AU604136B2 - A device for determining the blood group of a sample - Google Patents

Description

:I I I I LILLL l~

AUSTRALIA

PATENTS ACT 1952 COMPLETE SPECIFICATION Form

I

(ORIGINAL)

FOR OFFICE USE 64136 Short Title: Int. Cl: Application Number: Lodged: This document contajn thl amendments made under Section 49and iscorrect for printing.

Complete Specification-Lodged: Accepted: Lapsed: Published: Priority: Related Art: TO BE COMPLETED BY APPLICANT o 4* *a I Name of Applicant: Address of Applicant: Actual Inventor: Address for Service:

A.B.X.

52/56, RUE KLEBER 92300 LEVALLOIS

FRANCE

GRIFFITH HACK CO., 601 St. Kilda Road, Melbourne, Victoria 3004, Australia.

Complete Specification for the invention entitled: A DEVICE FOR DETERMINING THE BLOOD GROUP OF A SAMPLE The following statement is a full description of this invention including the best method of performing it known to me:-

N

A DEVICE FOR DETERMINING THE BLOOD GROUP OF A SAMPLE The invention relates to a device fox: determining the blood group of a sample.

BACKGROUND OF THE INVENTION The basic principle applied in the various different devices for determining blood groups relies on showing up the positive or negative nature of agglutination reactions of the red blood cells or corpuscles in the blood to be analyzed when subjected to the action of various different reactive serums.

Suchn toglunthero s:hows:uto n anotherbme ofruce in Suche ggltitinsowkping tio en fnorbmefscorpsce macomoeclescaledantibodies. The antibodies present in are sectiic serum asctewith other macromolecules which arespeifi tothe antibodies and which are called antigens, 2 15 said antigens being included in the outer walls of the corpuscles. Agglutination is thus obtained," by this antibodyantigen association.

Whenthe corpuscles in the sample have antigen sites or antigens specific to the antibody contained in the reactive serum, then the agglutination reaction is positive.

Otherwise, when the antigen sites or the antigens of the '1 corpuscles are not specific to the antibody in the reactive serum, then the agglutination reaction is negative.

The classical technique of determining blood groups consists in putting a drop of the blood to be analysed on a glass slide and in adding a drop of one of the reactive serums.

Thereafter the glass slide is shaken and the agglutination reaction is visually interpreted in order to determine whether it is positive or negative.

It is necessary to shake the glass slide in order to be able to observe the agglutination reaction as clearly as possible.

However, the viscosity of the blood may lead to an erroneous interpretation when the reaction is not clear, for example wheni; the patient has been subjected to one or more transfusions.

Automated devices are also known for blood group determination, and they make use of the basic principles mentiond above. These devices include at least one measuring 2 cell suitable for receiving a fraction of the blood sample and a fraction of a reactive serum, means for shaking the cell in order to facilitate a possible agglutination reaction between the sample and the reactive se.rur, and means for detecting said agglutination reaction.

Such automated devices suffer from the same drawbacks as mentioned above. In addition, they require an assembly of complex mechanical means for shaking the measuring cells which act as supports for the sample and the various reactive serums.

Further, such automated devices do not avoid the difficulties in interpreting the agglutination reaction.

Consequently, one of the aims of the invention is to provide a device for determining the blood group of a sample which avoids the above-mentioned drawbacks.

S 15 In particular, one of the aims of the invention is to provide such a blood group determining device in which the Vmeans suitable for performing shaking are particularly simple and compact, while still being effective for making it easier to obtain clear agglutination reactions.

Another object of the invention is to provide such a device which is capable of being automated in order to perform various different agglutination tests without manual intervention.

SUMMARY OF THE INVENTION More particularly, the present invention provides a device for determining the blood group of a sample, the device being of the type comprising at least one measuring cell suitable for receiving a fraction of the sample and a fraction of a reactive serum, shaking means for shaking the cell in order to give rise to a possible agglutination reaction between the sample and the reactive serum, and detection means for detecting agglutination reaction, wherein said shaking means comprise a source of ultrasound fixed on the measuring cell.

