Analytical systems and methods

Abstract

To provide optimal analytical systems and methods.SOLUTION: The present invention provides a system, a method and a computer readable medium, wherein the system, the method and the computer readable medium enable a user to specify user-defined assay parameters of an assay protocol for processing a sample and causing a computer-controlled analyzer to perform an assay in accordance with the assay protocol.SELECTED DRAWING: Figure 34A

Description

[Technical Field]

[0001] The present disclosure relates to systems, methods, and computer-readable media that allow a user to specify user-defined assay parameters for an assay protocol to be performed on an automated analyzer. [Background technology]

[0002] Molecular assays are nucleic acid-based tests used to detect the presence or quantity of an analyte of interest, such as a microorganism or virus, in a sample, or to detect genetic abnormalities or mutations in an organism, in clinical diagnostics, screening, monitoring, industrial and environmental testing, health science research, and other applications. Molecular assays enable clinicians to determine the degree of infection or monitor the effectiveness of treatment. As known to those skilled in the art, molecular assays generally involve multiple steps that result in the detection or quantification of a target nucleic acid of an organism or virus of interest in a sample. Most molecular assays include a detection step in which the sample is exposed to a detection probe or amplification primers that exhibit specificity for the target nucleic acid. To increase the sensitivity of the assay, the target nucleic acid can be amplified by a nucleic acid amplification reaction, such as the polymerase chain reaction ("PCR"), which amplifies the nucleic acid ("amplicon") by several orders of magnitude. PCR uses thermal cycling, which consists of repeated cycles of heating and cooling the reaction mixture. The reaction is generally initiated with an amplification primer (e.g., a short DNA fragment containing a sequence complementary to the target nucleic acid region) along with an enzyme and additional reaction materials. The increase in amplicon over time can be monitored in "real time" (i.e., during an ongoing amplification reaction) or at the end of the reaction (i.e., "endpoint" monitoring). The increase in amplicon can be detected using a signal detection device (e.g., a fluorescence detection device) that measures a signal emission (e.g., a level of fluorescence at a predetermined wavelength or range of wavelengths) indicative of the presence of the amplicon.

[0003] Molecular assays can generally be categorized as in vitro diagnostic ("IVD") assays and laboratory-developed assays (referred to herein as "laboratory-developed tests" or "LDTs") that are developed, validated, and used by a customer or other third party. In a world of emerging pathogens and variants, customers or other third parties may desire the development of an LDT to detect an analyte of interest for which an IVD is not commercially available, or customers or third parties may desire to incorporate analyte-specific reagents ("ASRs") into an IVD to supplement the IVD.

[0004] Molecular LDTs ​​typically require amplification oligomers, detection probes, etc. specific to the particular LDT. Known analytical systems capable of performing LDTs ​​are designed to perform IVD assays and LDTs ​​in batch mode or without using common modules or resources. When performed in batch mode, a first assay type (e.g., IVD or LDT) on a first collection of samples is completed before initiating a second assay type on a second collection of samples. Often, reagents and consumables for performing the second assay type are not introduced into the system until after the first assay type is completed.

[0005] Molecular assays, such as nucleic acid amplification assays, are performed by computer-controlled automated molecular systems according to different parameters that define the protocol for performing the assay. Generally, these parameters define the steps performed by the system during the assay (e.g., the type and amount of reagents to be used, incubation conditions, temperature cycling parameters (e.g., cycle time, temperatures including denaturation, annealing, and extension temperatures, choice of RNA or DNA target, etc.)). These parameters also define data processing, data reduction, and interpretation of results for the data generated by the protocol.

[0006] In many cases, the protocols (i.e., parameters) of IVD assays performed on molecular systems are pre-installed / pre-loaded onto the system. Because IVD assays are known, standardized (and regulated) assays, their parameters are typically known and / or fixed and cannot be changed by the user. Because LDTs ​​are developed or established by the user or a third party, a custom protocol may be required, as at least some of the parameters defining the LDT protocol are provided by the user / third party.

[0007] Therefore, there is a need to improve the flexibility of molecular systems to allow for assay protocols that are not pre-installed / pre-loaded on the system, and to facilitate user configurability in the operation of molecular systems. Summary of the Invention [Problem to be solved by the invention]

[0008] A method and system is disclosed that allows a user to define an LDT by selecting user-defined assay parameters associated with the assay. [Means for solving the problem]

[0009] The software tool can generate assay protocols for molecular systems. Each assay may be defined in an assay definition file (ADF), which may include information describing how results will be processed, the process steps to be performed, the order in which they are performed, the interpretations to be generated, etc. The software tool allows the user to develop and define the LDT through one or more windows, screens, or graphical user interfaces ("GUIs") containing interactive buttons, menus, and / or icons that provide access to various functions and information.

[0010] As described in more detail below, after an LDT has been performed or implemented by a molecular system and a dataset has been acquired, the controller may allow a user to process the data and review the results of the assay. The controller may also allow a user to modify at least some of the user-defined assay parameters, re-run the dataset using the modified user-defined assay parameters, and review the results to investigate the impact of the selected user-defined assay parameters on the assay results. In this manner, in some embodiments, the controller may allow a user to determine an optimized set of user-defined assay parameters for performing an LDT (e.g., a set of user-defined assay parameters that produces results approved by the user). The controller may then allow the user to associate the optimized user-defined parameters with a created (or established) LDT protocol and finalize and lock the parameters for the developed LDT (e.g., to prevent them from being inadvertently changed).

[0011] In embodiments of the present disclosure, systems and methods for performing multiple nucleic acid amplification assays on an automated analyzer are disclosed.

[0012] In one embodiment, a method for performing multiple nucleic acid amplification assays on an automated analyzer is disclosed. The method may include (a) loading multiple sample-containing containers onto the analyzer; and (b) assigning a first nucleic acid amplification assay to be performed on a first sample contained in one of the multiple sample-containing containers. The first nucleic acid amplification assay may be performed according to a first set of assay parameters, which may comprise system-defined assay parameters. The method may also include (c) assigning a second nucleic acid amplification assay to be performed on a second sample contained in one of the multiple sample-containing containers. The second nucleic acid amplification assay may be performed according to a second set of assay parameters, which may comprise one or more user-defined assay parameters. The method may also include (d) producing purified forms of the first and second samples by exposing each of the first and second samples to reagents and conditions suitable for isolating and purifying a first analyte and a second analyte that may be present in the first and second samples, respectively. The method may also include (e) forming a first amplification reaction mixture containing the first sample in purified form and a second amplification reaction mixture containing the second sample in purified form, wherein the first amplification reaction mixture contains a first set of amplification oligomers for amplifying a first region of a first analyte or nucleic acid bound to the first analyte in a first nucleic acid amplification reaction of a first nucleic acid amplification assay, and the second amplification reaction mixture contains a second set of amplification oligomers for amplifying a second region of a second analyte or nucleic acid bound to the second analyte in a second nucleic acid amplification reaction of a second nucleic acid amplification assay. The method may also include (f) exposing the first and second amplification reaction mixtures to heating conditions to amplify the first and second regions, respectively, and (g) determining the presence or absence of the first and second analytes in the first and second amplification reaction mixtures, respectively.In some embodiments, in step (b) above, the first nucleic acid amplification assay is performed according to a first set of assay parameters that consists solely of system-defined assay parameters such that user-defined assay parameters are not used to perform the first nucleic acid amplification assay.

[0013] Various embodiments of the disclosed methods may alternatively or additionally include one or more of the following aspects: the plurality of sample-containing receptacles may be supported by one or more receptacle-holding racks during step (a); the first and second samples may be the same sample contained in the same sample-containing receptacle; the first and second samples may be contained in different sample-containing receptacles; the allocating step may include identifying the assay to be performed using a touchscreen or a keyboard; one or more of the user-defined assay parameters may be communicated to a controller of the analytical device using a touchscreen or a keyboard; the allocating step may include reading machine-readable indicia on the sample-containing receptacle or the receptacle-holding rack, machine-readable indicia identifying which assay to run; the allocating step may be performed during or after step (a); the user-defined assay parameters may be used to process raw data generated by the analytical device in step (g); The assays may each include a PCR reaction, wherein the user-defined assay parameters may include a temperature profile, and the temperature profile of the first nucleic acid amplification reaction may be the same as or different from the temperature profile of the second nucleic acid amplification reaction; the PCR reactions may be performed in real time; the temperature profiles of the first and second nucleic acid amplification reactions may differ in at least one of the number of cycles, time to completion, denaturation temperature, annealing temperature, and extension temperature; step (d) may include immobilizing the first and second analytes on a solid support; the solid support may be magnetically responsive; step (d) may include exposing the first and second samples to a magnetic field and removing non-immobilized components from the first and second samples; in step (d), the magnetic field may be supplied by the same source for the first and second samples; step (d) may include resuspending the solid support in a buffer after removing non-immobilized components from the first and second samples.

[0014] Various embodiments of the disclosed method may alternatively or additionally include one or more of the following aspects: the first and second analytes, if present in the first and second samples, may be specifically immobilized on the solid support in step (d); nucleic acids in the first and second samples may be non-specifically immobilized on the solid support in step (d); the disclosed method may include, prior to forming a first amplification reaction mixture, dissolving a first amplification reagent containing a polymerase and a first set of amplification oligomers, the first amplification reagent being dissolved in a first solvent, the first solvent not containing amplification oligomers or polymerase, and, prior to forming a second amplification reaction mixture, dissolving a second amplification reagent containing a polymerase, the second amplification reagent being dissolved in a second solvent, the second solvent containing a second set of amplification oligomers, the second amplification reagent not containing any amplification oligomers. each of the first and second amplification reagents may be a lyophilizate; each of the first and second amplification reagents may be a unit-dose reagent; the first amplification reagent may contain all of the oligomers necessary to perform a first nucleic acid amplification reaction, and the second solvent may contain all of the oligomers necessary to perform a second nucleic acid amplification reaction; the first unit-dose reagent and the second amplification reagent may each contain a detection probe; the first and second solvents may further contain nucleoside triphosphates; the second solvent may be contained in a first vial supported by the first holder; the first holder may support one or more additional vials, each of which may contain a solvent containing a set of amplification oligomers not contained in the second solvent; the method may further include the step of associating the first vial in the first holder with a second nucleic acid amplification assay.

[0015] Various embodiments of the disclosed methods may alternatively or additionally include one or more of the following aspects: the first solvent may be a universal reagent for dissolving amplification reagents containing different sets of amplification oligomers; the first solvent may be contained in a second holder having a sealed liquid reservoir and an access chamber fluidly connected thereto, the access chamber being accessible by a fluid transfer device for removing the first solvent from the second holder; the first and second amplification reagents may be stored and reconstituted or dissolved in mixing wells of the same or different reagent packs, each reagent pack including multiple mixing wells. Each of the first and second analytes may be a nucleic acid or a protein; the first and second amplification reaction mixtures may be formed in first and second reaction vessels, respectively; oil may be dispensed into each of the first and second reaction vessels before step (f); the method may further include closing each of the first and second reaction vessels with a cap before step (f), which cap may engage the corresponding first or second vessel with a friction fit or an interference fit; the method may further include centrifuging the closed first and second reaction vessels before step (f), which centrifugation step may be performed in a centrifuge having at least one access port for receiving the first and second reaction vessels; each of the first and second reaction vessels may be a different, separate vessel that is not physically connected to any other reaction vessel as part of an integrated unit.

[0016] Various embodiments of the disclosed method may alternatively or additionally include one or more of the following aspects: prior to step (e) in forming the first and second amplification reaction mixtures, contacting the first and second samples in purified form with an elution buffer such that the first and second samples in purified form are contained in first and second eluates, respectively; the method may further include transferring an aliquot of at least one of the first and second eluates to a storage container prior to step (e); the method may further include closing the storage container with a cap, which may engage the corresponding storage container with a friction fit or an interference fit; the method may further include retaining the storage container within the analytical device at least until completion of step (g); the method may include assigning a third nucleic acid amplification assay to be performed to the aliquot of the stored sample, the third nucleic acid amplification assay being performed according to a third set of assay parameters, the third set of assay parameters being a function of the first and second nucleic acid amplification assays. The method may further include steps in which the assay parameters of the first and second amplification reaction mixtures may differ from those of the first set, forming a third amplification reaction mixture with the aliquot of storage container after step (g), wherein the third amplification reaction mixture may contain a third set of amplification oligomers for amplifying a third region of a third analyte or a nucleic acid that binds to the third analyte in a third nucleic acid amplification reaction, exposing the third amplification reaction mixture to thermal conditions to amplify the third region, and determining the presence or absence of the third analyte in the third amplification reaction mixture; the third nucleic acid amplification assay may be assigned after step (g); step (f) may be initiated at different times for the first and second amplification reaction mixtures; the first nucleic acid amplification assay may be an IVD assay and the second nucleic acid amplification assay may be an LDT; the LDT may be performed using an ASR containing the second set of amplification oligomers; the first and second amplification reaction mixtures may be exposed to thermal conditions simultaneously in step (f).

[0017] In another embodiment, a non-transitory computer-readable medium is disclosed, the computer-readable medium being encoded with computer-executable instructions that, when executed by a computer controller of an automated system, can be adapted to perform a nucleic acid amplification assay on a sample provided to the system and can cause the system to: (a) receive and store user input specifying one or more user-defined assay parameters; and (b) receive (i) input specifying a first nucleic acid amplification assay to be performed on the first sample according to a first set of assay parameters, which may consist of system-defined assay parameters, and input specifying a second nucleic acid amplification assay to be performed on the second sample according to a second set of assay parameters, which may include one or more user-defined assay parameters. The instructions also cause the system to (c) generate purified forms of the first and second samples by exposing each of the first and second samples to reagents and conditions suitable for isolating and purifying a first analyte and a second analyte that may be present in the first and second samples, respectively; (d) form a first amplification reaction mixture by combining first amplification reagents specified by a first set of assay parameters with the purified form of the first sample; and (e) form a second amplification reaction mixture by combining second amplification reagents specified by a second set of assay parameters with the purified form of the second sample. The instructions also cause the system to (f) expose the first amplification reaction mixture to amplification conditions specified by a first set of assay parameters, (g) expose the second amplification reaction mixture to amplification conditions specified by a second set of assay parameters, and (h) determine the presence or absence of a first analyte in the first amplification reaction mixture and determine the presence or absence of a second analyte in the second amplification reaction mixture after performing system processes (f) and (g).

[0018] Various embodiments of the non-transitory computer-readable medium of the present disclosure may alternatively or additionally cause the system to perform the following system processes: system process (b) includes receiving user input from a touchscreen or keyboard specifying an assay to be performed with at least one of the first and second samples; system process (b) includes receiving user input from a graphical user interface; one or more of the user-defined assay parameters are entered using a touchscreen or keyboard; one or more of the user-defined assay parameters are entered using a graphical user interface; one or more of the user-defined assay parameters are entered using a portable storage medium; system process (b) includes reading machine-readable indicia identifying which assay to perform with at least one of the first and second samples; The system process includes a system process in which the Say parameters include parameters used to process data generated by the system in system process (h), the first and second nucleic acid amplification assays each include a PCR reaction, the user-defined assay parameters include a temperature profile defining the amplification conditions for system process (g), the temperature profile of the first nucleic acid amplification assay being the same as or different from the temperature profile of the second nucleic acid amplification assay, and the temperature profiles of the first and second nucleic acid amplification assays differing in at least one of the number of cycles, time to completion, denaturation temperature, annealing temperature, and extension temperature, and system process (c) includes exposing the first and second samples to a solid support adapted to immobilize the first analyte and the second analyte, if present in the first and second samples, and system process (c) includes immobilizing the solid support and removing non-immobilized components of the first and second samples.

[0019] Various embodiments of the non-transitory computer-readable medium of the present disclosure may alternatively or additionally cause the system to perform the following system processes: system process (c) includes resuspending the solid support in a buffer after removing non-immobilized components of the first and second samples; the computer-executable instructions further cause the system to perform system processes for dissolving a first amplification reagent in a first solvent before forming a first amplification reaction mixture in system process (d) and dissolving a second amplification reagent in a second solvent before forming a second amplification reaction mixture in system process (e); oil is dispensed into each of the first and second amplification reaction mixtures before system processes (f) and (g); and the computer-executable instructions further cause the system to perform system processes for dissolving a first amplification reagent in a first solvent before forming a first amplification reaction mixture in system process (d) and dissolving a second amplification reagent in a second solvent before forming a second amplification reaction mixture in system process (e); oil is dispensed into each of the first and second amplification reaction mixtures before system processes (f) and (g); the computer-executable instructions further cause the system to transfer the first and second amplification reaction mixtures to a centrifuge; the computer-executable instructions further cause the system to contact the first sample in purified form with an elution buffer prior to system process (d) in forming the first amplification reaction mixture such that the first sample in purified form is contained in a first eluate; and the computer-executable instructions further cause the system to contact the second sample in purified form with an elution buffer prior to system process (e) in forming the second amplification reaction mixture such that the second sample in purified form is contained in a second eluate; and the computer-executable instructions further cause the system to transfer at least one aliquot of the first and second eluates to a storage container prior to system processes (d) and (e), respectively.

[0020] Various embodiments of the non-transitory computer-readable medium of the present disclosure may alternatively or additionally cause the system to perform the following system processes: the computer-executable instructions further cause the system to receive an input specifying a third nucleic acid amplification assay to be performed on the aliquot in the storage container, the third nucleic acid amplification assay to be performed according to a third set of assay parameters, the third set of assay parameters being different from the first and second sets of assay parameters; and after system process (g), combining a third amplification reagent specified by the third set of assay parameters with the aliquot in the storage container. and exposing the third amplification reaction mixture to amplification conditions specified by the third set of assay parameters to determine the presence or absence of a third analyte in the third amplification reaction mixture; after system process (g), an input specifying a third nucleic acid amplification assay is received; and system process (h) is initiated at different times for the first and second amplification reaction mixtures, the first nucleic acid amplification assay is an IVD assay and the second nucleic acid amplification assay is an LDT; and system processes (f) and (g) comprise exposing the first and second amplification reaction mixtures to amplification conditions simultaneously.

[0021] In another embodiment, an automated system for performing a nucleic acid amplification assay on a sample provided to the system is disclosed.The system includes: (a) a data input component configured to allow input specifying one or more user-defined assay parameters; (b) a data storage medium storing a first set of assay parameters, the first set of assay parameters may consist of system-defined assay parameters and a second set of assay parameters, the second set of assay parameters may include one or more user-defined assay parameters; (c) a command input component configured to allow input specifying (i) a first nucleic acid amplification assay to be performed on a first sample according to the first set of assay parameters, and (ii) a second nucleic acid amplification assay to be performed on a second sample according to the second set of assay parameters; and (d) a command input component configured to generate purified forms of the first and second samples by exposing each of the first and second samples to reagents and conditions sufficient to isolate and purify a first analyte and a second analyte that may be present in the first and second samples, respectively. (e) a fluid transfer device configured and controlled to form a first amplification reaction mixture by combining first amplification reagents specified by a first set of assay parameters with a purified form of the first sample and to form a second amplification reaction mixture by combining second amplification reagents specified by a second set of assay parameters with a purified form of the second sample; (f) a heat treatment station configured and controlled to expose the first amplification reaction mixture to first amplification conditions specified by the first set of assay parameters and to expose the second amplification reaction mixture to second amplification conditions specified by the second set of assay parameters; and (g) a detection system configured and controlled to detect the presence or absence of the first analyte in the first amplification reaction mixture and to determine the presence or absence of the second analyte in the second amplification reaction mixture during or after the first and second amplification reaction mixtures are exposed to the first and second amplification conditions, respectively.

[0022] Various embodiments of the system of the present disclosure may alternatively or additionally include the following aspects: the first and second samples are provided to the system in sample-containing containers supported by one or more container-holding racks of the system; the first and second samples are the same sample contained in the same sample-containing container; the first and second samples are contained in different sample-containing containers; the command input component includes one or more of a touch screen, a keyboard, and a graphical user interface; the data input component includes one or more of a touch screen, a keyboard, and a graphical user interface; and may further include a reader configured to read machine-readable indicia identifying which assays to perform on the first and second samples; and one or more user-defined assay parameters are detected by the detection system. The assay parameters include parameters used to process the generated data; the first and second nucleic acid amplification assays each include a PCR reaction, and the user-defined assay parameters include a temperature profile achieved by the thermal processing station, wherein the temperature profile of the first nucleic acid amplification assay is the same as or different from the temperature profile of the second nucleic acid amplification assay; the detection system is configured to determine the presence or absence of a first analyte in the first amplification reaction mixture in real time during the temperature profile of the first nucleic acid amplification assay and to determine the presence or absence of a second analyte in the second amplification reaction mixture in real time during the temperature profile of the second nucleic acid amplification assay; the temperature profiles of the first and second nucleic acid amplification assays differ in at least one of the number of cycles, time to completion, denaturation temperature, annealing temperature, and extension temperature.

[0023] Various embodiments of the disclosed system may alternatively or additionally include the following aspects: one or more wash stations are configured to immobilize first and second analytes on a solid support; the solid support is magnetically responsive; the one or more wash stations are configured to remove non-immobilized components from the first and second samples while exposing the first and second samples to a magnetic field; the magnetic field is provided by the same source for the first and second samples; the one or more wash stations are configured to resuspend the solid support in a buffer after removing non-immobilized components from the first and second samples; the system dissolves a first non-liquid reagent containing a polymerase and a first set of amplification oligomers (wherein the first non-liquid reagent is dissolved in a first solvent, and the first solvent does not contain amplification oligomers or polymerase) before forming a first amplification reaction mixture, and dissolves a second non-liquid reagent containing a polymerase (wherein the second non-liquid reagent the first solvent is dissolved in a second solvent containing a second set of amplification oligomers, the second non-liquid reagent not containing any amplification oligomers; the second solvent is contained in a vial supported by the first holder; the first holder supports a plurality of vials, at least one of the vials containing a solvent containing a set of amplification oligomers that is not contained in the second solvent; the system is further configured and controlled to, upon receiving a command, associate the vial in the first holder with a second nucleic acid amplification assay; the first solvent is contained in a second holder having a fluidically connected sealed liquid reservoir and an access chamber, the access chamber being accessible by a fluid transfer device for removing the first solvent from the second holder; the first and second non-liquid reagents are stored and dissolved in mixing wells of the same or different reagent packs, each reagent pack including a plurality of mixing wells; and first and second amplification reaction mixtures are formed in first and second reaction vessels, respectively.

[0024] Various embodiments of the disclosed system may alternatively or additionally include the following aspects: the fluid transfer device is further configured and controlled to dispense oil into each of the first and second reaction vessels before exposing the first and second amplification reaction mixtures to the first and second amplification conditions, respectively; the fluid transfer device is further configured and controlled to close each of the first and second reaction vessels with a cap before exposing the first and second amplification reaction mixtures to the first and second amplification conditions, respectively, the cap engaging the corresponding first or second vessel with a friction fit or an interference fit; a centrifuge for centrifuging the closed first and second reaction vessels before exposing the first and second amplification reaction mixtures to the first and second amplification conditions, respectively, the centrifuge including at least one access port for receiving the first and second reaction vessels; each of the first and second reaction vessels being part of an integrated unit. the fluid transfer device is further configured and controlled to: contact the first sample in purified form with an elution buffer before forming the first amplification reaction mixture such that the first sample in purified form is contained in the first eluate when forming the first amplification reaction mixture; and contact the second sample in purified form with an elution buffer before forming the second amplification reaction mixture such that the second sample in purified form is contained in the second eluate when forming the second amplification reaction mixture; the fluid transfer device is further configured and controlled to transfer at least one aliquot of the first and second eluates to the storage containers before forming the first and second amplification reaction mixtures, respectively; the fluid transfer device is further configured and controlled to close the storage containers with caps, which engage the corresponding storage containers with a friction fit or an interference fit.

[0025] Various embodiments of the disclosed system may alternatively or additionally include the following aspects: the command input component may be further configured and controlled to allow input specifying a third nucleic acid amplification assay to be performed on the aliquot in the storage container, the third nucleic acid amplification assay being performed according to a third set of assay parameters, the third set of assay parameters being different from the first and second sets of assay parameters; and the fluid transfer device may be further configured and controlled to form a third amplification reaction mixture with the aliquot in the storage container, wherein the third amplification reaction mixture is performed according to the third set of assay parameters. the heat treatment station may be further configured and controlled to expose the third amplification reaction mixture to third amplification conditions, and the detection system may be further configured and controlled to determine the presence or absence of a third analyte in the third amplification reaction mixture; the first and second amplification reaction mixtures are exposed to the first and second amplification conditions, respectively, at different times; the first nucleic acid amplification assay is an IVD assay and the second nucleic acid amplification assay is an LDT; the heat treatment station is configured and controlled to simultaneously expose the first and second amplification reaction mixtures to the first and second amplification conditions, respectively.

[0026] In another embodiment, a method for performing multiple nucleic acid amplification assays on an automated analyzer is disclosed, the method comprising the steps of: (a) loading a plurality of sample-containing vessels onto the analyzer; (b) generating a first sample in purified form contained in one of the plurality of sample-containing vessels by exposing the first sample to reagents and conditions suitable for isolating and purifying a first analyte that may be present in the first sample; (c) after initiating step (b), generating a second sample in purified form contained in one of the plurality of sample-containing vessels by exposing the second sample to reagents and conditions suitable for isolating and purifying a second analyte that may be present in the second sample; and (d) forming a first amplification reaction mixture containing the first sample in purified form and a second amplification reaction mixture containing the second sample in purified form, wherein the first amplification reaction mixture is capable of isolating and purifying the first analyte. The method may include the steps of: (a) containing a first set of amplification oligomers for amplifying a first region of the first analyte or nucleic acid bound to the first analyte in a first nucleic acid amplification reaction; and (b) containing a second set of amplification oligomers for amplifying a second region of the second analyte or nucleic acid bound to the second analyte in a second nucleic acid amplification reaction; (e) exposing the second amplification reaction mixture to thermal conditions for amplifying the second region in the second nucleic acid amplification reaction; (f) after the start of step (e), exposing the first amplification reaction mixture to thermal conditions for amplifying the first region in the first nucleic acid amplification reaction; (g) determining the presence or absence of the second analyte in the second amplification reaction mixture; and (h) after step (g), determining the presence or absence of the first analyte in the first amplification reaction mixture.

[0027] Various embodiments of the disclosed methods may alternatively or additionally include the following aspects: a plurality of sample-containing containers are individually and sequentially loaded into an analytical device, wherein during step (a), the plurality of sample-containing containers are supported by one or more container-holding racks; a first sample is contained in a first sample-containing container and a second sample is contained in a second sample-containing container, the first and second sample-containing containers being supported by first and second container-holding racks, respectively; the second sample is loaded into the analytical device during or after step (b); the first and second samples are contained in a single sample-containing container; the first and second samples are contained in different sample-containing containers; steps (b) and (c) include immobilizing the first or second analyte, if present in the first and second samples, respectively. the solid support is magnetically responsive; steps (b) and (c) involve removing non-immobilized components of the first or second sample, respectively, while exposing the first or second sample to a magnetic field; the magnetic field is supplied by the same source for the first and second samples in steps (b) and (c), respectively; steps (b) and (c) involve resuspending the solid support in a buffer after removing non-immobilized components of the first or second sample, respectively; steps (b) and (c) involve specifically immobilizing the first or second analyte when the first or second sample is present on the solid support; steps (b) and (c) involve non-specifically immobilizing the first or second analyte when the first or second sample is present on the solid support.

[0028] Various embodiments of the disclosed system may alternatively or additionally include the following aspects: (a) prior to forming a first amplification reaction mixture, dissolving a first amplification reagent containing a polymerase and a first set of amplification oligomers, the first amplification reagent being dissolved in a first solvent, the first solvent not containing amplification oligomers or a polymerase; and (b) prior to forming a second amplification reaction mixture, dissolving a second amplification reagent containing a polymerase, the second solvent not containing amplification oligomers or a polymerase. The amplification reagent is dissolved in a second solvent containing a second set of amplification oligomers, the second amplification reagent not containing any amplification oligomers; each of the first and second amplification reagents is a lyophilizate; each of the first and second amplification reagents is a unit dose reagent; the first amplification reagent contains all the oligomers necessary to perform a first nucleic acid amplification reaction, and the second solvent contains all the oligomers necessary to perform a second nucleic acid amplification reaction; the first unit dose reagent and the second solvent each contain a detection probe. the first and second amplification reagents further contain nucleoside triphosphates; the second solvent is contained in a first vial supported by a first holder; the first holder supports one or more vials in addition to the first vial, at least one of the one or more vials containing a solvent containing a set of amplification oligomers that are not contained in the second solvent; the first solvent is a universal reagent for dissolving amplification reagents containing different sets of amplification oligomers; the first solvent is contained in a second holder having a fluidically connected sealed liquid reservoir and an access chamber, the access chamber being accessible by a fluid transfer device for removing the first solvent from the second holder; the first and second amplification reagents are stored and dissolved in mixing wells of the same or different reagent packs, each reagent pack including multiple mixing wells; the first set of amplification oligomers is used to perform an IVD assay and the second set of amplification oligomers is used to perform an LDT.

