WO2016046403A1

WO2016046403A1 - Device for mixing magnetic particles and liquid in a reaction cup, adapted to be used in an apparatus for separation, washing and mixing of the contents of said reaction cup, in an immunoanalyzer system

Info

Publication number: WO2016046403A1
Application number: PCT/EP2015/072177
Authority: WO
Inventors: Qingwen TANG; Chao YU; Shenguang SU; Luca MELILLO
Original assignee: Altergon Italia S.R.L.
Priority date: 2014-09-25
Filing date: 2015-09-25
Publication date: 2016-03-31
Also published as: CN204134550U

Abstract

The present invention provides for a device for mixing magnetic particles and liquid in a reaction cup, adapted to be fixed in an apparatus for separation, washing and mixing of the contents of said reaction cup, in an immunoanalyzer system, the reaction cup being inserted in a supporting mechanism of the apparatus so as the head of the reagent cup is substantially still, comprising: - a motor (1, 31) with a rotating axis, - a mixing head (7, 314) adapted to fit with the lower end of the reaction cup (30, 316); - a device (18) connected between said motor and said mixing head, adapted to transform the circular movement of the rotating axis into an eccentric movement of the mixing head and of the lower end of the reaction cup, said device causing a circular oscillation of the mixing head around the rotating axis of the motor, without rotation of the mixing head own axis.

Description

DEVICE FOR MIXING MAGNETIC PARTICLES AND LIQUID IN A REACTION CUP, ADAPTED TO BE USED IN AN APPARATUS FOR SEPARATION, WASHING AND MIXING OF THE CONTENTS OF SAID REACTION CUP, IN AN IMMUNO ANALYZER SYSTEM

DESCRIPTION

Field of the invention

The present invention relates the field of immunoanalyzer systems, and in particular to a device for mixing magnetic particles and liquid in a reaction cup, adapted to be used in an apparatus for separation, washing and mixing of the contents of said reaction cup, in an immunoanalyzer system.

Description of the prior art

In the framework of the development of magnetic separation technology, immunoanalyzer technology is getting more and more widely used in medical industry. The automatic immunoanalyzer, during testing, needs to use nanometric magnetic beads to let immuno- complex antibody, antigen molecules binding by means of a chemical agent. After binding of nanometer magnetic beads with antibody and antigen, the residual liquid in the reaction cup is needed to be cleaned.

Then, magnetic separation mechanism is needed; many items of current immunoanalyzer need secondary hatch for the materials in the reaction cup. This needs a mixing mechanism to mix the magnetic particles and reagent in the reaction cup. At present, most of the magnetic separation mechanisms among the automatic immunoanalyzers are externally equipped with mixing mechanisms making chemiluminescent immune analyzing flow prolonged; and the space cannot be fully used. In addition this worsen the complexity of the overall structure. Therefore externally equipping a mixing mechanism for mixing will increase cost and long action process will influence on the efficiency.

In addition mixing action must ensure the right behavior of the liquid inside the cup, avoiding to wet parts of the internal surface of the cup that cannot be reached by the washing liquid. Summary of the invention

Therefore it is the main object of the present invention to provide a device for mixing magnetic particles and liquid in a reaction cup, adapted to be used in an apparatus for separation, washing and mixing of the contents of said reaction cup, in an immunoanalyzer system, which overcomes the above problems/drawbacks.

The mixing mechanism of the present invention can be integrated in the magnetic separation and washing mechanism, while action process of a certain workstation is being performed, and action process of the other workstations are also performed: this way the overall device operation speed shall be higher. Treating various samples synchronously benefits a simpler flow and improved analysis efficiency.

An object of the present invention is a device for mixing magnetic particles and liquid in a reaction cup, adapted to be fixed in an apparatus for separation, washing and mixing of the contents of said reaction cup, in an immunoanalyzer system, the reaction cup being inserted in a supporting mechanism of the apparatus so as the head of the reagent cup is substantially still, characterized in that it comprises:

- a motor with a rotating axis ,

- a mixing head adapted to fit with the lower end of the reaction cup;

- a device connected between said motor and said mixing head, adapted to transform the circular movement of the rotating axis into an eccentric movement of the mixing head and of the lower end of the reaction cup, said device causing a circular oscillation of the mixing head around the rotating axis of the motor, without rotation of the mixing head own axis.

