EP2687294A1 - Rotor pour cycleur thermique et cycleur thermique - Google Patents

Rotor pour cycleur thermique et cycleur thermique Download PDF

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Publication number
EP2687294A1
EP2687294A1 EP12176913.7A EP12176913A EP2687294A1 EP 2687294 A1 EP2687294 A1 EP 2687294A1 EP 12176913 A EP12176913 A EP 12176913A EP 2687294 A1 EP2687294 A1 EP 2687294A1
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EP
European Patent Office
Prior art keywords
rotor
holding fixtures
thermal cycler
holding
fixtures
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP12176913.7A
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German (de)
English (en)
Inventor
Harald Quintel
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Qiagen Instruments AG
Original Assignee
Qiagen Instruments AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Qiagen Instruments AG filed Critical Qiagen Instruments AG
Priority to EP12176913.7A priority Critical patent/EP2687294A1/fr
Publication of EP2687294A1 publication Critical patent/EP2687294A1/fr
Withdrawn legal-status Critical Current

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • 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
    • B01L9/00—Supporting devices; Holding devices
    • B01L9/06—Test-tube stands; Test-tube holders
    • B01L9/065—Test-tube stands; Test-tube holders specially adapted for capillary tubes
    • 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
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0654—Lenses; Optical fibres
    • 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
    • B01L2300/0832—Geometry, shape and general structure cylindrical, tube shaped
    • 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
    • B01L2300/0832—Geometry, shape and general structure cylindrical, tube shaped
    • B01L2300/0841—Drums

