WO1996007918A1

WO1996007918A1 - Automatic apparatus for immunological analyses

Info

Publication number: WO1996007918A1
Application number: PCT/IT1995/000145
Authority: WO
Inventors: Alberto Innocenti
Original assignee: S.E.A.C. S.R.L.
Priority date: 1994-09-08
Filing date: 1995-09-01
Publication date: 1996-03-14
Also published as: EP0731919A1; IT1278570B1; ITFI940171A1; ITFI940171A0

Abstract

The apparatus for immunological analyses comprises: a first support (3) for a pluarlity of biological liquid samples to be analysed; a second support (5) for a plurality of flasks containing reagents; a third support (13) for micro-plates (26) with cavities (26A) inside which the biological liquid to be analysed and the reagent are dispensed; a dispensing arm (7.10, 7.11) with dispensing means (9, 11, 25) which selectively remove the samples of biological liquid and dispense them into the cavities (26A). The third support (13) for the plates (26) comprises a rotating table (13) with a substantially vertical axis of rotation (A), with a plurality of stations (13A) for corresponding plates (26); washing means (15Z, 16A, 16B) are associated with the rotating table (13) in order to wash the cavities (26A) of the plates (26), said means being controlled in accordance with a system of polar coordinates.

Description

"AUTOMATIC APPARATUS FOR IMMUNOLOGICAL ANALYSES"

Description

Technical field

The invention relates to an apparatus for carrying out immunological analyses on biological liquids, such as sera, plasmas, urines or the like, or similar analyses.

State of the art

Immunological analyses envisage the use of plates, or micro-plates, with a plurality of cavities or wells, to the walls of which a substance containing the specific antibody of the test has been adhered. ' A quantity of biological liquid to be analysed (for example blood plasma) is dispensed into a cavity. With the addition of any suitable reagent, the enzyme reaction, in particular an antibody- antigen reaction, takes place. The antibodies present on the walls of the cavity react with the antigens which may be present in the sample and give rise to antigen-antibody complexes which remain adherent to the wall of the cavity. Before reading the result of the enzyme reaction, the individual cavities of each plate are washed in order to eliminate the liquids contained therein, leaving the film intact, containing the antigen-antibody complexes, and adherent to the internal wall of each cavity. After washing, the plate is read by a suitable reading unit which supplies the result of the analysis.

An apparatus of this type is known from EP- A-0 500 506, comprising: a first support for a plurality of biological liquid samples to be analysed; a second support for one or more reagents; - 2 -

a third support for plates having cavities inside which the biological liquid to be analysed and the reagent are dispensed; a dispensing arm carrying dispensing means which selectively remove said biological liquid samples and said reagent or said reagents and dispense them into said cavities; and washing means for washing said cavities. The dispensing arm is movable along two orthogonal and horizontal axes and carries both the washing means and the dispensing means. The plates are installed on a fixed support and after dispensing of the samples and reagents and after the necessary incubation time, if necessary with temperature regulation and agitation, they are extracted manually and inserted into a separate reading unit.

This apparatus of known type is extremely versatile and compact, but has a limitation in the fact that it does not have an incorporated reading unit. Furthermore, the integration of all the dispensing and washing members on a single arm has the advantage of greater compactness, but the disadvantage of increasing the working times, since the sample and reagent removal and dispensing operations cannot be performed at the same time as the washing operations.

A similar apparatus is described in EP-A-0 210 014. Here the plates are carried on a table which performs a translating movement in order to displace the plates themselves with respect to the dispensing and washing means.

WO-A-8 706 008 discloses an apparatus for immunological analyses, in which the reading unit is also incorporated. The apparatus has an arm movable along a vertical axis and a horizontal axis, perpendicular to one another. The plates are carried by a support provided with a translational movement along a third axis, orthogonal with respect to the axes of translation of the arm. The arm may be equipped alternately with sample and reagent dispensing means, with washing means and with an optical reading head. The said assembly movable along two orthogonal axes has the task of performing all the dispensing, washing and reading operations, in extremely long periods of time and hence with low productivity. WO-A-8 602 168 discloses an apparatus for im uno-enzyme analyses or the like, in which a single table movable along a horizontal axis is provided and a group which comprises the dispensing and washing systems is positioned above said table. The group is movable along a single vertical axis. The table has arranged on it both the samples, the reagents and also a single plate with the wells or cavities inside which the preparation containing the antibodies is present. The table carries alternately below the vertically movable group the samples, the reagents and the plate with the cavities. After dispensing of the samples and the reagents, incubation and washing, the plate is brought by the translating table into a reading unit. This apparatus has the drawback of being able to handle only a single plate at a time. Expansion of the table and an increase in the number of plates would not be possible since said plates are in any case all moved at the same time by a single table which also carries the reagents and the samples, so that a reduction in the analysis times would not in any case be possible.

