U.S. patent number 3,624,223 [Application Number 04/419,128] was granted by the patent office on 1971-11-30 for blood type indicator.
This patent grant is currently assigned to Technicon Instruments Corporation. Invention is credited to William J. Smythe.
United States Patent |
3,624,223 |
Smythe |
* November 30, 1971 |
BLOOD TYPE INDICATOR
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.
Inventors: |
Smythe; William J. (Rye,
NY) |
Assignee: |
Technicon Instruments
Corporation (Chauncey, NY)
|
[*] Notice: |
The portion of the term of this patent
subsequent to July 31, 1984 has been disclaimed. |
Family
ID: |
23660914 |
Appl.
No.: |
04/419,128 |
Filed: |
December 17, 1964 |
Current U.S.
Class: |
435/7.25;
210/767; 422/73; 436/808; 436/520; 422/66; 422/82 |
Current CPC
Class: |
G01N
35/08 (20130101); G01N 33/80 (20130101); Y10S
436/808 (20130101) |
Current International
Class: |
G01N
35/08 (20060101); G01N 33/483 (20060101); G01N
33/80 (20060101); G01n 031/02 () |
Field of
Search: |
;167/84.5
;23/253,259,230 ;424/11,12,13 |
References Cited
[Referenced By]
U.S. Patent Documents
Primary Examiner: Meyers; Albert T.
Assistant Examiner: Drezin; Norman A.
Claims
What I claim is:
1. A liquid analysis apparatus comprising:
reacting means for supplying a reagent for an agglutinate-type
reaction with a liquid sample of 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 segregating any 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.
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.
Description
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. 1,
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;
FIG. 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; and
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 takeoff 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 vial.
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+) 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 O, 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 Jack Isreeli.
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. Alternatively, 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 fed to a computer, to
automatically determine the blood type, as shown in U.S. Pat. No.
3,320,618, issued to Bailin L. Kuch et al. on May 16, 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. 1.
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.
391,093, by Jack Isreeli, filed Aug. 21, 1964, and assigned to the
assignee of this application. The laminated webs are advantageously
automatically cut by a guillotine 114, 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 102 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, 1967.
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 from the underlying idea or principles of this invention
within the scope of the appended claims.
* * * * *