Definitions

  • the invention pertains to the field of laboratory equipment for chemical, biological or for biotechnological methods which require handling of multiple vessels.
  • the invention relates to a rotor for a thermal cycler.
  • PCR polymerase chain reaction
  • PCR is a technique in molecular biology that allows polynucleotide sequences to be amplified.
  • the basic principle of PCR is well known in the art and is described in many books, including, PCR: A Practical Approach M. J. McPherson, et al., IRL Press (1991 ), PCR Protocols: A Guide to Methods and Applications by Innis, et al., Academic Press (1990 ), and PCR Technology: Principals and Applications for DNA Amplification H. A. Erlich, Stockton Press (1989 ).
  • PCR is also described in many U.S. patents, including U.S.
  • Each PCR cycle usually comprises three basic discrete temperature steps, a denaturation step, an annealing step and an extension step.
  • Denaturation of DNA typically takes place at around 90 to 95°C
  • annealing a primer to the denatured DNA is typically performed at around 40 to 60°C
  • the step of extending the annealed primers with a polymerase is typically performed at around 70 to 75°C. Therefore, during a PCR cycle the temperature of the reaction mixture must be varied repeatedly.
  • the PCR technique has a wide variety of biological applications, including but not limited to for example, DNA sequence analysis, probe generation, cloning of nucleic acid sequences, site-directed mutagenesis, detection of genetic mutations, diagnoses of viral infections, molecular "fingerprinting" and the monitoring of contaminating microorganisms in biological fluids and other sources.
  • the PCR is usually carried out in a laboratory apparatus called thermal cycler or PCR cycler.
  • thermal cyclers Different designs of such thermal cyclers are known including devices for the thermal cycling of multiple samples.
  • a common format of such devices uses a block of heat conductive material which has a plurality of channels or cavities for receiving vessels - such as reaction tubes or plates - in which the desired reactions are executed. Monitoring of temperature is relatively easy in such devices since a temperature sensor can be associated with the block.
  • thermal cyclers have been developed in which a plurality of containers for holding reaction mixture(s) are supported on a rotor which is rotated in a controlled temperature environment (also known as "Rotor-Gene"). Temperature cycling is effected by heating and cooling of the environment.
  • the rotor has apertures, receptacles or slots for the containers, vials or tubes located at a circumference of the rotor.
  • Rotors are known, which have 60 or 72 receptacles for a corresponding number of vials or tubes.
  • An example of such a device is disclosed, for example, in WO 98/49340 A1 .
  • the rotor disclosed in WO 98/49340 A1 consists of a high temperature plastic and can be driven by a motor which is controlled by a computer.
  • the rotor comprises a number of slots and glass capillary tubes positioned at the circumference of the rotor.
  • the glass capillary tubes contain a reaction mixture, especially for carrying out the polymerase chain reaction.
  • the rotor is rotated and the reaction mixtures are monitored by a real time fluorescence optical system and the resulting data transferred to a computer analysis.
  • the present invention seeks to solve the problem of providing an improved rotor and a thermal cycler.
  • a rotor for a thermal cycler providing an environment, wherein the rotor comprises holding fixtures each for holding a reaction container providing a micro-environment capable of being filled with a reaction mixture, wherein at least two fixtures are provided which have different distance from the axis of the rotor.
  • the amount of reaction mixture during one run relates to the number of micro-environments which can be monitored in one run.
  • the present invention provides a new approach by providing holding fixtures even in an inner area of the rotor. With regard to the arrangement of the holding fixtures, the common thinking was overcome that the fixtures and the respective micro-environments need to be positioned at the peripheral circumference.
  • a high speed thermal cycler can be realized with the high number of reaction containers which may be used in one run of the thermal cycleras the position of the holding fixtures is not limited to the peripheral circumference of the rotor. It allows an even higher number of reaction containers to be held or positioned in the rotor without increasing the diameter of the rotor. Thus, a high speed thermal cycler with a high capacity can be obtained, maintaining a small volume of the thermal cycler.
  • a "thermal cycler” is a laboratory apparatus or device for carrying out thermal cycles with regard to a reaction process, especially a polymerase chain reaction.
  • the thermal cycler is capable of raising and lowering the temperature of an environment in which micro-environments are provided in discrete, pre-determined steps.
  • thermal cycler is particularly directed to a thermal cycler for nucleic acid amplification, wherein the reaction vessels are supported on a rotatable circular carousel or rotor rotatably mounted within a chamber.
  • thermal cyclers are the Rotor-Gene TM family of thermocyclers manufactured and distributed by Qiagen GMBH ( www.qiagen.com ), most preferably the Rotor-Gene Q.
  • Other similar devices are disclosed in WO 92/20778 A1 and WO 98/49340 A1 .
  • thermal cyclers are also to be intended.
  • environment means any temperature-controlled environment established in a device, e.g. in a chamber of an apparatus. E.g. the temperature in said environment can be controlled for a process or a step within a process to be carried out at a specific temperature.
  • environment preferably refers to a heatable reaction chamber, especially preferred a heatable reaction chamber of a thermal cycler. Temperature cycling is achieved in a respective thermal cycler by heating and cooling the environment, here the (insulated) chamber.
  • micro-environment relates to a volume in which a reaction mixture can be filled.
  • the volume of the micro-environment is in the range of 0.01 to 2.0 ml, preferably 0.1 to 0.6 ml.
  • reaction mixture means an amount of liquid, solution or suspension intended to be subjected to qualitative or quantitative determination of any of its properties, such as the presence or absence of a component, the concentration of a component, etc.
  • the reaction mixture is subjected to cyclic heating and/or cooling, especially in accordance to carry out a polymerase chain reaction.
  • holding fixture is intended to encompass any form of a bore, aperture, slot, receptacle or opening which is capable for holding a reaction container or otherwise providing the micro-environment in which the reaction mixture can be filled.
  • reaction container is intended to encompass inter alia a vial, vessel, well, tube or any other container suitable for being filled with the reaction mixture.
  • rotor according to the invention is intended to encompass any disc, plate or device which may be rotated around an axis.