[0029] Various embodiments of the disclosed system may alternatively or additionally include the following aspects: (a) prior to forming a first amplification reaction mixture, dissolving a first amplification reagent containing a polymerase, wherein the first amplification reagent is dissolved in a first solvent containing a first set of amplification oligomers, and the first amplification reagent does not contain amplification oligomers; (b) prior to forming a second amplification reaction mixture, dissolving a second amplification reagent containing a polymerase and a second set of amplification oligomers, wherein the second amplification reagent is dissolved in a first solvent containing a first set of amplification oligomers. The first and second amplification reagents are dissolved in two solvents, the second solvent not containing amplification oligomers or polymerase; each of the first and second amplification reagents is a lyophilizate; each of the first and second amplification reagents is a unit dose reagent; the first solvent contains all the oligomers necessary to perform a first nucleic acid amplification reaction, and the second amplification reagent contains all the oligomers necessary to perform a second nucleic acid amplification reaction; the first solvent and the second unit dose reagent each contain a detection probe; and the first and second amplification reagents further contain nucleoside triphosphates. the first solvent is contained in a first vial supported by a first holder; the first holder supports one or more vials in addition to the first vial, at least one of the one or more vials containing a solvent containing a set of amplification oligomers not contained in the first solvent; the second solvent is a universal solvent for dissolving amplification reagents containing a different set of amplification oligomers; the second solvent is contained in a second holder having a sealed liquid reservoir and an access chamber fluidly connected thereto, the access chamber the member is accessible by a fluid transfer device for removing the second solvent from the second holder; the first and second amplification reagents are stored and dissolved in mixing wells of the same or different reagent packs, each reagent pack including multiple mixing wells; the first set of amplification oligomers is used to perform an LDT, and the second set of amplification oligomers is used to perform an IVD; each of the first and second analytes is a nucleic acid or a protein; the first and second amplification reaction mixtures are formed in first and second reaction vessels, respectively;Dispensing oil into each of the first and second reaction vessels prior to steps (f) and (e); closing each of the first and second reaction vessels with a cap prior to steps (f) and (e), the cap engaging the corresponding first or second vessel with a friction fit or an interference fit;

[0030] Various embodiments of the disclosed system may alternatively or additionally include the following aspects: centrifuging the closed first and second reaction vessels before steps (f) and (e), wherein the centrifugation step is carried out in a centrifuge having at least one access port for receiving the first and second reaction vessels; each of the first and second reaction vessels being different and separate vessels that are not physically connected to any other reaction vessel as part of an integrated unit; contacting the first and second samples in purified form with an elution buffer before step (d) in forming the first and second amplification reaction mixtures, such that the first and second samples in purified form are contained in first and second eluates, respectively; transferring an aliquot of at least one of the first and second eluates to a storage container before forming the first or second amplification reaction mixture; closing the storage container with a cap, wherein the cap engages the corresponding storage container with a friction fit or an interference fit; and retaining the storage container within the analytical device at least until completion of step (g). forming a third amplification reaction mixture with the aliquot of the storage container after steps (g) and (h), the third amplification reaction mixture containing a third set of amplification oligomers for amplifying a third region of a third analyte or a nucleic acid that binds to the third analyte in a third nucleic acid amplification reaction; (j) exposing the third amplification reaction mixture to thermal conditions to amplify the third region; and (k) determining the presence or absence of the third analyte in the third amplification reaction mixture; ) is initiated after completion of step (b); step (f) is initiated after completion of step (e); each of the first and second nucleic acid amplification reactions requires thermal cycling; a temperature profile for the thermal cycling of the first nucleic acid amplification reaction is different from a temperature profile for the thermal cycling of the second nucleic acid amplification reaction; selecting a temperature profile for the second nucleic acid amplification reaction based on user input; the selecting a temperature profile includes selecting at least one of the number of cycles, time to completion, denaturation temperature, annealing temperature, and extension temperature;The first and second nucleic acid amplification reactions are PCR reactions; the first and second nucleic acid amplification reactions are real-time amplifications;

[0031] In another embodiment, a non-transitory computer-readable medium is disclosed that, when executed by a computer controller of an automated system, can be adapted to perform nucleic acid amplification assays on samples in multiple sample-receiving containers loaded into the system, and that includes system processes for: (a) generating a first sample in purified form by exposing the first sample to reagents and conditions suitable for isolating and purifying a first analyte that may be present in the first sample; (b) generating a second sample in purified form after initiating system process (a) by exposing the second sample to reagents and conditions suitable for isolating and purifying a second analyte that may be present in the second sample; and (c) combining a first amplification reagent with the first sample in purified form to form a first amplification reaction mixture. (d) forming a second amplification reaction mixture by combining second amplification reagents with the purified form of the second sample; (e) exposing the first amplification reaction mixture to amplification conditions for performing a first nucleic acid amplification reaction; (f) exposing the second amplification reaction mixture to amplification conditions for performing a second nucleic acid amplification reaction prior to initiation of system process (e); (g) determining the presence or absence of the second analyte in the second amplification reaction mixture after performance of system process (f) and prior to completion of system process (e); and (h) determining the presence or absence of the first analyte in the first amplification reaction mixture after performance of system process (e).

[0032] Various embodiments of the non-transitory computer-readable medium of the present disclosure may alternatively or additionally cause the system to perform the following system processes: system processes (a) and (b) include immobilizing a first or second analyte on a solid support if the first or second analyte is present in the first and second samples, respectively; the solid support is magnetically responsive, and system processes (a) and (b) include removing non-immobilized components of the first or second sample, respectively, while exposing the first or second sample to a magnetic field; system processes (a) and (b) include resuspending the solid support in a buffer after removing non-immobilized components of the first or second sample, respectively; the computer-executable instructions may further cause the system to dissolve a first reagent in a first solvent before forming a first amplification reaction mixture, and dissolve a second reagent containing a polymerase in a second solvent before forming a second amplification reaction mixture. the first amplification reagent may be used to perform an IVD assay, and the second amplification reagent may be used to perform an LDT; oil is dispensed into each of the first and second amplification reaction mixtures prior to system processes (e) and (f), respectively; the computer-executable instructions further cause the system to centrifuge the first and second amplification reaction mixtures prior to system processes (e) and (f), respectively; the computer-executable instructions further cause the system to contact the first and second samples in purified form with an elution buffer such that the first and second samples in purified form are contained in first and second eluates, respectively, prior to system processes (c) and (d), when forming the first and second amplification reaction mixtures; the computer-executable instructions further cause the system to transfer an aliquot of at least one of the first and second eluates to a storage container prior to forming the first or second amplification reaction mixture.

[0033] Various embodiments of the non-transitory computer-readable medium of the present disclosure may alternatively or additionally cause the system to perform the following system processes: the computer-executable instructions further cause the system to form a third amplification reaction mixture using the aliquot in the storage container after at least one of system processes (g) and (h), expose the third amplification reaction mixture to amplification conditions for performing a third nucleic acid amplification reaction, and determine the presence or absence of a third analyte in the third amplification reaction mixture; system process (b) is initiated after completion of system process (a); the amplification conditions for performing the first and second nucleic acid amplification reactions include thermal cycling; the temperature profile in the thermal cycling of the first nucleic acid amplification reaction is different from the temperature profile in the thermal cycling of the second nucleic acid amplification reaction; the computer-executable instructions further cause the system to select a temperature profile for the second nucleic acid amplification reaction based on user input; the first and second nucleic acid amplification reactions are PCR reactions.

[0034] In another embodiment, an automated system configured to perform nucleic acid amplification assays on samples in a plurality of sample-containing receptacles is disclosed. The system may include one or more wash stations configured to produce a purified form of a first sample by exposing the first sample to reagents and conditions suitable for isolating and purifying a first analyte that may be present in the first sample, and, after initiating production of the purified form of the first sample, produce a purified form of a second sample by exposing the second sample to reagents and conditions suitable for isolating and purifying a second analyte that may be present in the second sample. The system may also include a fluid transfer device configured and controlled to combine a first amplification reagent with the purified form of the first sample to form a first amplification reaction mixture and to combine a second amplification reagent with the purified form of the second sample to form a second amplification reaction mixture. The system may also include a heat treatment station configured and controlled to expose the first amplification reaction mixture to first amplification conditions to perform a first nucleic acid amplification reaction, and to expose the second amplification reaction mixture to second amplification conditions to perform a second nucleic acid amplification reaction before exposing the first amplification mixture to the first amplification conditions. The system may also include a detection system configured and controlled to determine the presence or absence of a second analyte in the second amplification reaction mixture after exposing the second amplification reaction mixture to the second amplification conditions and before exposure of the first amplification mixture to the first amplification conditions is complete, and to determine the presence or absence of a first analyte in the first amplification reaction mixture after exposing the first amplification mixture to the first amplification conditions.

[0035] Various embodiments of the system of the present disclosure may alternatively or additionally include one or more of the following aspects: a plurality of sample-containing vessels are loaded into the system individually and sequentially; a plurality of sample-containing vessels are loaded into the system in one or more vessel-holding racks; a first sample is contained in a first sample-containing vessel and a second sample is contained in a second sample-containing vessel, the first and second sample-containing vessels being supported by first and second vessel-holding racks, respectively; the first and second samples are contained in a single sample-containing vessel; the first and second samples are contained in different sample-containing vessels; one or more wash stations are configured to immobilize the first or second analyte on a solid support if the first or second analyte is present in the first and second sample, respectively; the solid support is magnetically responsive; the one or more wash stations are configured to remove non-immobilized components from the first or second sample while exposing the first or second sample to a magnetic field; the magnetic field is the same for the first and second samples. the second solvent is supplied by a single source; one or more wash stations are configured to resuspend the solid support in a buffer solution after removing non-immobilized components from the first or second sample; the system is further configured and controlled to dissolve a first non-liquid reagent containing a polymerase and a first set of amplification oligomers (wherein the first non-liquid reagent is dissolved in a first solvent, and the first solvent does not contain amplification oligomers or polymerase) before forming a first amplification reaction mixture, and to dissolve a second non-liquid reagent containing a polymerase (wherein the second non-liquid reagent is dissolved in a second solvent containing a second set of amplification oligomers, and the second non-liquid reagent does not contain any amplification oligomers) before forming a second amplification reaction mixture; the second solvent is contained in a vial supported by a first holder; the first holder supports a plurality of vials, at least one of the vials containing a solvent containing a set of amplification oligomers that is not contained in a second solvent;A first solvent is contained in a second holder having a fluidly connected sealed liquid reservoir and access chamber, the access chamber being accessible by a fluid transfer device for removing the first solvent from the second holder; first and second non-liquid reagents are stored and dissolved in mixing wells of the same or different reagent packs, each reagent pack including multiple mixing wells; a first set of amplification oligomers is used to perform an IVD assay, and a second set of amplification oligomers is used to perform an LDT;

[0036] Various embodiments of the disclosed system may alternatively or additionally include one or more of the following aspects: first and second amplification reaction mixtures are formed in first and second reaction vessels, respectively; the fluid transfer device is further configured and controlled to dispense oil into each of the first and second reaction vessels before exposing the first and second amplification reaction mixtures to first and second amplification conditions, respectively; the fluid transfer device is further configured and controlled to close each of the first and second reaction vessels with a cap before exposing the first and second amplification reaction mixtures to first and second amplification conditions, respectively, the cap engaging the corresponding first or second vessel with a friction fit or an interference fit; and a centrifuge for centrifuging the closed first and second reaction vessels before exposing the first and second amplification reaction mixtures to the first and second amplification conditions, respectively, the centrifuge and at least one access port for receiving a second reaction vessel; each of the first and second reaction vessels is a different and separate vessel not physically connected to any other reaction vessel as part of an integrated unit; the fluid transfer device is further configured and controlled to contact the first sample in purified form with an elution buffer before forming the first and second amplification reaction mixtures such that the first and second samples in purified form are contained in the first and second eluates upon forming the first and second amplification reaction mixtures; the fluid transfer device is further configured and controlled to transfer an aliquot of at least one of the first and second eluates to a storage vessel before forming the first or second amplification reaction mixtures; the fluid transfer device is further configured and controlled to close the storage vessel with a cap, the cap engaging the corresponding storage vessel with a friction fit or an interference fit;the fluid transfer device is configured and controlled to form a third amplification reaction mixture using the aliquot in the storage container after at least one of determining the presence or absence of a second analyte in the second amplification reaction mixture and determining the presence or absence of a first analyte in the first amplification reaction mixture, wherein the third amplification reaction mixture comprises a third set of amplification oligomers, the heat treatment station is further configured and controlled to expose the third amplification reaction mixture to third amplification conditions, and the detection system is further configured and controlled to determine the presence or absence of a third analyte in the third amplification reaction mixture; the first and second amplification conditions comprise thermal cycles; a first temperature profile of the first nucleic acid amplification reaction differs from a second temperature profile of the second nucleic acid amplification reaction in at least one of the number of cycles, time to completion, denaturation temperature, annealing temperature, and extension temperature; and the system further includes a command input component configured to enable selection of the second temperature profile based on user input; the first and second nucleic acid amplification reactions are PCR reactions; and the first and second nucleic acid amplification reactions are real-time amplifications. ;

[0037] In another embodiment, a method for analyzing a plurality of samples is disclosed. The method may include (a) holding a first container at a first position of an automated analyzer, the first container containing a first solvent. The first solvent may not contain any oligomers for performing a nucleic acid amplification reaction. The method may also include (b) dissolving a first unit-dose reagent in the first solvent in each of a plurality of first containers, thereby forming a first liquid amplification reagent in each of the first containers. The first unit-dose reagent may contain a polymerase and at least one amplification oligomer for performing a nucleic acid amplification reaction. The at least one amplification oligomer in each of the first containers may be the same or different. The method may further include (c) combining the first liquid amplification reagent from each of the first containers with one of the plurality of samples of the first set of samples in a first reaction container, thereby forming at least one first amplification reaction mixture with each sample of the first set of samples; (d) exposing the contents of the first reaction container to a first set of conditions for performing a first nucleic acid amplification reaction; and (e) holding a second container at a second position of the automated analyzer. The second container may hold one or more vials. Each of the one or more vials may contain a second solvent. The second solvent may contain at least one amplification oligomer for performing the nucleic acid amplification reaction. When the second container holds at least two of the one or more vials, the second solvent contained in each of the two or more vials may be the same or different solvents. The method may also include (f) dissolving a second unit-dose reagent in each of the plurality of second containers in a second solvent of one of the vials, thereby forming a second liquid amplification reagent in each of the second containers. The second unit-dose reagent may contain a polymerase for performing a nucleic acid amplification reaction, and wherein the second liquid amplification reagent in each of the second containers is the same or a different liquid amplification reagent.The method may also include (g) combining the second liquid amplification reagent from each of the second containers with one of the plurality of samples of the second set of samples in a second reaction container, thereby forming at least one second amplification reaction mixture with each sample of the second set of samples. The method may also include (h) exposing the contents of the second reaction container to a second set of conditions for conducting a second nucleic acid amplification reaction, wherein the first and second sets of conditions are the same or different. The method may further include (i) determining the presence or absence of one or more analytes in each of the first and second reaction containers, wherein at least one analyte in the first reaction container is different from at least one analyte in the second reaction container.

[0038] Various embodiments of the disclosed method may alternatively or additionally include one or more of the following aspects: each of the first unit-dose reagents is dissolved in one of a plurality of first wells of a first multi-well container, and each of the second unit-dose reagents is dissolved in one of a plurality of second wells of a second multi-well container; during the dissolving step, holding the first and second multi-well containers at first and second positions, respectively, on a first container support of an automated analyzer; the first container support is a transport structure; the transport structure rotates about an axis; before steps (b) and (f), transferring the first and second solvents from the first and second containers to the first and second wells of the first and second multi-well containers, respectively, by a liquid extractor; steps (c) and (g) are each a first transfer step. the method includes a step of transferring each dissolved first unit-dose reagent to one of a plurality of first reaction vessels in a first transfer step, and a step of transferring each dissolved second unit-dose reagent to one of a plurality of second reaction vessels in a second transfer step; steps (c) and (g) further include a step of transferring a sample of the first set of samples to the first reaction vessel after the first transfer step, and a step of transferring a sample of the second set of samples to the second reaction vessel after the second transfer step, respectively; the first and second transfer steps are performed by at least one liquid withdrawal device; the at least one liquid withdrawal device is a robotic pipetter; steps (b) and (f) further include a step of mixing the contents of the first and second wells of the first and second multi-well vessels, respectively, using the robotic pipetter.

[0039] Various embodiments of the disclosed method may alternatively or additionally include one or more of the following aspects: prior to step (b), the first solvent is contained within a liquid reservoir formed in the first container; the method further includes loading the first and second sets of samples onto an automated analyzer and exposing the samples of the first and second sets of samples to reagents and conditions suitable for extracting one or more analytes that may be present in each of the samples; before at least some of the samples of the first set are loaded onto the automated analyzer, one or more of the samples of the second set are extracted. at least a portion of the first and second sets of samples are loaded into the automated analyzer; at least one of the samples in each of the first and second sets of samples is the same sample; the first and second locations are first and second recesses formed in a container housing of the automated analyzer; the container housing is a component of a sliding drawer that moves between an open position that allows insertion of the first and second containers into the first and second recesses, respectively, and a closed position that allows formation of the first and second liquid amplification reagents in the first and second containers, respectively; the first and second recesses have substantially the same dimensions; the first container is covered by a pierceable seal that limits evaporation from the first container; each of the one or more vials is supported by a recess formed in a solid portion of the second container; the one or more vials include at least two vials, and the at least one amplification oligomer contained in the second solvent of the at least two vials is a different amplification oligomer; the first unit-dose reagent does not contain an amplification oligomer identical to the amplification oligomer of the at least two vials in the second holder; the first solvent is a universal reagent for dissolving reagents having amplification oligomers for amplifying different target nucleic acids; the second solvent contains at least one forward amplification oligomer and at least one reverse amplification oligomer; the second solvent contains a detection probe for performing a real-time amplification reaction; the first unit-dose reagent contains at least one forward amplification oligomer and at least one reverse amplification oligomer; the first unit-dose reagent contains a detection probe for performing a real-time amplification reaction; the first and second unit-dose reagents further contain nucleoside triphosphates;the first set of conditions includes cycling the temperature of the contents of the first reaction vessel; the second set of conditions includes cycling the temperature of the contents of the second reaction vessel; the first and second sets of conditions are different;

[0040] Various embodiments of the disclosed method may alternatively or additionally include one or more of the following aspects: the contents of at least a portion of the first reaction vessel are exposed to a first set of conditions before exposing at least a portion of the second reaction vessel to a second set of conditions; steps (d) and (h) overlap one another; the method further includes, prior to steps (d) and (h), respectively, transferring each of the first and second reaction vessels to a temperature-controlled station; the temperature-controlled station includes a plurality of vessel holders, each vessel holder having an associated heating element, and the first and second reaction vessels are heated by different vessel holders during steps (d) and (h). the first and second reaction vessels are capped before steps (d) and (h), respectively, thereby inhibiting or preventing evaporation of the contents of the first and second reaction vessels; an IVD assay is performed with the contents of the first reaction vessel and one or more LDT assays are performed with the contents of the second reaction vessel; the second unit-dose reagent does not contain amplification oligomers or detection probes for performing a nucleic acid amplification assay; the first location is a first container support and the second location is a second container support, the first and second container supports being different from each other; the first container support has a first temperature and the second container support has a second temperature that is different from the first temperature.

[0041] In another embodiment, a method for analyzing multiple samples using an automated analyzer is disclosed. The method may include (a) holding a first container unit containing a first solvent at a first position on the analyzer, and (b) holding a second container unit at a second position on the analyzer. The first solvent may not contain amplification oligomers for performing a nucleic acid amplification reaction. The second container unit may have a different structure from the first container unit and may be configured to support multiple vials. Each vial of the multiple vials may be configured to hold a solvent therein. The solvent in each vial contains at least one amplification oligomer for performing a nucleic acid amplification reaction. The method may also include (c) dissolving a first non-liquid reagent in the first solvent to form a first liquid amplification reagent. The first non-liquid reagent contains at least one amplification oligomer for performing a nucleic acid amplification reaction. The method may also include (d) dissolving a second non-liquid reagent in the solvent contained in a vial of the second container unit to form a second liquid amplification reagent. The second non-liquid reagent may not contain amplification oligomers for performing a nucleic acid amplification reaction, and the amplification oligomers of the first and second liquid amplification reagents may be different from each other. The method may also include (e) combining the first liquid amplification reagent with the first sample to form a first amplification reaction mixture, and (f) combining the second liquid amplification reagent with the second sample to form a second amplification reaction mixture. The method may also include (g) performing a first amplification reaction using the first amplification reaction mixture, (h) performing a second amplification reaction using the second amplification reaction mixture, and (i) determining the presence or absence of one or more analytes in each of the first and second amplification reaction mixtures.

[0042] Various embodiments of the disclosed method may alternatively or additionally include one or more of the following aspects: the first location and the second location are two locations within a single container compartment of an analytical device; the first location is a first container compartment of the analytical device and the second location is a second container compartment of the analytical device; the first container compartment has a first temperature and the second container compartment has a second temperature different from the first temperature; at least two vials of the plurality of vials of the second container unit contain different solvents; at least two vials of the plurality of vials of the second container unit contain the same solvent; the first container unit holds only a single solvent; loading a plurality of sample-containing containers into the analytical device, wherein first and second samples are contained in one or more sample-containing containers of the plurality of sample-containing containers; the first and second samples are the same sample contained in a single sample-containing container of the plurality of sample-containing containers; the first and second samples are contained in different sample-containing containers of the plurality of sample-containing containers.

[0043] Various embodiments of the disclosed methods may alternatively or additionally include one or more of the following aspects: (j) assigning a first nucleic acid amplification assay to be performed on a first sample and a second nucleic acid amplification assay to be performed on a second sample, wherein the first nucleic acid amplification assay is performed according to a first set of assay parameters and the second nucleic acid amplification assay is performed according to a second set of assay parameters, the first set of assay parameters consisting of system-defined assay parameters and the second set of assay parameters including one or more user-defined assay parameters; the assigning step includes selecting the assays to be performed on the first and second samples using a touch screen or keyboard; The user-defined assay parameters are communicated to a controller of the analytical device using a touch screen or keyboard; the assigning step includes reading machine-readable indicia associated with the first and second samples, the machine-readable indicia identifying which assays to perform on the first and second samples; user-defined assay parameters are used to process the raw data generated by the analytical device; the first and second nucleic acid amplification reactions each include performing a PCR reaction, the user-defined assay parameters including a temperature profile, the temperature profile of the first nucleic acid amplification reaction being the same as or different from the temperature profile of the second nucleic acid amplification reaction; the detection is performed in real time; the temperature profiles of the first and second nucleic acid amplification reactions differ in at least one of the number of cycles, time to completion, denaturation temperature, annealing temperature, and extension temperature.

[0044] Various embodiments of the disclosed methods may alternatively or additionally include one or more of the following aspects: (k) producing the first and second samples in purified form by exposing each of the first and second samples to reagents and conditions suitable for isolating and purifying a first analyte and a second analyte that may be present in the first and second samples, respectively; step (k) comprising immobilizing the first and second analytes on a non-liquid support; the non-liquid support being magnetically responsive; purifying comprising removing non-immobilized components from the first and second samples while exposing the first and second samples to a magnetic field; the magnetic field being applied to the first and second samples from a common magnetic source; purifying comprising resuspending the non-liquid support in a buffer after removing non-immobilized components from the first and second samples; In step (i), the first and second analytes, if present in the first and second samples, are specifically immobilized to the non-liquid support; in step (k), nucleic acids in the first and second samples are non-specifically immobilized to the non-liquid support; further comprising contacting the first and second samples in purified form with an elution buffer so that the first and second samples in purified form are contained in first and second elution solutions, respectively, when forming the first and second amplification reaction mixtures; further comprising transferring an aliquot of at least one of the first and second elution solutions to a storage container before step (e) or (f); closing the storage container with a cap, wherein the cap engages the corresponding storage container by a friction fit or an interference fit; and retaining the storage container within the analytical device at least until completion of step (i).

[0045] Various embodiments of the disclosed method may alternatively or additionally include one or more of the following aspects: forming a third amplification reaction mixture using an aliquot in a storage container, the third amplification reaction mixture containing a set of amplification oligomers for amplifying an analyte in a third nucleic acid amplification reaction, performing a third amplification reaction using the third amplification reaction mixture, and determining the presence or absence of the analyte in the third amplification reaction mixture; the third amplification reaction is performed after step (i); (g) and (h) are initiated at different times; each of the first and second non-liquid reagents is a unit-dose lyophilizate; the first lyophilizate contains all of the oligomers necessary to perform a first nucleic acid amplification reaction, and the solvent in the second container contains all of the oligomers necessary to perform a second nucleic acid amplification reaction; the first and second non-liquid reagents each contain detection probes; the first and second non-liquid reagents contain nucleoside triphosphates; the first solvent is a universal reagent for dissolving non-liquid reagents containing different sets of amplification oligomers; the analyzer includes a sealed liquid-receiving chamber, the liquid-receiving chamber being accessible by a fluid transfer device for removing the first solvent from the first container; the first and second non-liquid reagents are each contained in a different mixing well of the same or different reagent packs carried on the analytical device, each reagent pack including a plurality of mixing wells, step (c) being performed in the mixing well containing the first non-liquid reagent and step (d) being performed in the mixing well containing the second non-liquid reagent; each analyte of the one or more analytes being a nucleic acid or a protein; First and second amplification reaction mixtures are formed in first and second reaction vessels, respectively; prior to steps (g) and (h), further comprising dispensing oil into the first and second reaction vessels, respectively; prior to steps (g) and (h), closing each of the first and second reaction vessels with a cap, the cap engaging the corresponding first or second vessel by a friction fit or an interference fit; prior to steps (g) and (h), further comprising centrifuging the closed first and second reaction vessels, respectively, in a centrifuge;each of the first and second reaction vessels is a distinct and separate vessel that is not physically connected to any other reaction vessel as part of an integrated unit;

[0046] In another embodiment, a system is disclosed that includes a random access automated analytical device for performing multiple nucleic acid amplification assays. The system may include a controller configured to (a) receive information from multiple sample-containing receptacles stored in the analytical device, (b) send instructions to one or more devices of the analytical device to expose first samples in the multiple sample-containing receptacles to reagents and conditions suitable for immobilizing a first analyte on a first solid support, and (c) send instructions to one or more devices of the analytical device to remove non-immobilized components of the first sample from the first solid support and resuspend the first solid support in a first buffer to generate a purified form of the first sample. The controller may also (d) after step (b), send instructions to one or more devices of the analytical device to expose the second sample in the sample-receiving container to reagents and conditions sufficient to immobilize the second analyte on the second solid support, and (e) send instructions to one or more devices of the analytical device to remove non-immobilized components of the second sample from the second solid support and resuspend the second solid support in a second buffer to produce a purified form of the second sample. The controller may also send instructions to (f) one or more devices of the analytical device to dissolve a first unit dose reagent in a first solvent, where the first unit dose reagent contains a polymerase and a first set of amplification oligomers for amplifying a first region of a first analyte or a nucleic acid bound to a first analyte in a first nucleic acid amplification reaction, and the first solvent does not contain amplification oligomers or a polymerase for performing the first nucleic acid amplification reaction; and (g) one or more devices of the analytical device to dissolve a second unit dose reagent in a second solvent, where the second solvent contains a second set of amplification oligomers for amplifying a second region of a second analyte or a nucleic acid bound to a second analyte in a second nucleic acid amplification reaction, and the second unit dose reagent contains a polymerase for performing the second nucleic acid amplification reaction, and the second unit dose reagent does not contain any amplification oligomers for performing a nucleic acid amplification reaction.Furthermore, the controller may (h) transmit instructions to one or more devices of the analytical device to form a first reaction mixture by combining the dissolved second unit-dose reagent with the second sample in purified form in a first reaction vessel; (i) transmit instructions to one or more devices of the analytical device to expose the contents of the first reaction vessel to first temperature conditions for performing a second nucleic acid amplification reaction; (j) transmit instructions to one or more devices of the analytical device to determine the presence or absence of a second analyte in the second reaction mixture; and (k) transmit instructions to one or more devices of the analytical device to form a second reaction mixture by combining the dissolved first unit-dose reagent with the first sample in purified form in a second reaction vessel after step (h). Furthermore, the controller may (l) send instructions to one or more devices of the analytical device to expose the contents of the second reaction vessel to second temperature conditions for conducting a first nucleic acid amplification reaction, where the first and second temperature conditions are the same or different, and (m) send instructions to one or more devices of the analytical device to determine the presence or absence of a first analyte in the first reaction mixture. The system may also include an output device configured to output a result related to the presence or absence of the first and second analytes.

