• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
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    • 专利摘要:
    Method and System for Performing Automated Assay and Methods for Performing Reflective Testing on Multiple Copies The embodiments disclosed herein pertain to methods and systems for performing automated assays, and more specifically, for performing sequential assays on a sample in an automated instrument.
    公开号:BR112014025384B1
    申请号:R112014025384-6
    申请日:2013-03-13
    公开日:2022-01-25
    发明作者:Celine Roger Dalbert；Joel Daniel Krayer；Adam Bruce Steel；Denis Roy
    申请人:Becton, Dickinson And Company；
    IPC主号:
    专利说明:

    DESCRIPTIVE REPORT BACKGROUND Technical Field
    [001] The modalities disclosed herein pertain to methods and systems for performing automated sequential assays, such as nucleic acid test assays. Description of Related Technique
    [002] The automation of molecular testing of samples has become increasingly popular in part because automation is able to reduce the time from collecting a sample to obtaining the results, minimizing experimental variability and reducing the need for highly trained technicians. In addition to the benefits in the field of diagnostics, automation in sample processing and testing promotes high test throughput. Automated devices for processing copies or samples typically include hardware and consumables. Therefore, it is desirable to maximize the automation of molecular testing while minimizing the amount of consumables used.
    [003] The described modalities propose an improved automated testing of specimens and/or samples that can be advantageously used in clinical and research settings. SUMMARY
    [004] The present technology relates to methods and systems for performing automated sequential assays, such as nucleic acid test assays. Some modalities refer to sequential assays of one or more specimens performed on an automated instrument. In some embodiments of the technology presented in this document, methods are proposed for performing an automated multi-sample assay that allow greater reliability and simplicity of use when examining multiple specimens on an automated instrument. Methods may include: a) providing an automated instrument configured to receive and process multiple samples taken from multiple specimens for one or more target analytes in accordance with one or more respective assay workflows; b) provide several samples to be tested; c) automatically transferring a first fraction of each of several samples to be tested to respective first several reagent vessels for a first test for a first target analyte; d) automatically performing the first test on the fraction of the various samples to determine the presence of a first target analyte in accordance with a first assay workflow; e) selecting a subset of samples among the various samples in which the presence of the first target analyte was determined; f) automatically transferring a second fraction of the subset of samples selected in e) to a second vessel with reagents for a second test to determine the presence of a second target analyte in accordance with a second assay workflow; and g) automatically running the second test on the second fraction of the selected sample subset.
    [005] In some embodiments, each of the multiple samples comprises a preprocessed solution of nucleic acids isolated from respective multiple specimens. In some embodiments, the automated instrument automatically processes the multiple specimens to obtain the respective multiple samples with isolated nucleic acids.
    [006] In some embodiments, for each sample, the sample and the first vessel with reagents for a first test are arranged on a first test strip, in such a way that step f) also comprises automatically transferring the second fraction of the sample to the second vessel with reagents for the second test arranged on a second test strip.
    [007] In some embodiments, step e) further comprises: e1) identifying a subset of the various first test strips for the second test; and e2) for each first test strip in the subset, providing a corresponding second test strip containing a vessel of reagents for a second test for a second analyte.
    [008] In some embodiments, the second test strip comprises at least one pipette tip. In some embodiments, the method comprises, prior to step f), adding extra liquid to the sample.
    [009] In some embodiments, for each sample, the sample, the first vessel and a receptacle for the second vessel are arranged on the same test strip. In some embodiments, the method comprises, prior to step d), the steps of d1) identifying a subset of the plurality of first test strips to test for the presence of the second analyte; and d2) for each test strip in the subset, provide a second vial of reagents for the second test in the receptacle.
    [0010] In some embodiments, the method comprises, before step f), the step of providing a pipette tip configured to transfer the second fraction of the sample to the second vessel with reagents for the second test.
    [0011] In some embodiments, the pipette tip may be, for example, an unused pipette tip or a washed pipette tip. In some embodiments, the method comprises, prior to step f), the step of adding extra liquid to the sample.
    [0012] In some modalities, the first test comprises a reaction selected from the group consisting of: Polymerase Chain Reaction (PCR), Transcription-Mediated Amplification (TMA), Oligonucleotide Binding Assay (OLA), Ligase (LCR), Rolling Circle Amplification (RCA), Ribbon Shift Amplification (SDA) and a hybridization reaction.
    [0013] In some embodiments, the method further comprises the step of comparing identification indicia on a test strip to a set of test-specific identification data stored in the instrument.