Preferably, this source of ultrasound operates at a low frequency, preferably in the range 10 kHz to 100 kHz, and in particular at about 50 kHz.

By using this source of ultrasound, a low amplitude and low frequency vibratory motion is transmitted to the measuring x1 3 cell, thereby setting up random motion of the corpuscles within the sample. As a result, the antigen sites present on the surfaces of the corpuscles have a very high probability of being able to bind to the antibodies present in the reactive serum, thereby increasing the potential of the agglutination reaction, if positive.

Since the agglutination reaction is thus made more reliable, blood group determination can be performed on samples of blood which are diluted, and this provides the following 1 0 three advantages.

o°o °Firstly, the quantity of reactive serum required for the reaction can be reduced, thereby reducing the cost of each test.

Secondly, the agglutination reaction is easier to interpret because of the greater overall transparency of the sample. It becomes possible to distinguish within a single sample a population of positive reaction corpuscles from a population of negative reaction corpuscles. This phenomenon occurs, in particular, in patients who have received multiple transfusions and whose blood may contain red corpuscles of various different types from the antigen standpoint. With conventional blood group determination devices, this phenomenon may be visually masked as a function of the percentage of one or other population.

Thirdly, given the simplicity of the device's shaking means, the design of the device, both mechanically and electronically, is considerably simplified.

In a preferred embodiment of the invention, the measuring cell has an internal cavity with two inlets, namely a first inlet for filling said cavity with sample and optionally with diluant, and a second inlet for filling said cavi°ly with reactive serum, together with an outlet for evacuating the contents of the cavity.

Advantageously, the device includes a support member mounted to rotate about an axis and supporting a plurality of measuring cells together with a corresponding number of flasks each of which contains a different reactive serum and is associated with a respective one of the measuring cells, the

I

P 4 14support member being suitable for causing the measuring cells to pass one-by-one past the detection means.

It is thus possible to make an automated device whereby the diluted sample is distributed into the various measuring cells of the rotary support member and in which the various sample fractions are subjected to agglutination tests with different reagents in each of the measuring cells.

Advantageously, one of said inlets to each cell is connected via a duct and an electrically controlled valve to the corresponding flask of reactive serum, whereas the other inlets to the cells are connected via a commron duct to a dilution tank suitable for receiving the sample and a diluant, the respective outlets from the cells being connected via a commuon duct to a waste chamber connected to a source of reduced pressure.

The device may include a sample-taking needle capable of vertical and horizontal displacement, suitable for sucking up a sample of blood from an appropriate receptacle, e.g. from a test tube, and for subsequently expelling said sample into the dilution tank.

The sample-taking needle may be vertically displaceable under the action of an actuator relative to a needle-carrier block between a low position and a high position, said needlecarrier block is horizontally displaceable under the action of another actuator between a sample-taking position in which the needle is brought over the receptacle containing the sample and is lowered to its low position in order to suck up the sample and an expelling position in which the needle is brought over the dilution tank in order to expel the sample into said tank.

BRIEF DESCRIPTION OF THE DRAWINGS An embodiment of the invention is described by way of example with reference to the accompanying drawings, in which: Figure 1 is a perspective view of a measuring cell and of the detection means of an automated device in accordance with the invention; Figure 2 is a perspective view of the rotary support of the device; Figure 3 is a cross-section through the Figure 2 rotary support, also showing the flasks of reactive serum and the detection means of the device; Figure 4 is a simplified circuit diagram of the automated device as a whole; Figure 5 is a diagram of the means for controlling the I displacement of the sample-taking needle; Figure 6 is a diagram of the sample-taking needle and of the sample-taking syringe associated therewith, during the 0 10 sample suction stage; 0" Figure 7 shows the rinsing means provided in the needle carrier; StheFigure 8 shows a portion of the automated device during the stage in which a previously-taken sample is diluted; Figure 9 shows the circuit for focusing the detection means; Figure 10 is a block diagram of the electronic portion of the device; and Figure 11 is a flow chart showing the operation of the automated device.

