HK1069436B - Device for automatic analysis of a liquid sample - Google Patents

Description

The present invention relates to a device for the automated analysis of a liquid sample, the object of which is in particular, but not exclusively, to develop it into an automatic analytical apparatus which can be used for the determination of the time to change the physical state of a medium.

This apparatus is particularly suitable for determining the time of blood clotting by a process whereby the blood sample is placed in the bottom of a vessel containing a ferromagnetic ball which is periodically moved by an external magnetic field, and changes in the movements of the ferromagnetic ball (e.g. variations in amplitude and/or frequency) which are representative of changes in the physical state of the blood are then detected by appropriate means.

Such an apparatus is described in patent WO 99 64839 filed on behalf of Junior Instruments.

It consists of a single-use cup dispenser, each containing a curved bottom forming the ball's rolling path and an opening on the opposite side of the bottom. These cups are arranged side by side and attached removably to a flexible support film that closes their openings. The cup-equipped film can be rolled onto a coil that can engage on a hub provided in a storage and distribution compartment of the device. The cups are passed one by one through a detection station.

The support film sealing the openings of the vessels, it is necessary to make a slot by incision to allow the pipette to pass.

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In addition, the presence of the film implies the use of a powerful light source and the homogeneity of the beam generated by this source through the vessel will be disturbed both by the presence of the crack and by possible impurities present on the film.

The invention is therefore more specifically intended to address these disadvantages.

To this end, it proposes a device for the automated analysis of a liquid sample, consisting of a series of single-use vessels, each containing a bottom, an upper side opposite the bottom with an opening and two opposite edges extending on either side of the vessel considerably in the plane of the opening, the vessels being arranged side by side and held together by a flexible film fixed to the edges, covering at least partly the openings of the vessels and having a series of orifices located respectively to the right of the openings of the vessels, these orifices being dimensioned so as to allow the injection and/or lifting means to be engaged without contact.

The device is made of a diffuser material for infrared light making the light beam more homogeneous. The dimensions of the orifice will then be determined in particular by the dimensions of the pipette, its position and the desired homogeneity of the intensity of the light beams passing through a predetermined volume of the cup.

In the case where the device determines the time to change of physical state of a sample in the vessel by detecting the movement of a moving ball on the bottom of the vessel, the opening may be in the form of an oblong opening parallel to the ball's rolling path and slightly less wide than the diameter of the ball.

The advantage is that the film material may have liquid absorption properties, e.g. porosities, to fix any liquid projections and thus reduce the risk of contamination of samples in the containers adjacent to the test vessel.

This device may also include a pipetting station where a pipette is moved transversely in relation to the axis of rolling of the vessels. To avoid any imprecision in the movement of the pipette, the film or its edges may be detached by the application of the pipette and/or the projections, the film orifices being extended along a transverse axis of the axis of rolling of the vessels.

The device may also include a cutting station for the analysed vessels to be collected in a single container.

It should be noted that this film-tube set remains adaptable to existing models.

A method of execution of the invention will be described below, by way of example but not limited to, 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 film-mounted bowl; Figure 3 is a schematic view from above of the film with its bowl and rack drive system; Figure 4 is a schematic vertical cut according to A/A of Figure 3.

In this example, the automatic analyser 1 feeds a series of 100 vessels into a band 2.

As shown in Figure 2, the C-cubes, each made by moulding a transparent plastic material, 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-cubes have an opening at which its two opposite edges BO1, BO2 are extended at right angles by two respective edges R1, R2 each equipped with a cylindrical protrusion PC extending on the opposite side of the body. These two protrusions are designed to forcefully engage in two respective holes TR1, TR1, and TR1, respectively.

The film is flexible and consists of an absorbent material, such as paper, and is perforated above each bowl with an oblong hole 4 which extends along the longitudinal axis of the bowl transversely to the axis of rolling of the bowl.

As shown in Figure 4, the vessel strip 2 is guided by a rail 5 which has a U-shaped section with two vertical wings extended at right angles by two edges R3, R4, the edges R1, R2 of the vessels resting on the edges R3, R4. The strip passes successively through a pipetage station 6, a detection station 7 and a cutting station 8 at the exit of which each analysed vessel is collected in a container 9 provided for this purpose.

The operation of these various stations is managed by a P processor with a central unit and peripherals such as, for example, a screen 10/keyboard 11 assembly.

The drive of film 3 is provided by means of a drive mechanism involving an endless belt 12 guided at each end by pebbles 13, 14. This belt has a cranking with the crests spaced at a distance equal to a multiple of the width of the cups (for example 4-5 cups). These crests have a circular expanding profile which corresponds to a normal denture-shaped rack in such a way as to fit perfectly between the teeth of the dentured profile of the strip; they are thus able to drive the strip of teeth with precision, with self-centering and compensation of possible joints.

Pipette station 6 is served by an automated vertical pipette 15, 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 15 is attached to one end of a rotating arm 16 mounted at its other end around a vertical axis 17.

This particularly simple mechanism allows pipette 15 to be successively brought to the pipet area of pipet station 6, to a diametrically opposite rinsing area 18 equipped with one or more rinsing tanks and to two sampling areas 19, 20 symmetrically arranged with respect to the axis passing through pipet area 6 and rinsing area 18.

