WO1994013402A1 - Microtitre cups for performing immunological tests and automated device therefor - Google Patents

Microtitre cups for performing immunological tests and automated device therefor Download PDF

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Publication number
WO1994013402A1
WO1994013402A1 PCT/BE1993/000068 BE9300068W WO9413402A1 WO 1994013402 A1 WO1994013402 A1 WO 1994013402A1 BE 9300068 W BE9300068 W BE 9300068W WO 9413402 A1 WO9413402 A1 WO 9413402A1
Authority
WO
WIPO (PCT)
Prior art keywords
cups
microtitre
code
tests
carrier
Prior art date
Application number
PCT/BE1993/000068
Other languages
French (fr)
Inventor
Edgard Smets
Jean-François SPRING
Hubert Thomas
Marc-Olivier Demaurex
Original Assignee
Eurogenetics N.V.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Eurogenetics N.V. filed Critical Eurogenetics N.V.
Priority to EP93923986A priority Critical patent/EP0671979A1/en
Priority to AU53669/94A priority patent/AU5366994A/en
Publication of WO1994013402A1 publication Critical patent/WO1994013402A1/en

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Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/026Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations having blocks or racks of reaction cells or cuvettes
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00584Control arrangements for automatic analysers
    • G01N35/0092Scheduling
    • G01N35/0095Scheduling introducing urgent samples with priority, e.g. Short Turn Around Time Samples [STATS]
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/0099Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor comprising robots or similar manipulators
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1002Reagent dispensers
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N2035/00178Special arrangements of analysers
    • G01N2035/00277Special precautions to avoid contamination (e.g. enclosures, glove- boxes, sealed sample carriers, disposal of contaminated material)
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00584Control arrangements for automatic analysers
    • G01N35/00722Communications; Identification
    • G01N35/00732Identification of carriers, materials or components in automatic analysers
    • G01N2035/00742Type of codes
    • G01N2035/00752Type of codes bar codes
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/04Details of the conveyor system
    • G01N2035/0439Rotary sample carriers, i.e. carousels
    • G01N2035/0443Rotary sample carriers, i.e. carousels for reagents
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/04Details of the conveyor system
    • G01N2035/0439Rotary sample carriers, i.e. carousels
    • G01N2035/0451Rotary sample carriers, i.e. carousels composed of interchangeable sectors
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/04Details of the conveyor system
    • G01N2035/0474Details of actuating means for conveyors or pipettes
    • G01N2035/0482Transmission
    • G01N2035/0486Gearing, cams
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027General features of the devices
    • G01N2035/103General features of the devices using disposable tips
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1081Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices characterised by the means for relatively moving the transfer device and the containers in an horizontal plane
    • G01N35/109Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices characterised by the means for relatively moving the transfer device and the containers in an horizontal plane with two horizontal degrees of freedom