MORE DETAILED DESCRIPTION The measuring cell 10 shown in Figure 1 is formed in a transparent glass and is generally rectangular in shape being delimited by two parallel large faces 12 and 14. This cell is hollow and thus provides an internal cavity which is generally rectangular in shape and which communicates with two inlet end fittings 16 and 18 and with an outlet end fitting End fitting 16 serves to fill the internal cavity of the cell with a fraction of a blood sample which is preferably diluted, whereas inlet end fitting 18 serves to fill said cavity with a reactive serum as conventionally used for determining blood groups. Outlet end fitting 20 serves to evacuate the contents from the cavity, for example by suction using a vacuum source.

An ultrasound source 24 connected to an electrical power supply 26 is fixed to large face 12, i.e. the top face of the cell, e.g. by gluing. This ultrasound source may be J 4 6 constituted, for example, by a commercially available source such as that available under the reference RTC PXE5A. By way j of example, such a source may have a signal applied thereto II from an oscillator having a passband situated at around 50 kHz.

i 5 After a fraction of preferably diluted blood sample and a reactive serum have been inserted into the internal cavity of F the cell 10, a signal is applied to the ultrasound source, thereby increasing the potential of the agglutination reaction, if positive, as mentioned above.

The positive or negative nature of the agglutination reaction is interpreted by detection means comprising a light source 28 suitable for shining a beam of light 30 through the cell 10. This beam passes initially through large face 12 in order to enter the cell and subsequently leaves the cell by passing through the other large face 14. The light beam transmitted by the cell is picked up by a lens 32 suitable for forming an image representative of the agglutination reaction on a photosensitive surface 34.

In this example, the photosensitive surface 34 is a portion of a photosensitive integrated circuit 36 suitable for emitting output signals 38 representative of the positive or negative nature of the agglutination reaction produced inside the cell The electrical signals 38 serve to discriminate between a positive reaction and a negative reaction by virtue nf the sample image which is formed by the lens 32 on the photosensitive surface 34, with an appropriate degree of magnification.

For example, the photosensitive integrated circuit 36 could be of the RTC NXA 1011 type, or equivalent.

The automated device of the invention includes a rotary support 40 (Figures 2 and 3) suitable for being rotated about an axis X-X which is preferably vertical, by means of an electric motor 42. The support member 40 includes a ringshaped element 44 having eight radial forks 46 projecting therefrom at equal angle intervals around the element 44. Each of the forks 46 is constituted by two parallel arms and is 7 suitable for holding a measuring cell 10 as defined above. The element 44 also includes an orifice 48 for receiving a flask in association with and opposite to each of the forks 46, each of the flasks containing a different reactive serum and being associated with one of the measuring cells 10. The support member 40 is suitable for passing the eight measuring cells one-by-ohe through the above-described detection means.

The ring-shaped element 44 is connected via its inner circular edge to a cylindrical wall 52 which is connected to a 0 10 circular bottom wall 54 whose center is fixed to the shaft 56 a o:0 of the motor 42. The wall 52 serves as a support for eight electrically controlled valves 58 each of which co-operates with one of the flasks 50 and with one of the cells 10, as 0aa Sexplained below with reference to Figure 4.

S .o 15 The lens 32 (Figure 3) constitutes a portion of an image analysis unit which is given an overall reference 60. This Sunit includes uprights 62 connected to the frame of the device a and serving to hold the lens 32 in a non-adjustable position.

The photosensitive integrated circuit 36 is carried by an element 64 suitable for sliding vertically between the abovementioned uprights 62 in order to focus the image formed on the photosensitive surface 34 of the integrated circuit 36. The element 64 is moved vertically by an excentric cam 66 driven by a motor 68 received between the uprights 62, with the element 64 being subjected to the action of traction springs Reference is now made to Figure 4 in which only five of the eight analysis cells 10 are shown, and in which the rotary member 40 has been omitted, in order to simplify the drawing.