    [0014] Also proposed in this document is a system for performing an automated assay on multiple samples taken from respective multiple specimens, the system comprising an automated instrument configured to receive and process multiple samples in accordance with one or more assay workflows; the instrument comprising several test strips; a processor; a storage space; and a program for performing an automated assay, the program comprising instructions for a) providing an automated instrument configured to receive and process a plurality of samples in accordance with one or more assay workflows, the instrument comprising a plurality of test strips; b) automatically transferring a first fraction of each sample to respective several first vessels with reagents for a first test; c) performing the first test to determine the presence of a first targeted analyte; d) automatically transferring a second fraction of the samples, or a selected subset of the samples, to respective second vessels with reagents for a second test; and e) performing a second test on the second fraction of the samples, or selected subset of samples, to determine the presence of a second target analyte.
    [0015] In some embodiments of the above system, the program further comprises instructions for automatically isolating nucleic acids from the multiple exemplars in order to obtain respective multiple samples with isolated nucleic acids.
    [0016] In some embodiments of the above system, for each sample, the samples and the first vessel with reagents for the first test are situated on a first test strip, in which step e) comprises automatically transferring a fraction of the acid solution extracted nucleic acids to a second master mix tube situated on a second test strip.
    [0017] In some modalities of the system above, for each sample, the sample, the first vessel and a receptacle for the second vessel are arranged on the same test strip, in which the program comprises instructions for steps d1) to identify a subset of the various first test strips to test for the second analyte; and d2) for each test strip in the subset, provide a corresponding second vessel with reagents for the second test in the receptacle.
    [0018] Also proposed in this document is a method for performing reflective tests on multiple instances, the method comprising a) providing multiple instances to be tested; b) processing the various copies in order to obtain their various samples; c) transferring a first fraction of each of several samples to be tested to respective first several reagent vessels for a first test for a first target analyte; d) performing the first test on the fraction of the various samples to determine the presence of a first target analyte; e) selecting a subset of samples from among the various samples in which the presence of the first target analyte for the reflex test was determined; f) transferring a second fraction of the subset of samples selected in step e) to a second vessel with reagents for a second test to determine the presence of a second target analyte; and g) running the second test on the second fraction of the selected sample subset.
    [0019] In some embodiments of the above methods, the first test comprises a test for the simultaneous detection of methicillin-resistant Staphylococcus aureus and Staphylococcus aureus, wherein the second test comprises a test for the detection of a mupirocin resistance determinant. In some embodiments, the mupirocin resistance determinant comprises the mupA gene.
    [0020] Also proposed in this document is a method for performing reflective tests on an exemplar, the method comprising a) providing an exemplar to be tested; b) processing the copy to obtain a respective sample; c) transferring a first fraction of the sample to be tested to a first vessel with reagents for a first test for a first target analyte; d) performing the first test on the first fraction of the sample in order to determine the presence of the first targeted analyte; f) transferring a second fraction of the sample to a second vessel with reagents for a second test to determine the presence of a second target analyte if the first target analyte is detected in the first fraction of the sample; and g) performing the second test on the second fraction of the sample.
    [0021] In some embodiments of the above method, the first test comprises a test for the simultaneous detection of methicillin-resistant Staphylococcus aureus and Staphylococcus aureus, wherein the second test comprises a test for the detection of a mupirocin resistance determinant. In some embodiments, the mupirocin resistance determinant comprises the mupA gene. BRIEF DESCRIPTION OF THE DRAWINGS
    [0022] FIG. 1 illustrates a test strip according to one embodiment.
    [0023] FIG. 2 illustrates a test strip according to one embodiment.
    [0024] FIG. 3 illustrates several test strips arranged in a strip holder according to one embodiment. DETAILED DESCRIPTION
    [0025] The section titles used in this document are for organizational purposes only and should not be construed to limit the inventive material described in any way. All literature and similar materials cited in this application including, without limitation, patents, patent applications, articles, books, treatises and websites, regardless of the format of such literature, and similar materials are expressly incorporated by reference herein at in full for any purpose. In the event that one or more literature and similar incorporated materials define or use a term in a manner that contradicts the definition in the present application, the latter shall govern. While the present teachings are described in conjunction with various embodiments, it is not intended that they be limited to said embodiments. Rather, the present teachings encompass various alternatives, modifications and equivalents, as those skilled in the art will appreciate.
