EP1060396A1 - Procede et dispositif pour realiser un grand nombre d'essais biologiques/chimiques identiques a une petite echelle - Google Patents

Procede et dispositif pour realiser un grand nombre d'essais biologiques/chimiques identiques a une petite echelle

Info

Publication number
EP1060396A1
EP1060396A1 EP99900048A EP99900048A EP1060396A1 EP 1060396 A1 EP1060396 A1 EP 1060396A1 EP 99900048 A EP99900048 A EP 99900048A EP 99900048 A EP99900048 A EP 99900048A EP 1060396 A1 EP1060396 A1 EP 1060396A1
Authority
EP
European Patent Office
Prior art keywords
plates
plate
stack
treatment
stacks
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP99900048A
Other languages
German (de)
English (en)
Inventor
Ernst BÜRGISSER
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
EPR Labautomation AG
Original Assignee
Discovery Technologies AG
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 Discovery Technologies AG filed Critical Discovery Technologies AG
Publication of EP1060396A1 publication Critical patent/EP1060396A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02—Automatic 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
    • G01N35/04—Details of the conveyor system
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00279—Features relating to reactor vessels
    • B01J2219/00306—Reactor vessels in a multiple arrangement
    • B01J2219/00313—Reactor vessels in a multiple arrangement the reactor vessels being formed by arrays of wells in blocks
    • B01J2219/00315—Microtiter plates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0893—Geometry, shape and general structure having a very large number of wells, microfabricated wells
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B60/00—Apparatus specially adapted for use in combinatorial chemistry or with libraries
    • C40B60/14—Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02—Automatic 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
    • G01N35/04—Details of the conveyor system
    • G01N2035/0401—Sample carriers, cuvettes or reaction vessels
    • G01N2035/0418—Plate elements with several rows of samples
    • G01N2035/0422—Plate elements with several rows of samples carried on a linear conveyor
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02—Automatic 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
    • G01N35/04—Details of the conveyor system
    • G01N2035/0401—Sample carriers, cuvettes or reaction vessels
    • G01N2035/0418—Plate elements with several rows of samples
    • G01N2035/0425—Stacks, magazines or elevators for plates
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02—Automatic 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
    • G01N35/04—Details of the conveyor system
    • G01N2035/0496—Other details
    • G01N2035/0498—Drawers used as storage or dispensing means for vessels or cuvettes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/0099—Automatic 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

