Patent Description:
Embodiments disclosed herein relate in general to systems and methods for aligning containers and, more particularly, to systems and methods for aligning wedge containers and anti-evaporation tubes within the wedge containers in a server ring for in vitro diagnostics in a clinical analyzer.

In vitro diagnostics (IVD) allows labs to assist in the diagnosis of disease based on assays performed on patient fluid samples. IVD includes various types of analytical tests and assays typically conducted with automated clinical chemistry analyzers (analyzers) onto which fluid containers, such as tubes or vials containing patient samples, have been loaded. The analyzer extracts a fluid sample from the vial and combines the sample with various reagent fluids (reagents) in special reaction cuvettes or tubes (referred to generally as reaction vessels).

In some conventional systems, reagent inventory on analyzers is provided using wedge-shaped reagent containers (containers) arrayed in storage areas, such as a circular server assembly (server). The containers are held in slots within the circular server. The wedge-shape allows for an efficient utilization of reagent storage volume so that the maximum number of containers can be stored on board the analyzer and the maximum test menu may be available to the user. Reagents are typically packaged in different wedge-shaped containers such as low volume, mid-volume, and high volume depending on reagent stability and method use rate. The reagent containers typically have threaded necks for closure and are opened by removing a threaded closure and loaded into the servers manually. New containers are opened and manually loaded as analyzer.

A wedge-shaped container for dispensing and preserving chemical or biochemical reagents for use in an automated analyzer is disclosed in <CIT>. It comprises several compartments, each one having an opening, and a sealing lid common for all compartment openings. The containers are supported on a common carousel, such that a large number of reagents is made available. <CIT> teaches cartridge for use in an automated clinical chemistry analyzer. The cartridge comprises a molded body which defines a plurality of storage compartments having different volumes. <CIT>, <CIT> and <CIT> relate to various types of a vial insert comprising a tube which extends down into a reagent container. The vial insert reduces evaporation of a liquid reagent stored in the container. <CIT> teaches a reagent container which comprises a container body having a plurality of open holding sections, each one holding a reagent. The reagent container further comprises a lid which has a plurality of hollow piercing sections for piercing the seal member of each of the openings. A pierceable cap for a reagent container is disclosed in <CIT>.

The present invention is defined by the multi-well fluid container according to claim <NUM> and the method of operating an in vitro diagnostics automation system according to claim <NUM>.

In one embodiment, the container body is wedge-shaped and is further configured to be held in one of a plurality of substantially same sized wedged shaped compartments of a circular storage area.

In another embodiment, the first well opening is configured to provide access to the low volume of the first fluid when the openable first well closure is opened. The second well opening is further configured to provide access to the high volume of the second fluid when the openable second well closure is opened.

In an aspect of an embodiment, the multi-well fluid container further includes a third well configured to hold a mid-volume of a third fluid that is a larger volume than the low volume of the first fluid and a smaller volume than the high volume of the second fluid.

According to one embodiment, the multi-well fluid container further includes a third well adjacent to at least one of the first well and the second well. The third well has a third well size configured to hold a third fluid and an openable third well closure that covers a third well opening that is separate from the first well opening and the second well opening,. The third well opening is configured to provide access to the third fluid in the third well when the openable third well closure is opened.

According to the invention, the first well and the second well each include an anti-evaporation tube.

Embodiments provide an in vitro diagnostics automation system that includes a plurality of multi-well fluid containers each having substantially the same length and width and each of the plurality of multi-well fluid containers comprising a plurality of wells configured to hold a corresponding fluid. Each well has an openable closure that covers a corresponding opening configured to provide access to the corresponding fluid when the openable closure is opened. The system also includes a storage area having a plurality of compartments. Each of the plurality of compartments is configured to hold one of the plurality of multi-well fluid containers and having substantially the same length and width as the length and width of the plurality of multi-well fluid containers.

According to one embodiment, each openable closure is configured to be automatically opened while on board an analyzer.

According to another embodiment, each of the plurality of multi-well fluid containers has at least two different sized wells.

In one embodiment, the storage area is a circular storage area and each of the plurality of compartments in the circular storage area is wedged shaped and each of the plurality of multi-well fluid containers is wedge-shaped.

In another embodiment, the at least two different sized wells in each compartment are configured to hold different volumes of one or more fluids.