The present invention relates to an apparatus for immunological analyses and the like which is able to perform, automatically and at high speed, a large number of analyses and which is at the same time particularly versatile and able to perform different analyses on different samples, i.e. originating from several subjects.

Description of the invention These and other aims and advantages, which will become clear to persons skilled in the art from reading the text which follows, are obtained by the fact that the support on which the plates are arranged comprises a rotating table with a substantially vertical axis of rotation, on which a plurality of seats are arranged for corresponding plates. The rotating table moves the individual plates from one position to another among a plurality of positions. Moreover, according to the invention, said rotating table has associated with it washing means for washing the cavities of said plates, which are controlled in accordance with a system of polar coordinates having an axis coinciding with the axis of rotation of said rotating table. In this way, while one of the plates arranged on the rotating table is located in a position where the samples and any reagents are dispensed via the dispensing arm, any one of the other plates arranged on the rotating table is located in a position where washing of the cavities of the said second plate can be performed. The polar coordinates along which the washing means move make it possible to select the cavities to be washed, for example depending on the required incubation time and the sequence in which the samples and any reagents have been dispensed.

The use of the rotating table with washing means controlled along polar coordinates independent of those controlling the dispensing arm results in a high degree of operational flexibility and also enables the sample and reagent dispensing operations to be kept separate from the incubation and washing operations, with an obvious reduction in the analysis times since the dispensing operations can be performed at the same time as the washing operations. The use of a rotating table with washing means controlled autonomously along polar coordinates is particularly advantageous for the realization of an integrated apparatus which also performs reading of the results of the enzyme reaction. In fact, one of the stopping positions of the rotating table may be opposite a reading station. Since temperature- regulating and vibrating means are suitably associated with each seat of the rotating table it is appropriate that reading of the reaction results should not occur with the plate in position on the rotating table. Therefore, according to a particularly advantageous embodiment of the present invention, the reading unit is located alongside the rotating table and transfer means are provided in order to selectively transfer the plates from said rotating table to said reading unit and vice versa.

Advantageously, the washing means associated with the rotating table are carried by a carriage movable along a radial arm provided with rotary movement about the axis of rotation of said rotating table and extending in the radial direction above said rotating table. In this way, rotation along the angular coordinate of the washing means is independent of and not linked to rotation of the rotating table, resulting in greater versatility.

Each plate can be installed on a small carriage which is inserted into the respective seat of the rotating table by means of a system of guides. This system of guides is realized so as to be able to interface with corresponding guides of the reading unit. Transfer of each plate from the rotating table - 6 -

to the reading unit and vice versa is thus facilitated, and for this purpose a transfer slide may be provided which picks up the plate from the rotating table and transfers it to the reading unit and vice versa. The transfer slide may have an elastic engaging tooth for engagement with the carriage carrying the plate to be transferred, with the possibility of a release means, for example of the cam or eccentric type, being provided in order to disengage the carriage from the transfer slide.

In order to increase the capabilities of the machine and permit high incubation times without reducing the productivity, according to a particular embodiment the apparatus may have, associated with the rotating table, an intermediate store into which the plates in which the biological liquid samples to be analysed have been dispensed may be transferred and kept in incubation, transfer means being provided in order to transfer individual plates from said rotating table to said store and vice versa. The store may have a vertically movable intermediate- storage group, equipped with a plurality of receiving holes for said plates, each receiving hole being able to be selectively brought into alignment with said rotating table so as to transfer a respective plate from said rotating table to said receiving hole or vice versa. The means for transferring the plates from the rotating table to the intermediate-storage group and vice versa may be similar to the means used for transferring the plates into the reading unit.

Preferably, the dispensing arm is equipped, in a manner known per se (for example from the cited EP-A-0 500 506), with a dispensing assembly movable along two orthogonal horizontal axes, with at least one dispensing needle vertically movable along a third axis perpendicular to said two horizontal axes. Preferably the dispensing needles are two in number and advantageously have a variable inter-axial distance so as to be able to remove simultaneously two samples from two test-tubes arranged at a certain distance and dispense said samples into two cavities arranged at a different distance from one another.

Further advantageous features of the apparatus according to the invention are indicated in the accompanying dependent claims.

