EP1216098B1 - Dispositif pour realiser des reactions chimiques ou biologiques - Google Patents

Dispositif pour realiser des reactions chimiques ou biologiques Download PDF

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Publication number
EP1216098B1
EP1216098B1 EP00966090A EP00966090A EP1216098B1 EP 1216098 B1 EP1216098 B1 EP 1216098B1 EP 00966090 A EP00966090 A EP 00966090A EP 00966090 A EP00966090 A EP 00966090A EP 1216098 B1 EP1216098 B1 EP 1216098B1
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EP
European Patent Office
Prior art keywords
segments
reaction vessel
receiving element
segment
vessel receiving
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.)
Expired - Lifetime
Application number
EP00966090A
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German (de)
English (en)
Other versions
EP1216098A1 (fr
Inventor
Wolfgang Heimberg
Markus Schürf
Thomas Herrmann
Matthias KNÜLLE
Tilmann Wagner
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MWG Biotech AG
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MWG Biotech AG
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14—Process control and prevention of errors
    • B01L2200/143—Quality control, feedback systems
    • B01L2200/147—Employing temperature sensors
    • 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
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0829—Multi-well plates; Microtitration 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
    • B01L2300/18—Means for temperature control
    • B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • B01L2300/1822—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using Peltier elements
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/54—Heating or cooling apparatus; Heat insulating devices using spatial temperature gradients