Embodiments provide a method of operating an in vitro diagnostics automation system. The method includes holding a multi-well fluid container having a plurality of different sized wells in one of a plurality of compartments of a storage area. Each well of the plurality of different sized wells has an openable closure covering a corresponding opening. The method also includes accessing a low volume of a first fluid from a first well of the plurality of different sized wells and accessing a high volume of a second fluid from a second well of the plurality of different sized wells. The high volume of the second fluid is a larger volume than the low volume of the first fluid. The method further includes opening the multi-well fluid container from the one of a plurality of compartments of the storage area.

According to one embodiment, the further includes opening an openable first closure from a first well of the plurality of different sized wells to provide access to the first fluid from the first well and opening an openable second closure from a second well of the plurality of different sized wells to provide access to the second fluid from the second well.

According to another embodiment, opening the openable first closure further includes automatically opening the openable first closure while on board an analyzer and opening the openable second closure further includes automatically opening the openable second closure while on board the analyzer.

In one embodiment, opening the multi-well fluid container from the one of the plurality of compartments of the storage area occurs after at least a portion of the low volume of the first fluid is accessed from the first well and at least a portion of the high volume of the second fluid is accessed from the second well.

In another embodiment, the method further includes accessing a mid-volume of a third fluid from a third well of the plurality of different sized wells. The mid-volume of the third fluid is larger than the low volume of the first fluid and smaller than the high volume of the second fluid.

In an aspect of an embodiment, opening the fluid container from the one of the plurality of compartments of the storage area occurs after at least a portion of the low volume of the first fluid is accessed from the first well. At least a portion of the high volume of the second fluid is accessed from the second well and at least a portion of the mid-volume of the third fluid is accessed from the third well.

In yet another embodiment, the method further includes opening a first sealing portion of the openable first closure using a first cannula to provide access to the low volume of the first fluid of the first well and opening a second sealing portion of the openable second closure using a second cannula to provide access to the high volume of the second fluid of the second well.

The foregoing and other aspects of the embodiments disclosed herein are best understood from the following detailed description when read in connection with the accompanying drawings. For the purpose of illustrating the invention, there are shown in the drawings embodiments that are presently preferred, it being understood, however, that the embodiments disclosed herein are not limited to the specific instrumentalities disclosed. Included in the drawings are the following Figures:.

Testing may include a number of different reagent methods. During each of these methods, one or more reagents may be used. Further, different volumes of reagents may be needed for different reagent methods, causing some reagents to be used more than other reagents. Some conventional systems use same sized single-welled containers, each holding specific reagents, which are placed in equally sized compartments of a circular server. Some reagents may, however, have different expiration rates and different levels of open well stability. Therefore, in these conventional systems, some of the lesser used reagents having shorter expiration rates and/or lower levels of open well stability may become unusable reagents after the single-welled containers are opened.

Some conventional systems use different sized bottles to hold the different volumes of reagents. The larger bottles are sized substantially the same as the equally sized compartments of the circular server. The smaller sized containers, however, are smaller than the equally sized compartments of the circular server and may include buffers (e.g., portions of the container that do not hold reagents) to fill in the unused space of the equally sized compartments and limit movement of the containers in the equally sized compartments. Because these smaller sized bottles include portions that are not used to hold reagents, the storage capacity is not maximized.

To address these shortcomings described above as well as others, embodiments described herein provide a multi-well fluid container that can accommodate different volume methods (e.g., low-volume, mid-volume, and high-volume methods) that make efficient use of the server storage capacity. In some embodiments, the multi-well container may be opened while in the reagent server so that individual wells can be accessed without affecting the stability of the un-opened wells. After a first well of a container is consumed, a second well may be opened and accessed.

Embodiments improve storage inefficiency and load frequency with multi-well containers that may be automatically loaded and opened in reagent servers. Embodiments disclosed herein provide a multi-well container that improves reliability by reducing the reagent loading and overall unloading frequency. Some embodiments reduce the cost of low and mid-volume containers because, for example, each of the multi-well low and mid-volume containers may be the equivalent of two single-well low and mid-volume containers at the about the same cost per container. Another cost benefit may result from using only one barcode label which can be a significant portion of the overall manufacturing cost.