Definitions

  • the invention relates to microtitre cups for per ⁇ forming immunological tests of the ELISA test type.
  • Such cups consist of transparent plastic material and have small dimensions, that is, a height of about 13 mm and a diameter of about 8 mm.
  • microtitre cups available commercially in large numbers are manufactured in strips of 12 or 8 cups attached to each other, for instance according to an injection moulding process, and 8 or 12 of these strips are arranged removably in a carrier grid.
  • the cups are easy to separate from each other and are open at the top.
  • the protrusion lies horizontally on the top of an edge of the carrier grid such that the label with code carried by this protrusion is easily visible.
  • the invention provides improved microtitre cups in that the microtitre cups open at the top individually carry an automatically readable code, for example a bar code.
  • an automatically readable code for example a bar code.
  • the codes arranged on these cups are now not readable when they are situated in a carrier grid, arranging of the codes on the side or on the underside implies a significant enhancement relative to the known microtitre cups with codes which are readable in the carrier grid.
  • the microtitre cups can in any case be used individually. Known microtitre cups broken off the strips would no longer be identifiable, while the microtitre cups according to the invention would be.
  • the code can be arranged on the side and/or bottom of the cup.
  • the labels arranged on the sides do not impede the light shining vertically through a trans- parent microtitre cup when determining an optical densi ⁇ ty.
  • the label and the code of the cups according to the invention have a miniature format due to the small dimensions of the cups, it has still been found possible to arrange a reliable, well readable code on the cups.
  • coated cups are known for performing analog ELISA tests which are manufactured from plastic which may or may not be transparent and which have a larger format, for instance 2 cm high and 1 cm wide.
  • Fig. 1 and 2 show a perspective view of an automated device according to the invention respectively in closed and opened situation
  • Fig. 3 shows on larger scale a section along the line III-III in fig. 1,
  • Fig. 4 shows on larger scale a perspective view of detail IV in fig. 2,
  • Fig. 5A, 5B and 5C each show on a larger scale a perspective view of detail V in fig. 2 in different positions,
  • Fig. 6, 8 and 9 show on a larger scale a perspective view respectively of details VI, VIII and IX in fig. 3
  • Fig. 7 shows on larger scale a perspective view of detail VII of fig. 3 in another formation
  • Fig. 10 shows a fluid circuit diagram for the auto ⁇ mated device of fig. 1, and
  • Fig. 11 is a broken away perspective view of detail XI in fig. 5B.
  • the automated device 1 comprises a manipulation cabinet 2, a storage compartment 23 for containers 202, 205 and 206 of diverse liquids required in ELISA tests and a vacuum vessel 209, a feed platform 24, platforms 25 for carrying a computer 6 with monitor controlling the automated device, keyboard 26 and recorder 27.
  • the cabinet doors 29 can only be opened by operating an electric switch 30 after a relevant key has been entered as password in computer 6 by an authorized person. Errors due to interference in the inside of the automated device 1 by unauthorized persons is hereby avoided.
  • the manipulation cabinet 2 contains inter alia (see fig. 3) : a storage compartment 13 for holders 3 which are each adapted for receiving, in this embodiment, four microtitre cups 4; a storage compartment 15 for receiving primary tubes 5 which contain serums for testing, for instance blood serums of patients, respectively standard samples; storage compartments 16 for receiving diluent tubes 36; storage compartments 17 with locations 237 for receiving containers 37 for different conjugates, sub ⁇ strates and stop liquids; incubation areas 18 and 19 which are held at a temperature of 22°C respectively 37°C with a variation of at most 2°C in which holders 3 with cups 4 are kept for a prescribed time in accordance with the type of test; a pipette storage compartment 20 in which are accom ⁇ modated three grids filled with unused pipettes 7; a pipette storage compartment 21 for storing used, still usable pipettes 7; a checking device 118 for checking whether a pipette is hanging on the pipette arm 10; a cooling space 22 with locations
  • these containers 32 are then transferred to a storage compartment 17 to be brought to room temperature prior to being used) ; a device 33 for feeding and discharging test ingre ⁇ washers and primary tubes 5; an optical density measuring device 34; a washing device 35; a switching device 28; and a waste disposal device 31.
  • an extracted serum is sent in a primary tube 5 together with a form indicating the desired Elisa test or tests to a laboratory which performs such tests by means of the automated device 1.
  • the test assign ⁇ ment is numbered and entered in computer 6 matched with antecedents of the patient with mention of all required Elisa tests. It is conceivable that in a hospital or in a laboratory the test authorization is entered into a central computer coupled to computer 6. At the time of entry into the computer 6 a label 42 with bar code 43 containing the assignment number is printed and adhered to the primary tube 5. It is noted that throughout this text an automatically readable code, for instance bar code or dot code, can be understood instead of bar code.
  • the computer 6 contains the necessary instruction for all types of Elisa tests with respect to the manner of performing thereof, including the designation of the ingredients to be used.
  • these ingredients can be included microtitre cups which are coated inside with antibodies and/or antigens, hereinafter designated as cups 4, and conjugates which are held in conjugate con ⁇ tainers 32 which are each provided with a label 40 with bar code 41 which designates the relevant conjugate associated with a lot of testing ingredients of a partic ⁇ ular Elisa test.
  • the cups 4 which together with a determined conju ⁇ gate or number of conjugates form part of a particular lot also carry this information in their bar code togeth ⁇ er with the identification of these cups 4.
  • the code 39 on cups 4 contains for instance six letters X X P W W Y. Herein are intended: X X for code of test type P for production serial number W W for production week
  • the code 41 on containers 32 and 37 contains for instance ten letters C C X X P W W Y E E.
  • the primary tubes 5 which contain standard samples have for instance a fifteen-letter code
  • N N the method of standard test, namely: concentration calibration; negative check; positive check; or reference check.
  • Y V V V V V designations relating to use in respect of concentration,- F F F for designating use time limits in months and year.
  • a testing instruction is entered into the computer 6 in the form of a diskette, which instruc ⁇ tion also contains directions for realizing calibration values with limited time periods for the use of these calibration values and therefore directions for recali- bration, in addition to directions for refusing the input of ingredients of a determined lot when the reliable lifespan thereof has been exceeded.
  • the code is arranged on each cup 4 as bar code with a width of 6 mm which is printed with a fine-print print ⁇ er, for instance a 12-dot printer, on a label of wood- free paper adhered to one side of cup 4.
  • a fine-print print ⁇ er for instance a 12-dot printer
  • Eight or twelve such thus coded cups 4 open at the top are mutually joined on their upper edge by injection moulding to form a strip. Twelve or eight strips are received into a packing grid. During use these cups 4 are broken loose of each other.
  • the frame 44 of a collective manipulator 8 is driven and guided three- dimensionally as according to fig. 4.
  • Horizontal rails 45, 46 guide a horizontal traverse 47 which is driven by a motor 48, a toothed belt 49, a shaft 50 and two toothed belts 51.
  • a frame 52 is guided relative to traverse 47 in horizontal direction along rails 53 and is driven in horizontal direction by means of a motor 54, toothed belt 55, spline shaft 56 and toothed belt 57.
  • a frame 58 is guided in vertical direction relative to frame 52 by means of its rail 59, wherein the relevant guide rollers 60 are mounted on the same shafts 61 as the guide rollers 62 of the horizontal guiding.
