Recherche Images Maps Play YouTube Actualités Gmail Drive Plus »
Connexion
Les utilisateurs de lecteurs d'écran peuvent cliquer sur ce lien pour activer le mode d'accessibilité. Celui-ci propose les mêmes fonctionnalités principales, mais il est optimisé pour votre lecteur d'écran.

Brevets

  1. Recherche avancée dans les brevets
Numéro de publicationUS20100120100 A1
Type de publicationDemande
Numéro de demandeUS 12/689,214
Date de publication13 mai 2010
Date de dépôt18 janv. 2010
Date de priorité1 oct. 1999
Autre référence de publicationDE29917313U1, EP1216098A1, EP1216098B1, US7611674, US8389288, US8721972, US20070110634, US20070140926, US20100120099, US20120264206, US20140030170, WO2001024930A1
Numéro de publication12689214, 689214, US 2010/0120100 A1, US 2010/120100 A1, US 20100120100 A1, US 20100120100A1, US 2010120100 A1, US 2010120100A1, US-A1-20100120100, US-A1-2010120100, US2010/0120100A1, US2010/120100A1, US20100120100 A1, US20100120100A1, US2010120100 A1, US2010120100A1
InventeursWolfgang Heimberg, Thomas Herrmann, Matthias Knulle, Markus Schurf, Tilmann Wagner
Cessionnaire d'origineLife Technologies Corporation
Exporter la citationBiBTeX, EndNote, RefMan
Liens externes: USPTO, Cession USPTO, Espacenet
Device For The Carrying Out of Chemical or Biological Reactions
US 20100120100 A1
Résumé
An interactive radio network enables users to interact with the content of a radio broadcast, including commercials or messages, and to selectively save, store, review, fast forward, rewind, pause, forward, and respond to the radio programs and/or the commercials. The interactive radio network provides a widespread, international, and economical access to the radio stations, and reduces the need for advertisement billboards. It provides the users with an opportunity to selectively inquire about the products or services being advertised. Furthermore, the interactive radio network allows the users as well as various sectors of the advertisement industry to interact with the content of the radio broadcast. The advertisements are no longer limited to audio messages, but can further include elaborate video, text, and data information. The interactive radio network enables the users to communicate and interact with each others, based on the broadcast content. It also provides a widely accessible and affordable avenue for mass marketing and broadcasting of commercials to mobile users.
Images(8)
Previous page
Next page
Revendications(14)
1. A method for optimizing at least one parameter for polymerase chain reaction, comprising:
dividing a same reaction mixture into each of a plurality of reaction vessels of a standard microtiter plate;
inserting the standard microtiter plate into a polymerase chain reaction device comprising:
a reaction vessel receiving element physically divided into two or more segments that are thermally insulated from one another, wherein the standard microtiter plate spans an entirety of the reaction vessel receiving element upon insertion into the reaction vessel receiving element,
two or more physically distinct devices for heating and cooling the reaction vessel receiving element, wherein each device for heating and cooling is aligned with and dedicated to heat and cool only one respective segment such that each segment is aligned with a device for heating and cooling; and
a control unit for actuating the polymerase chain reaction device, wherein the devices for heating and cooling are actuated independently of one another to set and maintain different temperatures in two adjacent segments; and
heating and cooling the segments to different temperatures during a temperature cycle to optimize the at least one parameter for polymerase chain reaction.
2. The method of claim 1, wherein each segment of the reaction vessel receiving element comprises a base plate with one or more tubular, thin-walled reaction vessel holders, which form one piece together with the base plate.
3. The method of claim 1, wherein the segments are insulated from each other with an air gap formed between adjacent segments.
4. The method of claim 1, wherein the segments are insulated from each other with a thermal insulator inserted in a gap between adjacent segments.
5. The method of claim 1, wherein the devices for heating and cooling comprise Peltier elements, and wherein the Peltier elements are thermally coupled to each segment.
6. The method of claim 1, wherein the reaction vessel receiving element is divided into at least four segments.
7. The method of claim 1, wherein the individual segments each have a same number of reaction vessels.
8. The method of claim 1, wherein each segment is assigned a temperature sensor operatively connected to the control unit, with which the temperature of the segment concerned is sensed, with the temperature of each segment being controlled on the basis of the temperature sensed by the respective sensor.
9. The method of claim 1, wherein each segment is assigned one or more temperature equalization elements.
10. The method of claim 1, wherein the segments are actuated such that the temperature difference between adjacent segments is less than a predetermined temperature difference (AT).
11. The method of claim 1, wherein the at least one parameter optimized includes at least one of denaturing temperature, annealing temperature, and elongation temperature.
12. The method of claim 1, wherein the at least one parameter optimized comprises at least one of residence time at a temperature for at least one of denaturing temperature, annealing temperature, and elongation temperature.
13. The method of claim 1, wherein the at least one parameter optimized comprises rate of temperature change.
14. The method of claim 1, wherein the polymerase chain reaction device further comprises an additional control unit for actuating the two or more devices for heating and cooling, wherein each of the two or more devices for heating and cooling is individually actuated.
