fourth means, coupled to said third means, for continuously withdrawing the first stratum from the second stratum; fifth means comprising a movable web of sheet material in the form of a roll, having a surface;

said fourth means including means for depositing portions of one of said strata on said web surface.

12. Apparatus according to claim 11 wherein said first means includes means for dividing each of said samples into a plurality of parts to provide a plurality of flowing streams of said parts;

said second means includes a plurality of means each for supplying a difierent reagent and for mixing such reagent with a corresponding one of the streams of said parts;

said third means includes a plurality of means each for separating any agglutinated-type material into said first stratum; and

said fourth means includes a plurality of means each for continuously withdrawing the first stratum from the corresponding stream and for depositing portions of one of the strata from the last-mentioned stream on said web surface.

Claims

2. A blood-typing apparatus comprising: reacting means having an inlet and an outlet; means coupled to said reacting means inlet for automatically providing a plurality of blood samples seriatim thereto; means coupled to said reacting means inlet for automatically providing a blood-agglutinating reagent thereto, whereby agglutinated red cells are provided in samples of certain blood in said reacting means; said reacting means including means for automatically segregating such agglutinated red cells within each sample; means having an inlet coupled to said reacting means outlet for automatically withdrawing a portion of each sample containing any such segregated red cells seriatim, and having an outlet therefor; a web of sheet material in the form of a roll; and means for advancing said web past said withdrawing means outlet, whereby such withdrawn portions are deposited on said web seriatim.
3. A method of testing a plurality of liquid samples for a particular type comprising: transmitting the samples seriatim as a flowing stream of samples in a conduit; treating the samples with a reagent which provides an agglutination-type reaction with samples of the particular type; separating any agglutinated-type material produced by any such reaction in each sample in the flowing stream to a first stratum of each sample, whereby the flowing stream of samples has a first stratum, containing at least most of any agglutinated-type material, and a second stratum; depositing portions of one of said strata on a continuously advancing surface of a web of sheet material in the form of a roll; and examining the deposits while on said surface for the presence of agglutinated-type material.
4. A method according to claim 3 wherein said separating is accomplished by gravitational settling and said first stratum is the lowermost stratum, and said second stratum contains a uniform share of any nonagglutinated material.
5. A method according to claim 4 wherein said first stratum is the one of said strata from which said portions are deposited on said continuously advancing web surface.
6. A method according to claim 4 wherein portions of said second stratum are deposited on said continuously advancing web surface for examination.
7. A method according to claim 3 wherein each of the samples is divided into a plurality of parts to provide a plurality of flowing streams of said parts; each of the parts in a stream being mixed with a different reagent which provides an agglutination-type reaction with samples of a particular type; separating any agglutinated-type material produced in each part in each stream in said first stratum from said second stratum; and depositing portions of said first strata on a common advancing surface provided by said web.
8. A method according to claim 7 wherein said samples are blood, certain of said parts being red cells, which red cells comprise the material to be agglutinated.
9. A method according to claim 7 wherein said samples are blood, certain of said parts being sera, the respective reagents being added being red cells, which comprise the material to be agglutinated.
10. A method according to claim 7 further including: continuously overlaying said surface of the web, after the deposits thereon, with a protective web of sheet material in the form of a roll.
11. Apparatus for testing a plurality of liquid samples for a particular type, comprising: first means for supplying the samples seriatim as segments in a flowing stream, each sample segment being spaced from a succeeding sample segment and compartmentalized by a segment of a fluid immiscible therewith; second means, coupled to said first means, for supplying to and mixing with the samples in the flowing stream a reagent which provides an agglutinatioN-type reaction with samples of the particular type; third means, coupled to said second means, separating any agglutinated-type material produced by any such reaction to a first stratum of such segments, whereby the flowing stream of segments has a first stratum containing at least most of any agglutinated-type material, and a second stratum; fourth means, coupled to said third means, for continuously withdrawing the first stratum from the second stratum; fifth means comprising a movable web of sheet material in the form of a roll having a surface; said fourth means including means for depositing portions of one of said strata on said web surface.
12. Apparatus according to claim 11 wherein said first means includes means for dividing each of said samples into a plurality of parts to provide a plurality of flowing streams of said parts; said second means includes a plurality of means each for supplying a different reagent and for mixing such reagent with a corresponding one of the streams of said parts; said third means includes a plurality of means each for separating any agglutinated-type material into said first stratum; and said fourth means includes a plurality of means each for continuously withdrawing the first stratum from the corresponding stream and for depositing portions of one of the strata from the last-mentioned stream on said web surface.