Patent ID: 12208395

DETAILED DESCRIPTION

Before the embodiments are further described, it is to be understood that this invention is not limited to particular embodiments described, as such 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.

Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range is encompassed within the embodiments. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges and are also encompassed within the embodiments, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either both of those included limits are also included in the embodiments.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the embodiments belong. Although any methods and materials similar or equivalent to those described herein may also be used in the practice or testing of the embodiments, the preferred methods and materials are now described.

It must be noted that as used herein and in the appended claims, the singular forms “a,” “and,” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a method” includes a plurality of such methods and equivalents thereof known to those skilled in the art, and so forth.

Throughout the description and claims of the specification the word “comprise” and variations thereof, such as “comprising” and “comprises,” is not intended to exclude other additives, components, integers or steps.

The process tubes and carrier tray described herein can be used together to provide a safe and efficient system of preparing, storing, and transporting the process tubes prior to use in a thermal cycler and also for positioning the process tubes accurately and securely in the thermal cycler during amplification.

FIG.1Ashows an isometric view of an exemplary process tube strip100according to the embodiments described herein.FIG.1Bis a side plan view of the process tube strip ofFIG.1A.FIG.1Cis a top view of the process tube strip ofFIG.1A. As shown inFIGS.1A-1C, the process tube strip100is a collection of process tubes102, connected together by a connector tab104. The exemplary process tube strip100can also include a top end tab106, as shown inFIGS.1A-1C, indicating the top of the process tube strip100and a bottom end tab108indicating the bottom of the process tube strip100. The process tube strip100shown inFIGS.1A-1Cincludes eight process tubes102connected together in the process tube strip100. One skilled in the art will immediately appreciate however, that in other embodiments, the process tube strip100can include, for example any other number of process tubes, e.g., 40, 30, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 7, 6, 5, 4, 3, or 2 process tubes102connected in the process tube strip100. An embodiment of the process tube strip100can include an insignia or indication on the upper surface of the top and bottom end tabs106,108. In one embodiment, the top end tab106can be marked with an “A” indicating the top of the process tube strip100and the bottom end tab108can be marked with the letter of the alphabet corresponding to the number of process tubes102in the process tube strip100(for example, an “H” would be marked on the bottom end tab108of the process tube strip100for a process tube strip100having eight process tubes102connected together in the process tube strip100). The skilled artisan will readily appreciate, however, that various other characters, e.g., alphanumeric characters, such as “1” and “8” can also be readily used in marking the top and bottom end tabs of process tube strip100, to achieve the same purpose. Thus, the top and bottom end tabs106,108can be used to indicate the top and bottom of a process tube102and the number of process tubes102in a process tube strip100. In addition, the end tabs106,108can be marked with a color marking, a barcode, or some other designation to identify, for example, the contents of the process tubes102, the assay type being performed in the process tube strip100, and the date and location of manufacture of the process tube strip100.

FIG.1Dis another embodiment of the process tube strip100that includes a ledge extension110on each of the process tubes102.FIG.1Eis an additional embodiment of the process tube strip100that includes a tube tag112positioned on the ledge extension110of each process tube102. These embodiments will be discussed in further detail below.

Process tubes102can be receptacles for, or house, solids or liquids. For example, process tubes102can hold reagents and/or samples, e.g., nucleic acid samples to be used in amplification assays. The process tubes102can be circular in cross-section, but other cross sections are possible and consistent herewith. The process tubes102can be manufactured via a unitary construction, although in certain instances the process tubes may be constructed from two or more parts fused or otherwise joined together as applicable. Typically, the process tubes102have an opening that is configured to accept/receive a pipette tip for deposit and/or retrieval of fluids within the process tube102.

In some embodiments, the process tubes102can be constructed from polypropylene or other thermoplastic polymers known to those skilled in the art. Alternatively, process tubes102can be constructed from other appropriate materials, such as polycarbonate or the like. In some embodiments, the polypropylene is advantageously supplemented with a pigment, such as titanium dioxide, zinc oxide, zirconium oxide, or calcium carbonate, or the like. Preferably, the process tubes102are manufactured using materials such that they do not fluoresce and thus do not interfere with detection of the amplified nucleic acid in the process tubes102.