    [0026] Automated diagnostic instruments capable of processing and testing multiple specimens and/or samples in parallel have already been described. These devices can be used to advantage with high throughput to facilitate the preparation and testing of specimens and/or samples. By way of example, automated diagnostic instruments can prepare samples for diagnostic assays, such as nucleic acid amplification assays, and perform amplification and detection.
    [0027] Diagnostic tests are by nature hypothesis driven. When performing a hypothesis-driven test, such as testing a sample for a specific analyte, the test result may lead to a desire to test another target, that is, a reflexive test. However, often only a subset of the original samples is worth testing, and it would be uneconomical to test all samples. By way of example, in a clinical setting, it may be desirable to test a specimen for the presence of one or more pathogens. If the test reveals the presence of a specific pathogen, it may be desirable to perform other tests, for example, to determine the presence of antibiotic resistance determinants. Obtaining another specimen for a new test, for example from a patient whose specimen tested positive for an analyte indicative of the presence of a specific pathogen, can be difficult and further delay the desired test. In addition to the possible difficulty in obtaining multiple test specimens, if multiple specimens are tested, manual approaches to transferring patient specimens, or samples prepared from test specimens (e.g., nucleic acid tests), to a new vessel reaction can be error-prone as well as inefficient and labor-intensive. Furthermore, when specimens need to be processed prior to testing, it is desirable to minimize the costs associated with processing (eg, with reagents and the like). Therefore, there is a great need for improved methods to perform reflective tests in an automated manner.
    [0028] Thus, a “reflective test” refers to a subsequent test (eg a second test) to be performed based on the results of a previous test (eg a first test). Non-limiting examples of first tests and reflexive tests include, for example, a first test for the presence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus (MSSA). In the case of samples that test positive for MRSA or MSSA, it may also be desirable to determine whether they contain determinants of resistance to mupirocin (an antibiotic). As mupirocin resistance is generally only relevant in the case of samples that test positive for MRSA or MSSA, it would generally be uneconomical to test samples that test negative for MRSA and MSSA for mupirocin resistance. Various tests and reflex tests useful to the modalities revealed in this document are discussed in more detail below.
    [0029] The methods and systems proposed in this document advantageously utilize residual material from the original test rather than requiring a new specimen to be obtained from the patient. For example, it may be especially advantageous to use waste material that has been highly processed and requires little additional effort to perform the reflective test. Copies and Samples
    [0030] The modalities disclosed herein can be used to test specimens using automated molecular assays. As used herein, the term "sample" refers to a specimen or clinical sample from one or more sources, including, but not limited to, bodily fluids (including, but not limited to, blood, urine, serum, lymph, saliva, anal secretions, and vaginal fluids, perspiration, peritoneal fluid, pleural fluid, effusions, ascites, purulent secretions, lavage fluids, drained fluids, brush cytology specimens, biopsy tissue, removed medical devices, infected catheters, pus, biofilms and semen) of virtually any organism, with mammalian samples, in particular human samples, and environmental samples (including but not limited to air, agriculture, water and soil samples) that find use in the invention. In addition, samples can be taken from food processing, which can include both incoming samples (e.g. grain, milk or animal carcasses) and samples at intermediate processing stages, as well as ready-to-eat finished foods.
    [0031] In some embodiments, samples are prepared from the samples, and tests are performed on the samples. For example, in some embodiments, specimens may be processed to obtain samples suitable for molecular testing. In some embodiments, specimens can be analyzed directly and are not pre-processed before testing. For example, a "direct sample" is a specimen collected from a patient and tested using the methods disclosed herein without isolating or culturing bacteria from the specimen, or without processing the specimen to isolate nucleic acids prior to testing. As such, direct samples are usually only minimally processed prior to screening. In some embodiments, the specimens disclosed herein are processed to obtain samples suitable for testing. For example, specimens containing cells can be processed to lyse the cells and release cellular components, such as nucleic acids, proteins, and the like, prior to testing. In some embodiments, the specimens can be processed to produce samples with isolated nucleic acids. As used herein, the phrase "isolated nucleic acids" refers to the purification of nucleic acids from one or more cellular components. Those skilled in the art will appreciate that samples processed to "isolate nucleic acids" therefrom may include components and impurities other than nucleic acids. Samples with isolated nucleic acids can be prepared from specimens using any acceptable method known in the art. For example, cells can be lysed using known lysing agents, and nucleic acids can be purified or partially purified from other cellular components. Suitable reagents and protocols for DNA and RNA extractions can be found, respectively, in US Patent Application Publications US 2010-0009351 and US 2009-0131650, each of which is incorporated herein by reference in its entirety. In nucleic acid testing (e.g. amplification and hybridization methods discussed in more detail below), the extracted nucleic acid solution can be added directly to a reagent (e.g., or in liquid, bound to a substrate, in lyophilized form). or the like, as discussed in more detail below) required to run a test in accordance with the modalities disclosed in this document.