Each of the cells 10 has one of its inlets (the inlet corresponding to end fitting 18) connected to the corresponding flask 50 via a duct 72 in which the corresponding electrically controlled valve 58 is inserted. Thus, each of the cells 10 is capable of being fed with a particular reactive serum when the corresponding electrically controlled valve 58 is in its open position.

The other inlets of the cells 10 (those corresponding to end fittings 16) are connected via a common duct '74 to a i: 8 3r dilution receptacle or tank 76 suitable for receiving a diluant and the sample to be analyzed. The duct 74 ends at a junction 77 from which various different ducts 78 extend to respective ones of the inlet end fittings 16 of the cells The outlets from the cells 10 (corresponding to outlet end fittings 20) are each connected via respective ducts 80 to a common duct 82. This duct is connected to a waste chamber 84 which is itself connected to a source of reduced pressure 86 and to a source of high pressure 102.

j 10 The bottom of the dilution tank 76 is connected not only Sto the above-mentioned common duct 74, but also to an fiS evacuation duct 88 which leads directly to the waste chamber 84. An electrically controlld valve 90 is connected in series in both duct- 74 and 88 in order to enable the contents of the ii 15 tank 76 to be directed either to the various cells 10 via said common duct 74, or else to the waste chamber 84, with the contents of the dilution tank being sucked, in both cases, by the source 86.

The application of a pressure or a pressure reduction (vacuum) to the waste chamber 84 is controlled by an electrically controlled valve 92.

An electrically controlled valve 94 is also connected in series in said common duct 82. The contents of the waste chamber 84 can be emptied via an evacuation duct 96 having an electrically controlled valve 98 mounted thereon.

The vacuum source 86 serves to feed a vacuum or lowpressure circuit in order to transfer liquids by suction, be that the transfer of dilute sample from the tank 76 or the transfer of the various respective serums from the respective flasks 50. The vacuum source 86 is obtain[ed by a motorcompressor group 100 which also provides the pressure source 102 (Figure This pressure source feeds a high pressure i circuit whose function is explained below.

The automated device as shown in Figure 4 also includes ,a sanimple-taking needle 104 capable of vertical and horizontal displacements and suitable for sucking up a calibrated quantity of a blood sample into a tube 106 and for subsequently expelling said sample into the, dilution tank 76.

L 9 The sample-taking needle 104 is vertically displaceable relative to a needle-carrier block 108, between a low position and a high position, under the action of an actuator 110. The needle-carrier block 108 is horizontally displaceable under the action of an actuator 112 between a sample-taking position and a sample-expelling position. In the sample-taking position (Figure 4) the needle 104 is brought over the tube 106 and descends to its low position in order to take a sample. In the sample-expelling position, the needle is brought over the dilution tank 76 is lowered to its low position and then expels °0 the sample into the tank 76.

The actuators 110 and 112 are double-acting pneumatic actuators fed with compressed air from the high pressure source 102.

The body of the actuator 110 is vertically fixed to the needle-carrier block 108 and the end of its rod is fixed to the oooo", top end of the sample-taking needle 104 vid a link member 114.

The needle 104 slides vertically in a cylindrical passage 116 provided through the needle-carrier block 108.

The actuator 112 is a double-action pneumatic actuator driven by pressure from the high pressure source 102. The actuator body 112 is fixed to the frame in a horizontal position and the end of its rod is fixed to the needle-carrier block 108.

The high pressure source 102 feeds a high pressure circuit via a pressure regulator 118 for the purpose of feeding the actuators 110 and 112.

The actuator 110 is connected by ducts 120 and 122 to a slide valve 124 driven by an actuator 126 coupled to an electrically controlled valve 128 under electrical control 130.