  • Frame 58 is driven in vertical direction by means of a motor 63 via a toothed belt 64, spline shaft 65 and toothed belt 66, which in addition to horizontal parts on the traverse 47 has also guided vertical parts on the frame 58, wherein transition guide rollers 67 are mounted on the frame 52.
  • All positions in the diverse storage compartments for containers 32, 37, holders 3, cups 4 in holders 3, pipettes 7 as well as all other operational positions of manipulator 8, such as stampers 88, pick-up position 115, fountain 35, optical densimeter 34 and waste disposal device 31 are stored in the computer memory in accordance with a co-ordinate system and the stepping motors 48, 54 and 63 steer the manipulator 8 exactly to the required positions using as starting point some reference reflec- tion means 79 with which a sensor 78 to be described later co-acts in order to correct any eventual small deviation in its position.
  • the frame 58 bears a gripper 9, a pipette carrier 10 and a washer 12 (fig. 5A) .
  • Gripper 9 consists of Neuren- berger scissors 14, the gripper arms 68 of which are rotatably mounted on a pivot shaft 69 fixedly attached to frame 58, while the other pivot shaft 70 is moved in vertical direction by means of a stepping motor 71 via a threaded rod 72 with a nut 73 which is displaceable in vertical direction in a bearing block 74 but which is pulled into the lowest position against a stop 77 by means of pins 75 and draw springs 76 so that, when grip ⁇ per 9 clamps shut when taking hold of an object, the upper pivot shaft 70 is pulled downward as long as the nut 73 is held in engaged position with the stop 77 of bearing block 74.
  • a sensor 78 which pro ⁇ trudes downward when gripper 9 is opened but which is carried upward during closing of the gripper 9 by a pressure spring 80 which pushes against a support 81 which is fixed to the lower pivot shaft 69 and in which the sensor is vertically guided for sliding, while the pressure spring 80 presses against a transverse pin 82 of sensor 78 which is guided in vertical slots 83 of the frame 58.
  • the opened gripper position is detected by a switch 84, whereafter the motor 71 is stopped and comput- er 6 has the information that sensor 78 is exposed.
  • the pipette carrier 10 is displaceable between its rest position of fig. 5A and its operative position of fig. 5B in that it is adapted on its top end 85 for snap engagement into a per se known coupling 86, as shown for instance in fig. 11, which is released when the bottom end 87 of the pipette carrier 10 receives an upward impact which is brought about by stamping this bottom end 87 onto a fixed upright stamper 88.
  • coupling 86 is released the draw springs 89 pull the pipette carrier 10 downward until a support 90 thereof strikes on a guide bearing 91.
  • a switch 191 signals the pulled-up position of pipette carrier 10 to the computer 6.
  • pipette carrier 10 When pipette carrier 10 lifts up a pipette 7 the manipulator 8 shows the picked up pipette 7 to the checking device 118 prior to pipetting. Should the checking device 118 signal the absence of a pipette 7, the computer 6 then gives the alarm and stops the pipetting operations until the error is corrected.
  • the washer 12 is displaceable between its rest position of fig. 5A and its operational position of fig. 5C in that it is adapted on its top end with a coupling 86 which is released when the washer 12 receives an upward impact by stamping it onto a stamper 88.
  • a pressure spring 92 presses the washer downward until a stop head 93 of a stop rod 94 strikes against a guide bearing 95.
  • a switch 96 actuated by the stop head 93 signals the rest position of the washer 12 to computer 6.
  • a toothed belt 98 with external toothing is guided along the inside of a curved guide rail 97 by means of guide rollers 99 and guide discs 100 while this toothed belt is driven by means of a stepping motor 101 and tooth wheel 102.
  • Guide rail 97 extends from an inlet 103 to an outlet 104.
  • Fig. 7 shows four different carriers 111, 112, 113 and 114 which can be mutually coupled by means of a vertical pin 105 and a clamp 106 engaging elastically thereon. A plurality of each type of carrier 111-114 is present.
  • Each carrier 111-114 has a curved foot 110 which during transport in manipulation cabinet 2 is displaced between the rail 97 and the toothed belt 98 which then engages in external teeth 109 of these carriers.
  • Carriers 111-114 have on their underside a characteristic differ ⁇ ence, which can be detected by means of two switches 108 and 107; carriers 111 and 113 have a rear switch member 121 which co-acts with switch 107; carriers 113 and 114 have a front switch member 122 which co-acts with switch 108 and carrier 112 has no switch member 121, 122.
  • the carriers 111-114 are recognized by the combination of signals from switches 107, 108.
  • Carrier 111 is adapted for a substrate container 237 or a large conjugate con ⁇ tainer 37; carrier 112 for four cups 4; carrier 113 for two cups 4 and a primary tube 5 which is held in a sleeve 124 provided with a slot 123; and carrier 114 for a small conjugate container 32.
  • a switch 126 switching on motor 101 is actuated by incoming carriers.
  • the frame 127 of a level scanner 128 can swivel on a vertical shaft 129 and is pressed by a torsion spring 130 as according to arrow 131 with a stop nose 132 against a conjugate container 37 of carrier 111 or against a shoul ⁇ der 133 of carrier 114. In the case carriers 112 and 113 pass through, the frame 127 strikes against a vertical rod 134.
  • These parts are herein dimensioned such that a sensor 135 carried by the frame 127 is situated in each case at distance q from the nose 132 above the centre line of the containers 32, 37 or primary tube 5, so that sensor 135 can scan the liquid level therein.
  • Sensor 135 operates as a per se known light reflector and is carried by a rod 136 which is guided vertically in frame 127 and which is pulled downward through a determined stroke by a magnet 137 and pressed upward by a pressure spring 138.
  • a pressure spring 138 When the liquid level in a container is known and the container with its particular inner diameter is identi- fied, the volume of the container is known.
  • Each carrier 111-114 subsequently passes a light sensor 139 which responds to the leading edges of the carriers so that the motor 101 moves the relevant carrier further until a code detector 140 has read the bar codes 41, 39, 43. If necessary the motor 101 moves the carriers 111-114 reciprocally. Should for any reason a code not be readable, the computer 6 then controls the automated device 1 such that the relevant containers or cups are not picked up by the gripper 9 but leave the manipulator cabinet 2 by the outlet 104. If the codes have been read and the carriers 111-114 or cups 4 identified, they are then picked up one by one by the gripper 9 from the carriers 111-114 at a determined pick-up location 115 of the conveyor belt and set down in a free place in cabinet 2 adapted for this purpose.
  • the capacity of the automated device 1 is enlarged in that cups are collected in each case in a holder 3 on which the same type of Elisa test must be performed.
  • the collective manipulator (gripper 9), which must perform many movements, and also other members of automated device 1 are thereby used more effectively.
  • the auto ⁇ mated device 1 starts from a starting position in which storage compartment 13 is entirely filled with empty holders 3.
  • Incoming cups 4 which are identified by their bar codes 39 are placed sorted into holders 3 such that only cups 4 are found in the same holder 3 which are identical in respect of the tests to be performed there ⁇ with and which are thus only suitable for the same type of Elisa test.
  • the test is only started when a holder 3 is full.
  • test ⁇ ing with cups 4 is nevertheless still started after a predetermined period, for instance six hours, or still in due time before the end of a working day, also in the case the holder 3 is not full.
  • a test with cups from an incompletely filled holder 3 are moreover started when the ingredients and serum for an urgent assignment which has been entered into the computer 6 are present in cabinet 2.
  • the automated device 1 comprises a waste disposal device 31.
