U.S. patent number 3,607,097 [Application Number 04/750,654] was granted by the patent office on 1971-09-21 for analyzer for liquid samples.
This patent grant is currently assigned to U.S. Philips Corporation. Invention is credited to Michel Auphan, Jean Perilhou.
United States Patent |
3,607,097 |
Auphan , et al. |
September 21, 1971 |
**Please see images for:
( Certificate of Correction ) ** |
ANALYZER FOR LIQUID SAMPLES
Abstract
An apparatus for automatically transporting a plurality of
liquid samples, such as blood through a series of programmed steps
for colorimetric analysis of the samples. A first conveyor belt
carries the samples to be analyzed, an adjacent belt carries
working tubes in which the tests occur, and a third belt carries
substances to be added to the samples during the tests. Needles and
tubes are provided between the containers of substances on the
three belts for piercing container walls and then transferring
liquids between the containers.
Inventors: |
Auphan; Michel
(D'Orleans-Neuilly, FR), Perilhou; Jean (Arnoux-Bourg
la Reine, FR) |
Assignee: |
U.S. Philips Corporation (New
York, NY)
|
Family
ID: |
8636629 |
Appl.
No.: |
04/750,654 |
Filed: |
August 6, 1968 |
Foreign Application Priority Data
Current U.S.
Class: |
422/66; 422/65;
422/915; 356/39; 422/67 |
Current CPC
Class: |
G01N
35/02 (20130101); G01N 21/03 (20130101); G01N
35/04 (20130101); B01L 3/0296 (20130101); G01N
35/1002 (20130101); B01L 3/505 (20130101); G01N
35/1079 (20130101); G01N 2035/0408 (20130101); G01N
2035/0434 (20130101) |
Current International
Class: |
B01L
3/00 (20060101); G01N 21/03 (20060101); G01N
35/04 (20060101); G01N 35/02 (20060101); G01N
35/10 (20060101); G01n 001/14 (); G01n
033/16 () |
Field of
Search: |
;23/259,253,23A
;73/423,421.5,425.6 |
References Cited
[Referenced By]
U.S. Patent Documents
Primary Examiner: Wolk; Morris O.
Assistant Examiner: Serwin; R. E.
Claims
What is claimed is:
1. Apparatus for automatic analysis of liquid samples obtained from
a plurality of containers, comprising:
a. a housing,
b. a plurality of flexible working tubes,
c. first means for carrying the working tubes between different
positions along a path,
d. means for selectively compressing and releasing each working
tube which is subsequently expandable to develop suction
therein,
e. second means for carrying the containers of liquid samples along
a second path, whereby each container is disposed adjacent one
working tube,
f. first duct means for communicating the sample liquid from each
container to a working tube, with said liquid being drawable into
the working tube by said suction therein,
g. a plurality of auxiliary containers, each containing at least
one reagent,
h. third means for carrying auxiliary containers along a third path
and for disposing each to be closely adjacent a working tube,
and
i. second duct means for communicating each reagent from its
auxiliary container to a working tube, the reagent being drawable
onto the working tube by said suction therein, whereby each sample
is mixed within a working tube at least one reagent subsequent
analysis.
2. Apparatus according to claim 1 wherein at least one of the
auxiliary liquid containers comprises a first chamber separated
into two spaces, each adapted to house an ampulla containing a
constituent of a reagent, and a second chamber communicating with
said spaces for receiving and mixing said constituents and for
discharging the mixed constituents into the working tube.
3. Apparatus according to claim 2 further comprising means for
breaking open the ampullae in said spaces of the first chamber and
for urging the constituents into the second chamber.
4. Apparatus according to claim 1 wherein said means for
compressing and releasing each working tube comprises a plurality
of thrust feet, each movable between an inactive position, an an
active position in pressure contact with a working tube for
compressing same.
5. Apparatus according to claim 4 wherein said thrust feet are
selectively movable into pressure contact with each working tube to
mix the liquid sample and reagent therein and subsequently to
discharge the mixed fluid from the working tube.
6. Apparatus according to claim 2 wherein said first, second, and
third means for carrying respectively said working tubes, sample
containers, and auxiliary containers and belts movable about
drums.
7. Apparatus according to claim 6 wherein said tubes and containers
are disposed in parallel and oriented transverse to the direction
of their respective belt movement.
8. Apparatus comprising a device according to claim 6, further
comprising means for programming said belts to move in phased
relationship, for phased interrelationship between said tubes and
containers.