  • the term "circumference" according to the invention is intended to encompass the shape of a circle which surrounds the axisof the rotor.
  • the holding fixtures are preferably arranged such that the centers of the holding fixtures do not only lie on one circumference but on several different circumferences having a different distance to the axis of the rotor.
  • holding fixtures are provided which are positioned at least partly one behind the other in the radial direction from the axis of the rotor.
  • the holding fixtures are arranged in concentric circles around the axis of the rotor.
  • the holding fixtures can be arranged in concentric circles around the axis of the rotor.
  • the holding fixtures of different circumferences are positioned on a straight line from the outside to the inside of the rotor.
  • Such an arrangement is simple to handle and permits for an automated load and an automated removal to and from the micro-environments via a reaction mixture transfer device.
  • the reaction mixture transfer device With the reaction mixture transfer device a transfer of the reaction mixture and/or a reaction container comprising the reaction mixture is possible.
  • the straight line of the holding fixtures is offset with regard to the axis of the rotor.
  • the term "is offset” according to the invention is intended to encompass that the straight lines do not intersect the axis of the rotor.
  • Such an embodiment provides a simple geometry and permits for an automated load and an automated removal because holding fixtures can be arranged such that at least two straight lines of holding fixtures adjacent to each other can be obtained wherein the at least two straight lines extend parallel to each other.
  • the straight lines allow an automated transfer of the reaction mixtures from/to the micro-environments of the rotor.
  • the micro-environments or reaction containers can be automatically filled by a sample transport device, which can aspirate reaction mixtures from a plate with a rectangular arrangement of wells (96-well plate) and transport it to the micro-environments in the rotor and inject the reaction mixtures therein.
  • the transport device can have pipettes which are arranged in a rectangular shape in two columns and four lines.
  • the transport device can be arranged for a transport of the reaction containers being arranged in a pad or plate in rectangular shape.
  • the transport device may be arranged to move the reaction containers from the pad or plate into the holding fixtures of the rotor.
  • the transport device can grip or pick two columns of four lines of reactions containers arranged in a plate of twelve columns and eight lines. This enhances the efficacy of the reaction process because the time used for preparation is reduced.
  • the holding fixtures are arranged in at least one group such that in the at least one group of holding fixtures a connection line between holding fixtures of a line around the center of the rotor spans an angle of 80° to 100° with a connection line of two holding fixtures of different distance from the center of the rotor.
  • the specification of the angle as being 80° to 100° is intended to encompass all the values of angles in the mentioned interval, however, especially the angle of 90° with a small deviation is mostly preferred.
  • the mentioned arrangement permits an simple automatic transfer from or to a well plate in which the reaction mixtures are held in an rectangular manner with regard to each other.
  • the arrangement of the holding fixtures in the rotor is such that the rectangular arrangement of the reaction containers in a known 96-well plate can be transferred to the round cycler format of the rotor.
  • the reaction mixture is not transferred together with the reaction container but aspirated by several pipettes arranged in rectangular shape, especially two columns with four lines, at once and then injected to reaction containers held by the holding fixtures of the rotor.
  • reaction containers can be "bundled" such that several reaction containers can be transferred to and from the rotor at the same time.
  • the number of holding fixtures is at least 100, more preferably 200.
  • the holding fixtures are arranged in four concentric circles around the axis of the rotor which permits the arrangement of at least 192 reaction containers in the rotor and eight fixtures for additional use.
  • a thermal cycler which comprises an optical system and a receptacle for a rotor e.g. as described above.
  • the thermal cycler preferably at least two optical systems are provided and arranged such that at least two micro-environments having a different distance from the axis of the rotor or being on a different circumference may be analyzed by the optical systems.
  • the number of optical systems corresponds to the number of circumferences of micro-environments around the axis of the rotor.
  • the optical systems are provided in proximity to each other, i.e. adjacent to each other, which simplifies the arrangement for the wiring of the optical systems.
  • a thermal cycler is provided with a high sample or reaction mixture capacity which may not have bigger dimensions than known thermal cyclers.
  • optical system is intended to encompass an optical system which allows determination of at least one optical property of the reaction mixture in the micro-environment, i.e. the reaction container.
  • the optical system can include an illumination source, such as an LED, and a corresponding optical detector, e.g. a photomultiplier for detecting reflected illumination or emitted fluorescence.
  • the at least two optical systems comprise each two confocal systems which allows for two channels for each of the optical systems.
  • the at least two optical systems comprise each two confocal systems which allows for two channels for each of the optical systems.
  • two confocal systems per optical system it becomes possible to determine two channels (colours or wavelengths) for each of the lines of the micro-environments in the rotor at the same time. This determination enhances the efficacy of the process even more because the determination may include validation by two channels. Further, the occurrence of two different channels permits to use two different luminophores which can be determined with high accuracy.
  • the confocal systems comprise two excitation sources with different excitation wavelength which permits the use of two different luminophores and a simple detector system in which the focus or image point of one lens is the same as one focus of the next lens.
  • FIG 1 schematically depicts a rotor 1 for a thermal cycler, especially for real time PCR.
  • a thermal cycler provides an environment which can be subjected to heating and cooling and the rotor can be inserted into a thermal cycler.
  • the rotor 1 comprises holding fixtures 2.
  • the holding fixtures 2 are arranged to hold a reaction container 3 (see Fig. 3 ) which provides a micro-environment in which a reaction mixture might be filled.
  • the holding fixtures 2 are arranged in several circumferences around the axis/center 4 (indicated by an "+" in Fig. 1 and 2 ) of the rotor 1.
