HK1032264B - Automatic analysis apparatus used for timing blood coagulation - Google Patents

Description

The present invention relates to an automatic analytical apparatus which can be used for the determination of the time changes in the physical state of a fluid medium.

It applies in particular, but not exclusively, to the determination of the clotting time of blood according to a process whereby the blood sample is placed in the bottom of a vessel containing a ferromagnetic ball which is driven in periodic motion by an external magnetic field.

The principle of such detection is set out in European patent No EP 88403279.8 filed on behalf of SERBIO S.A.

In a high-rate analyzer of this type (about 360 tests/hour), each single-use bowl has a small, parallel-epipedal shape, the curved bottom of which forms the ball's rolling path, while the side opposite the bottom has an opening. These buckets are arranged side by side and detachable on a flexible support strip which temporarily closes their openings.

In this type of automatic machine, with a failure rate of about 3 operations per year, the buckets are removed from the tape and then placed in suitable places inside the machine. These machines therefore include relatively complex, fault-causing and expensive automatic means of grip and transfer. They are suitable for laboratories with large numbers of tests to be performed, in relation to the rates mentioned above, and who have a culture and expertise in laboratory automation.

At the same time, for small laboratories which do not have special skills in automation, there are manual or semi-automatic machines with high reliability (intervention rates for failures of any cause, of the order of 1 intervention/10 years).

It appears that between the two types of apparatus mentioned above, there is an unoccupied market for small and medium-sized automatic machines capable of running at rates of 60 to 120 tests per hour and which must be highly reliable because of the structure and competence of the laboratories to which these machines are intended.

By patent EP 0 525 273 A1 a device for determining the time of blood clotting was also proposed, using a plate in which a plurality of cavities are arranged in which the balls with the samples are arranged.

According to this document, an electronic camera takes an image of the plate with all its cavities to detect variations in ball movement

It turns out that the complexity of the solutions used for automation and its corresponding costs are a barrier to diffusion in small and medium-sized laboratories. In the first case, this complexity is mainly due to the manipulation of the vessels, which is necessary in the analysis cycle to make their capture, detach them from the film, bring them into the measuring well and extract them at the end of the measurement to be discharged into a discharge compartment, it being understood that these manipulations are necessary due to the nature of the means used to determine the time of blood clotting.

The invention therefore aims in particular at the development of a simpler and less expensive design, but which allows sufficient rates of change to be used in the field of small and medium-sized devices. e invention therefore proposes an automatic analysis apparatus of the type in which a liquid sample to be analysed is placed in a bowl containing a ferromagnetic ball driven in a periodic motion by a magnetic field, this apparatus comprising an electronic camera oriented towards the bowl and a processor capable of detecting from the image of the bowl changes in the ball's movements.

According to the invention, this apparatus is characterised by the use of a plurality of buckets fixed on a support strip running one by one through a detection station and by the fact that the detection station includes at least one electronic camera located below the buckets and electromagnetic means placed laterally relative to the strip to the right of the side faces of the buckets, so as to generate a magnetic field in the axis of movement of the ball contained in the bucket in the detection station, the rolling motion of the strip being of a stepwise or even continuous type.

The advantage is that the electronic camera will be placed below the bowl, with the electromagnetic means for generating the external magnetic field then being placed laterally, in the axis of movement of the ball.

It turns out that this combination of camera and electromagnetic means lends itself particularly well to online detection of the movements of the balls in the containers.

In this case, the receptacles, which remain attached to the flexible support band, are driven in a stepwise or even possibly continuous motion along a path successively passing through a pipette station into which a reagent is injected, a detection station comprising electromagnetic means placed laterally, on either side of the band and/or at least one electronic camera placed under the receptacle path in the magnetic field-emitting zone, and a storage station for used receptacles.

The pipetting station may be conveniently equipped with a pipette that moves vertically and horizontally in a circular path so that it can occupy an injection position to the right of the vessel path to allow the injection of reagents into the vessels, a rinsing position to the right of a rinsing tank and at least one reagent collection position to the right of a reagent dispenser collection area.

This reagent dispenser may consist of a carousel comprising a plurality of reagent tanks moving in a circular path so that they can be brought successively into the sampling area.

