US20100120100A1 - Device For The Carrying Out of Chemical or Biological Reactions - Google Patents
Device For The Carrying Out of Chemical or Biological ReactionsDownload PDFInfo
- Publication number
- US20100120100A1 US20100120100A1US12/689,214US68921410AUS2010120100A1US 20100120100 A1US20100120100 A1US 20100120100A1US 68921410 AUS68921410 AUS 68921410AUS 2010120100 A1US2010120100 A1US 2010120100A1
- Authority
- US
- United States
- Prior art keywords
- temperature
- segments
- reaction vessel
- segment
- heating
- 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.)
- Abandoned
Links
Images
Classifications
- 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 inventionrelates to a device for the carrying out of chemical or biological reactions with
- thermocyclersor 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.
- a device of this kindis known from U.S. Pat. No. 5,525,300.
- This devicehas four reaction vessel receiving elements, each with recesses arranged in a regular pattern.
- the pattern of the recessescorresponds 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.
- the heating and cooling devices of a reaction vessel receiving elementare 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.
- This temperature gradientis used to determine the optimal denaturing temperature, the optimal annealing temperature and the optimal elongation temperature of a PCR reaction.
- the same reaction mixtureis poured into the individual reaction vessels, and the temperature cycles necessary to perform the PCR reaction are executed.
- Such a temperature cyclecomprises 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 kindis repeated several times, leading to amplification of a predetermined DNA sequence.
- thermoelectricSince 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.
- the resultmay be optimised e.g. in respect of product volume or also product quality.
- the annealing temperatureat which the primer is added, has a powerful influence on the result.
- the elongation temperaturetoo can have beneficial or adverse effects on the result.
- the addition of the basesis accelerated, with the probability of errors increasing with higher temperature.
- the life of the polymeraseis shorter at a higher elongation temperature.
- thermocycling deviceby 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.
- Another important parameter for the success of a PCR reactionis the residence time at the individual temperatures for denaturing, annealing and elongation, and the rate of temperature change.
- these parameterscan 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.
- thermocycling deviceswith 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 testedmust be distributed over several microtiter plates, for testing independently of one another.
- thermocycling devices or a multiblock thermocycling deviceTo 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 deviceis costly and the carrying-out of several consecutive test series takes too long.
- handlingis 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.
- U.S. Pat. No. 5,819842discloses a device for the individual, controlled heating of several samples.
- This devicehas 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.
- a specially designed sample plateis placed on the work surface.
- This sample platehas 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 deviceis that no commonly available microtiter plate can be used.
- thermocyclersWith 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.
- the inventionis 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.
- the inventionis 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.
- the individual segments of the devicemay 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 inventionthus 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.
- thermocycling deviceis in particular suitable for optimising the multiplex PCR process, in which several different primers are used.
- FIG. 1a section through a device according to the invention for carrying out chemical or biological reactions in accordance with a first embodiment
- FIG. 2a section through an area of a device according to the invention for carrying out chemical or biological reactions in accordance with a second embodiment
- FIG. 3a schematic plan view of the device of FIG. 2 .
- FIG. 4a 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,
- FIGS. 6 to 9schematic plan views of reaction vessel receiving elements with differing segmentation
- FIG. 10a clamping frame in plan view
- FIG. 11a 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
- FIG. 12a 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 .
- FIG. 1shows a first embodiment of the device 1 according to the invention for carrying out chemical or biological reactions in a schematic sectional view.
- the devicehas 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.
- each of the bases 5 aMounted 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 6is 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 aare 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 devicehas altogether six such segment elements 10 .
- a heat conducting film or a heat conducting pastemay also be provided.
- Each of the segments 8 of the reaction vessel receiving element 9has a base plate 11 on which tubular, thin-walled reaction vessel holders 12 are integrally formed.
- 4 ⁇ 4 reaction vessel holders 12are arranged on a base plate 11 .
- the distance d between adjacent segments 8is 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 Dis chosen so that s standardised microtiter plate with its reaction vessels may be inserted in the reaction vessel holders 12 .
- the reaction vessel holders 12 of the device shown in FIG. 1form a grid with a total pf 96 reaction vessel holders, arranged in eight rows each with twelve reaction vessel holders 12 .
- the Peltier elements 7are each connected electrically to a first control unit 13 .
- Each of the heat exchangers 6is connected via a separate cooling circuit 14 to a second control unit 15 .
- the cooling medium usedis for example water, which is cooled in the cool temperature control unit before transfer to one of the heat exchangers 6 .
- the first control unit 13 and the second control unit 15are 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 .
- a cover 17Pivotably 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 18form 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.
- the segmentsare actuated with different temperatures, wherein the temperatures are so controlled that the temperature difference ⁇ T of adjacent segments 8 is less than a predetermined value K which amounts for example to 5°-15° C.
- Kwhich amounts for example to 5°-15° C.
- the value to be chosen for Kdepends on the quality of the thermal decoupling. The better the thermal decoupling, the greater the value which can be chosen for K.
- the temperature cycles input by the usermay 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.
- This second operating modemay 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 variedsuch 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.
- the segments 8In 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.
- the actuated segmentsare not influenced by the other segments, and their temperature may be set completely independently of the other actuated segments.
- the residence timesi.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.
- FIGS. 2 and 3A second embodiment of the device according to the invention is shown in FIGS. 2 and 3 .
- the basic designcorresponds to that of FIG. 1 , so that identical parts have been given the same reference number.
- the second embodimentdiffers 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.
- the individual segment elements 10are 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 2are made of a non heat conducting material.
- This embodimentmay 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 itform a part which may be handled separately during production and is bonded to the heating and cooling devices.
- FIGS. 4 and 5A third embodiment is shown schematically in FIGS. 4 and 5 .
- ties 22 of non heat conducting materialare 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 .
- hook elements 23On 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 8are offset relative to one another.
- the ties 22thus form a grid, into each of the openings of which a segment 8 may be inserted.
- This type of position fixingis 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.
- reaction vessel receiving elements 9Shown 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.
- the individual segments 8are joined by webs 24 of a thermally insulating material joined to form a single unit
- the ties 22are arranged between the side edges 20 of the base plates 11 , to which they are fixed for example by bonding.
- the segmentation of the reaction vessel receiving element of FIG. 6corresponds to that of the first and second embodiment ( FIG. 1-3 ), in which 4 ⁇ 4 reaction vessel holders are arranged on each segment 8 .
- the reaction vessel receiving element 9 shown in FIG. 7is 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 .
- each segment 8has only a single reaction vessel holder 12 .
- thermocycling deviceFor 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.
- Infrared sensorsmay 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.
- FIG. 9shows 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 8are 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.
- the segments 8 of the reaction vessel receiving element 9are made from a metal with good heat conducting properties, e.g. aluminium.
- the materials described above as non-heat conducting materials or thermally insulating materialsare either plastics or ceramics.
- FIG. 11A further embodiment of the device according to the invention is shown in FIG. 11 .
- the individual segments 8 b of the reaction vessel receiving element 9are fixed in position by means of a clamping frame 25 ( FIG. 10 ).
- the clamping frame 25is 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.
- the ties 26 , 27are 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 25is provided with holes 28 , through which pass bolts 29 for fixing the clamping frame to a thermocycling device 1 .
- each of the segments 8 bLocated 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 .
- the cooling element 30is 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 .
- the clamping frame 25is 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.
- a so-called heat pipe 33is fitted between every two rows of reaction vessel holders 12 .
- a heat pipeis 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 pipeis 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 usedis, for example, water or freon.
- thermocycling device 1A further embodiment of the thermocycling device 1 according to the invention is shown in FIG. 12 .
- the design of this thermocycling device 1is similar to that of FIG. 11 , therefore similar parts have been given the same reference numbers.
- thermocycling device 1has 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.
- the temperature equalisation platemay 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 elementssupport homogeneity and permit more rapid heating and/or cooling rates.
- a Peltier elementwhich generally does not have an even temperature distribution, is preferably combined with a flat heating element.
- reaction vessel receiving elementmay also have 384 recesses to receive a corresponding microtiter plate.
- a cooling device with a fluid cooling mediumis used.
- a gaseous cooling mediumin particular air cooling, instead of a fluid cooling medium.
- reaction vessel receiving elements described aboveare comprised of a base plate with roughly tubular reaction vessel holders.
- a metal blockin which recesses to receive the reaction vessels of the microtiter plate are made.
Landscapes
- 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)
Abstract
Description
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- To solve this problem the invention has the features specified in claim1. Advantageous developments thereof are set out in the additional claims.
- 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.
- 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.
- 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.
- The thermocycling device according to the invention is in particular suitable for optimising the multiplex PCR process, in which several different primers are used.
- 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.