Definitions

  • the invention is in the field of automated microanalysis and relates to a method according to the preamble of the first independent claim.
  • the method is used to carry out large numbers of identical biological / chemical tests (test series) on a micro scale.
  • Substance libraries are used to carry out such test series and all or selected substances present in the substance library are subjected to the same test.
  • the method can also be used to select substances from a substance library.
  • the invention also relates to a device according to the preamble of the corresponding independent patent claim, which device serves to carry out the method.
  • Substance libraries for example libraries of synthetic, organic molecules, are known in the form of large numbers of plates, each with a plurality of cavities, with one of the substances being introduced into each cavity in solution in a standard solvent, in an amount suitable for one large number of micro tests is sufficient.
  • plates with such large amounts of substance are called "library plates”.
  • to Carrying out a test series is based on library plates 'test plates' by taking test quantities of the substances from cavities of the library plates and inserting them into empty cavities of other plates. Test plates with only one substance per cavity and also test plates with substance mixtures in the Both library plates and test plates can be stored for longer periods if the appropriate means are used to ensure that contact with atmospheric oxygen is prevented or at least severely restricted.
  • each test plate is usually treated for a plurality of successive treatment steps at a plurality of treatment stations.
  • Such a treatment consists, for example, of the following steps: adding one or more liquid reagents to trigger a reaction with the substance to be tested; Incubation in a given atmosphere at a given temperature for a given time; Addition of further liquid reagents to stop the reaction and / or for a color reaction; Measurement of a specific property of the reaction mixture (color, fluorescence, radioactive radiation etc.).
  • a step of separating the reaction mixture e.g., filtration or centrifugation
  • removing a portion of the reaction mixture may also be provided.
  • standardized plates with, for example, 96 (8 ⁇ 12) cavities are usually used, which plates normally have means which stabilize stacks of such plates (for example a beaded edge on the top of the plate and a corresponding groove the underside of the plate).
  • the treatment stations necessary for loading the plates with the substances to be tested and for carrying out the test series as well as the means for transporting the plates from one treatment station to the next are controlled by a central control.
  • the treatment route from a first treatment station to a last treatment station, which each plate has to cover for a test can be different for different tests.
  • the plates usually follow one another on the treatment route in such a way that a plurality of plates are always on the way on the treatment route.
  • the transport of the individual plates from a warehouse to a first and subsequent treatment stations and possibly back to a warehouse is usually carried out with a controllable robot arm, within the reach of which all treatment stations and storage containers are arranged.
  • This robot arm through which all the plates on the treatment path are to be transported, carries out a very high number of different transport steps per unit of time, and with each such transport step it moves a plate over a section of the treatment path, for example from one treatment station to the next transported. It is obvious that the robot arm has to go through very complicated sequences of movements and that between the actual transport steps it also has to perform a large number of empty movements (without a plate). It also shows that the robot arm is the link in a test system that imposes an upper limit on the plate throughput per unit of time.
  • the object of the invention is to provide a method and a device with which significantly more tests can be carried out in the same time periods than is possible with the conventional methods and devices, and without a substantial increase in the number of apparatuses (treatment stations).
  • the method and the device according to the invention it should be possible to carry out services in the order of magnitude of 100,000 tests per day using known microtest plates with 96 cavities without parallel connections.
  • the method and the device should not be bound to these specific plates, so that further increases in performance can be achieved by using plates with more cavities.
  • the method should be able to be carried out with known treatment stations.
  • the basic idea of the method according to the invention consists essentially in handling stacked plates rather than individual plates as before, all plate stacks advantageously having the same size, that is to say always having the same number of plates.
  • all plates test plates, empty plates and library plates
  • plates are stored in such stacks
  • plates are manipulated in plate stacks
  • plates are transported in plate stacks. Plates from stacks are only combined for treatment in the treatment stations. time, treated as single plates and put back in stacks after the treatment. With such a stack management, the movement of the plates on the treatment path can be simplified and accelerated compared to the known single plate management, and the plate throughput can thereby be increased significantly.
  • a plate stack u holds, for example, ten plates, each plate covering the lower one and a cover plate without any other function being arranged on top of the stack to cover the top plate. Because the plates are arranged in a stack of plates for most of the time that they are underway for a test, in which they are covered by an upper plate, there is no need to cover the individual plates, which is a further advantage of the method according to the invention
  • a plurality of treatment stations are provided, each of which is equipped with at least one plate separating means, that is to say with a means by which a plate is removed from a stack of plates, positioned in a treatment position and after the treatment again in a stack can be classified.
  • a plurality of transport means are provided with which at least one stack of plates can be transported individually on a treatment path, and stack manipulation means with which stack of plates can be removed from storage containers and loaded onto transport means and removed from transport means and put back into storage.
  • the device according to the invention which essentially consists of treatment stations with plate separating means, stack transport means, storage containers and stack manipulation means, is controlled in the same way as is usual for devices with plate management, so that test series can be carried out runs fully automated. It turns out that it is advantageous if each specific plate has a constant place in a specific stack, to which it is returned after each separation. It also shows that it is advantageous in the same way if each specific stack of multiple-use plates (library plates) has a constant storage location for storage in a storage container, to which the stack is always returned.
