Systems, methods and apparatus for automated incubation

Abstract

To provide a suitable system for automated incubation, a method for automated incubation, and an apparatus for automated incubation.SOLUTION: According to the present invention, there are a system, apparatus, and method for cycling the temperature of at least one receptacle holder adapted for use in an automated instrument capable of conducting a nucleic acid-based amplification assay. There is also provided a method for using them to perform an automated random access incubation process.SELECTED DRAWING: Figure 7A

Description

[Technical field]

[0001] (Citation of Related Application) This application claims the benefit of priority under §119(e) of U.S. Ser. No. 61 / 677,976, filed July 31, 2012, and U.S. Ser. No. 61 / 783,952, filed March 14, 2013, the entire contents of each of which are incorporated herein by reference.

[0002] (Technical field) The present disclosure relates generally to systems and devices for automated heating and / or cooling of samples. [Background technology]

[0003] Although automated molecular analysis instrumentation offers many advantages, most automated instruments suffer from a limited set of analytical capabilities. These limited capabilities complicate or prevent parallel processing of multiple analyses, thereby reducing sample throughput and flexibility of analysis selection. This is especially true for analyses that require some type of incubation, such as the temperature cycling required for polymerase chain reaction (PCR)-based analyses. PCR instruments include thermocyclers that are capable of cycling the temperature of many samples, such as a batch of samples held in a 96-well microtiter plate. This analysis format requires preparation of an entire batch of samples prior to subjecting them to initial temperature cycling. For example, the first sample fully prepared for temperature cycling must wait until the last sample is prepared prior to temperature cycling. For 96-well plates, this wait time is significant, thus slowing instrument throughput. In addition, because all samples undergo the same temperature profile and cycling parameters, the types of analyses that can be performed in parallel are limited. Different analyses must often be performed in completely different thermocycler units or await the availability of a thermocycler from a previous batch of samples, again hindering the ability to provide rapid analytical results.

[0004] This disclosure addresses these and other needs in the art.

[0005] All documents referenced herein, or portions thereof as indicated, are hereby incorporated by reference, however, no document is admitted to be prior art to the claimed subject matter. Summary of the Invention [Means for solving the problem]

[0006] The present disclosure relates to a system and apparatus for altering the temperature of at least one receptacle holder adapted for use in an automated instrument capable of performing biochemical analyses.

[0007] In an aspect of the present disclosure, an apparatus is provided that includes one or more receptacle holders made from a thermally conductive material. Each receptacle holder includes a plurality of receptacle wells, each receptacle well configured to receive a receptacle therein; a plurality of through holes, each through hole extending from an inner surface of one of the receptacle wells to an outer surface of the receptacle holder; a plurality of optical fibers, each optical fiber having a first and second end, the first end in optical communication with one of the receptacle wells and the second end in optical communication with at least one of the excitation signal source and the emission signal detector, the first end of each optical fiber positioned outside, within, or extending through a corresponding through hole in each receptacle well, the first end of each optical fiber being moveably or fixedly positioned within one of the through holes relative to a surface of the receptacle well; and one or more thermal elements positioned proximate the receptacle holder to alter a temperature of one or more of the receptacle holders. In certain embodiments, the device includes a cover that is movable between an open position and a closed position relative to the receptacle holder, and one or more receptacles disposed inside one or more of the receptacle wells are seated or secured into the receptacle wells by the cover when the cover is moved to the closed position. In exemplary embodiments, the first end of the optical fiber moves within its corresponding through hole (1) when the cover is moved to the closed and / or open position, or (2) when a receptacle is present in the receptacle well and the cover is moved to the closed and / or open position. In various of these embodiments, the device does not include a cover. Also, in various of these embodiments, when the devices are included in a system, one or more of the devices include / do not include a cover.Often, one or more receptacle transport mechanisms are included in such systems to transport the receptacles to the receptacle wells, place the receptacles in the receptacle wells, optionally ensure that each receptacle is securely seated in its respective receptacle well, for example, by using physical contact, and remove each receptacle from its respective receptacle well. More than one receptacle transport mechanism may be utilized in such embodiments to affect one or more of these steps.

[0008] In various embodiments, the thermal element is positioned proximate a side of the receptacle holder and provides thermal energy through the receptacle holder to each of the plurality of receptacle wells. The thermal energy may be uniform. In many embodiments, the apparatus further includes one or more supports, each positioned proximate a side of one or more of the receptacle holders, and the thermal element is positioned between the supports and the receptacle holder. One or more thermistors may be disposed in contact with the receptacle holder. In various embodiments, the one or more thermistors and / or their associated wiring are disposed within channels formed in the receptacle holder. In certain embodiments, the apparatus further includes one or more closed-end channels formed on opposing sides of the receptacle wells of the receptacle holder, each having one of the thermistors disposed therein.

[0009] In certain embodiments, the apparatus further includes one or more cross braces positioned to provide a compressive force between the receptacle holder and the support. In other embodiments, the apparatus further includes one or more bodies having low thermal conductivity, each connected directly or indirectly to the linker, positioned to provide a compressive force between the receptacle holder and the support. In various embodiments, the support of the apparatus is a heat sink, or the support is provided in thermal communication with the heat sink. The apparatus may include a first controller electrically connected to the thermal element to cycle a temperature of the thermal element, and may include one or more motors electrically connected to the first controller disposed in movable communication with the cover, if present. In various embodiments, the cover, if present, may include a rigid element and one or more flexible extensions attached to the rigid element and extending laterally away from the rigid element to provide a force to at least a portion of the one or more receptacles when present in the receptacle well when the cover is in a closed position.

[0010] In an exemplary embodiment, the apparatus further includes a stripper plate movably associated with the receptacle holder for removing the receptacle from a receptacle transport mechanism that delivers the receptacle to the receptacle holder. The stripper plate may be movable into an unlocked and locked position relative to the receptacle well, the unlocked position allowing access of the receptacle to the receptacle well and the locked position preventing removal of the receptacle from the receptacle well without preventing access to the receptacle by the receptacle transport mechanism.

[0011] In another aspect, the present disclosure provides a system including one or more devices of the present disclosure. In various embodiments, each of the one or more devices is in independent thermal communication with a single heat sink. A thermal element corresponding to each receptacle holder in the system may be independently controllable to change the temperature of only its corresponding receptacle holder. In many embodiments, the system includes one or more controllers connected to one or more motors in electrical communication with the thermal element and disposed in movably communication with a cover corresponding to each receptacle holder. In various embodiments, the system does not include a cover. The system may include at least 10 receptacle wells and at least 10 corresponding optical fibers, with all second ends of the optical fibers in optical communication with one or more excitation signal sources and / or one or more emission signal detectors. In many embodiments, the system is disposed within a single housing.

[0012] In another aspect, the present disclosure provides a method for performing an automated random access incubation process. In one exemplary embodiment, the method includes an automated step of transferring a first set of receptacles to a first receptacle holder and subjecting the contents of the first set of receptacles to a first incubation process, and during the first incubation process, an automated step of transferring a second set of receptacles to a second receptacle holder and subjecting the contents of the second set of receptacles to a second incubation process. In another exemplary embodiment, the first and second receptacle holders are components of an apparatus as disclosed herein. Each of the first and second sets of receptacles can be sealed to prevent contamination and / or evaporation. In various exemplary embodiments, each of the first and second receptacle holders is in thermal communication with a single temperature cycling apparatus as described herein.

[0013] In many embodiments, the method further includes initiating a third of the three or more independent processes during the second incubation process, including transferring the third or more sets of receptacles to a third or more receptacle holder and subjecting the contents of the third or more sets of receptacles to a third or more incubation processes, with the transfer of each successive set of receptacles being initiated prior to completion of the incubation process for each immediately preceding set of receptacles. The transfer of the first and second sets of receptacles may be accomplished by a receptacle transport mechanism. As described herein, each set of receptacles may be removed from its respective receptacle holder prior to completion of the next successive incubation process.

[0014] In another aspect, the disclosure provides a method of establishing optical communication between a receptacle and an excitation signal source and / or an emission signal detector within a housing of an apparatus, the method including the automated steps of providing a receptacle in a well of a receptacle holder comprised of a thermally conductive material, applying a first force to the receptacle, thereby seating the receptacle in the well, and either (1) causing movement of an end of an optical fiber toward and into contact with the seated receptacle while the force is applied to the receptacle, or (2) the receptacle applying a second force to an end of an optical fiber disposed within the well, such that while the force is applied to the receptacle, the end of the optical fiber moves within the well in a direction opposite from the direction of the applied second force.

[0015] In various embodiments, the receptacle contacts the optical fiber during or after step (a) and applies a force to an end of the optical fiber disposed within the well such that while a force is applied to the receptacle, the end of the optical fiber moves within the well in a direction opposite from the direction of the applied force. The end of the optical fiber, or a region proximal to the end, may be directly or indirectly connected to the receptacle holder with a resilient element such that the resilient element contracts when a force is applied to the receptacle.

[0016] In yet another exemplary aspect, the present disclosure provides an apparatus including a housing, a plurality of receptacle holders contained within the housing, each of which is made of a thermally conductive material, each of which includes a plurality of receptacle wells, and one or more thermal elements positioned proximate each of the receptacle holders to change a temperature of one or more of the plurality of receptacle wells. In various embodiments, the apparatus further includes a plurality of covers, each of which is disposed in movably associated with the receptacle holder, and a first controller controls movement of each cover between an open position and a closed position. When at least one receptacle is present in the plurality of receptacle wells, it is secured within the receptacle well by the cover when the cover is located in the closed position. When the cover is in the open position, a receptacle transport mechanism can access the plurality of receptacle wells to introduce or remove a receptacle. In addition, each cover can be moved between an open position and a closed position, either together with or independent of one or more other covers. In various other embodiments, the device does not include a cover.

[0017] In various embodiments, the apparatus further includes an optical fiber associated with each receptacle well such that optical communication is established between an interior of each receptacle well and an excitation signal source and / or an emission signal detector. The apparatus may further include one or more receptacles within the plurality of receptacle wells, with the optical fiber establishing optical communication between each receptacle and the excitation signal source and / or the emission signal detector. In many embodiments, the apparatus further includes a stripper plate movably associated with each receptacle holder for removing the receptacle from the receptacle transport mechanism.

[0018] In various embodiments, the support of the apparatus is a heat sink or the support is provided in thermal communication with the heat sink. The apparatus may include a first controller electrically connected to the thermal element to cycle the temperature of the thermal element, and may include one or more motors electrically connected to the first controller disposed in movably communication with the cover, if present. In various embodiments, the cover, if present, may include a rigid element and one or more flexible extensions attached to the rigid element and extending laterally away from the rigid element to apply a force to at least a portion of the one or more receptacles when present in the receptacle wells when the cover is in the closed position.

[0019] In yet another exemplary aspect, the present disclosure provides an apparatus including a housing, a plurality of receptacle holders contained within the housing, each receptacle holder comprising a plurality of receptacle wells, and one or more thermal elements electrically connected to a first controller and positioned proximate each receptacle holder to alter a temperature of one or more of the plurality of receptacle wells. In various embodiments, the apparatus may further include a plurality of covers, each movable between a first disengaged position and a second engaged position relative to the receptacle holder, each cover comprising a series of flexible extensions, each individual flexible extension associated with a single receptacle well in the receptacle holder, and movement of each cover between the first disengaged position and the second engaged position controlled by the second controller. When at least one receptacle is present in the plurality of receptacle wells, it is secured within the receptacle well by the cover when located at the second position. When the cover is in the first position, the receptacle transport mechanism can access the plurality of receptacle wells to introduce or remove receptacles. In addition, each cover can move between the first and second positions together with or independent of one or more other covers. The first controller and the second controller can be the same unit. In various other embodiments, the device does not include a cover or a plurality of covers.

[0020] In various embodiments, the support of the apparatus is a heat sink or the support is provided in thermal communication with the heat sink. The apparatus may include a first controller electrically connected to the thermal element to cycle the temperature of the thermal element, and may include one or more motors electrically connected to the first controller disposed in movably communication with the cover, if present. In various embodiments, the cover, if present, may include a rigid element and one or more flexible extensions attached to the rigid element and extending laterally away from the rigid element to apply a force to at least a portion of the one or more receptacles when present in the receptacle wells when the cover is in the closed position.

[0021] In yet another exemplary aspect, the present disclosure provides an apparatus including one or more receptacle holders made of a thermally conductive material. Each receptacle holder includes a plurality of receptacle wells, each receptacle well configured to receive a receptacle therein, a plurality of through holes, each through hole extending from an inner surface of one of the receptacle wells to an outer surface of the receptacle holder, a plurality of optical fibers, each optical fiber having a first and second end, the first end in optical communication with one of the receptacle wells and the second end in optical communication with at least one of the excitation signal source and / or emission signal detector, the first end of each optical fiber disposed outside, inside, or extending through a corresponding through hole in each receptacle well, and one or more thermal elements positioned proximate the receptacle holder to change one or more temperatures of the receptacle holder. In various embodiments, the apparatus does not include a cover. In various embodiments, the apparatus further includes a primary cover fixedly positioned over the receptacle holder and having one or more locking arms aligned with and disposed in an array surrounding each receptacle well of the receptacle holder, where one or more receptacles disposed within one or more of the receptacle wells are mounted or secured therein by the locking arms, and a secondary cover fixedly positioned over the primary cover and having one or more release arms aligned with and in sliding contact with the locking arms of the primary cover. In an exemplary embodiment, application of a force to the release arms pushes the locking arms in a radially outward direction relative to an axial center of the receptacle well, thereby releasing a receptacle disposed within the receptacle well. One, two, three, four or more locking arms are contemplated. In various other embodiments, the apparatus does not include a primary or secondary cover. In various embodiments, the one or more thermistors and / or their associated wiring are disposed within a channel formed in the receptacle holder.In certain embodiments, the device further includes one or more closed-ended channels formed on opposing sides of the receptacle well of the receptacle holder having one of the thermistors disposed therein.

[0022] In yet another illustrative aspect, the present disclosure provides an apparatus that includes one or more receptacle holders made of a thermally conductive material. Each receptacle holder includes a plurality of receptacle wells, each receptacle well configured to receive a receptacle therein; a plurality of through holes, each through hole extending from an inner surface of one of the receptacle wells to an outer surface of the receptacle holder; a plurality of optical fibers, each optical fiber having a first and second end, the first end in optical communication with one of the receptacle wells and the second end in optical communication with at least one of the excitation signal source and the emission signal detector, the first end of each optical fiber positioned outside, within, or extending through a corresponding through hole in each receptacle well, and the first end of each optical fiber being movable within one of the through holes relative to a surface of the receptacle well; and one or more thermal elements positioned proximate the receptacle holder to change one or more temperatures of the receptacle holder. In various embodiments, the device may further include a cover that is movable between an open position and a closed position relative to the receptacle holder. When present, one or more receptacles disposed inside one or more of the receptacle wells are fixedly mounted to maximize contact with the inner surface of the receptacle well without the need for contact with the cover. In some embodiments, the device may not include a cover. In various embodiments, the one or more thermistors and / or their associated wiring are disposed within channels formed in the receptacle holder. In some embodiments, the device further includes one or more closed-end channels formed on opposing sides of the receptacle wells of the receptacle holder, each having one of the thermistors disposed therein.

[0023] In other embodiments, the present disclosure provides a method of introducing and removing a receptacle from a receptacle holder utilizing a fluid transfer device configured to securely introduce the receptacle into the receptacle holder and to release the receptacle from a securing mechanism disposed within the receptacle holder that securely holds the receptacle within the receptacle holder.