- The invention is explained in detail below with the aid of the drawings. These show in:
FIG. 1 a section through a device according to the invention for carrying out chemical or biological reactions in accordance with a first embodiment,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,FIG. 3 a schematic plan view of the device ofFIG. 2 ,FIG. 4 a schematic plan view of a device according to a third embodiment, an area of the device ofFIG. 4 in a sectional view along the line A-A,FIGS. 6 to 9 schematic plan views of reaction vessel receiving elements with differing segmentationFIG. 10 a clamping frame in plan viewFIG. 11 a device according to the invention in which segments of a reaction vessel receiving element are fixed by the clamping frame according toFIG. 10 , andFIG. 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 toFIG. 10 .FIG. 1 shows a first embodiment of the device1 according to the invention for carrying out chemical or biological reactions in a schematic sectional view.- The device has a
housing 2 with abottom 3 andside walls 4. Located just above and parallel to thebottom 3 is anintermediate wall 5, on which are formedseveral bases 5a.In the embodiment shown inFIG. 1 , a total of sixbases 5aare provided, arranged in two rows of threebases 5aeach. - Mounted on each of the
bases 5ais aheat exchanger 6, aPeltier element 7 and asegment 8 of a reactionvessel receiving element 9. Theheat exchanger 6 is part of a cooling device and thePeltier element 7 is part of a combined heating and cooling device. The elements (heat exchanger, Peltier element, segment) mounted on thebases 5aare 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 asegment element 10. the device has altogether sixsuch segment elements 10. Instead of adhesive resin, a heat conducting film or a heat conducting paste may also be provided. - Each of the
segments 8 of the reactionvessel receiving element 9 has abase plate 11 on which tubular, thin-walledreaction vessel holders 12 are integrally formed. In the embodiment depicted inFIG. 1 , in eachcase 4×4reaction vessel holders 12 are arranged on abase plate 11. The distance d betweenadjacent segments 8 is such that thereaction vessel holders 12 of allsegments 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 thereaction vessel holders 12. - By providing the distance d between adjacent segments, an air gap which thermally decouples the
segments 8 andsegment elements 10 respectively is formed. - The
reaction vessel holders 12 of the device shown inFIG. 1 form a grid with a total pf 96 reaction vessel holders, arranged in eight rows each with twelvereaction vessel holders 12. - The
Peltier elements 7 are each connected electrically to afirst control unit 13. Each of theheat exchangers 6 is connected via aseparate cooling circuit 14 to asecond 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 theheat exchangers 6. - The
first control unit 13 and thesecond control unit 15 are connected to acentral control unit 16 which controls the temperature cycles to be implemented in the device. Inserted in each coolingcircuit 14 is acontrol valve 19, which is controlled by thecentral control unit 16 to open or close therespective cooling circuit 14. - Pivotably attached to the
housing 2 is acover 17 in whichadditional heating elements 18 in the form of Peltier elements, heating films or semiconductor heating elements may be located. Theheating elements 18 form cover heating elements, each assigned to asegment 8 and separately connected to thefirst control unit 13, so that eachheating element 18 may be individually actuated. - The mode of operation of the device according to the invention is explained in detail below.
- There are three modes of operation.
- 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.
- 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. - The temperature cycles input by the user may be distributed automatically by the
central control unit 16 to thesegments 8, so that the temperature differences between adjacent segments are kept as small as possible. - 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. - In the third operating mode, only part of the segments is actuated. In plan view (
FIG. 3 ,FIG. 4 ,FIGS. 6 to 9 ) thesegments 8 have side edges20. In this operating mode, thesegments 8 adjacent to the side edges of an actuatedsegment 8 are not actuated. If thesegments 8 themselves form a regular pattern (FIG. 3 ,FIG. 4 ,FIG. 6 ,FIG. 7 andFIG. 8 ), then the actuated segments are distributed in a chessboard pattern. In the embodiments shown inFIGS. 1 to 4 , three of the sixsegments 8 can be actuated, namely the two outer segments of one row and the middle segment of the other row. - 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.
- In this operating mode it may be expedient to heat the non-actuated segments8 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.
- A second embodiment of the device according to the invention is shown in
FIGS. 2 and 3 . the basic design corresponds to that ofFIG. 1 , so that identical parts have been given the same reference number. - The second embodiment differs from the first embodiment by virtue of the fact that the side edges20 of the
segments 8 adjacent to theside walls 4 of thehousing 2 engage in aslot 21 running round the inner face of theside walls 4, and are fixed therein for example by bonding. By this means theindividual segment elements 10 are fixed in space, thereby ensuring that despite the form of the gaps between thesegment elements 10, allreaction vessel holders 12 are arranged in the pattern of the reaction vessels of a microtiter plate. Theside walls 4 of thehousing 2 are made of a non heat conducting material. This embodiment may also be modified such that theslot 21 is introduced in a frame formed separately from thehousing 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. - A third embodiment is shown schematically in
FIGS. 4 and 5 . In this embodiment, ties22 of non heat conducting material are located somewhat below thebase plates 11 of thesegments 8 in the areas between thesegment elements 10 and between thesegment elements 10 and theside walls 4 of thehousing 2. On the side edges20 of thesegments 8 and of thebase plates 11 respectively are formedhook elements 23 which are bent downwards. Thesehook elements 23 engage in corresponding recesses of the ties22 (FIG. 5 ), thereby fixing thesegments 8 in their position. Thehook elements 23 ofadjacent segments 8 are offset relative to one another. Theties 22 thus form a grid, into each of the openings of which asegment 8 may be inserted. - This type of position fixing is very advantageous since the boundary areas between the
segments 8 and theties 22 are very small, so that heat transfer via theties 22 is correspondingly low. Moreover this arrangement is easy to realise even in the confined space conditions between adjacent segment elements. - Shown in schematic plan view in
FIGS. 6 to 9 are reactionvessel receiving elements 9 which represent further modifications of the device according to the invention. In these reactionvessel receiving elements 9, theindividual segments 8 are joined bywebs 24 of a thermally insulating material joined to form a single unit Theties 22 are arranged between the side edges20 of thebase plates 11, to which they are fixed for example by bonding. - 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 eachsegment 8. - The reaction
vessel receiving element 9 shown inFIG. 7 is comprised of24segments 8 each with 4×4reaction vessel holders 12, while thesegments 8 are in turn connected by means of thermally insulatingwebs 24. - In the reaction
vessel receiving element 9 shown inFIG. 8 , eachsegment 8 has only a singlereaction vessel holder 12. - 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 thesegments 8 is regulated in a closed control loop on the basis of the temperature values determined by the temperature sensors. - 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.
FIG. 9 shows a reactionvessel receiving element 9 with sixsegments 8, rectangular in plan view, and a segment8ain the form of a double cross formed by three intersecting rows ofreaction vessel holders 12. The sixrectangular 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 therectangular segments 8 are not in contact with one another and may therefore be actuated simultaneously as desired, with only the segment8ain the form of a double cross not being actuated.- The
segments 8 of the reactionvessel 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. - A further embodiment of the device according to the invention is shown in
FIG. 11 . In this embodiment theindividual segments 8bof the reactionvessel receiving element 9 are fixed in position by means of a clamping frame25 (FIG. 10 ). - The clamping
frame 25 is grid-shaped and formed bylongitudinal ties 26 and cross ties, wherein theties reaction vessel holders 12 of thesegments 8b.In the present embodiment, theties reaction vessel holders 12 and with thebase plate 11 which protrudes from the reaction vessel holders. The25 is provided withholes 28, through which passbolts 29 for fixing the clamping frame to a thermocycling device1. - Located below each of the
segments 8bis a separatelyactuable Peltier element 7 and acooling element 30 which extends over the area of all thesegments 8b. Located in each case between the coolingelement 30 and thePeltier element 7, and between thePeltier element 7 and therespective segment 8bis aheat conducting foil 31. Thecooling element 30 is provided with holes through which extend thebolts 29, each fixed by anut 32 to the side of thecooling element 30 facing away from the reactionvessel receiving element 9. - The clamping
frame 25 is made from a non heat conducting material, in particular POM or polycarbonate. It therefore allows a fixing of thesegments 8bof the reactionvessel receiving element 9 wherein the individual elements between thesegments 8band thecooling 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 twoadjacent segments 8bis kept low. For further reduction of heat transfer between two adjacent segments, the surfaces of the clampingframe 25 in contact with thesegments 8bmay be provided with narrow webs, so that in the areas adjoining the webs, air gaps are formed between the clampingframe 25 and thesegments 8b. - In the embodiment shown in
FIG. 11 , a so-calledheat pipe 33 is fitted between every two rows ofreaction 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. - Through integration of such a heat pipe in the
segments 8bof the reactionvessel receiving element 9, a temperature equalisation is effected over thesegment 8b. By this means it is ensured that the same temperature is present over thewhole segment 8b. - A further embodiment of the thermocycling device1 according to the invention is shown in
FIG. 12 . The design of this thermocycling device1 is similar to that ofFIG. 11 , therefore similar parts have been given the same reference numbers. - The
segments 8cof this thermocycling device1, however, have no heat pipe. Instead of heat pipes, atemperature equalisation plate 34 is provided in the area beneath each of thesegments 8c.Thesetemperature equalisation plates 34 are flat elements with a surface corresponding to the basic surface of one of thesegments 8c.Thesetemperature 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 asegment 8c. - 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.
- The invention is described above with the aid of embodiments with96 recesses for receiving a microtiter plate with96 reaction vessels. The invention is not however limited to this number of recesses. Thus for example the reaction vessel receiving element may also have384 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.
- 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.
- 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.
- 1
thermocycling device 25 clamping frame - 2
housing 26 longitudinal tie - 3 bottom27 cross tie
- 4
side wall 28 hole - 5
intermediate wall 29 bolt - 5a
base 30 cooling element - 6
heat exchanger 31 heat conducting foil - 7
Peltier element 32 nut - 8
segment 33 heat pipe - 8asegment in the form of a34 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
Claims (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 ofclaim 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 ofclaim 1 , wherein the segments are insulated from each other with an air gap formed between adjacent segments.
4. The method ofclaim 1 , wherein the segments are insulated from each other with a thermal insulator inserted in a gap between adjacent segments.