  • the plate separating means must be designed in such a way that they can remove any plate from a stack and position it again in its place.
  • storage containers and stacking tanipu means are to be designed in such a way that each stored stack can be removed from or put into storage, regardless of which other stacks are stored.
  • the condition of the essentially unchangeable disk space in the stack and the unchangeable stack storage space is not essential for the method according to the invention.
  • the storage containers must be designed in such a way that arbitrary access to stacks is possible, such that the selection of plate stacks from a storage container is completely free for loading plates with substances and for carrying out tests and is completely independent of the storage regulations This does not apply to individual panels in the area of storage. If, for example, only one plate from a stack is to be treated, the entire stack is removed and transported and is sent to the only the individual plate to be treated. In other words, this means that arbitrary access to individual stacks must be guaranteed for storage and retrieval, and arbitrary access to individual disks for plate separation.
  • storage containers are used with pull-out trays on which the plate stacks are positioned at a distance from one another, such that each stack can be removed from a pulled-out tray and / or with the aid of a stack manipulating means which has a corresponding gripper can be positioned on such in a free place on the tray.
  • movable, individual stack transport means are provided on a rail system with controllable switches, which are loaded with at least one stack each by the stack manipulation means and travel to a predetermined sequence of treatment stations on a path predetermined for a specific test series.
  • FIG. 1 shows an exemplary plate stack as used in the method according to the invention
  • FIG. 2 shows a schematic illustration of a test implementation using the method according to the invention
  • FIG. 3 shows a schematic representation of the production of test plates from library plates or from a further generation of library counter tops from an existing generation of library tops according to the inventive method
  • FIG. 4 shows a schematic illustration of an exemplary embodiment of the device according to the invention for carrying out the method according to the invention.
  • FIG. 5 shows a diagram of an exemplary embodiment of a plate separating agent
  • Figure 6 shows a detail of the plate separating means.
  • FIG. 1 shows a stack 1 of plates 2 with cavities 3, as is used in the method according to the invention.
  • the stack 1 carries a cover plate 4 which, as shown, has no cavities or empty cavities and their only function is that Cover cavities of the second top plate. The covering function for all other plates in the stack is taken over by the plate above in the stack.
  • the plates 2 have stacking means matched to one another on their upper sides and on their undersides, for example bead-like edges 5 on the upper side and corresponding grooves (not shown) on the underside, so that the stack is relatively stable.
  • surfaces 6 on which stacks are positioned are also equipped with the same stacking means, for example trays of storage containers, support surfaces of transport means and treatment positions of treatment stations, so that the stacks can be easily and precisely positioned in definite positions.
  • the bottom plate of each stack for the position- tion has other positioning means cooperating with corresponding means of a support surface, or that each stack has a specific lowermost positioning plate for this function, as the cover plate serves no other function
  • FIG. 2 shows a very schematic illustration of an exemplary test implementation using the method according to the invention.
  • the stack or plate movements to be carried out are shown by arrows, groups of phases being repeated if necessary.
  • the individual phases are:
  • a a stack 1 of test plates is stored with other test plate stacks in a storage container 10 with trays 11.
  • a storage container 10 with trays 11.
  • Storage container 10 opened and the tray 11 pulled out;
  • the stack 1 is gripped by a stacking mamu means (not shown) and lifted from the tray 11;
  • the stack 1 is loaded onto a transport means 12 and transported to a treatment station 12;
  • a plate of the stack 1 (for example that directly below the cover plate) is positioned in the treatment position 13 of the treatment station 12 with the aid of a plate separating means (not shown) and is treated;
  • the plate is removed from the treatment position using the plate separating means (not shown) and is positioned again in stack 1; steps d and e are optionally repeated for further plates of stack 1;
  • steps d, e and f may be repeated at a next treatment station
  • the stack is transported back to the storage container 10 and repositioned on the tray 11 by the stack manipulation means (not shown);
  • FIG. 2 illustrates the treatment path of only one stack 1.
  • FIG. 3 shows in the same schematic manner as FIG. 2 a treatment in which two plates or two plate stacks are always involved, with for example the production of library plates (further generation) on which a selection of substances from a mother library are applied or the production of test plates with the help of library plates.
  • the outsourcing and storage of the plate stack is not shown. It takes place immediately, as has already been described in connection with FIG. 2.
  • Figure 3 shows in successive phases k to p with arrows the stack and plate movements to be carried out:
  • a stack 1.1 of library plates and a stack 1.2 of empty plates are each transported on a means of transport 12 to a treatment station 20, which treatment station 20 is equipped for removing liquid from cavities and for adding liquid
  • Cavities liquid handling station and which treatment station 20 is equipped with two plate separating means (not shown);
  • a library plate is removed from the stack 1.1 and brought into the treatment position and substance is removed from at least one cavity;
  • an empty plate is removed from the stack 1.2 and brought into the treatment position and the at least one substance removed from the library plate is introduced into a cavity, so that a test plate or a further library plate is produced from the empty plate;
  • test plate is positioned again in stack 1.2; steps 1 to o are optionally repeated with further plates from stack 1.1 and / or from stack 1.2;
  • the stacks are transported away, the stack 1.1 being stored again, for example, and the stack 12 being treated directly on a treatment path or likewise being stored again.