Definitions

  • the present invention relates to a device for carrying out chemical or biological reactions, with a reaction vessel receiving body for receiving reaction vessels, the reaction vessel receiving body having a plurality of arranged in a regular grid recesses for receiving reaction vessels, a heater for heating the reaction vessel receiving body, and a cooling device for cooling the reaction vessel receiving body.
  • thermal cyclers or thermal cycler devices and are used to generate certain temperature cycles, i. e. that set in the reaction vessels predetermined temperatures and predetermined Time intervals are kept.
  • Such a device is known from US 5,525,300.
  • This device has four reaction vessel receiving bodies, each with in a regular Grid arranged recesses are formed.
  • the grid of the recesses corresponds to one known from standardized microtiter plates Raster of reaction vessels, leaving microtiter plates with their reaction vessels can be used in the recesses.
  • the heating and cooling means of one of the reaction vessel receiving body are formed such that a over the reaction vessel receiving body extending temperature gradient can be generated. This means that while a temperature cycle in the individual reaction vessels different Temperatures can be achieved. This makes it possible to specific Perform experiments simultaneously with different temperatures.
  • This temperature gradient is used to determine the optimal denaturation temperature, the optimal annealing temperature and the optimal elongation temperature used a PCR reaction. This is done in the individual reaction vessels introduced the same reaction mixture and then to carry out the PCR reaction necessary temperature cycles executed.
  • Such a temperature cycle involves heating the reaction mixtures to the denaturation temperature, which is usually in the range of 90 ° -95 ° C, the cooling on the Annealing temperature, which is usually in the range of 40 ° -60 ° C, and the Heating to the elongation temperature, usually in the range of 70 ° -75 ° C. lies. Such a cycle is repeated several times, whereby a predetermined DNA sequence is amplified.
  • the annealing temperature at which the primers are annealed has a strong Influence on the result. But the elongation temperature can also be or adversely affect the result. At a higher elongation temperature the accumulation of the bases is accelerated, whereby the probability of higher temperature errors. In addition, at a higher elongation temperature the life of the polymerase shorter.
  • a thermal cycler device that adjusts a temperature gradient can, provides a significant facilitation in identifying the desired Temperatures, as a reaction mixture in a single Thermocyclervoriques simultaneously undergo cycles with different temperatures can.
  • Another important parameter for the success of a PCR reaction is the Dwell time at the individual temperatures for denaturation, annealing and the elongation and the rate of change of the temperature. These parameters can not in the known device in a series of experiments on a single Reaction vessel holder can be varied. Do you want different lengths of stay and rate of change, this can be done in several series of experiments either in a thermal cycler device sequentially or in multiple thermal cycler devices run at the same time.
  • US 5,819,842 is a device for individual, controlled heating several samples.
  • This device has a plurality of flat Heating elements, which are arranged like a grid on a work surface. Below the heating elements, a cooling device is formed which extends over all Heating elements extends.
  • a specially designed sample plate placed on the work surface.
  • This sample plate has a grid plate on, which is covered at the bottom with a foil. In the recesses the grid plate, the samples are introduced. The samples are at this Device only separated by the film on the individual heating elements on. As a result, an immediate heat transfer is achieved.
  • WO 98/20975 describes a thermal cycler which is divided into four segments is, which are separately controllable. Will the individual fields be different? controlled, so are temperature gradients over a wide range of the thermal cycler.
  • US 5,716,842 relates to a miniaturized thermal cycler device with a meandering trained reaction chamber. Individual sections the reaction chamber are adjusted to different temperatures, so that when flowing through the reaction liquid through the reaction chamber the reaction liquid depending on the location of different temperatures is suspended and a predetermined temperature profile decreases. This Temperature profile is adjusted so that the reaction liquid is a PCR reaction performs.
  • thermocycling apparatus comprising a tempering block 12, are integrated in the heat pipes, as uniform as possible Temperature distribution - here in the vertical direction - to ensure.
  • These heat pipes correspond to those described in the present patent application on page Heat pipes, which serve as a temperature compensation element.
  • heating elements and a cooling chamber are provided on the bottom this tempering block, with which the tempering be heated or cooled accordingly can.
  • EP 0 488 769 A2 shows a thermocycling device in which the temperature-controllable Area is divided into a central area and border areas, where the edge areas can be controlled independently of the central area.
  • the Edge areas are usually with greater heat output than the central area controlled, so that the greater heat dissipation in the area of the edge areas compensate. This is for uniform temperature adjustment via the entire temperature range.
  • the invention is based on the object, the device mentioned in the introduction to develop that the disadvantages described above are avoided and the parameters of the PCR process can be optimized very flexibly.
  • the invention is characterized in that the reaction vessel receiving body is divided into several segments, and the individual segments thermally are decoupled and each segment is assigned a heating device that is independent can be controlled from each other.
  • the individual segments of the device can be independent of each other be set to different temperatures. This allows in not only different temperature levels are set to the segments can, but also held for different lengths or with different Change rates can be changed.
  • the device according to the invention thus allows optimization of all critical for a PCR process physical Parameter, wherein the optimization process on a single reaction vessel receiving body can be performed in which a microtiter plate can be used.
  • the thermal cycler device according to the invention is in particular for optimization the multiplex PCR method, in which several different Primers are used.
  • Fig. 1 is a first embodiment of the device 1 according to the invention for carrying out chemical and / or biological reactions schematically in Section shown.
  • the device has a housing 2 with a bottom wall 3 and side walls 4 on. A piece above the bottom wall 3 is parallel to the bottom wall 3, an intermediate wall 5 is arranged, on which a plurality of base 5a are formed.