FIGS.2A and2Bshow, respectively, an isometric and a cross-sectional view of an exemplary single process tube102. Connector tabs104are shown inFIG.2A, connecting the process tube102to other process tubes102on either side of the process tube102. InFIG.2B, the shown connector tab104includes a connector recess232on the underside of the connector tab. In some embodiments, the connector recess232provides a separation point to easily break apart different process tubes102connected as part of a process strip100. The process tubes102can be broken apart by the end user in order to mix and match different process tubes102having different dried reagents, and rearranging the process tubes in the carrier tray300to match the necessary operation of the amplification assay in the thermal cycler. A connector tab104can also be positioned between the process tube102at the end of a process tube strip100and the top or bottom end tab106,108. Such a connector tab104allows the end process tube102to be removed easily and also mixed and matched with process tubes102from other process tube strips100or to be used individually in a thermal cycler.

As shown inFIGS.2A and2B, the process tube102can have a top ring202, the top ring202defining an opening226at the top of the process tube102. The top ring202extends around the circumference of the opening226. As part of the process tube102, an annular ledge204extends laterally out from the side of the process tube102below the top ring202. In this manner, the top ring202extends upwards from an upper surface206of the annular ledge204. In addition to the upper surface206, the annular ledge204is also defined by an outer surface208and a lower surface210. Below the annular ledge204is a neck228of the process tube102, which extends vertically from the annular ledge204, parallel to the longitudinal axis230of the process tube102. As shown inFIG.2B, the exterior of the process tube102at the neck228can be parallel to a longitudinal axis230running vertically through the process tube102. In another embodiment, the exterior neck228can be at an angle to the longitudinal axis230to aid in removal of the process tube102from an injection mold during the manufacturing process.

Below the neck228of the exemplary process tube102shown inFIGS.2A-2B, is a protrusion212extending laterally from the side of the process tube102. The protrusion212is defined by an upper slope214when extends from the neck228to an apex215of the protrusion212. The apex215of the protrusion212has the largest outside diameter of the protrusion212and then the protrusion212includes a lower slope216which extends from the apex215down the exterior of the process tube102. The upper slope214of the protrusion212slopes away from the longitudinal axis230and the lower slope216slopes back towards the longitudinal axis230. In some embodiments, as shown inFIGS.2A-2B, the angle of the upper slope214on the protrusion is steeper than the angle of the lower slope216on the protrusion212. The lower slope216of the protrusion212meets a longer body portion218of the process tube102. The body218, like the lower slope216of the protrusion212, slopes towards the longitudinal axis230, but has a less steep angle than the lower slope215of the protrusion212. The body218extends to a base220of the process tube102. The base220includes an annular bottom ring224on the bottom of the process tube102, defined by a divot222in the bottom of the process tube102. In this embodiment, the top ring202, the annular ledge204, the neck228, the protrusion212, and the body218are coaxial with the longitudinal axis230.

The annular ledge204, neck228, and protrusion212together define a securement region200of the process tube102. As will be explained in detail below, the securement region200provides a way to easily and securely attach the process tube102(or plurality of process tubes102in the form of a process strip100) to a carrier tray for transport and later processing in the heater of an thermal cycler.

As described above, the process tubes102can be manufactured as a strip100of tubes102connected together by a connector tab104. Multiple process tube strips100can then be inserted securely in a carrier tray300.FIG.3Ashows an exemplary carrier tray300. As seen inFIG.3A, the carrier tray300can house a plurality of ports306in a shelf302of the carrier tray300. The plurality of ports306can be configured to receive the individual process tubes102, and the number of ports306in a column of the carrier tray300can be advantageously designed to fit the length of the process tube strips100. Thus, the number of ports306in the y-direction can be designed to correspond to the number of process tubes102in a process tube strip100. In one embodiment, the carrier tray300can have eight ports306in the y-direction such that a process tube strip100consisting of eight process tubes102can be inserted and secured in the ports306of the carrier tray300in the y-direction.

In one embodiment, the ports306in the carrier tray300are elliptical in shape, having a larger cross-sectional diameter in the y-direction. In this manner, the larger diameter cross-sections of the elliptical ports306are lined up in the same direction as the process tube strips100when inserted in the carrier tray300.

FIG.3Bshows a plurality of process tube strips100securely fit in an exemplary carrier tray300. Once the process tubes102are inserted securely in the carrier tray300, assay reagents, e.g., amplification and detection reagents, can be added to the process tubes102in an automated manner. In some embodiments, liquid reagents can be pipetted into the individual process tubes102and then the carrier tray300can optionally be placed in a drier to dry the liquid reagents in the bottom of the process tubes as a solid mass formed to the shape of the internal base220of the process tube102. In some embodiments, liquid reagents are not dried down in the process tubes102. In some embodiments, each process tube102in a carrier tray300can be deposited with identical reagents. In other embodiments, some or each of the process tubes102in process tube strip100can be filled with differing reagents or samples.