Another object of the present invention is an apparatus for separation, washing and mixing of the contents of a reaction cup, in an immunoanalyzer system, the apparatus comprising a device for mixing magnetic particles and liquid as above, the apparatus comprising said supporting mechanism for the reaction cup, so as the head of the reagent cup is substantially still.

These and further objects are achieved by means of a device for mixing magnetic particles and liquid in a reaction cup, adapted to be used in an apparatus for separation, washing and mixing of the contents of said reaction cup, in an immunoanalyzer system, as described in the attached claims, which are considered an integral part of the present description.

Brief description of the drawings

The invention will become fully clear from the following detailed description, given by way of a mere exemplifying and non- limiting example, also with reference to the attached drawing figures, wherein: Fig. 1 is an illustration of an example of mixing device of the invention integrated with an apparatus for separation, washing and mixing;

Fig. 2 is an illustration of a first embodiment example of the mixing device mechanism of the invention; in the figure, 2(a) is a 3D view, and 2(b) is a section view;

Fig. 3 is an illustration of the elastic pressure plate (sinker) set of the invention; in the figure, 3(a) is a 3D view, and 3(b) is a section view;

Fig. 4 is an illustration of a magnified local part of the apparatus for separation, washing and mixing where the mixing device of the invention is inserted;

Fig. 5 is an illustration of a second embodiment example of the mixing device mechanism of the invention; in the figure, 5(a) is a 3D view from the bottom, and 5(b) is a 3D view from the top;

Fig. 6 is an illustration of the second embodiment example of the mixing device mechanism of the invention; in the figure, 6(a) is a first side view, and 6(b) is another side view;

Fig. 7 is an illustration of the second embodiment example of the mixing device mechanism of the invention in exploded view, showing the component parts;

Fig. 8 is an illustration explaining the kind of movement imparted to the reaction cup by the mixing device mechanism of the invention.

The same reference numerals and letters in the figures designate the same or functionally equivalent parts.

Detailed description of the preferred embodiments

With reference to Fig. 1, an embodiment example of apparatus for separation, washing and mixing of magnetic particles in at least one reaction cup, adapted to be used in an immunoanalyzer system, is shown. The reaction cup 30 is adapted to contain nano metric magnetic particles (beads) binding immuno-complex antibody, antigen molecules, and liquid. The apparatus comprises:

- a supporting dial mechanism 20 in the form of a rotating carousel, comprising an upper side with a number of holes adapted to host a corresponding number of reaction cups 30 in substantially vertical positions, and a lower side comprising a number of guide grooves (not shown) radially behind corresponding holes of the upper side;

- a number of magnet mechanisms (not shown) adapted to be inserted in the guide grooves and to slide therein, so as to radially approach to or depart from the side external surface of corresponding ones of the reaction cups;

- a number of washing mechanisms 40 installed around the supporting dial mechanism 20, able to move vertically in and out the reagent cup for charging or extracting the liquid;

- at least one mixing mechanism 70' installed behind and aside the supporting dial mechanism 5 20 (see also Fig. 4), adapted to shake (stir) at least one reaction cup so as to mix the content of the reaction cup.

A first embodiment of the invention is described below, with reference to Figures 2 - 5.

As shown in the Figures, the device for mixing magnetic particles of the invention comprises a motor 1, motor stand 2, eccentric shaft 3 with bearing on, mixing spindle 5 and mixing head i o 7.

The motor 1 is installed on the motor stand 2. Spindle of the motor 1 passes through the motor stand 2 to connect to the eccentric shaft 3 with bearing on. The eccentric shaft 3 with bearing on, mixing spindle 5 and mixing head 7 are connected in turn, and the mixing head 7 supports the reaction cup 30 to shake and to achieve mixing.

15 In non- limiting examples, the motor may be an electric brushless DC motor, or an electric step motor.

As explained above, the mixing mechanism is adapted to be integrated in the apparatus. When the reaction cup moves to the mixing mechanism, the mixing head 7 under the reaction cup 30 performs eccentric movement, as explained below, and that makes the reaction cup to perform 20 eccentric movement and thus materials (namely nanometric magnetic particles (beads) binding immuno-complex antibody, antigen molecules, and liquid) in the reaction cup are mixed.