[0024] In yet another exemplary aspect, the present disclosure provides a system including one or more devices of the present disclosure. In various embodiments, the system also includes a receptacle transport mechanism, which may be a modified pipettor. The receptacle transport mechanism includes a body having a plunger slidably disposed therein, and one or more rims hingedly attached to the body and positioned in sliding communication with a knob fixedly attached to the plunger. When the plunger is in a first position, a lower portion of the one or more rims is proximal to the body, and when the plunger is in a second position, a lower portion of the one or more rims is extended in a radially outward direction relative to the body. The present invention provides, for example, the following: (Item 1) An apparatus comprising one or more receptacle holders, each of the receptacle holders being made of a thermally conductive material, the apparatus comprising: The one or more receptacle holders include: a plurality of receptacle wells, each receptacle well configured to receive a receptacle therein; a plurality of through holes, each through hole extending from an inner surface of one of the receptacle wells to an outer surface of the receptacle holder; a plurality of optical fibers, each optical fiber having a first and second end, the first end in optical communication with one of the receptacle wells and the second end in optical communication with at least one of an excitation signal source and an emission signal detector, the first end of each optical fiber disposed outside, inside, or extending through a corresponding through hole in each receptacle well, the first end of each optical fiber being movable within one of the through holes relative to a surface of the receptacle well; one or more thermal elements positioned proximate the receptacle holder to change one or more temperatures of the receptacle holder; 13. An apparatus comprising: (Item 2) a cover movable between an open position and a closed position relative to the receptacle holder, wherein one or more receptacles disposed within one or more of the receptacle wells are seated or secured within the receptacle wells by the cover when the cover is moved to the closed position; 2. The apparatus of claim 1, wherein the first end of each optical fiber moves within its corresponding through hole when (1) the cover is moved to the closed and / or open position, or (2) a receptacle is present in the receptacle well and the cover is moved to the closed and / or open position. (Item 3) 2. The apparatus of claim 1, wherein the first end or a region proximal to the first end of each optical fiber is directly or indirectly associated with a respective through hole using a resilient element, and when the cover is closed or in the closed position and a receptacle is present in the well, the receptacle contacts the first end of the optical fiber and compresses the resilient element, thereby moving the first end of the optical fiber against the inner surface of the receptacle well. (Item 4) 4. The apparatus of any one of items 2 to 3, wherein when the cover is closed or in the closed position, the first end of the optical fiber is moved from within or outside the through hole toward the inner surface of the receptacle well or further into the receptacle well. (Item 5) 5. The apparatus of claim 4, wherein when a receptacle is present in the well, the first end of the optical fiber contacts the receptacle. (Item 6) 6. The apparatus of any one of items 1 to 5, wherein the thermal element is positioned proximate a side of the receptacle holder and provides thermal energy through the receptacle holder to each of the plurality of receptacle wells. (Item 7) 7. The apparatus of claim 6, wherein the thermal energy provided to each of the plurality of receptacle wells is uniform. (Item 8) 8. The apparatus of claim 6 or 7, further comprising one or more supports each positioned proximate one or more sides of the receptacle holder, the thermal element being positioned between the support and the receptacle holder. (Item 9) Item 10. The apparatus of item 8, further comprising one or more cross braces positioned to provide a compressive force between the receptacle holder and the support. (Item 10) 9. The apparatus of claim 8, further comprising one or more bodies having low thermal conductivity, the one or more bodies each connected directly or indirectly to a linker and positioned to provide a compressive force between the receptacle holder and the support. (Item 11) Item 11. The apparatus of item 10, wherein each of the one or more bodies applies a force to a side of the receptacle holder opposite from the thermal element and the support. (Item 12) 12. The device according to any one of claims 8 to 11, wherein the receptacle holder is in sliding engagement with the support. (Item 13) 13. The apparatus according to any one of items 8 to 12, wherein the support is provided with a heat sink or the support is provided in thermal communication with a heat sink. (Item 14) 14. The device according to any one of items 8 to 13, wherein two or more receptacle holders are in sliding engagement with the support. (Item 15) Item 15. The apparatus of any one of items 1 to 14, further comprising a first controller electrically connected to the thermal element to cycle the temperature of the thermal element. (Item 16) Item 16. The device of any one of items 1 to 15, further comprising one or more thermistors disposed in contact with the receptacle holder. (Item 17) Item 17. The apparatus of item 16, wherein the one or more thermistors and / or their associated wiring are disposed within a channel formed in the receptacle holder. (Item 18) Item 18. The apparatus of item 17, further comprising one or more closed end channels formed on opposing sides of the receptacle well of the receptacle holder, each of the one or more closed end channels having one of the thermistors disposed therein. (Item 19) Item 19. The apparatus of any one of items 1 to 18, further comprising one or more thermistors disposed in contact with each of the receptacle wells of the receptacle holder. (Item 20) 20. The apparatus of claim 19, wherein the one or more thermistors are disposed within open ended channels formed in the receptacle holder, with two open ended channels disposed on opposite sides of each receptacle well of the receptacle holder. (Item 21) 21. The device according to any one of claims 1 to 20, wherein the device comprises two or more receptacle holders. (Item 22) 22. The apparatus of claim 21, wherein each of the two or more receptacle holders includes five or more receptacle wells. (Item 23) 3. The apparatus of claim 2, further comprising one or more motors electrically connected to a first controller disposed in movable communication with the cover. (Item 24) 23. The apparatus of claim 22, further comprising one or more motors electrically connected to a second controller disposed in movable communication with the cover. (Item 25) 25. The apparatus of any one of items 2, 23, or 24, wherein the cover comprises a rigid element and a flexible extension attached to and extending laterally away from the rigid element, the flexible extension applying a force to at least a portion of one or more receptacles when present within the receptacle well when the cover is in the closed position. (Item 26) 24. The apparatus of claim 23, wherein the cover comprises two or more flexible extensions extending in the same direction away from the rigid element, each of the two or more flexible extensions corresponding to one or more receptacle wells, and wherein when the cover is in the closed position, each of the two or more flexible extensions applies a force to at least a portion of a single receptacle when present within the receptacle well. (Item 27) 24. The apparatus of claim 23, wherein the cover comprises two or more flexible extensions extending in the same direction away from the rigid element, each of the two or more flexible extensions corresponding to one or more receptacle wells, and each of the two or more flexible extensions exerts a force on at least a portion of one or more receptacles when present within the receptacle well when the cover is in the closed position. (Item 28) 28. The apparatus of any one of claims 1 to 27, further comprising a stripper plate movably associated with the receptacle holder, the stripper plate removing a receptacle from a receptacle transport mechanism that delivers the receptacle to the receptacle holder. (Item 29) 29. The apparatus of claim 28, wherein the stripper plate is movable into an unlocked and locked position relative to the receptacle well, the unlocked position allowing access of the receptacle to the receptacle well and the locked position preventing removal of the receptacle from the receptacle well without preventing access to the receptacle by the receptacle transport mechanism. (Item 30) 2. The device of claim 1, wherein the device does not include a cover. (Item 31) Item 30. The device of item 28, wherein the device does not include a cover. (Item 32) Item 32. The apparatus of item 30 or 31, wherein the first end of each optical fiber is fixedly positioned within one of the through holes relative to the surface of the receptacle well. (Item 33) A system comprising one or more devices according to any one of items 1 to 32. (Item 34) Item 34. The system of item 33, wherein the thermal element corresponding to each receptacle holder is independently controllable to change only the temperature of its corresponding receptacle holder. (Item 35) 35. The system of claim 33 or 34, wherein each of the one or more devices is in independent thermal communication with a single heat sink. (Item 36) 36. The system of any one of items 33 to 35, wherein all devices are in thermal communication with a single heat sink. (Item 37) 37. The system of any one of items 33 to 36, further comprising a first controller electrically connected to each of the thermal elements. (Item 38) Item 38. The system of item 37, further comprising one or more motors electrically connected to the first controller, the one or more motors being disposed in movably communication with the covers corresponding to each receptacle holder. (Item 39) Item 39. The system of item 38, further comprising one or more motors electrically connected to a second controller and disposed in movably communication with the cover. (Item 40) Each device further comprises a cover movable between an open position and a closed position relative to the receptacle holder, wherein one or more receptacles disposed within one or more of the receptacle wells are seated or secured within the receptacle wells by the cover when the cover is moved to the closed position; Item 34. The system of item 33, wherein the first end of each optical fiber moves within its corresponding through hole when (1) the cover is moved to the closed and / or open position, or (2) a receptacle is present in the receptacle well and the cover is moved to the closed and / or open position. (Item 41) Item 41. The system of item 40, wherein the cover corresponding to each receptacle holder is independently controllable by the first controller to move between an open position and a closed position for only that corresponding receptacle holder. (Item 42) Item 41. The system of item 40, wherein the cover corresponding to each receptacle holder is independently controllable by the second controller to move between an open position and a closed position for only that corresponding receptacle holder. (Item 43) 43. The system of any one of claims 33 to 42, wherein the system comprises at least 10 receptacle wells and at least 10 corresponding optical fibers. (Item 44) Item 44. The system of item 43, wherein the second ends of all of the optical fibers are in optical communication with one or more excitation signal sources or emission signal detectors. (Item 45) Item 44. The system of item 43, wherein the second ends of all of the optical fibers are in optical communication with one or more excitation signal sources and one or more emission signal detectors. (Item 46) Item 46. The system of item 45, wherein the second ends of all of the optical fibers are in optical communication with an excitation signal source and an emission signal detector. (Item 47) Item 46. The system of item 45, wherein the second ends of all of the optical fibers are in optical communication with a single excitation signal source or mission signal detector. (Item 48) 1. A method for performing an automated random access incubation process, comprising: (a) an automated step of transferring a first set of receptacles to a first receptacle holder and subjecting the contents of said first set of receptacles to a first incubation process; (b) during said first incubation process, an automated step of transferring a second set of receptacles to a second receptacle holder and subjecting the contents of said second set of receptacles to a second incubation process; A method comprising: (Item 49) Item 49. The method of item 48, wherein each of the first and second sets of receptacles is sealed to prevent contamination and / or evaporation. (Item 50) 50. The method of claim 48 or 49, wherein each of the first and second receptacle holders is in thermal communication with a single heat sink. (Item 51) 51. The method of any one of items 48 to 50, wherein each of the first and second receptacle holders is in thermal communication with a single temperature cycling device. (Item 52) 1. A method for performing an automated random access incubation process, comprising: (a) an automated step of transferring a first set of receptacles to a first receptacle holder and subjecting the contents of said first set of receptacles to a first incubation process; (b) during said first incubation process, an automated step of transferring a second set of receptacles to a second receptacle holder and subjecting the contents of said second set of receptacles to a second incubation process; wherein the first and second receptacle holders are components of the device described in item 1. (Item 53) 53. The method of any one of items 48 to 52, wherein the transfer of the first and second sets of receptacles is accomplished by a receptacle transport mechanism. (Item 54) 54. The method of any one of items 48 to 53, further comprising initiating a third process of the three or more independent processes during the second incubation process, the third process comprising transferring a third or more set of receptacles to a third or more receptacle holder and subjecting the contents of the third or more set of receptacles to a third or more incubation process, the transfer of each successive set of receptacles being initiated prior to completion of the incubation process for each immediately preceding set of receptacles. (Item 55) 55. The method of any one of items 48 to 54, wherein each set of receptacles comprises one or more closed receptacles. (Item 56) Item 56. The method of item 55, wherein each set of closed receptacles comprises between 5 and 10 closed receptacles. (Item 57) 57. The method of any one of items 48 to 56, wherein the first set of receptacles is removed from the first receptacle holder prior to completion of the second incubation process. (Item 58) 58. The method of claim 57, wherein the first set of receptacles is removed from the first receptacle holder prior to completion of the second or more incubation processes. (Item 59) 58. The method of claim 57, wherein the second set of receptacles is removed from the third receptacle holder prior to completion of the third or more incubation processes. (Item 60) 58. The method of claim 57, wherein each set of receptacles is removed from its respective receptacle holder prior to completion of the next sequential incubation process. (Item 61) 61. The method of any one of items 48-60, wherein the receptacles of each set are mounted or secured into a respective receptacle holder through contact with a movable cover. (Item 62) Item 62. The method of item 61, wherein the cover comprises a rigid element and a flexible extension, the flexible extension being attached to the rigid element and extending laterally away therefrom. (Item 63) Item 62. The method of item 61, wherein the cover comprises two or more flexible extensions extending in the same direction away from the rigid element, each of the two or more flexible extensions corresponding to a single closed receptacle, and each of the two or more flexible extensions covering at least a portion of the single closed receptacle when the cover is in the closed position. (Item 64) Item 62. The method of item 61, wherein the cover comprises two or more flexible extensions extending in the same direction away from the rigid element, each of the two or more flexible extensions corresponding to one or more closed receptacles, and each of the two or more flexible extensions covering at least a portion of the one or more closed receptacles when the cover is in the closed position. (Item 65) Item 65. The method of any one of items 55 to 64, wherein each closure receptacle contacts a single optical fiber when installed or secured within the receptacle holder. (Item 66) 66. The method according to any one of items 48 to 65, wherein all of the receptacle holders are disposed within a single housing. (Item 67) 1. A method of establishing optical communication between a receptacle and an excitation signal source and / or an emission signal detector within a housing of a device, comprising: (a) providing a receptacle in a well of a receptacle holder made of a thermally conductive material; (b) applying a first force to the receptacle, thereby seating the receptacle within the well; (1) causing movement of an end of an optical fiber toward and into contact with the installed receptacle while the force is being applied to the receptacle; or (2) while the force is being applied to the receptacle, the receptacle applies a second force to an end of an optical fiber disposed within the well, the end of the optical fiber moving within the well in a direction opposite from the direction of the applied second force. Either A method comprising: (Item 68) Item 68. The method of item 67, wherein the receptacle contacts the optical fiber during or after step (a), and while the force is being applied to the receptacle, the receptacle contacts and applies a force to the end of the optical fiber disposed in the well, such that the end of the optical fiber moves within the well in a direction opposite from the direction of the applied force. (Item 69) Item 69. The method of item 67 or 68, wherein a cover applies the first force to the receptacle. (Item 70) 70. The method of claim 69, wherein the end of the optical fiber, or a region proximal to the end, is directly or indirectly connected to the receptacle holder using a resilient element, and when a force is applied to the receptacle, the resilient element contracts. (Item 71) 70. The method of claim 69, wherein the cover is movable between an open position and a closed position relative to the well. (Item 72) 72. The method of any one of items 67 to 71, wherein the well is receptacle-shaped to provide uniform contact between the well and the receptacle. (Item 73) A housing and a plurality of receptacle holders contained within the housing, each receptacle holder being made of a thermally conductive material, each receptacle holder including a plurality of receptacle wells; one or more thermal elements positioned proximate each receptacle holder to vary a temperature of one or more of the plurality of receptacle wells; a plurality of covers each disposed in movably associated relation with the receptacle holder; Equipped with A first controller controls movement of each cover between an open position and a closed position, (a) at least one receptacle is present in the plurality of receptacle wells, and when the cover is in the closed position, the at least one receptacle is secured within the receptacle well by the cover; (b) a receptacle transport mechanism is accessible to the plurality of receptacle wells for introducing or removing receptacles when the cover is in the open position; The apparatus, wherein each cover is movable between the open and closed positions together with or independently of one or more other covers. (Item 74) Item 74. The apparatus of item 73, wherein the cover comprises one or more flexible extensions, each individual flexible extension being associated with a single receptacle well in the receptacle holder. (Item 75) Item 74. The apparatus of item 73, wherein the cover comprises a series of flexible extensions, each individual flexible extension being associated with two or more receptacle wells in the receptacle holder. (Item 76) 76. The apparatus of any one of claims 73 to 75, wherein the cover secures the receptacles within the plurality of receptacle wells by applying a force directly to the receptacles, the cover flexing while the force is being applied. (Item 77) Item 77. The apparatus of item 76, wherein each of the multiple receptacle wells of a single receptacle holder are aligned with one another. (Item 78) 78. The apparatus of any one of items 73 to 77, wherein the one or more thermal elements are electrically connected to the first controller. (Item 79) 79. The apparatus of any one of items 73 to 78, wherein the one or more thermal elements are electrically connected to a second controller. (Item 80) 80. The apparatus of any one of items 73 to 79, further comprising an optical fiber associated with each receptacle well such that optical communication is established between the interior of each receptacle well and an excitation signal source and / or an emission signal detector. (Item 81) Item 81. The apparatus of item 80, further comprising one or more receptacles within the plurality of receptacle wells, the optical fibers establishing optical communication between each receptacle and the excitation signal source and / or the emission signal detector. (Item 82) Item 82. The apparatus of item 80 or 81, wherein optical communication is established when the cover is in the second position. (Item 83) Item 83. The apparatus of any one of items 73 to 82, further comprising a stripper plate movably associated with each receptacle holder for removing a receptacle from the receptacle transport mechanism. (Item 84) 84. The device of any one of items 73 to 83, wherein five receptacle wells are arranged in a row within the receptacle holder. (Item 85) A housing and a plurality of receptacle holders contained within the housing, each receptacle holder being made of a thermally conductive material, each receptacle holder including a plurality of receptacle wells; one or more thermal elements electrically connected to the first controller and positioned proximate each receptacle holder to vary a temperature of one or more of the plurality of receptacle wells; a plurality of covers each movable between a first disengaged position and a second engaged position relative to the receptacle holder; Equipped with Each cover includes a series of flexible extensions; Each individual flexible extension is associated with a single receptacle well in the receptacle holder, and movement of each cover between the first disengaged position and the second engaged position is controlled by a second controller, whereby (a) at least one receptacle is present in the plurality of receptacle wells and is secured within the receptacle well by the cover when in the second position; (b) when the cover is in the first position, a receptacle transport mechanism is accessible to the plurality of receptacle wells for introducing or removing receptacles; The apparatus, wherein each cover is movable between said first and second positions together with or independently of one or more other covers. (Item 86) Item 86. The apparatus of item 85, wherein the first controller and the second controller are the same unit. (Item 87) 1. An apparatus comprising one or more receptacle holders, each of which is made of a thermally conductive material; The one or more receptacle holders include: a plurality of receptacle wells, each receptacle well configured to receive a receptacle therein; a plurality of through holes, each through hole extending from an inner surface of one of the receptacle wells to an outer surface of the receptacle holder; a plurality of optical fibers, each optical fiber having a first and second end, the first end in optical communication with one of the receptacle wells and the second end in optical communication with at least one of an excitation signal source and an emission signal detector, the first end of each optical fiber disposed outside, inside, or extending through a corresponding through hole in each receptacle well; one or more thermal elements positioned proximate the receptacle holder to change one or more temperatures of the receptacle holder; a primary cover fixedly positioned over the receptacle holder, the primary cover having one or more fixation arms arranged in an array that aligns with and surrounds each receptacle well of the receptacle holder, one or more receptacles disposed within one or more of the receptacle wells being mounted or secured into the receptacle wells by the fixation arms; a secondary cover fixedly positioned over the primary cover, the secondary cover having one or more release arms aligned with and in sliding contact with the fixed arms of the primary cover; The apparatus wherein application of a force to the release arm pushes the locking arm in a radially outward direction relative to an axial center of the receptacle well, thereby releasing the receptacle disposed within the receptacle well. (Item 88) 88. A system comprising one or more devices according to item 87. (Item 89) The receptacle transport mechanism further includes: a body having a plunger slidably disposed therein; one or more rims hingedly attached to the body, the one or more rims positioned in sliding communication with a knob fixedly attached to the plunger; Equipped with Item 90. The system of item 88, wherein when the plunger is in a first position, a lower portion of the one or more rims is proximal to the body, and when the plunger is in a second position, the lower portion of the one or more rims is extended in a radially outward direction relative to the body. (Item 90) 29. A system comprising one or more devices according to item 28. (Item 91) The receptacle transport mechanism further includes: a body having a plunger slidably disposed therein; one or more rims hingedly attached to the body, the one or more rims positioned in sliding communication with a knob fixedly attached to the plunger; Item 91. The system of item 90, comprising: when the plunger is in a first position, a lower portion of the one or more rims is proximal to the body, and when the plunger is in a second position, the lower portion of the one or more rims is extended in a radially outward direction relative to the body. (Item 92) 1. A method for performing an automated random access incubation process, comprising: (a) an automated step of transferring a first set of receptacles to a first receptacle holder and subjecting the contents of said first set of receptacles to a first incubation process; (b) during said first incubation process, an automated step of transferring a second set of receptacles to a second receptacle holder and subjecting the contents of said second set of receptacles to a second incubation process; 88. A method according to claim 87, wherein the first and second receptacle holders are components of the apparatus described in item 87. (Item 93) 1. An apparatus comprising one or more receptacle holders, each of which is made of a thermally conductive material; One or more receptacle holders may be a plurality of receptacle wells, each receptacle well configured to receive a receptacle therein; a plurality of through holes, each through hole extending from an inner surface of one of the receptacle wells to an outer surface of the receptacle holder; a plurality of optical fibers, each optical fiber having a first and second end, the first end in optical communication with one of the receptacle wells and the second end in optical communication with at least one of an excitation signal source and an emission signal detector, the first end of each optical fiber disposed outside, inside, or extending through a corresponding through hole in each receptacle well; one or more thermal elements positioned proximate the receptacle holder to change one or more temperatures of the receptacle holder; Including, When present, one or more receptacles disposed within one or more of said receptacle wells are fixedly mounted to maximize contact with said inner surface of said receptacle well. (Item 94) Item 94. The device of item 93, wherein the device does not include a cover. (Item 95) Item 94. The apparatus of item 93, further comprising a cover movable between an open position and a closed position relative to the receptacle holder. (Item 96) 94. A system comprising one or more devices according to item 93. (Item 97) 1. A method for performing an automated random access incubation process, comprising: (a) an automated step of transferring a first set of receptacles to a first receptacle holder and subjecting the contents of said first set of receptacles to a first incubation process; (b) during said first incubation process, an automated step of transferring a second set of receptacles to a second receptacle holder and subjecting the contents of said second set of receptacles to a second incubation process; Including, Item 94. The method, wherein the first and second receptacle holders are components of the apparatus described in item 93. [Brief description of the drawings]