Once filled with the desired reagents, e.g., following drying of the reagents in embodiments wherein the reagents are dried, or simply following deposition of the reagents in embodiments wherein the reagents are not dried, the process tubes102can be marked with an indicator to identify the contents (for example, the specific reagents) of the process tubes102. In some embodiments, marking of the process tubes102can be accomplished by hot stamping the top ring202of the process tubes102with a specific color indicating the contents (e.g., reagents) of the process tubes102. The top ring202also provides a surface to which an adhesive seal can be applied to seal the opening226of the process tube102.

As described above,FIG.1Dshows a process tube strip100wherein each process tube100includes a ledge extension110extending from one side of the annular ledge204of the process tube100. The ledge extension110provides additional surface area on the annular ledge204for marking of the individual process tubes102. In one embodiment, the ledge extension110can be pre-marked with an alphanumeric identifier (e.g., A, B, C, etc, or 1, 2, 3, etc.) to identify an individual process tube102within a process tube strip100. In one embodiment, as an alternative to hot stamping the top ring202, the ledge extension110of the process tubes102can be hot stamped, or otherwise marked, to identify the contents (e.g., reagents) of the process tubes102following the deposit of the reagents in the process tubes102. Furthermore, a 2-D bar code (ink or laser) can be printed directly on the ledge extension110.

As shown inFIG.1E, the individual process tubes102of the process tube strip100can include a tube tag112affixed to the top of the ledge extension110. The tag112can be used in addition to, or in conjunction with, marking (e.g., hot stamping) the top ring202of the process tubes102to identify the contents, such as reagents, in a particular process tube102. The tag112can be a 2-dimensional matrix bar code (for example, a QR code or Aztec code) encoded with data identifying the contents of the associated process tube102. In using a tag112to indicate the contents of the process tube102, a camera (e.g., a CCD camera) can be used to scan and verify the contents of the process tube102and ensure the correct amplification assays are being performed with the associated reagents. The camera can efficiently and quickly verify the contents of each process tube102by reading the tag112, thus avoiding the possibility of user error in pairing incorrect reagents with a specific amplification assay required for a given polynucleotide sample.

In some instances, identical reagents can be added to each process tube in a carrier tray300. In one example, each tube strip100can include eight process tubes102and then 12 tube strips can be securely fit into a 96-port carrier tray300. Identical reagents can then be added to each of the 96 process tubes in the carrier tray300. If all process tubes102are provided with identical reagents, all process tubes102in the entire carrier tray300can be hot stamped with the same color. A number of carrier trays300can be stacked and sent together to the end user. In some embodiments, each or some of the process tubes102in tube strip100can include different reagents. In such instances, process tubes102that contain identical reagents can be marked with the same color. Different colors can be used to identify process tubes102containing different reagents.

The end user may need different stamped process tubes102to run different amplification assays with the different reagents provided. In some instances the end user may need to use different reagents in an amplification assay, so a carrier tray300having process tubes102of all the same reagents could not be used. In this case, the end user can remove one or more process tube strips100from a single-color carrier tray300and exchange them with differently colored process tube strips100in a different carrier tray300to achieve the desired number and type of reagents for a given amplification assay. It is also contemplated that the manufacturer could provide the end user with a carrier tray300having different colored process tube strips100.

The end user can further refine the collection of different reagents in an amplification assay by breaking apart an individual process tube strip100at the connector recess232between process tubes102. For example, an eight-tube process tube strip100can be broken into smaller collections of process tubes102having 1, 2, 3, 4, 5, 6, or 7 process tubes102. Breaking apart the process tube strips100allows the end user to include process tubes102of different reagents in the same column of the carrier tray300.

As described above,FIG.3Bprovides an illustration of the process tubes102when the process tubes are already securely fit into the carrier tray300.FIG.4is a cross-sectional view of 12 process tubes102positioned in the carrier tray300prior to securing the process tubes102in the carrier tray300. This view is analogous to the cross-sectional view6A shown inFIG.3, but shows the process tubes102resting in the ports306of the carrier tray300prior to securing the process tubes102in the carrier tray300. As shown inFIG.3BandFIG.4, the carrier tray300has a base304and a shelf302, the base304being wider and longer than the shelf302and, thus, having a larger planar surface area than shelf302. The shelf302of the carrier tray300includes a shelf side308and a shelf top310. The shelf top310is the horizontal, planar portion of the shelf302and covers the top of the carrier tray300. The shelf top310includes an exterior surface312and an interior surface314. As the base304of the carrier tray300is wider and longer than the shelf302, the base304includes a bridge320running horizontally connecting the shelf side308and a base side305. The bridge320includes an interior side322. The shelf side308of the shelf302on the carrier tray300extends down from the shelf top310and joins the base304of the carrier tray300at the bridge320. As shown inFIG.4, the process tubes102of a process tube strip100can be positioned in the ports306in the shelf302of the carrier tray300.