  • a housing 2 with a bottom wall 3 and side walls 4 on.
  • a piece above the bottom wall 3 is parallel to the bottom wall 3, an intermediate wall 5 is arranged, on which a plurality of base 5a are formed.
  • Fig. 1 are total six sockets 5a provided, which are arranged in two rows á three sockets 5a.
  • a respective heat exchanger 6 On the bases 5a is a respective heat exchanger 6, a Peltier element 7 and a Segment 8 of a reaction vessel receiving body 9 is arranged.
  • the heat exchanger 6 is part of a cooling device and the Peltier element 7 is part a combined heating and cooling device.
  • the on the sockets 5a arranged elements heat exchanger, Peltier element, segment
  • the on the sockets 5a arranged elements are with a glued good heat-conductive adhesive resin, creating between these elements a good heat transfer is realized, and the elements also become one Segment part 10 are connected.
  • the device has a total of six such Segment parts 10 on.
  • adhesive resin may also be a heat conducting or a plantepaste be provided.
  • the segments 8 of the reaction vessel receiving body 9 each have a base plate 11 integrally formed thereon tubular, thin-walled reaction vessel holders 12 on.
  • a base plate 11 integrally formed thereon tubular, thin-walled reaction vessel holders 12 on.
  • 4 x 4 reaction vessel holder 12 are arranged on a base plate 11.
  • the distance d between adjacent segments 8 is dimensioned such that the reaction vessel holder 12 of all segments 8 in a regular grid with constant grid spacing D are arranged.
  • the grid spacing D is chosen that a standardized microtiter plate with their reaction vessels in the Reaction vessel holder 12 can be used.
  • the reaction vessel holders 12 of the device shown in Fig. 1 form a grid with a total of 96 reaction vessel holders in eight rows á twelve reaction vessel holder 12 are arranged.
  • the Peltier elements 7 are each electrically connected to a first control device 13 connected.
  • the heat exchangers 6 are each via a separate cooling circuit 14 connected to a second control device 15.
  • a cooling medium For example, water used in the cooling temperature control device is used is before it is transported to one of the heat exchanger 6.
  • the first control device 13 and the second control device 15 are connected to a central control device 16 connected to the to be executed in the device Temperature cycles controls.
  • a switching valve 19th introduced by the central control unit 16 for opening or closing the respective cooling circuit 14 is controlled.
  • a lid 17 is pivotally mounted, in which further heating elements 18 in the form of Peltier elements, heating foils or semiconductor heating elements can be arranged.
  • the heating elements 18 form Deckelloomamine, the each associated with a segment 8 and individually with the first control device 13 are connected so that each heating element 18 are controlled individually can.
  • the segments are at different temperatures controlled, the temperatures being controlled so that the temperature difference ⁇ T of adjacent segments 8 less than a predetermined value K is, for example, 5 ° -15 ° C.
  • K is, for example, 5 ° -15 ° C.
  • the value to be chosen for K depends on the quality of the thermal decoupling. For K, a higher value can be chosen the better the thermal decoupling.
  • the user entered temperature cycles can be from the central Control device 16 are automatically distributed to the segments 8, so that the Temperature differences between adjacent segments as small as possible being held.
  • This second operating mode can be provided with a function with which the User enters only a single temperature cycle or PCR cycle, and the central controller 16 then automatically varies this cycle.
  • the too varying parameters such as temperature, residence time or temperature change rate, can be selected by the user individually or in combination. The variation of the parameters takes place either after a linear or sigmoidal Distribution.
  • the Segments 8 In the third operating mode, only a part of the segments are activated.
  • the Segments 8 have side edges 20 in plan view (FIGS. 3, 4, 6 to 9). In this mode of operation, they become a driven segment 8 whose side edges adjacent segments 8 are not driven. Educate the Segments 8 themselves a regular grid (Fig. 3, Fig. 4, Fig. 6, Fig. 7 and Fig. 8), the driven segments are distributed as in a checkerboard pattern. In the embodiments shown in FIGS. 1 to 4, three of the six Segments 8 are driven, namely the two outer segments of a row and the middle segment of the other row.
  • the driven segments are not affected by the affected other segments, whereby their temperature completely independent can be adjusted by the other driven segments. hereby It is possible to different temperature cycles on the individual To descend segments, wherein one of the segments, for example, to the denaturation temperature heated and kept another at the annealing temperature becomes. So it is possible to keep the dwell times, i.e., the time intervals during the the denaturation temperature, annealing temperature and elongation temperature is held, as well as the temperature change rates set arbitrarily and at the same time leave at the individual segments. This makes it possible not only the temperatures, but also the dwell times and the rates of temperature change to optimize.
  • the non-driven Segments 8 may be appropriate, so that their temperature is approximately in the range of lowest temperature of the adjacent adjacent driven segments. This avoids that the non-driven segments a heat sink form for the driven segment and their temperature profile disadvantageous influence.
  • FIG. 2 and 3 A second embodiment of the device according to the invention is shown in FIG. 2 and 3.
  • the basic structure corresponds to that of FIG. 1, why the same Parts are provided with the same reference numerals.
  • the second embodiment differs from the first embodiment in that the adjacent to the side walls 4 of the housing 2 Side edges 20 of the segments 8 in one on the inner surface of the side walls Engage 4 circumferential groove 21 and therein, for example, are fixed by gluing. hereby the individual segment parts 10 are spatially fixed, thereby ensuring is that despite the formation of the gap between the segment parts 10 all reaction vessel holder 12 arranged in the grid of the reaction vessels of a microtiter plate are.
  • the side walls 4 of the housing 2 are made of a non-heat-conducting Material formed. This embodiment may also be so be modified so that the groove 21 in a separate from the housing 2 trained frame is introduced. The frame and its inserted Segments form a separately manageable part in the production, which on the Heating and cooling devices is glued.
  • FIGS. 4 and 5 A third embodiment is shown schematically in FIGS. 4 and 5.
  • Struts 22 of a non-thermally conductive material just below the base plates 11 of the segments 8 arranged.
  • At the side edges 20 of the segments eighth or the base plates 11 are formed downwardly angled hook elements 23.
  • These hook elements 23 engage in corresponding recesses of the Struts 22 a (Fig. 5), whereby the segments 8 are fixed in position.