[0025] [Figure 1] FIG. 1 is a pictorial diagram showing an apparatus of the present disclosure. [Diagram 2] FIG. 2 is a pictorial diagram showing an apparatus of the present disclosure mounted within an enclosure. [Figure 3A] 3A-3C are pictorial diagrams showing a receptacle holder of the present disclosure. [Figure 3B] 3A-3C are pictorial diagrams showing a receptacle holder of the present disclosure. [Figure 3C] 3A-3C are pictorial diagrams showing a receptacle holder of the present disclosure. [Figure 4] FIG. 4 is a pictorial diagram showing a top view of an apparatus of the present disclosure mounted within a housing. [Figure 5A] 5A-5C are pictorial diagrams showing a receptacle holder mounted in sliding engagement with a support. The support is mounted in thermal communication with a heat sink (FIG. 5A). A cross brace may be mounted to the support to exert a force on the front face of the receptacle holder (FIG. 5B). A detailed view of the support is shown in FIG. 5C. [Figure 5B]5A-5C are pictorial diagrams showing a receptacle holder mounted in sliding engagement with a support. The support is mounted in thermal communication with a heat sink (FIG. 5A). A cross brace may be mounted to the support to exert a force on the front face of the receptacle holder (FIG. 5B). A detailed view of the support is shown in FIG. 5C. [Figure 5C] 5A-5C are pictorial diagrams showing a receptacle holder mounted in sliding engagement with a support. The support is mounted in thermal communication with a heat sink (FIG. 5A). A cross brace may be mounted to the support to exert a force on the front face of the receptacle holder (FIG. 5B). A detailed view of the support is shown in FIG. 5C. [Figure 5D] 5D and 5E are pictorial diagrams showing an exemplary receptacle holder. The receptacle holder may include a channel through which wiring and / or electrical connections for one or more thermistors may be placed (FIG. 5D). The receptacle holder may also include one or more ridges formed corresponding to closed through holes disposed within the channel for containing one or more thermistors (FIG. 5E). [Figure 5E] 5D and 5E are pictorial diagrams showing an exemplary receptacle holder. The receptacle holder may include a channel through which wiring and / or electrical connections for one or more thermistors may be placed (FIG. 5D). The receptacle holder may also include one or more ridges formed corresponding to closed through holes disposed within the channel for containing one or more thermistors (FIG. 5E). [Figure 6A] 6A and 6B are pictorial diagrams showing the receptacle holder mounted in sliding engagement with the support. [Figure 6B] 6A and 6B are pictorial diagrams showing the receptacle holder mounted in sliding engagement with the support. [Figure 7A] 7A and 7B are pictorial diagrams showing multiple rows of receptacle holders disposed within a device of the present disclosure (FIG. 7A) and that cartridge heaters may be disposed within the heat sink of the device (FIG. 7B). [Figure 7B] 7A and 7B are pictorial diagrams showing multiple rows of receptacle holders disposed within a device of the present disclosure (FIG. 7A) and that cartridge heaters may be disposed within the heat sink of the device (FIG. 7B). [Figure 8A] 8A-8E are pictorial diagrams showing an exemplary cover and stripper plate disposed within an apparatus of the present disclosure. [Figure 8B] 8A-8E are pictorial diagrams showing an exemplary cover and stripper plate disposed within an apparatus of the present disclosure. [Figure 8C] 8A-8E are pictorial diagrams showing an exemplary cover and stripper plate disposed within an apparatus of the present disclosure. [Figure 8D] 8A-8E are pictorial diagrams showing an exemplary cover and stripper plate disposed within an apparatus of the present disclosure. [Figure 8E] 8A-8E are pictorial diagrams showing an exemplary cover and stripper plate disposed within an apparatus of the present disclosure. [Figure 9A] 9A-9C are pictorial diagrams showing the movement of an optical fiber of an apparatus of the present disclosure and the forces associated therewith before and after seating of the receptacle within a receptacle well of a receptacle holder. [Figure 9B] 9A-9C are pictorial diagrams showing the movement of an optical fiber of an apparatus of the present disclosure and the forces associated therewith before and after seating of the receptacle within a receptacle well of a receptacle holder. [Figure 9C] 9A-9C are pictorial diagrams showing the movement of an optical fiber of an apparatus of the present disclosure and the forces associated therewith before and after seating of the receptacle within a receptacle well of a receptacle holder. [Figure 10] FIG. 10 is a pictorial diagram showing an apparatus in optical communication with an excitation signal source and / or an emission signal detector within the housing of an instrument for performing biochemical analysis. [Figure 11A]11A and 11B are flow charts illustrating exemplary steps involved in a method for establishing optical communication between a receptacle and an excitation signal source and / or an emission signal detector within an apparatus housing while allowing maximum contact between the surface of the receptacle well and the receptacle. [Figure 11B] 11A and 11B are flow charts illustrating exemplary steps involved in a method for establishing optical communication between a receptacle and an excitation signal source and / or an emission signal detector within an apparatus housing while allowing maximum contact between the surface of the receptacle well and the receptacle. [Figure 12A] 12A-12D are pictorial diagrams illustrating exemplary steps involved in loading a receptacle into a receptacle well of a receptacle holder of a device of the present disclosure. [Figure 12B] 12A-12D are pictorial diagrams illustrating exemplary steps involved in loading a receptacle into a receptacle well of a receptacle holder of a device of the present disclosure. [Figure 12C] 12A-12D are pictorial diagrams illustrating exemplary steps involved in loading a receptacle into a receptacle well of a receptacle holder of a device of the present disclosure. [Figure 12D] 12A-12D are pictorial diagrams illustrating exemplary steps involved in loading a receptacle into a receptacle well of a receptacle holder of a device of the present disclosure. [Figure 13] FIG. 13 is a flow chart illustrating exemplary steps involved in a method for performing an automated random access temperature cycling process. [Figure 14A] 14A-14D are pictorial diagrams showing a second exemplary embodiment of an apparatus of the present disclosure. [Figure 14B] 14A-14D are pictorial diagrams showing a second exemplary embodiment of an apparatus of the present disclosure. [Figure 14C] 14A-14D are pictorial diagrams showing a second exemplary embodiment of an apparatus of the present disclosure. [Figure 14D]14A-14D are pictorial diagrams showing a second exemplary embodiment of an apparatus of the present disclosure. [Figure 15] 15A-15C are pictorial diagrams showing a modified pipettor for use as a receptacle transport mechanism in the systems of the present disclosure. [Figure 16] FIG. 16 is a pictorial diagram showing a perspective view of an alternative exemplary embodiment of a cover mechanism for the device. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0026] The present disclosure relates to systems, devices, and methods for incubating at least one receptacle holder adapted for use in an automated instrument capable of performing nucleic acid-based amplification tests, as well as methods for using the same to perform an automated random access temperature cycling process.

[0027] Before the present systems, methods, and devices are described, it is to be understood that this disclosure is not limited to the particular methods, and experimental conditions, such as methods and conditions, described may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present disclosure will be limited only by the appended claims.

[0028] As used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural references unless the context clearly dictates otherwise. Thus, reference to "the method" includes one or more methods, and / or steps of the type described herein that will be apparent to those skilled in the art upon reading this disclosure, etc.

[0029] The term "comprising," which is used interchangeably with "comprise," "contain," "have," and "characterized by," is an inclusive or open-ended term and does not exclude additional, unrecited elements or method steps. The phrase "consisting of" excludes any element, step, or ingredient not specified in the claim. The phrase "consisting essentially of" limits the scope of the claim to the specified materials or steps, and those that do not materially affect the basic and novel characteristics of the disclosed subject matter. This disclosure contemplates example embodiments of the apparatus and methods of use thereof that correspond to the scope of each of these phrases. Thus, an apparatus or method that comprises recited elements or steps contemplates specific embodiments of the apparatus or method that consist essentially of, or consist of, those elements or steps.

[0030] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing disclosed herein, the preferred methods and materials are described herein.

[0031] As used herein, "reaction mixture" refers to a volume of fluid that contains one or more of a buffer for a nucleic acid amplification reaction, one or more nucleotides, an enzyme, and a sample containing or suspected of containing nucleic acids.

[0032] As used herein, "sample" or "test sample" refers to any material suspected of containing a target organism or biological molecule, such as a nucleic acid. The material may be, for example, an unprocessed clinical specimen, a buffer medium containing the specimen, a medium containing the specimen and a lysis agent for releasing nucleic acid belonging to the target organism, or a medium containing nucleic acid from a target organism that has been isolated and / or purified in a reaction receptacle and / or on a reaction material or device. In some cases, the sample or test sample may contain a product of a biological specimen, such as an amplified nucleic acid to be detected.

[0033] As used herein, "analyte" refers to a substance, such as a nucleic acid or protein, that is detected or measured in an analytical procedure. The analyte may be contained in the sample being tested.

[0034] As used herein, "polynucleotide" refers to either RNA, DNA, or chimeric molecules that contain both RNA and DNA.

[0035] As used herein, "nucleic acid" refers to a polymeric compound that includes nucleosides or nucleoside analogs with nitrogen-containing heterocyclic bases or base analogs linked by phosphodiester or other bonds to form a polynucleotide. Nucleic acids include RNA, DNA, or chimeric DNA-RNA polymers, and analogs thereof. The nucleic acid "backbone" can be composed of a variety of linkages, including one or more of sugar phosphodiester linkages, peptide nucleic acid (PNA) linkages (PCT WO95 / 32305), phosphorothioate linkages, methylphosphonate linkages, or combinations thereof. The sugar portion of the nucleic acid can be either ribose or deoxyribose, or analogs with known substitutions such as 2' methoxy and 2' halide substitutions (e.g., 2'-F). The nitrogen-containing bases can be any of the conventional bases (A, G, C, T, U), their analogs (e.g., inosine), N, N-glycosyltransferase (N-glycosyltransferase), or the like. 4 -Methyldeoxyguanosine (N 4-methyl deoxygaunosine), derivatives of purine or pyrimidine bases such as deazapurines or azapurines, deazapyrimidines or azapyrimidines, pyrimidine bases having a substituent at the 5- or 6-position, 2-amino-6-methylaminopurine, O 6 -methylguanine, 4-thio-pyrimidine, 4-amino-pyrimidine, 4-dimethylhydrazine-pyrimidine, and O 4 The nucleic acid may be a purine base with modified or replaced substituents at the 2-, 6-, and / or 8-positions, such as 3-alkyl-pyrimidines, and pyrazolo-compounds, such as unsubstituted or 3-substituted pyrazolo[3,4-d]pyrimidines (U.S. Pat. Nos. 5,378,825, 6,949,367, and PCT WO 93 / 13121). Nucleic acids may contain "abasic" positions, in which the backbone does not contain a nitrogenous base for one or more residues (see U.S. Pat. No. 5,585,481). Nucleic acids also include "locked nucleic acids" (LNAs), which are analogs that contain one or more LNA nucleotide monomers with bicyclic furanose units locked into the RNA to mimic the sugar conformation (Vester et al., 2004, Biochemistry 43(42):13233-41). The nucleic acids can contain only conventional sugars, bases, and linkages as found in RNA and DNA, or can contain conventional components and substitutions (e.g., nucleic acids containing conventional bases attached through a 2' methoxy backbone, or mixtures of conventional bases and one or more base analogues). Methods for synthesizing nucleic acids in vitro are well known in the art.

