Note: Descriptions are shown in the official language in which they were submitted.
214908~
SYSTEM FOR THE OPTICAL ANALYSIS
OF A SAMPLE OF A REACTION MIXTURE
The present invention relates to a system for the
optical analysis of a sample of a reaction mixture.
More particularly, the present invention relates to an
optical analysis system comprising an optical analysis cell
provided with a source of light and photoelectric measuring
means disposed on opposite sides of a circulation vessel of
transparent material of a fluid circuit, comprising a part
for connecting the circulation vessel to means for taking
and rejecting the sample of the reaction mixture to be
studied, and a pump for the aspiration of said mixture into
said vessel and the discharge of said mixture out of said
vessel.
Systems for the optical analysis of samples of a
reaction mixture are well known in the art, for example in
medical biology for colorimetric, nephelometric or
turbidimetric analyses.
An embodiment of such a system is to be found in the
document US-A-2 797 149 which discloses an apparatus having
a large part of the previously-mentioned characteristics for
a study of suspensions.
Other embodiments of analysis systems of this type are
to be found in the documents FR-A-2 262 307, FR-A-2 125 000
and DE-A-20 35 915.
Still further embodiments of optical analysis devices
are to be found in the documents US-~-4 398 894 and
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US-A-4 253 846.
The document US-A-4 398 894 discloses an optical
analysis device comprising a fluid circulation circuit and
optical analysis means disposed on opposite sides of the
fluid circulation circuit. This device permits determining
the degree of agglutination of particles in a mixture but
requires a specific measuring system. Moreover, it does
not permit the analysis of a sample circulating in the
circulation circuit at relatively high speed.
The document US-A-4 253 846 discloses a device for the
analysis of samples circulating in an analysis conduit, by
means of an optical analysis system comprising elements
disposed along the conduit for adding to each sample a
corresponding reagent. This device permits ensuring the
reaction between different reagents and a sample to be
titrated in the conduit but comprises a very complex fluid
circuit.
Further, all these systems have a number of drawbacks
since, as they are used for achieving in series analyses of
samples of different reaction mixtures, there is a risk of
contamination of a sample by the other samples and in
particular by the preceding sample because these samples
pass through the same fluid circuit.
In an attempt to overcome these problems, it has been
proposed to employ means for cleaning this fluid circuit,
for example by circulating in the latter a cleaning fluid
between each sample, but it has been found that problems of
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contamination remain related to the complex structure of
this fluid circuit.
An object of the invention is therefore to overcome
these problems by providing an optical analysis system
which is simple and reliable.
The invention therefore provides a system for the
optical analysis of a sample of a reaction mixture, of the
type comprising an optical analysis cell, provided with a
source of light and photoelectric measuring means disposed
on opposite sides of an optical circulation vessel which is
of transparent material and is a part of a fluid circuit
comprising a part connecting the circulation vessel to
means for taking and rejecting the sample of the reaction
mixture to be studied and a pump for the aspiration of said
mixture into said vessel and the discharge of said mixture
out of said vessel, characterized in that the circulation
vessel and the connecting part are in the form of a tube of
which one end is associated with an aspiration and
discharge pump and the other end is connected directly to
the sample taking means, the inside diameters of the vessel
and the connecting part being identical so as to form a
continuous fluid circuit, and the circulation vessel, the
connecting part and the sample taking means are constituted
either by a single cylinder tapered at an end thereof, or
by the assembly of different tubes, including a flexible
tube, which have identical inside diameters. In the second
case, the flexible tube is the connecting part.
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A better understanding of the invention will be had
from the following description of a nephelometric
application of the invention given solely by way of example
with reference to the accompanying drawing in which:
Fig. 1 is a block diagram of the general structure of
an optical analysis system according to the invention with
a flexible connecting pipe;
Fig. 2 is a block diagram of the structure of an
optical analysis cell which is part of an analysis system
according to the invention, and
Fig. 3 is a side elevational view of a diaphragm which
is part of the structure of an optical analysis system
according to the invention.
As can be seen in these Figures, a system according to
the invention for the optical analysis of a sample of a
reaction mixture comprises an optical analysis cell
generally designated by the reference numeral 1 in said
Figures, provided with a source of light 2 and
photoelectric measuring means 3 disposed on opposite sides
of a circulation vessel 4 of transparent material
constituting an element of a fluid circuit.
This fluid circuit comprises either a flexible pipe or
tube 5 connecting the circulation vessel 4 to means 6 for
taking and rejecting the sample of the reaction mixture, or
a cylinder tapered at one end so as to constitute the
sam~le taking means 6 and a pump 7 for the aspiration of
said mixture into said vessel and the discharge of said
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mixture out of said vessel.