[0047] Various embodiments of the system of the present disclosure may alternatively or additionally include one or more of the following aspects: the sample-containing vessels of the plurality of sample-containing vessels are loaded individually and sequentially; the sample-containing vessels of the plurality of sample-containing vessels are loaded into a plurality of vessel-holding racks, a first sample being contained in the first sample-containing vessel and a second sample being contained in the second sample-containing vessel, and the first and second sample-containing vessels being supported by the first and second vessel-holding racks, respectively; the second sample is loaded into the analytical device during or after step (b); the first and second solid supports are magnetically responsive; step (c) further comprises exposing the first solid support to a magnetic field and step (e) further comprises exposing the second solid support to a magnetic field; the magnetic field of step (c) is provided by the same source as the magnetic field of step (e); in step (b) a first analyte is specifically immobilized on the first solid support and in step (d) a second analyte is specifically immobilized on the second solid support. the nucleic acids in the first and second samples are non-specifically immobilized to the first and second solid supports in steps (b) and (d), respectively; the first and second buffers are the same buffer; the first unit-dose reagent contains all of the oligomers necessary to perform a first nucleic acid amplification reaction, and the second solvent contains all of the oligomers necessary to perform a second nucleic acid amplification reaction; the first unit-dose reagent and the second solvent each contain a detection probe; each of the first and second unit-dose reagents is a lyophilizate; each of the first and second solvents further contains nucleoside triphosphates; the second solvent is contained in a vial supported by a holder; the first holder supports a plurality of vials, at least some of the vials containing a solvent containing one set of amplification oligomers that is not contained in the second solvent; and the first solvent is a universal reagent for dissolving unit-dose reagents containing different sets of amplification oligomers.

[0048] Various embodiments of the disclosed methods may alternatively or additionally include one or more of the following aspects: the first solvent is contained in a second holder having a fluidically connected sealed liquid reservoir and an access chamber, the access chamber being accessible by a fluid transfer device for removing the solvent from the second holder; the first and second unit-dose reagents are stored and dissolved in mixing wells of the same or different reagent packs, each reagent pack including multiple mixing wells; the controller is configured to send instructions to one or more devices of the analytical device to expose the second sample in purified form to an elution buffer prior to step (h) and to expose the first sample in purified form to an elution buffer prior to step (k); the controller is configured to send instructions to one or more devices of the analytical device to transfer an aliquot of at least one of the first and second samples in purified form to a storage container for use after completion of at least one of steps (j) and (m); the controller is configured to send instructions to one or more devices of the analytical device to transfer an aliquot of at least one of the first and second samples in purified form to a storage container for use after completion of at least one of steps (j) and (m). the controller is configured to send instructions to one or more devices of the analytical device to close the first and second reaction vessels, respectively, before steps (i) and (l); step (l) is initiated before step (i) is completed; step (i) is completed before step (l) is initiated; the first and second nucleic acid amplification reactions require thermal cycling; the first and second nucleic acid amplification reactions are PCR reactions; the first and second nucleic acid amplification reactions are real-time amplifications; the amplification oligomers of the first unit dose reagent are used to perform an IVD assay and the amplification oligomers of the second solvent are used to perform an LDT.

[0049] In another embodiment, a method for developing a nucleic acid amplification assay using an automated analyzer is disclosed. The method may include: (a) associating a nucleic acid amplification assay with a sample contained in a sample-receiving container, the nucleic acid amplification assay being defined, at least in part, by a set of user-defined assay parameters; and (b) performing the nucleic acid amplification assay on the sample. The performing the nucleic acid amplification assay may include: (i) dissolving a unit-dose reagent in a solvent, the solvent including one or more amplification oligomers suitable for amplifying a region of the analyte or a nucleic acid bound to the analyte in the nucleic acid amplification assay, the unit-dose reagent not including amplification oligomers for performing the nucleic acid amplification assay; (ii) forming a reaction mixture from the dissolved unit-dose reagent and the sample; and (iii) exposing the reaction mixture to temperature cycling conditions associated with the nucleic acid amplification assay. The method may also include (c) recording raw data related to the nucleic acid amplification assay from the analytical device; (d) processing the recorded raw data using one or more of the user-defined assay parameters; (e) using the processed data to generate intermediate results of the nucleic acid amplification assay; (f) modifying one or more of the user-defined assay parameters based on the generated results to generate a modified set of user-defined assay parameters; (g) reprocessing the recorded raw data using one or more of the modified set of user-defined assay parameters; and (h) using the reprocessed data to generate results of the nucleic acid amplification assay.

[0050] Various embodiments of the disclosed method may alternatively or additionally include one or more of the following aspects: the method may further include (i) prior to step (f), determining whether the intermediate results generated in step (e) match the expected results; (j) performing step (f) if the intermediate results generated in step (e) do not match the expected results; and (k) associating an altered set of user-defined assay parameters with the nucleic acid amplification assay if the intermediate results generated in step (e) match the expected results; wherein the solvent is contained in a vial of a plurality of vials supported by a container support disposed in an analytical device, and each vial of the plurality of vials is identical. one or more assay parameters from the set of user-defined assay parameters define a temperature profile to be used in the temperature cycling conditions used in step (b)(iii); processing the recorded raw data in step (d) includes removing data corresponding to a selected cycle number from the recorded raw data, the selected cycle number being based on an assay parameter from the set of user-defined assay parameters; processing the recorded raw data in step (d) includes correcting a slope of the recorded raw data based on one or more assay parameters from the set of user-defined assay parameters.

[0051] In another embodiment, a computer-implemented method for determining the amount of an analyte in a sample is disclosed. The method may include: (a) associating a nucleic acid amplification assay with the sample, the nucleic acid amplification assay being defined at least in part by a set of user-defined assay parameters; (b) performing the nucleic acid amplification assay on the sample, where performing the nucleic acid amplification assay may include: (i) dissolving a unit-dose reagent in a solvent, the solvent including one or more amplification oligomers suitable for amplifying a region of the analyte or a nucleic acid bound to the analyte in the nucleic acid amplification assay, the unit-dose reagent not including amplification oligomers for performing the nucleic acid amplification assay; (ii) forming a reaction mixture from the dissolved unit-dose reagent and the sample; and (iii) exposing the reaction mixture to temperature conditions to form an amplification product. The method may also include (c) collecting data using a signal measurement device contemporaneously with the formation of amplification product, wherein collecting data includes periodic measurements of fluorescence indicative of the amount of amplification product formed during the exposure; and (d) when performed by a computer, using a computer programmed with an algorithm configured to cause the computer to access the collected data of step (c), (i) receive one or more user-defined assay parameters from a user, wherein the one or more user-defined assay parameters are variables used to process the collected data, (ii) process the collected data using one or more of the user-defined assay parameters to create processed data, (iii) calculate a result indicative of the amount of analyte in the sample from the processed data using one or more of the user-defined assay parameters, and (iv) determine whether the result determined in step (d)(iii) is a valid result using one or more of the user-defined assay parameters.

[0052] In another embodiment, a method for developing a nucleic acid amplification assay for an automated analyzer is disclosed. The method may include (a) inputting user-defined assay parameters into a computer system that at least partially define a nucleic acid amplification assay to be performed on a sample placed on the analyzer. The inputting step may include (i) selecting one or more detection parameters, each detection parameter indicating a wavelength of fluorescence data recorded by the analyzer during the nucleic acid amplification assay, and (ii) selecting one or more temperature profile parameters, the temperature profile parameters defining a temperature profile to which an amplification reaction mixture in the analyzer is exposed during the nucleic acid amplification assay. The amplification reaction mixture is configured to be formed in the analyzer by (1) dissolving a unit-dose reagent that does not contain amplification oligomers for performing the nucleic acid amplification assay in a solvent that includes one or more amplification oligomers configured to amplify an analyte of interest in the sample during the nucleic acid amplification assay, and (2) forming an amplification reaction mixture with the dissolved unit-dose reagent and the sample. The inputting step may also include (iii) selecting data analysis parameters, which are variables used in a data processing algorithm that processes data re-encoded by the analyzer during the nucleic acid amplification assay before a result of the nucleic acid amplification assay is calculated. The method may also include (b) defining an assay protocol for the nucleic acid amplification assay using the input user-defined assay parameters, and (c) associating the assay protocol with the sample.

[0053] In another embodiment, a method for establishing an assay protocol for performing a nucleic acid amplification assay on an automated analyzer is disclosed. The automated analyzer can be configured to perform a nucleic acid amplification assay on one or more samples placed in the analyzer using one or more system-defined assay parameters and one or more user-defined assay parameters. The method can include (a) inputting, into a computer independent of the analyzer, a plurality of user-defined assay parameters that at least partially define the nucleic acid amplification assay. The inputted plurality of user-defined assay parameters includes one or more user-defined assay parameters used by the analyzer during the nucleic acid amplification assay. The inputting step can include (i) selecting one or more detection parameters, each detection parameter indicating a wavelength of fluorescence recorded by the analyzer during the nucleic acid amplification assay; (ii) selecting one or more assay process parameters, each assay process parameter indicating process conditions to which the reaction mixture is exposed during the nucleic acid amplification assay; and (iii) selecting one or more data analysis parameters, each data analysis parameter being a variable used in a data processing algorithm that processes data recorded by the analyzer during the nucleic acid amplification assay before a result of the nucleic acid amplification assay is calculated. The method may also include (b) establishing an assay protocol using at least a plurality of user-defined assay parameters entered into the computer, and (c) transferring the established assay protocol from the computer to an analytical device, where the analytical device is not configured to change any of the plurality of user-defined assay parameters entered into the computer. The method may also include, on the analytical device, (a) associating the transferred assay protocol with samples of the one or more samples placed in the analytical device, (b) performing a nucleic acid amplification assay on the sample, and (c) recording data from the performed nucleic acid amplification assay.

[0054] In another embodiment, a method for performing a lab-developed test for extracting, amplifying, and detecting a nucleic acid analyte on an automated analytical device is disclosed. The method may include (a) using a computer to select, define, or modify one or more user-defined assay parameters of a protocol for performing the lab-developed test on the analytical device. Each parameter of the protocol defines a step to be performed by the analytical device during the lab-developed test. The method may also include (b) performing the lab-developed test using the protocol of step (a). The analytical device stores one or more system-defined assay parameters for performing the lab-developed test.

[0055] Various embodiments of the disclosed method may alternatively or additionally include one or more of the following aspects: during step (b), dissolving a non-liquid reagent comprising a polymerase and a nucleoside triphosphate in a solution containing oligonucleotides for performing a lab-developed test; during step (b), dissolving a non-liquid reagent comprising a polymerase, a nucleoside triphosphate, and an oligonucleotide for performing an in vitro diagnostic assay, wherein the analytical device does not support a container containing the non-liquid reagent comprising the oligonucleotides for performing a lab-developed test; the computer is a personal computer; the computer is not connected to an analytical device; the method further comprises: After step (a) and before step (b), the method further includes exporting the protocol and installing the protocol on the analytical device; user-defined assay parameters are selected, defined, or modified on one or a series of screens displayed on the computer; step (a) includes selecting a default temperature profile; step (a) includes defining one or more parameters of a temperature profile for performing a thermal cycling reaction, the one or more parameters including the temperature of each temperature step of the thermal cycling reaction, the duration of each temperature step, and the number of temperature cycles of the thermal cycling reaction; each cycle of the thermal cycling reaction consists of at least two different temperature steps.

[0056] In another embodiment, a method for determining whether any of multiple forms of nucleic acid analytes are present in a sample is disclosed. The method may include (a) providing the sample to an analytical device, (b) producing a purified form of the sample by exposing the sample to reagents and conditions suitable for isolating and purifying multiple forms of nucleic acid analytes, and (c) dissolving an amplification reagent in a first solvent. The amplification reagent may contain oligonucleotides sufficient to amplify and detect a first region of the first form of the analyte, and the first solvent may contain one or more oligonucleotides that, in combination with the oligonucleotides of the amplification reagent, may be sufficient to amplify and detect a second region of the second form of the analyte. The one or more oligonucleotides of the first solvent may be insufficient to amplify and detect the first or second form of the analyte. The first and second regions may each contain a different nucleotide base sequence. The method may also include (d) contacting the purified form of the sample with dissolved amplification reagents, thereby forming an amplification reaction mixture; (e) exposing the amplification reaction mixture to temperature conditions sufficient to amplify first and second regions of the first and second forms of the analyte, respectively; and (f) determining whether at least one of the first and second forms of the analyte is present in the sample.

[0057] Various embodiments of the disclosed methods may alternatively or additionally include one or more of the following aspects: the sample is provided to the analytical device during step (a) in a container supported by a container-holding rack; the sample in a purified form contains at least one of the analytes in first and second forms; step (b) comprises immobilizing at least one of the analytes in the first and second forms on a solid support; the solid support is magnetically responsive; step (b) comprises removing non-immobilized components of the sample while exposing the sample to a magnetic field; step (b) comprises resuspending the solid support in a buffer after removing the non-immobilized components of the sample; step (b) comprises exposing the sample to a capture probe capable of specifically immobilizing the analytes in the first and second forms on the solid support; step (b) comprises non-specifically immobilizing at least one of the analytes in the first and second forms on the solid support; the amplification reagent is a dry reagent; the amplification reagent contains a polymerase and nucleoside triphosphates; the first solvent does not contain a polymerase or nucleoside triphosphates; the first solvent is contained in a vial supported by a first holder; the first holder supports a plurality of vials, at least some of which contain a solvent containing a set of amplification oligonucleotides that are not contained in the first solvent; the analytical device contains a second solvent for dissolving the amplification reagent, the second solvent not containing any oligonucleotides; the second solvent is contained in a second holder having a fluidically connected sealed liquid reservoir and an access chamber, the access chamber being accessible by a fluid transfer device for removing the second solvent from the second holder; the amplification reagent is stored and dissolved in a mixing well of a reagent pack, the reagent pack including a plurality of mixing wells; the amplification reaction mixture is formed in a reaction vessel different from the reagent pack.

[0058] Various embodiments of the disclosed method may alternatively or additionally include one or more of the following aspects: closing the reaction vessel with a cap prior to step (e), wherein the cap engages the reaction vessel with a friction fit or an interference fit; centrifuging the closed reaction vessel prior to step (e), wherein the centrifugation step is performed in a centrifuge having at least one access port for receiving the reaction vessel; the reaction vessel is a distinct and separate vessel that is not physically connected to any other reaction vessel as part of an integrated unit; the temperature conditions include thermal cycling associated with a PCR reaction; the determining step is performed in real time; the first solvent contains at least one amplification oligonucleotide for amplifying a second region of the analyte in a second form, and the first solvent is the amplification reagent does not contain a detection probe for determining the presence of the analyte in any form; the amplification reagent contains detection probes for detecting the analyte in first and second forms; the first solvent contains a first detection probe for determining the presence of the analyte in the second form; the amplification reagent contains a second detection probe for determining the presence of the analyte in the first form, and the first and second probes are distinguishable from each other in step (f); the amplification reagent contains a second detection probe for determining the presence of the analyte in the first form, and the first and second probes are indistinguishable from each other in step (f); the first and second forms of the analyte are different types, subtypes, or variants of organisms or viruses; the second form of the analyte is a mutant form of the first form of the analyte; the amplification reagent is a component of an IVD assay and the first solvent is an ASR.

[0059] In another embodiment, a method for determining whether any of multiple forms of nucleic acid analytes are present in a sample is disclosed. The method may include (a) providing the sample to an analytical device; (b) producing a purified form of the sample by exposing the sample to reagents and conditions sufficient to isolate and purify the multiple forms of nucleic acid analytes; and (c) dissolving an amplification reagent in a first or second solvent. Each of the first and second solvents may be supported by the analytical device. The amplification reagent may contain oligonucleotides sufficient to amplify and detect a first region of the first form of the analyte but not a region of the second form of the analyte. The first solvent may not contain any oligonucleotides. The second solvent may contain one or more oligonucleotides that, in combination with the oligonucleotides of the amplification reagent, may be sufficient to amplify and detect a second region of the second form of the analyte. The oligonucleotides of the second solvent may be insufficient to amplify and detect the first or second form of the analyte. The first and second regions may each contain a different nucleotide base sequence. The method may also include (d) contacting the purified form of the sample with dissolved amplification reagents, thereby forming an amplification reaction mixture; (e) exposing the amplification reaction mixture to temperature conditions sufficient to amplify first and second regions of the first and second forms of the analyte, respectively; and (f) determining whether at least one of the first and second forms of the analyte is present in the sample.

[0060] Various embodiments of the disclosed methods may alternatively or additionally include one or more of the following aspects: the sample is provided to the analytical device during step (a) in a container supported by a container-holding rack; prior to step (c), selecting a first or second solvent for dissolving the amplification reagent; the selecting step includes reading a machine-readable label on the container that instructs the analytical device to perform a first or second assay with the sample, wherein the amplification reagent is dissolved in the first solvent in the first assay and the amplification reagent is dissolved in the second solvent in the second assay; the machine-readable label is a barcode label, and the machine-readable label is read by a barcode reader of the analytical device; the selecting step includes providing a user input to instruct the analytical device to perform a first or second assay with the sample, wherein the amplification reagent is dissolved in the first solvent in the first assay and the amplification reagent is dissolved in the second solvent. the sample is dissolved in a second solvent in an assay; user input is received via a mouse, keyboard, or touchscreen of the analytical device; the sample in a purified form contains at least one of the analytes in the first and second forms; step (b) includes immobilizing at least one of the analytes in the first and second forms on a solid support; the solid support is magnetically responsive; step (b) includes removing non-immobilized components of the sample while exposing the sample to a magnetic field; step (b) includes resuspending the solid support in a buffer after removing the non-immobilized components of the sample; step (b) includes exposing the sample to a capture probe capable of specifically immobilizing the analytes in the first and second forms on the solid support; step (b) includes non-specifically immobilizing at least one of the analytes in the first and second forms on the solid support; the amplification reagent is a dry reagent.

[0061] Various embodiments of the disclosed methods may alternatively or additionally include one or more of the following aspects: the amplification reagents are lyophilized; the amplification reagents are unit-dose reagents; the amplification reagents contain a polymerase and nucleoside triphosphates; the first and second solvents do not contain a polymerase or a nucleoside triphosphate; the first solvent is contained in a vial supported by a first holder; the second solvent is contained in a second holder having a fluidically connected sealed liquid reservoir and an access chamber, which may be accessible by a fluid transfer device for removing the second solvent from the second holder; the amplification reagents are stored and dissolved in mixing wells of a reagent pack, which reagent pack includes a plurality of mixing wells; the amplification reaction mixture is formed in a reaction vessel separate from the reagent pack; the reaction vessel is not capped prior to step (e). the step of closing the reaction vessel with a cap, the cap engaging the reaction vessel with a friction fit or an interference fit; the step of centrifuging the closed reaction vessel before step (e), the centrifugation step being carried out in a centrifuge having at least one access port for receiving the reaction vessel; the reaction vessel being a different and separate vessel not physically connected to any other reaction vessel as part of an integrated unit; the temperature conditions including thermal cycling associated with a PCR reaction; the determining step being carried out in real time; the first solvent containing at least one amplification oligonucleotide for amplifying a second region of the second form of the analyte, and the first solvent not containing a detection probe for determining the presence of any form of the analyte; the amplification reagent containing detection probes for detecting the first and second forms of the analyte.

[0062] Various embodiments of the disclosed methods may alternatively or additionally include one or more of the following aspects: the first solvent contains a first detection probe for determining the presence of the analyte in a second form; the amplification reagent contains a second detection probe for determining the presence of the analyte in a first form, and the first and second probes are distinguishable from each other in step (f); the amplification reagent contains a second detection probe for determining the presence of the analyte in a first form, and the first and second probes are indistinguishable from each other in step (f); the first and second forms of the analyte are different types, subtypes, or variants of organisms or viruses; the second form of the analyte is a mutant form of the first form of the analyte; the amplification reagent and the second solvent are each components of an IVD assay, and the first solvent is an ASR.

[0063] In another embodiment, a method for determining the presence of multiple nucleic acid analytes in a sample is disclosed. The method may include (a) providing the sample to an analytical device; (b) producing a purified form of the sample by exposing the sample to reagents and conditions sufficient to isolate and purify the multiple nucleic acid analytes; and (c) dissolving an amplification reagent in a first solvent. The amplification reagent may contain a first set of oligonucleotides sufficient to amplify and detect a first region of a first analyte of the multiple nucleic acid analytes. The first solvent may contain a second set of oligonucleotides sufficient to amplify and detect a second region of a second analyte of the multiple nucleic acid analytes. The first set of oligonucleotides may be insufficient to amplify and detect a region of the second analyte. The second set of oligonucleotides may be insufficient to amplify and detect a region of the first analyte. The method may also include (d) contacting the purified form of the sample with dissolved amplification reagents, thereby forming an amplification reaction mixture; (e) exposing the amplification reaction mixture to temperature conditions sufficient to amplify first and second regions of the first and second analytes, respectively; and (f) determining whether at least one of the first and second analytes is present in the sample.

[0064] Various embodiments of the disclosed methods may alternatively or additionally include one or more of the following aspects: the sample is provided to the analytical device during step (a) in a container supported by a container-holding rack; the sample in a purified form contains at least one of the first and second analytes; step (b) comprises immobilizing at least one of the first and second analytes on a solid support; the solid support is magnetically responsive; step (b) comprises removing non-immobilized components of the sample while exposing the sample to a magnetic field; step (b) comprises resuspending the solid support in a buffer after removing the non-immobilized components of the sample; step (b) comprises exposing the sample to a capture probe capable of specifically immobilizing the first and second analytes on the solid support; step (b) comprises non-specifically immobilizing at least one of the first and second analytes on the solid support; the amplification reagent is a drug; the amplification reagent is a lyophilized product; the amplification reagent is a unit-dose reagent; the amplification reagent contains a polymerase and nucleoside triphosphates; the first solvent does not contain the polymerase or the nucleoside triphosphates; the first solvent is contained in a vial supported by a first holder; the first holder supports a plurality of vials, at least some of which contain a solvent containing a set of amplification oligonucleotides that are not contained in the first solvent; the analytical device contains a second solvent for dissolving the amplification reagent, the second solvent not containing any of the oligonucleotides; the second solvent is contained in a second holder having a fluidically connected sealed liquid reservoir and an access chamber, the access chamber being accessible by a fluid transfer device for removing the second solvent from the second holder; the amplification reagent is stored and dissolved in a mixing well of a reagent pack, the reagent pack including a plurality of mixing wells.

[0065] Various embodiments of the disclosed method may alternatively or additionally include one or more of the following aspects: the amplification reaction mixture is formed in a reaction vessel separate from the reagent pack; prior to step (e), closing the reaction vessel with a cap, the cap engaging the reaction vessel with a friction fit or an interference fit; prior to step (e), centrifuging the closed reaction vessel, the centrifugation step being performed in a centrifuge having at least one access port for receiving the reaction vessel; the reaction vessel is a distinct and separate vessel that is not physically connected to any other reaction vessel as part of an integrated unit; the temperature conditions are such that the reaction vessel undergoes thermal cycling associated with a PCR reaction. the determining step is performed in real time; the amplification reagent contains detectably labeled probes for determining the presence of the first and second analytes; the amplification reagent contains a first detection probe for determining the presence of the first analyte and the first solvent contains a second probe for determining the presence of the second analyte; the first and second probes are distinguishable from each other in step (f); the first and second probes are indistinguishable from each other in step (f); the first and second analytes are not different forms of the same analyte; the first and second analytes are different genes that confer antibiotic resistance to an organism; the amplification reagent is a component of an IVD assay and the first solvent is ASR.

[0066] In another embodiment, a method for quantifying a target nucleic acid analyte in a sample is disclosed. The method may include: (a) performing a cyclic amplification reaction on a sample containing or suspected of containing the target nucleic acid analyte in the presence of a first probe comprising a first fluorophore, wherein the first probe exhibits target nucleic acid analyte-dependent fluorescence; and (b) acquiring fluorescence measurements from the first probe during multiple cycles of the cyclic amplification reaction, wherein the multiple acquired fluorescence measurements constitute a baseline segment. The method may also include: (c) smoothing at least a portion of the fluorescence measurements; (d) determining the slope of the baseline segment; and (e) adjusting the fluorescence measurement for each cycle or time at which the fluorescence measurement is acquired by subtracting a value that depends on the slope of the baseline segment and the time or cycle at which the measurement was acquired, resulting in an adjusted fluorescence measurement. The method may further include (f) determining a cycle threshold (Ct) value from a value comprising at least a portion of the adjusted fluorescence measurements, or determining that the target nucleic acid analyte is absent or not present in an amount above the limit of detection, thereby quantifying the target nucleic acid analyte.

[0067] Various embodiments of the disclosed methods may alternatively or additionally include one or more of the following aspects: where smoothing at least a portion of the fluorescence measurements includes providing a moving average to a portion of the fluorescence measurements; where applying a moving average includes averaging over M cycles, where M is 3, 4, 5, 6, 7, 8, 9, 10, or 11, and optionally, the fluorescence measurements from cycles 1 through M / 2 (rounded down) and N / M / 2 (rounded up) through N are not moving averaged, and N is the number of cycles over which fluorescence measurements are taken; where applying a moving average includes averaging over 5 cycles, optionally, the fluorescence measurements from cycles 1, 2, N-1, and N are not moving averaged, and N is the number of cycles over which fluorescence measurements are taken; or where smoothing at least a portion of the fluorescence measurements includes polynomial fitting. the method may further include determining an established baseline value and subtracting the estimated baseline value from the fluorescence measurements; embodiments in which determining the estimated baseline value includes fitting the fluorescence measurements to a logistic regression model; embodiments in which the logistic regression model is a four-parameter logistic regression model; embodiments in which the estimated baseline value is a minimum asymptote of the logistic regression model; embodiments in which determining the estimated baseline value and subtracting the estimated baseline value from the fluorescence measurements is performed after smoothing at least a portion of the fluorescence measurements; and embodiments in which determining the estimated baseline value and subtracting the estimated baseline value from the fluorescence measurements is performed before adjusting the fluorescence measurements by subtracting a value that depends on the slope of the baseline segment and the time or cycle in which the measurements were made.

[0068] Various embodiments of the disclosed methods may alternatively or additionally include one or more of the following aspects: the method may further include leveling the fluorescence measurements by additively adjusting the fluorescence measurements so that no fluorescence measurements have a value less than zero; performing crosstalk correction on the fluorescence measurements from the first probe; aspects in which the crosstalk correction includes subtracting an estimate of the bleed-through signal from the second probe from the fluorescence measurements from the first probe, wherein the second probe comprises a second fluorophore, and the second fluorophore and the first fluorophore have overlapping emission spectra, and the estimate of the bleed-through signal is dependent on a concurrent fluorescence measurement from the second probe and a predetermined ratio of the observed fluorescence from the second probe to the estimated bleed-through signal from the second probe in the fluorescence measurement of the first probe; the method may further include subtracting a bleed-through signal from a third probe from the fluorescence measurement from the first probe, wherein the third probe comprises a third fluorophore, the third fluorophore and the first fluorophore have overlapping emission spectra, and the estimate of the bleed-through signal depends on a concurrent fluorescence measurement from the third probe and a predetermined ratio of the observed fluorescence from the third probe to the estimated bleed-through signal from the third probe in the fluorescence measurement of the first probe; an embodiment in which the concurrent fluorescence measurement from the second probe is obtained during the same cycle of the cyclic amplification reaction as the fluorescence measurement from the first probe from which the estimate of the bleed-through signal is subtracted; an embodiment in which the concurrent fluorescence measurement from the second probe is obtained within 1 minute, 30 seconds, 15 seconds, or 10 seconds of the fluorescence measurement from the first probe from which the bleed-through signal is subtracted; an embodiment in which the first and second probes are in first and second reaction vessels, the second reaction vessel being sufficiently close to the first reaction vessel such that fluorescence from the second probe is detected during the acquisition of the fluorescence measurement from the first probe; and an embodiment in which the first and second probes comprise the same fluorophore or fluorophores with indistinguishable emission spectra.