More particularly, with reference to Figures 4 and 8, the head 7 under the reaction cup performs eccentric movement, namely a circular oscillation around the motor axis, without

25 rotating on its own axis (of the head 7), and that brings the lower end of the reaction cup 30 to perform the same eccentric movement, without rotating on its own axis, and thus materials in the reaction cup are mixed. The head of the cup remains substantially still, due to the constrains in the hole of the supporting dial mechanism 20, with only a slight oscillation due to the eccentric movement of the lower end of the cup (see Fig 8, the arrows and dotted lines

30 in correspondence of the cup).

This kind of movement ensures the right behavior of the liquid inside the cup, avoiding to wet parts of the internal surface of the cup that cannot be reached by the cleaning liquid dispensed by the washing mechanisms 40.

The upper surface of the mixing head has a form adapting to the form of the lower end of the cup, ensuring a firm adhesion: in an example, the lower end of the cup has a convex form, therefore the upper surface of the mixing head is concave.

Preferably the apparatus comprises climbing and lifting mechanism. The climbing and lifting mechanism comprises low level climbing block 8 and high level climbing block 9.

The mixing head 7 equipped on mixing work station is located between the low level climbing block and high level climbing block.

Both of the highest point of the low level climbing block and the lowest point of the high level climbing block are at the same level of the mixing head.

By rotation of the supporting dial mechanism 20, the reaction cup climbs up to the mixing head of the mixing work station along the low level climbing block during moving with the dial, and climbs up to the cup getting work station along the high level climbing block.

Surface of the climbing and lifting mechanism is tangent with arc surface of the reaction cup bottom.

Along with rotation of the dial, arc surface of the reaction cup slides along surface of the climbing block. Along with rising of the climbing block, it rises up.

The lifting and climbing block may lift up the reaction cup by level, and it firstly reaches mixing height, and then rises to the cup catching height. At the cup catching position, it is possible to easily catch the cup, and no other lifting mechanism to lift the reaction cup up is needed.

There is spare room for the reaction cup when being placed in the dial hole, and it can swing and move upward and downward. Design of the climbing block is in tangency with bottom arc surface of the reaction cup. Thus, along with rotation of the dial, arc surface of the reaction cup slides along surface of the climbing block. Along with rising of the climbing block, it rises up.

The mixing mechanism is equipped with mixing base 6, the mixing base is fixed on the motor stand 2, on turn fixed behind and aside the supporting dial mechanism 20 on the installation plate 21 ; the mixing rotation shaft passes through the mixing base. Between the mixing base and the mixing rotation shaft, the mixing rotation shaft is covered with pressure spring 4.

The apparatus is equipped with elastic pressure plate (sinker) set 10 able to exert a pressure over the head of the reagent cup. The elastic pressure plate set 10 consists of elastic pressure plate installation seat 11, extension spring 12, pop-rivet 13, pressure plate 14, No. 2 pin roll 15 and adjusting screw 16.

The elastic pressure plate installation seat 11 is fixed on the installation plate 21 of the supporting dial mechanism 20. The pressure plate 14 connects to the elastic pressure plate installation seat 11 with the pin roll 15. The adjusting screw 16 is screwed into the elastic pressure plate installation seat 11 to jack up the pressure plate 14. One end of the extension spring 12 hooks the pressure plate 14, and the other end hooks the pop-rivet 13 fixed on the elastic pressure plate installation seat 11.

The pressure plate is equipped with adjusting holes 17. With the adjusting holes 17, height of the adjusting screws can be changed; diameter of the adjusting holes 17 is bigger than the internal diameter of the adjusting screw 16, and smaller than external diameter of the adjusting screw.

The adjusting screw is the set screw.

Turn the adjusting screw bolts with socket head wrench passing through the adjusting hole 17 to change depth of the adjusting screw bolt in the elastic pressure plate installation seat. By this way, it is possible to change the angle between the pressure plate and the horizontal surface, meaning to adjust tilt angle of the pressure plate 14 to make edge of the reaction cup smoothly reach the mixing position. During mixing, the pressure plate blocks the reaction cup to prevent the reaction cup from being ejected from the placing hole during mixing.

By virtue of the elastic pressure plate , the reagent cup is effectively prevented from being ejected from the placing hole during mixing; the overall structure features simple, and convenient installation. It can be simply and closely integrated with magnetic separation system of the immunoanalyzer to complete mixing and no other independent mixing system needed.