[0036] As used herein, "oligonucleotide" or "oligomer" refers to a polymer composed of two or more nucleoside or nucleobase subunits linked together. Oligonucleotides preferably have lengths ranging from 10 to 100 nucleotides, more preferably from 10 to 80 nucleotides, and even more preferably from 15 to 60 nucleotides. Oligonucleotides can be DNA and / or RNA, as well as analogs thereof. The sugar groups of the nucleoside subunits can be, for example, ribose, deoxyribose, and analogs thereof, including ribonucleosides with 2'-O-methyl substitutions to ribofuranosyl moieties. Oligonucleotides having nucleoside subunits with 2' substitutions and useful as detection probes, capturing oligos and / or amplification oligonucleotides, are disclosed in U.S. Pat. No. 6,130,038. Nucleoside subunits can be linked by linkages such as phosphodiester linkages, modified linkages, or by non-nucleotide moieties that do not prevent hybridization of the oligonucleotide to its complementary target nucleic acid sequence. Modified linkages include those in which the standard phosphodiester linkage is replaced with a different linkage, such as a phosphorothioate linkage or a methylphosphonate linkage. Nucleobase subunits can be linked, for example, by replacing the natural deoxyribose phosphate backbone of DNA with a pseudopeptide backbone, such as a 2-aminoethylglycine backbone, using a carboxymethyl linker to link the nucleobase subunit to a central secondary amine. (DNA analogs with pseudopeptide backbones are commonly referred to as "peptide nucleic acids" or "PNAs" and are disclosed in U.S. Pat. No. 5,539,082). Other non-limiting examples of oligonucleotides or oligomers contemplated by the present disclosure include nucleic acid analogs containing bicyclic and tricyclic nucleoside and nucleotide analogs, referred to as "locked nucleic acids," "locked nucleoside analogs," or "LNAs" (see, e.g., U.S. Pat. Nos. 6,083,482, 6,268,490, and 6,670,461).Any nucleic acid analog is contemplated by this disclosure, provided that the modified oligonucleotide is capable of hybridizing to the target nucleic acid under either stringent hybridization or amplification reaction conditions.

[0037] As used herein, the term "biochemical analysis" refers to a scientific research procedure for quantitatively assessing or quantitatively measuring the presence or amount or functional activity of a target entity, such as, but not limited to, a biochemical substance, a cell, an organic sample, or a target nucleic acid sequence. The term "biochemical analysis" includes nucleic acid amplification and thermal denaturation (i.e., melting). Nucleic acid melting typically involves precise warming of a double-stranded nucleic acid molecule to a temperature at which the two strands separate or "melt" apart. The melting process typically occurs at a temperature of about 50°C to about 95°C.

[0038] As used herein, "target nucleic acid sequence" or "target sequence" refers to the strand of a nucleic acid molecule that is being analyzed. Thus, when used in the context of an amplification analysis, a target sequence refers to a sequence of nucleotides or a portion of a nucleic acid molecule that is intended to be replicated.

[0039] As used herein, "amplification" or "amplifying" refers to an in vitro procedure for obtaining multiple copies of a target nucleic acid sequence, its complement, or a fragment thereof. For example, an in vitro amplification reaction is an enzyme-catalyzed reaction that results in the synthesis of multiple copies of a target nucleic acid sequence, its complement, or a fragment thereof. Examples of amplification methods that can be used to prepare an in vitro amplification reaction are shown below. Preferred in vitro amplification methods include: In vitro amplification reaction means exponential synthesis of amplicons, with one amplicon serving as a template for the production of new amplicons. As used herein, the term "amplicon" or "amplification product" refers to a nucleic acid molecule produced in a nucleic acid amplification reaction. The amplicon or amplification product contains a target nucleic acid sequence, which may be the same or opposite sense as the target nucleic acid.

[0040] Target nucleic acid amplification involves the use of amplification oligonucleotides (e.g., primer sequences) and enzymes (e.g., polymerases) to synthesize nucleic acid amplification products (copies) that contain sequences that are either complementary or homologous to the template nucleic acid sequence being amplified. As used herein, "amplification oligonucleotide" refers to a nucleic acid strand that serves as a starting point for the production of an amplification product. An amplification product can be either an extension product or a transcript, which is generated in a transcription-based amplification procedure. The amplification oligonucleotides can be provided to the reaction mixture free in solution, or one or more of the amplification oligonucleotides can be immobilized on a solid support, including the inner surface of one or more chambers in a receptacle. See, for example, U.S. Patent Nos. 5,641,658 and 7,582,470. Examples of nucleic acid amplification procedures practiced in the art include, but are not limited to, polymerase chain reaction (PCR), strand displacement amplification (SDA), helicase-dependent amplification (HDA), loop-mediated isothermal amplification (LAMP), and various transcription-based amplification procedures, including transcription-mediated amplification (TMA), nucleic acid sequence-based amplification (NASBA), and self-sustained sequence replication (3SR).See, e.g., Mullis, "Process for Amplifying, Detecting, and / or Cloning Nucleic Acid Sequences," U.S. Pat. No. 4,683,195; Walker, "Strand Displacement Amplification," U.S. Pat. No. 5,455,166; Kong et al., "Helicase Dependent Amplification of Nucleic Acids," U.S. Pat. No. 7,282,328; Notomi et al., "Process for Synthesizing Nucleic Acid," U.S. Pat. No. 6,410,278; Kacian et al., "Nucleic Acid Sequence Amplification Methods," U.S. Pat. No. 5,399,491; Becker et al., "Single-Primer Nucleic Acid Amplification Methods," U.S. Pat. No. 7,374,885; Malek et al., "Enhanced Nucleic Acid Amplification Process," U.S. Pat. No. 5,130,238; and Lizardi et al. (1988) BioTechnology 6:1197. With some procedures, the formation of detectable amplification products depends on an initial antibody / antigen interaction. See, for example, Cashman, "Blocked-Polymerase Polynucleotide Immunoassay Method and Kit," U.S. Patent No. 5,849,478. Nucleic acid amplification is particularly beneficial when the amount of analyte (e.g., target nucleic acid, antigen, or antibody) present in the sample is very low. Since less analyte is required at the start of the analysis to ensure detection of the analyte, the sensitivity of the analysis can be greatly improved by amplifying the target sequence associated with the analyte and detecting the synthesized amplification product.

[0041] As used herein, the terms "cultivating," "incubation," "incubation process," and all variations thereof, collectively refer to changing the temperature of an object in a controlled manner such that conditions are sufficient to perform a desired biochemical analysis. The term is therefore intended to encompass heating a receptacle to a desired temperature and maintaining such temperature for a fixed time interval. The term also includes the act of subjecting the receptacle to one or more heating and cooling cycles (i.e., "temperature cycling"). Temperature cycling typically occurs at a relatively high rate of change of temperature, but the term is not so limited and can encompass any rate of change of temperature.

[0042] As used herein, "detectable label" or simply "label" refers to a chemical moiety that can be detected or can lead to a detectable response. According to the present disclosure, a detectable label can be attached to a probe, such as a hybridization probe, either directly or indirectly. Examples of detectable labels include, but are not limited to, radioisotopes, enzymes, haptens, chromophores such as dyes or particles that impart detectable color (e.g., latex beads or metal particles), luminescent compounds (e.g., bioluminescent, phosphorescent, or chemiluminescent moieties), and fluorescent compounds.

[0043] (Receptacle holder) The conditions for nucleic acid amplification reactions may be substantially isothermal or may require periodic temperature changes, similar to PCR thermal cycling. The devices described herein may be used to heat and maintain a nucleic acid-containing sample to a constant or ambient temperature, or may be used to vary its temperature. The target nucleic acid amplification reaction may be either a "real-time" or "end-point" analysis. Thus, in an exemplary aspect, a device is provided that performs the heating (i.e., isothermal or temperature cycling) required for nucleic acid amplification analysis. As shown in FIG. 1, the device 100 includes one or more (i.e., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or any integer between 1 and 20, or more) receptacle holders 110 (see also FIG. 3). In an exemplary embodiment, the device 100 includes two or more receptacle holders 110. Such devices may include a housing 50 (see FIGS. 2 and 4) within which one or more receptacle holders 110 are located. Housing 50 may be made from any suitable material of construction such as, for example, plastic or metal.

[0044] When multiple receptacle holders 110 are provided in the device described herein, each receptacle holder 110 disposed within the device may be arranged in alignment with one another to facilitate automated processing steps involved in nucleic acid amplification analysis. It should be understood that any arrangement may be used according to the size and shape of the device. In an exemplary embodiment, the receptacle holders are arranged within the device in one or more rows of two receptacle holders per row (i.e., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more), as shown in FIG. 4. Thus, two receptacle holders may be arranged in a row either thermally connected to one another or thermally isolated from one another. In an exemplary embodiment, the device 100 includes six rows of two receptacle holders per row.

[0045] 3A-3C, the receptacle holder 110 optionally includes a plurality (i.e., two or more) of receptacle wells 120 configured to receive receptacles 130 containing samples or reaction mixtures 140. For purposes of description, the surface of the receptacle holder into which the receptacle 130 is inserted is referred to as its "top" 150. Similarly, the surface of the receptacle holder opposite the surface into which the receptacle 130 is inserted is referred to as its "bottom" 160. In an exemplary embodiment, each receptacle holder 110 includes five or more (i.e., 5, 6, 7, 8, 9, 10, or any integer between 1 and 10, or more) receptacle wells 120. In another exemplary embodiment, each receptacle holder 110 includes between 1 and 10 receptacle wells. In another exemplary embodiment, each receptacle holder includes between three and six receptacle wells. In yet another exemplary embodiment, each receptacle holder includes five receptacle wells. Each of the multiple receptacle wells in each receptacle holder may be positioned in alignment with one another. In an exemplary embodiment, the receptacle wells 120 are arranged in a row extending along the length of the top surface 150 of the receptacle holder 110.

[0046] Exemplary materials from which the receptacle holder may be made include, but are not limited to, aluminum, titanium, copper, steel, magnesium, metal composites, metal alloys, ceramics, plastics, plastic composites, or any suitable thermally conductive material.

[0047] As used herein, a receptacle well of a receptacle holder that is "configured to receive" a receptacle of a particular size or shape refers to a receptacle well whose dimensions are substantially similar to the size and shape of the receptacle 130 (i.e., a sample tube) that fits snugly within the receptacle well 120, thereby maximizing contact between a surface of the receptacle well 120 and the receptacle 130. In an embodiment, this maximum contact refers to physical contact of the receptacle well 120 with at least a portion of the receptacle 130. In various embodiments, receptacles 130 according to the present disclosure are individual reaction vessels made from a suitable rigid or flexible material and shaped and sized to fit within the receptacle wells of the devices described herein. In other embodiments, two or more (i.e., 2, 3, 4, 5 or more) receptacles may be manufactured as a single unit configured to fit within the receptacle holder. Each receptacle 130 may be closed or sealed to prevent contamination and / or evaporation of the contents therein and / or to facilitate handling or transportation of each receptacle. Such seals may be permanent or semi-permanent and may be fluid-tight. In some embodiments, the seal comprises a cap or lid 135.

[0048] Within each receptacle well 120 is at least one through hole 170 that extends from the inner surface 180 of the receptacle well to the outer surface of the receptacle holder. In an exemplary embodiment, the through hole 170 of a particular receptacle well 120 extends from the center of the bottom of the inner surface 180 of the receptacle well 120 and extends to the surface of the receptacle holder 110 that is opposite the surface of the receptacle holder into which the receptacle 130 is inserted (i.e., in this embodiment, the through hole extends from the bottom of the receptacle well 120 to the bottom surface 160 of the receptacle holder 110). In an embodiment, the diameter of the through hole 170 is the same as the diameter of the bottom 190 of the inner surface 180 of the receptacle well 120. In other embodiments, the through hole 170 comprises a hole or opening having a dimension smaller than the bottom 190 of the inner surface 180 of the receptacle well 120. In other embodiments, the through hole 170 comprises a hole or opening having a dimension the same as or larger than the bottom 190 of the inner surface 180 of the receptacle well 120. The exact dimensions of the through hole 170 may vary, provided that the presence of the through hole 170 does not adversely affect the ability of the receptacle holder 110 to efficiently transfer heat to and from the receptacle 130 held within the receptacle well 120.

[0049] (Heat Element) As shown in Figures 5A and 5B, one or more thermal elements 200 are positioned proximal to the receptacle holder for varying one or more temperatures of the receptacle holder 110. As used herein, the term "thermal element" may include any known heating element for heating and cooling applications. In one embodiment, the thermal element is a resistive heating element, such as a thin metal film applied to the receptacle holder 110 by using well-known methods such as sputtering or controlled vapor deposition. The heating element can also be provided as a molded or machined insert (e.g., cartridge, etc.) for incorporation into the receptacle holder 110.

[0050] In an exemplary embodiment, the thermal element 200 is a thermoelectric element, such as a "Peltier element," constructed generally from an electron-doped np-type semiconductor pair that acts as a miniature heat pump. When a current is applied to the semiconductor pair, a temperature difference is established, with one side becoming hotter and the other side becoming colder. If the current direction is reversed, the hot and cold sides will be reversed. Typically, a layer of non-conductive material, such as aluminum nitride or polyimide, is placed over the substrate surface of the thermoelectric module to allow for proper isolation of the semiconductor element array.

[0051] As used herein, "one or more altered temperatures" of a receptacle holder refers to an increase or decrease in temperature of the receptacle holder 110. Often, the increase or decrease in temperature is determined relative to the ambient temperature. The term includes the ability to individually adjust the temperature of one or more receptacle wells 120 while separately adjusting the temperatures of other receptacle wells within the same receptacle holder. Thus, the term may refer to uniformly increasing / decreasing the temperature of all receptacle wells 120 within a receptacle holder 110, or may refer to altering a portion of the receptacle wells 120 within a single receptacle holder 110. As used herein, "ambient temperature" refers to the temperature of the surrounding environment, which may include fluids (e.g., air or liquid) or solid structures.

[0052] The thermal element 200 may be electrically connected to a controllable power source 210 for applying an electrical current across the element to change its temperature. Control of the power source 210 may be performed by a suitably programmed processor 220 (such as a computer) that receives signals from one or more thermal sensors 610 (see FIGS. 5A and 6A) in thermal communication with the receptacle holder 110, and / or signals from another processor that controls automated process steps involved in the temperature cycling process, as discussed below.

[0053] The thermal element 200 may be held in contact with the side 115 (see FIG. 3A) of the receptacle holder 110 by one or more supports 240 (see FIG. 5C) that may be positioned in sliding engagement with the receptacle holder 110. As used herein, being positioned "in sliding engagement" refers to non-fixed contact between adjacent surfaces of different parts of the device described herein. Thus, when the device 100 includes two or more receptacle holders 110, each of the two or more receptacle holders is configured in sliding engagement with a support 240. As used herein, the term "support" refers to a rigid structure that may be thermally conductive. Exemplary materials from which the support may be made include, but are not limited to, aluminum, titanium, copper, steel, magnesium, metal composites, metal alloys, ceramics, plastics, plastic composites, or any suitable rigid thermally conductive material. The support may also comprise a combination of materials, such as structures formed of or from plastics, metals (including alloys and composites), ceramics, combinations of one or more different types of these materials.

[0054] As is known in the art, a thermal element may require a certain force to achieve sufficient thermal contact with the component to be heated. For example, some Peltier elements require a mounting force of about 150-300 psi to effectively transfer thermal energy to the element. Referring to FIG. 5B, the apparatus may include one or more cross braces 248 mounted to the support 240 and exerting a force F1 on the front surface 117 of the receptacle holder 110. The force F1 is sufficient to achieve thermal transfer of energy from the thermal element 200 to the receptacle holder 200. In some embodiments, the apparatus includes one cross brace 248 for each receptacle holder 110. In other embodiments, the apparatus includes one cross brace 248 per row of receptacle holders 110. In such embodiments, the cross brace generally incorporates a portion or layer having a low thermal conductivity as the portion in direct contact with the receptacle holder 110. As discussed below, in other embodiments, a body 300 having a low thermal conductivity is used to exert the force required for the thermal transfer of energy to the receptacle holder 110 .

[0055] (Support) As shown in FIG. 5C, the support 240 may be formed in a shape suitable for use in the devices described herein. In an exemplary embodiment, the support is a solid member having a base portion 245 and an upright portion 247. In an embodiment, the base portion 245 and the upright portion 247 comprise a single adjacent material. The upright portion 247 may intersect the base portion at a right angle, or may intersect the base portion 245 at an angle greater than or less than 90°. Disposed within the base portion are a plurality of through holes 242 that are preferably aligned with through holes 170 in the bottom surface 160 of the receptacle holder 110 that will be positioned in sliding engagement therewith. Each of the through holes 242 in the base portion 245 of the support 240 forms a channel through which an optical fiber 400 and / or associated components, such as, for example, a fixed or movable ferrule, may pass, thereby providing optical communication between each receptacle well 120 and an excitation signal source and / or an emission signal detector, as discussed below.