[0069] Various embodiments of the disclosed methods may alternatively or additionally include one or more of the following aspects: a first and a second probe are in a first reaction vessel, and the second probe exhibits nucleic acid analyte-dependent fluorescence for a second target that is different from the target nucleic acid for which the first probe exhibits nucleic acid analyte-dependent fluorescence; a first and a second probe comprise fluorophores that have distinct but overlapping emission spectra; a subtraction of an estimate of the bleed-through signal from the second probe from the fluorescence measurement from the first probe is performed after smoothing at least a portion of the fluorescence measurement; a subtraction of an estimate of the bleed-through signal from the second probe from the fluorescence measurement from the first probe is performed before adjusting the fluorescence measurement by subtracting a value that is dependent on the slope of the baseline segment and the time or cycle at which the measurement was taken; a determination of the slope of the baseline segment includes determining a slope between each adjacent cycle pair of a plurality of cycles of the amplification reaction until a predetermined slope is reached or exceeded for at least the cycle pair, and and identifying the baseline segment as consisting of fluorescence measurements from a cycle earlier than the one after the cycle pair at which the slope was reached or exceeded; embodiments in which determining the slope of the baseline segment comprises determining the difference between fluorescence measurements from each adjacent cycle pair of multiple cycles of the amplification reaction until a predetermined difference is reached or exceeded for at least the cycle pair, and identifying the baseline segment as consisting of fluorescence measurements from a cycle earlier than the one after the cycle pair at which the predetermined difference was reached or exceeded; embodiments in which subtracting a value dependent on the slope of the baseline segment and the time or cycle at which the measurement was obtained reduces the slope of the baseline segment to zero; embodiments in which the slope of the baseline segment is determined to be zero if the squared Pearson correlation coefficient of the linear regression of the baseline segment is less than a predetermined threshold; and embodiments in which the slope of the baseline segment is determined to be zero if the linear regression of the baseline segment has a negative slope with increasing time or cycle number.

[0070] Various embodiments of the disclosed methods may alternatively or additionally include one or more of the following aspects: aspects in which determining a Ct value from the adjusted fluorescence measurements, or determining that the target nucleic acid analyte is absent or not present in an amount above the detection limit, includes (a) subtracting the minimum adjusted fluorescence measurement value from the maximum adjusted fluorescence measurement value, thereby resulting in a fluorescence range value, and (b) determining that the target nucleic acid analyte is not present in an amount above the detection limit if the fluorescence range value is below the predetermined threshold; aspects in which at least one adjusted fluorescence measurement is above the predetermined threshold and the Ct value is determined as the earliest cycle number at which an adjusted fluorescence measurement is above the predetermined threshold; aspects in which at least one adjusted fluorescence measurement is above the predetermined threshold and the Ct value is determined as (a) the cycle at which the earliest adjusted fluorescence measurement above the predetermined threshold occurred, (b) the earliest adjusted fluorescence measurement above the predetermined threshold, (c) the cycle at which the earliest adjusted fluorescence measurement above the predetermined threshold occurred, or (d) the earliest adjusted fluorescence measurement above the predetermined threshold. an embodiment in which the Ct value is determined from values ​​including the fluorescence value of an adjusted fluorescence measurement from a cycle preceding the cycle in which the earliest adjusted fluorescence measurement equal to or greater than the predetermined threshold occurred; an embodiment in which the Ct value is predicted from interpolation of fluorescence values ​​between the adjusted fluorescence measurement from the cycle in which the earliest adjusted fluorescence measurement equal to or greater than the predetermined threshold occurred and the adjusted fluorescence measurement from the preceding cycle; an embodiment in which the Ct value is a cycle fraction corresponding to the predetermined threshold in the interpolation; an embodiment further including authentication of the fluorescence measurement obtained from the first probe; an embodiment in which the authentication includes confirming that the fluorescence measurement includes at least one measurement from each cycle of multiple cycles of the cyclic amplification reaction; an embodiment in which the authentication includes confirming that the adjusted fluorescence measurement does not include both (i) an adjusted fluorescence measurement equal to or greater than the predetermined threshold from the first cycle and (ii) an adjusted fluorescence measurement less than the predetermined value from a second cycle that is slower than the first cycle.

[0071] Various embodiments of the disclosed methods may alternatively or additionally include one or more of the following aspects: aspects in which the method is performed using a system including one or more fluorescence detectors configured to measure fluorescence from the sample, a thermocycling device configured to regulate the temperature of the sample, and a processor and memory operatively coupled to the one or more fluorescence detectors and the thermocycling device, thermocycling the sample, obtaining fluorescence measurements, smoothing at least a portion of the fluorescence measurements, determining the slope of a baseline segment, adjusting the fluorescence measurements, and determining a Ct value, or the absence or absence of a target nucleic acid analyte in an amount above the limit of detection; aspects in which the one or more fluorescence detectors are configured to detect fluorescence in multiple channels; aspects in which the first probe further comprises a quencher or a FRET acceptor and (i) comprises a self-complementary region, (ii) undergo a conformational change upon hybridization to the target nucleic acid analyte that quenches or reduces FRET transfer from the first fluorophore, or (iii) undergoes exonucleolysis after hybridization to the target nucleic acid analyte that releases the first fluorophore, thereby resulting in increased fluorescence, or (iv) undergoes cleavage after hybridization to a fragment of the primary probe that is cleaved after hybridization to the target nucleic acid analyte, where cleavage of the first probe releases the first fluorophore, thereby resulting in increased fluorescence; embodiments in which the cyclic amplification reaction is PCR; embodiments in which the plurality of cycles of the cyclic amplification reaction comprises 10 to 20, 21 to 25, 26 to 30, 31 to 35, 36 to 40, 41 to 45, or 46 to 50 cycles; and embodiments in which the plurality of cycles of cyclic amplification is an uninterrupted series of cycles.

[0072] The reagents described in the various embodiments above can be in liquid or non-liquid form. If the reagents are in non-liquid form, they can be in dry form, for example, lyophilized. In some embodiments, the reagents provided are conveniently provided in unit dose form. The present specification also provides, for example, the following items: (Item 1) 1. A system that allows a user to specify user-defined assay parameters of an assay protocol for processing a sample suspected of containing a target analyte, the assay protocol comprising computer-executable instructions that cause a computer-controlled automated analyzer to perform an assay in accordance with the assay protocol, the user-defined assay parameters comprising a portion of the computer-executable instructions, the system comprising: a first graphical user interface configured to allow the user to define analyte extraction parameters, the analyte extraction parameters including one or more computer-executable instructions to be executed by the analytical device to perform an extraction process to extract the target analyte from the sample; and a second graphical user interface configured to allow the user to define target parameters, the target parameters including one or more computer-executable instructions that specify one or more channels of a multi-channel signal detector of the analytical device to be used to detect the target analyte; and a third graphical user interface configured to enable the user to define one or more temperature parameters of a temperature profile, the one or more temperature parameters of the temperature profile including computer-executable instructions specifying temperature conditions to which a reaction mixture will be exposed by the analytical device to amplify the target analyte; and (Item 2) 2. The system of claim 1, wherein the user-defined assay parameters of the assay protocol are defined using a first computer that is separate from a second computer controlling the analytical instrument. (Item 3) 3. The system of claim 1 or 2, wherein the first graphical user interface is further configured to allow the user to specify a name for the assay protocol. (Item 4) 4. The system of claim 1, wherein the third graphical user interface is further configured to allow the user to specify an analyte type for the temperature profile, the analyte type comprising one of DNA and RNA / DNA. (Item 5) 5. The system of any one of items 1 to 4, wherein the extraction process includes computer-executable instructions that define the types and amounts of reagents to be combined with the sample by the analytical device. (Item 6) 6. The system of any one of items 1 to 5, wherein the extraction process further comprises computer-executable instructions defining a sample aspiration height. (Item 7) 7. The system of any one of items 1 to 6, wherein the extraction process comprises a target capture procedure. (Item 8) 8. The system of any one of items 1 to 7, wherein the first graphical user interface is configured to allow the user to select analyte extraction parameters from two or more predefined analyte extraction parameters. (Item 9) 9. The system of any one of items 1 to 8, wherein the multi-channel signal detector is configured to detect a signal associated with amplification of the target analyte. (Item 10) 10. The system of item 9, wherein the signal is a fluorescent signal having a specific wavelength or range of wavelengths. (Item 11) 11. The system of any one of items 1 to 10, wherein the second graphical user interface is configured to visually present a plurality of channels, each of which is individually selectable by a user. (Item 12) Item 12. The system of item 11, wherein the second graphical user interface is further configured to visually present an input area in which the user may input an analyte name to be associated with each selected channel. (Item 13) 13. The system of any one of items 1 to 12, wherein the one or more temperature parameters include one or more of a temperature of each temperature step of a thermal cycling reaction, a duration of each temperature step, and a number of temperature cycles for the thermal cycling reaction. (Item 14) 14. The system of any one of items 1 to 13, wherein the third graphical user interface is configured to present a graph of temperature along a first axis and time along a second axis, the graph being divided into stages, each stage including one or more steps of constant temperature, and the third graphical user interface is configured to present interactive input elements that allow the user to define or modify the temperature and duration of each step and the number of at least one stage. (Item 15) 15. The system of any one of items 1 to 14, further comprising a protocol export graphical user interface configured to enable the user to define computer-executable instructions for exporting the assay protocol to a storage medium or a controller of the analytical device. (Item 16) 16. The system of any one of items 1 to 15, further comprising at least one data analysis parameter graphical user interface configured to allow the user to input one or more data analysis parameters, the data analysis parameters comprising computer-executable instructions executed by a data analysis computer for analyzing data collected by the analysis device while performing the assay according to the assay protocol. (Item 17) 17. The system of claim 16, wherein the data analysis computer and the computer on which the user-defined assay parameters are specified are the same computer. (Item 18) 18. The system of claim 16 or 17, wherein the at least one data analysis parameter graphical user interface includes a curve correction parameter graphical user interface configured to allow the user to input one or more curve correction parameters, the curve correction parameters including computer-executable instructions that specify one or more modifications to be made by the data analysis computer to data collected by the analytical device while performing the assay according to the assay protocol. (Item 19) Item 19. The system of item 18, wherein the one or more curve correction parameters are defined for analyzing data for each of one or more channels of the multichannel signal detector and include one or more of: an analysis start cycle defining a cycle in the data before which any collected data is discarded; a selectable baseline correction for subtracting background signal from the data; a baseline correction slope limit defining a curve slope beyond which baseline correction is not applied; and a crosstalk correction parameter for suppressing inter-channel signal crosstalk. (Item 20) 20. The system of any one of items 16 to 19, wherein the at least one data analysis parameter graphical user interface includes a positivity criteria parameter graphical user interface configured to allow the user to input one or more data evaluation positivity criteria, the data evaluation positivity criteria including computer-executable instructions specifying one or more criteria to be applied by the data analysis computer to determine a positive or negative result for the data collected by the analytical device while performing the assay according to the assay protocol. (Item 21) 21. The system of claim 20, wherein the one or more data evaluation positivity criteria are defined for evaluating data from each of one or more channels of the multichannel signal detector and include one or more of: a signal threshold above which the presence of the target analyte is indicated; a minimum slope at threshold defining the minimum slope of the curve crossing the signal threshold for which a positive result will be determined; and a maximum threshold cycle parameter defining the maximum number of cycles before reaching the signal threshold for which a positive result will be determined. (Item 22) 22. The system of claim 21, further comprising a data analysis graphical user interface configured to allow the user to select one or more channels of the multichannel signal detector for which data collected by the analytical device while performing the assay according to the assay protocol will be presented, display data analysis results for the one or more selected channels in at least one of tubular and graphical form along with one or more criteria from the data evaluation positivity criteria defined by the user using the positivity criteria parameter graphical user interface, and allow the user to modify one or more of the data evaluation positivity criteria and display the modified data analysis results in at least one of tubular and graphical form. (Item 23) 23. The system of claim 22, wherein the user-defined assay parameters of the assay protocol are specified and the data analysis graphical user interface is provided using a first computer that is separate from a second computer controlling the analytical instrument. (Item 24) 24. The system of any one of items 16 to 23, wherein the at least one data analysis parameter graphical user interface includes a channel validity criteria parameter graphical user interface configured to allow the user to input one or more channel validity criteria parameters, the channel validity criteria parameters including computer-executable instructions that assign values ​​to the data analysis computer for determining whether a signal measured by the multi-channel signal detector is within an expected range. (Item 25) 25. The system of claim 24, wherein the multi-channel signal detector comprises a fluorometer, and the one or more channel validity criteria parameters are defined for evaluating data from each of the one or more channels of the multi-channel signal detector and include one or more of a maximum background fluorescence, a minimum background fluorescence, and a minimum threshold cycle parameter that defines a minimum number of cycles before the signal threshold is reached for which a positive result will be determined. (Item 26) 26. The system of any one of items 16 to 25, wherein the at least one data analysis parameter graphical user interface includes a sample validity criteria parameter graphical user interface configured to allow the user to input one or more channel validity criteria parameters, the sample validity criteria including computer-executable instructions specifying one or more criteria to be applied by the data analysis computer to evaluate the validity of data collected by the analytical device while performing the assay according to the assay protocol. (Item 27) Item 27. The system of item 26, wherein the channel validity criteria parameters specify (i) whether the user is using or not using an internal standard in a channel of the multichannel signal detector, (ii) if the user is using an internal standard, whether a positive internal standard is required to indicate a valid test or whether any positive channel indicates a valid test, and (iii) if the user is not using an internal standard, whether any positive channel indicates a positive test. (Item 28) 28. The system of any one of items 1 to 27, further comprising a reagent graphical user interface that enables the user to define computer-executable instructions that specify locations within the analytical device for accessing one or more reagents for amplifying and detecting the target analyte while performing the assay according to the assay protocol. (Item 29) 30. The system of claim 28, wherein the user-defined assay parameters of the assay protocol are defined using a first computer that is separate from a second computer on which the reagent graphical user interface is provided. (Item 30) 30. The system of claim 29, wherein the second computer is the computer of the analytical device. (Item 31) 31. The system of any one of items 1 to 30, wherein the assay protocol comprises a combination of the user-defined assay parameters and one or more system-defined assay parameters. (Item 32) 32. The system of claim 31, wherein one or more of the system-defined assay parameters are pre-programmed into the analytical device, and optionally, the system-defined assay parameters are stored in a protocol library. (Item 33) 1. A method for performing a nucleic acid assay on an automated analyzer, comprising: (a) presenting an interface on a computer to enable a user to use the computer to select, define, or modify one or more user-defined assay parameters of a protocol for extracting, amplifying, and detecting nucleic acid analytes on the analytical device; (b) receiving input of user-defined assay parameters into the interface by the user; (c) assembling said protocol from said received user-defined assay parameters in combination with one or more system-defined assay parameters; (d) storing the protocol as a series of computer-executable instructions for execution by the analytical device, the user-defined assay parameters and the system-defined assay parameters of the protocol defining steps to be performed by the analytical device to perform the nucleic acid assay; (e) executing the computer-executable instructions of the protocol with the analytical device to perform the nucleic acid assay. (Item 34) 34. The method of claim 33, wherein step (e) is performed while another nucleic acid assay is being performed on the analytical device according to a protocol based solely on system-defined assay parameters. (Item 35) 35. The method according to any one of items 33 to 34, wherein the computer is a personal computer. (Item 36) 36. The method of claim 35, wherein the computer is not connected to the analytical device. (Item 37) 37. The method of claim 35, wherein step (d) comprises exporting the protocol from a personal computer and installing the protocol on the analytical device. (Item 38) 38. The method of any one of items 33 to 37, wherein the interface comprises one or a series of screens displayed on the computer. (Item 39) 39. The method of any one of items 33 to 38, wherein the user-defined assay parameters comprise a default temperature profile selected by the user via the interface. (Item 40) 39. The method of any one of items 33 to 38, wherein the user-defined assay parameters include one or more parameters of a temperature profile for performing a thermocycling reaction, the one or more parameters of the temperature profile comprising computer-executable instructions specifying temperature conditions to which a reaction mixture will be exposed by the analytical device while performing the nucleic acid assay, and the one or more parameters of the temperature profile including one or more of a temperature of each temperature step of the thermocycling reaction, a duration of each temperature step, and a number of temperature cycles for the thermocycling reaction. (Item 41) Item 41. The method according to item 40, wherein each cycle of the thermocycling reaction consists of at least two different temperature steps. (Item 42) 42. The method of any one of items 33 to 41, wherein the user-defined assay parameters include analyte extraction parameters comprising computer-executable instructions executed by the analytical device to perform a process for extracting the nucleic acid analyte from a sample. (Item 43) 43. The method of claim 42, wherein step (e) comprises executing the computer-executable instructions of the analyte extraction parameters by the analytical device to perform the process for extracting the nucleic acid analyte from the sample, if present in the sample. (Item 44) 44. The method of any one of items 33 to 43, wherein the user-defined assay parameters include target parameters comprising computer-executable instructions that specify one or more channels of a multi-channel signal detector of the analytical device to be used for detecting the nucleic acid analyte. (Item 45) 45. The method of claim 44, wherein step (e) comprises executing the computer-executable instructions for the target parameter to determine the presence or absence of the nucleic acid analyte using the designated channel. (Item 46) 46. ​​The method of any one of items 33 to 45, wherein the user-defined assay parameters further comprise data analysis parameters, the data analysis parameters comprising computer-executable instructions executed by a data analysis computer for analyzing data collected by the analytical device during step (e). (Item 47) Item 47. The method of item 46, wherein the method further comprises the step of the analytical device collecting assay result data during step (e), and further comprising analyzing the data collected during step (e) based on the data analysis parameters. (Item 48) Item 48. The method of item 46 or 47, wherein the data analysis parameters include curve correction parameters, the curve correction parameters comprising computer-executable instructions that specify one or more modifications to be made by the data analysis computer to the data collected during step (e). (Item 49) 49. The method of claim 48, wherein the curve correction parameters include one or more of an analysis start cycle, which defines a cycle in the data before which any collected data is discarded; a selectable baseline correction for subtracting background signal from the data; a baseline correction slope limit, which defines a curve slope beyond which baseline correction is not applied; and a crosstalk correction parameter for suppressing inter-channel signal crosstalk. (Item 50) 50. The method of claim 49, further comprising the data analysis computer modifying the collected assay result data according to one or more of the analysis initiation cycle, the baseline correction, the baseline correction slope limit, and the crosstalk correction parameters. (Item 51) 51. The method of any one of items 33 to 50, wherein the data analysis parameters include one or more data evaluation positivity criteria. (Item 52) 52. The method of claim 51, further comprising the step of the data analysis computer determining a positive or negative result of the nucleic acid assay performed during step (e) based on the data evaluation positivity criteria. (Item 53) 53. The method of claim 51 or 52, wherein the one or more data evaluation positivity criteria comprise one or more of a signal threshold above which the presence of the nucleic acid analyte is indicated, a minimum slope at threshold defining the minimum slope of the curve across the signal threshold for which a positive result will be determined, and a maximum threshold cycle parameter defining the maximum number of cycles before the signal threshold is reached for which a positive result will be determined. (Item 54) 54. The method of any one of items 33 to 53, wherein the data analysis parameters further include efficacy criteria parameters, and the method further comprises the step of the data analysis computer determining whether the signal measured by the signal detector of the analytical device during step (e) is within an expected range based on the efficacy criteria parameters. (Item 55) 55. The method of any one of items 33 to 54, further comprising presenting an interface that allows the user to specify a location within the analysis device to access one or more reagents for amplifying and detecting the nucleic acid analyte. (Item 56) calculating the results of the nucleic acid assay; receiving input of modified user-defined assay parameters into the interface by the user; assembling a modified protocol from said modified user-defined inputs in combination with one or more system-defined assay parameters; storing the modified protocol as a series of computer-executable instructions to be executed by the analytical device; executing the computer-executable instructions of the modified protocol with the analytical device to perform a modified nucleic acid assay; 56. The method of any one of items 33 to 55, further comprising the step of calculating the results of the modified nucleic acid assay. (Item 57) 57. The method of any one of items 33 to 56, wherein step (d) includes locking the protocol upon receiving a lock command from the user to prevent further modification of the locked protocol. (Item 58) 58. An automated analyzer comprising a processor adapted / configured to carry out the steps of the method according to any one of items 33 to 57. (Item 59) A computer program product comprising instructions that, when the program is executed by a computer, cause the computer to perform the method according to any one of items 33 to 57. (Item 60) A computer-readable medium comprising instructions that, when executed by a computer, cause the computer to perform the method of any one of items 33 to 57. (Item 61) 58. A computer-readable medium comprising a memory storing one or more user-defined assay parameters that, when received by the system of any one of items 1 to 32 or the analytical device of item 58 and assembled into a protocol for extracting, amplifying, and detecting nucleic acid analytes on the analytical device, enable the computer to perform the method of any one of items 33 to 57. (Item 62) 58. A computer program product comprising one or more user-defined assay parameters that, when received by the system of any one of items 1 to 32 or the analytical device of item 58 and assembled into a protocol for extracting, amplifying, and detecting nucleic acid analytes on the analytical device, enable the computer to perform the method of any one of items 33 to 57. [Brief explanation of the drawings]

[0073] The accompanying drawings, which are incorporated herein and form a part of the specification, illustrate various non-limiting embodiments of the present disclosure. Where appropriate, reference numerals indicating similar structures, components, materials, and / or elements in different drawings are similarly labeled. It is understood that various combinations of structures, components, and / or elements other than those specifically shown in the drawings are contemplated and within the scope of the present disclosure. For simplicity and clarity of explanation, the drawings show the general structure and / or method of construction of the described embodiments, as well as related manufacturing methods. Well-known features (e.g., fasteners, electrical connections, control systems, etc.) are not shown in these figures (and, for brevity, are not described in the corresponding description) to avoid obscuring other features because these features are well known to those skilled in the art. Features in the drawings are not necessarily drawn to scale. The dimensions of some features may be exaggerated relative to other features to improve understanding of the illustrative embodiments. Cross-sectional views are provided to help illustrate the relative placement of various features. Those skilled in the art will understand that cross-sectional views are not necessarily drawn to scale and should not be considered to represent proportional relationships between different features. It should be noted that aspects and features described with reference to one embodiment are applicable to and may be used in other embodiments, unless specifically stated otherwise. [Figure 1A] 1 is a perspective view of an analysis system according to an embodiment. [Figure 1B] 1 is a perspective view of an analysis system according to an embodiment. [Figure 2A] 1B is a plan view of different regions of an exemplary first module of the analytical system of FIG. 1A. [Figure 2B] 1B is a plan view of different regions of an exemplary first module of the analytical system of FIG. 1A. [Figure 2C] 1B is a plan view of different regions of an exemplary first module of the analytical system of FIG. 1A. [Figure 2D] 1B is a plan view of different regions of an exemplary first module of the analytical system of FIG. 1A. [Figure 2E] 1B is a plan view of different regions of an exemplary first module of the analytical system of FIG. 1A. [Figure 2F] FIG. 1B is a perspective view of an exemplary magnetic washing station of the analytical system of FIG. 1A. [Figure 2G] FIG. 2F is a perspective view of an exemplary magnetic transfer device of the magnetic washing station of FIG. 2F. [Figure 3A] FIG. 1B is a perspective view of an exemplary sample storage section of the analytical system of FIG. 1A. [Figure 3B] FIG. 1B is a perspective view of an exemplary sample storage section of the analytical system of FIG. 1A. [Figure 3C] FIG. 1B is a perspective view of an exemplary sample storage section of the analytical system of FIG. 1A. [Figure 4A] 3B is a perspective view of an exemplary sample holding rack that can be used in the sample store of FIG. 3A. [Figure 4B] 3B is a perspective view of an exemplary sample holding rack that can be used in the sample store of FIG. 3A. [Figure 5A] 1B is a plan view of different regions of an exemplary second module of the analytical system of FIG. 1A. [Figure 5B] 1B is a plan view of different regions of an exemplary second module of the analytical system of FIG. 1A. [Figure 5C] 1B is a plan view of different regions of an exemplary second module of the analytical system of FIG. 1A. [Figure 5D] 1B is a plan view of different regions of an exemplary second module of the analytical system of FIG. 1A. [Figure 5E]1B is a plan view of different regions of an exemplary second module of the analytical system of FIG. 1A. [Figure 5F] 1B is a plan view of different regions of an exemplary second module of the analytical system of FIG. 1A. [Figure 6A] 1B is a different view of an exemplary reagent container carrier of the analytical system of FIG. 1A. [Figure 6B] 1B is a different view of an exemplary reagent container carrier of the analytical system of FIG. 1A. [Figure 6C] 1B is a different view of an exemplary reagent container carrier of the analytical system of FIG. 1A. [Figure 6D] 1B is a different view of an exemplary reagent container carrier of the analytical system of FIG. 1A. [Figure 7A] 1B is a different view of another exemplary reagent container carrier of the analytical system of FIG. 1A. [Figure 7B] 1B is a different view of another exemplary reagent container carrier of the analytical system of FIG. 1A. [Figure 7C] 1B is a different view of another exemplary reagent container carrier of the analytical system of FIG. 1A. [Figure 8] 1B is a perspective view of an exemplary reagent container transfer mechanism of the analytical system of FIG. 1A. [Figure 9A] 1B is a different view of an exemplary reagent container carrier of the analytical system of FIG. 1A. [Figure 9B] 1B is a different view of an exemplary reagent container carrier of the analytical system of FIG. 1A. [Figure 9C] 1B is a different view of an exemplary reagent container carrier of the analytical system of FIG. 1A. [Figure 10A] 1B is a different view of an exemplary reagent container of the analytical system of FIG. 1A. [Figure 10B] 1B is a different view of an exemplary reagent container of the analytical system of FIG. 1A. [Figure 10C] 1B is a different view of an exemplary reagent container of the analytical system of FIG. 1A. [Figure 11A] 1B is a different view of another exemplary reagent container of the analytical system of FIG. 1A. [Figure 11B] 1B is a different view of another exemplary reagent container of the analytical system of FIG. 1A. [Figure 12A] 1B is an exemplary graphical user interface (GUI) displayed on a display device of the analysis system of FIG. 1A. [Figure 12B] 1B is an exemplary graphical user interface (GUI) displayed on a display device of the analysis system of FIG. 1A. [Figure 13A] 1B is a different view of an exemplary reagent pack of the analytical system of FIG. 1A. [Figure 13B] 1B is a different view of an exemplary reagent pack of the analytical system of FIG. 1A. [Figure 13C] 1B is a different view of an exemplary reagent pack of the analytical system of FIG. 1A. [Figure 13D] 1B is a different view of an exemplary reagent pack of the analytical system of FIG. 1A. [Figure 14A] FIG. 1B is a perspective view of an exemplary fluid transfer and handling system of the analytical system of FIG. 1A. [Figure 14B] FIG. 14B is a perspective view of the bottom of an exemplary pipettor of the fluid transfer and handling system of FIG. [Figure 14C] FIG. 14B is a perspective view of the bottom of an exemplary pipettor of the fluid transfer and handling system of FIG. [Figure 15A] 1B is a different view of an exemplary cap / vial assembly of the analytical system of FIG. 1A. [Figure 15B] 1B is a different view of an exemplary cap / vial assembly of the analytical system of FIG. 1A. [Figure 16A] 1B is a different view of the thermal cycler of the analysis system of FIG. 1A. [Figure 16B] 1B is a different view of the thermal cycler of the analysis system of FIG. 1A. [Figure 16C] 1B is a different view of the thermal cycler of the analysis system of FIG. 1A. [Figure 16D] 1B is a different view of the thermal cycler of the analysis system of FIG. 1A. [Figure 16E] 1B is a different view of the thermal cycler of the analysis system of FIG. 1A. [Figure 16F] 1B is a different view of the thermal cycler of the analysis system of FIG. 1A. [Figure 16G] 1B is a different view of the thermal cycler of the analysis system of FIG. 1A. [Figure 16H] 1B is a different view of the thermal cycler of the analysis system of FIG. 1A. [Figure 16I] 1B is a different view of the thermal cycler of the analysis system of FIG. 1A. [Figure 17A] 1B is a different view of an exemplary signal detector of the analytical system of FIG. 1A. [Figure 17B] 1B is a different view of an exemplary signal detector of the analytical system of FIG. 1A. [Figure 18A] 1B is a different view of an exemplary centrifuge of the analytical system of FIG. 1A. [Figure 18B] 1B is a different view of an exemplary centrifuge of the analytical system of FIG. 1A. [Figure 18C] 1B is a different view of an exemplary centrifuge of the analytical system of FIG. 1A. [Figure 19] FIG. 1B is a perspective view of an exemplary multicontainer unit (MRU) of the analytical system of FIG. 1A. [Figure 20A] FIG. 1B is a perspective view of an exemplary container dispensing system of the analytical system of FIG. 1A. [Figure 20B] FIG. 1B is a perspective view of an exemplary container dispensing system of the analytical system of FIG. 1A. [Figure 21A] 20B shows different views of an exemplary container dispenser of the container dispensing system of FIG. 20A. [Figure 21B] 20B shows different views of an exemplary container dispenser of the container dispensing system of FIG. 20A. [Figure 21C] 20B shows different views of an exemplary container dispenser of the container dispensing system of FIG. 20A. [Figure 21D] 20B shows different views of an exemplary container dispenser of the container dispensing system of FIG. 20A. [Figure 22A]1B is a different view of an exemplary container transfer device of the analytical system of FIG. 1A. [Figure 22B] 1B is a different view of an exemplary container transfer device of the analytical system of FIG. 1A. [Figure 23A] 1B is a different view of an exemplary reagent pack loading station of the analytical system of FIG. 1A. [Figure 23B] 1B is a different view of an exemplary reagent pack loading station of the analytical system of FIG. 1A. [Figure 24] 1B is a perspective view of an exemplary reagent pack carousel of the analytical system of FIG. 1A. [Figure 25] 1B illustrates an exemplary fluid transfer device of the analytical system of FIG. 1A. [Figure 26] 1B is a flow chart of an exemplary extraction process using the analytical system of FIG. 1A. [Figure 27] 1B is a flow chart of an exemplary reaction setup process using the analytical system of FIG. 1A. [Figure 27-1] 1B is a flow chart of an exemplary reaction setup process using the analytical system of FIG. 1A. [Figure 28] 1B is a flow chart of an exemplary thermal cycling process using the analytical system of FIG. 1A. [Figure 29] 1B is a flow chart of an exemplary sample preparation process using the analytical system of FIG. 1A. [Figure 30] 1B is a flow chart of an exemplary reaction mixture preparation process using the analytical system of FIG. 1A. [Figure 31] 1B is a flow chart of an exemplary nucleic acid amplification reaction process (eg, PCR) using the analytical system of FIG. 1A. [Figure 32] 1B is a flowchart of a method for performing multiple assays using the analytical system of FIG. 1A. [Figure 33] FIG. 1B is a schematic diagram of an exemplary control system for the analytical system of FIG. 1A. [Figure 34A] FIG. 1B is an exemplary GUI used to develop an LDT protocol for the analysis system of FIG. 1A. [Figure 34B] FIG. 1B is an exemplary GUI used to develop an LDT protocol for the analysis system of FIG. 1A. [Figure 34C] FIG. 1B is an exemplary GUI used to develop an LDT protocol for the analysis system of FIG. 1A. [Figure 34D] FIG. 1B is an exemplary GUI used to develop an LDT protocol for the analysis system of FIG. 1A. [Figure 34E] FIG. 1B is an exemplary GUI used to develop an LDT protocol for the analysis system of FIG. 1A. [Figure 34F] FIG. 1B is an exemplary GUI used to develop an LDT protocol for the analysis system of FIG. 1A. [Figure 34G] FIG. 1B is an exemplary GUI used to develop an LDT protocol for the analysis system of FIG. 1A. [Figure 34H] FIG. 1B is an exemplary GUI used to develop an LDT protocol for the analysis system of FIG. 1A. [Figure 34I] FIG. 1B is an exemplary GUI used to develop an LDT protocol for the analysis system of FIG. 1A. [Figure 34J] FIG. 1B is an exemplary GUI used to develop an LDT protocol for the analysis system of FIG. 1A. [Figure 34K] FIG. 1B is an exemplary GUI used to develop an LDT protocol for the analysis system of FIG. 1A. [Figure 34L] FIG. 1B is an exemplary GUI used to develop an LDT protocol for the analysis system of FIG. 1A. [Figure 34M] FIG. 1B is an exemplary GUI used to develop an LDT protocol for the analysis system of FIG. 1A. [Figure 35A] 1B is a flowchart of an exemplary method for performing data analysis on data generated by the analysis system of FIG. 1A. [Figure 35B] 1B is a flowchart of an exemplary method for performing data analysis on data generated by the analysis system of FIG. 1A. [Figure 35C] 1B is a flowchart of an exemplary method for performing data analysis on data generated by the analysis system of FIG. 1A. [Figure 35C-1] 1B is a flowchart of an exemplary method for performing data analysis on data generated by the analysis system of FIG. 1A. [Figure 36A] 1B is an exemplary plot illustrating the effect of different data analysis operations on data generated by the analysis system of FIG. 1A. [Figure 36B] 1B is an exemplary plot illustrating the effect of different data analysis operations on data generated by the analysis system of FIG. 1A. [Figure 36C] 1B is an exemplary plot illustrating the effect of different data analysis operations on data generated by the analysis system of FIG. 1A. [Figure 36D] 1B is an exemplary plot illustrating the effect of different data analysis operations on data generated by the analysis system of FIG. 1A. [Figure 36E] 1B is an exemplary plot illustrating the effect of different data analysis operations on data generated by the analysis system of FIG. 1A. [Figure 36F] 1B is an exemplary plot illustrating the effect of different data analysis operations on data generated by the analysis system of FIG. 1A. [Figure 37A] FIG. 1B is an exemplary GUI used to install an LDT protocol for the analysis system of FIG. 1A. [Figure 37B] FIG. 1B is an exemplary GUI used to install an LDT protocol for the analysis system of FIG. 1A. [Figure 37C] FIG. 1B is an exemplary GUI used to install an LDT protocol for the analysis system of FIG. 1A. [Figure 38] 1B is an exemplary GUI illustrating the association of assays with samples in the analytical system of FIG. 1A. [Figure 39] FIG. 1 is a schematic diagram of the protocol optimization workflow. DETAILED DESCRIPTION OF THE INVENTION