Brief description of the drawings

The invention will be better understood with reference to the description and accompanying drawing which shows a practical non-limiting embodiment of the invention itself. In the drawing:

Fig. 1 shows a simplified plan view of an apparatus according to the invention;

Figs. 2, 3, 4, 6 and 7 are side views sectioned along vertical planes indicated respectively by II-II, III-III, IV-IV, VI-VI and VII- VII in Fig. 1;

Fig. 5 is a perspective view of a reaction plate;

Fig. 8 is a plan view along a horizontal plane indicated by VIII-VIII in Fig. 7;

Fig. 9 is a side view of Fig. 7 along IX-IX of Fig. 7;

Fig. 10 is a plan view, on a larger scale, of the intermediate store; Fig. 11 is a section along XI-XI of Fig.

10;

Fig. 12 is a plan view, on a larger scale, of the reading unit; and

Fig. 13 is a section along XIII-XIII of Fig. 12. Detailed description of the preferred embodiment

The apparatus comprises a rectangular base plate 1 (Fig. 1) on which are mounted the following assemblies which will be described in more detail below:

- a first sample-carrying support 3, in which the test-tubes containing the biological liquids to be examined are located; a second reagent-carrying support 5 located adjacent to said first support; a system for dispensing biological liquids and reagents, comprising a translation mechanism 7 for moving a pair of slides 9, 11 with movements derived from the combination of displacements along two orthogonal axes x-x, y-y, said slides each carrying a vertical needle for dispensing liquids;

- a circular table 13 rotating about its own vertical axis and comprising four stations 13A each with a seat for a respective reaction plate 26, said plates being provided with cavities in which biological liquids are made to react with the reagents;

- a rotating arm 15 carrying members for washing the cavities of said plates;

- an intermediate store 17 for said plates 26, so as to allow lapsing of the time required for the reactions to develop in the cavities of the said plates; - a reading unit 19 designed to read the result of the reaction which has occurred in each said cavity.

The sample-support 3 The support has the form of a circular tray provided with receiving holes 3.1, each designed to contain in a vertical position a test-tube for receiving a biological liquid; said receiving holes are distributed uniformly on said support in circular arrangements concentric with the tray itself. Said support 3 is supported by the base plate 1 via bearings not shown in the drawing, which allow it to rotate about a vertical axis w-w and is positioned in the desired angular position by means of an electric stepper motor 3.2 and a pulley transmission system comprising a first and a second toothed belt 3.3, 3.4.

The reagent support 5

The reagent support 5 has the form of tray in plan view which is mainly rectangular with a recessed angle so that it can be arranged alongside the support 3 for the biological liquids, thus making the best possible use of the space available. The reagent support has a series of receiving holes 5.1 designed to contain, in a position slightly inclined with respect to the vertical, the flasks 21 (Fig. 3) containing the reagents; said receiving holes being regularly distributed, in plan view, in the support 5 in parallel rows on the sides of the support itself. The support may, if necessary, be temperature- regulated, be kept at a constant temperature, and electronically controlled.

The system for dispensing the biological liquids and reagents

The mechanism for translating the dispensing system comprises a first carriage 7.1 (Figs. 1 and 2) travelling along two parallel guides 7.2, 7.3 which define a horizontal axis x-x and are fixed at their ends to the base plate 1 by means of supports 7.4, 7.5. The carriage 7.1 is moved along said guides by an electric stepper motor 7.6, mounted on the support 7.4, via a drive pulley 7.7, a toothed belt 7.8 and a driven pulley 7.9 mounted rotatably on the support 7.5, the toothed belt 7.8 being fixed at a point to a small bracket 7.9 integral with the carriage 7.1.

The carriage 7.1 has integrally fixed to it in cantilever fashion a cylindrical guide 7.10 (Fig. 4) and a prismatic guide 7.11 which form a dispensing arm and define a horizontal axis y-y orthogonal with respect to the axis x-x and along which the two slides 9, 11 are able to travel. Each slide 9, 11 is connected to said guides 7.10, 7.11, respectively, via a sliding bush 7.12 and a pair of idle rollers 7.13 (Fig. 4) and is moved along said guides by its own electric stepper motor 9.1, 11.1, respectively, integral with the first carriage 7.1, via a drive pulley 9.2, 11.2, a toothed belt 9.3, 11.3 and a driven pulley 9.4, 11.4 (Figs. 2 and 4), said driven pulleys being supported idle by a bracket 9.5 integral with the ends of said guides 7.10, 7.11 opposite to said first carriage 7.1 and each of said belts 9.3, 11.3 being fixed at a point to the respective slide 9, 11 with a bracket such as that indicated by 9.6 in Fig. 4 so as to drive the slide when the associated motor 9.1, 11.1 is made to rotate.