9. Apparatus according to claim 1 further comprising in each
working tube a filter for filtering the sample after it is mixed
with the reagent.
10. Apparatus for automatic colorimetric analysis of liquid fluid
samples obtained from a plurality of containers, comprising:
a. a frame,
b. a plurality of flexible working tubes, each having an external
hollow needle communicating with the tubes's interior,
c. first belt for carrying the working tubes between different
positions along a first path,
d. a plurality of thrust feet, each movable between an inactive
position, an an active position in pressure contact with a working
tube for selectively compressing same, the tube being subsequently
expanded to develop suction therein when each thrust foot is
returned to its inactive position,
e. means for moving said feet between said active and inactive
positions,
f. second belt for carrying the containers of liquid samples along
a second path, whereby each container is disposed adjacent one
working tube, and for urging the needle of the working tube to
penetrate a container, with said liquid sample then being drawable
from the container into the working tube by said suction
therein,
g. a plurality of auxiliary containers, each having a discharge
needle and containing at least one reagent,
h. third belt for carrying the auxiliary containers and for
disposing each to be closely adjacent a working tube and for then
urging the needle of each auxiliary container to penetrate a
working tube, the reagent then being drawable into the working tube
by said suction therein, whereby each blood sample is mixed within
a working tube with at least one reagent for subsequent
colorimetric analysis.
Description
This invention relates to U.S. Pat. No. 3,490,876 in which an
automatic analyzer for liquid samples is described, in which
colorimetry is used in the liquid phase or in the flame. Such an
apparatus is particularly suitable for the automatic quantitive
analysis of the main chemical constituents of blood (urea, glucose,
cholesterol, sodium, potassium, etc., by means of a minimum number
of operations on a large number of samples to be subjected to the
same analysis.
In the apparatus described a sequence of tubes having flexible
walls and filled with the liquid samples to be analyzed (termed
herein working tubes) are arranged parallel to each other on a belt
which is adapted to run around drums carrying out predetermined
movements, means being provided for carrying out the treatments
required for the analysis in a given order of succession of the
sample in each tube, for instance, injection of auxiliary liquids,
mixtures and so on.
For this purpose the apparatus comprises rows of thrust feet
arranged parallel to the tubes, each row cooperating with a single
stationary member associated with a row, the number of rows being
at least equal to the number of auxiliary liquids to be introduced
into the samples. A programming device controls the thrust feet,
each of which can be pressed against the wall of the opposite tube
so that the liquid is displaced against the wall of the length of
the tube and the predetermined treatment can be carried out. Each
working tube comprises in its interior filters for performing the
number of required filtrations during the analysis.
The invention has for its object to provide further mechanization
of the apparatus, and accordingly the invention there is provided a
second belt having parallel tubes for the auxiliary liquids
consisting of flexible material and being displaceable by actuating
at least one pushbutton into a position near the working tube, each
auxiliary liquid tube having an injection needle for injecting the
auxiliary liquid into the working tube.
The invention will be described more fully with reference to the
accompanying drawing, in which:
FIG. 1 shows schematically an elevation of the various belts
provided with tubes in an apparatus according to the invention,
FIG. 2 is a sectional view of an auxiliary liquid tube comprising
two chambers, and
FIG. 3 is a schematic elevation of a detail of the cooperating
tubes connected with thrust feet.
The improvement provided by the invention relates particularly to
the quantitative analysis of one or more constituents of the blood
of a large number of patients. The analysis of glucose described
before is chosen by way of example. For the blood analysis of a
patient all treatments are carried out within a single working tube
2 of small diameter, for example, of a synthetic resin resistant to
the chemical reagents. The working tubes 2 are arranged parallel to
each other on a belt 1, termed the working belt. The belt is
adapted to move along two drums, one of which is shown at 3. In the
spaces 4 between every two tubes 2 the working belt is provided
with the patient's data and the coded analysis in the form of
perforations.
In the example described each working tube has at one end a hollow
needle 5 for taking in the blood serum, which will be described
more fully hereinafter. The working belt is associated with a
number of rows of thrust feet (not shown in FIG. 1), the number of
rows being at least equal to the number of reagents or auxiliary
liquids to be introduced during the same analysis into the sample
to be analyzed.