  • the holding fixtures 2 are arranged in circumferences around the center 4 of the rotor 1.
  • the circumferences have the shape of concentric circles around the center 4 of the rotor 1.
  • the number of concentric circles around the center 4 of the rotor 1 is four.
  • fifty holding fixtures 2 are arranged on each of the concentric circles.
  • the holding fixtures 2 can be grouped in four groups containing 50 holding fixtures 2 each, each group containing holding fixtures 2 having the same distance with regard to the center 4 of the rotor 1.
  • the reaction containers 3 are held in the holding fixtures 2 substantially parallel to the rotation axis of the rotor 1 which is perpendicular to the paper plane in Fig. 1 and intersects the center 4 of the rotor 1.
  • the reaction containers 3 extent through the holding fixtures 2 of the rotor 1.
  • the reaction containers 3 extent through the rotor 1 parallel to the rotation axis of the rotor 1.
  • the holding fixtures 2 of different circumferences are arranged such that a straight line connects holding fixtures 2 (center of the holding fixtures 2) of different circumferences from the outside to the inside of the rotor 1.
  • Two of the different circumferences are visualized by the dashed lines c and d which extend radially from the center 4 of rotor 1, wherein the line c denotes the circumference for the holding fixtures 2 next to the center 4 and the line d denotes the neighbouring circumference for the holding fixtures 2 which are arranged next to the holding fixtures with circumference c.
  • the straight line connecting the holding fixture 2 of the outer circumference and the holding fixture 2 of the inner circumference is visualized by the dashed line denoted by "a".
  • Each straight line is offset to the center 4 of the rotor 1 such that the straight lines do not intersect the center 4. The offset of the straight lines can be small.
  • the holding fixtures 2 are arranged in at least one group such that in the at least one group of holding fixtures 2 a connection line (visualized by the dashed line denoted by "b") between holding fixtures 2 of a circumference spans an angle of substantially 90° with a connection line of two holding fixtures 2 of different distance from the center 4 of the rotor 1.
  • a connection line (visualized by the dashed line denoted by "b") between holding fixtures 2 of a circumference spans an angle of substantially 90° with a connection line of two holding fixtures 2 of different distance from the center 4 of the rotor 1.
  • a connection line (visualized by the dashed line denoted by "b") between holding fixtures 2 of a circumference spans an angle of substantially 90° with a connection line of two holding fixtures 2 of different distance from the center 4 of the rotor 1.
  • the group comprises eight holding fixtures 2.
  • the eight holding fixtures 2 are arranged in the shape of a rectangular with sides a and b. As can be seen from Fig. 1 the side
  • the number of holding fixtures 2 in the rotor 1 is two hundred.
  • the thermal cycler includes a chamber establishing an environment and containing at least one reaction container as a micro-environment which contains the reaction mixture and is arranged in the rotor 1.
  • the thermal cycler typically includes a controller, for example a processor, coupled to a heater and a cooler.
  • the heater is typically a convection heater, or similar, arranged to heat air in the chamber. Heating/cooling the chamber will influence the temperature of the micro-environment and thus the temperature of the reaction mixture contained therein.
  • a temperature sensor is arranged which is connected to the controller. With the temperature sensor the temperature of the air inside the chamber can be sensed by the controller. Further, the controller is operatively connected to the heater and the cooler.
  • the rotor 1 is insertable into the thermal cycler and the thermal cycler provides a motor by which means the rotor 1 can be rotated around an axis which intersects the center 4 of the rotor 1 and which is perpendicular to the paper plane of Fig.1 .
  • each micro-environment can be placed by rotating the rotor 1 in a position that the micro-environment held in the respective holding fixture 2 can be irradiated by a light source, which is preferably a LED.
  • a light source which is preferably a LED.
  • the reaction containers 3 are transparent with regard to the light which impinges the reaction container 3.
  • the light emitted from the light source passes a filter on the optical way.
  • a light detector is provided for detecting light intensity as a function of wavelength.
  • the detector can comprise a filter as well as a photomultiplier tube.
  • the detector is operatively connected to the controller for receiving the measured fluorescence intensity as well as for setting a gain of the detector.
  • Fig. 2 a schematic diagram of the rotor 1 according to Figure 1 in a thermal cycler is shown.
  • the position of optical systems 6 of the thermal cycler is indicated.
  • Three different positions of the optical systems 6 are indicated by reference signs 5', 5" and 5"'.
  • For each of the lines (concentric circles) one optical system 6 is provided.
  • the four optical systems 6 are shown for each of the depicted three positions 5', 5", 5"'.
  • the arrangement of the four optical systems 6 of each of the three positions 5', 5", 5"' is such that four micro-environments /reaction containers 3 having different distance from the center 4 of the rotor 1 can be analyzed by the optical systems 6.
  • the motor that rotates the rotor 1 is controllable by the controller of the thermal cycler such that the reaction containers 3 can be moved / rotated such that each of the reaction containers 3 can be analyzed by the optical detectors.
  • Each optical system 6 comprises two confocal systems and the confocal systems comprise two excitation sources with different excitation wavelength. Further, the confocal systems comprise two detectors corresponding to the two different excitation wavelengths. Especially, the fluorescence of the reaction mixture in the reaction container 3 can be determined by the optical systems 6.
  • Fig. 3 an isometric view of a part of the thermal cycler (the rotor 1 and the optical systems 6 of the thermal cycler) is shown. Further, 96-well plates 7 are shown which are capable of holding reaction containers 3. The arrangement of the reaction containers 3 in the 96-well plate 7 is such that the reaction containers 3 are held in a rectangular shape in columns and lines. The geometry of the holding fixtures 2 in the rotor 1 permits to transfer the reaction containers 3 held by the 96-well plate 7 to the holding fixtures 2 in the rotor 1. The transfer can be carried out by a manipulator arranged to grip the eight reaction containers 3 shown in the 96-well plate 7 at once and put them in the holding fixtures 2 of the rotor 1.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
EP12176913.7A 2012-07-18 2012-07-18 Rotor pour cycleur thermique et cycleur thermique Withdrawn EP2687294A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP12176913.7A EP2687294A1 (fr) 2012-07-18 2012-07-18 Rotor pour cycleur thermique et cycleur thermique