Each slide 9, 11 carries a vertical plate 23, 25 with a dispensing needle; since said plates are shaped in a similar manner, for the sake of brevity of the description, reference will be made only to the plate 25 (Figs. 3 and 4). The plate 25 has fixed to it, by means of blocks 25.1, 25.2, a vertical rectilinear guide 25.3 on which a carriage 25.4 is able to travel, the latter having fixed to it a hollow needle 25.5 projecting downwards. Said carriage 25.4 is therefore able to travel parallel to a vertical axis z-z and has a flat surface in the vicinity of the visible face of said plate 25 in Fig. 3, so that rotation of the carriage itself about a vertical axis is prevented. The carriage 25.4 is moved along said guide by an electric stepper motor 25.6 which, by means of a drive pulley 25.7 and a driven pulley 25.8, drives a toothed belt 25.9 which is fixed via a small plate 25.10 to the carriage 25.4.

When the carriage 25.4 is completely lowered, as shown in the left-hand part of Fig. 3, the needle 25.5 integral therewith projects mostly underneath the plate 25 and can be inserted into a reagent bottle 21 or into one of the test-tubes containing biological liquid until it nearly touches the bottom thereof. The inclined position of the bottles 21 enables most of the liquid contained therein to be sucked out. The top part of the needle is connected via a pipe 25.11 to a pump not shown in the drawing, said pump being bidirectional so as to suck up or expel liquid through said needle.

When the needle-holding carriage is completely raised, the free tip of the dispensing needle remains completely above the bottom edge of the plate 25, as shown for the plate 23 in the right- hand part of Fig. 3, and in this position the needle can be displaced in plan view, by means of a combination of displacements along the axes x-x and y-y obtained respectively with programmed rotations of the motors 7.6, 9.1 of the translation system described, so as to remove a metered quantity of a biological liquid from any test-tube 3.1 of the first support 3 or of a reagent from any bottle 5.1 of the second support 5, or in order to release a metered quantity into a cavity 26A of a reaction plate 26 in a loading station on the rotating table 13, as will be described below.

In a known manner the needle 25.5 passes through a hole 25.12 (Fig. 4) in the block 25.1 located in the bottom part of the plate 25 during its raising and lowering movement, said hole being connected to a pipe 25.13 (Fig. 3) supplying washing water and to a pipe 25.14 sucking off the washing water. This arrangement enables the external part of the needle 25.5 to be washed during its raising and lowering movements so as not to contaminate the liquid in a container with the liquid of another container with which the needle has previously come into contact. The presence of two needle-carrying slides

9, 11 provided with independent drive systems for displacements along the axes y-y and z-z enables the equipment to be programmed so as to perform simultaneously the removal or delivery of liquid with both the dispensing needles so as to increase the productivity of the equipment itself.

The reaction plates and the rotating table

The equipment operates with reaction plates 26 (Fig. 5), already known for use in automatic analysis equipment, usually made of transparent plastic and having an approximately rectangular shape. Said plates in their upper surface have a multiplicity of cylindrical cavities 26A, for example 96, onto the walls of which anti-bodies specific for the type of test to be performed have been deposited. The cavities 26A are intended to receive a biological liquid from a test-tube 3.1 and one or more reagents from a bottle 5.1 by means of the dispensing system described above. Each of the said reaction plates is inserted with slight friction inside an opening of a small carriage 27, said carriage comprising a rectangular frame 27.1, on the long sides of which two pairs of wheels 27.2 are mounted. Each wheel has an annular groove 27.3.

The rotating table 13 (Fig. 1) is supported by the base plate 1 by means of bearings not shown in the drawing and can be made to rotate by a motor 13M, located underneath the base plate 1, via a transmission system with two toothed belts 13N, 13P and a speed-reducing group 13Q and a pulley 13R coaxial and integral with the table 13. Said rotating table has four stations 13A arranged at 90° with respect to one another about the axis of rotation A of the table. Each station comprises a seat for a carriage 27 provided with a reaction plate 26, said seat being formed by a pair of rails 29 designed to receive the grooves 27.3 of the respective wheels of the carriage 27.

The table can have each of the four reaction plates 26 in one of the following positions, with reference to Fig. 1 and rotating in an anti¬ clockwise direction about the axis of rotation of the table:

- a position in the vicinity of the bottom edge of the drawing, for manual loading of the plates 26 with the associated carriage 27; a position rotated through 90° with respect to the preceding one, in which the dispensing device is able to load biological liquids and reagents into the cavities 26A; a position rotated through 90° with respect to the preceding one, for incubation of the reactions and washing of the cavities 26A at the end thereof; - a position rotated through about 45° with respect to the preceding one, for transfer, where necessary, of the carriage 27 and the associated plate 26 of the table 13 into the incubation store 17 and vice versa; a position rotated through 45° with respect to the preceding one, for transfer of the carriage 27 and the associated plate 26 from the table 13 to the reading unit 19 for reading the result of the reactions which have occurred in the cavities 26A, and vice versa.