  • the gripper 9 By means of the gripper 9 the finished cups 4 are placed with an edge 145 of their holder 3 on a swivel plate 143, and into a recess 144.
  • the swivel plate 143 is turned over as according to arrow 146 by means of a stepping motor 147, while a fork-like detainer 150 mounted on the swivel shaft 148 and coupled to this swivel shaft via a torsion spring 149 is carried along from a raised rest position to a position above the inlet 152 of a waste container 151.
  • the holder 3 is herein held in place by the detainer 150.
  • the empty holder 3 In the return stroke of motor 147 the empty holder 3 is set down again and is then picked up by gripper 9 and placed in storage compartment 13.
  • pipette carrier 10 Used and no longer usable pipettes 7 are placed by pipette carrier 10 as according to arrows 154 through a large hole 155 in device 31 and stripped off in the slot 156. All the waste falls into a plastic bag 157.
  • the optical densimeter 34 com ⁇ prises the usual light source 158, light filters 159 and glass fibre cables 160 which cast the light rays 161 through cups 4 and their content onto the light sensors 162.
  • Four sensors 162 herein receive light for measuring of cups 4 while one sensor 163 is intended for a compara ⁇ tive zero object 164.
  • the densimeter 34 comprises a closed box 165 into which a holder 3 with cups 4 is introduced by being placed in a slide 166 by the gripper 9 and the slide 166 then being pushed inside using the pipette carrier 10 which for this purpose performs to ⁇ gether with gripper 9 the movement as according to arrows 167, while the pipette carrier 10 engages in a hole 168 of the handle 169.
  • washing tubes 170 of the washer 12 are washed in a fountain 171, wherein washing liquid is supplied by feed tubes 172 and sprayed on the outside of the washing tubes 170. This washing water is then drained via a drain tube 173 to waste washing liquid containers 205.
  • the washing treatment with the fountain 171 is started by computer 6 only when the washing tubes 170 are situated in fountain 171.
  • the switching device 28 of fig. 10 comprises a vacuum pump 211 of 0.7 bar which is driven by a motor 210 and which creates a vacuum in a vacuum vessel 209 which is connected to two mutually communicating containers 205 for used liquid which are connected via valves 215 and 216 to the washing tubes 170 of the washer 12 respective- ly the drain tube 173 of fountain 171.
  • An air pressure pump 219 driven by a motor 218 is connected to a buffer vessel 220, to containers 206 with different diluents and to containers 202 with different washing liquids. These containers 202 are selected by means of valves 21 in the case of a determined washing treatment and then connected via valves 213 onto washing tubes 170.
  • washing tubes 170 in the washing fountain 171 selected washing liquid is supplied via an opened valve 212 and an opened valve 215.
  • the device 186 for filling diluent tubes 36 with diluent from one of the containers 206 comprises a large cylinder 182 of 500 ⁇ l and a small cylinder 183 of 250 ⁇ l which are connected according to the diagram of fig. 10 to the containers 206 via rotating valves 181, 188 driven by motors 180, 187 and to the tubular pipette carrier 10.
  • the conduit system Prior to filling of the diluent tubes the conduit system is flushed with the diluent for use, wherein the pipette carrier 10 is held in the fountain 171 and this flushed diluent passes into the containers 25.
  • a plurality of diluent tubes 36 is now preferably filled one after another with this same diluent using the filled conduit system, this as required by means of one or more complete or partial fillings of cylinders 182 and/or 183 which are driven reciprocally for this purpose by motors 189, 190.
  • the storage compartments 16 are continually shaken by means of a shaker 230 except during filling with diluent and during pipetting.
  • the rotat ⁇ ing valve 188 is closed and the cylinder 183 then first presses diluent out of the pipette carrier 10 into the fountain 171 so that an air buffer is situated therein, while the bottom end is washed with water.
  • a pipette 7 is then lifted out of the storage compartment 20 or 21 and a measured quantity of serum is drawn up out of a primary tube 5, wherein the small cylinder 183 makes a measured stroke and this serum is transferred into a cup 4 or a diluent tube 36.
  • These operations can be repeated quickly with the same pipette 7 in the case of one or more filled holders 3 with cups 4 for identical tests.
  • this still usable pipette 7 is stored in the storage compartment 21.
  • the computer 6 records the amounts of used washing agents, diluents, conjugates and serums so that the pipette 7 is immersed each time to the correct level into the liquid to be drawn up and computer 6 detects, if necessary, a practically empty container 32, 36, 5, 202, 206.
  • the pipettes 7 employed for instance for serum which can no longer be used are removed immediately through the slot 156. Serums are either carried directly from primary tubes 5 into cups 4 and/or carried into the diluent tubes 36, from which they are transferred in diluted state into cups 4 after some shaking of the mixtures using a shaker 230.
  • a start is made with filled containers 202 and 206, empty containers 205, cleaned conduits, filled pipette storage compartment 20, storage compartments 16 filled with empty diluent tubes 36, holder storage compartment 13 filled with empty holders 3, empty incubation spaces 18, empty pipette storage compartment 21, empty cooling space 22, an empty storage compartment 15 for primary tubes 5, an empty storage compartment 217 for substrate containers 237 and an empty storage compartment 17 for conjugate containers
  • the automated device 1 checks everything relating hereto in that the manipulator 8 scans all positions. Thereafter the substrate containers, conjugate contain- ers, primary tubes 5 and cups 4 can be introduced, which can take place throughout the day in random sequence as test assignments arrive, wherein the automated device 1 itself collects together the test assignments according to types and, in an efficient manner, performs the same tests simultaneously as far as possible, wherein even tests requiring the same washing agent and/or the same diluent, the same conjugate and/or substrate are prefera ⁇ bly performed successively.
  • the test results are linked by the computer 6 to the relevant assignments and thereby to the correct patient due to the coupling of the tests and test results to the assignment number read from the primary tube 5.
  • the automated device 1 not only operates efficiently because similar tests are collected and performed simul- taneously and/or immediately after one another and be- cause operations for tests with use of the same washing agents and/or diluents are performed immediately one after another, but also operates reliably in the sense that directions for incubation times and any required short intervals between successive operations are re ⁇ spected, in any case within the tolerance time limits.
  • the automated device 1 operates according to a manipulator agenda in which the utilization periods of the manipulator 8 for all operations of initiated test assignments are reserved. An incubation will for instance never be initiated if the manipulator 8 would not be available to perform the operations required at the end of the incubation.
  • the computer 6 is preferably adapted to search for free periods in the manipulator agenda and preferably even such that periods already reserved for other non ⁇ urgent tests are deferred, while respecting the required directions relating to already initiated tests.
  • the cabinet doors 29 are opened the storage compartments are removable and thus easy to clean thor ⁇ oughly and to autoclave.
  • the computer 6 detects any disturbance and any obstacle which prevents performing of the test in accor- dance with the assignment, for instance the absence of a required cup 4 and other ingredients. It is conceivable that instead of only one manipulator 8 the automated device 1 has a number of mutually adjacent manipulators 8, in which case the computer 6 controls the operations for performing and these manipulators 8 such that they do not conflict with each other.
  • the gripper 9, the washing device 12 and the pipette carrier 10 could be carried by different manipulators.
  • the carriers 111-114 may as alternative carry an identification code which is read by the code detector 140.