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP12176913.7A EP2687294A1 (fr) 2012-07-18 2012-07-18 Rotor pour cycleur thermique et cycleur thermique

Publications (1)

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EP2687294A1 true EP2687294A1 (fr) 2014-01-22

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU216333U1 (ru) * 2022-07-08 2023-01-30 Товарищество с ограниченной ответственностью "7R Bio" Амплификатор

Citations (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4683202A (en) 1985-03-28 1987-07-28 Cetus Corporation Process for amplifying nucleic acid sequences
US4683195A (en) 1986-01-30 1987-07-28 Cetus Corporation Process for amplifying, detecting, and/or-cloning nucleic acid sequences
US4800159A (en) 1986-02-07 1989-01-24 Cetus Corporation Process for amplifying, detecting, and/or cloning nucleic acid sequences
US4889818A (en) 1986-08-22 1989-12-26 Cetus Corporation Purified thermostable enzyme
US4965188A (en) 1986-08-22 1990-10-23 Cetus Corporation Process for amplifying, detecting, and/or cloning nucleic acid sequences using a thermostable enzyme
US4988617A (en) 1988-03-25 1991-01-29 California Institute Of Technology Method of detecting a nucleotide change in nucleic acids
US5023171A (en) 1989-08-10 1991-06-11 Mayo Foundation For Medical Education And Research Method for gene splicing by overlap extension using the polymerase chain reaction
US5066584A (en) 1988-09-23 1991-11-19 Cetus Corporation Methods for generating single stranded dna by the polymerase chain reaction
US5075216A (en) 1988-09-23 1991-12-24 Cetus Corporation Methods for dna sequencing with thermus aquaticus dna polymerase
US5079352A (en) 1986-08-22 1992-01-07 Cetus Corporation Purified thermostable enzyme
US5091310A (en) 1988-09-23 1992-02-25 Cetus Corporation Structure-independent dna amplification by the polymerase chain reaction
US5104792A (en) 1989-12-21 1992-04-14 The United States Of America As Represented By The Department Of Health And Human Services Method for amplifying unknown nucleic acid sequences
WO1992020778A1 (fr) 1991-05-24 1992-11-26 Kindconi Pty Limited Temoin de reaction biochimique
WO1998049340A1 (fr) 1997-04-30 1998-11-05 John Michael Corbett Dispositif et procede d'etablissement de cycle
US20020155591A1 (en) * 2001-04-24 2002-10-24 Dade Behring Inc. Indentification test device in a random access microbiological analyzer
WO2008102772A1 (fr) * 2007-02-22 2008-08-28 Toyo Boseki Kabushiki Kaisha Système d'amplification d'acide nucléique
WO2009067744A1 (fr) * 2007-11-30 2009-06-04 Corbett Research Pty Ltd Dispositif d'application de cycles thermiques
EP2107125A1 (fr) * 2008-03-31 2009-10-07 Eppendorf Array Technologies SA (EAT) PCR en temps réel de cibles sur un micro-réseau