It is understood that incubation and washing can occur in more than one of the positions listed above, depending on the operating conditions of the machine and the distribution of the metering and incubation times.

In each station 13A the rails 29 are mounted on a structure which comprises a plate 13B (Fig. 13) supported by the table 13 by means of resilient rubber elements 13C and carrying a small electric motor 13D which causes rotation of an eccentric mass 13E. The rotation of said eccentric mass 13E and the fact that the plate 13B is mounted on resilient elements 13C generates a vibrating movement of the plate 13B and the parts integral therewith, including the reaction plate 26, causing agitation of the liquids contained in the cavities 26A thereof.

Furthermore, in the vicinity of the bottom surface of the reaction plate 26, the plate 13B supports a metal plate 13F to which heating elements 13H, such as electrical resistances or the like, are applied at the bottom in order to keep the plates 13F, 26 and the liquids contained in the cavities 26A of the latter at a suitable incubation temperature. In this way during the period where the plates 26 are present in the stations 13A of the table 13 it is possible to agitate and heat the contents of the cavities 26A of the plates 26 so as to favour development of the reactions.

The electric motor 13D for vibration and the heating elements 13H are powered via electric cables, not shown, which extend between the bottom side of the table 13 and the base plate 1 in a loop- shaped path, so as to allow rotation of the table 13 sufficient to transfer each station from the manual loading position to the reading position and vice versa with rotations of the table itself in both directions without the need for rubbing contacts.

System for washing the cavities of the reaction plates

Once the time programmed for the reactions has lapsed, the antibodies deposited on the walls of the cavities 26A are -bonded with any antigens present in the biological liquid, resulting in antibody-antigen complexes, and the residual liquid must be eliminated from the cavities 26A prior to proceeding with reading of the result. For this purpose an arm 15 (Figs. 1, 7, 8, 9), supported rotatably by a column 14 coaxial with the rotating table 13 and fixed to the base plate 1, carries a system for removing the liquids from the cavities 26A and washing the cavities themselves. Said arm 15 carries at the top a motor 15B which, by means of a toothed-belt transmission system 15C between its drive pulley 15D and a pulley 15E fixed coaxially with respect to the column 15A, is able to rotate the arm 15 into any position about said column. The arm 15 also carries two parallel rectilinear guides 15F which extend horizontally along the arm itself, radially with respect to the rotating table 13, and on which a carriage 15M is able to travel. Said carriage 15M can be moved in either direction along said guides by a motor 15N, fixed at the top to the arm 15, by means of a toothed belt 15P fixed at one point to the carriage itself via a small plate 15R and suitably driven by means of two pulleys 15S mounted on the arm 15.

The carriage 15M is integral with a small frame 15T of rectangular shape located vertically underneath it (Fig. 9), said small frame supporting two vertical guides 15U on which a slide 15Z carrying the washing means is able to travel, said slide being able to be displaced vertically by a geared motor 15W. For this purpose the geared motor 15W is fixed to the small frame 15T and the power output shaft has mounted on it a disc 15X which has a pin located at a distance from the centre, said pin being slidable inside an eyelet 15Y of a small bracket integral with the slide 15Z.

The bottom of the slide 15Z has fixed to it a rack provided with a row of pairs of vertical pipes 16A, 16B oriented orthogonally with respect to the radial guides 15F of the arm 15, the number of said pairs being equal to the number of cavities 26A present in each row of the plates 26 parallel to said rack, eight cavities in the example, and being located at the same distance from one another as said cavities.

The horizontal travel of the carriage 15M is such that the rack can be brought opposite any one of said rows of cavities 26A of the respective plate 26, and the vertical travel of the slide 15Z is sufficient to convey the bottom end of at least one of said vertical pipes 16A, 16B so that it nearly touches the bottom of the cavities 26A and to raise said pipes out of the volume of the plate 26 so as to allow horizontal displacements of the rack. The pipes 16A, 16B of the rack are connected respectively to a duct 16C supplying the washing water and to a suction duct 16D, the pipes 16B being slightly longer than the pipes 16A so as to ensure that, with suction through the duct 19, most of the liquid contained in the cavities 26A is sucked up through the duct 19.

The possibility of rotating the arm 15 by means of the motor 15N enables the washing operation to be performed in any station and in any angular position of the table 13, even during its movement.