[0056] The upright portion 247 of the support 240 includes a first side 243 and a second side 244. The first side 243 is configured to be positioned proximate to the side 115 of the receptacle holder 110, and the thermal element 200 is positioned between the first side 243 of the support 240 and the receptacle holder 110. The second side 244 of the upright portion 247 of the support 240 provides a solid surface on which at least one body 300 having low thermal conductivity may be positioned (see FIGS. 6A, 6B, and 7A).

[0057] (Main and linker) 6A, 6B, and 7A, when apparatus 100 includes a plurality of supports 240 oriented in a row, as discussed above, the apparatus may include one or more bodies 300 having low thermal conductivity, each associated with a respective receptacle well 120 of receptacle holder 110. In an embodiment, the apparatus will include a linker for exerting a force F1 through body 300 to receptacle holder 110.

[0058] As used herein, the term "linker" refers to any device capable of exerting a force in a direction extending away from a surface on which it is mounted. Exemplary linkers useful in the present apparatus include, but are not limited to, springs, spacers, linear expanders, materials formed of elastic or rubber-like materials, piezoelectric elements, levers, screws, and the like. Thus, in an exemplary embodiment, a first end 312 of a linker 310 (e.g., a spring) is mounted to a second side 243 of an upright portion 247 of a support 240, while a second end 314 contacts and exerts a force F1 on a body 300 having a lower thermal conductivity (e.g., a glass or plastic bead, cap, or insert). Each body 300 then transfers the force F1 exerted on it by the linker 310 onto the side 117 of the receptacle holder 110 opposite the side 115 of the receptacle holder 110 that is in contact with the thermal element 200, thereby ensuring maximum contact between the thermal element 200 and the receptacle holder 110. In one embodiment, the device 100 includes one to ten linkers 310 per support 240, depending on the number of receptacle holders 110 that are positioned in sliding engagement therewith. In another embodiment, the device 100 includes one linker 310 per receptacle well 120. In yet another embodiment, the device 100 includes two linkers 310 per support 240. In yet another embodiment, the device 100 includes five linkers 310 per support 240.

[0059] It should be noted that the body 300 should have a lower thermal conductivity than the receptacle holder 110 to prevent thermal energy from being transferred from the receptacle holder 110 to the body 300 and / or the support 240. Exemplary bodies used in the present device include, but are not limited to, glass or plastic beads that are connected to the receptacle holder either directly or indirectly by a linker 310 located between the support 240 and the body 300.

[0060] 7A, the supports 240 of one row of receptacle holders 110 may be provided as solid surfaces by which the bodies 300 and linkers 310 exert a force F1 on a receptacle holder 110 positioned in sliding engagement with a support 240 located in the immediately succeeding row. For example, the body 300 of a first support 240 positioned in a first row 101 of receptacle holders 110 exerts a force F1 on a side 117 of a receptacle holder 110 positioned in sliding engagement with a second row 102, the first row 101 and second row 102 being adjacent to one another in the device 100 as described herein.

[0061] In certain embodiments, the device may include a single support 240 in sliding engagement with all of the receptacle holders 110, or may include a single support 240 in sliding engagement with each row of receptacle holders 110 (101-106 in FIGS. 4 and 7A), or may include a single support 240 in sliding engagement with each individual receptacle holder 110.

[0062] (Thermistor) In various embodiments, the device may further include one or more (i.e., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) thermal sensors 610 to monitor the temperature of the receptacle holder 110. A wide variety of microsensors are available for determining temperature, including, for example, thermocouples having a bimetallic junction that generates a temperature-dependent electromotive force (EMF), resistance thermometers including a material that has an electrical resistance proportional to the temperature of the material, thermistors, IC temperature sensors, quartz crystal thermometers, and the like. See, for example, Horowitz and Hill, The Art of Electronics, Cambridge University Press 1994 (2nd Ed. 1994). As used herein, the term "thermistor" refers to a type of resistor whose resistance changes significantly with temperature. Such a thermistor 610 may be placed in direct or indirect contact with the receptacle holder 110. In one embodiment, two or more thermistors 610 are placed in contact with the receptacle holder 110. In another embodiment, one or more thermistors 610 are placed in contact with each of the receptacle wells 120 of a single receptacle holder 110 to allow monitoring of the temperature of each individual receptacle well 120.

[0063] As shown in FIG. 5D, in an exemplary embodiment, the receptacle holder 110 may include a channel 612 disposed within the side 115. In various embodiments, the channel extends from an edge of the side 115 to a location corresponding to the central-most receptacle well 120 of the receptacle holder 110. For example, in an embodiment in which the receptacle holder 110 includes five receptacle wells 120, the channel 612 often extends to a location corresponding to the third / central receptacle well 120. The channel 612 is configured to receive therein wires and / or electrical connections for the thermistor 610 of the receptacle block. Locating the wires and / or electrical connections of the thermistor 610 within the channel 612 protects the thermistor and their associated wiring from the heat sinking effects of the ambient temperature, thereby ensuring accurate monitoring of the temperature of the receptacle holder 110. The end of the channel 612 corresponding to the central-most receptacle well 120 may be provided with one or more closed through holes 614 through which a thermistor may be provided such that the thermistor contacts the central-most receptacle well 120. In an embodiment, two through holes 614 are provided in the channel 612 such that two thermistors may be positioned therein to monitor the temperature of the receptacle holder 110 on opposite sides of the central-most receptacle well 120. Although not shown, the channel 612 may extend the length of the receptacle holder 110 and two closed through holes 614 may be provided therein corresponding to each of the receptacle wells 120.

[0064] 5E, receptacle holder 110 may be formed to include one or more ridges 616 disposed on opposite sides of center-most receptacle holder 120 to accommodate thermistors inserted through through holes 614. The ridges 616 provide closed-ended channels surrounding a portion of receptacle well 120, extending from side 115 of receptacle holder 110 and terminating at side 117 opposite side 115 of receptacle holder 110. Thus, when two thermistors 610 are provided to monitor the temperature of receptacle holder 110, one thermistor 610 is provided in each of the ridges 616 thereof. Although not shown, when the channel 612 extends the length of the receptacle holder 110 and two through holes 614 are provided corresponding to each of the receptacle wells 120, the receptacle holder 110 may include one ridge 616 per through hole 614 to accommodate an individual thermistor therein. It is contemplated that additional through holes 614 may be provided corresponding to two or more of the receptacle wells, including one or more through holes 614 for each receptacle well.

[0065] (heat sink) In an exemplary embodiment, each support 240 is a heat sink or is in thermal communication with a respective heat sink 330. As used herein, the term "heat sink" refers to a component that transfers thermal energy from a higher temperature to a lower temperature fluid medium. The fluid medium is often air, but can also be water, or in the case of heat exchange, refrigerants and oils. A variety of suitable heat sink configurations and associated materials are known in the art. As used herein, the term "thermal communication" refers to the ability to transfer thermal energy from one body to another body or from one body to a fluid medium.

[0066] As shown in FIG. 7A, in an embodiment, each support 240 is provided in thermal communication with a single heat sink 330. Each heat sink 330 positioned in thermal communication with one or more supports 240 of the device 100 may further include a plurality of through holes 332 (see FIG. 7B) disposed within its surface. Each through hole 332 may be directly aligned with the through holes 242 of the support and / or with the through holes 170 in the bottom surface 160 of the receptacle holder 110 positioned in sliding engagement therewith. Such through holes 332 form channels through which, for example, optical fibers and / or associated components may pass, thereby providing optical communication between each receptacle well 120 and an excitation signal source and / or an emission signal detector, as discussed below.

[0067] In certain embodiments, one or more thermal elements may be disposed within the heat sink 330, separate from those used to heat the receptacle holder, to preheat the heat sink prior to amplification analysis. Preheating the heat sink may be desirable to reduce the temperature difference between the receptacle holder 110 undergoing heating and the heat sink, thereby avoiding the theft of thermal energy being transferred to the receptacle holder 110 by the thermal element 200. Among other things, preheating the heat sink has been found to improve the rate of temperature cycling and reduce electrical and thermal strain on the thermal element, thus reducing power consumption and increasing the life of the thermal element. The heat sink may be preheated to a temperature above ambient temperature but below the nucleic acid annealing temperature, e.g., below about 50°C-64°C, but above about 20°C-22°C. In another embodiment, the heat sink may be preheated to a temperature between the annealing temperature and the stretching / extension temperature, e.g., between about 50°C-64°C and about 72°C-80°C. In another embodiment, the heat sink can be preheated to a temperature between the stretching / expansion temperature and the melting / denaturation temperature, e.g., between about 72°C-80°C to about 94°C-98°C. In another embodiment, the heat sink can be preheated to a temperature between the annealing temperature and the melting / denaturation temperature, e.g., between about 50°C-64°C to about 94°C-98°C. Exemplary thermal elements used to preheat the heat sink 330 include, but are not limited to, cartridge heaters 334. In various embodiments, one or more cartridge heaters 334 preheat the heat sink 330, e.g., to about 45°C-50°C prior to the amplification analysis. As should be appreciated, additional thermistors can be provided in thermal contact with one or more portions of the heat sink to monitor its temperature and avoid the theft of thermal energy being transferred by the thermal element 200 to the receptacle holder 110.

[0068] (cover) As shown in FIGS. 1, 2, 8, and 12, the device 100 may also include a cover 350 positioned in movably associated with the receptacle holder 110. As may be expected, the cover 350 is movable between an open position (FIG. 8B) and a closed position (FIG. 8C) relative to the receptacle holder 110, and may be moved to any position between open and closed as needed. In the open position, the cover 350 does not obstruct access to the receptacle well 120 in the receptacle holder 110 (see FIG. 8A). When in the closed position, the cover 350 will block and / or obstruct access to the receptacle well 120. Additionally, when closed, the cover 350 may exert a force F2 on any receptacle in the receptacle well 120 to seat or secure the receptacle 130 into the receptacle well 120 (see FIG. 8C). As discussed above, because the receptacle well 120 is configured to receive the receptacle 130, the force F2 exerted by the cover 350 serves to ensure that the receptacle 130 fits securely within the receptacle well 120, thereby allowing maximum contact between the inner surface 180 of the receptacle well 120 and the receptacle 130.

[0069] The cover 350 may be made from any rigid or semi-rigid material suitable for exerting a downward pressure on a receptacle disposed within the receptacle well. Exemplary materials from which the cover may be made include, but are not limited to, beryllium copper, spring steel, chrome vanadium, chrome silicon, phosphor bronze, stainless steel, aluminum, titanium, tungsten, metal alloys, metal composites, plastics, or any suitable rigid or semi-rigid material.

[0070] The cover 350 may be movable by any suitable mechanical element included in the device. In one embodiment, the cover 350 is hingedly attached to the device 100 to allow movement between an open position and a closed position. The attachment point includes, but is not limited to, any of the one or more supports of the device, or any suitable location within the housing containing the device. As shown in FIG. 1, the cover 350 may be fixedly attached to a rigid rotatable member 352 in movably communication with one or more electric motors 355. The rotatable members may be rotatably mounted on opposing sides of the housing 50 of the device, or on opposing sides of additional housing support members thereof, and may extend the length of the device parallel to the orientation of one or more receptacle holders 110 such that actuation of the rotatable members 352 moves the cover 350 to an open or closed position relative to the one or more receptacle holders 110. In an exemplary embodiment, the rotatable member 352 is a cylindrical rod with a circular cross-section and an axis of rotation at its center, as shown in FIG. 8E, a cross-sectional view taken along A'-A' of FIG. 8D. Exemplary materials from which the rigid rotatable member may be made include, but are not limited to, steel, titanium, aluminum, or any suitable hard material. As used herein, the term "rotatably mounted" refers to any mounting orientation that allows the rotatable member to rotate about its central axis.

[0071] The cover 350 may include one or more (i.e., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) flexible extensions 360 attached to and extending laterally away from the rigid rotatable member 352. Such flexible extensions 360 are configured to contact at least a portion of a receptacle 130 disposed within the receptacle holder 110 when the cover is approaching a closed position or a short distance after leaving the closed position. When contact is made between the flexible extensions 360 and at least a portion of the receptacle 130, the flexible extensions 360 bend while exerting a force F2 directly on at least a portion of the receptacle 130. In an exemplary embodiment, the cover 350 includes two or more (i.e., 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) flexible extensions 360 extending in the same direction away from the rigid rotatable member 352. In some embodiments, the flexible extensions 360 extend laterally away from the hinged attachment of the cover 350 to the device 100. In many embodiments, the cover 350 includes one flexible extension 360 per receptacle well 120 of the receptacle holder 110. Also, in many embodiments, one flexible extension 360 of the cover 350 may contact at least a portion of more than one receptacle 130 disposed within the receptacle holder 110. Similarly, more than one flexible extension 360 may contact at least a portion of more than one receptacle 130 disposed within the receptacle holder 110.

[0072] The cover 350 of the present disclosure often includes multiple components, such as the flexible extension 360, the rotatable member 352, or other elements, either as a single molded cover unit or among multiple elements that make up the entire cover unit. For example, the flexible extension 360 may be attached to the rotatable member 352, or a single piece of material may include the rotatable member 352 and the flexible extension 360.

[0073] The device 100 may include a single cover 350 movably associated with all of the receptacle holders 110 (not shown), or may include a single cover 350 for each row of receptacle holders 110, or may include a single cover 350 for each individual respective receptacle holder 110. Movement of each cover 350 may be actuated by an electric motor 355 disposed either within the device 100 or within the housing 50 in which the device is located. When the device 100 includes more than one cover 350, each cover 350 may be actuated by its own motor 355, or more than one cover 350 may be actuated by the same motor 355. Thus, when the device 100 includes more than one cover 350, each cover 350 may move independently of the next cover, and / or more than one cover 350 may be moved simultaneously. Those skilled in the art will appreciate that independent movement of multiple covers may be provided utilizing a single motor, for example through appropriate camming of its connections to each cover. The electric motor 355 is electrically connected to a controllable power source 210 for applying current thereto. Control of the power source 210 may be performed by a suitably programmed processor 370 (such as a computer) which may receive signals from another processor that controls automated process steps involved in the temperature cycling process.

[0074] Although some embodiments of the devices and methods of the present disclosure include a cover, a cover is not required and is often not included or desired. For example, in particular in many embodiments, the receptacle holder does not have a cover in operable orientation therewith. In such embodiments, the receptacle is often held in place in the receptacle holder, for example, by gravity, friction, and / or another mode. When the device is provided without a cover for the receptacle, it will often lack a cover but will have any of the configurations of the device described herein, including all relevant instrumentation and mechanical and / or electrical elements associated therewith. Often, in such embodiments, the pipettor or receptacle transport mechanism will have unconstrained access to the receptacle holder and will introduce or remove the receptacle at will. An example of a device without a cover is depicted in FIG. 14B. Such a device can be easily attached to a heat sink, in communication with a detection system and a power source, and can be fully operational. In many embodiments, multiple of these devices are incorporated onto a single heat sink.

[0075] (Optical Fiber) 9A-9C, the device 100 further includes a plurality (i.e., more than one) optical fibers 400 to provide optical communication of the receptacle well with at least one of the excitation signal source 500 and the emission signal detector 510 (see FIG. 10). In one embodiment, the device 100 includes one optical fiber 400 per receptacle well 120. Thus, when the device 100 includes ten receptacle wells 120, at least ten optical fibers 400 would be provided to establish optical communication between the receptacle wells 120 and the one or more excitation signal sources 500 and / or one or more emission signal detectors 510.

[0076] As used herein, "optical fiber" refers to a flexible, transparent fiber made of glass or plastic that functions as a waveguide to transmit light between two ends of the fiber (i.e., a first end and a second end). Typically, an optical fiber includes a transparent core surrounded by an opaque cladding material with a lower refractive index and low or no autofluorescence properties. It should be understood that an optical path or assembly comprising an optical fiber may optionally include one or more filters, lenses, spheres, etc. to modify and / or focus the excitation or emission signal passing therethrough. Optionally, the device 100 may include an optical interface 440 between the first end 410 of each optical fiber 400 and the receptacle 130 (see FIG. 9C). Such an optical interface 440 may include a filter, lens, sphere, nose, cap, or any other element having desired optical properties. It should be understood, however, that in various embodiments, the interface 440 is not a lens and / or does not function as a lens. Exemplary interfaces 440 useful in the present apparatus include, but are not limited to, a glass or plastic ball, a nose or cap that covers the first end 410 of the optical fiber 400, or any suitable optically transparent material.