A method of execution of the invention will be described below with reference to the attached drawings in which: Figure 1 is a schematic representation of a medium-sized automatic analyser;Figure 2 is a schematic perspective view of a bowl mounted on its band;Figure 3 is a schematic view from above of the band with its bowl fittings as it passes through the incision, pipetting and detection stations;Figure 4 is a schematic vertical cut according to A/A of Figure 3;Figure 5 is a view schematically showing the movements of the ball contained in a bowl, within the field of view of a camera;Figure 6 is a graph showing the amplitude of the ball movements with time.

In this example, the automatic analyser 1 uses a container feeder with a coil 2 on which a strip B containing several containers C is wrapped.

As shown in Figure 2, the C-boxes, made by moulding a transparent plastic material, each have a flat body with a parallel-epipedal shape, the curved bottom FI of which forms a rolling path for a BE ball made of ferromagnetic material. Opposite to this bottom FI, the C-bowl has an opening at which its two opposite edges BO1, BO2 are extended at right angles by two respective edges R1, R2 each with a cylindrical protrusion PC extending on the opposite side of the body. These two protrusions are intended to be forced into two respective TR holes provided on the two side edges of the B-band.

Coil 2 is mounted rotatively inside a receptacle to allow strip B to be run in a straight line through a strip incision station 3 (if the strip is not already pre-cut), a pipet station 4, a detection station 5 and then a strip recovery station 6 with used containers.

The operation of these various stations is managed by a P processor with a central unit and peripherals such as, for example, a display 8/keyboard 9 assembly.

The drive of the B-band along its journey is provided by a step-by-step drive mechanism involving two endless B1, B2 bands guided by pebbles and resting on the side faces of the C-bins carried by the B-band.

Pipette station 4 is served by an automated vertical pipette 10, which moves in height so that it can be positioned in a low pipetting or rinsing position and in a high position allowing its movement in a horizontal plane.

This pipette 10 is attached to one end of a rotating mounted arm 11 by its other end around a vertical axis 12.

This particularly simple mechanism allows pipette 10 to be successively brought to the pipet area of pipet station 4, to a diametrically opposite rinsing area 13 equipped with one or more rinsing tanks and to two sampling areas 14, 15 arranged symmetrically with respect to the axis passing through pipet area 4 and rinsing area 13.

Sampling areas 14, 15 are located in the path of vessels R1, R2 carried by two respective CR1, CR2 mobile carousels rotating around two vertical axes 17, 18 and controlled by two servo motors driven by the processor P.

One of these CR1 carousels is intended to contain R1 vessels of blood samples to be analysed while the other CR2 contains R2 vessels assigned to the various reagents to be used in the analyses to be carried out.

The P processor is of course programmed to command pipet sequences appropriate to the nature of the analyses to be performed, and may consist of: a pre-rinsing of pipette 10, a dose of samples taken from one of the CR1 carousel's R1 containers, an injection of this dose into a C-bowl in the pipette 4, a rinsing of the pipette 10, a dose of reagent taken from one of the CR2 carousel's R2 containers, an injection of this reagent into the C-bowl, the identification of the blood samples to be analysed and the reagents are automatically performed by a 19 barcode reader capable of reading the barcodes on the containers carried by the CR1 carousels R1, R2

In this example, a single barcode reader 19 is used for these readings, mounted on the end of an arm 20 rotating about a vertical axis 21 so that it can occupy three positions, namely: a barcode reading position P1 from CR1 carousel containers R1, a barcode reading position P2 from CR2 carousel containers R2 and a barcode reading position P3 from containers placed by the operator in a reading post, for example for inputting information processed by the processor in the operation of the apparatus.

Measurement item 4 here comprises three successive units of measurement each comprising (Figures 3 and 4): a pair of coaxial electromagnets E1, E1 - E2, E'2 - E3, E'3 located on either side of band B, to the right of the side faces of the C-bottles, and an electronic camera CM1, CM3 with a lens located below the C-bottles carried by band B.

The electromagnets E1, E1 - E2, E'2-E3, E'3 are excited by a PR power circuit driven by the processor P in such a way as to generate an impulsive magnetic field capable of driving the BE ball alternately to the bottom of the bowl C.

The CM1 - CM3 camera is coupled to the P processor which analyses the image in real time by means of appropriate software in order to measure the amplitude of BE ball oscillations and determine the critical moment when this amplitude drops below a certain threshold (e.g. 50% of the initial amplitude) (Figures 5 and 6).