    [0032] In some embodiments, tests, eg the first tests and the reflex tests described in this document are tests used to determine the presence of a target analyte in an exemplar or sample. As used herein, the term "target analyte" can refer to various types of analytes of interest, including, for example, target nucleic acids, target proteins, or other target molecules of interest. In some embodiments, the devices and methods described herein are used to perform reflex tests to determine the presence of target nucleic acids, although those skilled in the art will appreciate that the modalities disclosed herein can be readily adapted for other types of target analytes.
    [0033] In accordance with the foregoing, the modalities disclosed herein advantageously propose improved methods to automatically test specimens and samples for the presence of targeted analytes. Methods for performing an automated assay on multiple samples. In some embodiments, the method may a) provide an automated instrument configured to receive and process multiple samples taken from said multiple specimens for one or more target analytes in accordance with one or more respective assay workflows; b) provide several samples to be tested; c) automatically transferring a first fraction of each of said multiple samples to be tested to respective first multiple reagent vessels for a first test for a first target analyte; d) automatically performing the first test on the fraction of said multiple samples to determine the presence of a first targeted analyte in accordance with a first assay workflow; e) selecting a subset of samples among the various samples in which the presence of the first target analyte was determined; f) automatically transferring a second fraction of the subset of samples selected in e) to a second vessel with reagents for a second test to determine the presence of a second target analyte in accordance with a second assay workflow; and g) automatically running the second test on the second fraction of the selected sample subset.
    [0034] Automated instruments that can be used in the embodiments disclosed herein include, for example, those described in US Patent No. 8,133,671 and US Patent Application No. 2009-01 1 1059, which are incorporated herein. by reference in full. Those skilled in the art will appreciate, however, that the embodiments disclosed herein may be readily adaptable to any automated system suitable for processing and testing specimens and/or samples. Desirably, automated systems are configured to allow processing and testing of multiple samples according to one or more workflows. As used in this document, the terms "workflow", "assay workflow", "assay", "assay protocol", "test" and similar terms refer to a procedure for processing a specimen and/or sample. In typical embodiments, a workflow includes steps for sample preparation, such as cell lysis, nucleic acid extraction, nucleic acid purification, nucleic acid digestion, nucleic acid modification, protein extraction, protein purification and their similar. Various methods for extracting nucleic acids useful in the embodiments disclosed herein are known in the art. Exemplary discussions of nucleic acid extraction can be found, for example, in US Patent Application Publication No. 2009-0131650, US Patent Application Publication No. 2010-0009351, and US Patent Application Publication No. 1/281,247, which are incorporated herein by reference in their entirety. Similarly, exemplary discussions of protein extraction can be found, for example, in US Patents 8,053,239 and 6,864,100, both of which are incorporated herein by reference in their entirety.
    [0035] In some typical embodiments, a workflow may also include nucleic acid amplification reactions. In some typical embodiments, a workflow may also include data analysis procedures.
    [0036] As described above, in some embodiments, a fraction (eg, a first fraction and, in some cases, a second fraction) of the sample being examined or analyzed is transferred to a vessel with reagents for a test. As used herein, the term "vessel" refers to any type of object capable of holding a sample, including but not limited to tubes, microtiter plate vessels, and the like. In some embodiments, the vessel is located within a test strip. As used herein, the terms “test strip” or “reagent strip” refer to a package that contains one or more consumable components for an automated assay. The test strips can therefore be configured for use by an apparatus which performs automated preparation of specimens and/or samples, which apparatus is described, for example, in International Patent Application Publication No. WO 09/054870, which is incorporates this document by reference in its entirety.