[0074] The features and advantages of the present disclosure will become more apparent from the following detailed description taken in conjunction with the drawings. There are numerous embodiments described herein with reference to the figures. Each aspect / feature described with respect to one embodiment may be used in combination with aspects / features disclosed with respect to another embodiment. For the sake of brevity, many of these combinations and permutations are not individually described herein.

[0075] Unless otherwise defined, all technical terms, notations, and other scientific or technical terms used herein generally have the same meaning as commonly understood by those skilled in the art to which this disclosure pertains. Many of the techniques and procedures described or referenced herein are well known and generally employed by those skilled in the art using conventional methodologies. Procedures involving the use of commercially available kits and reagents, if necessary, are generally carried out according to manufacturer-defined protocols and / or parameters unless otherwise noted. All patents, applications, published applications, and other publications referenced herein are incorporated by reference in their entirety. If the definitions set forth in this disclosure are contrary to or inconsistent with the definitions in these references, the definitions set forth in this disclosure shall prevail over the definitions incorporated herein by reference. None of the references described or referenced herein are admitted to be prior art for this disclosure.

[0076] References herein to "one embodiment," "an embodiment," "a further embodiment," "exemplary embodiment," "some aspects," "further aspects," "aspects," etc. indicate that the described embodiment may include a particular feature, structure, or characteristic, but not all embodiments necessarily include that particular feature, structure, or characteristic. Moreover, such phrases do not necessarily refer to the same embodiment. Furthermore, when a particular feature, structure, or characteristic is described in connection with one embodiment, such feature, structure, or characteristic is also described in connection with other embodiments, whether or not explicitly described. As used herein, "a" or "an" means "at least one" or "one or more."

[0077] As used herein, "sample" refers to any material suspected of containing an organism, virus, or cell of interest, or an analyte derived from an organism, virus, or cell of interest, or any material suspected of containing an analyte of interest. The material may be, for example, an unprocessed clinical specimen such as a blood or urogenital specimen, a buffer medium containing the specimen, a medium containing a lysing agent for releasing the specimen and analytes belonging to the organism, virus, or cell, or a medium containing an analyte derived from an organism, virus, or cell that has been isolated and / or purified ("extracted") in a container or on a reaction material or device. For this purpose, the term "sample" will be understood to mean a specimen in its raw form, or a specimen up to any processing stage for releasing, isolating, and purifying ("extracting") an analyte derived from the organism, virus, or cell. Thus, reference to a "sample" can refer to a material suspected of containing an analyte derived from an organism, virus, or cell at different processing stages, and is not limited to the initial form of the material.

[0078] With respect to nucleic acids, the term "extraction" refers to the recovery of nucleic acid molecules (e.g., DNA or RNA in any form) from a sample containing non-nucleic acid components, such as the natural environment of the nucleic acid molecule, a partially purified sample, or a crude sample (i.e., a sample in substantially the same form as when obtained from its source). Extraction can yield substantially purified nucleic acid molecules, or nucleic acid molecules in a purer form than they were in the sample prior to extraction, and can be used to obtain such molecules for use in analytical procedures from samples containing biological material, such as cells (including cells isolated directly from a source or cultured cells), blood, urine, mucus, semen, saliva, or tissue (e.g., biopsies). Many extraction methods are available. In various embodiments, extraction can involve one or more of cell lysis, removal of insoluble material, such as by centrifugation or filtration, chromatography, precipitation of nucleic acids, or capture of nucleic acids with a capture probe.

[0079] "Analyte" refers to a molecule present in a sample or suspected to be present in a sample and targeted for detection in an assay. Exemplary types of analytes include nucleic acids, polypeptides, and biopolymers such as prions.

[0080] "Nucleic acid" and "polynucleotide" refer to polymeric compounds containing nucleosides or nucleoside analogs with nitrogenous heterocyclic bases or base analogs linked together to form polynucleotides, including polymers that are conventional RNA, DNA, mixed RNA-DNA, and analogs thereof. The nucleic acid "backbone" can be composed of various linkages, including sugar-phosphodiester linkages, peptide-nucleic acid linkages ("peptide nucleic acids" or PNA; WO 95 / 32305), phosphorothioate linkages, methylphosphonate linkages, or combinations thereof. The sugar portion of the nucleic acid can be ribose, deoxyribose, or analogs with substitutions (e.g., 2' methoxy or 2' halide substitutions). The nitrogenous bases can be conventional bases (A, G, C, T, U), their analogs (e.g., inosine or others; The Biochemistry of the Nucleic Acids 5-36, Adams et al., ed., 11 th ed., 1992), purine or pyrimidine derivatives (e.g., N 4 -methylguanine, N 6 -methyladenine, deazapurines or azapurines, deazapyrimidines or azapyrimidines, pyrimidine bases with substituents at the 5 or 6 positions (e.g., 5-methylcytosine), purine bases with substituents at the 2, 6, or 8 positions, 2-amino-6-methylaminopurine, O 6 -methylguanine, 4-thio-pyrimidine, 4-amino-pyrimidine, 4-dimethylhydrazine-pyrimidine, and O 4-alkyl-pyrimidines; U.S. Pat. No. 5,378,825 and WO 93 / 13121). Nucleic acids may contain one or more "abasic" residues, in which the backbone does not contain a nitrogenous base at one or more positions in the polymer (U.S. Pat. No. 5,585,481). Nucleic acids may contain only conventional RNA or DNA sugars, bases, and linkages, or may contain both conventional components and substitutions (e.g., conventional bases with 2' methoxy linkages, or polymers containing conventional bases and one or more base analogs). Nucleic acids include "locked nucleic acids" (LNAs), analogs containing one or more LNA nucleotide monomers with bicyclic furanose units locked into the RNA that mimic the sugar configuration, which enhances hybridization affinity to complementary RNA and DNA sequences (Vester and Wengel, 2004, Biochemistry 43(42):13233-41). Examples of oligomers that may affect the stability of a hybridization complex include PNA oligomers, oligomers containing 2'-methoxy or 2'-fluoro substituted RNA, or oligomers that affect the overall charge, charge density, or steric association of a hybridization complex, including oligomers containing charged linkages (e.g., phosphorothioates) or neutral groups (e.g., methylphosphonates). Unless otherwise specified, methylated cytosines, such as 5-methylcytosine, may be used with any of the above-mentioned backbones / sugars / linkages, including RNA or DNA backbones (or mixtures thereof). RNA and DNA equivalents have different sugar moieties (i.e., ribose versus deoxyribose) and may differ by the presence of uracil in RNA and thymine in DNA. Because equivalents have the same degree of complementarity to a specific sequence, differences between RNA and DNA equivalents do not contribute to differences in homology. When referring to a range for the length of an oligonucleotide, amplicon, or other nucleic acid, it is understood that the range includes all integers (e.g., a length of 19 to 25 contiguous nucleotides includes 19, 20, 21, 22, 23, 24, and 25).

[0081] "Nucleic acid amplification" or simply "amplification" refers to any in vitro procedure that generates multiple copies of a target nucleic acid sequence or its complementary sequence or a fragment thereof (i.e., an amplified sequence that contains less than the entire target nucleic acid). Amplification methods include, for example, replicase-mediated amplification, polymerase chain reaction (PCR), ligase chain reaction (LCR), strand displacement amplification (SDA), helicase-dependent amplification (HDA), transcription-mediated amplification (TMA), and nucleic acid sequence-based amplification (NASBA). TMA and NASBA are both forms of transcription-based amplification. Replicase-mediated amplification uses self-replicating RNA molecules and a replicase, such as QB replicase (see U.S. Pat. No. 4,786,600). PCR uses DNA polymerase, primer pairs, and thermal cycling to synthesize multiple copies of two complementary strands of dsDNA or cDNA (see U.S. Patent Nos. 4,683,195, 4,683,202, and 4,800,159). LCR uses four or more different oligonucleotides to amplify a target and its complementary strand by employing multiple cycles of hybridization, ligation, and denaturation (see U.S. Patent Nos. 5,427,930 and 5,516,663). SDA uses primers containing recognition sites for restriction endonucleases and an endonuclease that nicks one strand of a semi-modified DNA duplex containing the target sequence, resulting in amplification in a series of primer extension and strand displacement steps (see U.S. Patent Nos. 5,422,252, 5,547,861, and 5,648,211). HDA uses a helicase to separate the two strands of a DNA duplex to generate a single-stranded template, followed by hybridization of a sequence-specific primer that hybridizes to the template and extension by DNA polymerase to amplify the target sequence (see U.S. Patent No. 7,282,328). Transcription-based amplification uses DNA polymerase, RNA polymerase, deoxyribonucleoside triphosphates, ribonucleoside triphosphates, promoter-containing oligonucleotides, and optionally other oligonucleotides, to ultimately generate multiple RNA transcripts from a nucleic acid template.Examples of transcription-based amplification are described in U.S. Patent Nos. 4,868,105, 5,124,990, 5,130,238, 5,399,491, 5,409,818, and 5,554,516; and WO 88 / 01302, WO 88 / 10315, and WO 95 / 03430. Amplification can be linear or exponential.

[0082] In cyclic amplification methods that detect amplicons in real time, the term "threshold cycle" (Ct) is a measure of the time of the appearance of a signal associated with target amplification, and may be, for example, approximately 10 times the standard deviation of the normalized reporter signal. When amplification reaches the "threshold cycle," it is generally considered that there is a positive amplification product of the sequence to which the probe binds. Probe binding generally provides important information about the identity of the product (e.g., that the product is an amplicon from a specific target sequence, or, in the case of one or more allele-specific probes, that it is a member of a certain class of alleles of a gene). In addition, the amplification product can be further characterized by methods known to those skilled in the art, such as gel electrophoresis, nucleic acid sequencing, and other such analytical procedures.

[0083] "Oligomer" or "oligonucleotide" generally refers to a nucleic acid less than 1,000 nucleotides (nt), including those in a size range having a lower limit of about 2-5 nt and an upper limit of about 500-900 nt. Some specific embodiments are oligomers in a size range having a lower limit of about 5-15, 16, 17, 18, 19, or 20 nt and an upper limit of about 50-600 nt, while other specific embodiments are oligomers in a size range having a lower limit of about 10-20 nt and an upper limit of about 22-100 nt. Oligomers can be purified from naturally occurring sources or synthesized using any well-known enzymatic or chemical method. Oligomers may be referred to by their functional name (e.g., capture probe, primer, or promoter primer), although those skilled in the art will understand that such terms refer to oligomers. Oligomers can form secondary and tertiary structures by self-hybridizing or by hybridizing to other polynucleotides. Such structures can include, but are not limited to, duplexes, hairpins, cruciforms, bends, and triplexes. The oligomers can be generated by any method, including chemical synthesis, DNA replication, reverse transcription, PCR, or a combination thereof. In some embodiments, oligomers that form invasive cleavage structures are generated in a reaction (e.g., by extension of a primer in an enzymatic extension reaction).

[0084] "Amplicon" or "amplification product" refers to a nucleic acid molecule produced in a nucleic acid amplification reaction and derived from a target nucleic acid. The amplicon or amplification product contains a target nucleic acid sequence that may be of the same or opposite orientation as the target nucleic acid. In some embodiments, the amplicon has a length of about 100-2000 nucleotides, about 100-1500 nucleotides, about 100-1000 nucleotides, about 100-800 nucleotides, about 100-700 nucleotides, about 100-600 nucleotides, or about 100-500 nucleotides.

[0085] "Amplification oligonucleotide" or "amplification oligomer" refers to an oligonucleotide, or its complement, that hybridizes to a target nucleic acid and participates in a nucleic acid amplification reaction (e.g., functions as a primer and / or promoter-primer). Certain amplification oligomers contain at least 10 contiguous bases, optionally at least 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 contiguous bases, that are complementary to a region of the target nucleic acid sequence or its complementary strand. The contiguous bases can be at least 80%, at least 90%, or fully complementary to the target sequence to which the amplification oligomer binds. In some embodiments, an amplification oligomer contains an intervening linker or non-complementary sequence between two segments of complementary sequence; for example, the two complementary segments of the oligomer contain a total of at least 10 complementary bases, optionally at least 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 complementary bases. Those of skill in the art will understand that the stated ranges include all integers and rational numbers within the range (e.g., 92% or 98.377%). Particular amplification oligomers are 10-60 bases in length and may contain modified nucleotides, as desired.

[0086] "Primer" refers to an oligomer having a 3' end that hybridizes to a template nucleic acid and is extended by polymerization. A primer can be modified, if desired, for example, by including a 5' region that is non-complementary to the target sequence. Such modifications can include functional additions, such as tags, promoters, or other sequences that can be used or useful for manipulating or amplifying the primer or target oligonucleotide. Examples of primers incorporating tags or tag and promoter sequences are described in U.S. Pat. No. 9,284,549. A primer modified with a 5' promoter sequence can be referred to as a "promoter-primer." Those skilled in the art of molecular biology or biochemistry will understand that an oligomer that can function as a primer can be modified to include a 5' promoter sequence and then function as a promoter-primer; similarly, any promoter-primer can function as a primer with or without its 5' promoter sequence.

[0087] A "forward amplification oligomer" (e.g., a forward primer) is configured to hybridize to the (-) strand of a target nucleic acid and may have a sequence that is partially or completely identical to that of the (+) strand of the target nucleic acid. A "reverse amplification oligomer" (e.g., a reverse primer) is configured to hybridize to the (+) strand of a target nucleic acid and may have a sequence that is partially or completely identical to that of the (-) strand of the target nucleic acid. Unless otherwise specified, the (+) strand refers to the coding strand of a nucleic acid that encodes a protein, the transcribed strand of non-coding sequences such as ribosomal RNA and transfer RNA and their corresponding DNA, and the (-) strand refers to the reverse complement of the (+) strand.

[0088] As used herein, "detection oligomer" or "detection probe" refers to an oligomer that interacts with a target nucleic acid to form a detectable complex. The target sequence of a probe generally refers to the specific sequence within a larger sequence (e.g., a gene, amplicon, locus, etc.) to which the probe specifically hybridizes. A detection oligomer can include target-specific sequences and sequences that are not complementary to the target. Such non-target complementary sequences can include sequences that impart desired secondary or tertiary structure (e.g., flap or hairpin structures) that can be used to facilitate detection and / or amplification (see, e.g., U.S. Pat. Nos. 5,118,801, 5,312,728, 6,835,542, 6,849,412, 5,846,717, 5,985,557, 5,994,069, 6,001,567, 6,913,881, 6,090,543, and 7,482,127; WO 97 / 27214 and WO 98 / 42873; Lyamichev et al., Nat. Biotech., 17:292 (1999); and Hall et al., J. Am. Chem. Soc., 1999, 10:101-102 (2000)). al., PNAS, USA, 97:8272 (2000). Probes of a defined sequence can be produced by techniques known to those skilled in the art, such as by chemical synthesis and by in vitro or in vivo expression from recombinant nucleic acid molecules.

[0089] As used herein, "label" or "detectable label" refers to a moiety or compound that is detected or provides a detectable signal. The label may be directly or indirectly linked to the probe or may be, for example, an intercalating dye (e.g., SYBR® Green). Direct linkage may use covalent or non-covalent interactions (e.g., hydrogen bonding, hydrophobic or ionic interactions, and chelate or coordination complex formation), while indirect linkage may use a bridging moiety or linker (e.g., via an antibody or additional oligonucleotide(s)). Optional detectable moieties may include, for example, radionuclides, ligands such as biotin or avidin, enzymes, enzyme substrates, reactive groups, chromophores such as dyes or particles that impart a detectable color (e.g., latex or metal beads), luminescent compounds (e.g., bioluminescent, phosphorescent, or chemiluminescent compounds), and fluorescent compounds (i.e., fluorophores). Exemplary fluorophores include those that absorb light (e.g., have peak absorption wavelengths) in the range of 495-690 nm and emit (e.g., have peak emission wavelengths) in the range of 520-710 nm, including those known as FAM®, TET®, HEX®, CAL FLUOR® (orange or red), CY®, and QUASAR® compounds. Fluorophores may be used in combination with a quencher molecule that absorbs light when in close proximity to the fluorophore, thereby reducing background fluorescence. Such quenchers are well known in the art and include, for example, BLACK HOLE QUENCHER® (or BHQ®), Blackberry Quencher® (or BBQ-650®), Eclipse®, or TAMRA™ compounds.Certain embodiments include "homogeneous detectable labels" that are detectable in a homogeneous system in which bound labeled probes in a mixture exhibit a detectable change compared to unbound labeled probes, allowing for detection of the label without physically removing hybridized labeled probes from unhybridized labeled probes (e.g., U.S. Pat. Nos. 5,283,174, 5,656,207, and 5,658,737). Exemplary homogeneous detectable labels include chemiluminescent compounds, including acridinium ester ("AE") compounds, such as well-known standard AEs or AE derivatives (U.S. Pat. Nos. 5,656,207, 5,658,737, and 5,639,604). Methods for synthesizing labels, attaching labels to nucleic acids, and detecting signals from labels are known (e.g., Sambrook et al., Molecular Cloning, A Laboratory Manual, 2nd ed. (Cold Spring Harbor Laboratory Press, Cold Spring, NY)). (Harbor, NY, 1989) at Chapter 10, as well as U.S. Patent Nos. 5,658,737, 5,656,207, 5,547,842, 5,283,174, 5,585,481, 5,639,604, and 4,581,333, and European Patent No. 0 747 706). Other detectably labeled probes include FRET cassettes, TaqMan® probes, and probes that undergo a conformational change in the presence of target nucleic acid, such as molecular torches and molecular beacons. FRET cassettes are described in U.S. Patent Application Publication No. 2005 / 0186588 and U.S. Patent No. 9,096,893. TaqMan® probes contain donor and acceptor labels, where fluorescence is detected upon enzymatic cleavage of the probe during amplification to release the fluorophore from the presence of the quencher. The chemistry for performing TaqMan assays is described in PCT Application No. PCT / US2018 / 024021, filed March 23, 2018, and U.S. Patent No. 5,723,591. Molecular torches and beacons exist in open and closed configurations; the closed configuration quenches the fluorophore, and the open position separates the fluorophore from the quencher, allowing for a detectable change in fluorescent signal. Hybridization to the target opens the otherwise closed probe. Molecular torches are described in U.S. Patent No. 6,361,945, and molecular beacons are described in U.S. Patent No. 6,150,097.

[0090] As used herein, "target capture" or "target capture procedure" refers to a procedure for immobilizing a target analyte on a solid support and purifying the analyte by removing potential amplification reaction inhibitors (e.g., heparin, proteins, and heme).

[0091] The terms "capture probe," "target capture probe," "capture oligonucleotide," "capture oligomer," "target capture oligomer," and "capture probe oligomer" are used interchangeably herein to refer to a nucleic acid oligomer that specifically hybridizes to a target sequence in a target nucleic acid through standard base pairing and binds to a binding partner on an immobilized probe to capture the target nucleic acid to a support. In one embodiment, "target capture" refers to a process in which a target nucleic acid is purified or isolated by hybridization to a capture probe. In another embodiment, "target capture" refers to the direct immobilization of a target nucleic acid to a solid support. One example of a capture probe typically contains two binding regions on the same oligomer: a sequence binding region (e.g., a target-specific portion) and an immobilized probe binding region, although the two regions may be present on two different oligomers connected by one or more linkers. Another embodiment of a capture probe uses a target sequence binding region containing a random or nonrandom poly-GU, poly-GT, or poly-U sequence to nonspecifically bind to the target nucleic acid and link the target nucleic acid to the immobilized probe on the support.

[0092] An "internal standard" refers to a molecule detected to confirm an assay result, e.g., a negative assay result in which the analyte was not detected. The internal standard may be provided in an assay kit or composition, or it may be an endogenous molecule present in essentially all samples tested in the assay (e.g., a housekeeping gene or mRNA for assays testing samples containing cells). In assays in which the analyte is a nucleic acid, the internal standard usually has a sequence that is at least partially different from the analyte, but it may have properties that result in similar amplification and detection characteristics (e.g., similar GC content). A nucleic acid internal standard may be amplified by a dedicated amplification oligomer or by the same amplification oligomer as the analyte. The internal standard nucleic acid may lack the sequence targeted by the analyte's probe oligomer and contain the sequence targeted by the internal standard-specific probe oligomer.

[0093] As used herein, the term "buffer" refers to any solution with a controlled pH that can serve to dissolve solid (e.g., lyophilized) substances (e.g., reagents, samples, or combinations thereof) or as a diluent for diluting liquids (e.g., liquid reagents, liquid samples, or combinations thereof; or solutions of reagents, samples, or combinations thereof).

[0094] "Elution buffer" refers to a buffer used to release nucleic acids from solid supports, including from capture probes associated with the solid support. The elution buffer can destabilize at least one interaction that contributes to the association of nucleic acids with solid supports. For example, if nucleic acids are ionically associated, the elution buffer can contain a sufficient amount of salt to destabilize the association; if nucleic acids are hydrophobically associated, the elution buffer can contain a sufficient amount of organic solvent or cosolvent to destabilize the association; if nucleic acids are associated by base pairing (hybridization), the elution buffer can contain a sufficient amount of denaturant to destabilize the association; if nucleic acids are associated by specific binding (for example, a tag-labeled capture probe binds to the binding partner of the tag), the elution buffer can contain a sufficient amount of free tag to destabilize the association.

[0095] As used herein, a "reconstitution solution" refers to a solvent (including water, organic solvents, and mixtures thereof) or a buffer solution that can be used to dissolve another substance, such as a dry substance (e.g., a lyophilized product). As used herein, the terms "reconstitution solution" and "solvent" may be used interchangeably, as may the terms "reconstitution" and "dissolution."

[0096] As used herein, an "assay" is a technique for detecting and / or quantifying an analyte in a sample. A sample containing or suspected of containing an analyte is contacted with one or more reagents and placed under conditions that allow for the production of a detectable signal that provides information about the presence or amount (e.g., mass or concentration) of the analyte in the sample.

[0097] As used herein, a "unit dose reagent" refers to a reagent provided in an amount or concentration sufficient for use in performing one or more steps of a single assay or test.

[0098] As used herein, a "molecular assay" is a technique for specifically detecting and / or quantifying a target molecule, such as a target nucleic acid. A sample containing or suspected of containing a target molecule is contacted with one or more reagents, including at least one reagent specific to the target molecule, and placed under conditions that allow the generation of a detectable signal that provides information on whether the target molecule is present. For example, if the molecular assay is PCR, the reagents include target-specific primers, and the generation of a detectable signal can be achieved, at least in part, by providing a labeled probe that hybridizes to the amplicon generated by the primers in the presence of the target. Alternatively, the reagents can include an intercalating dye for detecting the formation of double-stranded nucleic acids.