Of course, the P processor counts the time between the time the reagent was injected into the C bowl and the critical moment, so as to deduce a clotting time.

The use of several units of measurement staggered along the B-band path has the advantage of allowing greater flexibility of operation and, above all, of greatly extending the range of clotting times of the blood samples to be analysed.

Of course, the stepwise movement of the strip is synchronized with the operating times of each of the machine's stations and in particular with the magnetic field pulses generated by the coils.

The pipetting station may be located in the same location as the measuring station.

The invention is not, of course, limited to the method of execution described above.

For example, each camera may present a field including several buckets each excited by a separate pair of electromagnets, so as to follow the bucket several steps ahead with a P processor programmed to detect the movement of balls from different buckets simultaneously.

Claims (9)

1. Automatic analysis apparatus of the type in which a liquid sample to be analysed is placed in a cup (C) containing a ferromagnetic ball (BE) driven in a periodic movement under the effect of a magnetic field, this apparatus including an electronic camera (CM₁ to CM₃) orientated towards the cup (C), and a processor (P) for detecting from the image of the cup (C) the modifications of the movements of the ball (BE), characterised in that it uses a plurality of cups secured to a support strip (B) running one by one into a detection station (5), and in that the detection station includes at least one electronic camera (CM₁, CM₂) situated below the cups and electromagnetic means placed laterally with respect to the strip (B) at the right of the side faces of the cups so as to generate a magnetic field inside the movement axis of the ball contained in the cup located in the detection station, the unwinding movement of the strip (B) able to be of the step-by-step or even continuous type.
2. Apparatus according to claim 1, characterised in that the strip (B) follows a rectilinear path passing successively through a possible incision station of the strip (B), a pipette station (4), a detection station (5) and a recovery station (6) of the strip provided with its used cups.
3. Apparatus according to one of the preceding claims, characterised in that the pipette station (4) is served by a vertical pipette (10) abler to move upwards and fixed to one of the extremities of an arm (11) mounted rotating around a vertical spindle so as to be able to be brought by successively rotating to a pipette station, a rinsing station and to two sampling areas (14, 15).
4. Apparatus according to claim 3, characterised in that the sampling areas (14, 15) are situated on the path of the receptacles (R₁, R₂) borne by two respective carrousels (CR₁, CR₂) able to move in rotation around two vertical spindles (17, 18) controlled by two servomotors, one of the carrousels (CR₁) being used to contain the blood samples receptacles (R₁), whereas the other (CR₂) contains the receptacles (R₂) allocated to the reactive agents able to be used as part of the analyses it is desired to be carried out.
5. Apparatus according to claim 4, characterised in that it includes a processor (P) programmed so as to control pipette sequences successively comprising:

   - a prior rinsing of the pipette (10),

   - the taking of a dose of samples contained in one of the receptacles (R₁) of the carrousel (CR₁),

   - the injection of this dose into a cup (C) situated on the pipette station (4),

   - the rinsing of the pipette (10),

   - the taking of a dose of the reactive agent contained in one of the receptacles (R₂) of the carrousel (CR₂),

   - the injection of this reactive agent dose into the cup (C).
6. Apparatus according to claim 5, characterised in that the blood samples to be analysed and that of the reactive agents is made automatically by means of a bar code reader (19) able to read the bar codes present on the receptacles (R₁, R₂) borne by the carrousels (CR₁, CR₂).
7. Apparatus according to claim 6, characterised in that it includes a single bar code reader (19) mounted at the extremity of an arm (20) pivoting around a vertical spindle (21) so as to be able to occupy three positions, namely:

   - a position (P₁) for reading the bar codes of the receptacles (R₁) of the carrousel (CR₁),

   - a position (P₂) for reading bar codes of the receptacles (R₂) of the carrousel (CR₂), and

   - a position (P₃) for reading receptacles placed by the operator in a reading station, for example for picking up information exploited by the processor as part of the functioning of the apparatus.
8. Apparatus according to one of the preceding claims, characterised in that the field of the camera (CM₁ - CM₃) includes several cups (C) each excited by separate electromagnetic means.
9. Apparatus according to claim 8, characterised in that the processor (P) is programmed so as to simultaneously detect the movements of the balls (BE) of said cups (C).