  • the hook elements 23 adjacent segments 8 are arranged offset to one another.
  • the struts 22 thus form a grid, in whose openings in each case a segment. 8 can be used.
  • This type of positional fixation is very advantageous because the interfaces between the Segments 8 and the struts 22 are very small, causing heat transfer is correspondingly low over the struts 22.
  • this arrangement can also in the confined spaces between adjacent segment parts easy will be realized.
  • reaction vessel receiving body 9 are schematically in plan view reaction vessel receiving body 9, the further modifications of the device according to the invention represent.
  • reaction vessel receiving bodies 9 are the individual Segments 8 by means of webs 24 of a heat-insulating material to a Unit connected.
  • the struts 22 are between the side edges 20 of the base plates 11 arranged and fixed to this example. By gluing.
  • the segmentation of the reaction vessel receiving body of Fig. 6 corresponds those of the first and second embodiments (Figs. 1-3), wherein on each Segment 8 4 x 4 reaction vessel holder are arranged.
  • the reaction vessel receiving body 9 shown in FIG. 7 is composed of 24 segments 8 each with 4 x 4 Reaction vessel holder 12 composed, wherein the segments 8 are in turn connected by means of thermally insulating webs 24.
  • each segment has 8 only a single reaction vessel holder 12.
  • the thermal cycler temperature sensors which scan the temperatures of the individual segments, so that after the Temperature values determined by the temperature sensors, the temperature of the segments 8 is regulated in a closed loop.
  • Infrared sensors can be used, the e.g. are arranged in the lid. With this sensor arrangement, it is possible to Sensing temperature of the reaction mixture directly.
  • Fig. 9 shows a reaction vessel receiving body 9 with six in plan view rectangular segments 8 and one in the shape of a double cross of three itself intersecting rows of reaction vessel holders 12 formed segment 8a.
  • the Six rectangular segments 8 are each a row or column of reaction vessel holders spaced from the next rectangular segment. This segmentation is particularly advantageous for the third operating mode explained above, because the rectangular segments 8 do not touch and therefore simultaneously can be controlled arbitrarily, with only the segment 8a in Form of a double cross is not controlled.
  • the segments 8 of the Christsgafäßability stresses 9 are made of a good heat conducting Metal, e.g. Aluminum, formed.
  • a good heat conducting Metal e.g. Aluminum
  • the above as non-heat-conducting Materials or materials designated as heat-insulating are either plastics or ceramics.
  • FIG. 11 A further embodiment of the device according to the invention is shown in FIG. 11 shown.
  • the individual segments 8b of the reaction vessel receiving body 9 fixed by means of a clamping frame 25 (Fig. 10).
  • the clamping frame 25 is a lattice-shaped longitudinal struts 26 and transverse struts 27th formed, wherein the struts 26, 27 span openings. Through these openings extend the reaction vessel holder 12 of the segments 8b. At present Embodiment are the struts 26, 27 approximately positively the Christsgefäßhaltem 12 and on the on the reaction vessel holders above Base plate 11 on.
  • the clamping frame 25 is provided with holes 28, that of bolts 29 for fixing the tenter on a thermal cycler device 1 be penetrated.
  • the heat sink 30 is provided with holes through which extend the bolt 29, which at the from the reaction vessel receiving body 9 facing away from the heat sink 30 are each fixed with a nut 32.
  • the clamping frame 25 is made of a non-thermally conductive material, in particular made of POM or polycarbonate. It thus allows a fixation of the segments 8b of the reaction vessel receiving body 9, wherein the individual elements between the segments 8b and the heat sink 30 are under tension, so that in the vertical direction a good heat transfer between the individual elements is guaranteed. Since the clamping frame itself is battle-heat-conducting, the heat transfer between two adjacent segments 8b becomes low held. To further reduce the heat transfer between two adjacent Segments may be those in contact with the segments 8b Be provided surfaces of the clamping frame 25 with narrow webs, so that in the areas adjacent to the webs air gaps between the clamping frame 25 and the segments 8b are formed.
  • a heat pipe 33 is installed between two rows of Reaction vessel holders 12 each have a so-called heat pipe 33 is installed.
  • a heat pipe is, for example, from the company THERMACORE INTERNATIONAL, Inc., USA. It consists of a gas-tight jacket in which only a small amount of fluid is located. There is such a thing in the heat pipe low pressure, that the liquid fluid in a state of equilibrium between the liquid and the gaseous state of aggregation and consequently vaporized on a warmer section of the heat pipe and on a cooler one Condensed section. As a result, between the individual sections the Temperature balanced. For example, water or freon is used as the fluid.
  • FIG. 11 A further embodiment of the inventive thermal cycler device 1 is shown in FIG. This thermal cycler device 1 is similar to that in FIG. 11 shown formed, which is why the same parts designated by the same reference numerals are.
  • the segments 8c of this thermal cycler device have no heat pipes on. Instead of heat pipes are in the area below the segments 8c in each case a temperature compensation plate 34 is provided. These temperature compensation plates 34 are sheet-like elements whose area of the base one of the segments 8c corresponds. These temperature compensation plates 34 are Hollow body with a small amount of fluid and work the same way Working principle like the heat pipes. This in turn ensures that it within a segment 8c there are no temperature fluctuations.
  • the temperature compensation plate can also be made of very good thermal conductivity Materials such as e.g. Copper, be formed.
  • additional heating and / or cooling elements e.g. Heaters, Heating coils or Peltier elements, be integrated.
  • the heating and cooling elements support homogeneity and allow faster heating and / or cooling rates.
  • a Peltier element which usually does not have a uniform temperature distribution has, is preferably combined with a flat heating element.
  • the invention is above based on embodiments with 96 recesses for receiving a microtiter plate with 96 reaction vessels.
  • the invention is not limited to this number of recesses. So
  • the reaction vessel receiving body may also have 384 recesses for Have a corresponding microtiter plate.
  • a cooling device with used a liquid cooling medium In the embodiments described above, a cooling device with used a liquid cooling medium. It is also within the scope of the invention possible, instead of a liquid cooling medium and a gaseous cooling medium, in particular to use an air cooling.
  • reaction vessel receiving bodies are made of a base plate formed with approximately tubular reaction vessel holders.
  • a metal block in the recesses for accommodating the reaction vessels of the microtiter plate are.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)