The pump 7 may be connected to the circulation vessel
by means of a valve 8 also connected to a source of
cleaning fluid 9 to permit, as will be described in more
detail hereinafter, injecting cleaning fluid into the fluid
circuit upon the discharge of the reaction mixture out of
the circuit for the purpose of cleaning the latter.
The means 6 for taking and rejecting the sample may be
for example a needle connected to the corresponding end of
10 . the flexible connecting pipe 5, the latter being for
example fixed to an arm 10 of a manipulator 11 whereby it
is possible to place this needle in front of reaction
containers, such as small microtitration plate tubes or
wells, for example 12, disposed on receiving means and in
which different reaction mixtures to be analyzed are
placed.
It will therefore be understood that, when effecting
the analysis, the arm 10 of the manipulator 11 places the
means 6 for taking and rejecting the sample in one of the
containers 12 to permit the pump 7 to aspirate a sample of
the reaction mixture contained in this container into the
fluid circuit and cause it to enter the circulation vessel
4 for its optical analysis.
When this analysis has been effected, the arm 10 of
the manipulator 11 shifts the means 6 for taking and
rejecting the sample for example to a position in front of
means for draining off this sample and the pump 7 is
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actuated to discharge this sample from the fluid circuit.
At the same time, the valve 8 may be actuated to
permit the injection into this fluid circuit of cleaning
fluid for cleaning the latter and removing any trace of the
sample.
According to the invention and as shown in the
Figures, the circulation vessel may be in the form of a
tube 4, for example of glass, of which one end is
associated with the pump 7 and the other end is connected,
for example by adhesion, welding or pressure, to the
corresponding end of the flexible connecting pipe 5, and
the inside diameters of the tube forming the vessel and
the flexible connecting pipe are identical so as to form a
continuous fluid circuit and facilitate the cleaning of the
latter and avoid any problem of contamination between the
samples or by the cleaning liquid.
The term "identical" is intended to refer to diameters
whose sizes may be exactly e~ual or differ from one another
by substantially 10%.
According to an alternative embodiment of the
invention, the inside diameters of the tube constituting
the vessel 4 and the connecting pipe 5 are identical in the
region of their joint but, following on this joint, it is
possible to envisage a gradual and continuous reduction in
the inside diameter of the connecting pipe 5 to a reduction
of substantially 50% and preferably 25%.
It will of course be understood that this analysis
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system may also act as a segmentation system by means of
air in which a certain amount of air is drawn into the
fluid circuit before the sample of the reaction mixture.
According to one embodiment, the inside diameters of
the tube and the pipe may advantageously be around 2 mm and
the speed of circulation of the reaction mixture in the
tube during the sample taking stage may be for example
equal to 55 mm per second, which results in a regular flow
in the case of an air segmentation system.
As can be seen in Fig. 2, the source of light 2 may
comprise a laser diode disposed on one side of the tube 4.
Disposed on the other side of this tube in a
conventional manner are a window 13, a diaphragm 14, a
deflecting mirror 15, means 16 for trapping light, a lens
system 17, a photoelectric measuring cell 18 and means 19
for processing output signals of said photoelectric
measuring cell.
An embodiment of the diaphragm 14 which is
particularly suitable for a nephelometric measurement is
shown in Fig. 3.
This diaphragm is interposed between the tube 4 and
the photoelectric measuring cell and may comprise a central
aperture 20 in front of which there is placed the
deflecting mirror 15 for deviating the light beam passing
through this aperture in the direction toward the trapping
means 16 to eliminate this beam of direct light.
This diaphragm may further comprise at least two
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openings 21, 22 which are symmetrical relative to the axis
of the diaphragm and adapted to allow through the beams of
light deviated by the particles in suspension upon its
passage through the tube, in the direction toward the
photoelectric measuring cell.
This diaphragm is preferably arranged to allow through
the beams of light dispersed within an angle of 8 to 16
relative to the optical axis of the laser diode.
In order to improve the precision of the measurements
effected on the reaction mixtures containing particles in
suspension, resulting for example from an agglutination, it
is preferred to effect a plurality of successive
measurements, from 50 to 200 per second, on the fluid in
motion in the measuring tube, which permits, by means of
the means 19 for processing the output signals of the
measuring cell, for example eliminating the aberration
values and calculating a mean of the measured signals to
obtain a single value considered as the signal
corresponding to the analyzed sample.
It wil be observed that the processing means 19 may
comprise any suitable computer which also permits
controlling the various previously-described elements.