FIG.5is a close-up, cross-sectional view of two exemplary process tubes102positioned in an exemplary carrier tray300, prior to securing the process tubes102in the carrier tray300. Prior to securing a process tube102in the carrier tray300, the process tube102is able to rest in the port306of the carrier tray300. The outside diameter of the body218of the process tube102is smaller than the diameter of the port306, thus, the body218of the process tube102can be inserted through the port306. The protrusion212on the process tube102has a larger diameter than at least one diameter of the port306. For example, in the instance of the port306being elliptical, the smaller diameter of the port306(for example the width diameter in the x-direction ofFIGS.3A and3B) is smaller than the diameter of the protrusion212. In some embodiments, the larger diameter of the port306(for example the length diameter in the y-direction ofFIGS.3A and3B) can be larger than the diameter of the protrusion212. Thus, when the body218of the process tube102is inserted into the port306, the body218enters the underside area of the carrier tray300, but a top portion of the process tube102, including the securement region200(comprising the protrusion212, the neck228, and the annular ledge204) and the top ring202, is prevented from entering the port306. In this manner, the protrusion212comes to rest on a top edge318of the port306. More specifically, the lower slope216of the protrusion212comes to rest on the port top edge318.

In some embodiments, the apex212of the protrusion212is circular, having a constant outside diameter. For an elliptical port306, in one embodiment, the port306can have a length diameter larger than the width diameter. In this embodiment, the diameter of the port306width (in the x direction) can be less than the diameter of the apex215of the protrusion212. Thus, the process tube102comes to rest, at the protrusion212, on the top edge318of the port306. In one embodiment, the length diameter (in the y direction) of the port306can be greater than the diameter of the apex215of the protrusion212. Thus, a small gap on two ends (in the y-direction) of the port306is provided that facilitates easier securement of the process tube102in the port306and also facilitates easier removal of the process tube102from the port306, if needed. In other embodiments, the port306can be round, having a constant diameter.

As the process tube102rests in the port306against the port top edge318, a force can be applied to the top of the process tube102to press the process tube102further into the port306to secure the process tube102in the port306of the carrier tray300. The force to secure the process tube102into the port306can be applied to the top ring202of the process tube102or the force can be applied to the upper surface206of the annular ledge204.

Securing the process tube102in the port306initially involves applying sufficient force to the top of the process tube102to force the lower slope216of the protrusion212into the port306. The lower slope216is angled towards the longitudinal axis230of the process tube102. As continued pressure is applied to the top of the process tube102, the lower slope216of the protrusion212slides down along the port top edge318until the apex215of the protrusion212reaches the port top edge318. The port top edge318can be rounded or sloped to facilitate the travel of the protrusion212through the port306.

As the process tube102is pushed into the port306, the portions of the lower slope216of the protrusion212that have passed into the port306do not contact the port interior wall316because the lower slope216is angled towards the longitudinal axis230. The lower slope216of the protrusion212gradually widens (the outside diameter increases) as the lower slope216extends upwards towards the apex215of the protrusion212. The wider the diameter of the lower slope216, the greater resistance to pushing the process tube102into the port306. Thus, a resistive force is generated which counters the force applied to push the process tube102into the port306. The resistive force against the process tube102increases (and the force necessary to push the process tube102increases), the farther down the process tube212travels into the port306. The resistive force against the process tube102continues to increase until the apex215of the protrusion212reaches the port top edge318.

In an embodiment of the carrier tray300having elliptical ports306, the larger diameter of the port306in the y direction may more easily allow the process tube102to be pushed into the port306and secured in the carrier tray300, thus reducing the force required to secure the process tube. An elliptical port306can provide extra space (e.g., a gap) between the protrusion212of the process tube102and the port interior316on two ends that allows the process tube102to flex and elongate in the y direction and compress in the x direction.

Once the entirety of the lower slope216passes through the port top edge318, and the apex215of the protrusion passes through the port top edge318, the apex215of the protrusion212comes into contact with the port interior wall316. The apex215is the widest portion (largest outside diameter) of the protrusion212. As the apex215is being fit through the port306and pressed against the port interior wall316, the process tube102undergoes maximum strain and is maximally flexed. As continued force is applied to the top of the process tube102, the apex215is forced to slide down the port interior wall316until it completely passes through the port306at the bottom edge319of the port306. Once the apex215breaches the bottom edge319, the strain on the process tube102is released and the process tube102“snaps” securely into place in the port306and becomes secured in the carrier tray300. The force necessary to secure each process tube102of the process tube strips100in a carrier tray300can range from approximately 0.7 lbs. force to approximately 1.7 lbs. force. In one embodiment, the force necessary to insert and secure process tube102in a port306can be approximately 1 lb. force. In one embodiment, the force necessary to secure a process tube102in a port306can be approximately 1.18 lbs. force.

The carrier tray300can be advantageously designed for efficient stacking and transport of the carrier trays300. The carrier tray300can be constructed from polycarbonate resin thermoplastic. Referring toFIGS.3,4, and5, the carrier tray300can include a bridge320at the top of the base220. The bridge320provides a platform on which the bottom surface326of another empty carrier tray300can positioned. When two carrier trays300are stacked on top of each other, the bridge interior322of a top carrier tray300comes to rest on the shelf top310of a bottom carrier tray300and the bottom surface326of the top carrier tray300comes to rest on the bridge320of the bottom carrier tray300.

When the carrier trays300are populated with the process tube strips100, they can be efficiently stacked in a similar manner. The body218of the process tubes102in a top carrier tray300can be placed in the opening226of the process tubes102in a bottom carrier tray300. Likewise, the process tubes102in the top carrier tray300can further receive the body218of the process tubes102in another carrier tray300to be stacked on top of it.

FIG.6Ais a cross-sectional view, taken along line6A inFIG.3B, of the 12 process tubes102shown inFIG.4.FIG.6Ashows the process tubes102now secured in the carrier tray300. The direction of cross-section6A inFIG.3Bprovides a view of 12 process tubes102, each from a different process tube strip100.FIG.6Bis a cross-sectional view, taken along line6B inFIG.3B, of an entire process tube strip100positioned in the carrier tray300after securing the process tubes102in the carrier tray300. As shown inFIG.6B, the cross-sectional diameter of the elliptical port306in the y direction can be larger than the diameter of the protrusion212.

FIG.7is a close-up view of two of the process tubes102shown inFIG.6Aand corresponds to the process tubes102ofFIG.5after securing the process tubes102in the carrier tray300. As shown inFIG.7, the cross-sectional diameter of the elliptical port in the x direction can be smaller than the diameter of the protrusion212. When the apex215of the protrusion212breaches the bottom edge319, the upper slope214of the protrusion212comes into contact with, and lodges against, the bottom edge319of the port306, at the bottom of the securement region200. Also, when the apex215breaches the bottom edge319, the lower surface210of the annular ledge204comes into contact with, and lodges against, the shelf top exterior312of the shelf302, at the top of the securement region200. At the top of the securement region200, the annular ledge204is sufficiently wide at least two points around the port306that the annular ledge204cannot pass through the port306. In one embodiment, the annular ledge204can have a sufficiently large diameter to cover all points around the port306. For example, the annular ledge204can have a larger diameter than the width and length diameters of the port306. The height of the securement region200(from the lower surface210of the annular ledge204to a location on the upper slope214of the protrusion212) corresponds approximately to the height of the port306, between the port top edge318and the port bottom edge319.

As shown inFIG.7, the neck228of the process tube102can have a smaller outside diameter than the diameter of the port306, creating a gap324between the process tube102and the port interior wall314. In one embodiment, the outside diameter of the neck228can be a fixed circular diameter. As the port306can be elliptical in shape and have a larger length diameter on one side and a smaller width diameter on the other side, the width of the gap324can vary between the length side (y direction) and width side (x direction) of the port306. For example, the size of the gap324on each length side of the port306can be approximately twice the size of the gap on each width side of the port306.

The gap324provides a point of adjustment for the process tube102in the securement region200. The gap324exists primarily between the neck228of the process tube102and the port interior wall316, but the gap324also exists along a portion of the upper slope214of the protrusion212and along a portion of the lower surface210of the annular ledge204. The gap324is enlarged slightly at the top portion of the securement region200because the rounded corners of the port top edge318provide additional distance between the port306and the neck228of the process tube102. The gap324can provide the process tube102some degree of freedom of movement within the port306of the carrier tray300, even when the process tube102is secured in the port306.

The process tube102can be adjusted in the port306while being maintained securely in the port306because the point of contact between the upper slope214of the protrusion212and the port bottom edge319can adjust as the process tube102needs to tilt. When a process tube102tilts, the locations of the points of contact between the securement region200of the process tube102and the port306of the carrier tray300will adjust. For example, when the process tube tilts to one side, a point of contact on one side of the process tube102between the upper slope214and port bottom edge319moves near the top of the upper slope214; on the other side of the tube, another point of contact moves to be near the bottom of the upper slope214(near the apex215). Similar adjustment is possible at the top of the securement region200, such that the neck228can be tilted towards the rounded port top edge318on one side of the process tube102and can be tilted away from the port top edge318on the other side of the process tube102.

The gap324allows the process tube102to adjust when placing a plurality of process tubes into the carrier tray100as part of a process tube strip100. Because of possible manufacturing variations of the carrier trays300and the process tubes102, each carrier tray300may be sized slightly differently and each process tube102may fit in the carrier trays300differently. Given that the process tubes102are often attached together as part of a process tube strip102when inserted in the carrier tray300, it is possible that, without mitigating considerations, the manufacturing variations of the carrier tray300and process tubes102could prevent accurate placement of an entire process tube strip100in a carrier tray300. For example, accurate insertion of a process tube102at one end of a process tube strip100into the carrier tray300could prevent accurate insertion of the process tubes102at the other end of the process tube strip100into the carrier tray300because the process tubes102could be misaligned in either the x direction (lateral) or y direction (front to back). Even if a rigid process tube strip100is forced into the ports306of a carrier tray300despite being misaligned, the rigid attachment of the process tubes102would prevent the process tubes102from lying flat on the carrier tray300which could inhibit the hot stamping process.

The present disclosure addresses these issues in a number of ways, including allowing the process tubes102to tilt and adjust in the port306when the process tube strip100is being maneuvered and inserted in the carrier tray300. The process tubes102can tilt and adjust in the port306because the gaps324allow for such motion. The elliptical shape of the ports306also enhances the adjustment available in the y direction. Also, the connector tabs104connecting the process tubes102are thin and pliable enough to allow maneuverability and adjustment between the individual process tubes102when inserting them in the carrier tray300. In addition, the connector recess232(seen inFIG.2B) on the connector tab104allows increased flexibility between the individual process tubes102when inserting them in the ports306. In this manner, the gaps324, the elliptical-shaped ports306, and the connector tabs104afford the process tube102the capacity to adjust and always lay flat on the carrier tray300when inserting a process tube strip100into the carrier tray300. Furthermore, the capacity of a process tube102to tilt or adjust in the carrier tray300facilities insertion of the process tube102into a heater of the thermal cycler, as discussed below in more detail.

When the process tubes102are secured in the ports306of the carrier tray300, the process tubes102can undergo processing in preparation for use in a thermal cycler. Liquid reagents can be inputted into the secured process tubes102. The process tubes102in the carrier tray300can be subjected to heat or other processes for drying or lyophilization in order to dry the liquid reagents in the process tubes102. While secured in the carrier tray300, the process tubes102can also be hot stamped to mark the process tubes102, indicating the type of reagents added to the process tubes102. The hot stamping can be in the form of a color stamped on the top ring202and/or the annular ledge204.

The process of applying force to securing the process tubes102in the ports306of the carrier tray300, the process of inputting liquid reagents into the secured process tubes102, the process of drying the liquid reagents in the process tubes102, and the process of hot stamping the process tubes102in carrier tray300can all be automated and performed at the site of manufacture and assembly of the process tubes102and carrier trays300. The assembled carrier trays300containing the prepared process tubes102can then be shipped to the end user for additional processing such as depositing extracted nucleic acid samples in the process tubes102prior to running amplification assays on the samples the process tubes102in a thermal cycler. The addition of the extracted nucleic acid samples to the process tubes102acts to reconstitute the dried reagents to allow the reagents to associate with the nucleic acid samples in the reconstituted solution.

As described above, an end user can remove one or more process tube strips100from a single-color carrier tray300and exchange them with differently colored process tube strips100in a different carrier tray300to achieve the desired number and type of reagents for a given amplification assay. The force necessary to remove the process tube strip100can be approximately half of the force required to insert it. In one embodiment, the insertion force for a process tube strip100can have a range of approximately 0.7 lbs. force to 1.7 lbs. force and the removal force for the process tube strip100can have a range of approximately 0.3 lbs. force to 0.8 lbs force. In one embodiment, the insertion force for a process tube strip100can be approximately 1 lb. force and the removal force for the process tube strip100can be approximately 0.5 lb. force. In one embodiment, the force necessary to secure a process tube strip100in the ports306can be approximately 1.18 lbs. force and the force necessary to remove the process tube strip is 0.60 lbs. force. The insertion and removal forces prescribed for the process tube strips100insure that a process tube strip100is not overly difficult to insert or remove from the carrier tray300and also prevent the process tube strips100from falling out of the carrier tray under normal handling conditions.

It is of note that the same carrier tray300(housing the process tubes102) in which the mixing of reagents and nucleic acid samples occurs can be input directly into the thermal cycler. Thus, the end user is not required to do the mixing of reagents and nucleic acid in one tube and then transport that mixed solution to another tube, or even move the first tube to another tray. In the present disclosure, the process tubes102containing the reagents and secured in the carrier tray300can receive the samples, e.g., nucleic acid samples, and, then without removing the process tubes102from the carrier tray300, can be input into the thermal cycler for amplification assays.

It is also contemplated that solid reagents may be added to the process tubes102in addition to, or instead of, the liquid reagents. It is also contemplated that empty process tubes102and carrier trays300can be supplied to the end user and the end user can deposit the solid or liquid reagents in the process tubes102prior to adding the nucleic acid samples.

The securement force, the force necessary to push the process tube102securely into the port306, can be applied simultaneously to multiple (or all) process tubes102in the carrier tray300. Alternatively, the securement force can be applied separately to individual process tubes102one at a time, as needed. The securement force can be applied in an automated manner and can be conducted concurrently along with the automated steps of filling the process tubes102with reagents and hot stamping the process tubes102. In some instances, the same apparatus can be used to hot stamp and apply the securement force to the process tubes102. Alternatively, separate apparatuses can be used for hot stamping and applying the securement force.

When a separate securement force device and a hot stamping device are used, the securement force can first be applied to secure the process tubes102in the ports306of the carrier tray300prior to hot stamping the top ring202of the process tubes102. In some instances, the automated hot stamping apparatus may stick to the top ring202of the process tubes102when applying pressure to the top ring202. Because of the novel way in which the process tubes102are secured in the carrier tray300in the embodiments described herein, a process tubes102are not pulled up and out of the carrier tray300when the hot stamping apparatus pulls apart from the process tube102being stamped. Furthermore, because the process tubes102are secured in the carrier tray300, the process tubes102can be transported without risk of the process tubes102falling out of the carrier tray300. The embodiments disclosed herein also advantageously overcome other issues that present in other PCR tube trays, such as bunching of tubes on one side of the tray or tubes falling out of alignment in the tray.

FIG.8is an isometric view of an exemplary heater assembly400to be used in a thermal cycler (not shown). Amplification assays (such as PCR or isothermal amplification) can be performed in the thermal cycler. The heater assembly400is part of temperature cycling-subsystem of the thermal cycler and can work in conjunction with other subsystems of the thermal cycler, such as a detection subsystem. The exemplary heater assembly400shown inFIG.8is a 96-well assembly containing 96 heater wells402, although other assemblies are contemplated (e.g., 48-well assemblies, etc.). The heater assembly400includes a flat top surface404between the heater wells402, and a side surface410. Each heater well402is conical in shape and is comprised of an interior wall406and a well bottom412. The heater wells402in the heater assembly400are arranged in an array of 8 rows and 12 columns to correspond to the spatial arrangement of process tubes102in a carrier tray300.

Each heater well402can receive a process tube102. The carrier tray300can be placed directly over the heater assembly400in the thermal cycler in order to place all process tube102in the carrier tray300into the heater assembly400simultaneously. Not shown inFIG.8is the casing around the heater assembly400or the necessary circuitry to provide heat to the heater wells402.

Because of possible manufacturing variations of the carrier trays300and the process tubes102, each carrier tray300may be sized slightly differently and each process tube102may fit in the carrier trays300differently. If the process tubes102were rigidly attached to the carrier tray300, the manufacturing tolerances could prevent all of the process tubes in a 96-tube carrier tray300from accurately being placed in the heater wells402. For example, fitting a process tube102in a heater well402on one side of the heater assembly400may prevent a process tube102on the other side of the heater assembly400from being accurately and securely placed into its respective heater well402. As described above, the process tubes102are able to float or adjust slightly when secured in the carrier tray300because of the gap324between the port interior wall316and the securement region200of the process tube102. The connector recess232(seen inFIG.2B) on the connector tab104also allows flexibility between the individual process tubes102when inserting them in the heater wells402. Allowing the process tubes102to float within ports306of the carrier tray300permits the process tubes102to adjust position to fit accurately and securely into the heater wells402of the heater assembly400.

FIG.9is a cross-sectional view of two exemplary process tubes102positioned in heater wells402of the heater assembly400. When the process tube102is placed in the heater well402, the body218of the process tube102comes in physical contact with, and is mated to, the interior wall406of the heater well402. In some embodiments, the heater well402is deeper than the body218of the process tube102, such that when the process tube102is secured in a port306of the carrier tray300and the carrier tray300is positioned over the heater assembly400, the base220of the process tube102does not extend to the well bottom412. In this manner, a gap414is created between the base220of the process tube102and the well bottom412. The gap414ensures that the body218of the process tube102remain in physical contact with the well interior wall406; if the base220of the process tube102were to bottom out in the heater well bottom412first, before the body218contacts the well interior wall406, a gap could exist between the wall406and the body218of the process tube102and cause poor heat transfer between the heater well402and the process tube102. Thus, the gap414below the process tube102ensures that a gap does not exist between the wall406and the body218of the process tube102. The heater well402can surround the body218of the process tube102and provide uniform heating to the contents of the process tube102during the thermal cycling steps of the amplification assay. When the process tube102is placed in the heater well402, the heater well402can surround the body218of the process tube to a location just below the lower slope216of the protrusion212.

The above description discloses multiple methods and systems of the embodiments disclosed herein. The embodiments disclosed herein are susceptible to modifications in the methods and materials, as well as alterations in the fabrication methods and equipment. Such modifications will become apparent to those skilled in the art from a consideration of this disclosure or practice of the invention disclosed herein. Consequently, it is not intended that the embodiments disclosed herein be limited to the specific embodiments disclosed herein, but that it cover all modifications and alternatives coming within the true scope and spirit of the invention.

Example 1

This example illustrates a specific process for preparing a carrier tray300with process tubes102to be provided to an end user.1. Manufacturing 12 process tube strips containing eight connected process tubes formed from polypropylene.2. Manufacturing a carrier tray from polycarbonate having 96 ports in an 8×12 array.3. The 12 process tube strips are placed in the carrier tray.4. The process tubes of the process tube strips are secured in the ports of the carrier tray by applying a force to the top ring of the process tube.5. Each process tube in the carrier tray is filled with the same specific liquid reagents.6. The carrier tray is heated to dry the reagents in the process tubes.7. The process tubes are hot stamped with specific colors to indicate the assay for which they will be used.8. The carrier tray is stacked and packaged with other carrier trays having the same or different reagents and shipped to the end user.9. The end user can use the entire carrier tray as is, or may depopulate the carrier tray and repopulate the carrier tray or trays with a mix of individual process tube strips or tubes of various reagent types.

Example 2

This example describes the test procedure and results of a test to determine the force necessary to secure the process tube strips100in the ports306of the carrier tray300and the force necessary to subsequently remove the process tube strips100from the ports306.

An Amtek AccuForce Cadet Force Gage, (0-5 lbs) was used to measure the force necessary to secure and remove the process tubes102in the ports306.

Test Procedure

1. Lay one strip of tubes in a column of the carrier tray. (Not yet secured in the carrier tray)2. Turn on the gage.3. Zero the gage with the gage in the upright position.4. Clear the gage.5. Slowly press down on each tube within the strip starting at the “A” row with the gage at a slight angle ˜2-3 degrees from vertical on each tube until all the tubes snap into place.6. Record the force value on the gauge and the column number as insertion values.7. Press the clear button to clear the memory.8. Lay the second strip of tubes in the second column. Repeat steps 5-7.9. Repeat steps 5-7 for the remaining strips 3-12.10. Turn the carrier tray upside down and starting with the first strip slowly press the tubes out of the carrier starting at the “A” row.11. Record the force value and the column number as removal values.12. Press the clear button to clear the memory.13. Repeat steps 10, 11 and 12 for the remaining process tube strips.14. Rearrange the 12 process tube strips in the carrier tray and repeat steps 3-13.
Results

The results of the force testing are provided in Table 1. Table 1 shows the force necessary to insert and secure all the process tubes102of a process tube strip100in a carrier tray300. As shown, the average insertion force to secure the process tube strips100in the carrier tray300was 1.18 lbs force and the average removal force was 0.60 lbs force.

TABLE 1Process Tube Insertion and Removal TestingTube Strips1stRound1234567Insertion0.7081.0841.1371.4670.9451.4760.866Removal0.3130.4780.5730.5890.5200.5180.5531stRound89101112AvgInsertion1.0751.4080.9691.0251.2171.115Removal0.9780.7670.3880.6020.4850.5642ndRound-tube strips randomly rearranged1234567Insertion0.6680.9041.6611.7271.6771.2961.536Removal0.4390.5340.6990.6300.5840.6520.7232ndRound-tube strips randomly rearranged89101112AvgInsertion1.0511.2801.0561.0120.9831.238Removal0.6750.7780.7500.6190.5140.633Average Insertion1.18Average Removal0.60