5. The method ofclaim 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 ofclaim 1 , wherein the reaction vessel receiving element is divided into at least four segments.
7. The method ofclaim 1 , wherein the individual segments each have a same number of reaction vessels.
8. The method ofclaim 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 ofclaim 1 , wherein each segment is assigned one or more temperature equalization elements.
10. The method ofclaim 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 ofclaim 1 , wherein the at least one parameter optimized includes at least one of denaturing temperature, annealing temperature, and elongation temperature.
12. The method ofclaim 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 ofclaim 1 , wherein the at least one parameter optimized comprises rate of temperature change.
14. The method ofclaim 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.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12/689,214US20100120100A1 (en) | 1999-10-01 | 2010-01-18 | Device For The Carrying Out of Chemical or Biological Reactions |
| US13/471,380US8721972B2 (en) | 1999-10-01 | 2012-05-14 | Device for the carrying out of chemical or biological reactions |
| US14/042,069US9914125B2 (en) | 1999-10-01 | 2013-09-30 | Device for the carrying out of chemical or biological reactions |
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE29917313UDE29917313U1 (en) | 1999-10-01 | 1999-10-01 | Device for carrying out chemical or biological reactions |
| DE29917313.5 | 1999-10-01 | ||
| PCT/EP2000/009569WO2001024930A1 (en) | 1999-10-01 | 2000-09-29 | Device for carrying out chemical or biological reactions |
| EPPCT/EP00/09569 | 2000-09-29 | ||
| US8913602A | 2002-12-23 | 2002-12-23 | |
| US12/689,214US20100120100A1 (en) | 1999-10-01 | 2010-01-18 | Device For The Carrying Out of Chemical or Biological Reactions |
Related Parent Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US10089136Continuation | 2000-09-29 | ||
| PCT/EP2000/009569ContinuationWO2001024930A1 (en) | 1999-10-01 | 2000-09-29 | Device for carrying out chemical or biological reactions |
| US8913602AContinuation | 1999-10-01 | 2002-12-23 |
Related Child Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US13/471,380ContinuationUS8721972B2 (en) | 1999-10-01 | 2012-05-14 | Device for the carrying out of chemical or biological reactions |
| US14/042,069ContinuationUS9914125B2 (en) | 1999-10-01 | 2013-09-30 | Device for the carrying out of chemical or biological reactions |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US20100120100A1true US20100120100A1 (en) | 2010-05-13 |
Family
ID=8079714
Family Applications (6)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US11/651,985Expired - Fee RelatedUS7611674B2 (en) | 1999-10-01 | 2007-01-11 | Device for the carrying out of chemical or biological reactions |
| US11/651,986AbandonedUS20070110634A1 (en) | 1999-10-01 | 2007-01-11 | Device for the carrying out of chemical or biological reactions |
| US12/689,214AbandonedUS20100120100A1 (en) | 1999-10-01 | 2010-01-18 | Device For The Carrying Out of Chemical or Biological Reactions |
| US12/689,212Expired - Fee RelatedUS8389288B2 (en) | 1999-10-01 | 2010-01-18 | Device for the carrying out of chemical or biological reactions |
| US13/471,380Expired - Fee RelatedUS8721972B2 (en) | 1999-10-01 | 2012-05-14 | Device for the carrying out of chemical or biological reactions |
| US14/042,069Expired - Fee RelatedUS9914125B2 (en) | 1999-10-01 | 2013-09-30 | Device for the carrying out of chemical or biological reactions |
Family Applications Before (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US11/651,985Expired - Fee RelatedUS7611674B2 (en) | 1999-10-01 | 2007-01-11 | Device for the carrying out of chemical or biological reactions |
| US11/651,986AbandonedUS20070110634A1 (en) | 1999-10-01 | 2007-01-11 | Device for the carrying out of chemical or biological reactions |
Family Applications After (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US12/689,212Expired - Fee RelatedUS8389288B2 (en) | 1999-10-01 | 2010-01-18 | Device for the carrying out of chemical or biological reactions |
| US13/471,380Expired - Fee RelatedUS8721972B2 (en) | 1999-10-01 | 2012-05-14 | Device for the carrying out of chemical or biological reactions |
| US14/042,069Expired - Fee RelatedUS9914125B2 (en) | 1999-10-01 | 2013-09-30 | Device for the carrying out of chemical or biological reactions |
Country Status (9)
| Country | Link |
|---|---|
| US (6) | US7611674B2 (en) |
| EP (1) | EP1216098B1 (en) |
| JP (1) | JP2003511221A (en) |
| KR (1) | KR100696138B1 (en) |
| AT (1) | ATE245487T1 (en) |
| AU (1) | AU774199B2 (en) |
| DE (2) | DE29917313U1 (en) |
| NO (1) | NO20021340L (en) |
| WO (1) | WO2001024930A1 (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012075360A1 (en) | 2010-12-03 | 2012-06-07 | Idaho Technology, Inc. | Thermal cycler apparatus and related methods |
| US9457351B2 (en) | 2002-12-23 | 2016-10-04 | Applied Biosystems, Llc | Device for carrying out chemical or biological reactions |
| US9914125B2 (en) | 1999-10-01 | 2018-03-13 | Applied Biosystems, Llc | Device for the carrying out of chemical or biological reactions |
| US10137452B2 (en) | 2010-04-09 | 2018-11-27 | Life Technologies Corporation | Thermal uniformity for thermal cycler instrumentation using dynamic control |
| US10471431B2 (en) | 2014-02-18 | 2019-11-12 | Life Technologies Corporation | Apparatuses, systems and methods for providing scalable thermal cyclers and isolating thermoelectric devices |
| US10512915B2 (en) | 2010-05-07 | 2019-12-24 | Hitachi High-Technologies Corporation | Nucleic acid amplifier and nucleic acid inspection device employing the same |
| US10835901B2 (en) | 2013-09-16 | 2020-11-17 | Life Technologies Corporation | Apparatuses, systems and methods for providing thermocycler thermal uniformity |
| US12427525B2 (en) | 2019-01-17 | 2025-09-30 | Invitros Co., Ltd. | Gene amplification module |
Families Citing this family (65)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7133726B1 (en)* | 1997-03-28 | 2006-11-07 | Applera Corporation | Thermal cycler for PCR |
| AU2002230524A1 (en) | 2000-11-16 | 2002-05-27 | California Institute Of Technology | Apparatus and methods for conducting assays and high throughput screening |
| DE10062889A1 (en)* | 2000-12-12 | 2002-06-27 | Eppendorf Ag | Laboratory temperature control device for temperature control at different temperatures |
| DE10062890A1 (en)* | 2000-12-12 | 2002-06-27 | Eppendorf Ag | Laboratory temperature control device for temperature control of reaction samples |
| EP1228804B1 (en)* | 2001-02-05 | 2005-11-23 | Eppendorf Ag | Device for tempering reaction samples |
| AU2002307152A1 (en) | 2001-04-06 | 2002-10-21 | California Institute Of Technology | Nucleic acid amplification utilizing microfluidic devices |
| JP4639558B2 (en)* | 2001-09-07 | 2011-02-23 | 株式会社島津製作所 | Microwell chip |
| WO2003085379A2 (en) | 2002-04-01 | 2003-10-16 | Fluidigm Corporation | Microfluidic particle-analysis systems |
| DE10221763A1 (en)* | 2002-05-15 | 2003-12-04 | Eppendorf Ag | Thermal cycler with temperature control block controlled in cycles |
| GB0219393D0 (en)* | 2002-08-20 | 2002-09-25 | Quanta Biotech Ltd | Control apparatus |
| GB0221167D0 (en)* | 2002-09-12 | 2002-10-23 | Quanta Biotech Ltd | Control apparatus |
| JP2006501056A (en) | 2002-09-25 | 2006-01-12 | カリフォルニア インスティテュート オブ テクノロジー | Micro fluid large scale integration |
| EP1546412B1 (en) | 2002-10-02 | 2014-05-21 | California Institute Of Technology | Microfluidic nucleic acid analysis |
| US7604965B2 (en) | 2003-04-03 | 2009-10-20 | Fluidigm Corporation | Thermal reaction device and method for using the same |
| JP4705035B2 (en)* | 2003-05-23 | 2011-06-22 | バイオ−ラッド ラボラトリーズ，インコーポレイティド | Localized temperature control for spatial arrangement of reaction medium |
| US20040241048A1 (en)* | 2003-05-30 | 2004-12-02 | Applera Corporation | Thermal cycling apparatus and method for providing thermal uniformity |
| NL1024578C2 (en)* | 2003-10-21 | 2005-04-22 | Univ Delft Tech | Device for carrying out a reaction. |
| US20060030036A1 (en) | 2004-05-28 | 2006-02-09 | Victor Joseph | Chips for multiplex analyses |
| US7799283B2 (en)* | 2004-11-12 | 2010-09-21 | Ortho-Clinical Diagnostics, Inc. | Heating and cooling multiple containers or multi-chamber containers |
| EP1710017B1 (en)* | 2005-04-04 | 2012-12-19 | Roche Diagnostics GmbH | Thermocycling of a block comprising multiple samples |