Intermediate store for development of the reactions

If particularly long reaction times are required, so as not to reduce the productivity of the apparatus the carriages 27, which have been loaded onto the table 13 together with the associated plates 26, may be made to remain for a programmed period of time inside the store 17. The store comprises an intermediate-storage group consisting of a box-shaped structure formed by two vertical side walls 17A, 17B, connected together by two horizontal plates 17C, 17D, said side walls having fixed to them superimposed pairs of rails indicated by 17E, each pair being designed to receive a carriage 27. Said box-shaped structure of the store can be made to travel vertically along two guides 17F, 17H fixed to the base plate 1 by means of a bracket 17L, the movement being provided by a motor 17M via a toothed belt 17N wound round a drive pulley 17P and an idle pulley 17R and fixed to a small bracket 17S integral with the box-shaped structure. The vertical travel of the box-shaped structure of the store 17 is such as to allow any pair of rails 17E of the store to be brought facing the extension of the rails 29 of a station of the table 13 when the latter is stopped opposite the store itself; in this way a device for translating the carriage 27 is able to transfer said carriage from the station on the table 13 to one of said pairs of rails 17E and vice versa. The device which performs said translatory movement comprises a transfer carriage 18 provided with two pairs of wheels such as those of the carriage 27 and with the same distance between them, travelling on two short rails 18A integral with the base plate 1 and aligned with the rails 29 of the rotating table 13 in the position for transfer to the store 17. Said carriage 18 can be moved in the direction of said rails by a motor 18B via a toothed belt 18C which is wound onto a pulley 18D mounted on the shaft of the motor 18B and onto an idle drive pulley 18E mounted on a support integral with the base plate 1, said belt being fixed at one point to a small bracket 18F integral with the carriage 18.

The carriage 18 comprises a hook 18H (Fig. 10) designed to enter into engagement with a pin 27.4 of the carriage 27 carrying the reaction plate 26, said hook being biased by a spring 18L so as to keep contact with said pin 27.4. A pusher 18M can be biased so as to release the hook 18, overcoming the action of the spring 18L, from the pin 27.4 by means of the action of two eccentric cams 18N, 18P which, mounted on respective shafts of two electric motors 18R, 18S fixed to the base plate 1, are located along the travel path of the carriage 18. The eccentric cam 18P is used to effect disengagement of the carriage 27 when the latter is re-positioned on the rotating table 13, and the eccentric cam 18N is used to effect disengagement when the carriage 27 is located in the store 17, in the position shown in broken lines in Fig. 10. In this way, after rotating the table 13 into the position with the rails 29 of one of its stations 13A aligned with those of the rails 18A of the carriage 18 and bringing (with a vertical movement of the box-shaped structure of the store 17) a pair of rails 17E of the store 17 into alignment with both said pairs of rails 29, 18A, it is possible, via a suitable command sequence of the motor for translating the carriage 18 and the motors of the eccentric cams 18N, 18P, to translate the carriage 27 from said station 13A into the store 17 or vice versa.

Unit for reading the result of the reaction

The reading unit 19 comprises a pair of rails 19A (Figs. 12 and 13) integral with a structure fixed to the base plate 1, which can be aligned with the rails 29 of any one of the stations 13A of the table 13 by means of suitable angular positioning of the table itself 13. A transfer carriage 19B, similar to the carriage 18 of the store 17, can be translated along said rails 19A so as to couple up a carriage 27 with the associated reaction plate 26 which is located in the station 13A of the table 13 temporarily aligned with the reading unit, and bring it with a row of cavities 26A underneath the illumination group 19C mounted on a gantry structure.

For this purpose the carriage 19B is moved by an electric stepper motor 19D fixed to the base plate 1, via a toothed belt 19E which is wound onto a drive pulley 19F and onto a driven pulley 19H supported by a support fixed to the base plate 1, said belt being fixed at one point to a bracket 19M of the carriage 19B. A release device with motor 19R and eccentric cam 19P, located in the vicinity of the rotating table 13, is able to act on the pusher 19N of the carriage 19B so as to release the hook 19S of the carriage itself from the pin 27.4 of the carriage 27 carrying the reaction plate 26 when the latter has been brought back onto the rotating table 13 after reading, so as to allow a new rotation of the table 13.

The illumination group 19C comprises a row of light sources each located opposite a cavity 26A of a row of said cavities 26A provided in the reaction plate 26, said row being perpendicular to the direction of translation of the carriage 19B. Each light source comprises an optical fibre 19V which illuminates from above a single cavity 26A, with the light emitted by a lamp (not shown) located at a distance from the group 19C, for example in the area located underneath the reading unit 19.

