Source: https://patents.google.com/patent/EP0285654B1/en
Timestamp: 2019-07-21 11:03:06
Document Index: 610800718

Matched Legal Cases: ['art 28', 'art 28', 'art 28', 'art 29', 'art 29', 'art 29', 'art 29', 'art 29']

EP0285654B1 - Automated analytical apparatus for measuring antigens or antibodies in biological fluids - Google Patents
EP0285654B1
EP0285654B1 EP19870907102 EP87907102A EP0285654B1 EP 0285654 B1 EP0285654 B1 EP 0285654B1 EP 19870907102 EP19870907102 EP 19870907102 EP 87907102 A EP87907102 A EP 87907102A EP 0285654 B1 EP0285654 B1 EP 0285654B1
EP19870907102
EP0285654A1 (en
BIOCHEM IMMUNOSYSTEMS LLC;ARS HOLDING 89 N.V.
1986-10-14 Priority to CH409686A priority Critical patent/CH669266A5/en
1986-10-14 Priority to CH4096/86 priority
1987-10-10 Application filed by Applied Research Systems ARS Holding NV filed Critical Applied Research Systems ARS Holding NV
1988-10-12 Publication of EP0285654A1 publication Critical patent/EP0285654A1/en
1992-02-26 Publication of EP0285654B1 publication Critical patent/EP0285654B1/en
Apparatuses of a type capable of effecting various kinds of biological analyses on different liquids have already been reported. Since every kind of analyses requires the use of at least one specific reagent, it is generally inconvenient to store several of these reagents in the apparatus itself. It is preferable to have the reagents closely associated with each respective analytical cells; hence, when carrying out one specific kind of analyses, one has to use a specific reaction cell containing a specific analytical reagent associated with that cell. In some cases, the reagents are in the form of coatings on the cell walls. In other cases, reagents specific of analytes are deposited on beads and the coated beads react with the analyte after introduction into the cell. The advantage of these techniques is to avoid separation steps by centrifugation; however, a disadvantage is the relatively small area of the available reagent coated surfaces, meaning decreased sensitivity.
Other embodiments exist in which the reagents are incorporated into very small particles such as latex particles, i.e. coated with antigen or antibody reactants. In these embodiments where antigen/antibody complexes are formed, one measures the percent of particles harboring said complexes relative to the total number of particles. Thus, a technique of this kind requires somewhere a separation step by centrifugation. For this, one can either gather on a single rotor all cells subjected to the same reaction conditions or, otherwise, in the case of a plurality of cells subjected to different conditions, the latter must be transferred at some stage from a reaction station to the centrifugation rotor. Consequently, the first case only enables to perform reactions of a same kind as, with different kinds of reactions, the incubation times would be different, and in the second case, the transfer step will require using mechanisms of sophisticated complexity.
US-A-4,540,549 discloses a chemical analyzing apparatus comprising a turntable for removably supporting reaction vessels. Along the circumference of turntable are arranged a reagent delivery unit for delivering a given amount of reagent into successive reaction vessels, a sample delivery unit for delivering a given amount of sample into successive reaction vessels. Below the turntable is arranged a thermostat. The reaction vessels are disposed in the thermostat and the liquids in the reaction vessels are maintained at a given constant temperature to proceed the reaction. A unit for mixing samples and reagent in the reaction vessels is also provided at a position along the circumference of turntable. The absorbance of the liquids in the reaction vessels is measured by photometering units. This apparatus does not permit to modify the incubation period between the reaction vessels which are simultaneously processed on the turntable.
The object of the present invention is an automated apparatus for measuring antigens or antibodies in a biological fluid and capable of carrying out several types of analyses simultaneously, i.e. with this apparatus it becomes unnecessary to gather together several cells subjected to a same analysis on a common rotating disk and to wait until the analysis is terminated before undertaking analyses of a different type by using another series of cells.
Thus, an analytical apparatus suitable for the automated measuring of antigens or antibodies in a biological liquid is defined in annexed claim 1.
This apparatus of the invention has many advantages. It is very versatile and can simultaneously effect a large number of tests of different kinds. For this, each cell is worked independently of other cells located before or after it. The magnetic particles used for reagent immobilization are very small and they have an extensive specific area for building antigen/antibody immunocomplexes which allows excellent sensitivity. No centrifugation step is necessary to effect separation which is performed by simply using a magnet. This separation can be controllably effected at a desired time which enables to vary the incubation periods in function to different analytes and reactants. No radioactive markers are necessary and problems of protection from radiation can be ignored.
Under practical conditions, the present apparatus is conceptually simple, easy to use and, because of its flexibility, it is adapted to hospital laboratory work as well as to medical home practice. Indeed, during daily consultations, a doctor may wish to measure at short intervals various fluids involving immunoreactions of different kinds. In contrast to what normally happens in laboratories, it is not readily convenient for him to collect during a day a number of analytical samples of a same kind sufficient to fully load the rack of an apparatus only designed to this kind of analyte. Contrarywise, with the apparatus of the invention, a doctor may for instance collect daily many samples of different fluids and subject them to analyses practically simultaneously, each cell being worked independently according to the kind of analyses desired.
Fig. 1 is a view in perspective of the apparatus as a whole.
Fig. 2 is a view of the underside of the apparatus.
Fig. 3 is an enlarged plan view of part of fig. 1
Fig. 4 is a cross-section along line IV-IV of fig. 3
Fig. 5 is a first radial cross-sectional view of fig. 1
Fig. 6 is a second radial cross-sectional view of fig. 1
Fig. 7 is a third radial cross-sectional view of fig. 1
Fig. 8 is a fourth radial cross-sectional view of fig. 1
Fig. 9 is a fifth radial cross-sectional view of fig. 1
Fig. 10 is a cross-section along line X-X of fig. 9
Fig. 11 is a cross-section along line XI-XI of fig. 10
The present analytical apparatus comprises a transfer disk-shaped rack 1 provided with peripheral radial housing recesses 2, evenly spaced, for holding the reaction cells 3 of the samples to be analyzed. This transfer disk 1 is rotatably mounted on a frame 4 by means of a shaft 5 which crosses this frame 4 and which bears, underside thereof, a radially slotted wheel 6, 6a (fig. 2, 7). A driving gear 7 fastened to a step-by-step motor 8 carries two pegs 9 whose radial separation matches with that of two consecutive radial slots in wheel 6. The axle of this driving pinnion 7 coincides with the edge of the radially slotted wheel 6, so after each half-turn of the driving pinnion 7, the pegs 9 re-engage with two adjacent radial slots 6a, the wheel 6 being driven one step forward. Obviously, each displacement step of the wheel 6 corresponds to one of the advancing steps of the radial recesses 2 of the transfer rack 1.
Electrical heating elements R (fig 4-7) are embedded in the body of aluminium of the transfer disk 1 and are under control from a thermostat element T adapted to maintain the temperature of the transfer disk 1 to a desired value which depends on the incubation temperature required for reacting the analyte samples in the cells 3 with the respective corresponding reagents.
Several working stations are distributed over frame 4 around the transfer rack 1. The first station is a loading unit 10 in which the cells 3 are set up in the radial recesses 2 of the transfer rack 1. (fig. 1, 3 and 4). This unit 10 comprises an approaching-ramp 11 for the cells 3 which opens opposite to one of the radial recesses 2. This unit also carries a spring-blade 12 and a roller journalled on a horizontal shaft. This blade 12 and the roller 13 are made of a resilient material and are designed to press, respectively sidewise and topwise, the loaded cells 3 on the disk 1 to provide a contact as tight as possible of the walls of the radial recess 2 and the cell walls to ensure appropriate thermostatting of the samples within the cells and consequent reproducible incubation conditions.
The side wall of each cell 3 which faces the outside of the transfer disk 1 carries an identification sign coded in relation with the kind of analyses to be carried out. The coding is preferably digital and comprises a series of successively spaced bars of varying thickness which can be probed by a special sensor constituted by a high sensitivity reflexion detector from Hewlett-Packard. This sensor corresponds to the second working station which is connected to the input of a control unit 15 illustrated by the block-diagram of fig. 12 which will be described hereafter. The two following working stations are represented by two pipetting stations 16 and 17, each having a jig 18 and 19, respectively. An arm of each jig 18 and 19 bears at the free end thereof a hollow pointed dropper 20 and 21, respectively connected by flexible hoses 22 and 23, respectively to two calibrated pipettes 24 and 25, respectively constituted by calibrated tubes and pistons.
The vertical portion of each jig 18, 19 (fig 2, 5) comprises a tubular section 26, 27 respectively, fastened between frame 4 and an auxiliary fixture 4a, this section 26 containing a movable slidingly mounted tubular part 28, 29 respectively, whose upper end is provided with the jig's arm 18, 19 respectively.
The lower end of the movable tubular part 28 protrudes beyond the under-side of the auxiliary fixture 4a. This end is provided with a ball-bearing 30 whose outside ring comprises a lug 31 engaging in a rod 32 whose other end is in mesh with another lug 33 fastened crankwise to a disk 34 itself integral with a driving shaft of a synchronous motor 35 attached to the auxiliary fixture. This lower end of the movable tubular part 28 further carries an arm 36 which engages, through a slit 36a, with a pin 37 fastened to a disk 38 fixed to the driving shaft of a synchronous motor 39. This disk 38 (fig.2) is provided with peripheral radial slits 40 which move in front of a light source 41 facing a photo-detector 42. By means of these slits, the angular position of disk 38 can be checked as a function of the desired angular position of the arm 36. The cut 36a which opens at the free end of the latter also engages with cylindrical guiding rods 43 fastened to the auxiliary fixture 4a in each of the angular position to be occupied by arm 36.
The first of the transfer pipettes 16 is to transfer a suspension of magnetic particles carrying an immobilized antibody into a reservoir 44 (fig.1) fixed to an oscillating base 45 intermittently tilted in one way or the other. The reservoir keeps the level of the liquid constant according to the principle of canary-fountains. It comprises at the bottom center a double incline 44a for providing a stirring action consecutive to the intermittent oscillations given by the base 45 which maintains the particles in suspension in the liquid.
The two liquid delivery stations 16 and 17 are followed by a first washing station 46 (fig.6) and, before this and coupled therewith, 4 identical magnetic separation devices 47 (fig. 2 and 6) each located opposite to the periphery of the transfer disk 1 and angularly separated from each other by a distance corresponding to a step between two radial recesses 2. As all these magnetic separation devices are identical, only one of them is described herein. This device 47 comprises a permanent magnet 48 fastened to an oscillating carrier 49 journalled about a horizontal shaft 50 oriented in a tangent direction relative to the transfer disk 1. A connecting pin 51 is fastened, in parallel to shaft 50, to the oscillating carrier 49 and crosses one end of a push-rod 52 whose other end is hinged to a movable armature 53 of an elecromagnet 54. The push-rod 52 is surrounded by a compression return spring 55 compressed between this push-rod and a small plate 56 which links the device 47 to the framework 4. The reason of the existence of four magnetic separation stations, of which three are ahead of the washing station, is to provide a time sufficient for allowing all the magnetic particles to gather on the wall 3b of the reaction cells 3, this wall being adjacent to the permanent magnets 48 when the latter are brought very close to these walls by the rocking motion of the oscillating carrier 49, under the action of the electro-magnet 54 which operates the push-rod 52 through the action of the movable amature 53 and against the force of the return spring 55.
The first washing station 46 comprises a C-shaped bracket 57 of which one of the parallel arms is fastened to the frame 4. A slide guiding member 58 is located between the two arms of the C-bracket and guides a slide 59 provided with a side-arm 59a carrying at the end two pairs of hoses 60a and 60b (the only one represented on fig. 6), 61 and 61b respectively (fig 1), each pair being disposed above one of the two reaction compartments 3b of each cell 3 when positioned at the wash station 46. The slide is connected to a synchronous driving motor 68 by means of a rod 69 of which one end is hinged to the slide 59 and the other end is excentrically coupled to a disk 70 fastened to the driving shaft of the motor 68.
One of the hoses 60a, 61a in each pair is connected to a suction source 62 by means of a spout 63 controlled by a valve 64 elastically pressed against the seat of the spout 63 by a spring 65. A push-rod 66 coupled to a movable amature of an electromagnet 67 is arranged under the valve 64 to draw the valve from the seat of the spout 63 against the push of the spring 65, when the sucking action in reaction-compartments 3b is to be interrupted.
The first washing station 46 is followed by a first mixing station 77 comprising a rod 78 (fig. 7, 8) integrally fastened to an electromagnet 79 which provides thereto a longitudinal oscillating motion. An incline 73 fastened to frame 4 enables to slightly lift the cell 3 during the mixing operation. This rod 78 is oriented in facing relationship with the portion of cell 3 located above the transfer disk 1, so its longitudinal displacement toward the disk center rocks the cell 3 around the upper plane of said disk 1. A return spring 80 maintains the lower part of the cell 3 against the wall of the radial recess 2 in which the cell 3 is positioned, so when the electromagnet 79 is no longer energized, the lower part of the cell 3 is pushed back against the wall of the radial recess 2, this succession of moves being at a frequency sufficient to agitate the content of the cell. To improve the mixing efficiency, a small weight, for instance in this example a bead, is initially introduced in each of the reaction compartments 3b of this cell 3. Adjacent to the mixing station 77, is a roller 13 of the loading station 10; the blade 12 for providing a lateral pressure is not visible but, nevertheless, it exists on the apparatus.
The two pipetting stations 82, 83 (fig. 1) are identical, so only one needs being described in more detail. As for the washing stations 46 and 81, these pipetting stations each comprises a C-shaped supporting bracket 84 whose lower horizontal portion is fastened to frame 4. A slide guiding member 85 is located between the two parallel portions of bracket 84 to guide a slide 86 provided with a side arm 86a which carries at the end two hollow points 87, 88, which are connected by two flexible hoses 89 and 90, respectively, to a double channel peristaltic pump 91. In this Example, the pump is a high precision model manufactured by ISMATEC SA, Zurich, model "MINI-S-8".
This pump comprises a semi-circular base 92 against which lie the two flexible hoses 89, 90 which extend to a reservoir (not represented) of the product to be dispensed. A disk is rotatably mounted in the center of the semi-circular base 92 and is bolted to the driving shaft 94 of a motor (not represented). This disk carries, peripherically mounted, a series of cylinders 95 whose longitudinal axes are parallel to the rotation shaft 94 of the disk. The diameter of these cylinders is selected for allowing between them and the semi-circular base 92 a space amounting to twice the wall thickness of the flexible hoses 89, 90 i.e. to the thickness when the two hoses are pinched. When they turn around the rotation shaft 94, the cylinders 95 squeeze the flexible hoses 89, 90 at regular intervals which mean catching a volume increment of liquid therebetween and driving away this volume as the rotation of the cylinders 95 continues. The angular displacement selected for the disk carrying the cylinders 95 determines the number of pumped volume increments and, as a consequence, the volume of the dispensed liquid.
The slide 86 is connected to an excentric 97 (fig.2) of a driving plate clamped to a shaft of a synchronous motor 99 through a rod 100.
A second mixing station 101, (fig.1) identical to the mixing station 77 is placed after the pipetting station 83. An arm 102 is integral with a vertical shaft 103 oscillatingly mounted on frame 4 and switches the cells to a discharge ramp 104. The lower end of the vertical shaft 103 carries a horizontal arm 105 (fig.2) provided with a longitudinal groove which engages with an excentric 106 integral with a driving plate 107 clamped on the shaft of a synchronous motor 76.
A photo-electric cell 108 acting as a presence detector (fig.3) precedes the loading unit 10 and is positioned opposite to the recess 2 which is one step before the recess 2 located opposite to the access-ramp 11. There is a second presence detector photo-cell in the access ramp 11. A loading push-rod 110 (fig.3 and 4) is slidingly mounted on the loading unit 10 in the direction of extension of ramp 11. This push-rod 110 is fastened to an arm 111 extending sidewise, provided with a longitudinal groove in engagement with an excentric 112 protruding from a rotating sheave fastened on the shaft of a synchronous motor 114.
A last station, constituted by a measuring unit 115 is positioned somewhere around the transfer rack 1. Since the reaction cells are programmed individually and that some may have to rotate with the transfer rack 1 a number of revolutions different from others, the measuring station 115, which constitutes the last working station, can be anywhere around the transfer rack 1. In this example, one position was free between pipets 24 and 25 and peristaltic pumps 91, and it was chosen for practical reasons.