Description
  • [0001]
    The present invention relates to a device for the carrying out of chemical or biological reactions with
    • a reaction vessel receiving element for receiving reaction vessels, wherein the reaction vessel receiving element has several recesses arranged in a regular pattern to receive reaction vessels, a heating device for heating the reaction vessel receiving element, and a cooling device for cooling the reaction vessel receiving element.
  • [0003]
    Such devices are described as thermocyclers or thermocycling devices and are used to generate specific temperature cycles, i.e. to set predetermined temperatures in the reaction vessels and to maintain predetermined intervals of time.
  • [0004]
    A device of this kind is known from U.S. Pat. No. 5,525,300. This device has four reaction vessel receiving elements, each with recesses arranged in a regular pattern. The pattern of the recesses corresponds to a known pattern of reaction vessels of standard microtiter plates, so that microtiter plates with their reaction vessels may be inserted in the recesses.
  • [0005]
    The heating and cooling devices of a reaction vessel receiving element are so designed that a temperature gradient extending over the reaction vessel receiving element may be generated. This means that, during a temperature cycle, different temperatures may be obtained in the individual reaction vessels. This makes it possible to carry out certain experiments at different temperatures simultaneously.
  • [0006]
    This temperature gradient is used to determine the optimal denaturing temperature, the optimal annealing temperature and the optimal elongation temperature of a PCR reaction. To achieve this, the same reaction mixture is poured into the individual reaction vessels, and the temperature cycles necessary to perform the PCR reaction are executed. Such a temperature cycle comprises the heating of the reaction mixture to the denaturing temperature, which usually lies in the range 90°-95° C., cooling to the annealing temperature, which is usually in the range 40°-60° C., and heating to the elongation temperature, which is usually in the range 70-75° C. A cycle of this kind is repeated several times, leading to amplification of a predetermined DNA sequence.
  • [0007]
    Since a temperature gradient can be set, different but predetermined temperatures are set in the individual reaction vessels. After completion of the cycles it is possible to determine, with the aid of the reaction products, those temperatures at which the PCR reaction will give the user the optimal result. Here the result may be optimised e.g. in respect of product volume or also product quality.
  • [0008]
    The annealing temperature, at which the primer is added, has a powerful influence on the result. However the elongation temperature too can have beneficial or adverse effects on the result. At a higher elongation temperature, the addition of the bases is accelerated, with the probability of errors increasing with higher temperature. In addition, the life of the polymerase is shorter at a higher elongation temperature.
  • [0009]
    A thermocycling device, by which the temperature gradient may be set, makes it much easier to determine the desired temperatures, since a reaction mixture my simultaneously undergo cycles at different temperatures in a single thermocycling device.
  • [0010]
    Another important parameter for the success of a PCR reaction is the residence time at the individual temperatures for denaturing, annealing and elongation, and the rate of temperature change. With the known device, these parameters can not be varied in one test series for an individual reaction vessel holder. If it is desired to test different residence times and rates of change, this can be done in several test series either consecutively on one thermocycling device or simultaneously in several thermocycling devices.
  • [0011]
    For this purpose there are so-called multiblock thermocycling devices with several reaction vessel receiving elements, each provided with separate cooling, heating and control devices (see U.S. Pat. No. 5,525,300). The reaction mixture to be tested must be distributed over several microtiter plates, for testing independently of one another.
  • [0012]
    To determine the optimal residence times and rates of temperature change it is necessary to have either several thermocycling devices or a multiblock thermocycling device, or to carry out tests in several consecutive test series. The acquisition of several thermocycling devices or of a multiblock thermocycling device is costly and the carrying-out of several consecutive test series takes too long. In addition, handling is laborious when only part of the reaction vessels of several microtiter plates is filled, with each of the latter being tested and optimised in separate test series. This is especially disadvantageous in the case of device which operate automatically and in which the reaction mixtures are subject to further operations, since several microtiter plates must then be handled separately. It is also extremely impractical when only part of the reaction vessels of the microtiter plates is filled, since the devices for further processing, such as e.g. sample combs for transferring the reaction products to an electrophoresis apparatus, are often laid out on the grid of the microtiter plates, which means that further processing is correspondingly limited if only part of the reaction vessels of the microtiter plate is used.
  • [0013]
    U.S. Pat. No. 5,819842 discloses a device for the individual, controlled heating of several samples. This device has several flat heating elements arranged in a grid pattern on a work surface. Formed below the heating elements is a cooling device which extends over all the heating elements. In operation a specially designed sample plate is placed on the work surface. This sample plate has a grid plate, covered on the underside by a film. The samples are poured into the recesses of the grid plate. In this device the samples lie on the individual heating elements, separated from them only by the film. By this means, direct heat transfer is obtained. The drawback of this device, however, is that no commonly available microtiter plate can be used.
  • [0014]
    With increasing automation in biotechnology, thermocyclers are increasingly being used in automated production lines and with robots as one of several work stations. Here it is customary for the samples to be passed in microtiter plates from one work station to the next. If the device according to U.S. Pat. No. 5,819,842 were to be used in such an automated production process, it would be necessary for the samples to be pipetted out of a microtiter plate into the specially designed sample plate before temperature adjustment, and from the sample plate into a microtiter plate after temperature adjustment. Here there is a risk of contamination of the samples. The use of this specially designed sample plate must therefore be regarded as extremely disadvantageous.