| JP4630786B2 (en)* | 2005-10-04 | 2011-02-09 | キヤノン株式会社 | Biochemical treatment apparatus, DNA amplification and purification apparatus, and DNA testing apparatus including the apparatus |
| DE102006004157A1 (en)* | 2006-01-30 | 2007-08-02 | Eppendorf Ag | Device for incubating cells, comprises a sterile or sterilizable portable container, which encloses an integrated- and/or culture container for the reception of the cells, and an arrangement having a sterile filter and incubator |
| EP2535427A3 (en)* | 2006-05-17 | 2013-04-24 | California Institute of Technology | Thermal cycling system |
| US8232091B2 (en) | 2006-05-17 | 2012-07-31 | California Institute Of Technology | Thermal cycling system |
| EP2057435A4 (en)† | 2006-06-23 | 2011-04-20 | Life Technologies Corp | Systems and methods for cooling in biological analysis instruments |
| DE102007003754A1 (en)* | 2007-01-19 | 2008-07-24 | Eppendorf Ag | Temperature control device with calibration device |
| JP2010516281A (en) | 2007-01-22 | 2010-05-20 | ウェハージェン，インコーポレイテッド | High-throughput chemical reaction equipment |
| US9475051B2 (en) | 2007-02-27 | 2016-10-25 | Sony Corporation | Nucleic acid amplifier |
| CN101641150B (en)* | 2007-03-23 | 2014-05-07 | 皇家飞利浦电子股份有限公司 | Integrated microfluidic device with reduced peak power |
| DE202007018930U1 (en)* | 2007-11-28 | 2009-11-19 | Nickl, Julius, Dr. | Thermal oscillation for the cyclic tempering of biological medical and chemical samples |
| JP4544335B2 (en) | 2008-04-15 | 2010-09-15 | ソニー株式会社 | Reaction processing equipment |
| JP2009254260A (en)* | 2008-04-15 | 2009-11-05 | Sony Corp | Reaction treatment device |
| DE102008023660B4 (en)* | 2008-04-21 | 2010-02-11 | Hirt Zerspanungstechnik Gmbh | Device for heating an object by means of a water bath |
| WO2012033396A1 (en)* | 2008-12-18 | 2012-03-15 | Universiti Sains Malaysia | A disposable multiplex polymerase chain reaction (pcr) chip and device |
| CN103675303B (en) | 2010-07-23 | 2016-02-03 | 贝克曼考尔特公司 | Sensing system |
| DE102010040685A1 (en)* | 2010-09-14 | 2012-03-15 | Hamilton Bonaduz Ag | Temperature control device for the thermal consolidation of drug beads |
| JP5689274B2 (en)* | 2010-10-05 | 2015-03-25 | 株式会社日立ハイテクノロジーズ | Nucleic acid test apparatus and container transport method |
| US8945843B2 (en)* | 2010-12-09 | 2015-02-03 | Analogic Corporation | Thermocooler with thermal breaks that thermally isolate a thermocycling region from at least one guard heat region |
| JP2011160811A (en)* | 2011-05-20 | 2011-08-25 | Sony Corp | Reaction treatment device |
| JP5759818B2 (en)* | 2011-07-25 | 2015-08-05 | 株式会社日立ハイテクノロジーズ | Nucleic acid testing equipment |
| KR20140091032A (en) | 2011-11-07 | 2014-07-18 | 베크만 컬터, 인코포레이티드 | Magnetic damping for specimen transport system |
| CN104040357B (en) | 2011-11-07 | 2016-11-23 | 贝克曼考尔特公司 | Halver system and workflow |
| CN104105969B (en) | 2011-11-07 | 2016-10-12 | 贝克曼考尔特公司 | Centrifuge system and workflow |
| WO2013070754A1 (en) | 2011-11-07 | 2013-05-16 | Beckman Coulter, Inc. | Robotic arm |
| BR112014011043A2 (en) | 2011-11-07 | 2017-06-13 | Beckman Coulter Inc | specimen container detection |
| BR112014010955A2 (en) | 2011-11-07 | 2017-06-06 | Beckman Coulter Inc | system and method for processing samples |
| DE102011119174A1 (en) | 2011-11-23 | 2013-05-23 | Inheco Industrial Heating And Cooling Gmbh | Vapor Chamber |
| JP5801334B2 (en)* | 2013-03-08 | 2015-10-28 | 株式会社日立ハイテクノロジーズ | Nucleic acid amplification apparatus and nucleic acid test apparatus using the same |
| US20140338860A1 (en)* | 2013-05-17 | 2014-11-20 | Anthony Walter Demsia | Combination Vessel Holder for Heat Block Incubation |
| GB201319759D0 (en) | 2013-11-08 | 2013-12-25 | Thomsen Lars | Device and method for heating a fluid chamber |
| CN103642683A (en)* | 2013-12-19 | 2014-03-19 | 江苏金太生命科技有限公司 | Polymerase chain reaction (PCR) instrument capable of performing multiple PCR experiments |
| GB201401584D0 (en)* | 2014-01-29 | 2014-03-19 | Bg Res Ltd | Intelligent detection of biological entities |
| DE102014018308A1 (en)* | 2014-12-10 | 2016-06-16 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Temperature control body for a multiwell plate and method and apparatus for freezing and / or thawing biological samples |
| EP3259602B9 (en) | 2015-02-20 | 2021-05-19 | Takara Bio USA, Inc. | Method for rapid accurate dispensing, visualization and analysis of single cells |
| SG10201700260XA (en)* | 2016-06-10 | 2018-01-30 | Star Array Pte Ltd | Rapid thermal cycling for sample analyses and processing |
| US11460405B2 (en) | 2016-07-21 | 2022-10-04 | Takara Bio Usa, Inc. | Multi-Z imaging and dispensing with multi-well devices |
| CN106244447A (en)* | 2016-07-29 | 2016-12-21 | 车团结 | A kind of Polymerized human serum albumin and temperature control system thereof |
| CN106047688A (en)* | 2016-07-29 | 2016-10-26 | 车团结 | PCR (polymerase chain reaction) instrument and temperature control system for same |
| EP3552707B1 (en)* | 2016-09-01 | 2020-10-21 | Roche Diagnostics GmbH | Assembly, instrument for performing a temperature-dependent reaction and method for performing a temperature-dependent reaction in an assembly |
| US10427162B2 (en) | 2016-12-21 | 2019-10-01 | Quandx Inc. | Systems and methods for molecular diagnostics |
| GB2576304B (en)* | 2018-07-26 | 2020-09-09 | Evonetix Ltd | Accessing data storage provided using double-stranded nucleic acid molecules |
| EP3941634A4 (en)* | 2019-03-18 | 2023-01-11 | Seegene, Inc. | Thermal cycler comprising sample holder assembly |
| KR102821325B1 (en)* | 2019-12-16 | 2025-06-13 | 주식회사 코사이언스 | Portable lamp pcr device for diagnosis of molecular of genome |
| CN112604616A (en)* | 2020-11-17 | 2021-04-06 | 华东师范大学 | Automatic control system and method for continuous synthesis of microchemical reaction and online monitoring |
| MX2024003654A (en) | 2021-09-23 | 2024-06-19 | N6 Tec Inc | Methods and systems for sample analysis. |
Citations (95)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3036893A (en)* | 1960-03-14 | 1962-05-29 | Scientific Industries | Automatic chemical analyzer |
| US3128239A (en)* | 1962-06-29 | 1964-04-07 | Robert Z Page | Biological detection equipment |
| US3216804A (en)* | 1962-01-31 | 1965-11-09 | Scientific Industries | Automatic chemical analyzer and sample dispenser |
| US3260413A (en)* | 1964-08-31 | 1966-07-12 | Scientific Industries | Automatic chemical analyzer |
| US3573747A (en)* | 1969-02-24 | 1971-04-06 | Institutional Networks Corp | Instinet communication system for effectuating the sale or exchange of fungible properties between subscribers |
| US3581072A (en)* | 1968-03-28 | 1971-05-25 | Frederick Nymeyer | Auction market computation system |
| US4412287A (en)* | 1975-05-29 | 1983-10-25 | Braddock Iii Walter D | Automated stock exchange |
| US4674044A (en)* | 1985-01-30 | 1987-06-16 | Merrill Lynch, Pierce, Fenner & Smith, Inc. | Automated securities trading system |
| US4677552A (en)* | 1984-10-05 | 1987-06-30 | Sibley Jr H C | International commodity trade exchange |
| US4789928A (en)* | 1986-02-17 | 1988-12-06 | Flex Japan Inc. | Auction information transmission processing |
| US4799156A (en)* | 1986-10-01 | 1989-01-17 | Strategic Processing Corporation | Interactive market management system |
| US4823265A (en)* | 1987-05-11 | 1989-04-18 | Nelson George E | Renewable option accounting and marketing system |
| US4864516A (en)* | 1986-03-10 | 1989-09-05 | International Business Machines Corporation | Method for implementing an on-line presentation in an information processing system |
| US4903201A (en)* | 1983-11-03 | 1990-02-20 | World Energy Exchange Corporation | Automated futures trading exchange |
| US5038852A (en)* | 1986-02-25 | 1991-08-13 | Cetus Corporation | Apparatus and method for performing automated amplification of nucleic acid sequences and assays using heating and cooling steps |
| US5061630A (en)* | 1988-05-13 | 1991-10-29 | Agrogen Foundation, Seyffer & Co. & Ulrich C. Knopf | Laboratory apparatus for optional temperature-controlled heating and cooling |
| US5063507A (en)* | 1990-09-14 | 1991-11-05 | Plains Cotton Cooperative Association | Goods database employing electronic title or documentary-type title |
| US5077665A (en)* | 1989-05-25 | 1991-12-31 | Reuters Limited | Distributed matching system |
| US5101353A (en)* | 1989-05-31 | 1992-03-31 | Lattice Investments, Inc. | Automated system for providing liquidity to securities markets |
| US5136501A (en)* | 1989-05-26 | 1992-08-04 | Reuters Limited | Anonymous matching system |