[0077] A first end 410 of each of the plurality of optical fibers 400 is disposed outside, inside, or extending through the through hole 170 of the receptacle well 120, thereby providing optical communication with the receptacle well 120 and / or a receptacle 130 disposed within the receptacle well 120. As shown in FIG. 9A, when disposed within the receptacle well 120, the first end 410 of the optical fiber 400 may be movable within the through hole 170 of the receptacle well 120 relative to its inner surface 180. Various means of movement of the first end 410 of the optical fiber 400 within the through hole 170 are contemplated. For example, a first end 410 of the optical fiber 400 may extend into the receptacle well 120, and when the receptacle 130 is disposed within the well 120, the receptacle 130 will contact the first end 410 of the optical fiber 400, thereby providing optical communication between the receptacle 130 and the optical fiber 400. In an exemplary embodiment, the presence of the receptacle 130 within the receptacle well 120 will cause the optical fiber 400 to move (e.g., through application of a direct force) within the through hole 170 in a direction opposite from the inner surface 180 of the receptacle well 120 so that the receptacle 130 can make maximum contact with the inner surface 180 of the receptacle well 120 while maintaining optical communication with the optical fiber 400, as shown in FIG. In another embodiment, a downward force F2 exerted by cover 350 and / or flexible extension 360 of cover 350 on at least a portion of receptacle 130 disposed within receptacle well 120 causes optical fiber 400 to move within through hole 170 when receptacle 130 contacts optical fiber 400. In such an embodiment, receptacle 130 may exert a force F3 on a first end 410 of optical fiber 400 in substantially the same direction as force F2 being exerted on the receptacle disposed within the well such that end 410 of optical fiber 400 moves within well 120.

[0078] As is known in the art, optical fibers are rigid members and thereby have a certain amount of inherent resiliency to movement. Thus, one skilled in the art will appreciate that an optical fiber useful in device 100 should have sufficient rigidity to resist bending or otherwise deforming within receptacle holder 120 upon application of force F3 on its first end 410. Alternatively, a flexible optical fiber 400 may be utilized, but the first end 410 of the optical fiber 410 may be surrounded or protected by a rigid ferrule, for example, that optionally moves within the through hole in response to application or release of force F3.

[0079] In many cases, the first end 410 of each of the plurality of optical fibers 400, or a region 420 proximal to the first end 410 of each of the plurality of optical fibers 400, is directly or indirectly connected to a respective through hole 170 of the receptacle well 120 with a resilient element 600. The resilient element 600 contracts and / or deforms as the optical fiber 400 moves within the through hole 170 and returns to its uncompressed and / or original form when the optical fiber 400 returns to its rest position, thereby moderating the movement of the optical fiber 400. As used herein, the "rest position" of an optical fiber refers to the position of its first end 410 when a receptacle is not present within the receptacle well and / or when a downward force F2 is not being exerted by the cover 350 on at least a portion of a receptacle 130 disposed within the receptacle well 120. Exemplary resilient elements include, but are not limited to, springs, plastics, open and closed cell foams, rubber, dampers, pneumatic elements, hydraulic elements, electromagnetic elements, or combinations thereof.

[0080] Those skilled in the art will appreciate that the inherent resilience / stiffness of the optical fiber 400 should be considered when selecting a resilient element 600 for use in the device 100 to avoid interfering with the optical fiber's inherent stiffness with its ability to move within the through hole 170. Thus, in many embodiments, each optical fiber 400 in the device 100 has one or more dedicated resilient elements 600. Also, in many embodiments, two or more optical fibers 400 are in contact with a single resilient element 600, which allows for individual or coordinated movement of the two or more optical fibers 400.

[0081] In yet another exemplary embodiment, the movement of the optical fiber 400 within the through hole 170 of the receptacle well 120 is associated with the movement of the cover 350 of the device 100. For example, in such an embodiment, the optical fiber 400 may be disposed outside, inside, or extending through the through hole 170 of the receptacle well 120 (as shown in FIG. 9A ). Here, the optical fiber 400 may be movably connected to a motor 355 that actuates the cover 350, for example, the same motor 355 actuating the movement of the optical fiber 400 within the through hole 170. Alternatively, the optical fiber 400 may be movably connected to a motor (not shown) that is different from the motor 355 that actuates the cover 350, for example, but the action of the motor on the cover 350 and the optical fiber 400 may be coordinated such that the optical fiber 400 moves within the through hole 170 in a time period that corresponds to the movement of the cover 350. This corresponding time period may include overlapping time periods or different but related time periods. For example, the fiber 400 may move simultaneously with the cover 350, the fiber 400 may move only a portion of the time that the cover 350 is moving, or the fiber 400 may move during a time period before or after the movement of the cover 350. In some non-overlapping period embodiments, the first end 410 of the optical fiber 400 may move within the through hole 170 toward the inner surface 180 of the receptacle well 120 before the cover 350 begins to move toward the closed position. Alternatively, in some other non-overlapping period embodiments, the cover 350 moves toward the closed position before the first end 410 of the optical fiber 400 begins to move toward the inner surface 180 of the receptacle well 120. However, in many cases, the movement of the optical fiber 400 and the cover 350 is coordinated such that the first end 410 of the optical fiber 400 moves toward the inner surface 180 of the receptacle well 120 after the cover 350 begins to move and approaches the closed position. In such an embodiment, the first end 410 of the optical fiber 400 can be actuated to move toward the interior of the receptacle well 120 at the initiation of movement of the cover 350 away from the closed position, or at another time period.

[0082] In another exemplary embodiment, the resting position of the first end 410 of the optical fiber 400 is below the inner surface 180 of the receptacle well 120. In other words, the first end 410 of the optical fiber 400 is resting within the through hole 170 of the receptacle holder 110. In such an embodiment, the first end 410 of the optical fiber 400 is thus moved toward the interior of the receptacle well before, during, or after the cover 350 is moved to the closed position to bring the first end 410 into contact with at least a portion of the receptacle 130 disposed within the receptacle well 120, or is otherwise positioned proximate to, but not in direct contact with, a portion of the receptacle 130 to achieve optical communication therewith. As discussed above, the optical fiber 400 may be movably connected to, for example, a motor 355 that actuates the cover 350, the same motor 355 actuating the movement of the optical fiber 400 within the through hole 170. Alternatively, the optical fiber 400 may be movably connected to, for example, a different motor (not shown) than the motor 355 that actuates the cover 350, but the action of the motor on the cover 350 and the optical fiber 400 may be coordinated such that the optical fiber 400 moves within the through hole 170 in a period corresponding to the movement of the cover 350.

[0083] In yet another exemplary embodiment, movement of the optical fiber 400 within the through hole 170 (either into or out of the interior of the receptacle well 120) may be actuated through a mechanical connection to the rigid rotatable member 352 of the cover 350. For example, a geared or camming mechanical connection (not shown) with the rigid rotatable member 352 may be used to coordinate movement of the first end 410 of the optical fiber 400 into or away from the interior of the receptacle well 120 as the cover 350 is moved to an open or closed position. Thus, the optical fiber 400 of the device 100 may move into and out of the receptacle well 120 in conjunction with the opening and closing of the cover 350 of the device 100.

[0084] In certain embodiments, placement of the receptacle 130 within the receptacle well 120 will generally not cause the optical fiber 400 to move within the through hole 170. However, as discussed above, the force F2 exerted by the cover 350 on at least a portion of the receptacle 130 will prevent movement of the receptacle 130 within the receptacle well 120 and will allow optical communication between the receptacle 130 and the optical fiber 400 while maintaining maximum contact between the receptacle 130 and the inner surface 180 of the receptacle well 120. In embodiments where the rest position of the optical fiber 400 is disposed with its first end 410 below the inner surface 180 of the receptacle well 120, the force F2 maintains the receptacle 130 in a seated position within the receptacle well 120 even after actuated movement of the optical fiber 400 into the interior of the receptacle well 120. As should be understood, actuation of optical fiber 400 in contact with receptacle 130 often exerts a force F4 (FIG. 9C) on the proximate bottom end 138 of receptacle 130. In the absence of force F2 exerted by cover 350 on at least a portion of receptacle 130, force F4 may remove or otherwise weaken optimal contact of receptacle 130 with inner surface 180 of receptacle well 120. Thus, in such embodiments, force F4 will generally have the same magnitude or a smaller magnitude than force F2 or force F3.

[0085] (Method of Establishing Optical Communication) In another aspect, provided herein is a method for establishing optical communication between a receptacle and an excitation signal source and / or an emission signal detector within a housing of the device while allowing maximum contact between a surface of the receptacle well and the receptacle (FIG. 11A). As discussed in detail above, the method includes providing a receptacle 130 in a receptacle well 120 of a receptacle holder 110 (step S110). Thereafter, a force F2 is applied to the receptacle 130 or at least a portion of the receptacle 130 such that the receptacle 130 fits securely into the receptacle well 120, thereby allowing maximum contact between an inner surface 180 of the receptacle well 120 and the receptacle 130 (step S120). While the force F2 is applied to at least a portion of the receptacle 130, a movement of the first end 410 of the optical fiber 400 is caused toward the inner surface 180 of the receptacle well 120 (step S130). In such an embodiment, the receptacle 130 may apply a force F3 to the optical fiber 400 in a substantially same direction as the force F2 being applied to the receptacle 130, to the first end 410 of the optical fiber 400 disposed within the receptacle well 120, such that optical communication is established between the bottom 138 of the receptacle 130 and the first end 410 of the optical fiber 400 (step S140). As discussed above, the movement of the first end 410 of the optical fiber 400 is coordinated with the movement of the cover 350 to the closed position. Thus, the method may further include the movement of the cover 350 in coordination with the movement of the first end 410 of the optical fiber 400.

[0086] Another exemplary embodiment of a method for establishing optical communication between a receptacle and an excitation signal source and / or an emission signal detector within the housing of the device while allowing maximum contact between the surface of the receptacle well and the receptacle is shown in FIG. 11B. In this embodiment, the method includes providing a receptacle 130 in the receptacle well 120 of the receptacle holder 110 (step S210). The cover 350 is then moved to a closed position (step S220), thereby exerting a force F2 on the receptacle 130 or at least a portion of the receptacle 130 such that the receptacle 130 fits tightly into the receptacle well 120, thereby allowing maximum contact between the inner surface 180 of the receptacle well 120 and the receptacle 130 (step S230). Before, during, or after the movement of the cover 350 to the closed position, movement of the first end 410 of the optical fiber 400 is accomplished toward and into contact with the installed receptacle 130 (step S240). Upon contact of the first end 410 of the optical fiber 400 with the closed end 138 of the receptacle 130, a force F4 is exerted by the first end 410 on the receptacle 130. In such an embodiment, the receptacle 130 may exert a force F3 on the first end 410 of the optical fiber 400 in substantially the same direction as the force F2, which is greater than the force F4. Thus, optical communication is established between the first end 410 of the optical fiber and the receptacle 130 while ensuring maximum contact between the receptacle 130 and the inner wall 180 of the receptacle well 120 (step S250). As discussed above, the movement of the first end 410 of the optical fiber 400 is coordinated with the movement of the cover 350 to the closed position.

[0087] Often, the first end 410 of each of the plurality of optical fibers 400, or a region 420 proximal to the first end 410 of each of the plurality of optical fibers 400, is directly or indirectly connected to a respective through hole 170 of the receptacle well 120 with a resilient element 600, as discussed above, such that the resilient element 600 contracts and / or deforms as the optical fiber 400 moves within the through hole 170, and returns to its uncompressed and / or original form when the optical fiber 400 returns to its rest position.

[0088] (Stripper plate) 12A-12D, the apparatus 100 may further include one or more stripper plates 650 mounted in movably associated relation with the receptacle holder 110. Like the cover 350, the stripper plate 350 is movable between an open position and a closed position, which will be referred to as the "release position" and the "locked position" with reference to the stripper plate 650. When in the release position (FIG. 12B), the stripper plate 650 allows the transfer of a receptacle 130 into and removal out of the receptacle well 120. When in the locked position, the stripper plate 650 prevents removal of a receptacle 130 disposed within the receptacle well 120, thereby allowing a receptacle transport mechanism 700, such as a pipettor or pick-and-place robot, to disengage from the receptacle 130 (FIG. 12D). It should be appreciated that when in the locked position, the stripper plate 650 will not block access to the top of the receptacle 130 by the receptacle transport mechanism 700 used to deliver to and / or remove from the receptacle 130, but will prevent removal of the receptacle 130. Thus, removal of the receptacle 130 can only occur if the stripper plate 650 is present when the stripper plate 650 is in the released position.

[0089] When present, the stripper plate 650 may be made from any rigid material that is suitable for removing the receptacle 130 from the receptacle transport mechanism 700. Exemplary materials from which the stripper plate may be made include, but are not limited to, beryllium copper, spring steel, aluminum, titanium, plastic, or any suitable rigid material.

[0090] In various embodiments, the apparatus 100 may include a single stripper plate 650 movably associated with all of the receptacle holders 110, or may include a single stripper plate 650 for each row of receptacle holders 110, or may include a single stripper plate 650 for each individual receptacle holder 110. Movement of the stripper plate 650 may be actuated by an electric motor 660 disposed either within the apparatus 100 or within the housing 50 in which the apparatus is located. When more than one stripper plate 650 is provided in the apparatus, each stripper plate 650 may be actuated by its own motor 660, or more than one stripper plate 650 may be actuated by the same motor 660. Thus, when the apparatus 100 includes more than one stripper plate 650, each stripper plate 650 may move independently of the next stripper plate, and / or more than one stripper plate 650 may be moved simultaneously. The electric motor 660 which causes the movement of the one or more stripper plates 650 is electrically connected to a controllable power source 210 for applying current thereto. Control of the power source 210 can be performed by a suitably programmed processor 670 (such as a computer), which may receive signals from another processor which controls the automated process steps involved in the temperature cycling process.

[0091] Similar to the movement of the optical fiber 400 discussed above, the movement of the stripper plate 650 between the locked and unlocked positions may be associated with the movement of the cover 350 of the apparatus 100. For example, in such an embodiment, the stripper plate 650 may be placed in movably connection with the motor 355 that actuates the cover 350, such that the same motor 355 actuates the movement of the stripper plate 650 as needed. Thus, the action of the motors on the cover 350 and the stripper plate 650 may be coordinated such that the stripper plate 650 moves during a period of time corresponding to the movement of the cover 350. This corresponding period of time may include overlapping periods of time, or different but related periods of time. For example, the stripper plate 650 may move simultaneously with the cover 350, the stripper plate 650 may move during only a portion of the time that the cover 350 is moving, or the stripper plate 650 may move during a time period before or after the movement of the cover 350. However, the movement of the stripper plate must be timed so that the receptacle transport mechanism 700 can disengage from the receptacle 130 without interfering with the movement of the cover 350.

[0092] In other exemplary embodiments, the stripper plate 650 may be movable between the locked and unlocked positions by any suitable mechanical element included in the apparatus. In an exemplary embodiment, the stripper plate 650 is hingedly attached to the apparatus 100 to allow movement between the locked and unlocked positions. Attachment points include, but are not limited to, any of the one or more supports of the apparatus or any suitable location within the housing 50 that contains the apparatus 100. In another embodiment, the stripper plate 650 is hingedly attached to opposing sides of the support of the apparatus 100. For example, the stripper plate 650 may slide laterally in a direction perpendicular to the orientation of the rows (101-106) of the receptacle holders 110. While a stripper plate may be utilized in certain embodiments described herein, in many cases it is not incorporated as a feature when the receptacle transport mechanism 700 is provided with a receptacle release such as a tip stripper, ejection mechanism, or other receptacle release mechanism known in the art.

[0093] (Second Exemplary Embodiment of the Apparatus) 14A-14D and 16, a second exemplary embodiment of the apparatus 800 described herein is provided. This description is provided based on the differences from the first exemplary embodiment discussed above. Thus, any reference to similar elements should be understood as described above.

[0094] As in the previous exemplary embodiment, the device 800 includes one or more (i.e., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or any integer between 1 and 20, or more) receptacle holders 110 (see also FIG. 3). When multiple receptacle holders 110 are provided in the devices described herein, each receptacle holder 110 disposed within the device may be aligned with one another to facilitate automated processing steps involved in nucleic acid amplification analysis. Such a device 800 may include a housing 50 (see FIGS. 2 and 4) within which the one or more receptacle holders 110 are located. The housing 50 may be made of any suitable material of construction, such as, for example, plastic or metal.

[0095] As shown in FIG. 14A, the upright portion 247 of the support 240 includes a mount 810 protruding from its third side for attachment to a controller board 820. Attachment of the controller board 820 to the mount 810 of the support 240 may be accomplished by any means known in the art. For example, the controller board 820 may be fixedly attached by rivets or screws 825. In many cases, attachment is via a mechanism that allows independent lateral movement between the support 240 and the controller board 820. Such attachment may be via the use of shoulder screws or machining attachment points in the support 240 so that the controller board can move laterally relative thereto, regardless of the type of fastening means utilized, including standard threaded screws. Such lateral movement of the controller board 820 facilitates mounting of the support 240 / controller board 820 unit to the heat sink 330 and allows proper alignment of the through holes 242 of the support 240 with the through holes 332 of the heat sink 330, thereby providing optimal positioning of the optical fiber 400 for inspection of the contents of the receptacle well 120.