A row of optical sensors 19W is located opposite the row of light sources 19T and vertically underneath the reaction plate 26 being read (illustrated in dot-dash lines in Fig. 13), each of said sensors being struck by the light which has passed through an individual cavity 26A. A filter- carrying plate 19X carrying filters for the light, not shown, is positioned between the reaction plate 26 and the optical sensors 19W, so as to allow to pass through to the optical sensors the wavelength range where the absorption is maximum owing to the compounds developed by the reaction. Said filter- carrying plate 19X can contain several filters varying from one another depending on the type of analysis to be performed and the plate 19X is carried by a carriage 19Y travelling parallel to the rails 19A on special guides 19Z. An electric motor 20, by means of a belt 20A, effects the movement of said plate 19X in a similar manner to that described for the carriage 19B, so as to bring in each case the required filter under the sources 19T.

The central control unit

Activation and deactivation of the electric motors, the heating elements, the pumps and in general all the actuators of the equipment described are programmable by means of a central control unit, not illustrated, provided with integrated circuits with a coded program and amplification circuits so as to allow: - direct correspondence between any test- tube containing biological liquid located in a given position on the support 3, and a cavity 26A of a reaction plate loaded in the apparatus;

- the carrying out of programmed sequences for each type of analysis, with the metered removal of the reagents, the carrying out of incubation cycles (temperature-regulation, agitation and intermediate storage) , washing of the cavity and optical reading; - recording of the values read by the apparatus ccmbined with the alphanumeric code of the associated biological liquid test-tube and the type of analysis performed.

The structure of the apparatus described is such that, while the means 9, 11, 23, 25 carry out, on the cavities 26A of the plate 26, located in the position adjacent to the support 5, the operations involving dispensing of the samples, taken from the test-tubes arranged on the support 3, and of any reagents taken from the flasks 21 on the support 5, the following operations may be performed on the other three plates 26 arranged on the rotating table 13:

- incubation with agitation where necessary and temperature-regulation (at temperatures and vibration speeds which can be selected independently for each station 13A) ;

- washing by means of the arm 15 via which the washing means are controlled along polar coordinates defined by the angle of rotation of the arm 15 about the column 14 (and hence the axis A-A of the rotating table 13) and by the position of the carriage 15M along the guides 15F;

- reading of the result of the analyses by means of the reading unit 19; - manual unloading of the plate which has already undergone reading and manual loading of a virgin plate.

When the incubation times are particularly long or when it is required to process at the same time a large number of plates 26, the latter can be transferred to the intermediate store 17.

The support 3 for the biological liquid samples may have associated with it one or more bar¬ code readers, in a manner known per se. A first one of these readers may be located in a radial position outside the support, while the second reader, if present, may be located in an internal radial position between the axis of rotation w-w of the support 3 and the innermost row of receiving holes 3.1. These receiving holes are suitably staggered with respect to each other in a circumferential direction so as to allow reading of the bar codes present on two concentric (and staggered) circumferential rows of test-tubes housed in the support 3. The intermediate zone of the support 3, where it is not possible to perform reading of the bar codes by means of the two readers, can be used to accommodate a series of test-tubes for carrying out dilution of the samples to be analysed, in accordance with methods known to persons skilled in the art. It is understood that the drawing shows only a possible embodiment of the invention, which can vary as regards the forms and arrangements, without departing from the scope of the inventive idea. The presence of reference numbers in the accompanying claims does not limit the protective scope of the latter, but is merely intended to facilitate reading thereof with reference to the description of the example of embodiment.

Claims

1. An apparatus for immunological analyses comprising: a first support (3) for a plurality of biological liquid samples to be analysed; a second support (5) for a plurality of flasks containing reagents; a third support (13) for plates (26) with cavities (26A) inside which the biological liquid to be analysed and the reagent are dispensed; a dispensing arm (7.10, 7.11) carrying dispensing means (9, 11, 25) which selectively remove said biological liquid samples and dispense them into said cavities (26A); and washing means (15Z, 16A, 16B) for washing said cavities, characterized in that - said third support (13) for said plates

(26) comprises a rotating table (13) with a substantially vertical axis of rotation (A) , with a plurality of stations (13A) for corresponding plates (26), which displaces said plates from one position to another among a plurality of positions; and said rotating table (13) has associated with it said washing means (15Z, 16A, 16B) for washing the cavities (26A) of said plates (26), which means are controlled in accordance with a system of polar coordinates with respect to the axis of rotation (A) of said rotating table.

2. Apparatus according to Claim 1, comprising a unit (19) for reading the plates (26) and transfer means (19B, 19D, 19E) which selectively transfer the plates (26) from said rotating table (13) to said reading unit (19) and vice versa.

3. Apparatus according to Claim 1 or 2, in which said washing means (15Z, 16A, 16B) are carried by a carriage (15M) movable along a radial arm (15) provided with a rotary movement about the axis of rotation (A) of said rotating table (13) and extending in the radial direction above said rotating table.

4. Apparatus according to Claim 3, in which said washing means are movable vertically with respect to said carriage (15M).