  • [0015]
    The invention is based on the problem of developing the device described above in such a way that the disadvantages described above are avoided and the parameters of the PCR process may be optimised with great flexibility.
  • [0016]
    To solve this problem the invention has the features specified in claim 1. Advantageous developments thereof are set out in the additional claims.
  • [0017]
    The invention is characterised by the fact that the reaction vessel receiving element is divided into several segments, with the individual segments thermally decoupled and each segment assigned a heating device which may be actuated independently.
  • [0018]
    By this means the individual segments of the device may be set to different temperatures independently of one another. This makes it possible not only to set different temperature levels in the segments, but also for them to be held for varying lengths of time or altered at different rates of change. The device according to the invention thus permits optimisation of all physical parameters critical for a PCR process, while the optimisation process may be carried out on a single reaction vessel receiving element in which a microtiter plate may be inserted.
  • [0019]
    With the device according to the invention it is therefore also possible to optimise the residence times and rates of temperature change without having to distribute the reaction mixture over different microtiter plates for this purpose.
  • [0020]
    The thermocycling device according to the invention is in particular suitable for optimising the multiplex PCR process, in which several different primers are used.
  • [0021]
    The above problem, and the features and advantages according to the present invention, may be better understood from the following detailed description of preferred embodiments of the present invention and with reference to the associated drawings.
  • [0022]
    The invention is explained in detail below with the aid of the drawings. These show in:
  • [0023]
    FIG. 1 a section through a device according to the invention for carrying out chemical or biological reactions in accordance with a first embodiment,
  • [0024]
    FIG. 2 a section through an area of a device according to the invention for carrying out chemical or biological reactions in accordance with a second embodiment,
  • [0025]
    FIG. 3 a schematic plan view of the device of FIG. 2,
  • [0026]
    FIG. 4 a schematic plan view of a device according to a third embodiment, an area of the device of FIG. 4 in a sectional view along the line A-A,
  • [0027]
    FIGS. 6 to 9 schematic plan views of reaction vessel receiving elements with differing segmentation
  • [0028]
    FIG. 10 a clamping frame in plan view
  • [0029]
    FIG. 11 a device according to the invention in which segments of a reaction vessel receiving element are fixed by the clamping frame according to FIG. 10, and
  • [0030]
    FIG. 12 a further embodiment of a device according to the invention in section, in which segments of a reaction vessel receiving element are fixed by the clamping frame according to FIG. 10.
  • [0031]
    FIG. 1 shows a first embodiment of the device 1 according to the invention for carrying out chemical or biological reactions in a schematic sectional view.
  • [0032]
    The device has a housing 2 with a bottom 3 and side walls 4. Located just above and parallel to the bottom 3 is an intermediate wall 5, on which are formed several bases 5 a. In the embodiment shown in FIG. 1, a total of six bases 5 a are provided, arranged in two rows of three bases 5 a each.
  • [0033]
    Mounted on each of the bases 5 a is a heat exchanger 6, a Peltier element 7 and a segment 8 of a reaction vessel receiving element 9. The heat exchanger 6 is part of a cooling device and the Peltier element 7 is part of a combined heating and cooling device. The elements (heat exchanger, Peltier element, segment) mounted on the bases 5 a are bonded by an adhesive resin with good heat conducting properties, so that good heat transfer is realised between these elements, and the elements are also firmly connected to a segment element 10. the device has altogether six such segment elements 10. Instead of adhesive resin, a heat conducting film or a heat conducting paste may also be provided.
  • [0034]
    Each of the segments 8 of the reaction vessel receiving element 9 has a base plate 11 on which tubular, thin-walled reaction vessel holders 12 are integrally formed. In the embodiment depicted in FIG. 1, in each case 4×4 reaction vessel holders 12 are arranged on a base plate 11. The distance d between adjacent segments 8 is such that the reaction vessel holders 12 of all segments 8 are arranged in a regular pattern with constant grid spacing D. The grid spacing D is chosen so that s standardised microtiter plate with its reaction vessels may be inserted in the reaction vessel holders 12.
  • [0035]
    By providing the distance d between adjacent segments, an air gap which thermally decouples the segments 8 and segment elements 10 respectively is formed.
  • [0036]
    The reaction vessel holders 12 of the device shown in FIG. 1 form a grid with a total pf 96 reaction vessel holders, arranged in eight rows each with twelve reaction vessel holders 12.
  • [0037]
    The Peltier elements 7 are each connected electrically to a first control unit 13. Each of the heat exchangers 6 is connected via a separate cooling circuit 14 to a second control unit 15. The cooling medium used is for example water, which is cooled in the cool temperature control unit before transfer to one of the heat exchangers 6.
  • [0038]
    The first control unit 13 and the second control unit 15 are connected to a central control unit 16 which controls the temperature cycles to be implemented in the device. Inserted in each cooling circuit 14 is a control valve 19, which is controlled by the central control unit 16 to open or close the respective cooling circuit 14.