[0099] "Analyte-specific reagent" or "ASR" refers to a reagent that specifically interacts with a single analyte or a substance produced in the presence of an analyte. For example, in a PCR assay, primers and probes for a single analyte are considered ASRs. In an ELISA assay, a primary antibody that recognizes a single analyte is considered an ASR.

[0100] An "in vitro diagnostic" or "IVD" is a product used to perform an assay on a biological sample, independent of the source of the sample. When the source is a multicellular organism, the sample is generally taken from the organism and then subjected to an analytical procedure (e.g., amplification and / or binding reaction) in an artificial environment (e.g., a reactor). IVDs are regulated products, e.g., those requiring CE marking or approval by a government agency such as the Food and Drug Administration.

[0101] A "laboratory-developed test" or "LDT" is an assay that is designed, validated, and used by a laboratory, but for which kits or devices for performing the assay are not commercially available or sold as products for use by other laboratories.

[0102] As used herein, "reagent" refers to any substance or combination of substances that participate in a molecular assay other than the sample materials and products of the assay. Exemplary reagents include nucleotides, enzymes, amplification oligomers, probes, and salts.

[0103] As used herein, "PCR master mix" refers to a composition containing buffers, salts, and polymerase enzymes for use in amplifying DNA by PCR. PCR master mixes generally do not contain samples or primers and probes that may be necessary for performing PCR amplification or detecting specific products, although of course, samples and reagents such as primers and probes can be combined with the PCR master mix to form a complete reaction mixture.

[0104] As used herein, the terms "lyophilization," "lyophilized," and "freeze-dried" refer to a process in which the material to be dried is first frozen, and then the ice or freezing solvent is removed by sublimation in a vacuum environment. A "lyophilized product" refers to a freeze-dried material. A "lyophilized reagent" is a freeze-dried product that includes at least one reagent.

[0105] As used herein, " time-dependent " monitoring of nucleic acid amplification or " real-time " nucleic acid amplification monitoring refers to the process in which the amount of amplicon present in nucleic acid amplification reaction is measured as a function of reaction time or cycle number, and then used to determine the starting amount of template present in the reaction mixture at the time the amplification reaction is initiated.For example, the amount of amplicon can be measured before starting each full cycle of amplification reaction, including thermal cycles, such as PCR.Alternatively, isothermal amplification reaction, which does not require physical intervention to initiate the transition between amplification cycles, can be monitored continuously or at regular time intervals to obtain information about the amount of amplicon present as a function of time.

[0106] As used herein, "real-time amplification" refers to an amplification reaction in which time-dependent monitoring of amplification is performed.

[0107] "Endpoint amplification" refers to an amplification reaction in which the presence or amount of product (amplicon) is determined near or at completion of the reaction, as opposed to continuously or at regular intervals.

[0108] As used herein, "random access" capability refers to the ability of a system to perform two or more different assays on multiple samples in any order independent of the order in which the samples were grouped or loaded into the system. For example, if samples are loaded sequentially (or simultaneously as a group) as samples 1, 2, 3, 4, and 5, a system with random access capability will run assays on the samples in any order, such as 4, 3, 2, 5, and 1, and the assays may vary in their reagents and conditions depending on the sample. This includes the ability to run the same assay on samples that are not necessarily grouped together. For example, assay A may be run on samples 4 and 2, assay B on sample 3, and assay C on samples 5 and 1. In some embodiments, a random access system runs or is capable of running IVD assays on one or more samples simultaneously with assays using LDTs ​​and / or ASR(s) on other sample(s).

[0109] As used herein, "target nucleic acid analyte-dependent fluorescence" refers to fluorescence emitted from a fluorophore that results directly or indirectly from the interaction of the probe with a target nucleic acid analyte. This includes (but is not limited to) fluorescence produced by: (i) self-hybridizing probes, such as molecular torches or molecular beacons in assays where the torch or beacon hybridizes to a target and undergoes a conformational change that increases the distance between the fluorophore and the quencher or FRET acceptor, thus increasing the observable emission by the fluorophore; (ii) hybridization of a probe to a target, such as 5'-3' exonucleolysis of the probe and quenching of the fluorophore and the quencher or FRET acceptor; or FRET acceptor, thereby increasing the distance between the quencher and the TaqMan® probe in an assay, thereby increasing the observable emission by the fluorophore; and (iii) a secondary Invader probe in an assay, for example, where the primary probe hybridizes to the target and undergoes cleavage to release a fragment that hybridizes to a secondary Invader probe, which then itself undergoes cleavage to release a fragment containing the fluorophore, thus increasing the distance of the fluorophore from the quencher or FRET acceptor and increasing the observable emission by the fluorophore.

[0110] Nucleic acid amplification assays are performed by system 1000 according to parameters that define the steps to be performed in the assay. These parameters may include, among other things, the type / amount of extract, the amplification and detection reagents to be used, process conditions (e.g., incubation conditions, mixing speed and time, temperature cycling parameters, etc.), analyte, etc. As used herein, "assay parameters" refers to the parameters that define an assay (e.g., an IVD assay, an LDT, or an assay requiring ASR reagents).

[0111] As used herein, "graphical user interface" or "GUI" refers to a graphics-based user interface that allows a user to visually interact with a computer system. A user can select files, programs, commands, or enter data and text by pointing to interactive pictorial representations such as windows, icons, and buttons, or by pointing to interactive, selectable menus, or by entering text into text fields located among such windows, icons, buttons, and menus.

[0112] For known, standardized assays, the assay parameters are fixed and cannot be changed by the user (e.g., IVD assays). Thus, assay parameters associated with known, standardized assays are referred to herein as "system-defined assay parameters." In contrast, for assays developed by a user or a third party (e.g., LDTs, including assays using ASR), at least some of the assay parameters that define the assay are developed / determined / provided by the user / third party. In this disclosure, the term "user-defined assay parameters" is used to refer to assay parameters that are defined by the user.

[0113] The present description may use relative spatial and / or orientation terms when describing the location and / or orientation of components, devices, locations, features, or portions thereof. Unless specifically stated or otherwise indicated by the context of the description, such terms, including but not limited to top, bottom, above, below, under, above, upper, lower, left, right, front, back, next to, adjacent, between, horizontal, vertical, diagonal, longitudinal, lateral, radial, axial, etc., are used for convenience when referring to such components, devices, locations, features, or portions thereof in the drawings, but are not intended to be limiting. Furthermore, relative terms such as "about," "substantially," and "nearly" are used to indicate a possible variation of ±10% of a stated numerical value or range. The headings used in this application are intended merely to direct the reader's attention to various aspects of the disclosed system and are not intended to limit the disclosure. Similarly, headings are not intended to suggest that a material, feature, aspect, method, or procedure described in one section does not apply to another section.

[0114] Aspects of the present disclosure include analytical systems and methods that can be used with nucleic acid analytical assays, including "real-time" and "endpoint" amplification assays. Assays performed according to the description herein can involve capturing, amplifying, and detecting nucleic acids from cells or target organisms or viruses in a patient sample using conventional techniques. Such conventional techniques include target capture on solid supports, such as glass beads or magnetic particles, to isolate and purify the target nucleic acid, nucleic acid amplification reactions to increase the copy number of the targeted nucleic acid sequence (or its complement), and detection modalities to determine the presence or amount of the target nucleic acid.

[0115] 1A and 1B show an exemplary analytical system 1000 that can be used to simultaneously analyze multiple samples. FIG. 1A is a perspective view of system 1000, and FIG. 1B is a view of system 1000 with its lid removed to show internal features. Reference is made to both FIGS. 1A and 1B in the following description. System 1000 is configured to isolate and purify nucleic acids from multiple samples introduced into the system and to amplify and detect target nucleic acids contained in any of the samples using differently configured assay reagents. In some embodiments, as described in more detail below, system 1000 can be a random access system that allows IVD assays and LDTs ​​to be performed in an alternating manner. System 1000 can be configured to perform any type of molecular assay. In some embodiments, system 1000 can be configured to perform multiple different (e.g., differently configured) molecular assays on multiple samples. For example, multiple samples can be loaded into system 1000 and processed to specifically or non-specifically isolate and purify target nucleic acids (or other macromolecules such as polypeptides or prions), subjecting a first subset of the samples to a first set of conditions for performing a first nucleic acid amplification, and simultaneously subjecting a second subset of the samples to a second set of conditions for performing a second nucleic acid amplification, where the reagents for performing the first and second nucleic acid amplifications are configured differently, as described in more detail below.

[0116] In some embodiments, system 1000 may have a modular structure and may be comprised of multiple operatively connected modules. However, it should be noted that the modular structure of system 1000 is merely exemplary, and in some embodiments, system 1000 may be an integrated system having multiple regions or zones, each performing a specific step of an assay, which may be unique to that region, for example. System 1000 includes a first module 100 and a second module 400 that are operatively connected. The first module 100 and the second module 400 may each be configured to perform one or more steps of an assay. In some embodiments, the first and second modules 100, 400 may be separate modules that are selectively connected. That is, the first module 100 may be selectively and operatively connected to the second module 400, or the first module 100 may be selectively separated from the second module 400 and connected to a different second module 400. The first and second modules 100, 400 are connected by any method. For example, fasteners (e.g., bolts or screws), clamps, belts, straps, or any combination of fastening / attachment devices may be used to connect the modules. As previously mentioned, the modular structure of system 1000 is merely exemplary, and in some embodiments, system 1000 may be an integrated, self-contained structure (e.g., having first module 100 forming a first region and second module 200 forming a second region within the integrated structure). Note that in this disclosure, the term "module" is used to refer to a region (zone, location, etc.) of an analytical system. In some embodiments, each region may be configured to perform a particular step of an assay that may be unique to that region of the system.

[0117] In some embodiments, power, data, and / or utility piping or conduits (air, water, vacuum, etc.) may extend between the first and second modules 100, 400. In some embodiments, the first module 100 may be a system previously purchased by a customer, and the second module 400 may be a subsequently acquired module that increases the analytical capabilities of the combined system. For example, in one embodiment, the first module 100 may be a Panther® system (Hologic Inc., Marlborough, MA) configured to perform sample processing and transcription-based isothermal amplification assays (e.g., TMA or NASBA) on samples provided to the system, and module 400 may be an add-on configured to expand the functionality of the Panther® system by, among other things, adding thermal cycling capabilities, for example, to enable real-time PCR reactions. An example system 1000 having exemplary first and second modules 100, 400 is the Panther Fusion® system (Hologic Inc., Marlborough, MA), which is described in U.S. Patent Nos. 9,732,374, 9,465,161, and 9,604,185 and U.S. Patent Application Publication No. 2016 / 0032358. Exemplary systems, functions, devices, or components and capabilities of the first and second modules 100, 400 are described in the publications mentioned above (and in the publications specified below) and therefore will not be detailed herein for the sake of brevity.

[0118] First Module In some embodiments, the first module 100 may include multiple vertically stacked decks. FIGS. 2A and 2B show plan views of a representative embodiment of a middle deck of the first module 100, FIG. 2C shows a plan view of the top deck of the first module 100 of an exemplary embodiment, and FIGS. 2D and 2E show plan views of a representative embodiment of the bottom deck of the first module 100. Reference is made to FIGS. 2A-2E in the following description. Note that some of FIGS. 2A-2E show plan views of different embodiments of the system 1000. Thus, some components described with respect to one figure may not be visible or may be located in a different position in another figure. As shown, the first module 100 may be configured to perform one or more steps of a multi-step molecular assay designed to detect at least one analyte (e.g., a target nucleic acid). The first module 100 may include a vessel-receiving component configured to receive and hold a reaction vessel and, in some examples, to perform a process step on the contents of the vessel. Exemplary process steps may include: dispensing sample and / or reagents, including, for example, target capture reagents, buffers, oils, primers and / or other amplification oligomers, probes, polymerase, etc., into a reaction vessel; aspirating material, including, for example, non-immobilized components of the sample or wash solutions, from the reaction vessel; mixing the contents of the reaction vessel; maintaining and / or changing the temperature of the contents of the reaction vessel; heating or cooling the contents of the reaction vessel or reagent container; changing the concentration of one or more components of the contents of the reaction vessel; separating or isolating components of the contents of the reaction vessel; detecting a signal, such as electromagnetic radiation (e.g., visible light), from the contents of the reaction vessel; and / or deactivating nucleic acids or terminating an ongoing reaction.

[0119] In some embodiments, the first module 100 may include a vessel drawer or compartment 102 configured to receive and support multiple empty reaction vessels. The compartment 102 may include a cover or door for accessing the compartment and loading the reaction vessels. The compartment 102 may further include a vessel feeder for moving the reaction vessel to a vessel pickup location (e.g., a registered or known location) to facilitate removal of the reaction vessel by the vessel dispenser. The first module 100 may further include one or more compartments (e.g., compartment 103 in Figures 2D and 2E) configured to store containers configured to hold bulk reagents (i.e., sufficient reagent amounts to perform multiple assays) or to receive and hold waste materials. The bulk reagents may include liquids, such as water, buffers, target capture reagents, and nucleic acid amplification and detection reagents. In some embodiments, the bulk reagent container compartment may be configured to maintain the containers at a desired temperature (e.g., at a predetermined storage temperature) and includes a support structure that holds and / or agitates the containers to maintain their contents in solution or suspension. Exemplary support structures for supporting and agitating liquid containers are described in U.S. Patent No. 9,604,185.

[0120] The first module 100 may further include a sample storage section 8 supporting one or more sample holding racks 10 with sample-containing vessels (see FIGS. 2C, 3A-3C). The first module 100 may also include one or more fluid transfer devices (see fluid transfer device 805 in FIG. 25) for transferring liquids (e.g., sample fluids, reagents, bulk fluids, waste fluids, etc.) to and from reaction vessels and / or other containers. In some embodiments, the fluid transfer devices may include one or more robotic pipettors (e.g., pipettors 810, 820 in FIG. 25) configured for controlled, automated movement and access to reaction vessels, bulk containers holding reagents, and containers holding samples. In some embodiments, the fluid transfer devices may also include a fluid dispenser, e.g., a nozzle disposed within the other device and connected to a pump or other device for causing the movement of fluids to and from containers (e.g., bulk containers holding reagents) by appropriate fluid conduits to the dispenser. First module 100 may further include multiple load stations (e.g., heated load stations), such as load stations 104, 106, 108, configured to receive sample vessels (see FIGS. 2A and 2B) and other forms of holders for supporting sample vessels and reagent containers. Exemplary load stations and vessel holders are described in U.S. Pat. No. 8,309,036.

[0121] In some embodiments, the sample storage section 8 is a box-like structure having side walls 12, 16 and a bottom plate 20. Figures 3A and 3B show different embodiments of the sample storage section 8 that can be used with the system 1000. Reference will be made to Figures 3A and 3B in the following description. The walls 12, 16 can be insulated. The sample storage section 8 further includes a sample storage section cover 40 whose edges are held by the walls 12, 16. The front 32 of the sample storage section 8 is open to allow sample holding racks 10 having sample-containing containers 107 to be inserted into and removed from the sample storage section 8 (see Figure 3B). Figure 3C shows the sample holding racks 10 having sample-containing containers 107 inserted into the sample storage section 8. As seen in FIG. 3B, the base plate 20 may further include sample rack guides 22 that engage mating guides formed on the bottom of each sample holding rack 10 to accurately and reproducibly position each rack (see FIG. 3B). The sample storage unit 8 further includes a barcode bracket 34 attached to the sidewall 12 and configured to hold the barcode reader 18 in an operative position relative to a barcode window 14 (seen in FIG. 3A) formed in the sidewall 12 (see FIGS. 2C and 3B). The barcode reader 18 is configured to read the barcodes of the individual sample containers 107 held in each of the sample holding racks 10 and the barcode of the sample holding rack 10 itself (see FIG. 3C). The barcodes may be read through the barcode window 14 when the sample holding rack 10 is inserted into or removed from the sample storage unit 8.

[0122] 4A and 4B illustrate different embodiments of a sample holding rack 10 that can be used with the sample storage unit 8. Reference will be made to FIGS. 4A and 4B in the following description. The sample holding rack 10 is adapted to receive and hold a plurality of vessels 107 containing samples. In some embodiments, the vessels 107 can be or include tubular containers, such as test tubes. The sample holding rack 10 includes a vessel holder 2 and a cover 3. The vessel holder 2 includes a handle 4 for grasping and inserting the sample holding rack 10 into the sample storage unit 8. As illustrated in FIGS. 3C and 4B, the vessels 107 containing samples can be loaded into the rack 10, and the rack 10 can be inserted into the sample storage unit 8 of the load station 104. In some embodiments, the load station 104 is configured to allow the vessels 107 containing samples to be loaded into the sample storage unit 8 in any order and at any time (e.g., while the system 1000 is performing assays on some of the samples). For example, racks 10 with different, new, or recently arrived samples may be loaded into racks 10 and the loaded racks 10 inserted into sample storage section 8 of the load station while system 1000 is in the process of performing assays on other samples. In one embodiment, a machine-readable label, such as a bar code, is provided on vessel holder 2 near handle 4 (see FIG. 3C).

[0123] 2A and 2B, in some embodiments, first module 100 may include one or more magnetic accumulation stations 110 and heated incubators 112, 114, 116 configured to heat (and / or maintain) the contents of reaction vessels at a temperature above ambient temperature, and one or more cooling modules 122 configured to cool (and / or maintain) the contents of reaction vessels at a temperature below ambient temperature. Cooling module 122 may be used to promote oligo hybridization and to cool vessels (e.g., MRU 160, described below with reference to FIG. 19 ) before performing luminescence measurements. In some embodiments, incubator 112 (which may be referred to as a transition incubator) may be set to a temperature of approximately 43.7°C and may be used for process steps such as lysis, target capture, and hybridization. Incubator 114 may be a high-temperature incubator that may be set to a temperature of approximately 64°C and may be used for process steps such as lysis, target capture, and hybridization. The incubator 116 (referred to as the amplification incubator) may be set at a temperature of approximately 42°C and may be the incubator used for amplification during the assay. The incubator 116 may include a real-time fluorometer for detecting fluorescence during amplification. An exemplary temperature ramping station is described in U.S. Pat. No. 8,192,992, and exemplary incubators are described in U.S. Pat. Nos. 7,964,413 and 8,718,948. The first module 100 may include sample processing equipment, such as magnetic wash stations 118, 120, suitable for separating or isolating target nucleic acids or other analytes (e.g., immobilized on magnetically responsive solid supports) from the remaining contents of a container.

[0124] Figure 2F shows an exemplary magnetic wash station 120 of the first module 100 with the side panel removed (to show internal details). In some assays, samples are treated with separation materials that can interfere with the detection of analytes (e.g., target nucleic acids) in the magnetic wash stations 118, 120. To remove these interfering materials, the sample can be treated with a target capture reagent containing a magnetically responsive solid support for immobilizing the analytes. A suitable solid support can include paramagnetic particles (0.7-1.05 micron particles, Sera-Mag™ MG-CM (available from Seradyn, Inc., Indianapolis, Indiana)). When the solid support is brought into close proximity with a magnetic force, it is drawn out of suspension and clumps close to the surface of the sample-holding container, thereby isolating any immobilized analytes in the container. Non-immobilized components of the sample can then be aspirated or otherwise separated from the immobilized analytes. The magnetic washing station 120 includes a module housing 256 having an upper section 255 and a lower section 257. Mounting flanges 258, 259 extend from the lower section 257 and mount the washing station 120 to a support surface of the first module 100. An insertion port 263 extends through the front wall of the lower section 257 and enables the container dispenser 150 (see FIG. 2A ) of the first module 100 to place an MRU 160 (described with reference to FIG. 19 ) (or another container) into (and remove) the housing 256 of the magnetic washing station 120. A container transport unit 265 is positioned adjacent to the insertion port 263 to support the MRU 160 within the magnetic washing station 120. In some embodiments, the container transport unit 265 may include a spring clip (or another retention mechanism) for removably holding the MRU 160 to the container transport unit 265. An orbital mixer assembly 266 is coupled to the transport unit 265 for orbital mixing the contents of the MRUs 160 held by the container transport unit 265.The orbital mixer assembly 266 includes a stepper motor 267 that is coupled (by a drive mechanism) to the container transport unit 265 so that as the motor 267 rotates, the transport unit 265 moves in a horizontal track to mix the contents of the MRU 160.

[0125] The magnetic washing station 120 includes a magnet moving device 268 configured to move one or more magnets toward and away from the MRUs 160 of the receptacle-transport unit 265. In the embodiment shown in FIG. 2F , the magnet moving device 268 is a rotatable structure configured to rotate about a center of rotation 269. The magnet moving device 268 carries permanent magnets 270, which are positioned on either side of a slot 271 formed in the magnet moving device 268. In some embodiments, the magnet moving device includes five magnets 270, one for each individual receptacle 162 of the MRUs 160 carried by the receptacle-transport unit 265. In some embodiments, the magnets 270 may be made of neodymium iron boron (NdFeB). An electric actuator, generally represented by 272, rotates the magnet moving device 268 up and down, thereby moving the magnets 270 between an operative position and a non-operative position relative to the MRUs 160 supported by the receptacle-transport unit 265. In the operative position, magnet 270 is positioned in close proximity to each vessel 162 of MRU 160, such that the magnetically-responsive solid supports mixed with the contents of each vessel 162 are pulled out of suspension by the attractive force of the magnetic field of magnet 270. In the non-operative position, magnet 270 is positioned sufficiently far from vessel 162 so as to have no substantial effect on the contents of vessel 162. In the context of the present invention, "no substantial effect" means that the magnetically-responsive solid supports are not pulled out of suspension by the attractive force of the magnetic field of magnet 270.

[0126] FIG. 2G illustrates another embodiment of the magnet moving device 268 of the magnetic washing station 120 (of FIG. 2F). The magnet moving device 268 of FIG. 2G includes a magnet slide 250 disposed within the lower section 257 (of the module housing 256) and a drive system 294 that moves the magnet slide 250 between a non-operational position (as shown in FIG. 2G) and an operational position relative to the MRU 160 supported by the container transport unit 265. The magnet slide 250 includes an elongated opening 288 (which in some embodiments has a substantially rectangular shape) extending longitudinally therethrough. A first magnet 290 is disposed on one side of the opening 288, and a second magnet 291 is disposed on the opposite side of the opening 288. In some embodiments, five separate magnets (which in some embodiments have a size of approximately 12 mm x 12 mm x 8 mm and are made of NdFeB, n-40 grade) may be provided on opposite sides of the slide 250 instead of the single magnets 290 and 291. Drive system 294 includes a threaded drive screw 292, the ends of which are journaled in the walls of lower section 257 for rotation about a longitudinal axis. A drive motor 296 is coupled to drive screw 292 via a drive belt 293. Rotation of drive motor 296 causes linear translation of magnet slide 250 longitudinally relative to drive screw 292. Rotation of drive screw 292 in one direction causes translation of magnet slide 250 toward MRU 160, moving magnets 290 and 291 to their operational positions. Rotation of drive screw 292 in the opposite direction causes translation of magnet slide 250 in the opposite direction, moving magnets 290 and 291 to their non-operational positions (the positions shown in FIG. 2G ). When the magnet slide 250 moves from the non-operating position to the operating position, the MRU 160 passes through the longitudinal opening 288 of the magnet slide 250 and is positioned between the first magnet 290 and the second magnet 291.

[0127] 2F, the magnetic washing station 120 includes a cleaning solution delivery tube 281 that extends through the module housing 256 to form a cleaning solution delivery network. Nozzles connected to the delivery tubes 281 are positioned above each container 162 of the MRU 160 supported by the container transport unit 265. In some embodiments, these nozzles may be positioned in an offset manner relative to each container 162 so that the cleaning solution runs down the sides of each container 162 of the MRU 160, washing away any material adhering to the sides. Suitable cleaning solutions are known to those skilled in the art; an example includes 10 mM Trizma base, 0.15 M LiCl, 1 mM EDTA, and 3.67 mM lithium lauryl sulfate (LLS) at a pH of 7.5. A suction tube 282 connected to a tube holder 284 also extends through the housing 256 of the magnetic washing station 120. A suction hose 283 connected to the suction tube 282 extends to a vacuum pump 824 (see FIG. 2D ). The tube holder 824 is attached to a drive screw 285 that is actuated by a lift motor 286. The tube holder 284 and suction tube 282 are lowered by the lift motor 286 and drive screw 285 so that each suction tube 282 frictionally engages a disposable tip (e.g., a tiplet 168 of an MRU 160, described below with reference to FIG. 19 ).

[0128] After successful engagement of the aspirator tube 282 with the tiplet 168 (see FIG. 19 ), the orbital mixer assembly 266 moves the vessel transport unit 265 to a fluid transfer position. The magnet moving device 268 then moves the magnet 270 (or magnets 290 and 291 in FIG. 2G ) to an operational position adjacent to either side of the vessel 162 of the MRU 160. When the contents of the vessel 162 are placed under the magnetic field of the magnet 270 (or magnets 290, 291 in FIG. 2G ), the magnetically responsive solid supports with immobilized target nucleic acids are drawn to the sides of the individual vessels 162 adjacent to the magnet 270 (or magnets 290, 291 in FIG. 2G ). The magnet moving device 268 is maintained in the operational position for an appropriate dwell time, as defined by the assay protocol, to allow the magnetic solid supports to adhere to the sides of the respective vessels 162. The aspirating tubes 282 are then lowered into the containers 162 of the MRUs 160 and the fluid contents of the individual containers 162 are aspirated while the magnetic solid supports remain clumped within the containers 162 along their sides adjacent to the magnets 270. Tiplets 168 attached to the ends of the aspirating tubes 282 ensure that the contents of each container 162 do not contact the sides of the aspirating tube 282 during the aspiration procedure. The tiplets 168 are discarded before the subsequent MRU 160 is processed in the magnetic washing station 120 to reduce the possibility of cross-contamination by the aspirating tubes 282.

[0129] After aspiration, the suction tube 282 is retracted, and the magnet moving device 268 moves the magnet 270 (or magnets 290, 291 in FIG. 2G ) to its non-operating position. The container transport unit 265 is then moved to a liquid dispensing position, and a predetermined amount of cleaning solution is dispensed into each container 162 of the MRU 160 through a nozzle connected to the cleaning solution delivery tube 281. The orbital mixer assembly 266 then moves the container carrier 265 in a horizontal orbit at a high frequency (in one embodiment, 14 Hz, accelerating from 0 to 14 Hz per second) to mix the contents of the MRU 160. After mixing, the orbital mixer assembly 266 stops the container transport unit 265 in the fluid transfer position. In some embodiments, the magnet moving device 268 is again moved to the operating position and maintained in the operating position for a predetermined dwell time. After magnetic residence, the aspiration tube 282 with the engaged tiplet 168 is lowered into the vessel 162 to aspirate the test sample fluid and wash solution as described above. In some embodiments, multiple wash cycles (each including a dispense, mix, magnetic residence, and aspiration sequence) may be performed as defined by the assay protocol. Exemplary magnetic wash stations are described in U.S. Patent Nos. 6,605,213 and 9,011,771.

[0130] 2A and 2B, first module 100 may include detector 124 configured to receive reaction vessels and detect signals (e.g., optical signals) emitted by the contents of the reaction vessels. In one embodiment, detector 124 may include a luminometer for detecting luminescence signals emitted by the contents of the reaction vessels and / or a fluorometer for detecting fluorescent emissions from the contents of the reaction vessels. First module 100 may also include one or more signal detection devices, such as fluorometers (e.g., coupled to one or more incubators 112, 114, 116), configured to detect signals (e.g., at periodic intervals) emitted by the contents of vessels contained in incubators while a process, such as nucleic acid amplification, occurs in the reaction vessels. Exemplary luminometers and fluorometers are described in U.S. Patent Nos. 7,396,509 and 8,008,066.

[0131] The first module 100 may further include a container transfer device, which in the illustrated embodiment includes a container distributor 150 configured to move containers between various devices of the first module 100 (e.g., sample storage 8, incubators 112, 114, 116, load stations 104, 106, 108, magnetic accumulation station 110, wash stations 118, 120, and cooling module 122). These devices may include container transfer portals (e.g., ports covered by openable doors) through which containers are inserted into or removed from the devices. The container distributor 150 may include a container dispense head 152 configured to move in the X direction, rotate in the theta (Θ) direction, and move in the R direction along a transport track assembly 154 to move containers into and out of the devices of the first module 100. An exemplary container distributor, an exemplary container transfer portal door, and a mechanism for opening the door are described in U.S. Pat. No. 8,731,712.