  • FIG. 3 could give the impression that the movements of the stacks 1.1 and 1.2 are simultaneous. This is in no way a condition for the method according to the invention. If, for example, library plates of a second generation or test plates containing only a selection of substances from a mother library are created, substances from several mother library plates are applied to only one empty plate and the stacking movements to and from the treatment station are in no way simultaneous.
  • FIG. 4 again shows a very schematic representation of an exemplary device for carrying out the method according to the invention, as was described in connection with FIGS. 1 to 3.
  • the device has a storage area shown on the left and a treatment area shown on the right.
  • a plurality of storage containers 10 with pull-out trays are provided in the storage area and can optionally be moved, for example on a rail 30 (dash-dotted line) into the area of a stacking manipulator 31.
  • the stack manipulator is shown as a double arrow connecting the storage area to the treatment area.
  • more than one stack manipulator 31 (for example two) is provided. such that plates from several storage containers can be treated simultaneously without the storage containers having to be moved.
  • At the locations of the stack manipulation means 31 means for opening the storage containers 10 and for pulling out the trays 11 are also to be provided.
  • the treatment area has a plurality of treatment stations 12 with a plate separation means 32 and treatment stations 20 with two or more plate separation means 32.
  • the plate separating means are shown as double arrows which connect a stack transport system to treatment stations 12 or 20.
  • the stack transport system consists of a rail system 33 (dash-dotted lines) with branches on which controllable switches are provided.
  • the rail system is advantageously self-contained and leads into the area of the stack manipulation means 31 and the plate separation means 32, these areas all being advantageously bypassable on a bypass 34 each.
  • Stack transport means 12 can be moved individually on the rail system.
  • the rail system can only be navigable in one direction (for example clockwise), with possible treatment routes differing by bypassing treatment stations.
  • the rail system can also have cross connections 35 and have areas that can be driven in two directions, such that, for example, treatment routes with different treatment sequences or an abbreviated return of stacks (library plates) are possible.
  • a plate stack represents a relatively large mass in which different positions reach a target temperature with very different delays if the stack is brought into an environment of the target temperature. For this reason, it is proposed to preheat the incubation in the stack, to isolate the plates and to preheat them in succession, for example by briefly positioning them on a metal plate at the desired temperature. The preheated plates are put back into the stack and this is fed into the incubator.
  • the incubator is advantageously a continuous device through which at least one rail part of the transport system leads
  • one of the treatment stations is equipped as a preheating station (12.1) and it is followed by a DurcMaufincubator 36, which is passed through by a plurality of stacks on transport means at such a speed that the stacks reach the exit if they have the specified one Incubation period has expired.
  • a treatment station for preheating or incubation is also conceivable, which is assigned a separating means at each of an entry point and an exit point and which has an internal plate transport means from the entry point to the exit point. Plates are fed individually from the first separating means to the entry point, transported from the entry point to the exit point and preheated or incubated, and are then individually received by the second separating means at the exit point and stacked again in a stack.
  • FIG. 5 shows a diagram of an exemplary embodiment of the plate separating means, which is shown schematically in FIG.
  • the plate separating agent is shown in three different functional phases labeled a, b and c
  • the plate separating means has a stacking bucket 40 and a plate slide 41. These can be moved into the following positions using appropriate drive means and control devices:
  • the stacking bucket 40 passes underneath a stack 1, which is kept ready on a transport means (not shown) in a transfer position 42.
  • the stacking bucket 40 moves the stack 1 from the reloading position 42 into a working position 43 (horizontal double arrow).
  • the stacking bucket 40 is brought to a height such that the plate to be removed from the stack 1 has the same height as the plate carriage 41 (vertical double arrow).
  • the plate 2 to be removed is conveyed with the aid of the plate carriage 41 into the treatment position 13 of the treatment station (horizontal double arrow).
  • the steps outlined above are carried out in reverse order.
  • FIG. 6 shows the means by which the stack 1 is brought into a configuration on the stacking bucket 40, which is moved up and down in the working position 43, in such a way that a plate 2 'can be removed from the stack 1 and integrated into the stack again.
  • FIG. 6 is a view from the left of the working position 43 of the stacking bucket 40, as shown in FIG. 5.
  • the means which interact with the stack 1 for separating a plate 2 ' are an upper and a lower pair 50 and 51 of pivotable support parts which can be pivoted independently of one another from a holding position into a rest position. In the holding position, the underlay parts of a pair 50 and 51 engage under each of those plates 2 and 2 'from opposite sides which have the corresponding height in a stack 1 positioned on the stacking bucket 40.
  • the lower pair 51 of support parts is arranged at a height such that a plate resting thereon can be grasped by the plate slide (not shown).
  • FIG. 6 shows two functional phases, designated a and b, of the pairs 50 and 51 of supporting parts. These are:
  • the stacking bucket 40 lifts the stack 1 to a height such that the plate positioned above the plate 2 'to be removed is at the height of the upper pair 50 of pad parts is positioned.
  • the upper pair 50 of support members are pivoted from the rest position to the holding position, while the lower pair 51 of support members remain in the rest position
  • the stacking bucket 40 is lowered slightly so that there is a gap between the plate resting on the upper pair 50 and the lower part of the stack. Then the lower pair 51 of support parts is pivoted into the holding position, so that the plate 2 ′ to be removed rests on these support parts, and the stacking bucket 40 is again slightly lowered. The plate 2 'to be removed is now separated from the adjacent plates in such a way that it can be removed from the stack 1 by the plate layer (not shown) and can be integrated into the stack again after processing.
  • the stacking shovel 40, plate layers 41 and pairs 50 and 51 of support parts shown in FIGS. 5 and 6 are to be driven according to their function with suitable drive means and with suitable control means. It is easily possible for the person skilled in the art to implement the necessary drives and control means, so that it is not necessary to describe them in detail in the above description.