  • [0039]
    Pivotably attached to the housing 2 is a cover 17 in which additional heating elements 18 in the form of Peltier elements, heating films or semiconductor heating elements may be located. The heating elements 18 form cover heating elements, each assigned to a segment 8 and separately connected to the first control unit 13, so that each heating element 18 may be individually actuated.
  • [0040]
    The mode of operation of the device according to the invention is explained in detail below.
  • [0041]
    There are three modes of operation.
  • [0042]
    In the first operating mode all segments are set to the same temperature, i.e. the same temperature cycles are run on all segments. This operating mode corresponds to the operation of a conventional thermocycling device.
  • [0043]
    In the second operating mode the segments are actuated with different temperatures, wherein the temperatures are so controlled that the temperature difference ΔT of adjacent segments 8 is less than a predetermined value K which amounts for example to 5°-15° C. The value to be chosen for K depends on the quality of the thermal decoupling. The better the thermal decoupling, the greater the value which can be chosen for K.
  • [0044]
    The temperature cycles input by the user may be distributed automatically by the central control unit 16 to the segments 8, so that the temperature differences between adjacent segments are kept as small as possible.
  • [0045]
    This second operating mode may be provided with a function by which the user inputs only a single temperature cycle or PCR cycle, and the central control unit 16 then varies this cycle automatically. The parameters to be varied, such as temperature, residence time or rate of temperature change, may be chosen by the user separately or in combination. Variation of the parameters is effected either by linear or sigmoidal distribution.
  • [0046]
    In the third operating mode, only part of the segments is actuated. In plan view (FIG. 3, FIG. 4, FIGS. 6 to 9) the segments 8 have side edges 20. In this operating mode, the segments 8 adjacent to the side edges of an actuated segment 8 are not actuated. If the segments 8 themselves form a regular pattern (FIG. 3, FIG. 4, FIG. 6, FIG. 7 and FIG. 8), then the actuated segments are distributed in a chessboard pattern. In the embodiments shown in FIGS. 1 to 4, three of the six segments 8 can be actuated, namely the two outer segments of one row and the middle segment of the other row.
  • [0047]
    In this operating mode the actuated segments are not influenced by the other segments, and their temperature may be set completely independently of the other actuated segments. By this means it is possible to run quite different temperature cycles on the individual segments, with one of the segments for example heated up to the denaturing temperature and another held at the annealing temperature. Thus it is possible for the residence times, i.e. the intervals of time for which the denaturing temperature, the annealing temperature and the elongation temperature are held, also the rates of temperature change, to be set as desired, and run simultaneously on the individual segments. In this way it is possible to optimise not only the temperatures, but also the residence times and the rates of temperature change.
  • [0048]
    In this operating mode it may be expedient to heat the non-actuated segments 8 a little, so that their temperature lies roughly in the range of the lowest temperature of the adjacent actuated segments. This avoids the non-actuated segments forming a heat sink for the actuated segments and affecting their temperature profile adversely.
  • [0049]
    A second embodiment of the device according to the invention is shown in FIGS. 2 and 3. the basic design corresponds to that of FIG. 1, so that identical parts have been given the same reference number.
  • [0050]
    The second embodiment differs from the first embodiment by virtue of the fact that the side edges 20 of the segments 8 adjacent to the side walls 4 of the housing 2 engage in a slot 21 running round the inner face of the side walls 4, and are fixed therein for example by bonding. By this means the individual segment elements 10 are fixed in space, thereby ensuring that despite the form of the gaps between the segment elements 10, all reaction vessel holders 12 are arranged in the pattern of the reaction vessels of a microtiter plate. The side walls 4 of the housing 2 are made of a non heat conducting material. This embodiment may also be modified such that the slot 21 is introduced in a frame formed separately from the housing 2. The frame and the segments inserted in it form a part which may be handled separately during production and is bonded to the heating and cooling devices.
  • [0051]
    A third embodiment is shown schematically in FIGS. 4 and 5. In this embodiment, ties 22 of non heat conducting material are located somewhat below the base plates 11 of the segments 8 in the areas between the segment elements 10 and between the segment elements 10 and the side walls 4 of the housing 2. On the side edges 20 of the segments 8 and of the base plates 11 respectively are formed hook elements 23 which are bent downwards. These hook elements 23 engage in corresponding recesses of the ties 22 (FIG. 5), thereby fixing the segments 8 in their position. The hook elements 23 of adjacent segments 8 are offset relative to one another. The ties 22 thus form a grid, into each of the openings of which a segment 8 may be inserted.
  • [0052]
    This type of position fixing is very advantageous since the boundary areas between the segments 8 and the ties 22 are very small, so that heat transfer via the ties 22 is correspondingly low. Moreover this arrangement is easy to realise even in the confined space conditions between adjacent segment elements.
  • [0053]
    Shown in schematic plan view in FIGS. 6 to 9 are reaction vessel receiving elements 9 which represent further modifications of the device according to the invention. In these reaction vessel receiving elements 9, the individual segments 8 are joined by webs 24 of a thermally insulating material joined to form a single unit The ties 22 are arranged between the side edges 20 of the base plates 11, to which they are fixed for example by bonding.