| US5168446A (en)* | 1989-05-23 | 1992-12-01 | Telerate Systems Incorporated | System for conducting and processing spot commodity transactions |
| US5205200A (en)* | 1990-07-26 | 1993-04-27 | Wright John J | Hydraulic booster device for linear actuator |
| US5243515A (en)* | 1990-10-30 | 1993-09-07 | Lee Wayne M | Secure teleprocessing bidding system |
| US5258908A (en)* | 1990-11-02 | 1993-11-02 | Foreign Exchange Transaction Services, Inc. | Detection and prevention of duplicate trading transactions over a communications network |
| US5280422A (en)* | 1990-11-05 | 1994-01-18 | Watlow/Winona, Inc. | Method and apparatus for calibrating and controlling multiple heaters |
| US5297031A (en)* | 1990-03-06 | 1994-03-22 | Chicago Board Of Trade | Method and apparatus for order management by market brokers |
| US5297032A (en)* | 1991-02-01 | 1994-03-22 | Merrill Lynch, Pierce, Fenner & Smith Incorporated | Securities trading workstation |
| US5305200A (en)* | 1990-11-02 | 1994-04-19 | Foreign Exchange Transaction Services, Inc. | Financial exchange system having automated recovery/rollback of unacknowledged orders |
| US5325297A (en)* | 1992-06-25 | 1994-06-28 | System Of Multiple-Colored Images For Internationally Listed Estates, Inc. | Computer implemented method and system for storing and retrieving textual data and compressed image data |
| US5329589A (en)* | 1991-02-27 | 1994-07-12 | At&T Bell Laboratories | Mediation of transactions by a communications system |
| US5375055A (en)* | 1992-02-03 | 1994-12-20 | Foreign Exchange Transaction Services, Inc. | Credit management for electronic brokerage system |
| US5394324A (en)* | 1993-12-08 | 1995-02-28 | Xerox Corporation | Auction-based control system for energy resource management in a building |
| US5426281A (en)* | 1991-08-22 | 1995-06-20 | Abecassis; Max | Transaction protection system |
| US5475610A (en)* | 1990-11-29 | 1995-12-12 | The Perkin-Elmer Corporation | Thermal cycler for automatic performance of the polymerase chain reaction with close temperature control |
| US5485510A (en)* | 1992-09-29 | 1996-01-16 | At&T Corp. | Secure credit/debit card authorization |
| US5553145A (en)* | 1995-03-21 | 1996-09-03 | Micali; Silvia | Simultaneous electronic transactions with visible trusted parties |
| US5557728A (en)* | 1991-08-15 | 1996-09-17 | International Business Machines Corporation | Automated image retrieval and scaling into windowed displays |
| US5596994A (en)* | 1993-08-30 | 1997-01-28 | Bro; William L. | Automated and interactive behavioral and medical guidance system |
| US5598557A (en)* | 1992-09-22 | 1997-01-28 | Caere Corporation | Apparatus 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 |
| US5601141A (en)* | 1992-10-13 | 1997-02-11 | Intelligent Automation Systems, Inc. | High throughput thermal cycler |
| US5640569A (en)* | 1995-04-28 | 1997-06-17 | Sun Microsystems, Inc. | Diverse goods arbitration system and method for allocating resources in a distributed computer system |
| US5657389A (en)* | 1995-05-08 | 1997-08-12 | Image Data, Llc | Positive identification system and method |
| US5664115A (en)* | 1995-06-07 | 1997-09-02 | Fraser; Richard | Interactive computer system to match buyers and sellers of real estate, businesses and other property using the internet |
| US5689652A (en)* | 1995-04-27 | 1997-11-18 | Optimark Technologies, Inc. | Crossing network utilizing optimal mutual satisfaction density profile |
| US5694546A (en)* | 1994-05-31 | 1997-12-02 | Reisman; 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 |
| US5706457A (en)* | 1995-06-07 | 1998-01-06 | Hughes Electronics | Image display and archiving system and method |
| US5710889A (en)* | 1995-02-22 | 1998-01-20 | Citibank, N.A. | Interface device for electronically integrating global financial services |
| US5715314A (en)* | 1994-10-24 | 1998-02-03 | Open Market, Inc. | Network sales system |
| US5715402A (en)* | 1995-11-09 | 1998-02-03 | Spot Metals Online | Method and system for matching sellers and buyers of spot metals |
| US5717989A (en)* | 1994-10-13 | 1998-02-10 | Full Service Trade System Ltd. | Full service trade system |
| US5727165A (en)* | 1990-12-17 | 1998-03-10 | Reuters Limited | Offer matching system having timed match acknowledgment |
| US5771291A (en)* | 1995-12-11 | 1998-06-23 | Newton; Farrell | User 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 |
| US5771380A (en)* | 1993-02-23 | 1998-06-23 | Hitachi, Ltd. | Method for information retrieval with scaled down images |
| US5790790A (en)* | 1996-10-24 | 1998-08-04 | Tumbleweed Software Corporation | Electronic document delivery system in which notification of said electronic document is sent to a recipient thereof |
| US5794219A (en)* | 1996-02-20 | 1998-08-11 | Health Hero Network, Inc. | Method of conducting an on-line auction with bid pooling |
| US5799285A (en)* | 1996-06-07 | 1998-08-25 | Klingman; Edwin E. | Secure system for electronic selling |
| US5803500A (en)* | 1997-03-27 | 1998-09-08 | Mossberg; Bjoern E. F. | Method and kit for conducting an auction |
| US5818914A (en)* | 1994-12-07 | 1998-10-06 | Aucnet Inc. | Auction information transmission processing system |
| US5819842A (en)* | 1991-12-05 | 1998-10-13 | Potter; Derek Henry | Method and apparatus for temperature control of multiple samples |
| US5826244A (en)* | 1995-08-23 | 1998-10-20 | Xerox Corporation | Method and system for providing a document service over a computer network using an automated brokered auction |
| US5835896A (en)* | 1996-03-29 | 1998-11-10 | Onsale, Inc. | Method and system for processing and transmitting electronic auction information |
| US5845266A (en)* | 1995-12-12 | 1998-12-01 | Optimark Technologies, Inc. | Crossing network utilizing satisfaction density profile with price discovery features |
| US5845265A (en)* | 1995-04-26 | 1998-12-01 | Mercexchange, L.L.C. | Consignment nodes |
| US5850442A (en)* | 1996-03-26 | 1998-12-15 | Entegrity Solutions Corporation | Secure world wide electronic commerce over an open network |
| US5872848A (en)* | 1997-02-18 | 1999-02-16 | Arcanvs | Method and apparatus for witnessed authentication of electronic documents |
| US5873069A (en)* | 1995-10-13 | 1999-02-16 | American Tv & Appliance Of Madison, Inc. | System and method for automatic updating and display of retail prices |
| US5884056A (en)* | 1995-12-28 | 1999-03-16 | International Business Machines Corporation | Method and system for video browsing on the world wide web |
| US5890138A (en)* | 1996-08-26 | 1999-03-30 | Bid.Com International Inc. | Computer auction system |
| US5905974A (en)* | 1996-12-13 | 1999-05-18 | Cantor Fitzgerald Securities | Automated auction protocol processor |
| US5905975A (en)* | 1996-01-04 | 1999-05-18 | Ausubel; Lawrence M. | Computer implemented methods and apparatus for auctions |
| US5924072A (en)* | 1997-01-06 | 1999-07-13 | Electronic Data Systems Corporation | Knowledge management system and method |
| US5922074A (en)* | 1997-02-28 | 1999-07-13 | Xcert Software, Inc. | Method of and apparatus for providing secure distributed directory services and public key infrastructure |
| US5926794A (en)* | 1996-03-06 | 1999-07-20 | Alza Corporation | Visual rating system and method |
| US5974412A (en)* | 1997-09-24 | 1999-10-26 | Sapient Health Network | Intelligent query system for automatically indexing information in a database and automatically categorizing users |
| US5991739A (en)* | 1997-11-24 | 1999-11-23 | Food.Com | Internet online order method and apparatus |
| US6035402A (en)* | 1996-12-20 | 2000-03-07 | Gte Cybertrust Solutions Incorporated | Virtual certificate authority |
| US6044363A (en)* | 1996-09-04 | 2000-03-28 | Hitachi, Ltd. | Automatic auction method |
| US6047274A (en)* | 1997-02-24 | 2000-04-04 | Geophonic Networks, Inc. | Bidding for energy supply |
| US6047264A (en)* | 1996-08-08 | 2000-04-04 | Onsale, Inc. | Method for supplying automatic status updates using electronic mail |
| US6055518A (en)* | 1996-02-01 | 2000-04-25 | At&T Corporation | Secure auction systems |
| US6058417A (en)* | 1998-10-23 | 2000-05-02 | Ebay Inc. | Information presentation and management in an online trading environment |
| US6061448A (en)* | 1997-04-01 | 2000-05-09 | Tumbleweed Communications Corp. | Method and system for dynamic server document encryption |
| US6073117A (en)* | 1997-03-18 | 2000-06-06 | Kabushiki Kaisha Toshiba | Mutual credit server apparatus and a distributed mutual credit system |
| US6085176A (en)* | 1995-04-26 | 2000-07-04 | Mercexchange, Llc | Method and apparatus for using search agents to search plurality of markets for items |