According to the invention there is added to the working belt 1 a
second belt 7, which can be moved by a drum 8 and which is provided
with tubes 9 of flexible synthetic resin containing the substances
to be added during the analysis. The belt 7 has a given thickness
so that the tubes 9, arranged parallel to each other, can be fixed
in openings in the direction of thickness of the belt 7. The tubes
9 can be pressed out of the openings by means of a thrust pin 10
and be moved to the area above a working tube 2 on the belt 1. Each
tube 9 has a needle 11, which is capable of piercing the wall of a
working tube 2.
Some reagents may be stored for a long time in a sealed glass
ampulla. In this case a tube 9 contains the glass ampulla sealed by
a "pigtail," which can be broken across the tube, for example, by
means of a thrust pin. However, if the reagent cannot be kept for
sufficient time not even in sealed ampullae, and if it has to be
freshly produced, the tube 9 may be shaped in the form shown in
FIG. 2. This tube comprises two separate chambers 91 and 92,
communicating with each other through openings 96, the chamber 91
being divided into separate spaces 93, separated from each other by
closed partitions 94. Each space contains a constituent of the
reagent, for example, in the sealed ampullae 95. Each separate
space 93 communicates with the chamber 92 via a hollow needle 96.
For producing the reagent "pigtails" are broken by exerting
pressure across the synthetic resin wall so that the liquids flow
into the spaces concerned. Thrust members (not shown) permit of
introducing into the chamber 92 the desired quantities of the
constituents which form the final reagent by mixing, if necessary
with the supply of heat. The chamber 92 has a hollow needle 11.
In the example chosen and in particular for the analysis of blood
the apparatus comprises a third belt 12, termed herein take-in
belt, adapted to be moved between two drums 13 and supporting
parallel tubes 14, each of which contains blood of a patient. The
tubes 14 are provided at one end with a lancet 15 and the blood can
be taken in, for example, from the patient's ear lobe manually or
automatically by means of an apparatus independent of the analyzer
into which the belt 12 has to be introduced subsequently. The tubes
14 are fixed on the belt 12 in rigid supports by means of a spring
(not shown) arranged on the tube.
The free space 16 between two tubes 14 contains all data relating
to the patient and the desired analysis in the form of coded
perforations which data can be transferred to the belt 1 by means
of a photoelectric cell. The take-in tubes 14 with the blood are
first centrifuged before the belt 12 is inserted into the analyzer
so that serum and corpuscles are separated from each other.
The operation of the analyzer will now be described briefly with
reference to the assessment of the glucose content of blood. The
drum 13 and the take-in belt 12 are moved so that invariable a tube
14 is located opposite a working tube 2. The belt 1 with the
working tubes 2 is arranged so that the needle of a working tube 2
can penetrate into the take-in tube 14 just above the portion
filled with corpuscles, after which the desired quantity of serum
can be sucked into the working tube 2. At the same time the
associated coded information of the belt 12 is read and punched in
the belt 1. A programming device receiving the punched information
of the belt 12 will control the course of the three belts 1, 7 and
12.
All desired analyses can be carried out in order of succession.
After the serum of the tube concerned is taken in, the belt 12
moves on by one step so that the tube 14 of a further patient
occupies the emptied space opposite a next-following working tube
2, which has arrived at the area of the preceding tube due to the
propagation of the belt 1. The serum of the next patient is taken
in and the coded indications of the belt 12 are transferred to the
belt 1.
The drum 8 and the belt 7 with the tubes 9 containing the reagents
are moved in accordance with the punched coded indications so that
each reagent is present at the area where it has to be inserted
into the working tube 2. For this purpose the belt 7 is suitable
arranged at the side of belt 1 so that the thrust pins 10 are
capable of removing the tubes 9 from their places and passing them
to the area above the relevant working tube 2. The desired quantity
of reagent can be sucked in by the needle 11 piercing the wall.
When all analyses are of the same nature, the belt 7 comprises a
number of tubes 9 containing reagents corresponding with the number
of patients.
With the glucose analysis and with the aid of reduction of ferric
cyanide it is necessary to introduce the following three reagents
in a given order of succession of the desired instant and at the
desired area of the working tube 2:
---------------------------------------------------------------------------
---------------------------------------------------------------------------
Reagent A (for expelling protein)
copper sulfate 5 H.sub.2 0 0.31 g. sodium tungstenate 2 H.sub.2 0
1.22 gs. barium chloride 2 H.sub.2 0 0.26 g. distilled water 100
cc.