  • [0054]
    The segmentation of the reaction vessel receiving element of FIG. 6 corresponds to that of the first and second embodiment (FIG. 1-3), in which 4×4 reaction vessel holders are arranged on each segment 8.
  • [0055]
    The reaction vessel receiving element 9 shown in FIG. 7 is comprised of 24 segments 8 each with 4×4 reaction vessel holders 12, while the segments 8 are in turn connected by means of thermally insulating webs 24.
  • [0056]
    In the reaction vessel receiving element 9 shown in FIG. 8, each segment 8 has only a single reaction vessel holder 12.
  • [0057]
    For the relatively finely sub-divided reaction vessel receiving elements 9 it is expedient to integrate temperature sensors in the thermocycling device. These temperature sensors sense the temperatures of the individual segments, so that the temperature of the segments 8 is regulated in a closed control loop on the basis of the temperature values determined by the temperature sensors.
  • [0058]
    Infrared sensors may for example be used as temperature sensors, located e.g. in the cover. With this sensor arrangement it is possible to sense the temperature of the reaction mixture directly.
  • [0059]
    FIG. 9 shows a reaction vessel receiving element 9 with six segments 8, rectangular in plan view, and a segment 8 a in the form of a double cross formed by three intersecting rows of reaction vessel holders 12. The six rectangular segments 8 are each separated from the next rectangular segment by a row or column of reaction vessel holders. This segmentation is especially advantageous for the third operating mode described above, since the rectangular segments 8 are not in contact with one another and may therefore be actuated simultaneously as desired, with only the segment 8 a in the form of a double cross not being actuated.
  • [0060]
    The segments 8 of the reaction vessel receiving element 9 are made from a metal with good heat conducting properties, e.g. aluminium. The materials described above as non-heat conducting materials or thermally insulating materials are either plastics or ceramics.
  • [0061]
    A further embodiment of the device according to the invention is shown in FIG. 11. In this embodiment the individual segments 8 b of the reaction vessel receiving element 9 are fixed in position by means of a clamping frame 25 (FIG. 10).
  • [0062]
    The clamping frame 25 is grid-shaped and formed by longitudinal ties 26 and cross ties, wherein the ties 26, 27 span openings. Through these openings extend the reaction vessel holders 12 of the segments 8 b. In the present embodiment, the ties 26, 27 are for instance in positive contact with the reaction vessel holders 12 and with the base plate 11 which protrudes from the reaction vessel holders. The 25 is provided with holes 28, through which pass bolts 29 for fixing the clamping frame to a thermocycling device 1.
  • [0063]
    Located below each of the segments 8 b is a separately actuable Peltier element 7 and a cooling element 30 which extends over the area of all the segments 8 b. Located in each case between the cooling element 30 and the Peltier element 7, and between the Peltier element 7 and the respective segment 8 b is a heat conducting foil 31. The cooling element 30 is provided with holes through which extend the bolts 29, each fixed by a nut 32 to the side of the cooling element 30 facing away from the reaction vessel receiving element 9.
  • [0064]
    The clamping frame 25 is made from a non heat conducting material, in particular POM or polycarbonate. It therefore allows a fixing of the segments 8 b of the reaction vessel receiving element 9 wherein the individual elements between the segments 8 b and the cooling element 30 are under tension, thereby ensuring good heat transfer in the vertical direction between the individual elements. Since the clamping frame itself has poor heat conducting properties, the heat transfer between two adjacent segments 8 b is kept low. For further reduction of heat transfer between two adjacent segments, the surfaces of the clamping frame 25 in contact with the segments 8 b may be provided with narrow webs, so that in the areas adjoining the webs, air gaps are formed between the clamping frame 25 and the segments 8 b.
  • [0065]
    In the embodiment shown in FIG. 11, a so-called heat pipe 33 is fitted between every two rows of reaction vessel holders 12. Such a heat pipe is distributed for example by the company THERMACORE INTERNATIONAL, Inc., USA. It is comprised of a gastight jacket, in which there is only a small amount of fluid. The pressure in the heat pipe is so low that the fluid is in a state of equilibrium between the liquid and the gaseous aggregate state, and consequently evaporates at a warmer section of the heat pipe and condenses at a cooler section. By this means, the temperature between the individual sections is equalised. The fluid used is, for example, water or freon.
  • [0066]
    Through integration of such a heat pipe in the segments 8 b of the reaction vessel receiving element 9, a temperature equalisation is effected over the segment 8 b. By this means it is ensured that the same temperature is present over the whole segment 8 b.
  • [0067]
    A further embodiment of the thermocycling device 1 according to the invention is shown in FIG. 12. The design of this thermocycling device 1 is similar to that of FIG. 11, therefore similar parts have been given the same reference numbers.
  • [0068]
    The segments 8 c of this thermocycling device 1, however, have no heat pipe. Instead of heat pipes, a temperature equalisation plate 34 is provided in the area beneath each of the segments 8 c. These temperature equalisation plates 34 are flat elements with a surface corresponding to the basic surface of one of the segments 8 c. These temperature equalisation plates 34 are hollow bodies with a small amount of fluid, and work on the same principle as the heat pipes. By this means it is once again ensured that there are no temperature variations within a segment 8 c.