[0132] Second Module In an exemplary embodiment, the second module 400 is configured to perform a nucleic acid amplification reaction (e.g., PCR) and measure fluorescence in real time. The system 1000 may include a controller (described in more detail below) that directs the system 1000 to perform different steps of a desired assay. The controller may accommodate LIS ("Laboratory Information System") connectivity and remote user access. In some embodiments, the second module 400 houses component modules that enable additional functionality, such as melt analysis. An example of a melt station that may be suitable for use in the second module is described in U.S. Patent No. 9,588,069. Other equipment may include a printer and an optional uninterruptible power supply.

[0133] With reference to FIG. 1B , in some embodiments, the second module 400 includes multiple vertically stacked levels (or decks) containing equipment configured for different functions. These levels include the amplification and processing deck 430 and the vessel processing deck 600. In the illustrated embodiment, the vessel processing deck 600 is located below the amplification and processing deck 430. However, this is not a requirement, and the vertical order of the decks (and their equipment) may vary depending on the intended use of the analytical system 1000. Schematic plan views of different embodiments of an exemplary amplification and processing deck 430 are shown in FIGS. 5A, 5B, and 5C. Schematic plan views of different embodiments of an exemplary vessel processing deck 600 are shown in FIGS. 5D, 5E, and 5F. In the following description, reference will be made to FIGS. 5A-5F. However, it should be noted that some of the features and components described below may not be visible in all of these figures. The second module 400 may include equipment located on different levels.These devices include, among others, a fluid transfer device in the form of one or more robotic pipettors 410 (see FIG. 1B), a thermal cycler 432 (see FIG. 16D) having a signal detector 4020, a tip compartment 580 configured to store trays of disposable tips for the pipettors 410, a cap / vial compartment 440 configured to store trays 460 of disposable processing vials and associated caps, a container dispensing system including a bulk reagent container compartment 500, a bulk reagent container transport mechanism 1700, a container handoff device 602, and (in the exemplary illustrated embodiment) The system 1000 includes a container dispensing system 200 including a container dispenser 312 (including a rotary dispenser in the example shown), container storage units 608, 610, 612 configured to store containers and / or multi-container units (MRUs) (e.g., including multiple containers linked as a single, integral unit), a magnetic slot 620, a waste bin connected to one or more waste chutes, a centrifuge 588, a reagent pack exchanger 700, a reagent pack loading station 640, and accessories such as one or more compartments 450 configured to store consumables and / or a storage tray 452 for post-cap / vial assembly (see FIG. 1B). An exemplary embodiment of a tray 460 for disposable process vials and caps is disclosed in U.S. Patent Application Publication No. 2017 / 0297027 A1. Some devices and features of the system 1000 are described in U.S. Patent No. 9,732,374 and other references herein. Therefore, for the sake of brevity, these devices and features will not be described in detail herein.

[0134] In the illustrated embodiment, the robotic pipettor 410 is located near the top of the second module 400. Below the robotic pipettor 410, the amplification processing deck 430 includes the bulk reagent container compartment 500, the centrifuge 588, the top of the thermal cycler 432, the tip compartment 580, and the cap / vial compartment 440. Below the amplification processing deck 430, the vessel processing deck 600 includes the vessel transfer device 602, the vessel distributor 312, the vessel storage units 608, 610, 612, the magnetic slot 620, the reagent pack exchange device 700, and the reagent pack load station 640. As seen in FIG. 4D , the magnetic slot 620 and the reagent pack load station 640 of the vessel processing deck 600 are accessible by the robotic pipettor 410 through gaps between the devices of the amplification processing deck 430.

[0135] The containers in the container storage units 608, 610, 612 may include individual containers (e.g., containers configured to store liquids) having an open end and an opposite closed end, or multiple (e.g., five) containers linked together as a unit (MRU). These MRUs may include handling structures configured to be engaged by engaging members (e.g., hooks) of a robotically controlled container dispensing system for moving the containers between different devices of the system 1000. Exemplary containers are described in U.S. Patent Nos. 6,086,827 and 9,732,374. As described in more detail below, the container dispensing system 200, including the container transfer device 602 and the container dispenser 312, is configured to receive containers or MRUs from the container dispenser 150 of the first module 100, transfer the containers to the second module 400, and move the containers to different locations on the second module 400.

[0136] Reagent Container Compartment With reference to FIG. 1B , the bulk reagent container compartment 500 of the second module 400 is configured to hold multiple reagent containers. A door or cover panel of the second module 400 can be opened to access the contents of the reagent container compartment 500. In some embodiments, an automatic lock (e.g., activated by a controller of the system 1000) can prevent the reagent container compartment 500 from being pulled open when the second module 400 is operating. In some embodiments, a visual and / or audible warning signal can be provided to indicate that the reagent container compartment 500 is not properly closed. FIG. 6A is a perspective view of a portion of the system 1000 with the reagent container compartment 500 in an open state. FIG. 6B is a perspective view of an exemplary reagent container compartment 500 separated from the second module 400. In the following description, reference is made to both FIGS. 6A and 6B. As shown in FIG. 6A, reagent container compartment 500 may be a cabinet that slides out from the main body of second module 400 for loading containers holding reagents for use in performing analytical procedures on system 1000. Reagent container compartment 500 may include one or more trays or container carriers configured to hold containers holding the same or different types of reagents. Generally, a container carrier may be a component including one or more pockets or cavities formed to receive liquid-filled containers therein. In some embodiments, the container carrier may be a component molded using a non-conductive plastic or polymeric material. As shown in FIG. 6B, in some exemplary embodiments, reagent container compartment 500 includes two reagent container carriers: first reagent container carrier 1500 and second reagent container carrier 1600. Note that in some embodiments, second module 400 may include multiple bulk reagent container compartments (similar to compartment 500, in some embodiments), each supporting one or more reagent containers.Some of these compartments may be configured to maintain reagent containers at different temperatures (cooled, heated, etc.).

[0137] First reagent container carrier Although not a requirement, in some embodiments, the first reagent container carrier 1500 may be a component including two pockets 1510, each configured to receive a reagent container 1520 containing a reagent, such as an elution buffer. The second reagent container carrier 1600 may be a component having multiple pockets 1610 (e.g., six pockets) configured to receive reagent-carrying containers therein. Figure 6C shows an exemplary reagent container compartment 500 having a first reagent container carrier 1500 and a second reagent container carrier 1600. In the embodiment illustrated in Figure 6C, the first reagent container carrier 1500 is shown with one reagent container 1520 disposed in one of its two pockets 1510, and the second reagent container carrier 1600 is shown with two solvent containers (e.g., an IVD solvent container 1620 and an LDT solvent container 1920) in two of its six pockets 1610. In some embodiments, the second reagent container carrier 1600 may include six pockets 1610, which may be configured to receive, for example, two oil containers 1820 and four solvent containers (e.g., two IVD solvent containers 1620 and two LDT solvent containers 1920, etc.) as illustrated in FIG. 6B. In general, the six pockets 1610 may include any of the containers 1620, 1820, 1920. FIG. 6D is a plan view of an exemplary second reagent container carrier 1600 having two oil containers 1820, one IVD solvent container 1620, and three LDT solvent containers 1920 in the pockets 1610. As illustrated in Figure 6D, the system 1000 may identify oil containers 1820 and solvent containers (1620 or 1920) located in different pockets 1610 of the container carrier 1600 as "Oil A," "Oil B," and "Recon 1," "Recon 2," etc. In some embodiments, as illustrated in Figure 6B, the oil container 1820 may be structurally similar to the IVD solvent container 1620. However, this is not a requirement and in general the oil container 1820 may be of any shape and configuration.Although not a requirement, in some embodiments, the first reagent container carrier 1500 and the second reagent container carrier 1600 may be separate components positioned adjacent to or apart from each other. In general, the reagent container compartment 500 may include any number of container carriers, each having any number of pockets. For example, in some embodiments, instead of a single second reagent container carrier 1600 having six pockets 1610, multiple single reagent container carriers (e.g., two) with pockets (e.g., three pockets each) may be provided in the reagent container compartment 500. The number and size of the pockets in the container carriers may be determined taking into account, among other things, the intended throughput and the desired period between required consumable replenishment. In some embodiments, the size and external shape of the pockets 1610 in the second reagent container carrier 1600 may be identical or substantially the same. In such embodiments, IVD solvent containers 1620 and LDT solvent containers 1920 having identical or substantially the same external dimensions may be placed in the pockets 1610. Containers in the reagent container compartment 500 may be identified by a machine-readable code, such as an RFID. A display panel 1300 having visible signals (e.g., red and green LEDs) and / or other indications (text, audible, etc.) may be provided in the reagent container compartment 500 (and / or on the container carrier) to provide feedback to the user regarding the status of the containers. The display panel 1300 may be located at any position within the reagent container compartment 500 or container carrier (note the different exemplary positions of the display panel 1300 in FIGS. 6A and 6B). The reagent container compartment 500 may include a reagent container transfer mechanism 1700 (see FIG. 6B) configured to move the first reagent container carrier 1500 from the reagent container compartment 500 in the second module 400 to a position within the first module 100.

[0138] 7A shows an exemplary first reagent container carrier 1500 with an exemplary reagent container 1520 in one of its two pockets 1510. FIG. 7B is a cross-sectional perspective view, and FIG. 7C is a cross-sectional schematic view of the exemplary first reagent container carrier 1500 having a reagent container 1520 in each of the two pockets 1510. The first reagent container carrier 1500 may include a base or receptacle portion 1530 forming the two pockets 1510 for receiving the reagent containers 1520 therein, and a frame 1540 attached to the receptacle portion 1530 for holding the reagent containers 1520 within the pockets 1510. In general, the shape and size of the pockets 1510 in the receptacle portion 1530 may correspond to the shape and size of the reagent containers 1520 to be received therein. In some embodiments, the pockets 1510 may be sized to snugly receive the reagent containers 1520 therein. When the container 1520 is placed in the pocket 1510 and the frame 1540 is attached to the receptacle portion 1530, a portion of the frame 1540 extends over a portion of the container 1520 to prevent removal of the container 1520 from the pocket 1510. As shown in Figures 7A and 7B, the frame 1540 may have a window-frame shape with an opening therethrough exposing the top of the container 1520. In some embodiments, some or all of the outer surface 1532 of the receptacle portion 1530 may be metallized or grounded to support capacitive detection of the liquid level in the reagent container 1520.

[0139] Reagent Container The reagent container 1520 may include a cup-shaped reservoir containing a liquid reagent with a pipettor-pierceable cover 1550 that covers the reservoir's mouth (see FIGS. 7A-7C). In some embodiments, the liquid reagent in the reagent container 1520 may be an elution buffer. In some embodiments, the cover 1550 may comprise one or more frangible materials (e.g., foil, elastomer, etc.) suitable for being pierced by an aspiration probe 415 or a disposable pipette tip 584 secured to the mounting end 425 of an aspiration probe 415 of a robotic pipettor (e.g., robotic pipettor 410; see FIGS. 14A-14C). During use, the aspiration probe 425 or the pipette tip 425 (attached to the aspiration probe 415) may pierce the pipettor-pierceable cover 1550 to access the liquid stored in the container 1520. 7C shows a schematic diagram of a pipette tip 584 (secured to the mounting end 425 of the aspiration probe 415 of the pipettor 410 of the second module 400) accessing a liquid reagent stored in a reagent container 1520 by penetrating the cover 1550. In some embodiments, as shown in FIG. 7A (and in more detail in FIGS. 10A and 10B ), a plastic (or another rigid material) lid 1552 having an opening can be attached over the pipetter-pierceable cover 1550, and a septum 1554 positioned between the frangible cover 1550 and the rigid lid 1552 to cover the opening. The septum 1554 can be made from a material that can be pierced by a pipettor, or can include a feature (e.g., a notch, etc.) that allows the pipette tip 584 secured to the aspiration probe 415 or the mounting end 425 of the pipettor 410 to access the container 1520 through the septum. In such an embodiment, the aspiration probe 425 or pipette tip 584 may contact and penetrate the frangible cover 1550 through the septum 1554. When withdrawing the pipette tip 584 from the container 1520, the portion of the frame 1540 above the container 1520 may prevent the container 1520 from being removed from the first reagent container carrier 1500.

[0140] In some embodiments, the reagent container 1520 may be structurally similar to the IVD solvent container 1620 described below with reference to Figures 10A and 10B. Some exemplary configurations of the reagent container 1520 are described in U.S. Patent Application Publication No. 2018 / 0290141, entitled "Fluid Receptacles."

[0141] In some embodiments, when the pipettor 410 contacts the liquid in the reagent container 1520, the liquid level in the container 1520 can be detected using capacitive level detection. To enable capacitive level detection, the metallized outer surface 1532 of the reservoir portion 1530 (of the first reagent container carrier 1500) can be connected to system ground (e.g., the ground surface of the system 1000), and the pipette tip 584 secured to the mounting end 425 of the aspiration probe 415 or pipettor 410 can be connected to a voltage source (e.g., an AC voltage source). In such an arrangement, the pipettor 410 (and optionally the pipette tip 584, which has conductive properties) functions as one conductor of a capacitor, and the grounded outer surface 1532 functions as the other conductor. A capacitance signal (a signal related to capacitance) measured between these two conductors can be used to detect the liquid level in the reagent container 1520. In use, as the aspiration probe 415 (or pipette tip 584 secured to the mounting end 425 of the pipettor 410) is lowered into the container 1520, the position (height) of the aspiration probe 415 (or pipette tip 584) is simultaneously monitored along with the capacitance signal. If the capacitance signal increases sharply (e.g., a sudden rise caused by the aspiration probe 415 or pipette tip 584 contacting the liquid), the height of the aspiration probe 415 (or pipette tip 584) is recorded, thereby determining the height of the fluid surface within the container 1520. Although aspiration of liquid within the container 1520 using the pipettor 410 of the second module 400 is described above, liquid can also be extracted from the container 1520 using other fluid transfer devices (e.g., the pipettor 810 of the first module 100).

[0142] Reagent container transfer mechanism When the reagent container compartment 500 is closed (see FIG. 1B ), the reagent container transfer mechanism 1700 of the second module 400 can engage a ledge on the frame 1540 of the first reagent container carrier 1500 to move the first reagent container carrier 1500 from the second module 400 to a position within the first module 100. FIG. 8 shows an exemplary reagent container transfer mechanism 1700 engaged with the first reagent container carrier 1500. The reagent container transfer mechanism 1700 is operatively connected to an electric motor 1730 and includes an articulation portion 1720 pivotally connected to a structural member of the second module 400 that is connected to system ground (i.e., the articulation portion 1720 is electrically grounded). Upon actuation of the reagent container transfer mechanism 1700, the articulating portion 1720 engages with the frame 1540 via the bearings 1710 and rotates about its respective axis of rotation to move the first reagent container carrier 1500 from the compartment 500 of the second module 400 to a position within the first module 100. Thus, when the articulating portion 1720 engages with the frame 1540, the metallized portion of the first reagent container carrier 1500 is electrically connected to system earth (or grounded) via the articulating portion 1720. When the first reagent container carrier 1500 is placed within the first module 100, the grounded conductive brush 1750 makes electrical contact with the metallized portion of the first reagent container carrier 1500 (e.g., the metallized outer surface 1532 of the reservoir portion 1530). When disposed within first module 100, a fluid transfer device of first module 100 (e.g., pipette tip 584 of pipettor 810, see FIG. 7C ) can access and aspirate a desired amount of reagent, such as elution buffer, from reagent container 1520. During the analytical procedure, the aspirated reagent is transported and released into a container or vial. In an exemplary embodiment, the reagent fluid is an elution buffer useful for eluting target nucleic acid from a solid support, such as magnetic particles or silica beads.

[0143] Reagent Container Carrier As previously described with reference to FIGS. 6A-6C, the plurality of pockets 1610 of the second reagent container carrier 1600 may include solvent containers (e.g., IVD solvent container 1620 and / or LDT solvent container 1920) that house a solvent (e.g., solvent) and an oil container 1820 that houses an oil (e.g., silicone oil). As known to those skilled in the art, the solvent and oil may be reagents used in molecular assays performed by the analytical system 1000. As best shown in FIG. 6C, similar to the first reagent container carrier 1500 described above, the second reagent container carrier 1600 may also include a base or reservoir portion 1630 that includes pockets 1610 (that support the solvent and oil containers therein) and a lid 1640 that holds these containers in their respective pockets 1610. FIGS. 9A, 9B, and 9C are side perspective, bottom, and cross-sectional views, respectively, of an exemplary second reagent container carrier 1600. In the following description, reference is made to Figures 6A-6C and 9A-9C. Generally, the shape and size of the pockets 1610 (of the container portion 1630) can correspond to the shape and size of the containers (e.g., IVD and LDT solvent containers 1620, 1920 and oil container 1820) to be received in the pockets 1610. In some embodiments, as illustrated in Figure 9B, opposing side surfaces of the container portion 1630 can include gaps separating the individual pockets 1610. Typically, the shape and size of the pockets 1610 can match the shape and size of the liquid-filled containers to be received in that pocket 1610. For example, the size and shape of the pockets 1610 can correspond to the shape and size of the solvent containers they support, thereby providing a static fit in some embodiments. In some embodiments, the pockets 1610 can all have the same or substantially the same shape and dimensions. However, it is contemplated that the pockets 1610 may have different shapes and / or sizes (eg, to receive containers of different shapes and / or sizes therein).

[0144] As best shown in FIG. 6C , the lid 1640 of the second reagent container carrier 1600 may include a top portion 1650 and a bracket portion 1660. While not a requirement, in some embodiments, the top portion 1650 may be formed from a non-conductive material, and the bracket portion 1660 may be formed from a conductive material. In some embodiments, the top portion 1650 may be a transparent or translucent plate-like member. The top portion 1650 and the bracket portion 1660 may be two portions attached together to form the lid 1640, or may be two regions of a single-piece lid 1640. When the lid 1640 is placed on the container portion 1630, the top portion 1650 of the lid 1640 may extend over a portion of the top surface of the container portion 1630. In this arrangement, the top portion 1650 extends over (and overlaps) a portion of the solvent container 1620, 1920 positioned in the pocket 1610, preventing the container 1620, 1920 from being accidentally removed from the pocket 1610. Although not a requirement, in some embodiments, the overlapping area of ​​the top portion 1650 may press down on an underlying area of ​​the container, restraining the container within the pocket 1610. The portion of the IVD solvent container 1620 and / or LDT solvent container 1920 (in the pocket 1610) that is not covered by the top portion 1650 of the lid 1640 provides access for the aspiration probe 415 or a pipette tip 584 secured to the mounting end 425 of the pipettor 410 to extract solvent from the container 1620, 1920.

[0145] 9A, the lid 1640 of the second reagent container carrier 1600 may be attached to the frame / chassis 1670 of the second module 400 such that, when the reagent container compartment 500 is closed (see FIG. 1A), an upper portion 1650 of the lid 1640 extends over the containers 1620, 1820, 1920 disposed in the pocket 1610 of the second reagent container carrier 1600. In this arrangement, the aspiration probe 415 of the robotic pipettor 410 or a pipette tip 584 (secured to the mounting end 425 of the aspiration probe 415) (see FIGS. 14B-14C) may extract solvent from the solvent containers 1620, 1920 (and oil from the oil container 1820) disposed in the second reagent container carrier 1600, as described in more detail below (with reference to FIGS. 10A-10C). After aspirating liquid, when the aspiration probe 415 of the pipettor 410 (or the pipette tip 584 secured to the mounting end 425) is withdrawn from the container (1620, 1820, 1920), the container may tend to come out of its respective pocket 1610. The top portion 1650 extends over a portion of the top of the container 1620, 1820, 1920 to prevent the container from being accidentally removed from its pocket. When the reagent container compartment 500 is opened (see FIG. 6A ), the receptacle portion 1630 of the second reagent container carrier 1600 slides out from under the lid 1640 to allow a user to load (and unload) the IVD solvent container 1620, the LDT solvent container 1920, and the oil container 1820 into (and from) the pocket 1610. In some embodiments, similar to that described with respect to the first reagent container carrier 1500, some surfaces of the container portion 1630 may be metallized so that when the second reagent container carrier 1600 is placed in the reagent container compartment 500, these metallized portions are electrically connected to the system earth (e.g., the housing of the system 1000) and act as a ground plane to enable capacitive fluid level detection using the aspiration probe 415 or the pipette tip 584 (fixed to the mounting end 425 of the pipettor 410).U.S. Patent Application Publication No. 2018 / 0282788, entitled "Systems and Methods for Capacitive Fluid Level Detection, and Handling Containers," describes exemplary first and second reagent container carriers 1500, 1600 that may be used in system 1000.

[0146] IVD Solvent Container In some embodiments, the IVD solvent container 1620 may be structurally similar to the previously described reagent container 1520. FIG. 10A shows an exploded perspective view of an exemplary IVD solvent container 1620, FIG. 10B shows a perspective view of the IVD solvent container 1620, and FIG. 10C is a cross-sectional view of the IVD solvent container 1620 containing solvent 1670 therein. Reference is made to FIGS. 10A-10C in the following description. In some embodiments, the IVD solvent container 1620 may be a heat-sealed pack (e.g., a foil pack) containing a reconstitution buffer suitable for known (e.g., FDA-approved or CE-marked) IVD assays. That is, the solvent 1670 in the IVD solvent container 1620 may be a reconstitution buffer (i.e., a general-purpose reagent suitable for reconstituting dried reagents including amplification oligomers and / or detection probes). Exemplary reconstitution buffers that may be used as solvent 1670 and exemplary dried reagents for use with the reconstitution buffer are described in WO 2017 / 136782. For some assays (e.g., PCR), multiple amplification oligomers (forward amplification oligomers or primers, reverse amplification oligomers or primers, etc.) and / or probes may be used. During an exemplary molecular assay, solvent 1670 (i.e., reconstitution buffer) in IVD solvent container 1620 may be used to reconstitute dried or lyophilized reagents (or reagents in another form (e.g., gel, etc.)) containing different types of amplification oligomers and probes for amplifying different target nucleic acids.

[0147] Similar to the reagent container 1520, the IVD solvent container 1620 may include a cup-shaped reservoir 1662 (containing reconstitution fluid 1670) sealed by a frangible (e.g., foil, elastomer, etc.) cover 1664 that is pierceable by a pipettor. In some embodiments, the reservoir 1662 may be configured to contain a volume 1670 of fluid sufficient to perform between about 50 and about 2,000 assays. However, the fluid volume 1670 may be sufficient to perform fewer than 50 assays or more than 2,000 assays. In some embodiments, the pipettor-pierceable cover 1664 of the reservoir 1662 may be covered by a lid 1652 (e.g., made from a relatively hard material, such as plastic) having an opening 1653. A septum 1654 may be disposed between the cover 1664 and the lid 1652 such that the septum covers the opening 1653 in the lid 1652.

[0148] 10C , the reservoir 1662 of the solvent container 1620 may exhibit multiple fluidly connected chambers configured to hold a reconstitution liquid 1670 therein. These chambers may include a first chamber 1656 and a second chamber 1658 fluidly connected to one another at the bottom of the chambers 1656, 1658 by a conduit 1672. The first chamber 1656 may have a larger volume than the second chamber 1658 and may therefore be configured to hold a larger amount of liquid 1670 than the second chamber 1658. After the chambers are filled with the desired amount of liquid 1670, a frangible cover 1664 pierceable by a pipetter is attached to the top surface 1661 of the reservoir 1662 to seal the chambers 1656 and 1658. The cover 1664 may be attached to the reservoir 1662 by any suitable method (such as adhesive, heat welding, ultrasonic welding, etc.). 10A, the lid 1652 is then attached to the reservoir 1662 over the cover 1664, with the septum 1654 covering the opening in the lid 1652. As seen in FIGS. 10A-10C, the lid 1652 includes features that engage with corresponding features on the reservoir 1662 to secure the lid 1652 to the reservoir 1662. These features may include a lip or protrusion 1659 on the reservoir 1662 (or lid 1652) that engages with a corresponding notch or recess 1649 in the lid 1652 (or reservoir 1662). When the lid 1652 is attached to the reservoir 1662, the septum 1654 is disposed over the second chamber 1658 of the reservoir 1662. Thus, the second chamber 1658 is an "access chamber" for receiving a fluid transfer device, such as the aspiration probe 415 of the robotic pipettor 410 or a pipette tip 584 secured to the mounting end 425 of the aspiration probe 415. During use, the pipettor (i.e., the aspiration probe 415 or the pipette tip 584) enters the second chamber 1658 (or access chamber) through the septum 1654 (after piercing a frangible cover 1664 over the second chamber 1658) and extracts liquid 1670 (e.g., aspirates liquid 1670) from the reservoir 1662.In some embodiments, the septum 1654 may include a structure that allows a pipettor to enter the second chamber 1658 through the septum 1654. In some embodiments, the septum 1654 may include star-shaped slits that flex and form flexible flaps that allow the aspiration probe 415 of the pipettor 410 or the pipette tip 584 (secured to the mounting end 425) to pass through. These slits may be preformed (e.g., pre-cut flaps) or may be formed after the aspiration probe 415 of the pipettor 410 (or the pipette tip 584) pierces a perforated pattern provided in the septum 1654. When the pipettor is withdrawn from the second chamber 1658 (of the reservoir 1662 after aspirating liquid 1670), the flap of the septum 1654 covers the opening in the frangible cover 1664 (formed by the aspiration probe 415 or pipette tip 584), reducing evaporation of the liquid 1670 from the reservoir 1662. Because the surface area of ​​the liquid in the second chamber 1658 is smaller than that in the first chamber 1656, extracting the liquid 1670 from the second chamber 1658 (as opposed to the first chamber 1656) further helps reduce liquid loss from the reservoir 1662 due to evaporation. Each time liquid 1670 is extracted from the second chamber 1658, liquid from the first chamber 1656 enters the second chamber 1658 through the conduit 1672, equalizing the liquid level in both chambers.

[0149] U.S. Patent Application Publication No. 2018 / 0290141 describes embodiments of the IVD solvent container 1620. As previously explained, in some embodiments, the reagent container 1520 and the oil container 1820 may have a structure similar to that of the IVD solvent container 1620. In a manner similar to that described with reference to the reagent container 1520, the pipettor 410 may detect the fluid level in the container 1620 by capacitive fluid level detection as the liquid 1670 is extracted from the IVD solvent container 1620. During capacitive fluid level detection, a metal-coated portion of the second reagent container carrier 1600 (connected to system ground) positioned near the bottom surface of the liquid 1670 in the IVD solvent container 1620 improves the accuracy and sensitivity of the liquid level measurement.

[0150] LDT Solvent Container In some embodiments, the LDT solvent container 1920 used in the system 1000 may have a different shape than the IVD solvent container 1620 described above. Figures 11A and 11B show an exemplary LDT solvent container 1920 that may be used in the system 1000. Figure 11A shows a perspective view of the container 1920, and Figure 11B shows a schematic cross-sectional view of the container 1920 disposed within the second reagent container carrier 1600. Reference is made to both Figures 11A and 11B in the following description. The LDT solvent container 1920 includes a body 1950 having a plurality of recesses 1930 (e.g., cavities formed in the solid portion of the body), each configured to support a liquid-containing vessel 1940 (e.g., a tube or vial containing reconstitution fluid) therein. For example, in some embodiments, four generally cylindrical recesses 1930 may be arranged in a rectangular arrangement (e.g., a 2x2 grid) in the body 1950. However, in general, the LDT solvent container 1920 may exhibit more or less than four recesses 1930, and the recesses 1930 may have any shape (e.g., conical, frustoconical, rectangular, etc.) and may be arranged in any suitable configuration (e.g., circular, linear, etc.). Although not a requirement, in some embodiments, each recess 1930 of the container 1920 may be sized to receive a similarly sized vessel 1940 therein. In some embodiments, some or all of the recesses 1930 may have different dimensions to receive correspondingly sized vessels 1940 therein.