| US6104815A (en)* | 1997-01-10 | 2000-08-15 | Silicon Gaming, Inc. | Method and apparatus using geographical position and universal time determination means to provide authenticated, secure, on-line communication between remote gaming locations |
| US6119137A (en)* | 1997-01-30 | 2000-09-12 | Tumbleweed Communications Corp. | Distributed dynamic document conversion server |
| US6178408B1 (en)* | 1999-07-14 | 2001-01-23 | Recot, Inc. | Method of redeeming collectible points |
| US6192407B1 (en)* | 1996-10-24 | 2001-02-20 | Tumbleweed Communications Corp. | Private, trackable URLs for directed document delivery |
| US6243691B1 (en)* | 1996-03-29 | 2001-06-05 | Onsale, Inc. | Method and system for processing and transmitting electronic auction information |
| US20040241048A1 (en)* | 2003-05-30 | 2004-12-02 | Applera Corporation | Thermal cycling apparatus and method for providing thermal uniformity |
| US20050273417A1 (en)* | 2004-06-04 | 2005-12-08 | Budish Eric B | System and method for conducting electronic commerce |
| US20060015436A1 (en)* | 2002-11-13 | 2006-01-19 | Trading Technologies International, Inc. | System and method for facilitating trading of multiple tradeable objects in an electronic trading environment |
| US20060259409A1 (en)* | 2002-03-05 | 2006-11-16 | Trading Technologies International, Inc. | System and method for estimating a spread value |
| US20060259406A1 (en)* | 2002-03-05 | 2006-11-16 | Trading Technologies International, Inc. | System and method for performing automatic spread trading |
| US20070088654A1 (en)* | 2000-10-23 | 2007-04-19 | Ebay Inc. | Methods and machine readable mediums to enable a fixed price purchase within an online auction environment |
Family Cites Families (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3063893A (en)* | 1959-11-24 | 1962-11-13 | Kenya Pyrethrum Board | Stabilized pyrethrum compositions |
| US3261668A (en) | 1962-08-14 | 1966-07-19 | Scientific Industries | Chemical analyzer tape |
| US3271112A (en) | 1962-12-12 | 1966-09-06 | Donald L Williams | Apparatus for laboratory testing |
| US3368872A (en) | 1964-08-31 | 1968-02-13 | Scientific Industries | Automatic chemical analyzer |
| DE3265723D1 (en) | 1982-03-18 | 1985-10-03 | Turgut Koruk | Quantized (digital) heating plate |
| US5333675C1 (en) | 1986-02-25 | 2001-05-01 | Perkin Elmer Corp | Apparatus and method for performing automated amplification of nucleic acid sequences and assays using heating and cooling steps |
| US5656493A (en) | 1985-03-28 | 1997-08-12 | The Perkin-Elmer Corporation | System for automated performance of the polymerase chain reaction |
| CA1339653C (en)* | 1986-02-25 | 1998-02-03 | Larry J. Johnson | Appartus and method for performing automated amplification of nucleic acid sequences and assays using heating and cooling steps |
| GB8814962D0 (en)* | 1988-06-23 | 1988-07-27 | Lep Scient Ltd | Biochemical reaction machine |
| US4865986A (en)* | 1988-10-06 | 1989-09-12 | Coy Corporation | Temperature control apparatus |
| DE8814398U1 (en) | 1988-11-17 | 1989-02-16 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften eV, 3400 Göttingen | Thermostat device |
| US4950608A (en)* | 1989-04-25 | 1990-08-21 | Scinics Co., Ltd. | Temperature regulating container |
| US5504007A (en) | 1989-05-19 | 1996-04-02 | Becton, Dickinson And Company | Rapid thermal cycle apparatus |
| DE4029004C1 (en)* | 1990-09-13 | 1992-04-02 | Max-Planck-Gesellschaft Zur Foerderung Der Wissenschaften Ev, 3400 Goettingen, De | |
| US5994056A (en) | 1991-05-02 | 1999-11-30 | Roche Molecular Systems, Inc. | Homogeneous methods for nucleic acid amplification and detection |
| DE4234086A1 (en) | 1992-02-05 | 1993-08-12 | Diagen Inst Molekularbio | METHOD FOR DETERMINING NUCLEIC ACID SEQUENCES AMPLIFIED IN VITRO |
| US5441576A (en)* | 1993-02-01 | 1995-08-15 | Bierschenk; James L. | Thermoelectric cooler |
| US5525300A (en)* | 1993-10-20 | 1996-06-11 | Stratagene | Thermal cycler including a temperature gradient block |
| DE4435107C1 (en)* | 1994-09-30 | 1996-04-04 | Biometra Biomedizinische Analy | Miniaturized flow thermal cycler |
| US6825047B1 (en) | 1996-04-03 | 2004-11-30 | Applera Corporation | Device and method for multiple analyte detection |
| US5802856A (en)* | 1996-07-31 | 1998-09-08 | Stanford University | Multizone bake/chill thermal cycling module |
| DE19646115C2 (en)* | 1996-11-08 | 2000-05-25 | Eppendorf Geraetebau Netheler | Use of temperature control devices for temperature control of a temperature control block |
| DE29623597U1 (en)* | 1996-11-08 | 1999-01-07 | Eppendorf - Netheler - Hinz Gmbh, 22339 Hamburg | Temperature control block with temperature control devices |
| EP2913109A1 (en)* | 1997-03-28 | 2015-09-02 | Applera Corporation | Assembly for thermal cycler for PCR |
| US6106784A (en)* | 1997-09-26 | 2000-08-22 | Applied Chemical & Engineering Systems, Inc. | Thawing station |
| US6558947B1 (en) | 1997-09-26 | 2003-05-06 | Applied Chemical & Engineering Systems, Inc. | Thermal cycler |
| AU9786798A (en)* | 1997-10-10 | 1999-05-03 | Biosepra Inc. | Aligned multiwell multiplate stack and method for processing biological/chemicalsamples using the same |
| US6093370A (en)* | 1998-06-11 | 2000-07-25 | Hitachi, Ltd. | Polynucleotide separation method and apparatus therefor |
| US6633785B1 (en) | 1999-08-31 | 2003-10-14 | Kabushiki Kaisha Toshiba | Thermal cycler and DNA amplifier method |
| DE29917313U1 (en) | 1999-10-01 | 2001-02-15 | MWG-BIOTECH AG, 85560 Ebersberg | Device for carrying out chemical or biological reactions |
| GB2366628B (en)* | 2000-09-11 | 2002-09-18 | Bookham Technology Plc | Method and apparatus for temperature control |
| US7727479B2 (en) | 2000-09-29 | 2010-06-01 | Applied Biosystems, Llc | Device for the carrying out of chemical or biological reactions |
| DE10221763A1 (en) | 2002-05-15 | 2003-12-04 | Eppendorf Ag | Thermal cycler with temperature control block controlled in cycles |
| US8676383B2 (en) | 2002-12-23 | 2014-03-18 | Applied Biosystems, Llc | Device for carrying out chemical or biological reactions |
| US7122799B2 (en) | 2003-12-18 | 2006-10-17 | Palo Alto Research Center Incorporated | LED or laser enabled real-time PCR system and spectrophotometer |
| WO2006002403A1 (en) | 2004-06-23 | 2006-01-05 | Applera Corporation | Thermal cycler |
| WO2011127386A2 (en) | 2010-04-09 | 2011-10-13 | Life Technologies Corporation | Improved thermal uniformity for thermal cycler instrumentation using dynamic control |
- 1999
- 1999-10-01DEDE29917313Upatent/DE29917313U1/ennot_activeExpired - Lifetime
- 2000
- 2000-09-29ATAT00966090Tpatent/ATE245487T1/ennot_activeIP Right Cessation
- 2000-09-29JPJP2001527919Apatent/JP2003511221A/enactivePending
- 2000-09-29WOPCT/EP2000/009569patent/WO2001024930A1/enactiveIP Right Grant
- 2000-09-29DEDE50003023Tpatent/DE50003023D1/ennot_activeExpired - Lifetime
- 2000-09-29EPEP00966090Apatent/EP1216098B1/ennot_activeExpired - Lifetime
- 2000-09-29AUAU76605/00Apatent/AU774199B2/ennot_activeCeased
- 2000-09-29KRKR1020027003719Apatent/KR100696138B1/ennot_activeExpired - Fee Related
- 2002
- 2002-03-18NONO20021340Apatent/NO20021340L/ennot_activeApplication Discontinuation
- 2007
- 2007-01-11USUS11/651,985patent/US7611674B2/ennot_activeExpired - Fee Related
- 2007-01-11USUS11/651,986patent/US20070110634A1/ennot_activeAbandoned
- 2010
- 2010-01-18USUS12/689,214patent/US20100120100A1/ennot_activeAbandoned
- 2010-01-18USUS12/689,212patent/US8389288B2/ennot_activeExpired - Fee Related
- 2012
- 2012-05-14USUS13/471,380patent/US8721972B2/ennot_activeExpired - Fee Related
- 2013
- 2013-09-30USUS14/042,069patent/US9914125B2/ennot_activeExpired - Fee Related
Patent Citations (99)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3036893A (en)* | 1960-03-14 | 1962-05-29 | Scientific Industries | Automatic chemical analyzer |
| US3216804A (en)* | 1962-01-31 | 1965-11-09 | Scientific Industries | Automatic chemical analyzer and sample dispenser |
| US3128239A (en)* | 1962-06-29 | 1964-04-07 | Robert Z Page | Biological detection equipment |
| US3260413A (en)* | 1964-08-31 | 1966-07-12 | Scientific Industries | Automatic chemical analyzer |
| US3581072A (en)* | 1968-03-28 | 1971-05-25 | Frederick Nymeyer | Auction market computation system |
| US3573747A (en)* | 1969-02-24 | 1971-04-06 | Institutional Networks Corp | Instinet communication system for effectuating the sale or exchange of fungible properties between subscribers |
| US4412287A (en)* | 1975-05-29 | 1983-10-25 | Braddock Iii Walter D | Automated stock exchange |