  • [0069]
    The temperature equalisation plate may however be made from materials with very good heat conducting properties, such as e.g. copper. Additional heating and/or cooling elements, e.g. heating foils, heating coils or Peltier elements, may be integrated in such a temperature equalisation plate. The heating and cooling elements support homogeneity and permit more rapid heating and/or cooling rates. A Peltier element, which generally does not have an even temperature distribution, is preferably combined with a flat heating element.
  • [0070]
    The invention is described above with the aid of embodiments with 96 recesses for receiving a microtiter plate with 96 reaction vessels. The invention is not however limited to this number of recesses. Thus for example the reaction vessel receiving element may also have 384 recesses to receive a corresponding microtiter plate. With regard to features of the invention not explained in detail above, express reference is made to the claims and the drawing.
  • [0071]
    In the embodiments described above, a cooling device with a fluid cooling medium is used. Within the scope of the invention it is also possible to use a gaseous cooling medium, in particular air cooling, instead of a fluid cooling medium.
  • [0072]
    The reaction vessel receiving elements described above are comprised of a base plate with roughly tubular reaction vessel holders. Within the scope of the invention it is also possible to use a metal block, in which recesses to receive the reaction vessels of the microtiter plate are made.
  • List of References
  • [0000]
    • 1 thermocycling device 25 clamping frame
    • 2 housing 26 longitudinal tie
    • 3 bottom 27 cross tie
    • 4 side wall 28 hole
    • 5 intermediate wall 29 bolt
    • 5 a base 30 cooling element
    • 6 heat exchanger 31 heat conducting foil
    • 7 Peltier element 32 nut
    • 8 segment 33 heat pipe
    • 8 a segment in the form of a 34 temperature equalisation plate double cross
    • 9 reaction vessel receiving element
    • 10 segment element
    • 11 base plate
    • 12 reaction vessel holder
    • 13 first control unit
    • 14 cooling circuit
    • 15 second control unit
    • 16 central control unit
    • 17 cover
    • 18 heating element
    • 19 control valve
    • 20 side edge
    • 21 slot
    • 22 ties
    • 23 hook element
    • 24 web
Citations de brevets
Brevet cité Date de dépôt Date de publication Déposant Titre
US3036893 *14 mars 196029 mai 1962Scientific IndustriesAutomatic chemical analyzer
US3128239 *29 juin 19627 avr. 1964Robert Z PageBiological detection equipment
US3216804 *31 janv. 19629 nov. 1965Scientific IndustriesAutomatic chemical analyzer and sample dispenser
US3260413 *31 août 196412 juil. 1966Scientific IndustriesAutomatic chemical analyzer
US3573747 *24 févr. 19696 avr. 1971Institutional Networks CorpInstinet communication system for effectuating the sale or exchange of fungible properties between subscribers
US3581072 *28 mars 196825 mai 1971Frederick NymeyerAuction market computation system
US4412287 *15 sept. 198225 oct. 1983Braddock Iii Walter DAutomated stock exchange
US4674044 *30 janv. 198516 juin 1987Merrill Lynch, Pierce, Fenner & Smith, Inc.Automated securities trading system
US4677552 *5 oct. 198430 juin 1987Sibley Jr H CInternational commodity trade exchange
US4789928 *30 janv. 19876 déc. 1988Flex Japan Inc.Auction information transmission processing
US4799156 *1 oct. 198617 janv. 1989Strategic Processing CorporationInteractive market management system
US4823265 *11 mai 198718 avr. 1989Nelson George ERenewable option accounting and marketing system
US4864516 *10 mars 19865 sept. 1989International Business Machines CorporationMethod for implementing an on-line presentation in an information processing system
US4903201 *3 nov. 198320 févr. 1990World Energy Exchange CorporationAutomated futures trading exchange
US5038852 *14 mars 199013 août 1991Cetus CorporationApparatus and method for performing automated amplification of nucleic acid sequences and assays using heating and cooling steps
US5061630 *12 mai 198929 oct. 1991Agrogen Foundation, Seyffer & Co. & Ulrich C. KnopfLaboratory apparatus for optional temperature-controlled heating and cooling
US5063507 *14 sept. 19905 nov. 1991Plains Cotton Cooperative AssociationGoods database employing electronic title or documentary-type title
US5077665 *25 mai 198931 déc. 1991Reuters LimitedDistributed matching system
US5101353 *31 mai 198931 mars 1992Lattice Investments, Inc.Automated system for providing liquidity to securities markets
US5136501 *26 mai 19894 août 1992Reuters LimitedAnonymous matching system
US5168446 *23 mai 19891 déc. 1992Telerate Systems IncorporatedSystem for conducting and processing spot commodity transactions
US5205200 *9 janv. 199227 avr. 1993Wright John JHydraulic booster device for linear actuator
US5243515 *30 oct. 19907 sept. 1993Lee Wayne MSecure teleprocessing bidding system