[0096] The controller board 820 may include logic and control circuitry for performing one or more of the powering and temperature control functions described above. In various embodiments, the controller board 820 includes at least one electrical connection point 830 for electrical connection to a second controller board 835 disposed on the device 800. In many embodiments, the entire unit (or device), including the circuitry on the controller board 820 depicted in FIG. 14B, represents an independent calibration unit that can be utilized when plugged into a power source and oriented in communication with a detection system, such as an optical system or another detection system. In such embodiments, the controller board 820 is configured to operate with the installed elements identified in FIGS. 14A-14D, with or without the primary or secondary cover 840 / 850, or any other cover means. In essence, the unit illustrated in FIG. 14B may operate and be utilized as a "plug and play" type device, whereby it can be installed, removed, or replaced with a different unit at will, without the need for independent calibration of the entire detection system after installation. As discussed above, a thermal element 200, such as a "Peltier element," is disposed between the receptacle holder 110 and the upright portion 247 of the support 240. A compression housing 855 having a top surface 857 is configured for fixable attachment over the receptacle holder 110. A plurality of through holes are disposed within the top surface 857 of the compression housing 855, each corresponding to and aligned with a receptacle well 120 of the receptacle holder 110. One or more cross braces 248 are mounted to the support 240 and exert a force F1 (FIG. 5B) on the side of the compression housing 855, which in turn exerts a force F1 on the receptacle holder 110. Each of the support 240 and the compression housing 855 may be formed from a material having a low thermal conductivity, such as plastic. In an embodiment, the materials from which the support 240 and the compression housing 855 are formed may be the same material or may be different materials.

[0097] FIG. 14D depicts a top view of a portion of the apparatus 800 provided in FIGS. 14A-14C. In various embodiments, the compression housing 855 is formed with a beveled edge 859 oriented toward the receptacle holder 110. The beveled edge 859 promotes uniformity of the compression force of the compression housing 855 to the receptacle holder 110 while simplifying the compression connection, ease of installation, and maintenance of the unit. In this embodiment, a screw 827 may be threaded through the upright portion 247 into the cross brace 248. As the screw 827 is tightened, the outer edge 249 of the cross brace 248 is drawn toward the upright portion 247, resulting in a curvature (not shown) of the cross brace 248 around the compression housing 855. The beveled edge 859 allows the cross brace 248 to bend while promoting the overall uniformity of the applied compression force F1. Those skilled in the art will appreciate that additional orientations and configurations of the cross brace 248 / compression housing 855 connection can be provided without departing from the scope of the present disclosure.

[0098] 16, each support 240 may be a heat sink, may be in thermal communication with an individual heat sink 330, or may be in thermal communication with a single heat sink 330. Each heat sink 330 positioned in thermal communication with one or more supports 240 of the device 800 may further include a plurality of through holes 332 (see FIG. 7B) disposed within its surface. Each through hole 332 may be directly aligned with the through holes 242 of the support and / or with the through holes 170 in the bottom surface 160 of the receptacle holder 110 positioned in sliding engagement therewith. Such through holes 332 form channels through which, for example, optical fibers and / or associated components may pass, thereby providing optical communication between each receptacle well 120 and an excitation signal source and / or an emission signal detector, as discussed below.

[0099] 14C, the device 800 may also include a primary cover 840 fixedly positioned over the receptacle holder 110. The primary cover 840 may be formed with one or more (i.e., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) fixed arms 845 that are directly aligned with and circumscribe each receptacle well 120 of the receptacle holder 110. In an embodiment, the primary cover 840 is formed with four fixed arms 845 arranged in an array that is directly aligned with and circumscribes each receptacle well 120 of the receptacle holder 110. The fixed arms 840 are configured for fixable attachment to at least a portion of the receptacle or cap 135 that is attached to the receptacle 130. Such a lockable attachment is similar to the force F2 exerted by cover 350, as discussed above, to ensure that receptacle 130 fits securely within receptacle well 120, thereby allowing maximum contact between inner surface 180 of receptacle well 120 and receptacle 130. The locking arms may be made of any suitable material, including plastic, metal, or metal composite.

[0100] The apparatus 800 may further include a secondary cover 850 fixedly positioned over the primary cover 840. The secondary cover 850 may be formed with one or more (i.e., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) release arms 855 each in direct alignment and sliding contact with the fixed arm 845 of the primary cover. In various embodiments, the fixed arm 845 of the primary cover includes an angled surface 847 over which a corresponding release arm 855 of the secondary cover 850 may slide when actuated during an automated process. The secondary cover 850 may further include one or more (i.e., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) actuators 860 fixedly connected to the release arm 855 and positioned such that when a force is applied thereto, the force is transferred from the actuator 860 to the release arm 855 which in turn compresses the sloped surface 847 of the primary cover 840 and releases the securable attachment to the cap 135 attached to the receptacle 130.

[0101] It is therefore contemplated that the housing 50 within which the device 800 is located will include at least one modified pipettor 900, as shown in Figures 15A and 15B. As shown in Figure 15A, the modified pipettor 900 is modified such that a plunger 910 is slidably connected to one or more limbs 915 that are hingedly attached to a body 920 of the modified pipettor 900. Thus, when the modified pipettor 900 urges the plunger 910 to a first position (as shown in Figure 15A), the one or more limbs 915 are in a retracted position such that a lower portion 915 thereof is disposed in close proximity to the body 920. When the modified pipettor 900 urges the plunger 910 to a second position (as shown in Figure 15B), then the one or more limbs 915 are in an extended position such that a lower portion 915 thereof is moved away from the body 920.

[0102] This modified pipettor 900 is useful for engaging the secondary cover 850 and compressing it with a downward movement that actuates the release of the fixed arm 845 by the physical action of the release arm 855. When the release arm 855 is pressed in this manner, the fixed arm 845 is pulled axially away from the receptacle 130 and cap 135, allowing its unhindered release and removal by the pipettor. In such circumstances, it is advantageous for the fixed arm to maintain contact with and press the release arm 855 radially outwardly for the period of time required for the pipettor plunger 910 to frictionally engage the receptacle cap and for the receptacle and cap to be vertically lifted to disengage the fixed arm 845.

[0103] 16 depicts an alternative embodiment of the cover mechanism 824 that is actuated by an automated or modified pipettor 900 as described above. In this embodiment, the end or plunger of the pipettor 910 contacts and depresses a cover release mechanism 852 that opens the cover 822 and allows the receptacle 130 access to the well 120. Once the receptacle 130 is placed into the well 120, the pipettor end or plunger is utilized to depress the cover lock mechanism 854, which then causes a force to be exerted on the cap 125 and / or receptacle 130 such that the receptacle 130 is securely seated within the well 120. The force is similar to the force F2 exerted by the cover 350, as discussed above, to ensure that the receptacle 130 fits securely within the receptacle well 120, thereby allowing maximum contact between the inner surface 180 of the receptacle well 120 and the receptacle 130. The cover 822 may be actuated by a motor, as discussed above, through one or more torsion springs disposed on a rigid rotatable member 352 (FIG. 8B) to which the cover 822 is fixedly attached, or by a spring mechanism that moves the cover 822 vertically relative to the receptacle holder 110. In various embodiments, the spring-loaded cover 822 may include a push-lock fastener that may lock the spring-loaded cover 822 in a locked position. The push-lock mechanism may be directly or indirectly associated with the cover release mechanism 852 and / or the cover securement mechanism 854.

[0104] In certain embodiments, any of the devices described herein will not include a cover or mechanism that exerts force F2 on the capped receptacle 130. In such embodiments, the receptacle 130 fits securely within the receptacle well 120, thereby allowing maximum contact between the inner surface 180 of the receptacle well 120 and the receptacle 130 without the need for force F2.

[0105] In certain embodiments, any of the devices described herein may include a cover, but would not include a mechanism that exerts force F2 on the capped receptacle 130. In such embodiments, the cover does not contact the capped receptacle because the receptacle 130 fits securely within the receptacle well 120, thereby allowing maximum contact between the inner surface 180 of the receptacle well 120 and the receptacle 130 without the need for force F2.

[0106] (Use of this device in biochemical analysis) The use of the device described herein is envisioned as being part of an automated process for performing biochemical analysis, such as nucleic acid amplification, but is not limited thereto. Thus, in another aspect, a method for performing an automated random access temperature cycling process is provided (see FIG. 13). First, a reaction mixture is prepared by providing oil to a first receptacle 130 or a first set of receptacles (step S310), reconstituting a PCR master mix (step S320), and providing the reconstituted PCR master mix to the receptacle 130 (step S330). The sample to be analyzed is then inserted into the receptacle 130 containing the PCR master mix (step S340), thereby forming a reaction mixture 140, and the receptacle 130 is capped (step S350). The first receptacle 130 or first set of receptacles, each containing a reaction mixture 140, is transferred by receptacle transport mechanism 700 to a first receptacle holder 110 of apparatus 100 (step S360). The step of preparing the reaction mixture may optionally be repeated to fill a particular receptacle holder 110 and / or a particular row (step S370).

[0107] If the cover 350 and / or stripper plate 650 with which a particular receptacle holder 110 is associated is present and in a closed and / or locked position, the cover and / or stripper plate is moved to an open and / or unlocked position to receive the first receptacle 130 or first set of receptacles. Alternatively, if the apparatus includes an alternative embodiment of cover 824, the receptacle transport mechanism 700, didi (i.e., the end of the pipettor), or modified pipettor 900 may depress the cover release mechanism 852, thereby moving the cover 822 to the open position. Moreover, in another alternative embodiment, if no cover is present, any steps involving movement of the cover are unnecessary and may therefore be omitted. Once the cover 350 and / or stripper plate 650 associated with the receptacle holder 110 are in the open and / or unlocked position, the receptacle transport mechanism 700 places the first receptacle 130 or first set of receptacles into one or more receptacle wells 120 of the first receptacle holder 110 (step S360). Prior to withdrawal of the receptacle transport mechanism 700, the stripper plate 650, if present, is moved to a locked position to prevent removal of the transferred first receptacle 130 or set of receptacles from the first receptacle holder 110 (not shown). In an alternative embodiment, the receptacle transport mechanism 700 is provided with a mechanism for removing receptacles without utilizing a stripper plate (see, e.g., U.S. Publication No. 2010 / 0179687, U.S. Publication No. 2005 / 0244303, U.S. Patent No. 6,869,571, U.S. Patent No. 6,824,024, and U.S. Patent No. 6,431,015), thus making the use of a stripper plate 650 or equivalent mechanism on the present apparatus optional. The transferred receptacle 130 or set thereof may then be released from the receptacle transport mechanism 700 upon contact with the stripper plate 650 as the receptacle transport mechanism 700 disengages therefrom. After the area surrounding the first receptacle holder is cleared of the receptacle transport mechanism, the cover 350 is moved to a closed position (step S380).If an alternative embodiment of the cover mechanism 824 is present in the device, the receptacle transport mechanism 700, Didi, or modified pipettor 900 depresses the cover locking mechanism 854, thereby moving the cover 822 to the closed position. As discussed above, when in the closed position, the cover may exert a force F2 on at least a portion of the receptacle 130 or set of receptacles. However, in some embodiments, the cover does not exert force F2 on the receptacle 130.

[0108] As used herein, a "set" of receptacles refers to one or more receptacles 130 held within a receptacle holder 110. For example, a "set" of receptacles 130 refers to the number of receptacles 130 required to at least partially or completely fill a particular receptacle holder 110. Thus, a set of receptacles 130 may refer to a single receptacle 130 being processed by the apparatus 100, or may refer to any integer number of receptacles 130, up to and including the maximum number of receptacle wells 120 in a particular receptacle holder 110.

[0109] The first receptacle holder 110 is then subjected to a first incubation process (step S390), which includes applying a voltage to a first thermal element 200 of the apparatus 100 so as to change the temperature of the first receptacle holder 110. By changing the temperature of one or more of the first receptacle holders 110, the first set of receptacles 130 in the first receptacle holder 110, including the reaction mixture 140 contained in each receptacle 130, are brought to a predetermined temperature and, optionally, maintained at that temperature for a predetermined period of time.

[0110] During the first incubation process, the second set of receptacles 130, each containing a reaction mixture 140, are optionally transferred by receptacle transport mechanism 700 to a second receptacle holder 110 of apparatus 100 (step S400). Similar to the first set of receptacles, if a cover 350 and / or stripper plate 650 associated with second receptacle holder 110 is present and in a closed and / or locked position, the cover and / or stripper plate are moved to an open and / or unlocked position to receive the second set of receptacles. When the cover 350 and / or stripper plate 650 associated with the second receptacle holder 110 are in the open and / or unlocked positions, the receptacle transport mechanism 700 places the second set of receptacles into the receptacle wells 120 of the second receptacle holder 110. Prior to withdrawal of the receptacle transport mechanism 700, if the stripper plate 650 is utilized, the stripper plate 650 is moved to a locked position to prevent removal of the transferred second set of receptacles from the second receptacle holder 110. The transferred second set of receptacles 130 may then be released from the receptacle transport mechanism 700 upon contact with the stripper plate 650 as the receptacle transport mechanism 700 disengages therefrom. When the area surrounding the second receptacle holder 110 is cleared of the receptacle transport mechanism 700, the cover 350 associated therewith is moved to a closed position. As discussed above, when in the closed position, the cover 350 exerts a force F2 on at least a portion of the receptacles of the respective set.

[0111] The second receptacle holder 110 then undergoes a second incubation process, which may be identical or different from the first incubation process in terms of its temperature and duration. It should be understood that the first and second incubation processes may occur simultaneously or after each other. Furthermore, it should be understood that a third or more (i.e., third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, eleventh, twelfth or more) set of receptacles 130 may be transferred to the device 100, which may then subject the third or more sets of receptacles 130 to a third or more (i.e., third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, eleventh, twelfth or more) incubation process. Such additional sets of receptacles 130 may be transferred to and / or subjected to additional incubation processes, either simultaneously or sequentially, as desired, with the transfer of each subsequent set of receptacles 130 beginning prior to the completion of the incubation process for each immediately preceding set of receptacles 130.

[0112] In one exemplary embodiment, the first set of receptacles 130 are removed from the first receptacle holder 110 immediately following placement of the last receptacle of the second or subsequent set of receptacles 130 in the second receptacle holder 110 (step S410 of FIG. 13 ). In a related exemplary embodiment, the second set of receptacles 130 are removed from the second receptacle holder 110 immediately following placement of the last receptacle of the third or subsequent set of receptacles 130 in the second receptacle holder 110, and so on. It will be understood by those skilled in the art that the terms “first”, “second”, “third” and further terms are relative terms and thus are not limited to the positioning or orientation of the receptacle holder 110 within the device 100. Likewise, it will be understood by those skilled in the art that the terms "first," "second," "third," and more are not limited to the timing of the incubation process relative to when the apparatus 100 is set up. These terms are merely intended to refer to the placement and timing of incubation of any particular set of receptacles 130 within each respective receptacle holder 110. For example, the 50th set of receptacles may be considered to be the first set of receptacles relative to the 51st set of receptacles.

[0113] The use of the second exemplary embodiment of the device 800 described herein is also envisioned, as with the first exemplary device, as being part of an automated process for performing biochemical analysis such as nucleic acid amplification, but is not limited thereto. As described above, if there is no cover, primary cover, or secondary cover, any step involving movement of the cover is unnecessary and may therefore be omitted. As described above, a reaction mixture is first prepared by providing oil to the first receptacle 130 or a first set of receptacles (step S310), reconstituting a PCR master mix (step S320), and providing the reconstituted PCR master mix to the receptacle 130 (step S330). The sample to be analyzed is then inserted into the receptacle 130 containing the PCR master mix (step S340), thereby forming a reaction mixture 140, and the receptacle 130 is capped (step S350). The first receptacle 130 or first set of receptacles, each containing a reaction mixture 140, is transferred by the receptacle transport mechanism 700 to a first receptacle holder 110 of the device 100 (step S360). The step of preparing the reaction mixture may be optionally repeated to fill a particular receptacle holder 110 and / or a particular row (step S370). The transfer of the first receptacle 130 or first set of receptacles is accomplished by first performing an automated motion of moving the plunger 910 of the modified pipettor 900 to a raised position (as shown in FIG. 15A), thereby bringing the knob 912 into slidable contact with one or more rims 915 such that its lower portion 915 is positioned in close proximity to the body 920 of the pipettor 900, and moving the rims 915 to a retracted position. The pipettor 900, having a first receptacle 130 or a first set of receptacles with a cap frictionally attached thereto, places the first receptacle 130 or the first set of receptacles into one or more receptacle wells 120 of the first receptacle holder 110 (step S360).As the first receptacle 130 or first set of receptacles is lowered into the receptacle well 120, the first receptacle 130 or first set of receptacles contacts at least a portion of the locking arms 845 of the primary cover 840. The downward force exerted by the receptacle on the locking arms 845 bends the locking arms 845 radially outwardly about the axial center of the receptacle well 120 such that a lower portion of the cap passes the locking arms 845. Once the lower portion of the cap 135 passes the locking arms 845, the locking arms return to their resting position, thereby lockably contacting at least a portion of the cap 135 and ensuring that the capped receptacle fits securely within the receptacle well 120, thereby allowing maximum contact between the inner surface 180 of the receptacle well 120 and the receptacle 130.