Abstract

The invention relates to microtitre cups for performing immunological tests of the ELISA test type. These microtitre cups available commercially in large numbers are manufactured in strips of 12 or 8 cups attached to each other, for instance according to an injection moulding process. It is known to injection mould a protrusion fixedly to each strip of cups and to provide this protrusion with a label or identifying mark with a code to identify this row of microtitre cups. The invention provides enhanced microtitre cups in that the microtitre cups open at the top individually carry an automatically readable code, for example a bar code. These microtitre cups can also be used individually. Known microtitre cups broken off the strips would no longer be identifiable, but the microtitre cups according to the invention would be.

Description

MICROTITRE CUPS FOR PERFORMING IMMUNOLOGICAL TESTS AND AUTOMATED DEVICE THEREFOR
The invention relates to microtitre cups for per¬ forming immunological tests of the ELISA test type. Such cups consist of transparent plastic material and have small dimensions, that is, a height of about 13 mm and a diameter of about 8 mm.
These microtitre cups available commercially in large numbers are manufactured in strips of 12 or 8 cups attached to each other, for instance according to an injection moulding process, and 8 or 12 of these strips are arranged removably in a carrier grid. The cups are easy to separate from each other and are open at the top.
It is known to injection mould a protrusion fixedly to each strip of cups and to provide this protrusion with a label or identifying mark with a code to identify this row of microtitre cups.
The protrusion lies horizontally on the top of an edge of the carrier grid such that the label with code carried by this protrusion is easily visible.
The invention provides improved microtitre cups in that the microtitre cups open at the top individually carry an automatically readable code, for example a bar code. Although the codes arranged on these cups are now not readable when they are situated in a carrier grid, arranging of the codes on the side or on the underside implies a significant enhancement relative to the known microtitre cups with codes which are readable in the carrier grid. The microtitre cups can in any case be used individually. Known microtitre cups broken off the strips would no longer be identifiable, while the microtitre cups according to the invention would be.
In the case of non-transparent microtitre cups on which measurements take place with a fluorescence measur¬ ing method, the code can be arranged on the side and/or bottom of the cup. The labels arranged on the sides do not impede the light shining vertically through a trans- parent microtitre cup when determining an optical densi¬ ty. Although the label and the code of the cups according to the invention have a miniature format due to the small dimensions of the cups, it has still been found possible to arrange a reliable, well readable code on the cups. It should be noted that coated cups are known for performing analog ELISA tests which are manufactured from plastic which may or may not be transparent and which have a larger format, for instance 2 cm high and 1 cm wide. These cups are closed on their top with a destruc¬ tible foil cover on which is printed a code which is readable from above when a plurality of these cups is situated mutually adjacent in a carrier grid. A destruc¬ tible foil is not however practically applicable in carrying out ELISA tests on microtitre cups because of the small size thereof.
Mentioned and other features of the invention will be elucidated in the description following hereinbelow and given by way of example. In the drawings in schematic form:
Fig. 1 and 2 show a perspective view of an automated device according to the invention respectively in closed and opened situation,
Fig. 3 shows on larger scale a section along the line III-III in fig. 1,
Fig. 4 shows on larger scale a perspective view of detail IV in fig. 2,
Fig. 5A, 5B and 5C each show on a larger scale a perspective view of detail V in fig. 2 in different positions,
Fig. 6, 8 and 9 show on a larger scale a perspective view respectively of details VI, VIII and IX in fig. 3, Fig. 7 shows on larger scale a perspective view of detail VII of fig. 3 in another formation, Fig. 10 shows a fluid circuit diagram for the auto¬ mated device of fig. 1, and
Fig. 11 is a broken away perspective view of detail XI in fig. 5B.
The automated device 1 according to the drawing comprises a manipulation cabinet 2, a storage compartment 23 for containers 202, 205 and 206 of diverse liquids required in ELISA tests and a vacuum vessel 209, a feed platform 24, platforms 25 for carrying a computer 6 with monitor controlling the automated device, keyboard 26 and recorder 27. The cabinet doors 29 can only be opened by operating an electric switch 30 after a relevant key has been entered as password in computer 6 by an authorized person. Errors due to interference in the inside of the automated device 1 by unauthorized persons is hereby avoided.
The manipulation cabinet 2 contains inter alia (see fig. 3) : a storage compartment 13 for holders 3 which are each adapted for receiving, in this embodiment, four microtitre cups 4; a storage compartment 15 for receiving primary tubes 5 which contain serums for testing, for instance blood serums of patients, respectively standard samples; storage compartments 16 for receiving diluent tubes 36; storage compartments 17 with locations 237 for receiving containers 37 for different conjugates, sub¬ strates and stop liquids; incubation areas 18 and 19 which are held at a temperature of 22°C respectively 37°C with a variation of at most 2°C in which holders 3 with cups 4 are kept for a prescribed time in accordance with the type of test; a pipette storage compartment 20 in which are accom¬ modated three grids filled with unused pipettes 7; a pipette storage compartment 21 for storing used, still usable pipettes 7; a checking device 118 for checking whether a pipette is hanging on the pipette arm 10; a cooling space 22 with locations 232 for receiving conjugate containers 32 which are each intended for a conjugate or other additive (The containers 32 are re¬ moved from this cooling space when a test must be taken therewith. For this purpose these containers 32 are then transferred to a storage compartment 17 to be brought to room temperature prior to being used) ; a device 33 for feeding and discharging test ingre¬ dients and primary tubes 5; an optical density measuring device 34; a washing device 35; a switching device 28; and a waste disposal device 31.
When a doctor prescribes tests for a patient, an extracted serum is sent in a primary tube 5 together with a form indicating the desired Elisa test or tests to a laboratory which performs such tests by means of the automated device 1. In this laboratory the test assign¬ ment is numbered and entered in computer 6 matched with antecedents of the patient with mention of all required Elisa tests. It is conceivable that in a hospital or in a laboratory the test authorization is entered into a central computer coupled to computer 6. At the time of entry into the computer 6 a label 42 with bar code 43 containing the assignment number is printed and adhered to the primary tube 5. It is noted that throughout this text an automatically readable code, for instance bar code or dot code, can be understood instead of bar code.
The computer 6 contains the necessary instruction for all types of Elisa tests with respect to the manner of performing thereof, including the designation of the ingredients to be used. Among these ingredients can be included microtitre cups which are coated inside with antibodies and/or antigens, hereinafter designated as cups 4, and conjugates which are held in conjugate con¬ tainers 32 which are each provided with a label 40 with bar code 41 which designates the relevant conjugate associated with a lot of testing ingredients of a partic¬ ular Elisa test.
The cups 4 which together with a determined conju¬ gate or number of conjugates form part of a particular lot also carry this information in their bar code togeth¬ er with the identification of these cups 4.
The code 39 on cups 4 contains for instance six letters X X P W W Y. Herein are intended: X X for code of test type P for production serial number W W for production week
Y for production year
The code 41 on containers 32 and 37 contains for instance ten letters C C X X P W W Y E E. Herein are intended: C C for code of the type of additive X X for code of test type P for production serial number W W for production week
Y for production year E E for designating the number of weeks of the time limit on use. The primary tubes 5 which contain standard samples have for instance a fifteen-letter code
S D X X N N V V V V V V F F F. Herein are intended: S D for distinguishing these standard tubes 5 relative to primary tubes of patient samples X X for test type
N N the method of standard test, namely: concentration calibration; negative check; positive check; or reference check.
Y V V V V V designations relating to use in respect of concentration,- F F F for designating use time limits in months and year. For each lot a testing instruction is entered into the computer 6 in the form of a diskette, which instruc¬ tion also contains directions for realizing calibration values with limited time periods for the use of these calibration values and therefore directions for recali- bration, in addition to directions for refusing the input of ingredients of a determined lot when the reliable lifespan thereof has been exceeded.