US5258908 *2 nov. 19902 nov. 1993Foreign Exchange Transaction Services, Inc.Detection and prevention of duplicate trading transactions over a communications network
US5280422 *5 nov. 199018 janv. 1994Watlow/Winona, Inc.Method and apparatus for calibrating and controlling multiple heaters
US5297031 *6 mars 199022 mars 1994Chicago Board Of TradeMethod and apparatus for order management by market brokers
US5297032 *1 févr. 199122 mars 1994Merrill Lynch, Pierce, Fenner & Smith IncorporatedSecurities trading workstation
US5305200 *2 nov. 199019 avr. 1994Foreign Exchange Transaction Services, Inc.Financial exchange system having automated recovery/rollback of unacknowledged orders
US5325297 *25 juin 199228 juin 1994System Of Multiple-Colored Images For Internationally Listed Estates, Inc.Computer implemented method and system for storing and retrieving textual data and compressed image data
US5329589 *3 juin 199312 juil. 1994At&T Bell LaboratoriesMediation of transactions by a communications system
US5375055 *3 févr. 199220 déc. 1994Foreign Exchange Transaction Services, Inc.Credit management for electronic brokerage system
US5394324 *8 déc. 199328 févr. 1995Xerox CorporationAuction-based control system for energy resource management in a building
US5426281 *29 oct. 199320 juin 1995Abecassis; MaxTransaction protection system
US5475610 *20 avr. 199212 déc. 1995The Perkin-Elmer CorporationThermal cycler for automatic performance of the polymerase chain reaction with close temperature control
US5485510 *1 sept. 199416 janv. 1996At&T Corp.Secure credit/debit card authorization
US5553145 *4 août 19953 sept. 1996Micali; SilviaSimultaneous electronic transactions with visible trusted parties
US5557728 *22 nov. 199417 sept. 1996International Business Machines CorporationAutomated image retrieval and scaling into windowed displays
US5596994 *2 mai 199428 janv. 1997Bro; William L.Automated and interactive behavioral and medical guidance system
US5598557 *22 sept. 199228 janv. 1997Caere CorporationApparatus and method for retrieving and grouping images representing text files based on the relevance of key words extracted from a selected file to the text files
US5601141 *13 oct. 199211 févr. 1997Intelligent Automation Systems, Inc.High throughput thermal cycler
US5640569 *28 avr. 199517 juin 1997Sun Microsystems, Inc.Diverse goods arbitration system and method for allocating resources in a distributed computer system
US5657389 *8 mai 199512 août 1997Image Data, LlcPositive identification system and method
US5664115 *7 juin 19952 sept. 1997Fraser; RichardInteractive computer system to match buyers and sellers of real estate, businesses and other property using the internet
US5689652 *27 avr. 199518 nov. 1997Optimark Technologies, Inc.Crossing network utilizing optimal mutual satisfaction density profile
US5694546 *31 mai 19942 déc. 1997Reisman; Richard R.System for automatic unattended electronic information transport between a server and a client by a vendor provided transport software with a manifest list
US5706457 *7 juin 19956 janv. 1998Hughes ElectronicsImage display and archiving system and method
US5710889 *7 juin 199520 janv. 1998Citibank, N.A.Interface device for electronically integrating global financial services
US5715314 *24 oct. 19943 févr. 1998Open Market, Inc.Network sales system
US5715402 *9 nov. 19953 févr. 1998Spot Metals OnlineMethod and system for matching sellers and buyers of spot metals
US5717989 *13 oct. 199410 févr. 1998Full Service Trade System Ltd.Full service trade system
US5722418 *30 sept. 19943 mars 1998Bro; L. WilliamMethod for mediating social and behavioral processes in medicine and business through an interactive telecommunications guidance system
US5727165 *27 déc. 199410 mars 1998Reuters LimitedOffer matching system having timed match acknowledgment
US5771291 *11 déc. 199523 juin 1998Newton; FarrellUser identification and authentication system using ultra long identification keys and ultra large databases of identification keys for secure remote terminal access to a host computer
US5771380 *7 oct. 199623 juin 1998Hitachi, Ltd.Method for information retrieval with scaled down images
US5790790 *24 oct. 19964 août 1998Tumbleweed Software CorporationElectronic document delivery system in which notification of said electronic document is sent to a recipient thereof
US5794219 *20 févr. 199611 août 1998Health Hero Network, Inc.Method of conducting an on-line auction with bid pooling
US5799285 *30 août 199625 août 1998Klingman; Edwin E.Secure system for electronic selling
US5803500 *27 mars 19978 sept. 1998Mossberg; Bjoern E. F.Method and kit for conducting an auction
US5818914 *27 mars 19956 oct. 1998Aucnet Inc.Auction information transmission processing system
US5819842 *18 août 199513 oct. 1998Potter; Derek HenryMethod and apparatus for temperature control of multiple samples
US5826244 *23 août 199520 oct. 1998Xerox CorporationMethod and system for providing a document service over a computer network using an automated brokered auction