    [0037] In typical embodiments, a test strip may comprise a vessel, such as a tube, cavity or the like, for containing a sample or solution preprocessed with isolated nucleic acids obtained from an exemplar. Typically, the test strip may also comprise a vessel to contain reagents for a molecular test, such as a nucleic acid test (e.g., reagents used in nucleic acid amplification, as discussed in more detail elsewhere in this document). In some embodiments, the test strip may include other vessels to perform sample preparation and to contain reagents and other consumables, such as pipette tips. In some embodiments, the test strip or reagent strip includes one or more receptacles or openings configured to receive reaction vessels with test reagents. Thus, in some embodiments, vessels containing reagents for use in the assays described herein are unitary or integral with the test strip, whereas, in some embodiments, vessels containing reagents for use in the assays described herein are not integral. to the test strip, but are adapted to fit into a receptacle or opening in the test strip. Non-limiting examples of test strips or reagent strips that can be used in the embodiments disclosed herein are defined in Figures 1 and 2, in US Patents D618820 and D637737 and in US Provisional Patent Application No. September 30, 2011 and titled “UNITZED REAGENT STRIP”, each of which is incorporated herein by reference in full. Figure 1 and Figure 2 illustrate exemplary test strips/reagent strips that can be used in the embodiments disclosed herein.
    [0038] An automated instrument may comprise or be configured to receive, for example, on a dock, one or more strip holders, each strip holder or shelf capable of holding several test strips and, optionally, tubes, for example , tubes for transporting specimens. In typical embodiments, test strips are positioned on one or more strip racks or racks accommodated in the automated instrument. Exemplary strip racks and racks that can be used in the embodiments disclosed herein are disclosed, for example, in Patent Application Publication No. use with an automated system as described in this document may be used. In some embodiments, test strip racks or racks are configured to hold multiple test strips or reagent strips, for example, in multiple rows. For example, the test strip holder can contain 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24 or more rows configured to accommodate any number from 2 to 24 respective test strips or reagent strips.
    [0039] In the methods discussed in this document, depending on the results of the first test performed on the sample, a reflective test is performed. If the results of the first test reveal the desirability of performing the reflective (subsequent) test, according to the methods disclosed herein, a second (residual) fraction of the sample remaining from the first test procedure is automatically transferred to a second vessel with reagents. for the reflexive (subsequent) test. Automatic transfer of the second sample fraction can be performed by any of several methodologies. For example, in some embodiments, the vessel containing the remaining or residual fraction of the sample after the first test may be transferred to a second test strip, after which at least a fraction of the sample is then automatically transferred to a second vessel with reagents for a second test. In some embodiments, the second sample fraction is automatically transferred directly from the first test strip to a second master mix tube disposed on a second test strip. In some embodiments, the second sample fraction is automatically transferred directly from the first test strip to a second vessel disposed on the first test strip. It will be appreciated that while various embodiments are described in more detail below, any methodology suitable for automatically transferring the extracted nucleic acid solution to a second master mix tube can be performed in accordance with the methods proposed herein. Transferring to a new test strip
    [0040] In certain embodiments, for each sample, the sample and a vessel or tube with reagents for the first test are placed on the same test strip, for example, a first test strip, and the step of automatically transferring a fraction of the sample involves automatically transferring a second fraction of the sample to a second master mix tube situated on a separate second test strip.
    [0041] In some embodiments, the first and second test strips are located on different strip racks or racks. As a non-limiting example, first test strips may be positioned in rows 1 to 6 of a first strip holder, and second test strips may be positioned in rows 1 to 6 of a second strip holder. An example of test strips placed in a strip holder is illustrated in Figure 3.
    [0042] In some embodiments, the first and second test strips are located on the same strip holder. In a non-limiting example, the first test strips are placed in rows 1, 3, 5, 7, 9 and 11 and corresponding second test strips are placed in rows 2, 4, 6, 8, 10 and 12 of the same holder. of strips. In another non-limiting example, the first test strips are positioned in rows 1 to 6 and the corresponding second test strips are positioned in rows 7 to 12 of the same strip holder. It will be appreciated that any configuration suitable for positioning the first and second test strips can be used. In some embodiments, the automated instrument may use identifying indicia, such as a bar code, RFID code, or the like, on each test strip to identify the position of the first and/or second test strip. In some embodiments, the method further comprises the step of comparing identification indicia on a test strip, a vessel within a test strip, or a tube of specimens to a set of test-specific identification data stored in the instrument.