Embodiments may include any number of wells, each having the same or different sizes. In some embodiments, multi-well containers may include reagents used for three or more reagent methods. In some embodiments, multi-well containers may include two or more wells, such as three wells, four wells or more.

In some embodiments, multi-well fluid containers may be used in an automation system, such as, for example, an in vitro diagnostics automation system described in <CIT>. Embodiments may, however, include multi-well containers used in other types of environments.

In some embodiments, the automation system may include a storage area (e.g., server ring <NUM> shown in <FIG>) for holding the multi-well wedge shaped fluid containers. The containers may be configured to be placed into one of a plurality of equally sized wedge-shaped compartments of the storage area with each compartment being configured to receive and hold a multi-well wedge shaped fluid container. The multi-well containers may be configured to hold one or more reagent fluids in the IVD automation system. The multi-well containers may be configured to hold other types of fluids (e.g., samples).

In one embodiment, multi-well wedge containers may be used in an automatic clinical chemistry analyzer (analyzer), such as analyzer <NUM> shown in <FIG>, taken with <FIG>, shows schematically the elements of the analyzer <NUM>, which may include, for example, the analyzer described in <CIT>. Analyzer <NUM> comprises a reaction carousel <NUM> supporting an outer carousel <NUM> having cuvette ports <NUM> (represented in <FIG>) formed therein and an inner carousel <NUM> having vessel ports <NUM> (represented in <FIG>) formed therein, the outer carousel <NUM> and inner carousel <NUM> being separated by an open groove <NUM>. Cuvette ports <NUM> are adapted to receive a plurality of reaction cuvettes <NUM>, as represented in <FIG>, that contain various reagents and sample liquids for conventional clinical chemistry and immunoassay assays. Vessel ports <NUM> can be adapted to receive a plurality of reaction vessels <NUM>, as represented in <FIG>, that contain specialized reagents for ultra-high sensitivity luminescent immunoassays. Cuvettes <NUM> and reaction vessels <NUM> can include bottom portions. While cuvettes and reaction vessels can have differing shapes, as used herein, the methods for mixing can be applied to the contents of reaction vessels <NUM> or cuvettes <NUM>, and the terms reaction vessels and cuvettes should be considered broadly and interchangeably. Reaction vessels can include, for instance, cuvettes, vials, tubes, or other suitable vessels for mixing reagents and solutions.

Reaction carousel <NUM> is rotatable using stepwise movements in a constant direction, the stepwise movements being separated by a constant dwell time during which reaction carousel <NUM> remains stationary and computer controlled assay operational devices <NUM>, such as sensors, reagent add stations, mixing stations, and the like, operate as needed on an assay mixture contained within a cuvette <NUM>.

Analyzer <NUM> is controlled by software executed by a computer <NUM> based on computer programs written in a machine language like that used on the Dimension® clinical chemistry analyzer sold by Siemens Healthcare Diagnostics Inc. of Deerfield, IL, and widely used by those skilled in the art of computer-based electromechanical control programming. Computer <NUM> also executes application software programs, such as the Dimension Vista® system software for performing assays conducted by various analyzing means <NUM> (e.g., detection units) within analyzer <NUM>. Analyzing means <NUM> can include, for instance, one or more photometers, turbidimeters, nephelometers, electrodes, electromagnets, and/or LOCI® readers for interpreting the results of reactions within the reaction vessels <NUM> or cuvettes <NUM>.

As seen in <FIG>, a bi-directional incoming and outgoing sample fluid tube transport system <NUM> comprises a mechanism for transporting sample fluid tube racks <NUM> containing open sample fluid containers such as sample fluid tubes <NUM> from a rack input load position at a first end of the input lane <NUM> to the second end of input lane <NUM> as indicated by open arrow 35A. Liquid specimens contained in sample tubes <NUM> may be identified by reading bar coded indicia placed thereon using a conventional bar code reader to determine, among other items, a patient's identity, tests to be performed, if a sample aliquot is to be retained within analyzer <NUM>, and, if so, for what period of time. It is also common practice to place bar coded or other indicia on sample tube racks <NUM> and employ a large number of bar code readers or other readers installed throughout analyzer <NUM> to ascertain, control, and track the location of sample tubes <NUM> and sample tube racks <NUM>.

