Nucleic acid amplification reaction apparatus
First Claim
1. An apparatus for performing a nucleic acid amplification reaction in a reaction mixture containing a target nucleic acid segment including denaturation, annealing and extension processes, said apparatus comprising:
- a capillary tube reaction chamber having a portion adapted to contain the reaction mixture at a predetermined position;
first temperature controlled movable heat exchange means adapted to contact said portion of the capillary tube reaction chamber for subjecting the reaction mixture at said position to a first temperature suitable to cause the denaturation process to occur in the reaction mixture;
second temperature controlled movable heat exchange means adapted to contact said portion of the capillary tube reaction chamber at said position for subjecting the mixture to a second temperature suitable to cause the annealing and extension process to occur in the mixture;
sample handling means connected to the capillary tube reaction chamber for automatically moving the reaction mixture into and out of the capillary tube reaction chamber and to and from said predetermined position; and
positioning means for automatically positioning the first and second heat exchange means sequentially in contact with the portion of the capillary tube reaction chamber,wherein each of the heating means is a segment of a cylindrical heat exchange drum.
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Accused Products
Abstract
Apparatus and method for performing a nucleic acid amplification reaction and preferably a polymerase chain reaction (PCR) in a reaction mixture in at least one capillary tube. Several different embodiments are disclosed. One embodiment cycles a sample through a capillary tube loop passing through two thermostatted fluid baths. Another embodiment has the capillary tube routed alternatingly between two heat exchangers to that the sample makes only one pass through the tube. Other embodiments maintain the heat exchangers stationary and translate the samples between them. Still further embodiments maintain the samples stationary and either automatically translate or rotate the heat exchangers past the samples contained within the capillary tubes to perform the thermal cycles necessary for the amplification reaction.
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Citations
49 Claims
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1. An apparatus for performing a nucleic acid amplification reaction in a reaction mixture containing a target nucleic acid segment including denaturation, annealing and extension processes, said apparatus comprising:
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a capillary tube reaction chamber having a portion adapted to contain the reaction mixture at a predetermined position; first temperature controlled movable heat exchange means adapted to contact said portion of the capillary tube reaction chamber for subjecting the reaction mixture at said position to a first temperature suitable to cause the denaturation process to occur in the reaction mixture; second temperature controlled movable heat exchange means adapted to contact said portion of the capillary tube reaction chamber at said position for subjecting the mixture to a second temperature suitable to cause the annealing and extension process to occur in the mixture; sample handling means connected to the capillary tube reaction chamber for automatically moving the reaction mixture into and out of the capillary tube reaction chamber and to and from said predetermined position; and positioning means for automatically positioning the first and second heat exchange means sequentially in contact with the portion of the capillary tube reaction chamber, wherein each of the heating means is a segment of a cylindrical heat exchange drum. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 44, 49)
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11. An apparatus for performing a reaction in a reaction mixture containing a target nucleic acid segment including denaturation, annealing and extension processes in a capillary tube, the apparatus comprising:
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a capillary tube reaction chamber for containing the reaction mixture; first temperature controlled movable heat exchange means adapted to be coupled to the capillary tube for subjecting a portion of the capillary tube reaction chamber to a first temperature suitable to cause the denaturation process to occur in the reaction mixture; second temperature controlled movable heat exchange means adapted to be coupled to the capillary tube for subjecting said portion of the capillary tube to a second temperature suitable to cause the annealing and extension processes to occur in the reaction mixture; means for automatically moving the reaction mixture into said portion of the capillary tube reaction chamber and discharging the reaction mixture from the capillary tube reaction chamber; and control means for sequentially coupling said first and second heat exchange means to the capillary tube in accordance with a reaction protocol to cause said reaction to take place in said reaction mixture. - View Dependent Claims (12, 13)
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14. An apparatus for simultaneously performing a nucleic acid amplification reaction including denaturation, annealing and extension processes in reaction mixtures in a plurality of capillary tubes, the apparatus comprising:
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a plurality of open ended capillary tubes each having a portion adapted to contain a reaction mixture suitable for causing the nucleic amplification reaction to create copies of a target nucleic acid segment; first temperature controlled movable heat exchange means for simultaneously subjecting said portion of each of the capillary tubes to a first temperature suitable to cause the denaturation process in the nucleic acid amplification reaction to occur in the mixtures; second temperature controlled movable heat exchange means for simultaneously subjecting said portion of each of the capillary tubes to a second temperature suitable to cause the annealing and extension processes in the nucleic acid amplification reaction to occur in the mixtures; positioning means for causing said temperature controlled movable heat exchange means to subject the reaction mixtures to the first and second temperatures in accordance with a predetermined sequence of steps; plurality of reaction tubes corresponding to said capillary tubes; and handling means for operatively connecting an open end of each of the capillary tubes to a corresponding reaction tube containing the reaction mixture and for cleansing the capillary tubes. - View Dependent Claims (15, 16, 17)