__________________________________________________________________________
---------------------------------------------------------------------------
Reagent B (ferric-ferrous cyanide)
pure potassium ferro-cyanide 0.006 g. pure potassium ferri-cyanide
0.033 g. pure dry sodium carbonate 0.4 g. distilled water 100 cc.
__________________________________________________________________________
---------------------------------------------------------------------------
Reagent C (ferric phosphate)
pure potassium ferri-cyanide 0.04 g. 85%-ic phosphoric acid 4.7 gs.
distilled water 100 cc.
__________________________________________________________________________
Since the first reagent having a pH value exceeding 8 can be kept
in good condition, it may be provided in the ready state in a glass
ampulla in a tube 9 and the sealing tip of the ampulla can be
broken at the exact instant.
The tube 9 is then moved to above the belt 1 with the working tubes
2, where the tube 9 stands still until the termination of the
glucose analysis. The hollow needle of the tube 9 can penetrate by
pressure into the working tube 2 by means of thrust feet. This is
shown in detail in FIG. 3. The tube 9 with the filled chamber 92 is
located above the working tube 2 and the needle 11 has pierced the
wall. The thrust feet 17 press the working tube 2 flat against the
member 18 and after the return movement of the feet the tube 2
sucks in a quantity of reagent. By pressing the correct number of
feet 17 against the member 18 a quantity of 10 .mu.L. is urged 20
times in order of succession forwardly in the tube portion serving
for the analysis and for taking in serum.
The serum is taken in the same manner by means of the needle 5. In
order to cause this needle to penetrate into the centrifuged
take-in tubes 14, the latter are pressed against the needle by a
thrust foot. The needles are adjusted so that they penetrate just
above the blood clot so that no serum gets lost.
After the serum is taken into the working tube 2, It is mixed with
the reagent by the alternate displacement of the even-numbered and
odd-numbered thrust feet 17. The mixture is then filtered by a
hard-glass filter 6 in the interior of the working tube 2. By the
action of the thrust feet the liquid is injected under pressure
through the walls of the filter. Then the working tube 2 is
displaced by one step, after which the same cycle is repeated for
the analysis of the glucose content of a further patient and so on
until the doses to be analyzed are exhausted or the tube 9 is
empty.
The second treatment of the filtrate consists in the introduction
of the ferri-ferro-cyanide, the glucose reduction of which is
measured. This reagent has to be produced separately, The tube 9
has in this case two chambers, one of which is divided into three
separate spaces 93 which contain the previously weighed quantities
of ferrous cyanide, ferric cyanide and a solution of sodium
carbonate in a glass ampulla. By a technique similar to the
preceding technique a quantity of, for example, 25 cc. accurately
determined by means of thrust pins can be readily supplied from the
ampulla containing sodium carbonate under gas pressure. This
quantity of the solution is then inserted into the other chamber 92
and mixed therein with the ferrous cyanide and the ferric
cyanide.
After these treatments the tube 9 is moved near the working tube 2
for the injection of the reagent. For each working tube 2 the
process is then as follows: In an accurately determined portion of
the tube 2 30 .mu. L. of the filtrate of the first treatment is
absorbed, after which this quantity is shifted upwards. In the same
tube portion is then absorbed a quantity of 4.times. 30 .mu.L. of
the ferri-ferro-cyanide. The filtrate is mixed as before with the
reagent and the same treatment is carried out on all tubes.
The reaction is completed by heating at near the boiling point of
the liquid for one quarter of an hour, for example, in a bath,
which may be a circulating heating bath. Each tube is passed
through the bath for the same period of time. After the bath a
quantity of 120 .mu. L. of ferric phosphide is introduced in the
same way as described above. For color stabilization the belt is
held for about 15 minutes at 20.degree. C. in a drying furnace. The
tubes 2 are then subjected to colorimetric analysis.
When several sequences of analyses have to be performed (glucose,
urea etc.), the belt 12 is moved back to its initial position after
termination of the first sequence of analyses and a new sequence of
tubes 2 is applied to the belt 1, each of which can take in a new
quantity of serum. At the same time the belt 7 with the reagents is
moved so that the tubes 9 are disposed in accordance with the new
sequence of analyses. By the supply of fresh tubes with the
reagents to above the working tubes 2, the tubes employed for the
preceding analysis are conducted away and rejected. For the
invention it is not essential whether the disposition of the belts
in this example, the shape of the tubes containing the reagents and
the displacing members are different.
* * * * *