Sampling areas 19, 20 are located in the path of RE1, RE2 vessels carried by two respective CR1, CR2 mobile carousels rotating around two vertical axes 21, 22 and controlled by two motors driven by the P processor.

One of these CR1 carousels is intended to contain RE1 vessels of blood samples to be analysed, while the other CR2 contains RE2 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: pre-rinsing of pipette 15, taking a dose of sample from one of the RE1 containers of the CR1 carousel, injecting this dose into a C container in the pipette 6, rinsing of pipette 15, taking a dose of reagent from one of the RE2 containers of the CR2 carousel, injecting this dose of reagent into the C container, identification of blood samples to be analysed and of reagents by automatically using a barcode reader 23 capable of reading the barcodes from RE1, RE2 containers carried by CR1 carousels,

In this example, for these readings, the single barcode reader 23 is mounted on the end of an arm 24 rotating about a vertical axis 25 so that it can occupy three positions, namely: a P1 reading position for barcode readings from CR1 carousel RE1 containers, a P2 reading position for barcode readings from CR2 carousel RE2 containers, and a P3 reading position for 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 7 here comprises three successive measurement positions each comprising (Figure 4) a pair of coaxial electromagnets E1, E1 - E2, E'2 - E3, E'3 located on either side of film 3, to the right of the side faces of the C-tubes.

Item 7 also includes: an infrared light source 26 above the bowl,a bar of charge transfer detectors (CTS) 27 below the C-boxes supported by the film on which the image of the light source-illuminated ball is projected.

The use of several measuring positions along the film path has the advantage of allowing greater flexibility of operation.

It should be noted that the light source support which is fixed to rail 5 also provides a support from the top of the vessel/film assembly to prevent the rail from coming out.

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 camera 27 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 the BE ball oscillations and determine the critical moment when this amplitude drops below a certain threshold (e.g. 50% of the initial amplitude).

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 film movements are synchronized with the operating times of each of the machine's positions 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 infrared source/camera assembly may have a field including several buckets each excited by a pair of separate electromagnets, so as to follow the bucket several steps ahead with a P processor programmed to simultaneously detect the movement of balls from different buckets.

Claims (14)

1. A device for automated analysis of a liquid sample, this device including a succession of disposable cells (C) each comprising a bottom, an upper face opposite to the bottom, having an aperture and two opposite rims (R1, R2) which extend on either side of the cell substantially in the plane of the aperture, the cells are positioned side by side and made integral with each other by a flexible film (3) fixed on said rims (R₁, R₂), at least partially covering the apertures of said cells (C), and having a succession of ports (4) respectively located at right angles to the apertures of said cells, these ports being dimensioned so as to allow contactless engagement of injection and/or sampling means, an optical detection station (7) comprising an optoelectronic detector (27) positioned underneath the bottom of the cell, characterized in that the optical detection station (7) further comprises a light source (26) located above the cell and illuminating the upper face of the latter and in that the film (3) is made in light-diffusing material.
2. The device according to claim 1, characterized in that the dimensions of the port (4) are determined according to the dimensions of the pipette, to its position as well as to the sought-after homogeneity of the intensity of the light beams passing through a predetermined useful volume of the cell.
3. The device according to claim 1, characterized in that the bottom of the cells (C) form the rolling path of a ball (BE) driven by an external magnetic field.
4. The device according to any of claims 2 and 3, characterized in that the aforesaid port (4) has the shape of an aperture with an axis parallel to the rolling path of the ball (BE) and the width of which is slightly less than the diameter of the ball.
5. The device according to claim 1, characterized in that the material forming the film has liquid absorption properties.
6. The device according to claim 1, characterized in that the succession of cells follows a course successively passing through a pipeting station (6), a detection station (7) and a station for cutting out (8) analyzed cells.
7. The device according to claim 1, characterized in that said analyzed cells (C) are collected in a single container (9).
8. The device according to claim 1, characterized in that said rims (R₁, R₂) have a shape such that they may engage between the notches of a drive belt.
9. The device according to claim 8, characterized in that said notches have a circle involute profile which corresponds to a rack with normal teeth.
10. The device according to any of claims 8 and 9, characterized in that said rims (R₁, R₂) have the shape of an isosceles trapezium, the large base of which is integral with the cell (C).
11. The device according to claim 10, characterized in that the side borders of the film (3) have in the interval of the rims (R₁ , R₂), successive cells of the trapezoidal cut-outs, the oblique edges of which extend at right angles to the oblique edges of the rims (R₁, R₂).
12. The device according to claim 1, characterized in that the light source of said detection station (7) is a source of infrared light (26) and the optoelectronic detector is a camera.
13. The device according to claim 1, characterized in that the support of the light source fixed on the rail (5) holds the cells (C)/film (3) assembly from the top.
14. The device according to claim 3, characterized in that the external magnetic field is generated by electromagnetic means (E₁, E'₁-E₂, E'₂-E₃, E'₃,) placed sideways relatively to the succession of cells at right angles to their side faces.