A second embodiment of the mixing mechanism of the invention is described below, with reference to Figures 5, 6, 7.

In the Figures, the second embodiment comprises the following components: a Brushless DC Motor 31 connected to a Motor Base Plate 32, in turn connected to a Mixing Base 38, comprising an Upper extension 38'. The mixing mechanism is fixed to the installation plate 21 of the apparatus through the Motor Base Plate 32.

A number of elements are connected in turn between the motor axis and a Mixing Head 314, namely: Plane Thrust Bearing 33; Set Collars 34; Leaf Spring 35; Oscillating Axle 36; Spherical Bearing 37; Ball Bearing 39; Plain Washer 310; Spring Lock Washer 311 ; Screw 312.

These elements are adapted to transform the circular movement of the motor axis into the eccentric movement of the mixing head 314 described above.

The Spherical Bearing 37 allows the mixing head 314, supporting plane of the cup, to describe a circumference. The size of the circumference is conditioned by the inclination of the oscillating axel 36, given in turn by the eccentricity of the structure composed of the leaf spring 35, and the set collar 34.

Preferably a spring 313 abuts against the mixing head 314 on one side and the Upper extension 38' on the other side: this contributes to avoid turning of the mixing head , and therefore of the reagent cup 316, on its own axis.

Preferably two Spring Clips 315 are fixed on the mixing head 314, able to engage with the lower end of the reaction cup, and contributing to keep the Reaction Cup 316 and create a damping effect on the eccentric movement of the reaction cup.

Therefore, in all the possible embodiments of the invention, the mixing mechanism comprises a device 18 (Fig. 8) between the motor 1 , 31 and the mixing head 7, 314, able to transform the circular movement of the motor axis into the eccentric movement of the mixing head described above.

Many changes, modifications, variations and other uses and applications of the subject invention will become apparent to those skilled in the art after considering the specification and the accompanying drawings which disclose preferred embodiments thereof. All such changes, modifications, variations and other uses and applications which do not depart from the scope of the invention are deemed to be covered by this invention.

The elements and characteristics described in the various forms of preferred embodiments can be mutually combined without departing from the scope of the invention.

Further implementation details will not be described, as the man skilled in the art is able to carry out the invention starting from the teaching of the above description.

Claims

1. Device for mixing magnetic particles and liquid in a reaction cup, adapted to be fixed in an apparatus for separation, washing and mixing of the contents of said reaction cup, in an immunoanalyzer system, the reaction cup being inserted in a supporting mechanism of the apparatus so as the head of the reagent cup is substantially still,

5 characterized in that it comprises:

- a motor (1, 31) with a rotating axis ,

- a mixing head (7, 314) adapted to fit with the lower end of the reaction cup (30, 316) ;

- a device (18) connected between said motor and said mixing head, adapted to transform the circular movement of the rotating axis into an eccentric movement of the mixing head and of o the lower end of the reaction cup, said device causing a circular oscillation of the mixing head around the rotating axis of the motor, without rotation of the mixing head own axis.

2. Device for mixing magnetic particles and liquid as in claim 1, wherein said mixing head (7, 314) has an upper surface with a form adapting to the form of the lower end of the reagent cup (30, 316).

5 3. Device for mixing magnetic particles and liquid as in claim 2, wherein the lower end of the reagent cup has a convex form, and the upper surface of the mixing head is concave.

4. Device for mixing magnetic particles and liquid as in claim 1, wherein it comprises spring clips (315) connected to said mixing head (7, 314) able to engage with said lower end of the reaction cup.

0 5. Device for mixing magnetic particles and liquid as in claim 1, wherein it comprises a spring (313) able to abut against the mixing head (314) on one side and an upper extension (38') of a base (38) of the device on the other side.

6. Apparatus for separation, washing and mixing of the contents of a reaction cup, in an immunoanalyzer system, the apparatus comprising a device for mixing magnetic particles and 5 liquid as in any of the preceding claims, the apparatus comprising said supporting mechanism for the reaction cup, so as the head of the reagent cup is substantially still.

7. Apparatus as in claim 6, further comprising an elastic pressure plate set (10) with an elastic pressure plate (14) able to press over the head of the reagent cup, so as the reagent cup is prevented from being ejected from said supporting mechanism during mixing action.