Claims (17)

  1. Appareil destiné à réaliser des réactions chimiques ou biologiques, comportant
       un corps de réception de réacteurs (9) destiné à recevoir une plaque microtitre comportant plusieurs réacteurs, le corps de réception de réacteurs (9) comportant plusieurs creux disposés suivant une trame régulière et destiné à recevoir le réacteur correspondant,
       un dispositif de chauffage (7) destiné à chauffer le corps de réception de réacteurs (9), et
       un dispositif de refroidissement (6) destiné à refroidir le corps de réception de réacteurs (9),
       le corps de réception de réacteurs (9) étant divisé en plusieurs segments (8), et
       un dispositif de chauffage étant associé à chaque segment, et les dispositifs de chauffage (7) pouvant être commandés indépendamment les uns des autres,
       caractérisé en ce que les segments individuels (8) sont découplés du point de vue thermique de telle sorte que des niveaux de température différents peuvent être ajustés et sont maintenus sur deux segments adjacents.
  2. Appareil selon la revendication 1, caractérisé en ce qu'un dispositif de refroidissement (6) est associé à chaque segment (8) du corps de réception de réacteurs (9), les dispositifs de refroidissement (6) pouvant être commandés indépendamment les uns des autres.
  3. Appareil selon la revendication 1 ou 2, caractérisé en ce que les segments (8) du corps de réception de réacteurs (9) se composent chacun d'une plaque de base (11) comportant un ou plusieurs supports de réacteur (12) de forme tubulaire et à parois minces qui sont conformés pour être d'une seule pièce avec la plaque de base (11).
  4. Appareil selon l'une des revendications 1 à 3, caractérisé en ce que les segments individuels (8) sont découplés du point de vue thermique en ménageant un interstice entre des segments adjacents (8).
  5. Appareil selon l'une des revendications 1 à 3, caractérisé en ce que les segments individuels (8) sont découplés du point de vue thermique en ménageant entre des segments adjacents une fente dans laquelle est introduit un isolateur thermique.
  6. Appareil selon l'une des revendications 1 à 5, caractérisé en ce que chacun des dispositifs de chauffage comporte un élément à effet Peltier (7), un élément à effet Peltier (7) étant associé à chaque segment (8) du corps de réception de réacteurs (9) et les éléments à effet Peltier (7) étant couplés du point de vue thermique aux segments correspondants (8).
  7. Appareil selon l'une des revendications 1 à 6, caractérisé en ce que les éléments de refroidissement comportent un élément à effet Peltier (7) et/ou un échangeur de chaleur (6), un élément à effet Peltier (7) et/ou un échangeur de chaleur (6) étant associés à chacun des segments (8) du corps de réception de réacteurs (9).
  8. Appareil selon la revendication 7, caractérisé en ce que les échangeurs de chaleur (6) sont dotés de canaux de refroidissement qui peuvent être traversés par un fluide, l'écoulement de fluide à travers les échangeurs de chaleur individuels (6) pouvant être commandés indépendamment les uns des autres.
  9. Appareil selon la revendication 8, caractérisé en ce que le fluide est un liquide de refroidissement, en particulier de l'eau.
  10. Appareil selon l'une des revendications 1 à 9, caractérisé en ce que le corps de réception de réacteurs (9) est divisé en au moins quatre segments (8).
  11. Appareil selon l'une des revendications 1 à 10, caractérisé en ce que chacun des segments individuels (8) comporte le même nombre de creux.
  12. Appareil selon l'une des revendications précédentes, caractérisé en ce que les segments (8) comportent au niveau de leurs bords latéraux (20) des éléments d'accrochage (23) pointant vers le bas permettant de les placer sur des montants (22).
  13. Appareil selon l'une des revendications 1 à 12, caractérisé en ce qu'il est associé à chaque segment (8) un capteur de température permettant de mesurer la température du segment correspondant (8), la température des segments (8) étant régulée conformément aux températures mesurées par les capteurs individuels.
  14. Appareil selon l'une des revendications 1 à 3, caractérisé en ce qu'au moins un élément de compensation de température (33,34) est associé à chaque segment (8b, 8c).
  15. Appareil selon l'une des revendications 1 à 14, caractérisé en ce qu'il comprend un dispositif de commande destiné à commander le dispositif de chauffage et le dispositif de refroidissement, le dispositif de commande (15, 16) étant conformé de telle sorte que les dispositifs de refroidissement des segments individuels (8) peuvent être commandés individuellement,
  16. Appareil selon la revendication 15, caractérisé en ce que le dispositif de commande (13, 15, 16) commande dans un mode de fonctionnement seulement une partie des segments, les segments (8) comportant des bords latéraux (20), et les segments (8) adjacents à un segment commandé (8) au niveau de ses bords latéraux (20) n'étant pas commandés.
  17. Appareil selon la revendication 15 ou 16, caractérisé en ce que les segments sont commandés dans un mode de fonctionnement de telle sorte que la différence de température entre des segments adjacents (8) est inférieure à une différence de température (ΔT) prédéterminée.
EP00966090A 1999-10-01 2000-09-29 Dispositif pour realiser des reactions chimiques ou biologiques Expired - Lifetime EP1216098B1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE29917313U 1999-10-01
DE29917313U DE29917313U1 (de) 1999-10-01 1999-10-01 Vorrichtung zur Durchführung chemischer oder biologischer Reaktionen
PCT/EP2000/009569 WO2001024930A1 (fr) 1999-10-01 2000-09-29 Dispositif pour realiser des reactions chimiques ou biologiques