[0114] The first receptacle holder 110 is then subjected to a first incubation process (step S390), which includes applying a voltage to a first thermal element 200 of the apparatus 100 so as to change the temperature of the first receptacle holder 110. By changing one or more temperatures of the first receptacle holder 110, the first set of receptacles 130 in the first receptacle holder 110, including the reaction mixture 140 contained in each receptacle 130, are brought to a predetermined temperature and, optionally, maintained at that temperature for a predetermined period of time or varied between a series of temperatures.

[0115] As described above, during the first incubation process, a second set of receptacles 130, each containing a reaction mixture 140, are optionally transferred by a receptacle transport mechanism 700 to a second receptacle holder 110 of the apparatus 100 (step S400).

[0116] Upon completion of the incubation process, removal of the first receptacle 135 or set of receptacles from the second exemplary embodiment of the device 800 is accomplished by performing an automated movement of the plunger 910 of the modified pipettor 900 to a lowered position (as shown in FIG. 15B), thereby causing the knob 912 to slidably contact one or more rims 915 such that its lower portion 917 is moved away from the body 920, and moving the rim 915 to an extended position. The modified pipettor 900 is then lowered into the open end of the cap 135 of the first receptacle 130 or set of receptacles. As shown in FIG. 15C, upon lowering the modified pipettor 900, the extended lower portion 917 of the rim 915 contacts and exerts a downward force on the actuator 860 of the secondary cover 850. The downward force brings release arm 855 into slidable contact with fixed arm 845 of primary cover 840, bending fixed arm 845 in a radially outward direction relative to the axial center of receptacle well 120 as modified pipettor 900 frictionally engages the open end of cap 135. Bending of fixed arm 845 releases capped receptacle 135 or set of receptacles, allowing the capped receptacles to be removed from receptacle well 120 as modified pipettor 900 is raised therefrom.

[0117] In certain embodiments, it may be desirable to pre-heat the heat sink 330 of the device 100 prior to or during the incubation process. In these embodiments, a voltage is applied to a thermal element 334 in thermal communication with the heat sink 330 before, during, or after a first receptacle 130 or a first set of receptacles, each containing a reaction mixture 140, is transferred by the receptacle transport mechanism 700 to the first receptacle holder 110 of the device 100. As discussed above, the heat sink may be warmed, for example, to about 45-50° C. prior to the biochemical analysis. The transferred receptacle 130 or set of receptacles may then be released from the receptacle transport mechanism 700 upon contact with the stripper plate 650 as the receptacle transport mechanism 700 disengages therefrom. After the area surrounding the first receptacle holder is cleared of the receptacle transport mechanism, the cover 350 is moved to a closed position. As discussed above, once in the closed position, the cover exerts a force F2 on at least a portion of the receptacle 130 or set of receptacles. Thereafter, the first receptacle holder 110 is then subjected to a first incubation process, which includes applying a voltage to the first thermal element 200 of the device 100 to change the temperature of the first receptacle holder 110. By changing the temperature of one or more of the first receptacle holders 110, the first set of receptacles 130 in the first receptacle holder 110, including the reaction mixture 140 contained in each receptacle 130, are brought to a predetermined temperature, and optionally maintained at that temperature for a predetermined time.

[0118] In various embodiments, the temperature of the receptacle holder 110 will be above ambient temperature as a result of a previous incubation process performed on the previous receptacle 130 or set of receptacles 130, or due to pre-heating of the heat sink 330. In these embodiments, pre-heating or additional heating of the heat sink 330 may or may not be desired due to reduced risk of heat steal as discussed above.

[0119] Each of the first and second sets of receptacles 130 (and / or any additional sets of receptacles) may be transported to the device 100 by a single receptacle transport mechanism 700, or may be transported by more than one receptacle transport mechanism 700, depending on the configuration of the device 100, system, or biochemical instrument.

[0120] Each set of receptacles 130 may undergo a single incubation process or multiple incubation processes prior to the completion of a biochemical analysis. Alternatively, or in addition, each set of receptacles 130 may undergo a single temperature gradient, for example for the purpose of melting curve analysis. If a set of receptacles 130 undergoes multiple temperature cycles, each subsequent temperature cycle may be the same or different from the temperature cycle immediately preceding it. During the single or multiple incubation processes, during the temperature gradient, or upon completion of a predetermined number of incubation processes, an excitation signal source 500 transmits an excitation signal to the set of receptacles 130 via the optical fiber 400 of the device 100. Any emission signals resulting therefrom are then transmitted via the optical fiber 400 to one or more emission signal detectors 510. 10 depicts separate optical fibers branching to the excitation signal source 500 and the emission signal detector 510, various embodiments of the present disclosure utilize a single optical fiber (i.e., light conductor) between the excitation signal source 500 and its corresponding emission signal detector 510. Those skilled in the art will appreciate that a collection of mirrors, dichroics, and / or filters can be utilized to split the excitation and emission signals traveling through the single optical fiber between the excitation signal source 500 and its corresponding emission signal detector 510. In these embodiments, one end of the single optical fiber terminates in or at a single receptacle well, and the other end of the single optical fiber terminates in optical communication with the excitation signal source 500 and its corresponding emission signal detector 510. Often, in such configurations, all receptacle wells in the device will be equipped with similar optical fiber arrangements.

[0121] After completion of all incubation processes and / or detection steps, each set of receptacles 130 is removed from its respective receptacle holder 110 of the device 100. Removal of a set of receptacles 130 often proceeds as follows: If present, the cover 350 associated with the receptacle holder 110 in which the analyzed receptacle 130 is mounted is moved to an open position. Either simultaneously or shortly thereafter, the stripper plate 650, if present and in a locked position, is moved to a release position. The receptacle transport mechanism 700 is moved into position and lowered towards the receptacle holder 110 so as to contact the top of each of the receptacles 130 mounted therein. In many embodiments, the receptacle transport mechanism 700 contacts a single receptacle 130 at any particular time. In an embodiment, the receptacle transport mechanism 700 is capable of contacting and removing a set of receptacles 130. When the receptacle transport mechanism 700 is withdrawn, any receptacles that have been contacted therewith are removed from the receptacle holder 110. It should be understood that the analyzed receptacle 130 or set thereof may be removed prior to, during, or after completion of the temperature cycling process of any previous or subsequent set of receptacles.

[0122] Thus, the first set of receptacles may be removed from the first receptacle holder 110 prior to completion of the second incubation process of the second set of receptacles 130 in the second receptacle holder 110. Similarly, the second set of receptacles 130 may be removed from the second receptacle holder 110 prior to completion of the third or more incubation processes of the third or more sets of receptacles 130 in the third or more receptacle holder 110.

[0123] Because the present apparatus 100, 800 is capable of performing a variety of different analyses simultaneously, it is also envisioned that the second set of receptacles 130 may be subjected to a shorter incubation process than the first set of receptacles 130, so that a second or subsequent set of receptacles may be removed prior to removal of the first set of receptacles due to the requirements of a particular analysis, sample, reagent, or for any other reason.

[0124] Thus, the devices 100, 800 described herein provide the ability to automate the incubation process with the same or different biochemical analyses simultaneously. In an exemplary embodiment, the device includes six rows (101-106) of receptacle holders 110 with two receptacle holders 110 per row and five receptacle wells 120 per receptacle holder 110. Thus, the device of the exemplary embodiment is capable of simultaneously incubating up to 60 receptacles 130 at a given time. Assuming a 60 minute incubation time for each set of receptacles 130 in each receptacle holder, and a population of each receptacle holder 110 (containing five receptacle wells 120) with a set of receptacles 130 every 5 minutes, the first set of receptacles will complete incubation approximately 65 minutes after the first receptacle 130 is placed into the receptacle well 120. Thereafter, every 5 minutes, another set of five receptacles will complete their incubation period. As each set of receptacles completes its incubation, it is removed from the receptacle holder and replaced with an unused set of receptacles for another incubation period. Thus, when the device 100, 800 is used in conjunction with an automated instrument for performing biochemical analyses such as PCR, the device increases instrument throughput productivity within a typical 8 hour shift.

[0125] (System for automated random access incubation) In another aspect, the present disclosure provides a system for automated random access incubation for nucleic acid amplification analysis. The system includes one or more of the devices 100, 800, allowing simultaneous or individualized analysis to be performed. The system includes a housing 50 in which one or more of the devices 100, 800 are located. As discussed above, the thermal element 200 corresponding to each receptacle holder 110 may be independently controllable to change only the temperature of its corresponding receptacle holder 110. Thus, the system may include more than one controller 220, each of which is connected to a controllable power source 212 electrically connected to a single thermal element 200 and one or more thermistors 610 of the individual receptacle holder 110, and / or connected to a motor 355 that causes movement to the cover 350, if present, and / or a motor 660 that causes movement of the stripper plate 650 of the individual receptacle holder 110, if present. It should be understood that any one or more of the controllers (220, 370, 670) may be combined to effect independent control of the controllable power sources 212 connected to more than one thermal element 200 and / or electric motors (355, 660). Thus, the system may include a single controller electrically connected to each of the thermal elements 200 and to one or more motors 355 disposed in movable communication with the cover 350 and / or stripper plate 650 corresponding to each receptacle holder 110. Similarly, the system may include a suitably programmed processor 750 (such as a computer) electrically connected to each controller (220, 370, 670) to send and / or receive signals / commands to perform the incubation process. In an embodiment, the controllers (220, 370, 670) and the processor 750 will be configured in the same unit, thereby reducing the number of components in the system.

[0126] As discussed above, the system will include at least one heat sink 330. Thus, each of the one or more devices 100, 800 in the system may be placed in independent thermal communication with a single heat sink 330 (i.e., one heat sink per device), or all of the devices 100, 800 may be in thermal communication with a single heat sink 330. In an embodiment, each receptacle holder 110 of each device 100, 800 in the system will be placed in independent thermal communication with a dedicated heat sink 330 (i.e., one heat sink per receptacle holder), as discussed above.

[0127] As shown in FIG. 10, the system may further include one or more excitation signal sources 500 and one or more emission signal detectors 510 in which the second end 430 of the optical fiber 400 of the device 100, 800 is contained and in optical communication. The excitation signal sources 500 and emission signal detectors 510 contemplated by the present disclosure include, but are not limited to, fluorometers, luminometers, spectrophotometers, infrared detectors, and charge-coupled devices. Each of these types of optical detection systems may be positioned within the housing of the device 100, 800, within the housing of the system, or within the overall housing of the biochemical analysis instrument, as appropriate. Multiple types of signal sources 500 and signal detectors 510 may be movably mounted on the platform to facilitate different detection methods for different processes. The system may also include multiple detectors of the same or different types for detecting signals emanating from different receptacles 130 simultaneously. As discussed above, while FIG. 10 depicts separate optical fibers branching to the excitation signal source 500 and the emission signal detector 510, certain embodiments of the present disclosure utilize a single optical fiber (i.e., light conductor) between the excitation signal source 500 and its corresponding emission signal detector 510.

[0128] The system may further include a receptacle transport mechanism 700 (e.g., a pick-and-place mechanism, a pipettor, or a modified pipettor) positioned within the system housing or within the overall housing of the instrument. The receptacle transport mechanism 700 is configured to transfer and / or remove one or more receptacles 130, either individually or as a set, from the receptacle holder 110 of the device 100. In various embodiments, the modified pipettor 900 includes a body having a plunger slidably disposed therein and one or more rims hingedly attached to the body and positioned in sliding communication with a knob fixedly attached to the plunger. When the plunger is in a first position, a lower portion of the one or more rims is proximal to the body, and when the plunger is in a second position, a lower portion of the one or more rims is extended in a radially outward direction relative to the body. In some embodiments, the receptacle transport mechanism 700 is additionally configured to dispense liquid into and / or remove liquid from individual receptacles 130 .

[0129] Although the present disclosure has been described with reference to the above examples, it will be understood that modifications and variations are encompassed within the spirit and scope of the disclosed subject matter. Accordingly, the disclosure is limited only by the following claims.

Claims

1. An apparatus for performing a nucleic acid amplification reaction, the apparatus comprising: a thermally conductive receptacle holder having a front and a rear surface, the front surface comprising a row of receptacle wells, an outer surface of each of the receptacle wells having a frusto-conical shape, an inner surface of each of the receptacle wells defined to receive a receptacle, each of the receptacle wells having a through hole extending between the inner and outer surfaces thereof; A support; one or more thermal elements for varying a temperature of the receptacle holder, the one or more thermal elements being held in contact with the rear surface of the receptacle holder by the support; and a plurality of optical fibers, each of the optical fibers providing optical communication between one of the receptacle wells and at least one of an excitation signal source and an emission signal detector, a first end of each of the optical fibers being disposed outside the through hole of a corresponding one of the receptacle wells, disposed inside the through hole of the corresponding receptacle well, or extending through the through hole of the corresponding receptacle well, and a second end of each optical fiber being in optical communication with the excitation signal source and / or the emission signal detector; a cross brace mounted to the support, the cross brace exerting a force on the front surface of the receptacle holder; An apparatus comprising:

2. The apparatus of claim 1 , further comprising two or more thermistors disposed in contact with the receptacle holder.

3. The apparatus of claim 2 , wherein the two or more thermistors include one or more thermistors disposed in contact with each of the receptacle wells.

4. 4. The apparatus of claim 2 or 3, further comprising a channel disposed in the rear surface, the channel containing wires and / or electrical connections for the two or more thermistors.

5. The device of claim 4 , wherein the channel extends from an edge of the rear face to a location corresponding to a central-most receptacle well of the receptacle holder.

6. 6. The device of claim 5, further comprising a pair of closed through holes provided in a location of the channel corresponding to the most central receptacle at an end of the channel, the closed through holes being disposed on opposite sides of the most central receptacle, and one thermistor of the two or more thermistors being provided through each of the closed through holes.

7. 7. The device of claim 6, further comprising a pair of ridges disposed on opposite sides of the central-most receptacle well, each of the ridges configured to receive one of the two or more thermistors inserted through the closed through hole.

8. An apparatus according to any one of claims 5 to 7, wherein the two or more thermistors consist of two thermistors.

9. An apparatus as described in any one of claims 1 to 8, wherein the support is coupled to each side of the one or more thermal elements such that the one or more thermal elements are positioned between a portion of the support and the rear surface of the receptacle holder.

10. The support is a base portion having a plurality of through holes, each of the through holes being aligned with the through hole of one of the receptacle wells; an upright portion extending from the base portion, the upright portion being coupled to the side of the thermal element; The apparatus of claim 9 , comprising:

11. The apparatus of claim 10 , further comprising a heat sink coupled to the base portion of the support, the heat sink comprising a plurality of through holes aligned with the plurality of through holes in the base portion of the support.

12. 12. The apparatus of claim 1, further comprising a controller electrically connected to the one or more thermal elements for cycling the temperature of each of the one or more thermal elements.

13. The apparatus of any preceding claim, wherein the first end of each optical fiber is fixedly disposed within the through hole of the corresponding receptacle well.

14. The device of any one of claims 1 to 13, further comprising a cover that is movable between an open position and a closed position relative to the receptacle holder, wherein one or more receptacles disposed in one or more of the receptacle wells are mounted or secured within the receptacle wells by the cover when the cover is moved from the open position to the closed position, and the first end of each optical fiber moves within its corresponding through hole (1) when the cover is moved to the open or closed position, or (2) when a receptacle is present in the receptacle well and the cover is moved to the open or closed position.

15. The device according to any one of claims 1 to 13, wherein the device does not include a cover.

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