The flexible hose 117 for drawing off the liquid is carried by an arm 119, journalled about a vertical shaft on a slide rod 120 mounted in a vertical slide guide 121 fastened to a C-shaped bracket 122 mounted on the frame 4. The arm 119 has a branch 119a whose end is in mesh with one or the other of grooves 123, 124 provided in the internal face of the vertical portion of the C-bracked 122. As shown in fig.10, the slide-rod 120 carries two fingers 120a, 120b in mesh with the two grooves 123, 124, respectively. Fig.11 shows that these two grooves 123, 124 communicate with each other by their upper ends.
Fig.10 shows that the connecting arm 119 is further coupled to a rod 125 by means of a knee-joint which gives this rod a certain degree of freedom relative to the angular displacement of the arm 119 whose amplitudes can be estimated from the positions sketched with solid and interrupted lines. This arm is normally in a return position sketched with solid lines by means of a return spring 129 an end of which is bound to the arm and the other end is fastened to the slide rod. This rod 125 crosses frame 4 to come to engage with an excentric 126 of a driving sheave fastened to the shaft of a driving motor 128 (fig.2).
A rod 130 is slidingly mounted in a side wall of the C-bracket 122 which defines the portion where the two grooves 123, 124 unite together. This rod 130 is coupled to a movable armature 131 of an electromagnet 132 and drawn back by a return spring 133.
Three general purpose input-output boards GP2, GP3, GP4 are used as follows: GP4 is programmed to operate as an input for the signals from a board DE working as an interface for the optical detectors 108 and 109 and for a thermostatting board TH coupled to a heating resistor R of the transfer rack 1 and to a gauge S to measure the temperature of this transfer rack 1. GP2 and GP3 are programmed to operate as output in interfaces for the interface boards IM and IS which control the several motors which drive the various components and the electromagnets of the magnetic separation and mixing station. All the boards connected to the BUS bar are available from the Company GESPAC, Geneva; the identifying reference numbers are: MEM-3 for memory ME; TlM-lA for board CC; PlA-2W for baord GP1; S10-IE for board SE; PlA-2W for boards GP2, GP3, GP4.
The thermostatting board provides proportional control, by means of a thermistor as dectector and a modulated power control acting on the pulse width. The control of the state of the board is achieved with two lines according to the following scheme.
unconnected/open thermistor
The latter is stabilized at 37± 0.2°C. If the thermistor is defective (state 00) the heating power is automatically interrupted.
In the present embodiment, the transfer disk or rack 1 comprises thirty radial recesses 2 and can therefore accomodate 30 cells simultaneously. The time interval of two successive steps of the transfer disk 1 is 15 sec, so one revolution of the disk lasts 30 X 15 sec. = 7.5 min. This 7.5 min. period does not correspond to the time of analyses of one sample but constitutes the basic incremental period to be used in all analyses carried out by the apparatus; in this connection, it is reminded that each cell 3 can remain on disk 1, the full time necessary to achieve the incubation of the analytical sample to be tested; this will be detailed hereafter.
When a cell becomes positioned on the access incline 11, it is detected by the detector probe 109 which transmits the signal to the computing and controlling unit. If, in simultaneity, the detector 108 does not detect the presence of a cell on the transfer disk 1 after the disk has advanced one step forward, the loading push-rod 110 is driven into alternative motion and pushes cell 3 into corresponding radial recess 2.
As said before, each cell is marked on the outside facing side with a bar-code. The transfer disk 1 moves the cell 3 stepwise to the bar-code read probe located between two successive angular stop positions of the recess 2 of the transfer disk 1. During this move, the cell 3 travels under blade 12 and the roller which tightly press the cell 3 into its recess 2. When it passes before the read detector 14, the computing and controlling unit identifies the type of analyses to be performed on the analytical sample. This information recorded on the cell requires that the user has selected a cell whose reservoirs 3a are already filled with one or more reagents suitable for testing that particular analytical sample. With this initial information, and taking into account that the computing and control units has memorized the angular setting of this cell relative to the initializing reference mark on disk 1, each further station will receive specific instructions on the operation to be performed therein.