US5835896 *29 mars 199610 nov. 1998Onsale, Inc.Method and system for processing and transmitting electronic auction information
US5845265 *7 nov. 19951 déc. 1998Mercexchange, L.L.C.Consignment nodes
US5845266 *12 déc. 19951 déc. 1998Optimark Technologies, Inc.Crossing network utilizing satisfaction density profile with price discovery features
US5850442 *26 mars 199615 déc. 1998Entegrity Solutions CorporationSecure world wide electronic commerce over an open network
US5872848 *18 févr. 199716 févr. 1999ArcanvsMethod and apparatus for witnessed authentication of electronic documents
US5873069 *13 oct. 199516 févr. 1999American Tv & Appliance Of Madison, Inc.System and method for automatic updating and display of retail prices
US5884056 *28 déc. 199516 mars 1999International Business Machines CorporationMethod and system for video browsing on the world wide web
US5890138 *26 août 199630 mars 1999Bid.Com International Inc.Computer auction system
US5905974 *13 déc. 199618 mai 1999Cantor Fitzgerald SecuritiesAutomated auction protocol processor
US5905975 *2 janv. 199718 mai 1999Ausubel; Lawrence M.Computer implemented methods and apparatus for auctions
US5922074 *28 févr. 199713 juil. 1999Xcert Software, Inc.Method of and apparatus for providing secure distributed directory services and public key infrastructure
US5924072 *6 janv. 199713 juil. 1999Electronic Data Systems CorporationKnowledge management system and method
US5926794 *6 mars 199620 juil. 1999Alza CorporationVisual rating system and method
US5974412 *24 sept. 199726 oct. 1999Sapient Health NetworkIntelligent query system for automatically indexing information in a database and automatically categorizing users
US5991739 *24 nov. 199723 nov. 1999Food.ComInternet online order method and apparatus
US6035402 *20 déc. 19967 mars 2000Gte Cybertrust Solutions IncorporatedVirtual certificate authority
US6044363 *2 sept. 199728 mars 2000Hitachi, Ltd.Automatic auction method
US6047264 *8 oct. 19964 avr. 2000Onsale, Inc.Method for supplying automatic status updates using electronic mail
US6047274 *13 févr. 19984 avr. 2000Geophonic Networks, Inc.Bidding for energy supply
US6055518 *12 nov. 199625 avr. 2000At&T CorporationSecure auction systems
US6058417 *23 oct. 19982 mai 2000Ebay Inc.Information presentation and management in an online trading environment
US6061448 *1 avr. 19979 mai 2000Tumbleweed Communications Corp.Method and system for dynamic server document encryption
US6073117 *13 mars 19986 juin 2000Kabushiki Kaisha ToshibaMutual credit server apparatus and a distributed mutual credit system
US6085176 *8 mars 19994 juil. 2000Mercexchange, LlcMethod and apparatus for using search agents to search plurality of markets for items
US6104815 *9 janv. 199815 août 2000Silicon Gaming, Inc.Method and apparatus using geographical position and universal time determination means to provide authenticated, secure, on-line communication between remote gaming locations
US6119137 *30 janv. 199712 sept. 2000Tumbleweed Communications Corp.Distributed dynamic document conversion server
US6178408 *14 juil. 199923 janv. 2001Recot, Inc.Method of redeeming collectible points
US6192407 *4 avr. 199720 févr. 2001Tumbleweed Communications Corp.Private, trackable URLs for directed document delivery
US6202051 *19 févr. 199913 mars 2001Merc Exchange LlcFacilitating internet commerce through internetworked auctions
US6243691 *29 mars 19965 juin 2001Onsale, Inc.Method and system for processing and transmitting electronic auction information
US7340429 *28 mars 20014 mars 2008Ebay Inc.Method and system to enable a fixed price purchase within a online auction environment
US20040241048 *30 mai 20032 déc. 2004Applera CorporationThermal cycling apparatus and method for providing thermal uniformity
US20050273417 *4 juin 20048 déc. 2005Budish Eric BSystem and method for conducting electronic commerce
US20060015436 *30 sept. 200419 janv. 2006Trading Technologies International, Inc.System and method for facilitating trading of multiple tradeable objects in an electronic trading environment
US20060259406 *3 mai 200616 nov. 2006Trading Technologies International, Inc.System and method for performing automatic spread trading
US20060259409 *3 mai 200616 nov. 2006Trading Technologies International, Inc.System and method for estimating a spread value
US20070088654 *20 déc. 200619 avr. 2007Ebay Inc.Methods and machine readable mediums to enable a fixed price purchase within an online auction environment
US20080015971 *11 juil. 200717 janv. 2008Ebay Inc.Dual purchase process within an online auction environment
Référencé par
Brevet citant Date de dépôt Date de publication Déposant Titre
US945735112 mars 20144 oct. 2016Applied Biosystems, LlcDevice for carrying out chemical or biological reactions
Classifications
Classification aux États-Unis435/91.2
Classification internationaleB01L7/04, C12M1/38, C12P19/34, B01J19/00, B01L7/00, F25B21/02, C12M1/00
Classification coopérativeB01L2300/0829, B01L7/54, B01L2300/1822, B01L7/52, B01L2200/147
Classification européenneB01L7/52