A conventional liquid sampling probe <NUM> is located proximate to the second end of the input lane <NUM> and is operable to aspirate aliquot portions of sample fluid from sample fluid tubes <NUM> and to dispense an aliquot portion of the sample fluid into one or more of a plurality of vessels in aliquot vessel array <NUM>. This provides a quantity of sample fluid to facilitate assays and to provide for a sample fluid aliquot to be retained by analyzer <NUM> within an environmental chamber <NUM>. After sample fluid is aspirated from all sample fluid tubes <NUM> on a rack <NUM> and dispensed into aliquot vessels in array <NUM> and maintained in an aliquot vessel array storage and transport system <NUM>, rack <NUM> may be moved, as indicated by open arrow 36A, to a front area of analyzer <NUM> accessible to an operator so that racks <NUM> may be unloaded from analyzer <NUM>.

Sample aspiration probe <NUM> is controlled by computer <NUM> and is adapted to aspirate a controlled amount of sample from individual aliquot vessels in array <NUM> positioned at a sampling location within a track (not shown) and is then shuttled to a dispensing location where an appropriate amount of aspirated sample is dispensed into one or more cuvettes <NUM> for testing by analyzer <NUM> for one or more analytes. After sample has been dispensed into reaction cuvettes <NUM>, conventional transfer means move aliquot vessel arrays <NUM>, as required, within aliquot vessel array storage and dispensing module <NUM> between aliquot vessel array storage and transport system <NUM>, environmental chamber <NUM>, and a disposal area (not shown).

Temperature-controlled storage areas or servers <NUM>, <NUM>, and <NUM> contain an inventory of multi-compartment elongated reagent cartridges <NUM> (shown in <FIG>) loaded into the system via input tray <NUM>, such as those described in <CIT> assigned to the assignee of the present invention. Cartridges <NUM> contain reagents in wells <NUM> to perform a number of different assays. Reagents may be moved and aligned within analyzer <NUM> by any conventional means, including those described in <CIT>, also assigned to the assignee of the present invention. Computer <NUM> can control and track the motion and placement of the reagent cartridges <NUM>. Reagents from server <NUM>, <NUM>, and <NUM> can be handled by one or more reagent probe arms <NUM>, <NUM>, and <NUM>.

<FIG> is a perspective view of an exemplary server ring <NUM> having a plurality of compartments <NUM> holding a multi-well fluid container <NUM>. For simplicity, only one container <NUM> is shown in <FIG>. In some embodiments, server ring <NUM> may hold any number of containers <NUM>. In some embodiments, container <NUM> may be used to hold reagent fluids. In other embodiments, container <NUM> may be used to hold other fluids, such as patient samples. As shown in <FIG>, the compartments <NUM> of a server ring <NUM> may be wedge-shaped and the container <NUM> may be wedge-shaped to fit securely within a corresponding compartment <NUM>. Server ring <NUM> may be positioned at a center of a reaction carousel, such as at the center of the reaction carousel <NUM> shown in <FIG>. In some embodiments, reagent server rings may be located on outer portions of carousels and the samples and/or cuvettes may be located on the inner portions of carousels. The server ring <NUM> shown in the embodiment in <FIG> includes an inner loop <NUM> and an outer loop <NUM>. Embodiments may include any number of loops.

In some embodiments, a compartment <NUM> may be configured to limit movement of containers <NUM> during operation. For example, as shown in <FIG>, a compartment <NUM> may be shaped substantially the same as each container <NUM>. In some aspects, multi-well wedge containers <NUM> may each have the same outer surface geometries and configured to be placed into wedge-shaped compartments <NUM> of the server ring <NUM>.

<FIG> is an exploded view of the multi-well fluid container <NUM> shown in <FIG>. <FIG> is a side view of the multi-well fluid container <NUM> shown in <FIG>. <FIG> is a top view of the multi-well fluid container shown in <FIG>. <FIG> is a perspective view of the multi-well fluid container shown in <FIG>. <FIG> is a rear view illustrating the rear of the second well of the multi-well fluid container shown in <FIG>. <FIG> is a left side view illustrating of the multi-well fluid container shown in <FIG>.