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18. An apparatus for performing a nucleic acid amplification reaction on a plurality of reaction mixtures contained in a plurality of capillary tubes simultaneously, the reaction including denaturation, annealing and extension processes to generate a nucleic acid amplification reaction product, the apparatus comprising:
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a first heat exchanger including a thermoregulating system for stabilizing the temperature of the first heat exchanger at a temperature in a range of temperatures suitable to cause the denaturation process to occur in the nucleic acid amplification reaction in the plurality of reaction mixtures; a second heat exchanger including another thermoregulating system for stabilizing the temperature of the second heat exchanger at a temperature in a range of temperatures suitable for causing the annealing and extension processes in the nucleic acid amplification reaction to occur in the mixtures; a plurality of capillary tubes each routed so that each has a portion in thermal contact with at least one of the first and second heat exchangers; sample handling means coupled to each of the capillary tubes for drawing the reaction mixture into the tube and positioning said mixtures in said portions, and for discharging finished reaction product from each of the tubes; and user controllable means for sequentially moving the first and second heat exchangers into thermal contact with the portions of the capillary tubes containing the reaction mixtures so as to cause the nucleic acid amplification reaction to take place in the mixtures in the capillary tubes. - View Dependent Claims (19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43)
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45. An apparatus for performing a nucleic acid amplification reaction in a reaction mixture containing a target nucleic acid segment including denaturation, annealing and extension processes, said apparatus comprising:
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a capillary tube reaction chamber having a portion adapted to contain the reaction mixture at a predetermined position; first temperature controlled movable heat exchange means adapted to contact said portion of the capillary tube reaction chamber for subjecting the reaction mixture at said position to a first temperature suitable to cause the denaturation process to occur in the reaction mixture; second temperature controlled movable heat exchange means adapted to contact said portion of the capillary tube reaction chamber at said position for subjecting the mixture to a second temperature suitable to cause the annealing and extension process to occur in the mixture; sample handling means connected to the capillary tube reaction chamber for automatically moving the reaction mixture into and out of the capillary tube reaction chamber and to and from said predetermined position; positioning means for automatically positioning the first and second heat exchange means sequentially in contact with the portion of the capillary tube reaction chamber; and a third heating means adapted to contact the portion of the capillary tube for subjecting the portion to a temperature above the first temperature.
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46. An apparatus for performing a nucleic acid amplification reaction on a plurality of reaction mixtures contained in a plurality of capillary tubes simultaneously, the reaction including denaturation, annealing and extension processes to generate a nucleic acid amplification reaction product, the apparatus comprising:
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a first heat exchanger including a thermoregulating system for stabilizing the temperature of the first exchanger at a temperature in a range of temperatures suitable to cause the denaturation process to occur in the nucleic acid amplification reaction in the plurality of reaction mixtures; a second heat exchanger including another thermoregulating system for stabilizing the temperature of the second heat exchanger at a temperature in a range of temperatures suitable for causing the annealing and extension processes in the nucleic acid amplification reaction to occur in the mixtures; a plurality of capillary tubes each routed so that each has a portion in thermal contact with at least one of the first and second heat exchangers; sample handling means coupled to each of the capillary tubes for drawing the reaction mixture into the tube and positioning said mixtures in said portions, and for discharging finished reaction product from each of the tubes; and user controllable means for sequentially causing relative motion between the first and second heat exchangers and the portions of the capillary tubes containing the reaction mixture so as to cause the nucleic acid amplification reaction to take place in the mixtures in the capillary tubes. - View Dependent Claims (47)
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48. An apparatus for performing a nucleic acid amplification reaction in a reaction mixture containing a target nucleic acid segment including denaturation, annealing and extension processes, said apparatus comprising:
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a capillary tube reaction chamber having a portion adapted to contain the reaction mixture at a predetermined position; first temperature controlled movable heat exchange means adapted to contact said portion of the capillary tube reaction chamber for subjecting the reaction mixture at said position to a first temperature suitable to cause the denaturation process to occur in the reaction mixture; second temperature controlled movable heat exchange means adapted to contact said portion of the capillary tube reaction chamber at said position for subjecting the mixture to a second temperature suitable to cause the annealing and extension process to occur in the mixture; sample handling means connected to the capillary tube reaction chamber for automatically moving the reaction mixture into and out of the capillary tube reaction chamber and to and from said predetermined position; and positioning means for automatically positioning the first and second heat exchange means sequentially in contact with the portion of the capillary tube reaction chamber; and a plurality of open capillary tube reaction chambers each having a portion adapted to receive a reaction mixture; wherein each of the heating means is a thermostatically controlled segment of a cylindrical heat exchange drum.
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Specification