| US4903201A (en)* | 1983-11-03 | 1990-02-20 | World Energy Exchange Corporation | Automated futures trading exchange |
| US4677552A (en)* | 1984-10-05 | 1987-06-30 | Sibley Jr H C | International commodity trade exchange |
| US4674044A (en)* | 1985-01-30 | 1987-06-16 | Merrill Lynch, Pierce, Fenner & Smith, Inc. | Automated securities trading system |
| US4789928A (en)* | 1986-02-17 | 1988-12-06 | Flex Japan Inc. | Auction information transmission processing |
| US5038852A (en)* | 1986-02-25 | 1991-08-13 | Cetus Corporation | Apparatus and method for performing automated amplification of nucleic acid sequences and assays using heating and cooling steps |
| US4864516A (en)* | 1986-03-10 | 1989-09-05 | International Business Machines Corporation | Method for implementing an on-line presentation in an information processing system |
| US4799156A (en)* | 1986-10-01 | 1989-01-17 | Strategic Processing Corporation | Interactive market management system |
| US4823265A (en)* | 1987-05-11 | 1989-04-18 | Nelson George E | Renewable option accounting and marketing system |
| US5061630A (en)* | 1988-05-13 | 1991-10-29 | Agrogen Foundation, Seyffer & Co. & Ulrich C. Knopf | Laboratory apparatus for optional temperature-controlled heating and cooling |
| US5168446A (en)* | 1989-05-23 | 1992-12-01 | Telerate Systems Incorporated | System for conducting and processing spot commodity transactions |
| US5077665A (en)* | 1989-05-25 | 1991-12-31 | Reuters Limited | Distributed matching system |
| US5136501A (en)* | 1989-05-26 | 1992-08-04 | Reuters Limited | Anonymous matching system |
| US5101353A (en)* | 1989-05-31 | 1992-03-31 | Lattice Investments, Inc. | Automated system for providing liquidity to securities markets |
| US5297031A (en)* | 1990-03-06 | 1994-03-22 | Chicago Board Of Trade | Method and apparatus for order management by market brokers |
| US5205200A (en)* | 1990-07-26 | 1993-04-27 | Wright John J | Hydraulic booster device for linear actuator |
| US5063507A (en)* | 1990-09-14 | 1991-11-05 | Plains Cotton Cooperative Association | Goods database employing electronic title or documentary-type title |
| US5243515A (en)* | 1990-10-30 | 1993-09-07 | Lee Wayne M | Secure teleprocessing bidding system |
| US5305200A (en)* | 1990-11-02 | 1994-04-19 | Foreign Exchange Transaction Services, Inc. | Financial exchange system having automated recovery/rollback of unacknowledged orders |
| US5258908A (en)* | 1990-11-02 | 1993-11-02 | Foreign Exchange Transaction Services, Inc. | Detection and prevention of duplicate trading transactions over a communications network |
| US5280422A (en)* | 1990-11-05 | 1994-01-18 | Watlow/Winona, Inc. | Method and apparatus for calibrating and controlling multiple heaters |
| US5475610A (en)* | 1990-11-29 | 1995-12-12 | The Perkin-Elmer Corporation | Thermal cycler for automatic performance of the polymerase chain reaction with close temperature control |
| US5727165A (en)* | 1990-12-17 | 1998-03-10 | Reuters Limited | Offer matching system having timed match acknowledgment |
| US5297032A (en)* | 1991-02-01 | 1994-03-22 | Merrill Lynch, Pierce, Fenner & Smith Incorporated | Securities trading workstation |
| US5329589A (en)* | 1991-02-27 | 1994-07-12 | At&T Bell Laboratories | Mediation of transactions by a communications system |
| US5557728A (en)* | 1991-08-15 | 1996-09-17 | International Business Machines Corporation | Automated image retrieval and scaling into windowed displays |
| US5426281A (en)* | 1991-08-22 | 1995-06-20 | Abecassis; Max | Transaction protection system |
| US5819842A (en)* | 1991-12-05 | 1998-10-13 | Potter; Derek Henry | Method and apparatus for temperature control of multiple samples |
| US5375055A (en)* | 1992-02-03 | 1994-12-20 | Foreign Exchange Transaction Services, Inc. | Credit management for electronic brokerage system |
| US5325297A (en)* | 1992-06-25 | 1994-06-28 | System Of Multiple-Colored Images For Internationally Listed Estates, Inc. | Computer implemented method and system for storing and retrieving textual data and compressed image data |
| US5598557A (en)* | 1992-09-22 | 1997-01-28 | Caere Corporation | Apparatus 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 |
| US5485510A (en)* | 1992-09-29 | 1996-01-16 | At&T Corp. | Secure credit/debit card authorization |
| US5601141A (en)* | 1992-10-13 | 1997-02-11 | Intelligent Automation Systems, Inc. | High throughput thermal cycler |
| US5771380A (en)* | 1993-02-23 | 1998-06-23 | Hitachi, Ltd. | Method for information retrieval with scaled down images |
| US5596994A (en)* | 1993-08-30 | 1997-01-28 | Bro; William L. | Automated and interactive behavioral and medical guidance system |
| US5722418A (en)* | 1993-08-30 | 1998-03-03 | Bro; L. William | Method for mediating social and behavioral processes in medicine and business through an interactive telecommunications guidance system |
| US5394324A (en)* | 1993-12-08 | 1995-02-28 | Xerox Corporation | Auction-based control system for energy resource management in a building |
| US5694546A (en)* | 1994-05-31 | 1997-12-02 | Reisman; 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 |
| US5717989A (en)* | 1994-10-13 | 1998-02-10 | Full Service Trade System Ltd. | Full service trade system |
| US5715314A (en)* | 1994-10-24 | 1998-02-03 | Open Market, Inc. | Network sales system |
| US5818914A (en)* | 1994-12-07 | 1998-10-06 | Aucnet Inc. | Auction information transmission processing system |
| US5710889A (en)* | 1995-02-22 | 1998-01-20 | Citibank, N.A. | Interface device for electronically integrating global financial services |
| US5553145A (en)* | 1995-03-21 | 1996-09-03 | Micali; Silvia | Simultaneous electronic transactions with visible trusted parties |
| US6085176A (en)* | 1995-04-26 | 2000-07-04 | Mercexchange, Llc | Method and apparatus for using search agents to search plurality of markets for items |
| US6202051B1 (en)* | 1995-04-26 | 2001-03-13 | Merc Exchange Llc | Facilitating internet commerce through internetworked auctions |
| US5845265A (en)* | 1995-04-26 | 1998-12-01 | Mercexchange, L.L.C. | Consignment nodes |
| US5689652A (en)* | 1995-04-27 | 1997-11-18 | Optimark Technologies, Inc. | Crossing network utilizing optimal mutual satisfaction density profile |
| US5640569A (en)* | 1995-04-28 | 1997-06-17 | Sun Microsystems, Inc. | Diverse goods arbitration system and method for allocating resources in a distributed computer system |
| US5657389A (en)* | 1995-05-08 | 1997-08-12 | Image Data, Llc | Positive identification system and method |
| US5706457A (en)* | 1995-06-07 | 1998-01-06 | Hughes Electronics | Image display and archiving system and method |
| US5664115A (en)* | 1995-06-07 | 1997-09-02 | Fraser; Richard | Interactive computer system to match buyers and sellers of real estate, businesses and other property using the internet |
| US5826244A (en)* | 1995-08-23 | 1998-10-20 | Xerox Corporation | Method and system for providing a document service over a computer network using an automated brokered auction |
| US5873069A (en)* | 1995-10-13 | 1999-02-16 | American Tv & Appliance Of Madison, Inc. | System and method for automatic updating and display of retail prices |
| US5715402A (en)* | 1995-11-09 | 1998-02-03 | Spot Metals Online | Method and system for matching sellers and buyers of spot metals |
| US5771291A (en)* | 1995-12-11 | 1998-06-23 | Newton; Farrell | User 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 |
| US5845266A (en)* | 1995-12-12 | 1998-12-01 | Optimark Technologies, Inc. | Crossing network utilizing satisfaction density profile with price discovery features |
| US5884056A (en)* | 1995-12-28 | 1999-03-16 | International Business Machines Corporation | Method and system for video browsing on the world wide web |
| US5905975A (en)* | 1996-01-04 | 1999-05-18 | Ausubel; Lawrence M. | Computer implemented methods and apparatus for auctions |
| US6055518A (en)* | 1996-02-01 | 2000-04-25 | At&T Corporation | Secure auction systems |
| US5794219A (en)* | 1996-02-20 | 1998-08-11 | Health Hero Network, Inc. | Method of conducting an on-line auction with bid pooling |
| US5926794A (en)* | 1996-03-06 | 1999-07-20 | Alza Corporation | Visual rating system and method |
| US5850442A (en)* | 1996-03-26 | 1998-12-15 | Entegrity Solutions Corporation | Secure world wide electronic commerce over an open network |
| US5835896A (en)* | 1996-03-29 | 1998-11-10 | Onsale, Inc. | Method and system for processing and transmitting electronic auction information |