Similarly, the actuator 112 is connected via two ducts 130 and 132 to a slide valve 134 which is driven by an actuator 136 coupled in turn to an electrically controlled valve 138 electrically controlled at 140. The Figure 5 circuit serves to move the needle 104 over a tube 106, to lower the needle into the tube 106 in order to take a sample, then to raise the needle through the block 108, then to displace the block 108 to bring it over the tank 76, and finally to lower the needle through the block 108 in order to expel the previously taken sample of blood.

The sample-taking needle 104 is connected via a flexible duct 142 to a sample-taking syringe 144 suitable for sucking the sample into the tube 106 and for evacuating said sample by expelling it into the dilution tank 76 (Figure 4).

The sample-taking syringe 144 (Figure 6) comprises a hollow cylindrical body 146 fixed vertically on the frame of the device and provided with an axial passage for a pistonforming rod 148, said axial passage having its top end connected to the duct 142.

teThe rod 148 is suitable for vertical displacement through teaxial passage of the body 146 under the action of a doubleaction pneumatic actuator 150 similarly driven from the high 00 0 15 pressure source 102. The rod 152 of the actuator 150 is o~oCC connected, via a link member 154 to the bottom portion of the rod 148. Thus, when the rod 152 of the piston 150 is deployed, the syringe 144 is operated to take up a calibrated quantity of the sample into the tube 106 by suction. Conversely, when the rod 152 of the actuator 150 is retracted, the syringe 144 is operated to expel the previously taken calibrated quantity of sample into the tmik 76.

The needle-carrier block 108 includes means (see Figures 4 and 7) suitable for externally rinsing the sample-taking needle 104 during its rising vertical displacement immediately after the sample-taking operation. As the needle 104 moves upwards, the passage 116 is fed with an appropriate diluant, e.g.

physiological serum, via a diluant dispenser 156 (Figure 4).

The dispenser 156 comprises a hollow cylinder 158 (see Figurs 4 and 8) in which a piston 160 is moved as driven by a doubleacting pneumatic actuator shown diagrammatically at 162 in Figure 4.

The actuator 162 for actuating the dispenser 156, and the actuator 150 for actuating the sample-taking syringe 144 are driven from the high pressure source 102.

The cylinder 158 is provided with an inlet/outlet orifice 164 connected via an inlet duct 166 both to a diluant supply 168 and to a detergent supply 170 via respective ducts 172 and 174 leading to the duct 166. An electrically controlled valve 176 coupltd to the ducts 172 and 174 serves to feed the dispenser 156 with diluant or with detergent at will.

An outlet duct 178 also leaves the orifice 164 of the dispenser 156 and is suitable for feeding the dilution tank 76, the sample-taking syringe 144, and the needle-carrier block 108. An electrically controlled valve 180 is mounted in the ducts 166 and 178 immediately downstream from the orifice 164, This valve allows diluant or detergent to pass into either of the two ducts 166 and 178 while passage through the other duct is interrupted. When passage through outlet duct 178 is interrupted, the piston 160 of the dispenser 156 is displaced in such a manner as to fill the dispenser with diluant or detergent. Once the dispenser has been filled in this way, the valve 180 is switched over so as to close the passage through inlet duct 166. Thereafter, when the piston 160 is moved towards the orifice 164, the diluant or the detergent contained in the dispenser is expelled via outlet duct 178. Duct 178 splits into two branches: one branch 182 is connected to an inlet end fitting 184 of the needle-carrier block 108; and another branch 186 which again splits into two branches 188 and 190. An electrically controlled valve 192 is fitted to the ducts 182 and 186 in order to send diluant or detergent either to the needle-carrier 108 or else to the tank 76 and the syringe 144.

Another electrically controlled valve 194 is provided on the duct 190, such that the liquid sent along the duct 186 is used either to feed the tank 76 on its own, or else to feed both the tank 76 and the sampled-taking syringe 144 simultaneously.