Patent Citations (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4683202A (en) 1985-03-28 1987-07-28 Cetus Corporation Process for amplifying nucleic acid sequences
US4683202B1 (fr) 1985-03-28 1990-11-27 Cetus Corp
US4683195A (en) 1986-01-30 1987-07-28 Cetus Corporation Process for amplifying, detecting, and/or-cloning nucleic acid sequences
US4683195B1 (fr) 1986-01-30 1990-11-27 Cetus Corp
US4800159A (en) 1986-02-07 1989-01-24 Cetus Corporation Process for amplifying, detecting, and/or cloning nucleic acid sequences
US4889818A (en) 1986-08-22 1989-12-26 Cetus Corporation Purified thermostable enzyme
US4965188A (en) 1986-08-22 1990-10-23 Cetus Corporation Process for amplifying, detecting, and/or cloning nucleic acid sequences using a thermostable enzyme
US5079352A (en) 1986-08-22 1992-01-07 Cetus Corporation Purified thermostable enzyme
US4988617A (en) 1988-03-25 1991-01-29 California Institute Of Technology Method of detecting a nucleotide change in nucleic acids
US5075216A (en) 1988-09-23 1991-12-24 Cetus Corporation Methods for dna sequencing with thermus aquaticus dna polymerase
US5066584A (en) 1988-09-23 1991-11-19 Cetus Corporation Methods for generating single stranded dna by the polymerase chain reaction
US5091310A (en) 1988-09-23 1992-02-25 Cetus Corporation Structure-independent dna amplification by the polymerase chain reaction
US5023171A (en) 1989-08-10 1991-06-11 Mayo Foundation For Medical Education And Research Method for gene splicing by overlap extension using the polymerase chain reaction
US5104792A (en) 1989-12-21 1992-04-14 The United States Of America As Represented By The Department Of Health And Human Services Method for amplifying unknown nucleic acid sequences
WO1992020778A1 (fr) 1991-05-24 1992-11-26 Kindconi Pty Limited Temoin de reaction biochimique
WO1998049340A1 (fr) 1997-04-30 1998-11-05 John Michael Corbett Dispositif et procede d'etablissement de cycle
US20020155591A1 (en) * 2001-04-24 2002-10-24 Dade Behring Inc. Indentification test device in a random access microbiological analyzer
WO2008102772A1 (fr) * 2007-02-22 2008-08-28 Toyo Boseki Kabushiki Kaisha Système d'amplification d'acide nucléique
WO2009067744A1 (fr) * 2007-11-30 2009-06-04 Corbett Research Pty Ltd Dispositif d'application de cycles thermiques
EP2107125A1 (fr) * 2008-03-31 2009-10-07 Eppendorf Array Technologies SA (EAT) PCR en temps réel de cibles sur un micro-réseau

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
H. A. ERLICH: "PCR Technology: Principals and Applications for DNA Amplification", 1989, STOCKTON PRESS
INNIS ET AL.: "PCR Protocols: A Guide to Methods and Applications", 1990, ACADEMIC PRESS
M. J. MCPHERSON ET AL.: "PCR: A Practical Approach", 1991, IRL PRESS

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU216333U1 (ru) * 2022-07-08 2023-01-30 Товарищество с ограниченной ответственностью "7R Bio" Амплификатор

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