The cell 3 which has just been set on the transfer disk 1, is not initially provided with a suspension of solid magnetic phase in reservoir 44, so pipet 24 coupled to jig 18 is not actuated. This cell 3 goes therefore to the second jig 19. Then, the movable tubular part 29 bound to the ball-bearing 30 is lowered by rod 32 driven by the journal 33 fastened to disk 34 fixed to the shaft of motor 35. This displacement of the tubular part 29 leads to the displacement of the jig's arm 19 and the hollow dropper point 21. During this move, the point pierces through a protective cap (not represented) on the side reservoir 3a located under said point 21 and the latter penetrates into it below the level of the reagent for instance the immunopartner to the analyte in this reservoir. The measuring piston of pipet 24 connected to the hollow point by flexible hose 22 is displaced through an unrepresented mechanism in a stroke corresponding to the volume of liquid desired. The rod 32 then lifts the tubular part 29 which is thereafter driven angularly by disk 38 in mesh with arm 36 by means of pin 37. When the hollow point is above one of the reaction compartments 3b of the cell, rod 33 again lowers the tubular part 29 to bring this hollow point 21 into the reaction compartment. The measuring piston of pipet 24 moves backwards in a stroke corresponding to the amount of reagent desired. The tubular part 29 is again lifted by rod 32 then it is angularly displaced by disk 38 in gear with arm 36 for putting the jig's arm in facing relation with the other reaction compartments 3b of cell 3. The hollow point is again lowered to dispense a same dose of reagent as in the neighboring compartment. Finally the jig 19 returns to its starting position, opposite to reservoir 3a in which the doses of reagents dispensed into reaction compartments 3b have been pumped and the hollow point can discharge therein the unused portion of reagent sampled initially. Then the jig 19 is once more lifted to remove the hollow point 21 from this reservoir.
The full reagent delivery cycles achieved in the 15 sec interval which seperates two consecutive displacement steps of the transfer disk 1. If, depending on the type of analyses to be effected, the second reservoir 3a of cell 3 contains a second reagent , the latter is distributed into both compartments 3b according to the same foregoing operation.
Then, transfer disk 1 continues its stepwise rotation. Naturally, the other cells which lie on the transfer disk 1 each receive a treatment in function to the analyses to be carried out therein, so each work station receives appropriate instructions relative to that cell which is positioned facing it.
In this Example the period of revolution is 7.5 min. (30 radial recesses = 30 steps of 15 sec each) to which one must add the time of a partial revolution depending on the position at which the liquid phase is removed from the cell after separation of the solid phase. The incubation periods are therefore an integer multiple of 7.5 min. Thus, depending on the kind of analyses, the computing and control unit decides on the number of revolutions of each cell to complete the incubation of the cell content.
When pipet 25 has sucked a given volume of this suspension in the hollow point 20, the jig brings this hollow point into, successively, each compartment 3b for adding a dose of the solid phase suspension to the liquid analyte. The cell is then displaced stepwise to the first mixing station 77 which follows the first washing station 46, after which a new incubation period is started.
The cell 3 is brought in the next step in front of the mixing station 77 which imparts a fast rocking movement to the cell around the upper internal edge of the radial opening 2, by means of the rod 78 actuated by electromagnet 79 and return spring 80. The magnetic particles of the solid phase are therefore redispersed in the washing liquid.
Once the incubation is over and when the cell again faces the pipet delivery station 83, which is fully identical to the corresponding station 82, a quantity of liquid for stopping the reaction with the substrate is introduced by the peristaltic pump associated with this delivery station into each reaction compartment 3b of the cell.
When the content of the compartments of this cell 3 which reaches the measuring station 115 is to be measured, the slide-rod 120 actuated by rod 125 lowers the arm 119 which brings the end of duct 117 into one of the two compartments of cell 3, the free end of this arm being guided in groove 123, once the liquid from this cuvette of cell 3 has been transferred to photometer 118, rod 125 lifts back slide-rod 120 and arm 119. When the free end of side branch 119 reaches the top of groove 123 (fig.11), the electro-magnet 132 moves the rod 130 against the force of return spring 133, so this rod 130, causes arm 119 to swivel and to bring the end of branch 119a to the top of groove 124. When rod 125 again lowers the slide rod 120, the arm is guided by branch 119a engaging in groove 124, so that the free end of the flexible pipe 117 is brought into the second compartment of cell 3, and this enables to transfer, to the photometer 118, the liquid to be analyzed of this second compartment.