The inlet end fitting 184 of the needle-carrier block 108 (Figure 7) opens out into the top portion of the cylindrical passage 116. The bottom portion of the cylindrical passage is in communication with an outlet end fitting 196 which is connected to the waste chamber 84 via a duct 198 on which an electrically controlled valve 100 is mounted (Figure 4).

_i Y d 12 Whe thedispenser 156 is operated to send a liquid (diuan ordetergent) towards the needle-carrier block 108 for the purpose of rinsing the needle 104, the liquid leaves the needle-carrier block 108 via the duct 198 and is expelled into the waste chamber 84, with the valve 200 being in the open 0 0 0 -00 The automated device also includes an electronic portion shown diagraimmatically in Figure Tephotosensitive crut36areasoitdwh 0 4 nteface 20 inorder to transform the analog electrical sgnas emtte bythe circuits 36 into digital signals which are m~led o acentral unit 206. This central unit may be consituedforexample, by a MOTOROLA type 68000 Thecenralunit 206 has a controlling keyboard 208 conctdtoa input and it has outputs to an interface 210, to a printer 212, and to a screen 214.

In addition, the central unit 206 is coupled to a set of memories 216.

The interface 210 serves to control the various electrically controlled valves of the device, i.e. both the valves in the fluid flow circuit shown in Figure 4 and the valves in the high pressure circuit driving the four pneumatic actuators.

This interface also drives the electric motors of the device, namely -the electric motor 42 of the rotary membler and the electric motor 68 of the image analysis unit (Figure 3).

The operation of the device is now described with reference to the figures illustrating the structure of the device and with reference to Figure 11 which is an operation flow chart, with the various operating stages being designated by references P1, P2, etc.

13 In the starting position, the needle-carrier block 108 is situated over the emplacement of the tube 106, with the sampletaking needle 104 in its low position. The tube 106 is then presented and the operating cycle is set into motion by pressing on a suitable control means.

The actuator 150 is actuated (Figure 6) for controlling the sample-taking syringe 144 so as to cause the rod 152 to move out from the actuator and suck up a calibrated quantity of blood by displacement of the rod 148 of the syringe 144.

Then, the sample-taking needle 104 is displaced from its low position to its high position by actuating the actuator 110. As the needle 104 rises through the needle-carrier block 108 the needle is rinsed with diluant supplied to the needlecarrier block 108 by the dispenser 156. To do this,. the valve 15 180 opens the passage through duct 178, the valve "92 opens the passage through duct 182, and the valve 200 opens the passage through duct 198, The diluant used for rinsing purposes is thus sent directly to the waste chamber 84.

This first operating stage or stage P1, conrstitutes the S2 sample-taking stage.

In the next operating stage, the needle-carrier block 108 is displaced under the action of the actuator 112 while the needle is in its high position, thereby positioning the needle 104 over the dilution tank 76. The needle 104 is then lowered under the action of actuator 110 so as to penetrate into the dilution tank 76 (Figure The piston 160 of the dispenser 156 is actuated by the actuator 162 in order to send diluant into branch 186 and feed both the sample-taking syringe 144 and the dilution tank 76. In order to do this, electrically controlled valves 192 and 194 (Figure 4) open the passages respectively through ducts 186 and 190. During this operation, the dilution tank 76 receives both the sample of blood together with diluant via the needle 104, and also diluant via duct 188 which opens out sideways into the tank 76.

Thereafter, the dilution (mixture of sample and diluant) contained in the dilution tank 76 is distributed to the various cells 10 by virtue of the vacuum source 86 of the motor i S 14 compressor group 100 (Figure In order to allow this suction to take place, electrically controlled valve 90 ope.ns the passage through duct 74 and the valve 94 also opens the passage through duct 82. During this second stage, or stage P2, the measuring cells 10 are filled solely with the dilution, and the electrically controlled valves 58 prevent flow through the various ducts 72. Each of the measuring cells 10 thus receives a portion of the dilution initially contained in the tank 76, without so far receiving any reactive serum.

10 During the next stage, or stage P3, ultrasound is appl-ied 0 00 0 000 to the cells 10 by applying signals to the ultrasound sources o 24 so as to shake the cells Thereafter, the cells 10 pass one-by-one past the image analysis unit 60 (Figure 3) by virtue of the rotary member rotating. The image received on the photosensitive surface 34 (gure 1) is acquired and stored in memory (stage P4) in order to serve as a light level reference for subsequent analysis of the agglutination reaction.

Given the small depth of field of the lens 32 in the image analysis unit 60, focusing is corrected by means of the circuit shown in Figure 9. The video signal from the photosensitive integrated circuit 36 is analyzed and converted into digital data by a converter 218 and is stored in memory by the central unit 206. The central unit 206 drives the focusing motor 68 of the image analysis unit 60 via an interface 220. The position of the lens is adjusted in such a manner that a maximum is detected in the signal after differentiation.

teAfter this first memory storage operation, the contents of tecells 10 are emptied and the cells are rinsed, where appropriate, with diluant.

Thereafter, the measuring cells are filled a second time 'using the above-described method, but with the various electrically controlled valves 58 being switched in such a manner as to simultaneously suck in a given quantity of tlae various reactive serums contained in the flasks 50. Each of the analysis cells thus receives a fraction of the dilution together with a specific reactive serum.

Thereafter (phase P5), ultra!sound is again applied under the same conditions as during phase P3 concerning the frequency of the signal applied to the ultrasound sources.

In order to improve the yield of -the agglutination reagent, supposing it to be positive, the amplitude of the signal is caused to decrease linearly during a period of time which is very long compared with the frequency of the signal.

The potentialization of the reaction obtained in this way serves to reduce the risk of erroneous interpretation and also 10 to reduce the time required for analysis.

0000 0000 During the next stage, or stage P6, a new image 0 00 0-0 acquisition and storage operation is performed, and this stage 000000is performed under the same conditions as stage P4. The image 0 0 00 1 is stored after the corresponding automatic focusing 0 0 15operations. Each of the cells thus gives an image which is the 000000 0o result of a positive or of a negative reaction.

Thereafter, the device automatically rinses the various 00 circuits after each analysis cycle.

000 0 Using the dispenser 156, a quantity of diluant or of deter- 0 00 20 gent, where appropriate, is sent to the dilution tank 76 and 0) this diluant is then sent to the analysis cell 10, thereby ex- 0 pelling, the sample to be found therein into the waste chamber 84.

This chamber is then emptied via the evacuation duct 96 0 o00 25 under the action of przssure from the high pressure source 102 0 0 0 5in the compressor group 100 (Figure 4).

0 The device then compares, during a stage P7, the two images stored during stages P4 and P5 respectively. For each analysis cell, and thus for each reactive serum, the memory of the device contains two recorded images: one image which was recorded using the dilution without any reactive serum and the other image recorded using the dilution with the reactive serum.

Each address in the memory space corresponds to an elementary zone of the area of the image under consideration.

In addition, the contents of the memory at each address corresponds to the level of the light transmitted through the analysis cell.

C9 U4

I

16 In order to compare the pairs of images, the contents of the memory space corresponding to the first image is subtracted address-by-address from the contents of the memory space corresponding to the second image. This gives rise, in a third memory space, to a synthetic image which has highly contrasted zones in the event that the agglutination reaction was positive Even when high contrast is obtained, the possibility of there being two different populations can still be analyzed i.e. one group of red corpuscles subject to a positive reaction and another group which is not.

Otherwise, if no high contrast is observed between the two 0 stored images, then the aggluo. ;.on reaction was negative.

In any event, comparisor., are performed (stage P11) with other previously stored channels (stage P12).

15 From this comparison, phenotype analysis is deduced (stage 1 0 °0 P13) as is possible genotype analysis (stage P14). The results obtained are output (stage P15) with the results being S°c automatically synthesized by the microprocessor of the central unit and with the results being delivered via the printer 212.

o'