The code is arranged on each cup 4 as bar code with a width of 6 mm which is printed with a fine-print print¬ er, for instance a 12-dot printer, on a label of wood- free paper adhered to one side of cup 4. Eight or twelve such thus coded cups 4 open at the top are mutually joined on their upper edge by injection moulding to form a strip. Twelve or eight strips are received into a packing grid. During use these cups 4 are broken loose of each other.
In the manipulation cabinet 2 the frame 44 of a collective manipulator 8 is driven and guided three- dimensionally as according to fig. 4. Horizontal rails 45, 46 guide a horizontal traverse 47 which is driven by a motor 48, a toothed belt 49, a shaft 50 and two toothed belts 51. A frame 52 is guided relative to traverse 47 in horizontal direction along rails 53 and is driven in horizontal direction by means of a motor 54, toothed belt 55, spline shaft 56 and toothed belt 57. A frame 58 is guided in vertical direction relative to frame 52 by means of its rail 59, wherein the relevant guide rollers 60 are mounted on the same shafts 61 as the guide rollers 62 of the horizontal guiding. Frame 58 is driven in vertical direction by means of a motor 63 via a toothed belt 64, spline shaft 65 and toothed belt 66, which in addition to horizontal parts on the traverse 47 has also guided vertical parts on the frame 58, wherein transition guide rollers 67 are mounted on the frame 52.
All positions in the diverse storage compartments for containers 32, 37, holders 3, cups 4 in holders 3, pipettes 7 as well as all other operational positions of manipulator 8, such as stampers 88, pick-up position 115, fountain 35, optical densimeter 34 and waste disposal device 31 are stored in the computer memory in accordance with a co-ordinate system and the stepping motors 48, 54 and 63 steer the manipulator 8 exactly to the required positions using as starting point some reference reflec- tion means 79 with which a sensor 78 to be described later co-acts in order to correct any eventual small deviation in its position.
The frame 58 bears a gripper 9, a pipette carrier 10 and a washer 12 (fig. 5A) . Gripper 9 consists of Neuren- berger scissors 14, the gripper arms 68 of which are rotatably mounted on a pivot shaft 69 fixedly attached to frame 58, while the other pivot shaft 70 is moved in vertical direction by means of a stepping motor 71 via a threaded rod 72 with a nut 73 which is displaceable in vertical direction in a bearing block 74 but which is pulled into the lowest position against a stop 77 by means of pins 75 and draw springs 76 so that, when grip¬ per 9 clamps shut when taking hold of an object, the upper pivot shaft 70 is pulled downward as long as the nut 73 is held in engaged position with the stop 77 of bearing block 74. When an object is clamped sufficiently fixedly in gripper 9 the spring tension of draw springs 76 is overcome and the nut 73 can displace somewhat further. Built into the gripper 9 is a sensor 78 which pro¬ trudes downward when gripper 9 is opened but which is carried upward during closing of the gripper 9 by a pressure spring 80 which pushes against a support 81 which is fixed to the lower pivot shaft 69 and in which the sensor is vertically guided for sliding, while the pressure spring 80 presses against a transverse pin 82 of sensor 78 which is guided in vertical slots 83 of the frame 58. The opened gripper position is detected by a switch 84, whereafter the motor 71 is stopped and comput- er 6 has the information that sensor 78 is exposed.
The pipette carrier 10 is displaceable between its rest position of fig. 5A and its operative position of fig. 5B in that it is adapted on its top end 85 for snap engagement into a per se known coupling 86, as shown for instance in fig. 11, which is released when the bottom end 87 of the pipette carrier 10 receives an upward impact which is brought about by stamping this bottom end 87 onto a fixed upright stamper 88. When coupling 86 is released the draw springs 89 pull the pipette carrier 10 downward until a support 90 thereof strikes on a guide bearing 91. A switch 191 signals the pulled-up position of pipette carrier 10 to the computer 6. When pipette carrier 10 lifts up a pipette 7 the manipulator 8 shows the picked up pipette 7 to the checking device 118 prior to pipetting. Should the checking device 118 signal the absence of a pipette 7, the computer 6 then gives the alarm and stops the pipetting operations until the error is corrected.
The washer 12 is displaceable between its rest position of fig. 5A and its operational position of fig. 5C in that it is adapted on its top end with a coupling 86 which is released when the washer 12 receives an upward impact by stamping it onto a stamper 88. When this coupling 86 is released a pressure spring 92 presses the washer downward until a stop head 93 of a stop rod 94 strikes against a guide bearing 95. A switch 96 actuated by the stop head 93 signals the rest position of the washer 12 to computer 6.
According to fig. 6 a toothed belt 98 with external toothing is guided along the inside of a curved guide rail 97 by means of guide rollers 99 and guide discs 100 while this toothed belt is driven by means of a stepping motor 101 and tooth wheel 102. Guide rail 97 extends from an inlet 103 to an outlet 104. Fig. 7 shows four different carriers 111, 112, 113 and 114 which can be mutually coupled by means of a vertical pin 105 and a clamp 106 engaging elastically thereon. A plurality of each type of carrier 111-114 is present. Each carrier 111-114 has a curved foot 110 which during transport in manipulation cabinet 2 is displaced between the rail 97 and the toothed belt 98 which then engages in external teeth 109 of these carriers. Carriers 111-114 have on their underside a characteristic differ¬ ence, which can be detected by means of two switches 108 and 107; carriers 111 and 113 have a rear switch member 121 which co-acts with switch 107; carriers 113 and 114 have a front switch member 122 which co-acts with switch 108 and carrier 112 has no switch member 121, 122. The carriers 111-114 are recognized by the combination of signals from switches 107, 108. Carrier 111 is adapted for a substrate container 237 or a large conjugate con¬ tainer 37; carrier 112 for four cups 4; carrier 113 for two cups 4 and a primary tube 5 which is held in a sleeve 124 provided with a slot 123; and carrier 114 for a small conjugate container 32. When a train of carriers 111-114 is fed manually according to arrow 125, a switch 126 switching on motor 101 is actuated by incoming carriers. The frame 127 of a level scanner 128 can swivel on a vertical shaft 129 and is pressed by a torsion spring 130 as according to arrow 131 with a stop nose 132 against a conjugate container 37 of carrier 111 or against a shoul¬ der 133 of carrier 114. In the case carriers 112 and 113 pass through, the frame 127 strikes against a vertical rod 134. These parts are herein dimensioned such that a sensor 135 carried by the frame 127 is situated in each case at distance q from the nose 132 above the centre line of the containers 32, 37 or primary tube 5, so that sensor 135 can scan the liquid level therein. Sensor 135 operates as a per se known light reflector and is carried by a rod 136 which is guided vertically in frame 127 and which is pulled downward through a determined stroke by a magnet 137 and pressed upward by a pressure spring 138. When the liquid level in a container is known and the container with its particular inner diameter is identi- fied, the volume of the container is known.
Each carrier 111-114 subsequently passes a light sensor 139 which responds to the leading edges of the carriers so that the motor 101 moves the relevant carrier further until a code detector 140 has read the bar codes 41, 39, 43. If necessary the motor 101 moves the carriers 111-114 reciprocally. Should for any reason a code not be readable, the computer 6 then controls the automated device 1 such that the relevant containers or cups are not picked up by the gripper 9 but leave the manipulator cabinet 2 by the outlet 104. If the codes have been read and the carriers 111-114 or cups 4 identified, they are then picked up one by one by the gripper 9 from the carriers 111-114 at a determined pick-up location 115 of the conveyor belt and set down in a free place in cabinet 2 adapted for this purpose. Conjugate for a determined type of Elisa test not belonging to the same lot of already introduced cups 4 is refused. Conversely, cups not belonging to the same lot of already introduced conjugate are refused. Likewise refused are ingredients which exceed the 'use by' date. When the duration limit of the calibration values of a lot has been exceeded or a new lot is introduced, the computer requests feed of standard samples, which are then introduced in primary tubes. Situated in the storage compartment 13 (fig. 3) are holders 3 which are each adapted to receive four cups 4. Fig. 8 shows such a holder 3 gripped by the gripper 9. Holders 3 with another multiple of four receiving spaces for cups 4 are conceivable. The capacity of the automated device 1 is enlarged in that cups are collected in each case in a holder 3 on which the same type of Elisa test must be performed. The collective manipulator (gripper 9), which must perform many movements, and also other members of automated device 1 are thereby used more effectively. At the beginning of a working day the auto¬ mated device 1 starts from a starting position in which storage compartment 13 is entirely filled with empty holders 3. Incoming cups 4 which are identified by their bar codes 39 are placed sorted into holders 3 such that only cups 4 are found in the same holder 3 which are identical in respect of the tests to be performed there¬ with and which are thus only suitable for the same type of Elisa test. The test is only started when a holder 3 is full. In the case of rarely occurring tests the test¬ ing with cups 4 is nevertheless still started after a predetermined period, for instance six hours, or still in due time before the end of a working day, also in the case the holder 3 is not full. A test with cups from an incompletely filled holder 3 are moreover started when the ingredients and serum for an urgent assignment which has been entered into the computer 6 are present in cabinet 2.