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  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

Dans le but de réaliser un grand nombre d'essais chimiques/biologiques identiques à une petite échelle, à l'aide d'un grand nombre de substances provenant de bibliothèques de substances, lesdites substances sont introduites dans les cavités de plaquettes d'essai et testées dans ces cavités, les plaquettes étant traitées dans différents postes de traitement (12, 12.1, 20). Les plaquettes sont stockées dans des récipients de stockage (10) sous forme de piles de plaquettes (1). Ces piles de plaquettes (1) sont chargées et déchargées à l'aide de moyens de manipulation de piles (31). Les piles de plaquettes sont ensuite chargées sur des moyens de transport (12) et transportées individuellement par ces derniers jusqu'aux postes de traitement (12, 12.1, 20) sur un système de rails (33/34/35). Les plaquettes sont séparées de la pile en vue de leur traitement une fois qu'elles ont atteint les postes de traitement (12, 12.1, 20), après quoi elles sont à nouveau placées dans une pile (1). Chaque poste de traitement (12, 12.1, 20) comprend au moins un élément de séparation de plaquette (32) destiné à réaliser cette fonction de séparation. Chaque pile de plaquettes (1) possède une pluralité de plaquettes empilées l'une sur l'autre et une plaque de recouvrement. Avantageusement, toutes les piles ont sensiblement la même taille.
EP99900048A 1998-01-16 1999-01-13 Procede et dispositif pour realiser un grand nombre d'essais biologiques/chimiques identiques a une petite echelle Withdrawn EP1060396A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CH10498 1998-01-16
CH10498 1998-01-16
PCT/CH1999/000015 WO1999036787A1 (fr) 1998-01-16 1999-01-13 Procede et dispositif pour realiser un grand nombre d'essais biologiques/chimiques identiques a une petite echelle

Publications (1)

Publication Number Publication Date
EP1060396A1 true EP1060396A1 (fr) 2000-12-20

Family

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Country Status (5)

Country Link
EP (1) EP1060396A1 (fr)
JP (1) JP2002509255A (fr)
AU (1) AU1746899A (fr)
CA (1) CA2318548A1 (fr)
WO (1) WO1999036787A1 (fr)

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See references of WO9936787A1 *

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AU1746899A (en) 1999-08-02
WO1999036787A1 (fr) 1999-07-22
JP2002509255A (ja) 2002-03-26
CA2318548A1 (fr) 1999-07-22

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