Publications (2)

Publication Number Publication Date
EP1216098A1 EP1216098A1 (fr) 2002-06-26
EP1216098B1 true EP1216098B1 (fr) 2003-07-23

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EP00966090A Expired - Lifetime EP1216098B1 (fr) 1999-10-01 2000-09-29 Dispositif pour realiser des reactions chimiques ou biologiques

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US (6) US20070110634A1 (fr)
EP (1) EP1216098B1 (fr)
JP (1) JP2003511221A (fr)
KR (1) KR100696138B1 (fr)
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KR20020038765A (ko) 2002-05-23
US7611674B2 (en) 2009-11-03
US20100120099A1 (en) 2010-05-13
US9914125B2 (en) 2018-03-13
WO2001024930A1 (fr) 2001-04-12
US20070140926A1 (en) 2007-06-21
EP1216098A1 (fr) 2002-06-26
US20120264206A1 (en) 2012-10-18
KR100696138B1 (ko) 2007-03-20
AU774199B2 (en) 2004-06-17
US8389288B2 (en) 2013-03-05
NO20021340D0 (no) 2002-03-18
AU7660500A (en) 2001-05-10
US20140030170A1 (en) 2014-01-30
US8721972B2 (en) 2014-05-13
DE29917313U1 (de) 2001-02-15
JP2003511221A (ja) 2003-03-25
NO20021340L (no) 2002-03-18
ATE245487T1 (de) 2003-08-15
US20100120100A1 (en) 2010-05-13
DE50003023D1 (de) 2003-08-28
US20070110634A1 (en) 2007-05-17

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