According to fig. 8 the automated device 1 comprises a waste disposal device 31. By means of the gripper 9 the finished cups 4 are placed with an edge 145 of their holder 3 on a swivel plate 143, and into a recess 144. After removal of gripper 9 the swivel plate 143 is turned over as according to arrow 146 by means of a stepping motor 147, while a fork-like detainer 150 mounted on the swivel shaft 148 and coupled to this swivel shaft via a torsion spring 149 is carried along from a raised rest position to a position above the inlet 152 of a waste container 151. The holder 3 is herein held in place by the detainer 150. In the return stroke of motor 147 the empty holder 3 is set down again and is then picked up by gripper 9 and placed in storage compartment 13.
Used and no longer usable pipettes 7 are placed by pipette carrier 10 as according to arrows 154 through a large hole 155 in device 31 and stripped off in the slot 156. All the waste falls into a plastic bag 157.
According to fig. 9 the optical densimeter 34 com¬ prises the usual light source 158, light filters 159 and glass fibre cables 160 which cast the light rays 161 through cups 4 and their content onto the light sensors 162. Four sensors 162 herein receive light for measuring of cups 4 while one sensor 163 is intended for a compara¬ tive zero object 164. The densimeter 34 comprises a closed box 165 into which a holder 3 with cups 4 is introduced by being placed in a slide 166 by the gripper 9 and the slide 166 then being pushed inside using the pipette carrier 10 which for this purpose performs to¬ gether with gripper 9 the movement as according to arrows 167, while the pipette carrier 10 engages in a hole 168 of the handle 169.
According to fig. 9 four washing tubes 170 of the washer 12 are washed in a fountain 171, wherein washing liquid is supplied by feed tubes 172 and sprayed on the outside of the washing tubes 170. This washing water is then drained via a drain tube 173 to waste washing liquid containers 205. The washing treatment with the fountain 171 is started by computer 6 only when the washing tubes 170 are situated in fountain 171.
The switching device 28 of fig. 10 comprises a vacuum pump 211 of 0.7 bar which is driven by a motor 210 and which creates a vacuum in a vacuum vessel 209 which is connected to two mutually communicating containers 205 for used liquid which are connected via valves 215 and 216 to the washing tubes 170 of the washer 12 respective- ly the drain tube 173 of fountain 171. An air pressure pump 219 driven by a motor 218 is connected to a buffer vessel 220, to containers 206 with different diluents and to containers 202 with different washing liquids. These containers 202 are selected by means of valves 21 in the case of a determined washing treatment and then connected via valves 213 onto washing tubes 170. They are herein all opened simultaneously when four cups 4 are situated in a holder 3 or a relevant smaller number when holders 3 are not completely filled. During washing of the inside of washing tubes 170 in the washing fountain 171 selected washing liquid is supplied via an opened valve 212 and an opened valve 215.
The device 186 for filling diluent tubes 36 with diluent from one of the containers 206 comprises a large cylinder 182 of 500 μl and a small cylinder 183 of 250 μl which are connected according to the diagram of fig. 10 to the containers 206 via rotating valves 181, 188 driven by motors 180, 187 and to the tubular pipette carrier 10. Prior to filling of the diluent tubes the conduit system is flushed with the diluent for use, wherein the pipette carrier 10 is held in the fountain 171 and this flushed diluent passes into the containers 25. A plurality of diluent tubes 36 is now preferably filled one after another with this same diluent using the filled conduit system, this as required by means of one or more complete or partial fillings of cylinders 182 and/or 183 which are driven reciprocally for this purpose by motors 189, 190. The storage compartments 16 are continually shaken by means of a shaker 230 except during filling with diluent and during pipetting. During pipetting the rotat¬ ing valve 188 is closed and the cylinder 183 then first presses diluent out of the pipette carrier 10 into the fountain 171 so that an air buffer is situated therein, while the bottom end is washed with water. A pipette 7 is then lifted out of the storage compartment 20 or 21 and a measured quantity of serum is drawn up out of a primary tube 5, wherein the small cylinder 183 makes a measured stroke and this serum is transferred into a cup 4 or a diluent tube 36. These operations can be repeated quickly with the same pipette 7 in the case of one or more filled holders 3 with cups 4 for identical tests. After ending of the filling process of one or more diluent tubes 36 this still usable pipette 7 is stored in the storage compartment 21. The computer 6 records the amounts of used washing agents, diluents, conjugates and serums so that the pipette 7 is immersed each time to the correct level into the liquid to be drawn up and computer 6 detects, if necessary, a practically empty container 32, 36, 5, 202, 206. The pipettes 7 employed for instance for serum which can no longer be used are removed immediately through the slot 156. Serums are either carried directly from primary tubes 5 into cups 4 and/or carried into the diluent tubes 36, from which they are transferred in diluted state into cups 4 after some shaking of the mixtures using a shaker 230.
At the beginning of a working day a start is made with filled containers 202 and 206, empty containers 205, cleaned conduits, filled pipette storage compartment 20, storage compartments 16 filled with empty diluent tubes 36, holder storage compartment 13 filled with empty holders 3, empty incubation spaces 18, empty pipette storage compartment 21, empty cooling space 22, an empty storage compartment 15 for primary tubes 5, an empty storage compartment 217 for substrate containers 237 and an empty storage compartment 17 for conjugate containers
37.
The automated device 1 checks everything relating hereto in that the manipulator 8 scans all positions. Thereafter the substrate containers, conjugate contain- ers, primary tubes 5 and cups 4 can be introduced, which can take place throughout the day in random sequence as test assignments arrive, wherein the automated device 1 itself collects together the test assignments according to types and, in an efficient manner, performs the same tests simultaneously as far as possible, wherein even tests requiring the same washing agent and/or the same diluent, the same conjugate and/or substrate are prefera¬ bly performed successively. The test results are linked by the computer 6 to the relevant assignments and thereby to the correct patient due to the coupling of the tests and test results to the assignment number read from the primary tube 5.
The automated device 1 not only operates efficiently because similar tests are collected and performed simul- taneously and/or immediately after one another and be- cause operations for tests with use of the same washing agents and/or diluents are performed immediately one after another, but also operates reliably in the sense that directions for incubation times and any required short intervals between successive operations are re¬ spected, in any case within the tolerance time limits. To this end the automated device 1 operates according to a manipulator agenda in which the utilization periods of the manipulator 8 for all operations of initiated test assignments are reserved. An incubation will for instance never be initiated if the manipulator 8 would not be available to perform the operations required at the end of the incubation.
When an urgent assignment arrives it is treated with priority. The computer 6 is preferably adapted to search for free periods in the manipulator agenda and preferably even such that periods already reserved for other non¬ urgent tests are deferred, while respecting the required directions relating to already initiated tests. When the cabinet doors 29 are opened the storage compartments are removable and thus easy to clean thor¬ oughly and to autoclave.
The computer 6 detects any disturbance and any obstacle which prevents performing of the test in accor- dance with the assignment, for instance the absence of a required cup 4 and other ingredients. It is conceivable that instead of only one manipulator 8 the automated device 1 has a number of mutually adjacent manipulators 8, in which case the computer 6 controls the operations for performing and these manipulators 8 such that they do not conflict with each other. The gripper 9, the washing device 12 and the pipette carrier 10 could be carried by different manipulators.
The carriers 111-114 may as alternative carry an identification code which is read by the code detector 140.
*****