| US6243691B1 (en)* | 1996-03-29 | 2001-06-05 | Onsale, Inc. | Method and system for processing and transmitting electronic auction information |
| US5799285A (en)* | 1996-06-07 | 1998-08-25 | Klingman; Edwin E. | Secure system for electronic selling |
| US6047264A (en)* | 1996-08-08 | 2000-04-04 | Onsale, Inc. | Method for supplying automatic status updates using electronic mail |
| US5890138A (en)* | 1996-08-26 | 1999-03-30 | Bid.Com International Inc. | Computer auction system |
| US6044363A (en)* | 1996-09-04 | 2000-03-28 | Hitachi, Ltd. | Automatic auction method |
| US6192407B1 (en)* | 1996-10-24 | 2001-02-20 | Tumbleweed Communications Corp. | Private, trackable URLs for directed document delivery |
| US5790790A (en)* | 1996-10-24 | 1998-08-04 | Tumbleweed Software Corporation | Electronic document delivery system in which notification of said electronic document is sent to a recipient thereof |
| US5905974A (en)* | 1996-12-13 | 1999-05-18 | Cantor Fitzgerald Securities | Automated auction protocol processor |
| US6035402A (en)* | 1996-12-20 | 2000-03-07 | Gte Cybertrust Solutions Incorporated | Virtual certificate authority |
| US5924072A (en)* | 1997-01-06 | 1999-07-13 | Electronic Data Systems Corporation | Knowledge management system and method |
| US6104815A (en)* | 1997-01-10 | 2000-08-15 | Silicon Gaming, Inc. | Method and apparatus using geographical position and universal time determination means to provide authenticated, secure, on-line communication between remote gaming locations |
| US6119137A (en)* | 1997-01-30 | 2000-09-12 | Tumbleweed Communications Corp. | Distributed dynamic document conversion server |
| US5872848A (en)* | 1997-02-18 | 1999-02-16 | Arcanvs | Method and apparatus for witnessed authentication of electronic documents |
| US6047274A (en)* | 1997-02-24 | 2000-04-04 | Geophonic Networks, Inc. | Bidding for energy supply |
| US5922074A (en)* | 1997-02-28 | 1999-07-13 | Xcert Software, Inc. | Method of and apparatus for providing secure distributed directory services and public key infrastructure |
| US6073117A (en)* | 1997-03-18 | 2000-06-06 | Kabushiki Kaisha Toshiba | Mutual credit server apparatus and a distributed mutual credit system |
| US5803500A (en)* | 1997-03-27 | 1998-09-08 | Mossberg; Bjoern E. F. | Method and kit for conducting an auction |
| US6061448A (en)* | 1997-04-01 | 2000-05-09 | Tumbleweed Communications Corp. | Method and system for dynamic server document encryption |
| US5974412A (en)* | 1997-09-24 | 1999-10-26 | Sapient Health Network | Intelligent query system for automatically indexing information in a database and automatically categorizing users |
| US5991739A (en)* | 1997-11-24 | 1999-11-23 | Food.Com | Internet online order method and apparatus |
| US6058417A (en)* | 1998-10-23 | 2000-05-02 | Ebay Inc. | Information presentation and management in an online trading environment |
| US6178408B1 (en)* | 1999-07-14 | 2001-01-23 | Recot, Inc. | Method of redeeming collectible points |
| US20070088654A1 (en)* | 2000-10-23 | 2007-04-19 | Ebay Inc. | Methods and machine readable mediums to enable a fixed price purchase within an online auction environment |
| US20080015971A1 (en)* | 2000-10-23 | 2008-01-17 | Ebay Inc. | Dual purchase process within an online auction environment |
| US7340429B2 (en)* | 2000-10-23 | 2008-03-04 | Ebay Inc. | Method and system to enable a fixed price purchase within a online auction environment |
| US20060259409A1 (en)* | 2002-03-05 | 2006-11-16 | Trading Technologies International, Inc. | System and method for estimating a spread value |
| US20060259406A1 (en)* | 2002-03-05 | 2006-11-16 | Trading Technologies International, Inc. | System and method for performing automatic spread trading |
| US20060015436A1 (en)* | 2002-11-13 | 2006-01-19 | Trading Technologies International, Inc. | System and method for facilitating trading of multiple tradeable objects in an electronic trading environment |
| US20040241048A1 (en)* | 2003-05-30 | 2004-12-02 | Applera Corporation | Thermal cycling apparatus and method for providing thermal uniformity |
| US20050273417A1 (en)* | 2004-06-04 | 2005-12-08 | Budish Eric B | System and method for conducting electronic commerce |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9914125B2 (en) | 1999-10-01 | 2018-03-13 | Applied Biosystems, Llc | Device for the carrying out of chemical or biological reactions |
| US9457351B2 (en) | 2002-12-23 | 2016-10-04 | Applied Biosystems, Llc | Device for carrying out chemical or biological reactions |
| US10137452B2 (en) | 2010-04-09 | 2018-11-27 | Life Technologies Corporation | Thermal uniformity for thermal cycler instrumentation using dynamic control |
| US10512915B2 (en) | 2010-05-07 | 2019-12-24 | Hitachi High-Technologies Corporation | Nucleic acid amplifier and nucleic acid inspection device employing the same |
| WO2012075360A1 (en) | 2010-12-03 | 2012-06-07 | Idaho Technology, Inc. | Thermal cycler apparatus and related methods |
| EP2646542A4 (en)* | 2010-12-03 | 2017-11-08 | BioFire Diagnostics, Inc. | Thermal cycler apparatus and related methods |
| US11376599B2 (en) | 2010-12-03 | 2022-07-05 | Biofire Defense, Llc | Thermal cycler apparatus and related methods |
| US10835901B2 (en) | 2013-09-16 | 2020-11-17 | Life Technologies Corporation | Apparatuses, systems and methods for providing thermocycler thermal uniformity |
| US10471431B2 (en) | 2014-02-18 | 2019-11-12 | Life Technologies Corporation | Apparatuses, systems and methods for providing scalable thermal cyclers and isolating thermoelectric devices |
| US12427525B2 (en) | 2019-01-17 | 2025-09-30 | Invitros Co., Ltd. | Gene amplification module |
Also Published As
| Publication number | Publication date |
|---|---|
| US20120264206A1 (en) | 2012-10-18 |
| US9914125B2 (en) | 2018-03-13 |
| US8389288B2 (en) | 2013-03-05 |
| KR100696138B1 (en) | 2007-03-20 |
| JP2003511221A (en) | 2003-03-25 |
| DE29917313U1 (en) | 2001-02-15 |
| US7611674B2 (en) | 2009-11-03 |
| KR20020038765A (en) | 2002-05-23 |
| ATE245487T1 (en) | 2003-08-15 |
| US20070110634A1 (en) | 2007-05-17 |
| NO20021340D0 (en) | 2002-03-18 |
| US20100120099A1 (en) | 2010-05-13 |
| DE50003023D1 (en) | 2003-08-28 |
| AU774199B2 (en) | 2004-06-17 |
| US20140030170A1 (en) | 2014-01-30 |
| EP1216098A1 (en) | 2002-06-26 |
| EP1216098B1 (en) | 2003-07-23 |
| AU7660500A (en) | 2001-05-10 |
| WO2001024930A1 (en) | 2001-04-12 |
| US8721972B2 (en) | 2014-05-13 |
| US20070140926A1 (en) | 2007-06-21 |
| NO20021340L (en) | 2002-03-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20100120100A1 (en) | Device For The Carrying Out of Chemical or Biological Reactions | |
| US7727479B2 (en) | Device for the carrying out of chemical or biological reactions | |
| EP0545736B1 (en) | Method and apparatus for temperature control of multiple samples | |
| US20070184548A1 (en) | Device for carrying out chemical or biological reactions | |
| US20080026483A1 (en) | Thermal-cycling devices and methods of using the same | |
| EP1510823B1 (en) | Performing polymerase chain reaction | |
| US9457351B2 (en) | Device for carrying out chemical or biological reactions | |
| EP0942781B1 (en) | Reaction vessels | |
| EP2076605B2 (en) | Cooling in a thermal cycler using heat pipes | |
| JP4550780B2 (en) | Temperature control for reactors with multiple vessels | |
| EP0542422A1 (en) | Multi-well microtiter plate | |
| US6640891B1 (en) | Rapid thermal cycling device | |
| CN105813754A (en) | Apparatus, system, and method for providing thermal uniformity to a thermal cycler | |
| US20120015365A1 (en) | Methods for Testing the Accuracy and Thermal Reliability of a PCR Thermal Cycler, and a Means for Implementing Said Methods | |
| US8722394B2 (en) | Laboratory apparatus with an arrangement for the tempering of samples and method of tempering samples | |
| EP3349902B1 (en) | System for biological analysis | |
| US20040001780A1 (en) | Laboratory apparatus fitted with wells and used for temperature-controlling specimens | |
| KR20130071645A (en) | Multiplex experiment device for separate temperature controlling | |
| AU741806B2 (en) | Thermal cycler for automatic performance of the polymerase chain reaction with close temperature control | |
| EP3344394B1 (en) | Thermal isolation of reaction sites on a substrate | |
| JP2002204961A (en) | Temperature adjustment apparatus for experiment for temperature adjustment of reaction sample |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| STCB | Information on status: application discontinuation | Free format text:ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |