Cover assembly and related methods of use

A cover assembly may include a tray assembly frame, a first cover supported by the tray assembly frame, the first cover extending in a first plane and defining one or more first openings; a second cover supported by the tray assembly frame, the second cover extending in a second plane and defining one or more second openings, wherein the first and second planes are different planes, and wherein the second cover is disposed above the first cover. The cover assembly may include one or more tray holders, each tray holder being configured to hold at least one tray in an upright orientation, wherein each tray holder is moveable between an open position and a closed position, the tray holders being accessible for loading or removing the trays in the open position, and the tray holders being positioned beneath the first and second covers in the closed position.

TECHNICAL FIELD

This disclosure is directed to a cover assembly, and related methods of use.

BACKGROUND

Automated analytical procedures for determining the presence of an analyte in a sample typically require the use, processing, and/or manipulation of fluid solutions and/or fluid suspensions. Such fluid solutions and/or suspensions are frequently stored within analytical instruments in containers that may be accessed by a fluid transfer apparatus (e.g., a robotic pipettor). The contents of the containers may be accessed through open ends of the containers (e.g., uncapped and exposed to the atmosphere) during the operation of an instrument. Leaving a container in an open state, however, may lead to contamination of samples contained therein by accidental dripping of material from the pipettor into the open containers.

SUMMARY OF THE DISCLOSURE

In one aspect, the disclosure is directed to a cover assembly comprising a tray assembly frame; a first cover supported by the tray assembly frame, the first cover extending in a first plane and defining one or more first openings; a second cover supported by the tray assembly frame, the second cover extending in a second plane and defining one or more second openings, wherein the first and second planes are different planes, and wherein the second cover is disposed above the first cover; one or more tray holders, each tray holder being configured to hold at least one tray in an upright orientation, wherein each tray holder is moveable between an open position and a closed position, the tray holders being accessible for loading or removing the trays in the open position, and the tray holders being positioned beneath the first and second covers in the closed position; one or more actuators coupled to the tray assembly frame and to the first and second covers, the actuators being configured to move the first and second covers between a closed configuration and one or more open configurations, wherein the tray holders are inaccessible from any position directly above the first and second covers in the closed configuration, and wherein at least one of the first openings and at least one of the second openings are aligned to permit access to a portion of at least one of the tray holders in the open configuration.

The cover assembly includes a cover frame coupled to at least a portion of a top surface of the tray assembly frame and dimensioned to permit access to the tray holders, the cover frame including at least two opposed, upwardly extending guide rails configured to limit longitudinal movement of the first and second covers, wherein each guide rail includes an inwardly extending tab configured to limit vertical movement of the first and second covers. The cover assembly includes one or more guide pins extending upwardly from or through the cover frame, the first cover defining one or more laterally extending, first guide slots that accommodate the guide pins, the second cover defining one or more laterally extending, second guide slots that accommodate the guide pins, wherein each of the first and second guide slots is associated with one of the guide pins, wherein the first and second guide slots are coextensive with each other, and wherein the guide pins and the first and second guide slots are dimensioned to limit lateral movement of the first and second covers. The cover frame is configured to limit vertical movement of one or more trays held by the one or more tray holders. The first and second planes are substantially parallel to each other. The first and second covers are configured for sliding engagement. The first cover defines a plurality of first openings. The second cover defines a plurality of second openings. In each of the open configurations, each of the first openings is aligned with a corresponding one of the second openings, and wherein each of the aligned first and second openings permits access to a portion of at least one of the tray holders in the open configurations. For each of the first openings there is a corresponding one of the second openings. The first and second covers have substantially the same dimensions, and wherein the locations and dimensions of the holes defined by the first and second covers are substantially the same. The first cover and the second cover are arranged as mirror images of each other. The first plane is defined by a first longitudinal axis and a first lateral axis that is perpendicular to the first longitudinal axis, the first cover being configured to move in the first plane along the first lateral axis and not along the first longitudinal axis, and wherein the second plane is defined by a second longitudinal axis and a second lateral axis that is perpendicular to the second longitudinal axis, the second cover being configured to move in the second plane along the second lateral axis and not along the second longitudinal axis. The actuators are configured to move the first and second covers independent of each other. The actuators comprise first and second actuators, the first actuator including a first motor coupled to the first cover and the second actuator including a second motor coupled to the second cover. The first cover comprises a first edge that defines a first end tab and a first lateral edge opposite the first edge, and wherein the second cover comprises a second edge that defines a second end tab and a second lateral edge opposite the second edge. The first end tab defines a first slot, the first actuator includes a first pin, the first slot receives the first pin, and rotation of the first pin causes linear movement of the first cover, and wherein the second end tab defines a second slot, the second actuator includes a second pin, the second slot receives the second pin, and rotation of the second pin causes linear movement of the second cover. In the closed configuration, each first opening of the first cover is blocked by the second cover and each second opening of the second cover is blocked by the first cover. The first and second openings are linear openings. The width of each linear opening is from about 5 mm to about 15 mm. The width of each linear opening is at least about 10 mm. The length of each linear opening is from about 5 to about 15 times the width of the linear opening. The length of each linear opening is about 10 times the width of the linear opening. The cover assembly includes one or more drawers, each tray holder being coupled to one of the drawers, and each drawer being coupled to a drawer face for moving the tray holders between the open and closed positions.

In another aspect, the disclosure is directed to a system comprising a cover assembly; and a fluid transfer device capable of movement over the cover assembly.

The fluid transfer device is capable of movement along the XYZ axes. The fluid transfer device comprises a pipettor having a fixed or disposable tip, and wherein the tray holders hold at least one tray supporting or comprising a plurality of receptacles. The tray is a microtiter plate, and wherein each of the plurality of receptacles of the microtiter plate is a well for containing a fluid. The receptacles are arranged in rows, each row comprising two or more receptacles, and wherein a content of each receptacle of at least one row of receptacles is accessible by the fluid transfer device when the first and second covers are in a first one of the open configurations, and wherein a content of each receptacle of least one row of receptacles is inaccessible by the fluid transfer device when the first and second covers are in the first one of the open configurations. The distance between the centers of the first and second rows is about 10 mm. The first openings comprise a pair of adjacent first openings, the distance between the centers of the adjacent first openings being about 30 mm, and wherein the second openings comprise a pair of adjacent second openings, the distance between the centers of the adjacent second openings being about 30 mm. The tray holders hold at least one tray comprising one or more rows of wells, the wells of each row supporting at least one receptacle and at least one cap positioned in a side-by-side relationship, the cap being configured to close the receptacle, wherein the fluid transfer device is configured for engaging the cap in a frictional fit, and wherein contents of each well of at least one row of wells is accessible by the fluid transfer device when the first and second covers are in at least one of the open configurations. In the closed configuration, the first and second covers are arranged to block the fluid transfer device from aspirating a fluid from or dispensing a fluid into any of receptacles. The system further comprises at least one of: one or more first sensors coupled to the fluid transfer device, the one or more first sensors being configured to track a location of the fluid transfer device; and one or more second sensors coupled to the cover assembly, the one or more second sensors being configured to track locations of the first and second covers.

In yet another aspect, the disclosure is directed to a method of aspirating or dispensing fluid with a system having a first cover, a second cover, and a fluid transfer device, wherein the first cover and the second cover are disposed above a plurality of receptacles, the method comprising the steps of (a) transitioning the first cover and the second cover from a first closed configuration, where access to at least a first group of the plurality of receptacles by the fluid transfer device is blocked by at least one of the first cover and the second cover, to a first open configuration where a first receptacle of the first group of receptacles is accessible by the fluid transfer device; (b) aspirating a fluid from the first receptacle using the fluid transfer device or dispensing a fluid into the first receptacle using the fluid transfer device; (c) after step (b), transitioning the first cover and the second cover from the first open configuration to the first closed configuration, or to a second closed configuration where access to at least a second group of the plurality of receptacles by the fluid transfer device positioned above the first cover and the second cover is blocked by at least one of the first cover and the second cover.

The first cover and the second cover move independent of each other during the transitioning steps. The inserting step includes lowering the fluid transfer device through a first opening of the first cover and a second opening of the second cover. The first cover is disposed in a first plane, the second cover is disposed in a second plane parallel to the first plane, and the first opening is aligned with the second opening in the first open configuration, thereby permitting the fluid transfer device to access the first receptacle. In step (c), the first cover and the second cover are transitioned to the second closed configuration, and in the second closed configuration, a subset of the receptacles are accessible by the fluid transfer device. Prior to step (a) or after step (c), the step of moving the fluid transfer device along a path that extends over at least one receptacle of the plurality of receptacles, the path being covered by at least one of the first and second covers. After step (c) and prior to aspirating a fluid from a second receptacle using the fluid transfer device or dispensing a fluid into the second receptacle using the fluid transfer device, the step of transitioning the first and second covers to a second open configuration where the second receptacle is accessible by the fluid transfer device and access to the first receptacle by the fluid transfer device is blocked by at least one of the first cover and the second cover. The method further comprises the step of aspirating a fluid from the second receptacle using the fluid transfer device or dispensing a fluid into the second receptacle using the fluid transfer device. One of the first and second covers is stationary when transitioning the first cover and the second cover from the first closed configuration to the first open configuration. The first and second covers move simultaneously when transitioning the first and second covers from the first closed configuration to the first open configuration. The first and second covers move sequentially when transitioning the first and second covers from the first closed configuration to the first open configuration. The method further comprises prior to step (a), the step of providing one or more trays to the system below the first and second covers, each tray supporting or comprising at least a portion of the plurality of receptacles. Each tray comprises a plurality of wells, each well being configured to hold one of the receptacles or a cap for closing the receptacle, and each receptacle being a vial. The method further comprising, with the fluid transfer device, the steps of engaging a cap supported by a first well of the plurality wells in a frictional fit and sealing a vial in a second well of the plurality of the wells with the cap, thereby forming a cap/vial assembly, wherein the first and second wells are adjacent wells. The method further comprising, while the cap of the cap/vial assembly is engaged by the fluid transfer device, moving the cap/vial assembly from a first location of the system where the engaging step is performed to a second location of the system. The second location of the system is a centrifuge or a thermal cycler. Step (b) comprises dispensing the fluid into the first receptacle, and wherein the fluid is a reaction fluid for performing a PCR reaction. After step (a) and prior to step (c), a row of the receptacles is accessible by the fluid transfer device, the row of receptacles including the first receptacle. The method further comprising, prior to step (b), the step of inserting a fixed or disposable tip of the fluid transfer device into the first receptacle.

DETAILED DESCRIPTION

Reference will now be made in detail to examples of the present disclosure, which are illustrated in the accompanying drawings. Wherever possible, the same reference numbers will be used throughout the drawings to refer to the same or like parts. In the discussion that follows, relative terms such as “about,” “substantially,” “approximately,” etc. are used to indicate a possible variation of ±10% in a stated numeric value.

Diagnostic System

FIG. 1illustrates a diagnostic system10configured to perform a plurality of different molecular assays on a plurality of samples. In some examples, diagnostic system10may be configured to perform different target nucleic acid amplification reactions. For example, diagnostic system10may be configured to perform a first target nucleic acid amplification reaction on a first subset of a plurality of samples, and perform a second, different target nucleic acid amplification reaction on a second subset of the plurality of samples. System10may perform any number of different reactions on different samples. In some examples, diagnostic system10comprises a first module100configured to perform at least one of the steps of a target nucleic acid amplification reaction, and a second module400configured to perform at least one of the steps of the target nucleic acid amplification. Diagnostic system10may include any of the components and functionalities described in U.S. Patent Application Publication Nos. 2016/0032358, 2014/0038192, and 2014/0263984.

Diagnostic system10may be configured such that first module100may be selectively and operatively coupled to second module400, and first module100may be selectively decoupled from second module400. This coupling may be achieved by any suitable mechanism(s), such as, e.g., mechanical fasteners (for example, bolts screws, or clamps). Suitable power and/or data lines may be provided between second module400and first module100. In some examples, second module400may extend the overall system capabilities of a diagnostic system including only first module100that was previously purchased by a customer or otherwise used by an operator.

First Module

First module100may include various components configured to receive one or more reaction receptacles, within each of which is performed one or more steps of a multi-step nucleic acid test (NAT) designed to detect, for example, a virus or organism (e.g., bacterium, fungus, or protozoan). As the focus of this disclosure includes components within second module400, this disclosure refers to U.S. Patent Application Publication No. 2016/0032358 for additional details of exemplary first modules100.

Second Module

Second module400may be integral with first module100, and in other examples, second module400may be selectively and operatively coupled to first module100as described above.

In one example, second module400is configured to perform nucleic acid amplification reactions, for example, PCR, and, in certain examples, to measure fluorescence in real-time (e.g., as the amplification reaction is occurring). A controller may direct the components of first module100, and components of second module400, to perform the assay steps. In one example, first module100houses a computer and all fluids, reagents, consumables, and mechanical modules needed to perform the specified amplification-based assays, such as assays based on transcription-based amplification methods, for example, TMA or nucleic acid sequence-based amplification (NASBA). TMA methods are described in U.S. Pat. Nos. 5,399,491 and 5,480,784; and NASBA methods are described in U.S. Pat. No. 5,409,818 and in U.S. Pat. No. 5,130,238. As explained above, the controller may comprise a computer and preferably can accommodate LIS (“laboratory information system”) connectivity and remote user access. In some examples, second module400houses component modules that enable additional amplification assays, melting analyses, and additional functionalities. Other components may include a printer and an uninterruptible power supply.

Examples of the general configuration of second module400are shown inFIGS. 1-3. Second module400can include, for example, a substance transfer device (for example, a fluid transfer device or robotic pipettor402), a thermal cycler/signal detector432, tip compartments580(e.g., two or more) configured to contain trays of disposable tips for the pipettor(s), tray assemblies440(e.g., two or more) configured to contain trays460of disposable processing vials and associated caps in an upright orientation, a bulk reagent container compartment500, and a bulk reagent container transport550. For purposes of this disclosure, a fluid transfer device may be referred to in the exemplary embodiments described herein, which is not intended to limit this disclosure from encompassing the use of other suitable substance transfer devices.

As shown inFIG. 1, components of second module400may be positioned on different levels, or decks, arranged vertically within a chassis of second module400. Fluid transfer device402is disposed near the top of second module400, above all other components, in some examples. The vertical order of the decks and components may vary according to the intended use of diagnostic system10. In the depicted example, below fluid transfer device402, an amplification processing deck430includes the bulk reagent container compartment500and bulk reagent container transport550, a centrifuge588, the top of the thermal cycler/signal detector432, tip compartments580, and tray assembly440. Tray assembly440may include a tray assembly frame450(referring toFIG. 16) mountable to the chassis of second module400, and may include drawers442(referring toFIG. 19) movable between an open position and a closed position via drawer faces (handles)446. Drawers442may include one or more tray holders444(e.g., exactly two), each configured to receive a tray460(shown in, e.g.,FIGS. 17 and 19, where each tray is shown with only some of its respective wells/receptacles). An exemplary tray is described in U.S. Patent Application Publication No. 20170297027A1. Tray holders444may be accessible for loading or removing trays460in the open position, and are positioned beneath covers of a cover assembly in the closed position (e.g., first and second covers2002and2004of a cover assembly2000, described below). Below the amplification processing deck430, magnetic elution slots620and reagent pack loading stations640on a receptacle processing deck are accessible to fluid transfer device402through a gap between modules of the amplification processing deck430.

Fluid Transfer Device

Fluid transfer device402, shown inFIGS. 1, 3, and 4, may be a dual arm system comprising a front arm408and a back arm416. Fluid transfer device402may be configured to dispense and/or aspirate substances into and/or from a container, receptacle, well, etc., in second module400. Front arm408includes a substance transfer pipettor410configured to aspirate fluid and dispense fluid, and includes a pump, for example, an integrated syringe pump. Back arm416includes a vial transfer arm418and may not perform substance transfer. Fluid transfer device402comprises a Cartesian gantry assembly with two transverse tracks404,406, a back arm longitudinal track420, and a front arm longitudinal track412. The designations “longitudinal” and “transverse” are merely for distinguishing the two sets of tracks, which may be orthogonal to one another, but otherwise the designations are arbitrary.

Substance transfer pipettor410may be driven back and forth along front arm longitudinal track412by a belt, drive screw, or other motion transmission device coupled to a motor. Vial transfer arm418may be driven back and forth along back arm longitudinal track420, front arm longitudinal track412may be driven back and forth along transverse tracks404,406, and back arm longitudinal track420may be driven back and forth along transverse tracks404,406, by similar mechanisms. Substance transfer pipettor410and vial transfer arm418may be movable simultaneously along multiple axes, such as, e.g., the X and Y axes. For example, substance transfer pipettor410may be moved along front arm longitudinal track412at the same time that front arm longitudinal track412is moved along transverse tracks404and406. Similarly, vial transfer arm418may be moved simultaneously along the same axes by moving vial transfer arm418along back arm longitudinal track420at the same time that back arm longitudinal track420is moved along transverse tracks404and406. The movement of substance transfer pipettor410and vial transfer arm418along multiple axes at the same time may allow for more direct and efficient paths of those devices between desired locations, potentially resulting in reduced procedure times. Substance transfer pipettor410and vial transfer arm418also may be driven along the Z, or vertical, axis, for example, by a motor and/or other suitable device. The Z axis may be substantially perpendicular to both the X and Y axes, and may correspond to the up/down direction within second module400.

In some examples, the motors of fluid transfer device402may be under the control of a system controller. The motors may be stepper motors and may include rotary encoders for controlling and monitoring the position of the track or pipettor to which it is coupled. Each of the tracks has home sensors (or limit switches) for indicating when substance transfer pipettor410or vial transfer arm418is in one or more designated positions, such as a designated “home” position. Similarly, each device may have a vertical home sensor for indicating when the probe is in one or more designated vertical positions, such as a designated vertical “home” position. Such sensors for indicating a home position may include optical sensors (e.g., slotted optical sensors), proximity sensors, magnetic sensors, capacitive sensors, etc.

In one example, substance transfer pipettor410is configured to accept TECAN 1 mL disposable pipette tips by inserting the probe thereof into a disposable pipette tip, and an interference fit between the probe and the pipette tip frictionally secures the pipette tip to the end of the probe. Front arm408and substance transfer pipettor410are configured to access at least parts of both amplification processing deck430and the receptacle processing deck on second module400. Substance transfer pipettor410may include integrated tip sensing for confirming the presence or absence of a disposable pipette tip, capacitive level sensing for detecting contact by the pipette tip with the surface of the fluid contents of a reaction receptacle or other container and determining the level of the fluid contents based on the detected vertical position of the pipettor, and pressure sensing for sensing pressure fluctuations within the substance transfer system during fluid dispensing or aspiration. Vial transfer arm418is configured to pick up a cap/vial assembly by inserting the probe thereof into a cap that is coupled to a vial, as will be described below.

Referring toFIGS. 5-8, processing vial464provides a receptacle for containing reaction fluids for performing PCR or other processes. Cap476is configured to be placed into or onto vial464in an automated manner so as to close off vial464. In some examples, cap476is configured to receive an end of vial transfer arm418via a friction fit, so that transfer arm418can pick up cap476and place it into or onto vial464. Cap476and vial464are configured to lock together so that once cap476is placed into or onto vial464, cap464and vial476are interlocked to form a cap/vial assembly. Vial transfer arm418can then transfer the cap/vial assembly from one location within second module400to another location. Exemplary caps and vials are disclosed in U.S. Provisional Patent Application No. 61/782,320.

In the example shown inFIGS. 5-7, processing vial464has a conical shape and an open top end465. Cap476has an open top end478and a closed lower end480. A lower portion of cap476defines a plug that fits into open top end465of processing vial464. This plug is sized so as to fit into vial464with an interference, friction fit.

The examples illustrated inFIGS. 6 and 7show, in cross-section, cap464, initially held in a cap well490of tray460, and vial464held in a vial well474of tray460. After fluids are dispensed into vial464with a disposable pipette tip584(connected to a robotic pipettor), vial464is capped by a cap476by inserting the closed lower end480of cap476into open top end465of vial464.

Trays

Referring to the illustrative example inFIG. 8, each tray460may define a plurality of wells1106each configured to receive vials464or caps476. In some examples, each well of the plurality of wells1106is configured to receive only one vial464or cap476. Wells1106also may be configured to receive other receptacles, containers, pipette tips, or the like. Tray460depicted inFIG. 8is merely illustrative, and is intended to be non-limiting with respect to the embodiments described herein. For example, the embodiments described herein encompass the use of microtiter well plates having a plurality of wells for containing a fluid, self-standing receptacles, other suitable types of holders for retaining receptacle vessels, and the like. Because wells1106themselves may contain a fluid (without a separate receptacle), wells1106, in some embodiments, may be considered receptacles.

In some examples, the plurality of wells1106can include two or more subsets of wells1106, and each subset of wells1106may be configured to contain a different item. For example, as shown inFIG. 8, wells1106of a first subset1106aare shaped and sized differently than wells1106of a second subset1106b.

In some examples as shown inFIG. 1, wells1106of first subset1106acan each be configured to contain a (receptacle) vial464, and wells1106of second subset1106bcan each be configured to contain a cap476. Thus, wells1106of first subset1106amay be substantially similar to wells474, and wells1106, and wells of second subset1106bmay be substantially similar to wells490, described above.

Additionally, as exemplified, wells1106of each tray460may be arranged in a plurality of columns1106cthat extend along a length of tray460. Each tray may have eight columns1106cand fourteen rows of wells1106. The fourteen rows may include seven rows of first subset1106aand seven rows of second subset1106b. However, it is contemplated that other suitable numbers of columns and rows may be utilized.

Tray460can include a surface1122defining the openings of the plurality of wells1106. Surface1122is positioned at the top of tray460in some examples as shown inFIG. 8. In some examples, surface1122is substantially rectangular when viewed from above. Tray460may include any suitable plastic, metal or other material.

Additional details of second module400and its components may be found in U.S. Patent Application Publication No. 2016/0032358.

Cover Assembly

Referring toFIGS. 9-14, a cover assembly2000may be configured to selectively permit access to the one or more trays460, and its wells1106, via front arm408and back arm416of fluid transfer device402. In one embodiment, cover assembly2000may selectively provide access to various sample wells, vials, microtiter plates, or the like, located on or below amplification deck430. Cover assembly2000may be positioned between fluid transfer device402and one or more trays460positioned on amplification deck430. Thus, cover assembly2000may be positioned above amplification deck430and below fluid transfer device402. Cover assembly2000may include tray assembly frame450(referring toFIG. 16), a cover frame2001(referring toFIGS. 16 and 17), a first cover2002, and a second cover2004. First cover2002and second cover2004each may be supported by tray assembly frame450and cover frame2001. Cover frame2001may be configured to limit the vertical movement of one or more trays460held by tray holders444. First cover2002and second cover2004may be composed of any suitable material, such as, e.g., injection molded plastic, although other materials, including metals or metal alloys may be used. First cover2002and second cover2004, in some examples, may be composed of absorbent materials on one or more surfaces, including a top surface, to capture any fluid that may leak or drip from fluid transfer device402. In one embodiment, first cover2002and second cover2004are made from polyoxymethylene (POM), which may have good sliding properties (e.g., low friction) and high wear resistance.

In various embodiments, cover assembly2000may extend along a longitudinal axis2300, and a lateral axis2302that is substantially perpendicular to longitudinal axis2300. In some examples, cover assembly2000may be fixed relative to longitudinal axis2300and movable along lateral axis2302. The dimensions of first cover2002, second cover2004, and their respective openings may depend on the size of trays, columns, and wells disposed beneath cover assembly2000. More particularly, first cover2002may extend in a first plane, and second cover2004may extend in a second plane that is different and parallel to the first plane. The first plane and the second plane each may include a longitudinal axis that is parallel to longitudinal axis2300, and a lateral axis that is parallel to lateral axis2302. First cover2002may move along its respective lateral axis, but not along its respective longitudinal axis (i.e., first cover2002may be fixed relative to its respective longitudinal axis). Similarly, second cover2004may move along its respective lateral axis, but not along its respective longitudinal axis (i.e., second cover2004may be fixed relative to its respective longitudinal axis). It should also be noted that the terms “longitudinal” and “lateral” used with respect to cover assembly2000do not imply any particular orientation of cover assembly2000within a larger system, such as, e.g., second module400.

In some examples, first cover2002and second cover2004may be substantially identical to one another. That is, first cover2002and second cover2004may have substantially the same dimensions, and the locations and dimensions of openings defined by first cover2002and second cover2004may be substantially the same. In other examples, first cover2002and second cover2004may have certain differing features. When first cover2002and second cover2004are substantially identical to one another, when assembled into cover assembly2000, first cover2002and second cover2004may be overlaid mirror images of each other. That is, before being assembled into cover assembly2000, second cover2004is rotated 180 degrees about lateral axis2302such that second cover2004is a mirror image of first cover2002. Then, second cover2004may be overlaid above first cover2002. First cover2002and second cover2004each may include a plurality of openings. Each of the openings may be completely defined and surrounded by material of the respective cover in which it is located. In other examples, a portion of one or more of the openings may include a slot or groove disposed in/recessed from an end surface of first cover2002or second cover2004. In various embodiments, it is contemplated that the slot and groove may be sized and shaped differently to accommodate a variety of cap, vial or receptacle holder configurations, e.g., a tray, microtiter well plate, etc. Additionally, each opening in first cover2002may have a corresponding opening in second cover2004so that a total number of openings in first cover2002is equal to a total number of openings in second cover2004.

First cover2002may include a first lateral end surface2002g, a second lateral end surface2002h, and an end tab2002i. End tab2002imay extend away from first lateral end surface2002gin a direction opposite of second lateral end surface2002h, and may include a slot2002s. Second cover2004may include a first lateral end surface2004g, a second lateral end surface2004h, an end tab2004i, and a slot2004sthat are arranged in a substantially similar manner as set forth above with respect to first cover2002. End tabs2002iand2004imay be offset from a centerline along lateral axis2302to allow for the connection of end tabs2002iand2004ito first motor2006and second motor2008, respectively. In some embodiments, first cover2002also may include a first lateral slot2002jand a first lateral slot2002k. First lateral slot2002jmay extend lengthwise along the lateral axis of first cover2002, and may be positioned adjacent to lateral edge2002h. First lateral slot2002kmay extend lengthwise along the lateral axis of first cover2002, and may be positioned adjacent to lateral edge2002g. Second cover2004may include a second lateral slot2004jand a second lateral slot2004kthat are adjacent to lateral edge2004hand lateral edge2004g, respectively. InFIG. 16, the dashed lines represent a portion of second lateral slot2004jhidden from view by top cover2002. Second lateral slot2004jand second lateral slot2004kmay be substantially similar, in terms of dimension and orientation relative to adjacent lateral edges, to first lateral slot2002jand first lateral slot2002k. First slot2002jmay be coextensive with second slot2004j, and first slot2002kmay be coextensive with second slot2004k.

In some examples, first cover2002may have a first column2002aand a second column2002bof openings2002o. First column2002aand second column2002bare arranged in the direction of lateral axis2302. Openings2002omay be any suitable shape including, e.g., rectangular, rounded rectangular, oval, stadium, or the like, Additionally, first cover2002may include additional columns of openings2002oto provide access to additional trays460positioned beneath cover assembly2000. For example, as shown inFIGS. 1 and 2, trays460are arranged in a two-by-two grid in second module400. However, if instead of a two-by-two grid, trays460were arranged in a three-by-three grid, first cover2002may include three columns of openings2002oinstead of two columns. Each opening2002oin first column2002amay be longitudinally spaced (along longitudinal axis2300) from an opening2002oin second column2002b. Laterally adjacent openings2002oin the same column may be spaced apart (along lateral axis2302) from one another at various intervals. Some laterally adjacent openings2002omay be spaced apart from one another at a first interval2002y, while other laterally adjacent openings2002omay be spaced apart from one another at a second interval2002zlarger than first interval2002y(e.g., to account for a gap between laterally adjacent trays460beneath cover assembly2000). Each opening2002omay be sized to expose a column of wells1106from tray460positioned underneath cover assembly2000, thereby allowing access to the column of wells1106through the opening2002o. The size of openings2002oand the spacing between adjacent openings may be dictated by the size and spacing of wells1106beneath cover assembly2000. Additionally, in some examples, first cover2002and/or second cover2004may include a single column of openings that provides access to wells in multiple trays.

First cover2002may be 296 mm long along longitudinal axis2300, and 207 mm long along lateral axis2302between edges2002gand2002h. End tab2002imay be 53 mm long in the direction of lateral axis2302and 50 mm long in the direction of longitudinal axis2300. Openings2002omay be about 5 mm to about 15 mm wide, at least about 10 mm wide, about 12.5 mm wide, or another suitable width, and at least about 100 mm long, about 50 mm to about 150 mm long, or at least about 124 mm long. The length of each opening2002omay be about 5 to about 15 times the width of each opening2002o, or about 10 times the width of each opening2002o. In one embodiment, a straight portion of each opening2002omay be about 124.75 mm long (not including the radiused on each end of the opening) and the overall end-to-end length of an opening2002omay be about 137.35 mm. The distance between the centers of laterally adjacent openings may be about 31.5 mm. The distance between centers of adjacent rows may be about 10 mm, from about 5 mm to about 15 mm, or about 10.5 mm. These dimensions are merely illustrative, and any other suitable dimensions may also be used.

Second cover2004may include a first column2004aand a second column2004bof openings2004o. Openings2004omay be substantially similar to openings2002oof first cover2002. Additionally the arrangement of, number of columns of, and spacings between openings2004omay be substantially similar in second cover2004as the arrangement of, number of columns of, and spacings between openings2002oin first cover2002.

First cover2002and second cover2004may be disposed in parallel planes and may be slidable relative to one another (e.g., configured for sliding engagement so that first cover2002and second cover2004contact one another), along lateral axis2302, by one or more actuators. In one example, the one or more actuators may include a first motor2006, coupled to first cover2002, and a second motor2008, coupled to second cover2004. First motor2006and second motor2008may be any suitable motor, e.g., a servomotor or stepper motor, configured to independently move first cover2002and second cover2004linearly along lateral axis2302. First motor2006may include a pin2006a, which is received by slot2002sof first cover2002. The rotation of pin2006amay cause linear movement of first cover2002. Second motor2008may include a pin2008a, which is received by slot2004sof second cover2004, and which may work in a substantially similar manner as set forth above with respect to first motor2006. First motor2006and second motor2008may be coupled to tray assembly frame450(referring toFIG. 16).

First motor2006and second motor2008each may include rotary encoders for controlling and monitoring the position of first cover2002and second cover2004. First cover2002and second cover2004each may have home sensors (or limit switches) for indicating when first cover2002and second cover2004are in one or more designated positions, such as the positions shown inFIGS. 11-14. Such sensors for indicating these positions may include optical sensors (e.g., slotted optical sensors), proximity sensors, magnetic sensors, capacitive sensors, etc.

Referring toFIG. 17, cover frame2001may be mounted to a top surface of tray assembly frame450, and may itself include a top surface2001a. Cover frame2001also may include openings2001bthrough which fluid transfer device402may access one or more receptacles. Openings2001bmay be arranged in the same manner in which trays460are arranged in second module400. That is, when trays460are arranged in a two-by-two grid, openings2001balso may be arranged in a two-by-two grid. Each opening2001bmay have dimensions suitable to enable fluid transfer device402to access wells positioned below cover frame2001. For example, each opening2001bmay have length and width dimensions that are equal to or greater than the length and width of each tray460. Alternatively, each opening2001bmay have a length and/or width that is less than the length and/or width of each tray460, so long as each well contained by a tray460is still accessible through opening2001b. However, if instead of a two-by-two grid, trays460were arranged in a three-by-three grid, openings2001bmay be arranged in a three-by-three grid.

Cover frame2001also may include one or more (e.g., at least two) guide rails2001cthat extend upward and away from top surface2001a. Guide rails2001cmay be positioned along longitudinal edges of cover frame2001, and may restrict and/or prevent the movement of first cover2002and second cover2004in the longitudinal direction. Guide rails2001calso may include an inwardly extending tab2001dthat are configured to limit vertical movement of first cover2002and second cover2004(in a direction perpendicular the first and second planes of first cover2002and second cover2004). Top surface2001aand guide rail2001cmay serve as guides for the lateral movement of first cover2002and second cover2004. In the examples shown, first cover2002is positioned beneath second cover2004, such that first cover2002slides against top surface2001a. Second cover2004may slide against tabs2001d, and both first cover2002and second cover2004may slide against inwardly facing surfaces of guide rails2001c. The interaction of first cover2002and second cover2004with top surface2001aand guide rails2001c(including tabs2001d) help ensure that first cover2002and second cover2004move only in lateral directions (and not in longitudinal or in vertical up/down directions).

In an alternative embodiment, a single motor may be coupled to both first cover2002and second cover2004. For this implementation, cover assembly2000is open when the two covers are aligned, and closed when the two covers are out-of-phase with each other. In addition, the open arrangement must be positioned above the vial of interest (in this case, one of 3 positions). It is conceivable that one cover could be driven by a motor. The second cover would be able to slide independently. However, the second cover would be attached to springs that constantly push the free cover against a hard stop on the driven cover, thus aligning the two covers in the open position. A secondary hard stop would be located on the chassis frame such that if the motor-driven cover were moved to its full end-of-travel, the fixed hard stop would engage the free cover preventing the free cover from moving full travel and the springs would allow the free cover to remain fixed in position while the driven cover continues moving the final distance (thus creating the misaligned closed position.

Cover assembly2000may be movable between one or more closed configurations (a fully closed configuration is shown inFIG. 11), and one or more open configurations, several examples of which are shown inFIGS. 12-14. In the fully closed configuration, at least one of first cover2002and second cover2004extends over each of the plurality of wells1106disposed underneath cover assembly2000to block or impede access to the plurality of wells. Thus, in the closed configuration, first cover2002and second cover2004may be laterally offset along lateral axis2302such that some openings of first cover2002are blocked by second cover2004, and some openings of second cover2004are blocked by first cover2002. In other words, in the closed configuration, tray holders444are inaccessible from any position directly above first cover2002and second cover2004. When first cover2002and second cover2004are identically constructed, first lateral edges2002gand2004gmay be distanced from one another along lateral axis2302, and second lateral edges2002hand2004hmay be distanced from one another along lateral axis2302. In exemplary closed configuration arrangements, substance transfer pipettor410cannot access, and is unable to establish fluid communication with, any well1106when cover assembly2000is in the closed configuration. In other contemplated embodiments that do not feature a tray, the first cover2002and second cover2004are arranged to block or impede access by any fluid transfer device, or the like, to the microtiter well, receptacle, etc.

In various embodiments, to transition from the fully closed configuration to one or more of the open configurations, one or both of first cover2002and second cover2004may be moved laterally along lateral axis2302such that openings2002oof first cover2002align with openings2004oof second cover2004, such that the aligned openings are situated over a column of wells1106. In some of the open configurations, first lateral edges2002gand2004gmay be aligned at the same position along lateral axis2302, and second lateral edges2002hand2004halso may be aligned at the same position along lateral axis2302. In the open configurations, a substantial entirety of first cover2002may be covered by second cover2004, except for end tab2002iof first cover2002. That is, when viewed from a perspective above cover assembly2000, end tab2002imay be the only visible material of first cover2002.

In various open configurations shown byFIGS. 12-14, a portion of at least one tray holder444and at least one of the plurality of wells1106are accessible through aligned openings of first cover2002and second cover2004by substance transfer pipettor410. For example, as shown inFIGS. 12-14, each opening2002oof first cover2002is aligned with an opening2004oof second cover2004. In the open configurations, a given pair of aligned openings2002oand2004omay be positioned over one or more wells, including, e.g., a column1106cof wells1106. Any well1106from the exposed column1106cmay be accessed through aligned openings2002oand2004o. In one example, a given pair of aligned openings2002oand2004ois positioned over only one column1106c. However, in other examples, a given pair of aligned openings may be positioned over multiple columns of wells depending on the size and spacings of the openings and wells. As shown in each ofFIGS. 12-14, multiple columns of a given tray460are accessible to substance transfer pipettor410while cover assembly2000is in a given open configuration. For example, as shown inFIG. 12, the first, fourth, and seventh columns of a tray460amay be accessed in the first open configuration, while the first, fourth, seventh and eighth columns of a tray460bmay be accessed. The numbering of the columns of trays460aand460bis based on the orientation of the columns relative to a lateral vector2012(shown inFIGS. 12-14), with the first column of a given tray being encountered before the second column of a given tray along vector2012, the second column being encountered before the third column, and so forth. Columns of tray460aare marked1a-8a, and columns of tray460bare marked1b-8b, inFIGS. 12-14.

In the second open configuration shown inFIG. 13, the second, fifth, and eighth columns of tray460amay be accessed, while the second, fifth, and eighth columns of tray460bmay be accessed. In the third open configuration shown inFIG. 14, the third and sixth columns of both trays460aand460bmay be accessed.

To move from the first open configuration shown inFIG. 12to the second open configuration shown inFIG. 13, at least one of first cover2002and second cover2004may be moved along lateral axis2302. In one example, both first cover2002and second cover2004may be moved by a same distance in a same direction along lateral axis2302. This lateral movement of both first cover2002and second cover2004allows for different columns of wells1106to be accessible to substance transfer pipettor410than are accessible to substance transfer pipettor410in the first open configuration. To move from the first open configuration to the second open configuration, first cover2002and second cover2004may be moved along lateral axis2302by a distance that is substantially equal to a distance between the centers of adjacent columns of wells1106. To move from the second open configuration to the third open configuration shown inFIG. 14, first cover2002and second cover2004may be moved along lateral axis2302in the same direction by the same distance as previously discussed.

First cover2002and second cover2004also may include additional closed configurations other than the fully closed configuration shown inFIG. 11. For example, instead of reverting to the closed configuration ofFIG. 11after each open configuration, first cover2002and second cover2004may be moved relative to one another to achieve different, intermediate closed configurations. For example, to move from any of the open configurations shown inFIGS. 12-14to an intermediate closed configuration, first cover2002may be kept stationary while second cover2004is moved linearly along lateral axis2302by a distance, or second cover2004may be kept stationary while first cover2002is moved linearly along lateral axis2302by the same distance. Keeping one of the first cover2002and second cover2004stationary allows each opening of first cover2002and second cover2004to be blocked without having to move both first cover2002and second cover2004to the positions shown inFIG. 11. This may result in reduced procedural times because, depending on the anticipated path of substance transfer pipettor410, first cover2002and second cover2004may be moved over a shorter distance while still covering wells1106underneath the travelling path of substance transfer pipettor410. The material of first cover2002and second cover2004that surround the openings of the covers may constitute a “flight path” of substance transfer pipettor410in some embodiments. That is, a path over which substance transfer pipettor410moves to limit contamination (e.g., droplets falling into the wrong vials).

Method of Use

A method1500is shown inFIG. 15. Method1500may start at step1502, where, while first cover2002and second cover2004are in a closed configuration, substance transfer pipettor410may be moved over one or more wells1106, until substance transfer pipettor410is positioned over a target well1106of the one or more wells1106. Because first cover2002and second cover2004are in a closed configuration, any fluids and/or other any substances that drip from substance transfer pipettor410may be caught by first cover2002and/or second cover2004, instead of dripping into wells1106.

Method1500then may proceed to step1504, where, first cover2002and second cover2004may be transitioned from a closed configuration to a first open configuration (e.g., one of the configurations shown inFIGS. 12-14), where the target well is accessible to substance transfer pipettor410. In the first open configuration, an opening2002oof first cover2002may be aligned with an opening2004oof second cover2004to provide access to the target well through the aligned openings. In certain open configurations of first cover2002and second cover2004, each receptacle of a given row of receptacles underneath first cover2002and second cover2004may be accessible to substance transfer pipettor140. Method1500then may proceed to step1506, where substance transfer pipettor410is inserted into the target well through the pair of aligned openings2002oand2004o. Then, method1500may proceed to step1508, where a liquid may be aspirated from the target well via substance transfer pipettor410, or a liquid may be dispensed from substance transfer pipettor410into the target well. For example, one or more of reagent, oil, and/or sample mixture may be dispensed by fluid transfer device402into a vial464positioned in the target well. For example, the reagent may be reconstituted reagent from a mixing well of a PCR reagent pack. The reagent may provide the ingredients necessary for performing PCR in a premixed and optimized format, such as, e.g., Taq DNA polymerase, deoxynucleoside triphosphates (dNTPs), and magnesium chloride (MgCl2). The sample mixture may include nucleic acid material to be amplified.

Once liquid has been dispensed or aspirated at step1508, method1500may proceed to step1510, where substance transfer pipettor410is removed from the target well, and to step1512, where, first cover2002and second cover2004are moved from the first open configuration to a closed configuration, such as, e.g., the fully closed configuration shown inFIG. 11, or one of the additional closed configurations described above. At step1514, with first cover2002and second cover2004in a closed configuration, substance transfer pipettor410may be moved along a path that extends over at least a subset of wells other than the target well. Thus, in some examples, substance transfer pipettor410may not travel over any wells1106unless one or both of first cover2002and second cover2004is disposed between substance transfer pipettor410and the wells1106.

The steps depicted inFIG. 15are not intended to limit the embodiments described herein to sequential steps. For example, some of the steps of method1500may occur simultaneously or overlap in time to some extent, if, for example, additional throughput is desired. For example, substance transfer pipettor410may be moved while one or both of first cover2002and/or second cover2004are moved. While this overlapping of steps may increase a chance of contamination by inadvertent dripping of sample or reagent into an exposed well1106, such an overlapping of steps may produce a benefit of improved workflow times and processes that is desirable in certain embodiments. Moreover, in some embodiments, the location of the target well in relation to the travel path of the substance transfer pipettor410may allow for the overlapping of one or more steps without subjecting any open wells1106to the risk of contamination. It can be appreciated then that an improved workflow may be achieved by the overlapping of steps, at various coordinated times, without the risk, or increased risk, of contamination.

In various embodiments, the movement of substance transfer pipettor410at steps1502and1514can be simultaneous along multiple axes. That is, substance transfer pipettor410may move simultaneously in X and Y directions (and in some cases, also in the Z direction). The ability to move simultaneously along multiple axes may allow substance transfer pipettor410to take shorter and more direct paths between different locations during a procedure, reducing overall procedure time. Because of the presence of cover assembly2000, the path of substance transfer pipettor410may travel directly over one or more wells1106positioned below substance transfer pipettor410, increasing path efficiency while reducing the risk of contaminating wells below the path of substance transfer pipettor410. Additionally, the reduced procedure time may increase throughput of diagnostic system10.

Likewise, intermediate closed configurations may be used in order to optimize procedure timing. For example, instead of returning to the fully closed configuration shown inFIG. 12after transitioning to each open configuration, which would require both first cover2002and second cover2004to move back to the positions shown inFIG. 11(regardless of where they were presently located), one of first cover2002and second cover2004can be kept stationary, while the other of first cover2002and second cover2004is moved. These alternative closed configurations may not cover each well underneath cover assembly2000, but could cover all wells underneath an anticipated path of substance transfer pipettor410. In other instances, an alternative closed configuration may cover all wells directly underneath an anticipated path, and additionally a subset of surrounding wells that may be at risk of contamination due to splashing of liquid. In some examples, therefore, the closed configuration selected during operation may depend on the path of substance transfer pipettor410.

In some examples, a controller may coordinate a travel path of substance transfer pipettor410, and the movement of cover assembly2000between open and closed configurations based on input from positioning sensors coupled to both substance transfer pipettor410and cover assembly2000. The controller may receive instructions regarding a procedure to be performed. Based on the received instructions, which may include a various locations for substance transfer pipettor410to travel to during the procedure, the controller may determine, in real-time, an optimal travel path of substance transfer pipettor410and an optimal sequence for opening and closing cover assembly2000. The optimal travel path and optimal sequence may be determined based on, e.g., the current and anticipated positions of substance transfer pipettor410and cover assembly2000. In some examples, the travel path of substance transfer pipettor410and the sequence for opening and closing cover assembly2000may be preset for certain procedures.

Each of the U.S. Patent Applications, U.S. Patent Application Publications and U.S. Patents referred to in the specification is incorporated herein by reference in its entirety.

It will be apparent to those skilled in the art that various modifications and variations may be made in the disclosed systems and processes without departing from the scope of the disclosure. Other examples of the disclosure will be apparent to those skilled in the art from consideration of the specification and practice of the disclosure disclosed herein. It is intended that the specification and examples be considered as exemplary only.