Claims

1. Microtitre cups (4) for performing immunological tests of the ELISA test type, which cups are provided with an identification code (39) and are open at the top, characterized in that the cups (4) open at the top indi- vidually carry an automatically readable code (39) , for example a bar code.
2. Microtitre cups (4) as claimed in claim 1, char¬ acterized in that the cups individually carry an adhered label (38) with an automatically readable code (39) on their sides.
3. Microtitre cups (4) as claimed in claim 2, char¬ acterized in that the code (39) is printed on the label (38) with a fine-print printer, for instance a 12-dot printer.
4. Microtitre cups (4) as claimed in claim 2 or 3 , characterized in that the label (38) is manufactured from wood-free paper.
5. Microtitre cups (4) as claimed in any of the foregoing claims, characterized in that the code (39) is a bar code or dot code, the width of which amounts to about 6 mm.
6. Automated device for performing immunological tests with the use of microtitre cups (4) as claimed in any of the foregoing claims.
*****
PCT/BE1993/000068 1992-12-04 1993-11-16 Microtitre cups for performing immunological tests and automated device therefor WO1994013402A1 (en)

Priority Applications (2)

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EP93923986A EP0671979A1 (en) 1992-12-04 1993-11-16 Automated device for performing immunological tests
AU53669/94A AU5366994A (en) 1992-12-04 1993-11-16 Microtitre cups for performing immunological tests and automated device therefor

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP92870194 1992-12-04
EP92870194.5 1992-12-04

Publications (1)

Publication Number Publication Date
WO1994013402A1 true WO1994013402A1 (en) 1994-06-23

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PCT/BE1993/000069 WO1994014074A1 (en) 1992-12-04 1993-11-16 Method and automated device for performing immunological tests
PCT/BE1993/000070 WO1994014073A1 (en) 1992-12-04 1993-11-16 Method and automated device for performing immunological tests and a lot of ingredients therefor

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PCT/BE1993/000070 WO1994014073A1 (en) 1992-12-04 1993-11-16 Method and automated device for performing immunological tests and a lot of ingredients therefor

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EP0672255A1 (en) 1995-09-20
EP0672254A1 (en) 1995-09-20
EP0671979A1 (en) 1995-09-20
AU5366994A (en) 1994-07-04
WO1994014073A1 (en) 1994-06-23

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