5. Apparatus according to one or more of the preceding claims, in which said rotating table (13) has our working positions: a position for loading of the plate, a position for dispensing of the samples and any reagents, an incubation position and a position for transfer to the reading unit (19), respectively.

6. Apparatus according to one or more of the preceding claims, in which each station (13A) of said rotating table has respective and independent temperature-regulation means (13H) and vibration means (13D, 13E) .

7. Apparatus according to one or more of the preceding claims, in which said rotating table (13) has, for each station (13A), a system of guides (29) for a corresponding carriage (27) carrying a respective plate (26).

8. Apparatus according to Claims 2 and 7, in which said reading unit (19) has its own system of guides (19A) and in which, for the transfer of a plate from the rotating table (13) to said reading unit (19), the system of guides (29) of the rotating table (13) associated with the station (13A), in which the plate to be transferred is located, is aligned with the system of guides (19A) of the reading unit (19), a transfer carriage (19B) removing the plate from the rotating table and transferring it to the reading unit and vice versa.

9. Apparatus according to Claim 8, in which said transfer carriage (19B) has an elastic engaging tooth (19S) for engagement with the carriage (27) carrying the plate to be transferred, a release means (19P, 19R) being provided in order to disengage said plate-carrying carriage frcm said transfer carriage (19B) .

10. Apparatus according to one or more of the preceding claims, in which said rotating table (13) has associated with it an intermediate store (17) into which the plates (26) in which the biological liquid samples to be analysed have been dispensed can be transferred and kept under incubation, transfer means (18) being provided in order to transfer individual plates from said rotating table to said store and vice versa.

11. Apparatus according to Claim 10, in which said intermediate store (17) has a vertically movable intermediate-storage group (17A, 17B, 17C, 17D) equipped with a plurality of receiving holes (17E) for said plates (26), each hole being able to be brought selectively into alignment with said rotating table in order to transfer a respective plate (26) from said rotating table (13) to said receiving hole (17E) or vice versa.

12. Apparatus according to Claims 7 and 11, in which each receiving hole (17E) of said intermediate-storage group (17A, 17B, 17C, 17D) has guides (17E) which are selectively brought into alignment with the system of guides (26) of a respective station (13A) of the rotating table (13) in order to transfer the carriage (27) with the respective plate (26) from the rotating table (13) to the intermediate-storage group (17A, 17B, 17C, 17D) or vice versa.

13. Apparatus according to Claim 12, in which said intermediate store (17) has associated with it a transfer carriage (18) with an elastic engaging tooth (18H) which engages with the carriage (27) to be transferred from the rotating table (13) to the intermediate store (17) or vice versa, two release means (18N, 18R, 18P, 18S) being provided in order to open said engaging tooth (18H) in two positions of the transfer carriage (18).

14. Apparatus according to one or more of the preceding claims, in which said dispensing arm (7.10, 7.11) is equipped with a dispensing assembly (9, 11) movable along two substantially horizontal orthogonal axes (x-x, y-y) , with at least one dispensing needle (25.5) vertically movable along a third substantially vertical axis (z-z).

15. Apparatus according to Claim 14, in which said dispensing assembly comprises two dispensing needles (25.5) located parallel with one another and at a variable distance from one another, each needle being movable independently with respect to the other one along said third axis (Z) .

16. Apparatus according to Claim 15, in which said two dispensing needles (25.5) have a distance between one another which is variable in a direction parallel to the dispensing arm (7.10, 7.11) and in which each of said needles is mounted on a respective slide (9, 11) actuated by its own actuator (9.1; 11.1), the independent movements of the two actuators causing a variation in the distance between said dispensing needles (25.5).

17. Apparatus according to Claim 2, in which said reading unit has a gantry structure (19C) on which there is a row of light-radiation sources (19T), underneath which corresponding detectors (19W) are arranged, the plate to be read (26) being made to pass between said sources (19T) and said detectors (19W) .

18. Apparatus according to Claim 17, in which a filter carrier (19X) is arranged between said _ _

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sources (19T) and said detectors (19W), said filter carrier having a plurality of filters which can be selectively positioned between said sources and said detectors, an actuator (20) being provided in order to effect the translatory movement of said filter carrier (19X).

19. Apparatus according to one or more of the preceding claims, characterized in that said first support (3) for the samples to be analysed is a support rotating about a substantially vertical axis (w-w) and equipped with a plurality of receiving holes (3.1) for accommodating corresponding test- tubes containing the samples of biological liquids to be analysed.

20. Apparatus according to Claim 19, in which said receiving holes (3.1) are arranged in at least two circumferentially staggered series, a bar¬ code reading system being provided in order to read any labels applied to the test-tubes inserted in said receiving holes.