1. Automated analytical apparatus for measuring antigens or antibodies in biological fluids by the formation of specific antigen/antibody immunocomplexes in reaction cells (3) using reagent partners adapted for providing each of said complexes, a solid phase carrier carrying one of the elements of the complex, this apparatus comprising thermostating means (T) for controlling the incubation temperature conditions in the cells, a regular step-by-step transfer means (1) for these cells providing a closed circuit transfer path from loading station (10) to a discharging station (104) through stations comprising reagent delivery (16), mixing (77, 101) and washing (46) stations which provide processing steps for carrying out a plurality of specific analyses of different kinds, these stations being distributed along said transfer path, characterized by a detector component (14) which reads a code carried by the cells for identifying the kind of analysis to be effected located after the loading station (10), this reading component being connected to a computing unit (MI) whose outputs are wired so as to control said aforementioned stations including the sequencing of the operations pertaining to each kind of analyses to be performed and identifed in conformity with said code, and the thermostating means are in contact with at least a part of the wall of the reaction cell (3) on the whole length of the closed-circuit, the revolution period of said transfer means (1) forms the base unit for the incubation periods of all analysis to be performed on this apparatus, the incubation period being an integral multiple of the revolution period of the transfer means plus a fraction of this revolution period the number of these base units to be accomplished by each cell depending on the kind of analyses to be performed and resulting from the sequence of the operations controlled by the computing unit (MI).
2. Apparatus according to claim 1, characterized in that said carrier of the complex is a magnetic particulate carrier.
3. Apparatus according to claim 2, characterized by magnetic separation stations which each of them comprises a permanent magnet (48) coupled to an actuating component (53, 54) capable of moving back and forth the magnet between two limit positions, in one of which the magnetic field (48) crosses the walls of said cell (3) and in the other of which the magnetic field is remote from said walls.
4. Apparatus according to claim 1, characterized in that said transfer means comprises a disk (1) of thermally conductive material embedding heating elements (R) and provided with recesses (2) for housing said cells (3).
5. Apparatus according to claim 1, characterized in that the cell loading station (10) is associated with two cell positioning photo-detectors (108, 109) one (108) of them in front of the cell path upstream of a loading ramp which opens vis-a-vis the path of said transfer means and the other one (109) within the said ramp (11) in facing relation with the position of the cell before the loading thereof.
6. Apparatus according to claim 4, characterized in that each of the holding recesses (2) of the transfer means (1) opens radially on the edge of said disk, each cell (3) is positioned in its recess so that it partly extends above the upper face of the disk, the mixing device (77) comprises on one hand an elastic component (80) which rests against the edge of the disk, and on the other hand, a rod (78) mounted to slide back and forth radially with respect to the disk (1) and above the upper face thereof with its front end adjacent to said cells, and an actuating electromagnetic part (79) for driving this rod into longitudinal oscillating motion with a frequency sufficient to bring the cell's content into agitation.
7. Apparatus according to claim 1, characterized in that the loading station (10) and each mixing station (77) are followed by pressure mechanisms (12, 13) which force the cell walls to stay in contact with the walls of the respective housing recess (2).
8. Apparatus according to claim 1, characterized in that said transfer means (1) is provided with a housing recess (2) whose shape closely matches the shape of a portion of the cells (3), the walls of the recesses being heated by said thermostatting means.
9. Apparatus according to claim 1, characterized in that one of the reagent delivery station (116) is in connection with a photometer (118).
10. Apparatus according to claim 1, characterized in that the station adapted for carrying out step of reagent delivery comprises a reservoir (44) containing a suspension of magnetic particles carrying an immobilized antibody or antigen, oscillating driving means (45) connected to said reservoir the bottom of which comprises two ramps (44a) inclined in two opposite directions for providing a stirring action as a consequence of the intermittent oscillations of said reservoir.
EP19870907102 1986-10-14 1987-10-10 Automated analytical apparatus for measuring antigens or antibodies in biological fluids Expired - Lifetime EP0285654B1 (en)
CH4096/86 1986-10-14
EP0285654A1 EP0285654A1 (en) 1988-10-12
EP0285654B1 true EP0285654B1 (en) 1992-02-26
EP19870907102 Expired - Lifetime EP0285654B1 (en) 1986-10-14 1987-10-10 Automated analytical apparatus for measuring antigens or antibodies in biological fluids
GB2005019B (en) * 1977-09-28 1982-08-18 Technicon Instr Magnetically attractable material
WO1988002866A1 (en) 1988-04-21
EP0502638B1 (en) 2000-05-31 Feed and orientation mechanism for cuvettes
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