[0151] Receptacles 1940 containing reconstitution fluids 1970A, 1970B, etc. are disposed in respective recesses 1930 of LDT solvent container 1920. Generally, different reconstitution fluids 1940 in container 1920 may contain the same or different reconstitution fluids (i.e., reconstitution fluids used for the same or different assays). For example, in some embodiments, reconstitution fluid 1970A may be a reagent containing one type of amplification oligomer and / or probe, and reconstitution fluid 1970B may be a reagent containing a different type of amplification oligomer and / or probe. In some embodiments, each set of amplification oligomers and probes in reconstitution fluids 1970A, 1970B may be designed to detect a different analyte, which may be a different nucleic acid or a different region of the same nucleic acid. In some embodiments, one or more of reconstitution fluids 1970A, 1970B may contain at least one forward amplification oligomer and at least one reverse amplification oligomer. In some embodiments, one or more of reconstitution fluids 1970A, 1970B may have a detectable label (or signaling moiety) or may include a probe that can be detected using an intercalating dye, such as SYBR® Green, when hybridized to a target nucleic acid. Body 1950 of container 1920 may include one or more indicia 1914 (e.g., unique indicia) for identifying each recess 1930. Indicia 1914 may include alphanumeric text, symbols, colors, or any other suitable indicia useful in distinguishing the liquids supported in recesses 1930, as shown in FIG. 11A . For example, indicia 1914 may identify the type of reconstitution fluid (e.g., amplification oligomers, probes, etc.) contained in the reconstitution fluid contained in vessel 1940. Indicia 1914 may be a label immobilized on body 1950 (e.g., adjacent to each recess 1930) or may be a mark integrally formed with body 1950. In some embodiments, body 1950 may also include a surface suitable for receiving one or more user-provided indicia 1918. Indicia 1918 may, for example, describe a process (e.g., an assay) to be performed using the liquid in container 1940 received in recess 1930.User-provided indicia 1918 may include alphanumeric text, a symbol, a color, or any other indicia having a known association with the liquid in recess 1930 (e.g., indicating the liquid, a particular process performed using the liquid, etc.). In some embodiments, user-provided indicia 1918 may identify the target analyte of the test. For example, a solvent for amplifying and detecting nucleic acids derived from Mycoplasma genitalium may be identified as "M.gen." in user-provided indicia 1918. In some embodiments, indicia 1918 may include the name of the test to be performed using the liquid in recess 1930. In some embodiments, user-provided indicia 1918 may be a mark applied by the user (e.g., with a writing implement) or a label affixed by the user (e.g., a sticker).

[0152] The solvent container 1920 may also include an RFID transponder 1932 attached thereto. The RFID transponder 1932 may be attached to a conductive portion of the solvent container 1920 or may be positioned so that it is separate from the conductive portion of the container 1920. The RFID transponder 1932 may be configured to wirelessly transmit information related to the container 1920 (e.g., a container identifier identifying each container 1940, a holder identifier identifying the container 1920, a process identifier identifying a process performed using the liquid contained in the container 1940, etc.) to an RFID reader 1934 of the system 1000. Although FIG. 11B shows the RFID reader 1934 attached to the second reagent container carrier 1600, this is merely exemplary. In general, the RFID reader 1934 may be attached to any portion of the system 1000 such that it receives information transmitted by the RFID transponder 1932. Any type of RFID transponder 1932 and reader 1934 may be used in the system 1000. Suitable RFID transponders 1932 and readers 1934 are known in the art and therefore will not be described in detail herein. US Provisional Application No. 62 / 530,743, entitled "For Capacitive Fluid Level Detection," describes an exemplary solvent container 1920 that may be used in the system 1000.

[0153] In the above description, two types of solvent containers (i.e., IVD solvent container 1620 and LDT solvent container 1920) are described. In some embodiments, both of these containers 1620 and 1920 can be sized to be placed in pocket 1610 of second reagent container carrier 1600 (see FIGS. 6A-6C). Any type of solvent container (e.g., container 1620 or 1920) can be used in system 1000. Typically, for IVD assays, an appropriate reconstitution buffer can be obtained (e.g., commercially obtained) in a sealed (e.g., heat-sealed) IVD solvent container 1620. Thus, when system 1000 is used to perform an IVD assay, a sealed IVD solvent container 1620 containing reconstitution buffer can be procured and loaded into second reagent container carrier 1600 for use in a nucleic acid amplification assay. During the assay, the reconstitution buffer can be used to reconstitute reagents (e.g., dried reagents) for amplification. Typically, the dry reagents used in IVD assays contain components necessary for the amplification reaction (e.g., amplification oligomers, probes, polymerase, etc.); therefore, the reconstitution buffer provided in the sealed IVD solvent container 1620 may not contain these components. In contrast, for assays developed or evaluated by a customer or other third party (i.e., LDTs), at least some of the components necessary for the amplification reaction (e.g., some or all of the amplification oligomers, probes, etc.) are typically designed, developed, and validated by the customer or third party. Thus, these components are not included in the reagents (e.g., dry reagents) used in such LDTs. Instead, the customer or other third party may prepare reconstitution fluids (e.g., 1970A, 1970B, etc.) containing one or more of the amplification oligomers, probes, etc., and provide them in vessel 1940 of the LDT solvent container 1920. For example, reconstitution fluids 1970A and 1970B may contain different amplification oligomers and probes targeting different nucleic acids or different regions of the same nucleic acid.Additionally, a reconstitution liquid containing amplification oligomers (and / or probes) can be used to reconstitute dried amplification reagents that do not contain any amplification oligomers and / or probes.

[0154] In some embodiments, only a single type of solvent container (e.g., container 1620 or 1920) may be used in system 1000 during an analysis. For example, if all samples are to be analyzed by system 1000 using one or more IVD assays, system 1000 may use only IVD solvent container 1620 having reconstitution buffer therein. Similarly, if all samples are planned to be analyzed by system 1000 using one or more LDTs, only LDT solvent container 1920 may be used. In some embodiments, system 1000 may be an open-channel system that allows a user to perform IVD assays and LDTs ​​on the same or different samples without exchanging or reloading solvent containers (and / or samples). In such embodiments, IVD solvent container 1620 and LDT solvent container 1920 may be used simultaneously in system 1000. For example, if during an analytical run, one or more samples are analyzed using IVD assay(s) and one or more samples are analyzed using LDT(s), IVD and LDT solvent containers 1620 and 1920 may be loaded into system 1000. In such a case, as illustrated in FIGS. 6A-6C , one or more IVD solvent containers 1620 having reconstitution buffer (e.g., without components such as amplification oligomers, probes, etc.) and one or more LDT solvent containers 1920 having reconstitution solution or solvent (e.g., with components such as amplification oligomers, probes, etc.) may both be loaded into a second reagent container carrier 1600 provided in reagent container compartment 500 of system 1000. The IVD assay may then be performed using the reconstitution buffer in IVD solvent container 1620, and the LDT may be performed using one or more of reconstitution fluids 1970A, 1970B (if required for the particular assay) in LDT solvent container(s) 1920. In some embodiments, the IVD assay and the LDT may be performed by the system 1000 in an alternating or random access manner.That is, IVD assays and LDTs ​​can be alternately performed by the system 1000 without the need to pause the system 1000 to exchange reagents or consumables between the IVD assays and LDTs. For example, an IVD assay (e.g., one or more IVD assays initiated with one or more samples) can be initiated first, followed by an LDT (e.g., one or more LDTs ​​initiated with one or more of the same or different samples), and then the IVD assay can continue without replacing, loading, or replenishing reconstitution fluids, reagents, and / or other consumables between the different assays. Although the IVD assays and LDTs ​​can be initiated at different times, these two assay types can be performed simultaneously by the system 1000 (i.e., processing of a sample by one assay type begins before processing of the sample by the other assay type is completed). Any number of IVD solvent containers 1620 and LDT solvent containers 1920 can be loaded into the second reagent container carrier 1600 (e.g., based on need). For example, if more reconstitution buffer 1656 (e.g., used in an IVD assay) is expected to be needed during a run than reconstitution fluid 1970A, 1970B, then more IVD solvent containers 1620 than LDT solvent containers 1920 (or vice versa) may be provided in the system 1000. The number of each type of solvent container 1620, 1920 required will also depend on the volumetric capacity of the different containers 1620, 1920.

[0155] As previously described, system 1000 can perform IVD assays and LDTs ​​in an alternating fashion. In embodiments in which the IVD assay and LDT performed by system 1000 both incorporate PCR amplification reactions, the amplification reactions for both assays (i.e., the IVD and the LDT) occur in second module 400 (e.g., in thermal cycler 432). However, in embodiments in which one assay (e.g., the IVD assay) is not subjected to PCR conditions and the other assay (e.g., the LDT) is subjected to PCR conditions, amplification of the IVD assay occurs in first module 100 (e.g., in amplification incubator 114) and amplification of the LDT occurs in second module 400 (e.g., in thermal cycler 432). When first module 100 is used for amplification, reagents 768 in reagent pack 760 (described below with reference to FIGS. 13A-13D) may not be used. Instead, liquid reagents stored within first module 100 may be used.

[0156] 11A and 11B, during use, containers 1940 containing reconstitution liquid 1970A, 1970B, etc. are placed in respective recesses 1930 of the LDT solvent container 1920, and the containers 1920 are inserted into pockets 1610 of a second reagent container carrier 1600 disposed in the reagent container compartment 500 (see FIGS. 6A-6C). In some embodiments, all four recesses 1930 of the container 1920 may be loaded with containers 1940 containing reconstitution liquid, while in other embodiments, fewer than all recesses 1930 of the container 1920 may include containers. As previously discussed, the reconstitution liquids (e.g., liquids 1970A, 1970B) in the containers 1940 of the LDT solvent container 1920 may be the same liquid or different liquids. After loading the second reagent container carrier 1600 with the desired number and type of containers (e.g., containers 1620, 1820, and 1920), the user closes the compartment 500. When the LDT solvent container 1920 is installed in the pocket 1610 of the container carrier 1600, the RFID transponder 1932 (see FIGS. 11A and 11B) of the container 1920 is positioned within the operational field of view of the RFID reader 1934. While in this position, the RFID reader 1934 transmits information about the container 1920 to a controller (e.g., controller 5000 of FIG. 33). This information may include, among other information, one or more of the following: (1) a container identifier identifying each vessel 1940 supported within the container 1920; (2) a holder identifier identifying the container 1920; and (3) a process identifier identifying the process (e.g., assay) to be performed using the reconstitution fluids 1970A, 1970B, etc. in the vessels 1940 of the container 1920. Additionally, the RFID reader 1934 may determine the presence of the container 1920 in the pocket 1610 of the second reagent container carrier 1600. For example, if the RFID reader 1934 does not receive any transmitted information normally transmitted by the RFID transponder 1932, this may indicate that no LDT solvent container 1920 is present in the pocket 1610.

[0157] Based on the information received from RFID reader 1934, the controller may determine a process to be performed using reconstitution fluids 1970A and 1970B contained in receptacles 1940 of container 1920 based on the received information's known association with a particular process (e.g., stored in system 1000). For example, the received information may indicate that a certain type of LDT should be performed using the fluids in container 1920, whose user-defined assay parameters are known to system 1000 (e.g., parameters previously stored in system 1000's memory). In some cases, the information received from RFID reader 1934 does not have a known association with a process known to system 1000. For example, reconstitution fluids 1970A and 1970B in LDT solvent container 1920 are intended to perform one or more assays that have not previously been performed (or stored) in system 1000. In some embodiments, if there is a known association with a protocol to be performed using reconstitution fluids 1970A and 1970B, system 1000 processes one or more samples by performing the associated protocol using these fluids without further user input based on the protocol stored in system 1000. However, if there is no known association, additional user input from a user may be required. In some such embodiments, system 1000 (e.g., controller 5000 of FIG. 33) may prompt the user for information, for example, using a graphical user interface (GUI) displayed on display device 50 of system 1000 (see FIG. 1A) or another display associated with system 1000 (e.g., a remote computer running a software tool for developing LDT protocols, described below), to define one or more parameters of an assay protocol that can be saved and later associated with LDT reconstitution fluids 1970A, 1970B.In this context, a first computer is "remote" from a second computer (and possibly one or more additional computers) if the first and second computers are separate computers with independent logic and computing capabilities and independent data input and output components. The first computer and the separate second computer may or may not be in communication with each other, such as by wire or wirelessly, and may or may not be networked with each other.

[0158] To load an LDT solvent container 1920 into the system 1000, the reagent container compartment 500 of the second module 400 is first opened. In some embodiments, the compartment 500 may be opened by selecting (e.g., pressing) an icon on the display 50. The LDT solvent container 1920 is placed in one of the pockets 1610 of the second reagent container carrier 1600 (e.g., the pocket labeled "Recon 4" in FIG. 6D). A pack loading screen or GUI 2100 is displayed on the display device 50. FIG. 12A shows an exemplary pack loading GUI 2100 displayed on the display device. The GUI 2100 includes regions 2102A-2102D representing / corresponding to each reconstitution container pocket of the container carrier 1600 (e.g., "Recon 1," "Recon 2," "Recon 3," and "Recon 4" in FIG. 6D). The controller 5000 (described below) of the system 1000 is configured to alter the characteristics of the regions 2102A-2102D to indicate the presence or absence of the container 1920 in the pocket 1610 of the container carrier 1600, for example, based on signals from the RFID reader 1934 and / or other sensors indicating the presence or absence of the container 1920.

[0159] When an LDT solvent container 1920 is loaded into the "Recon 1" position of the container carrier 1600, the appearance of region 2102A changes to indicate the presence of the container 1920 in this position, as shown in FIG. 12A. Window 2110 of GUI 2100 also changes to correspond to four regions 2106A-2106D. Each region 2106A-2106D corresponds to one of the four recesses 1930 of the container 1920 (marked A-D in FIG. 12A). If a vessel 1940 is present in a recess 1930 (e.g., recess A) of the container 1920, the user may select box 2108A in region 2106A (e.g., by clicking box 2108A) to indicate that the vessel 1940 is "loaded" in recess A. The "Set" button in region 2106A is then clicked to select an LDT protocol from a menu. Clicking "Set" may present the user with a menu (e.g., a drop-down menu) of available LDT protocols stored in system 1000. To associate the reconstitution fluid in well A's container 1940 with an LDT protocol, the user may then select from the presented menu the desired assay to be performed using the reconstitution fluid in well A's container 1940. GUI 2100 may then display the selected assay in subarea 2112A. For example, the user may select "LDT-CMV," which is then shown in subarea 2112A. Subarea 2112A also indicates whether the selected assay is an unlocked or locked assay. Subarea 2114A indicates the maximum number of times the selected assay may be performed using the fluid contained in well A's container 1940. In some embodiments, a default value (e.g., 40) may be shown in subarea 2114A, which may be changed by the user as needed. This completes the assignment or association of the reconstitution fluid in well A with an LDT.

[0160] If another container 1940 is present in another recess of container 1920 (e.g., one of recesses B-D), the above steps are performed for the corresponding area 2106B-2106D of window 2110. Indicators 2104A-2104D in area 2102A indicate when all containers have been assigned or associated. After information for recesses A-D has been entered into the corresponding area 2106A-2106D, the corresponding indicator 2104A-2104D in area 2102A changes color to indicate the status of the assignment. For example, when a container 1940 has been loaded into recesses A-D and all information has been entered into the corresponding area 2106A-2106D, the corresponding indicator 2104A-2104D will show a green light; if a container 1940 has been loaded but the required information has not been entered, the indicator will show a red light. If no container 1940 is loaded in a recess AD, the corresponding indicator 2104A to 2104D is black.

[0161] Once all of the receptacles 1940 in the container 1920 have been assigned or associated with LDTs, the user selects "Save" on the GUI 2100 and closes the reagent container compartment 500. After all desired containers (oil container 1820, reconstitution liquid containers 1620, 1920, and reagent container 1520) are loaded into the bulk reagent container compartment 500, the display device 50 displays a universal liquid storage GUI 2200. FIG. 12B shows an exemplary universal liquid storage GUI 2200. As shown in FIG. 12B, the GUI 2200 displays the status of all containers (e.g., loaded or unloaded), the type of container, and other information associated with each container in the reagent container compartment 500 (number or remaining tests, expiration date, etc.).

[0162] Using user input received using GUI 2100 (FIG. 12A), the controller of system 1000 can associate reconstitution fluids 1970A and 1970B in container 1920 with the assays selected by the user, and if one of these assays is to be performed on the sample, system 1000 will use the corresponding reconstitution fluid to perform the assay. When a step of one of the assays is to be performed, robotic pipettor 410 can move and align with receptacle 1940 (of container 1920) containing the required reconstitution fluid (e.g., liquids 1970A, 1970B, etc.), and aspiration probe 415 or pipette tip 584 of mounting end 425 of pipettor 410 can enter receptacle 1940 and aspirate a portion of the liquid from receptacle 1940. The levels of liquids 1970A and 1970B in receptacle 1940 can be determined by pipettor 410 using capacitive level detection (in a manner similar to that previously described) during aspiration. To enable capacitive level detection, the body 1950 of the solvent container 1920 may include a conductive region 1952 that is connected to the ground plane of the system 1000 (e.g., via the bottom surface of the second reagent container carrier 1600). In some embodiments, the vessel 1940 may be uncovered (i.e., not covered by a frangible cover or lid), and the aspiration probe 415 or pipettor tip 584 (secured to the mounting end 425 of the pipettor 410) may enter the vessel and extract liquid without having to penetrate the cover. However, it is also contemplated that in some embodiments, the vessel 1940 may be covered by a cover and / or lid that is penetrable by a pipettor, and the aspiration probe 415 or pipettor tip 584 (secured to the mounting end 425 of the pipettor 410) may enter the vessel 1940 by piercing the cover.

[0163] In the above description, the IVD and LDT solvent containers 1620 and 1920 are described as being held by the same support of the system 1000. That is, the IVD solvent container 1620, which has the reconstitution buffer for the IVD assay, and the LDT solvent container 1920, which has the reconstitution fluids 1970A and 1970B for the LDT, are both supported by a single second reagent container carrier 1600 located in the reagent container compartment 500 of the second module 400. However, this is not a requirement. In some embodiments, the solvent container 1620 may be provided in one reagent container carrier, and the solvent container 1920 may be provided in another reagent container carrier. These two container carriers may have the same (or different) shape as the second reagent container carrier 1600. Placing the IVD and LDT solvents in different container carriers may allow the system 1000 to support a greater number (and / or greater volume) of solvents and / or solvent containers of different shapes and / or sizes. In some embodiments, a second reagent container carrier 1600 supporting multiple (e.g., four) IVD solvent containers 1620 (having reconstitution buffer for the IVD assay) may be provided in the reagent container compartment 500 of the second module 400, and one or more LDT solvent containers 1920 (having reconstitution fluid for the LDT) may be provided in a different reagent container compartment of the module 400 (in some embodiments, supported in different container carriers). Providing the IVD and LDT solvents in different reagent compartments may also allow the solutions to be maintained at different ambient conditions (e.g., temperature, humidity, etc.). For example, in some embodiments, an LDT solvent container 1920 having solvent for the LDT may be provided in a cooled (or heated) reagent compartment of the second module 400, while a container 1620 having reconstitution buffer for the IVD assay may be maintained at ambient temperature (or a different temperature), or vice versa.

[0164] Reagent Pack Although not a requirement, in some embodiments, amplification and other reagents may be provided in the second module 400 in a reagent pack. As described in more detail below, the reagent pack may include a cartridge having wells into which the reagents are provided. FIGS. 13A-13D show different views of an exemplary reagent pack 760 that may be used in the system 1000. FIGS. 13A and 13B show top and bottom views of the exemplary reagent pack 760, while FIGS. 13C and 13D show cross-sectional views of the exemplary reagent pack 760, showing the contents of its wells 762. Reference is made to FIGS. 13A-13D in the following description. The reagent pack 760 may include multiple mixing wells 762, each of which contains a reagent 768. In some embodiments, the reagent 768 is a unit-dose reagent. Generally, the reagent 768 may be in any state (solid, liquid, etc.), but in some embodiments, the reagent 768 may be a non-liquid reagent. In some preferred embodiments, the reagents 768 may be solid or dried (e.g., lyophilized). In some embodiments, the reagent pack 760 includes 12 foil-covered mixing wells 762, each containing a dried unit-dose reagent 768 (see FIG. 13C). Exemplary unit-dose reagents that may be provided in the reagent pack 760 are described in WO 2017 / 136782. The reagent pack 760 may include a barcode (or other machine-readable indicia) that identifies the contents of the pack (e.g., the type of reagent 768). The unit-dose reagents 768 in each mixing well 762 may be configured to perform an amplification reaction corresponding to an IVD assay or an LDT. Typically, reagents 768 configured for IVD assays are assay-specific reagents, while reagents 768 configured for LDTs ​​are not assay-specific and may include a polymerase, nucleoside triphosphates, and magnesium chloride, among other possible components. In some embodiments, each reagent 768 is held to the bottom of its associated mixing well 762 using an electrostatic charge imparted to the reagent 768 and / or the mixing well 762 .In some embodiments, each reagent 768 is maintained at or near the bottom of its associated mixing well 762 using one or more physical features present in the mixing well 762, such as those described in U.S. Patent No. 9,162,228.

[0165] In some embodiments, the mixing well 762 is covered by a pierceable foil 766 adhered to the top of the reagent pack 760. During use, an aspiration probe 415 holding a previously described solvent (e.g., from a container 1620, 1920, etc.) or a pipette tip 584 secured to the mounting end 425 of the pipettor 410 (see FIGS. 14B-14C ) can pierce the foil 766 and dispense the solvent into the mixing well 762 to reconstitute the reagent 768 and form a liquid reagent 769 (see FIG. 13D ). Reconstitution refers to the act of returning a solid (e.g., dried or lyophilized) reagent 768 to a liquid state. The pipettor 410 can then aspirate the reconstituted liquid reagent 769 from the mixing well 762. As previously described, reagents 768 configured for an IVD assay may include components, such as amplification oligomers and probes, while reagents 768 configured for an LDT may not include such components (as the solvent used for the LDT may contain these components). In some embodiments, reagents 768 for an IVD assay and / or reagents 768 for an LDT may include one or more of a polymerase and a nucleoside triphosphate. In some embodiments, reagents 768 for an IVD assay may include at least one forward amplification oligomer and at least one reverse amplification oligomer. In some embodiments, reagents 768 used for an IVD assay may include probes for performing a real-time amplification reaction. Exemplary probes for real-time amplification reactions are described in Holland, PM, et al., "Detection of specific polymerase chain reaction product by utilizing the 5'--3' exonuclease activity of Thermus aquaticus DNA polymerase," PNAS, 88(16):7276-7280 (1991). Other exemplary probes for performing real-time amplification reactions are disclosed in U.S. Patent Nos. 6,361,945 and 5,925,517.In some embodiments, the reagents 768 for the IVD assay and the reagents 768 for the LDT may be provided in different reagent packs 760. However, this is not a requirement, and in some embodiments, the reagents 768 for the IVD assay and the reagents 768 for the LDT may be provided in different wells 762 of the same reagent pack 760.

[0166] In the embodiment illustrated in FIGS. 13A-13D, the reagent pack 760 includes 12 mixing wells 762 in a 2x6 pattern. However, in some embodiments, the reagent pack 760 may include more or less than 12 mixing wells in any suitable pattern (e.g., a linear pattern, a square grid, a circular pattern, etc.). Each mixing well 762 of a single reagent pack 760 may hold the same reagent, or each well 762 may hold a different reagent, or some wells 762 may hold the same reagent and some may hold different reagents. In some embodiments, the unit-dose reagent 768 used to perform an IVD assay contains the components needed to perform a nucleic acid amplification reaction according to a particular assay. These components may include a polymerase, nucleoside triphosphates, or any other suitable components. Such reagents may be specific for one target nucleic acid or multiple different target nucleic acids. A unit-dose reagent 768 configured for LDT may not include some or all of the components described above. Alternatively, in some embodiments, these missing components may be included in the reconstitution fluid used to reconstitute the reagent 768 .

[0167] In some embodiments, the reagent pack 760 further includes a handling structure 764 (e.g., in the form of a hook) configured to be engageable by a corresponding structure of the container-dispensing system 200 (e.g., a hook shaped to correspond to the container dispenser 312 described below). The reagent pack 760 may be configured to be stored within the compartment 702 of the second module 400, and in some embodiments, to be moved within the second module 400 by the dispenser 312 and inserted into and removed from the reagent pack interchange device 700 (see FIG. 5D). The reagent pack 760 may include a structure 770 configured to align the reagent pack within the reagent pack carrier. Exemplary reagent packs that may be used in the system 1000 are depicted in U.S. Pat. No. 9,162,228. Note that while dried (e.g., lyophilized) reagents are described above, this is not a requirement. That is, as will be generally recognized by those skilled in the art, reagents may be provided in other forms (e.g., gels, etc.).

[0168] Fluid Transfer and Handling Systems The second module 400 includes a fluid transfer and handling system, which includes a robotic pipettor 410 (see FIG. 1B ). FIG. 14A shows an exemplary fluid transfer and handling system 402 of the second module 400. The fluid transfer and handling system 402 can be configured to transfer (e.g., dispense and / or aspirate) liquids between different vessels (containers, wells, vials, etc.) of the second module 400. As shown in FIG. 14A , the system 402 can include a front arm 408 that includes the robotic pipettor 410 and a rear arm 416 that includes a vial transfer arm 418. The vial transfer arm 418 can be, for example, a pick-and-place mechanism without pipetting capabilities, or can be a separate pipettor (e.g., similar to the pipettor 410). In the illustrated embodiment, the fluid transfer and handling system 402 includes a gantry assembly with multiple tracks 404, 406, 412, 420 oriented in orthogonal directions (e.g., horizontally, vertically, etc.). The pipettor 410 and vial transfer arm 418 can be driven back and forth and laterally along the tracks 404, 406, 412, 420 as well as vertically using motors associated with these components.

[0169] The pipettor 410 is configured to aspirate and dispense liquid. As seen in FIG. 14A, the pipettor 410 includes an aspiration probe 415 at its lower end. As described above with respect to FIGS. 7C, 10C, 11B, 13C, etc., the aspiration probe 415 can be inserted into a container (possibly by piercing a pipettor-penetrable cover) and used to aspirate (and / or dispense) liquid from the container. In some embodiments, the lower end of the aspiration probe 415 forms a mounting end 425 that can be inserted into a container. FIGS. 14B and 14C show close-up views of the bottom of the pipettor 410 in a representative embodiment. Reference is made to FIGS. 14A-14C in the following description. In some embodiments, the aspiration probe 415 can be inserted directly into a container to aspirate (or dispense) liquid therefrom. In some embodiments, to reduce cross-contamination, disposable pipette tips 584 may be secured to the mounting end 425 of the aspiration probe 415 before the pipettor 410 is used to aspirate liquid from (and / or dispense liquid into) a vessel. As shown in FIG. 1B, the second module 400 includes a tip compartment 580 having a tray 582 (see FIG. 5A) of disposable pipette tips 584 that can be accessed by the pipettor 410. In some embodiments, the pipette tips 584 may be secured to the mounting end 425 of the aspiration probe 415 by a friction fit. That is, in some embodiments, the outer cylindrical surface of the aspiration probe 415 may frictionally engage the inner cylindrical surface of the pipette tip 584 to hold the pipette tip 584 on the aspiration probe 415. As previously described, the pipettor 410 may be configured to detect the liquid level in a vessel (e.g., container 1620, 1820, 1920) by capacitive liquid level testing. The pipette tip 584 may be made of a conductive material (eg, a carbon-based material) to allow capacitive liquid level testing by the pipettor 410.

[0170] In some embodiments, the pipettor 410 can have an ejection mechanism that allows a pipette tip 584 attached (or secured) to the mounting end 425 to be separated therefrom. In the embodiment illustrated in FIGS. 14B and 14C, the ejection mechanism includes a hollow sleeve 413 slidably disposed around the aspiration probe 415 and a mounting member 411 operatively connected to the sleeve 413 by a link assembly. The sleeve 413 can be attached to the aspiration probe 415 such that the mounting end 425 of the aspiration probe 415 is exposed below the sleeve 413. The pipette tip 584 can be secured to the aspiration probe 415 at the portion of the mounting end 425 exposed below the sleeve 413. FIG. 14B shows a view of the sleeve 413 with the pipette tip 584 attached. The mounting member 411 includes an actuator arm 414 pivotally connected thereto. The actuator arm 414 is connected to the sleeve 413 by a link assembly such that when the free end of the actuator arm 414 is pressed toward the mounting member 411, the sleeve 413 slides downward over the aspiration probe 415 (see FIG. 14C ), thereby ejecting the pipette tip 584 from the mounting end 425 of the aspiration probe 415. That is, when the actuator arm 414 is actuated (moves toward the mounting member 411), the sleeve 413 slides downward over the aspiration probe 415, pushing the pipette tip ...

Claims

[Claim 1] The invention described in this specification.

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