Apparatus for applying thermal energy to a receptacle and detecting an emission signal from the receptacle

Abstract

An apparatus for performing nucleic acid amplification reactions includes a thermally-conductive receptacle holder that includes multiple receptacle wells. Each well can receive a receptacle and has a through-hole extending from an inner surface of the well to an outer surface of the holder. The apparatus includes multiple optical fibers, and each optical fiber has a first end in optical communication with an associated well and a second end in optical communication with an excitation signal source and/or an emission signal detector. The first end of each optical fiber is moveable with respect to the through-hole. A cover is movable between an open position and a closed position relative to the receptacle holder, and the first end of each optical fiber moves with respect to the through-hole of the associated well as the cover moves to the open or closed position or when the cover moves into or out of contact with any receptacles within the wells.

What is claimed is: 
     
         1 . A method comprising:
 providing a receptacle to a receptacle well of a thermally-conductive receptacle holder, wherein a through hole extends from an inner surface of the receptacle well to an outer surface of the receptacle holder;   applying a first force to a top end of the receptacle disposed within the receptacle well;   contacting a bottom end of the receptacle disposed within the receptacle well with an end of an optical fiber disposed within the through hole; and   applying a second force to the bottom end of the receptacle with the end of the optical fiber, wherein the second force is less than the first force.   
     
     
         2 . The method of  claim 1 , wherein the receptacle holder includes a plurality of receptacle wells, and the through hole extends from an inner surface of each receptacle well to the outer surface of the receptacle holder, wherein providing a receptacle to a receptacle well comprises providing each of a plurality of receptacles to an associated one of the plurality of receptacle wells, and wherein applying a first force to a top end of the receptacle disposed within the receptacle well comprises simultaneously applying the first force to the top end of each of the plurality of receptacles disposed within its associated receptacle well. 
     
     
         3 . The method of  claim 2 , wherein contacting the receptacle disposed within the receptacle well with the end of the optical fiber disposed within the through hole comprises contacting each receptacle disposed within its associated receptacle well with an end of an associated optical fiber disposed within the through hole of the associated receptacle well, and wherein applying a second force to a bottom end of the receptacle with the end of the optical fiber comprises applying the second force to a bottom end of each receptacle disposed within its associated receptacle well with the end of the associated optical fiber disposed within the through hole of the associated receptacle well. 
     
     
         4 . The method of  claim 1 , further comprising adding a reaction mixture to the receptacle and closing the receptacle with a cap that is situated above a top surface of the receptacle holder when the receptacle is disposed within the receptacle well. 
     
     
         5 . The method of  claim 1 , further comprising at least one of transmitting an excitation signal from an excitation signal source through the optical fiber and to the receptacle and transmitting an emission signal from the receptacle through the optical fiber to an emission signal detector. 
     
     
         6 . The method of  claim 1 , wherein the first force is applied to the top end of the receptacle with a cover that is movable between an open position and a closed position relative to the receptacle holder, and wherein the first force is applied by moving the cover to the closed position to contact the top end of the receptacle. 
     
     
         7 . The method of  claim 1 , further comprising altering a temperature of the receptacle holder to thereby alter a temperature of the contents of the receptacle disposed within the receptacle well. 
     
     
         8 . The method of  claim 7 , wherein altering the temperature of the receptacle holder comprises applying a current across a thermal element disposed between the receptacle holder and a thermally-conductive support. 
     
     
         9 . The method of  claim 1 , wherein providing the receptacle to the receptacle well of the thermally-conductive receptacle holder comprises transferring the receptacle to the receptacle well with a receptacle transport mechanism. 
     
     
         10 . The method of  claim 9 , wherein the receptacle transport mechanism is a pipettor. 
     
     
         11 . The method of  claim 9 , further comprising removing the receptacle from the receptacle transport mechanism with a stripper plate, wherein the stripper plate is mounted to be moveable with respect to the receptacle holder between an unlocked position and a locked position, wherein a receptacle can be transferred to or removed from the receptacle well when the stripper plate is in the unlocked position, and wherein a receptacle disposed in the receptacle well is inhibited from removal from the receptacle well when the stripper plate is in the locked position, and wherein removing the receptacle from the receptacle transport mechanism with the stripper plate comprises moving stripper plate from the unlocked position to the locked position after the receptacle has been transferred to the receptacle well by the receptacle transport mechanism and before the receptacle transport mechanism is withdrawn from the receptacle well. 
     
     
         12 . The method of  claim 6 , wherein applying the second force to the bottom end of the receptacle with the end of the optical fiber comprises moving the end of the optical fiber within the through hole into contact with the bottom end of the-receptacle disposed within the receptacle well, and wherein the method comprises associating movement of the optical fiber within the through hole with movement of the cover from the open position to the closed position. 
     
     
         13 . The method of  claim 1 , wherein applying the second force to the bottom end of the receptacle with the end of the optical fiber comprises urging the end of the optical fiber into contact with the bottom end of the receptacle disposed within the receptacle well with a resilient element coupled to the optical fiber. 
     
     
         14 . The method of  claim 6 , wherein applying the second force to the bottom end of the receptacle with the end of the optical fiber comprises moving the end of the optical fiber within the through hole into contact with the bottom end of the receptacle disposed within the receptacle well prior to, during, or after moving the cover to the closed position. 
     
     
         15 . The method of  claim 6 , wherein applying the second force to the bottom end of the receptacle with the end of the optical fiber comprises moving the end of the optical fiber within the through hole into contact with the bottom end of the receptacle disposed within the receptacle well, and wherein movement of the end of the optical fiber within the through-hole of the receptacle well is caused by movement of the cover to the open position or by movement of the cover to the closed position. 
     
     
         16 . The method of  claim 3 , wherein the first force is applied to the top end of each of the plurality of receptacles with a cover that is movable between an open position and a closed position relative to the receptacle holder, wherein the first force is applied by moving the cover to the closed position to contact the top end of each of the plurality of receptacles. 
     
     
         17 . The method of  claim 16 , wherein the cover comprises a plurality of flexible extensions attached to and extending laterally away from a rotatable member so the cover rotates between the open and closed positions, wherein each of the flexible extensions is configured to contact one receptacle disposed within its associated receptacle well as the cover is rotated from the open position to the closed position, such that each of the flexible extensions contacts at least a portion of the receptacle disposed in its associated receptacle well. 
     
     
         18 . The method of  claim 8 , further comprising dissipating heat from the support with a heat sink in thermal communication with the support. 
     
     
         19 . The method of  claim 18 , wherein the support comprises a base portion and an upright portion, the base portion having a plurality of through-holes, wherein each of the through-holes of the base portion is in alignment with a corresponding one of the through-holes of the receptacle holder, wherein the thermal element is positioned between a side surface of the upright portion and an opposed side surface of the receptacle holder, and wherein the base portion of the support is disposed on a top surface of the heat sink, and wherein the heat sink comprises a plurality of through-holes, each of the through-holes of the heat sink being in alignment with one of the through-holes of the receptacle holder, and wherein each of the optical fibers passes through a corresponding one of the through-holes of the heat sink. 
     
     
         20 . The method of  claim 3 , wherein a resilient element is coupled to the end of each associated optical fiber and configured to urge the end of the associated optical fiber into the associated receptacle well.