As used herein, openable closures may be: (i) removable closures (e.g., threaded closures <NUM> removed by rotating and snap fit closures, magnetic closures and friction fit closures removed by pulling) that may be manually removed by an operator; and (ii) automatically openable closures (e.g., automatically openable closures in <FIG> that may include sealing portions <NUM> and <NUM> that may be opened by cannulas <NUM> and <NUM>). As shown in <FIG>, container <NUM> may include a container body <NUM> that includes a first well <NUM> and a second well <NUM>. First well <NUM> has a first well size configured to hold a first fluid (not shown). As shown in <FIG>, first well <NUM> has a removable first well closure <NUM> that covers a first well opening <NUM> when in a closed position. The first well opening <NUM> provides access to the first fluid in the first well when the removable first well closure <NUM> is removed from the closed position. In the embodiment shown in <FIG>, first well <NUM> may also hold a first anti-evaporation tube <NUM>.

As shown in <FIG> and <FIG>, second well <NUM> is adjacent to first well <NUM> and has a second well size configured to hold a second fluid (not shown). In some embodiments, the second fluid may be the same as the first fluid. In other embodiments, the second fluid may be different from the first fluid. Second well <NUM> has a removable closure <NUM> that covers a second well opening <NUM> that is separate from the first well opening <NUM>. The second well opening <NUM> is configured to provide access to the second fluid in the second well when the removable second well closure <NUM> is removed. Second well <NUM> may also be configured to hold a second anti-evaporation tube <NUM>.

In some embodiments, the removable first well closure <NUM> and the removable second well closure <NUM> may include an induction seal film <NUM>. As described below with regard to <FIG>, embodiments may also include openable closures having openable sealing portions <NUM> and cannulas <NUM> configured to open the openable sealing portions.

In the embodiment shown in <FIG>, the first well size of the first well <NUM> is larger than the second well size of the second well <NUM>. Embodiments may, however, include wells having the same size and shape.

For simplicity purposes, the container <NUM> shown in the embodiment at <FIG> and <FIG> includes two wells. Embodiments may, however, include containers having any number of wells (e.g., three wells, four wells, etc.). In some embodiments, each of the different sized wells <NUM> and <NUM> are configured to hold different volumes of reagents. For example, the first well <NUM> may be configured (e.g., sized) to hold a low volume of the first fluid. The second well <NUM> is further configured (e.g., sized) to hold a high volume of the second fluid that is a larger volume than the low volume of the first fluid. In embodiments, where more than two wells are used, a third sized well (not shown) may be configured to hold a mid-volume of a third fluid that is larger than the low volume of the first fluid and smaller than the high volume of the second fluid.

The size and shape of the wells of the multi-well container <NUM> shown in <FIG> and <FIG> is merely exemplary. Embodiments may include multi-well containers with wells of any size and shape. In some embodiments, different wells may be used to hold different fluids. In other embodiments, different wells may be used to hold the same fluids.

As shown in <FIG>, multi-well container <NUM> may include a label <NUM> disposed on a well <NUM>. The label <NUM> may include different types of information associated with the fluid in the well <NUM>, such as the type of fluid, the amount of fluid, scheduling and other information. The label may include a bar code area, a radio frequency identification RFID area (e.g., tag, sticker and the like) or another type of electronic information disposed on the label <NUM>. The label <NUM> shown in <FIG> is disposed on first well. Embodiments may, however, include labels on any well and any number of wells of a multi-well container.

<FIG> is an exploded view of an exemplary multi-well fluid container having cap closures <NUM> and <NUM> that include openable sealing portions <NUM> and <NUM> and cannulas <NUM> and <NUM> configured to open sealing portions <NUM> and <NUM> that can be used with embodiments disclosed herein. As shown in <FIG>, removable closures <NUM> and <NUM> include corresponding sealing portions <NUM> and <NUM>. Removable closures <NUM> and <NUM> may also include corresponding cannulas <NUM> and <NUM> configured to open sealing portions <NUM> and <NUM>.

An in vitro diagnostics automation system may include one or more analyzers. As described above, multi-well wedge containers <NUM> may be used in an analyzer, such as analyzer <NUM> shown in <FIG>. An exemplary method of operating an in vitro diagnostics automation system having an analyzer, such as analyzer <NUM>, will now be described.

The exemplary method may include holding a multi-well fluid container <NUM> having first well <NUM> and second well <NUM> in one of a plurality of compartments <NUM> of a storage area, such as server ring <NUM>. A first volume (e.g., low volume) of a first fluid may be accessed from the first well <NUM>. In some embodiments, the first removable closure <NUM> shown in <FIG> may be removed from first well <NUM> to provide access to the first volume of the first fluid. In other embodiments, sealing portion <NUM> shown in <FIG> may be opened from the openable first closure <NUM> using cannula <NUM> to provide access to the first volume of the first fluid.

The removable second closure <NUM> may then be removed from second well <NUM> and a second volume (e.g., high volume being a larger volume than the low volume of the first fluid) of a second fluid may be accessed from the second well of the plurality of different sized wells. In some embodiments, the removable second closure <NUM> shown in <FIG> may be removed from second well <NUM> to provide access to the second volume of the second fluid. In other embodiments, sealing portion <NUM> shown in <FIG> may be opened from the openable second closure <NUM> using cannula <NUM> to provide access to the second volume of the second fluid. The multi-well fluid container <NUM> may then be removed from the compartment <NUM> of the server ring <NUM>.

Embodiments may include accessing fluids from wells in any order. For example, openable second closures (e.g., removable closure <NUM> and openable closure504) may be opened and the second volume of the second fluid may be accessed prior to removing openable first closures (e.g., removable closure <NUM> and openable closure <NUM>) and accessing the first volume of the first fluid.

The removable first closure <NUM> and the removable second closure <NUM> are manually removed.

In some embodiments, the method may also include accessing a mid-volume of a third fluid from a third well of containers. As described above, the mid-volume of the third fluid may be larger than the low volume of the first fluid and smaller than the high volume of the second fluid.

In some embodiments, removing the fluid container <NUM> from the compartment <NUM> occurs after at least some portions of fluids are removed from each well <NUM> and <NUM> of a container <NUM>. In other embodiment, container <NUM> may be removed from the compartment <NUM> may occur before portions of fluids are removed from each well <NUM> and <NUM> of a container <NUM>.

As described above, some reagents may have different expiration rates. Reagents used less frequently but having shorter expiration rates may be held within smaller wells of the container <NUM>. Because the volumes of these reagents are lower, lower volumes of the reagents are likely to expire, thus decreasing the amount of unusable remaining reagents.

As further described above, some reagents may have different levels of open well stability. The less frequently used reagents having low-level open well stability may also be held within the smaller un-opened wells (e.g., well <NUM>), of the container <NUM>. Because smaller volumes of the low-level open well stability reagents are stored in the smaller wells (e.g., well <NUM>), these reagents are likely to be exposed for shorter amounts of time after the wells are opened. Accordingly, the likelihood of these reagents evaporating or becoming unstable due to exposure after the smaller wells (e.g., well <NUM>) are opened decreases, and in turn, decreases the amount of unusable remaining reagents.

Claim 1:
A multi-well fluid container (<NUM>) for use in an in vitro diagnostics automation system comprising:
a container body (<NUM>) comprising:
a first well (<NUM>) having a first well size configured to hold a first fluid and having an openable first well closure (<NUM>) that covers a first well opening (<NUM>), the first well opening (<NUM>) is configured to provide access to the first fluid in the first well (<NUM>) via the first well opening (<NUM>) when the openable first well closure (<NUM>) is opened; and
a second well (<NUM>) adjacent to the first well (<NUM>), the second well (<NUM>) having a second well size configured to hold a second fluid and having an openable second well closure (<NUM>) that covers a second well opening (<NUM>) that is separate from the first well opening (<NUM>), the second well opening configured to provide access to the second fluid in the second well (<NUM>) via the second well opening (<NUM>) when the openable second well closure (<NUM>) is opened,
wherein the openable first well closure (<NUM>) comprises:
a first sealing portion (<NUM>) configured to be opened by a first cannula (<NUM>), and
the openable second well closure (<NUM>) comprises:
a second sealing portion (<NUM>) configured to be opened by a second cannula (<NUM>),
wherein the first well (<NUM>) and the second well (<NUM>) each comprise an anti-evaporation tube (<NUM>, <NUM>),
wherein the first well size of the first well (<NUM>) is different than the second well size of the second well (<NUM>),
wherein the first well is configured to hold a low volume of the first fluid and the second well is configured to hold a high volume of the second fluid that is a larger volume than the low volume of the first fluid and
wherein the first openable closure (<NUM>) and the second openable closure (<NUM>) are configured to be automatically opened while on board an analyzer.