    [0043] Therefore, in some embodiments, the user can select one or more first test strips for a second reflective test and transfer the one or more selected test strips to a new shelf that contains second test strips with vessels containing reagents for the second reflex test. In some embodiments, the user may select one or more of the first test strips for a second reflective test, and the automated instrument or user may transfer a second fraction of the sample to a second test strip located on a second strip rack or rack. of different test. In some embodiments, the identification indicia on specimen tubes or test strips used in the first test can be accessed by the automated instrument, and this information can be used to monitor the samples as they are processed during a second reflective test. Thus, in some embodiments of the methods described above, the method may comprise, before transferring a second fraction of the sample to a second vessel, identifying a subset of the several first test strips for retesting, for example, for a second test; and, for each first test strip in the subset, providing a corresponding second test strip. The second test strip can include the second vial of reagents for the second test. In certain embodiments, the second test strip also includes at least one pipette tip. Transfer to the same test strip
    [0044] In certain embodiments, for each sample, the sample solution and the first vessel with reagents for the first test are situated on a first test strip, and the step of transferring a fraction of the extracted nucleic acid solution comprises transferring a fraction of the extracted nucleic acid solution to a second vessel with reagents for a second test also located on the first test strip.
    [0045] In some embodiments of the methods described above, the method may include, before transferring a second fraction of the sample to a second vessel, the steps of: identifying a subset of the various samples for retesting, for example, for a second test reflective; and, for each of the samples identified for retesting, providing a corresponding second vessel with reagents for the second reflective test on the first test strip. In a typical embodiment, the first test strips are configured with an open position, for example a receptacle or vessel, suitable for adding an extra master mix tube to the strip. For example, the test strip can be a strip with 4 slots, as shown in Figure 2, which allows the user to add the reflective master mix in the open position. In some embodiments, test strips are arranged by the user on a new test strip rack or rack before performing the second reflective test.
    [0046] Those skilled in the art will appreciate that it is desirable to minimize the risk of cross-contamination between reagents from the first test and reagents from the second reflective test. Therefore, in some embodiments, consumable items, such as pipette tips, may be replaced and/or cleaned using residual buffers on the test strip prior to performing the reflective test. Thus, in certain embodiments, the method comprises, prior to transferring the second fraction of the sample to the second vessel, the step of providing a pipette tip. In some embodiments, the pipette tip is an unused pipette tip. In some embodiments, the pipette tip is a used tip that has been washed to lessen or prevent contamination from previous liquid transfers. In certain embodiments, the method comprises, prior to transferring the second fraction of the sample to the second vessel, the step of washing a pipette tip used during the first test.
    [0047] During processing and/or testing of samples prior to a second reflective test, sample evaporation may occur. As such, sample evaporation can decrease the performance of a reflective test. The embodiments disclosed in this document propose a solution for evaporation using a fixed volume buffer, e.g. a wash buffer or nucleic acid elution buffer, to add to the residual sample to ensure there is sufficient volume for further processing. of the residual sample, for example in a second reflective test. Thus, in some embodiments, the method comprises, prior to performing a second reflective test, the step of adding extra liquid to the residual sample. By way of example only, in some embodiments, the initial volume of a sample can range from 1 μl to 1 ml and preferably is between 10 μl and 200 μl, for example from 25 μl to 75 μl. In some embodiments, a first fraction of about 5 μl to 25 μl, for example from 10 μl to 20 μl, of the sample is removed for the first test. By way of example, in some embodiments, 12.5 μl of the initial sample is used in the first test. In order to ensure that sufficient sample volume is available for the second test, in some embodiments, an extra volume of 0.5 μl, 1 μl, 2 μl, 3 μl, 4 μl, 5 μl, 6 μl, 7 μl , 8µl, 9µl, 10µl, 12µl, 14µl, 16µl, 18µl, 20µl, 25µl, 30µl, 35µl, 40µl, 45µl, 50µl, 55µl, 60µl than μl of extra liquid can be added to increase the liquid volume before transferring a second fraction of the sample to a vessel with reagents for a second reflective test. Therefore, adding solution to the remaining or residual sample can compensate for the risky evaporation that occurs before transferring the solution to the second master mix. In some modalities, a volume equal to 0.1%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25 %, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 120%, 140%, 160%, 180%, 200%, 250%, 300%, 350%, 400% or more relative to the volume of extracted nucleic acid solution remaining after the first aliquot is transferred to the first master mix can be added to increase the liquid volume and compensate for the risky evaporation taking place before transferring the solution to the reagent vessel for a second test. Nucleic Acid Test Assays (NAT) and Reagents for NAT
    [0048] As discussed above, the tests described herein may include, for example, nucleic acid tests. In some embodiments, testing includes testing for the presence of targeted nucleic acid sequences in a sample. Various forms of nucleic acid testing can be used in the embodiments disclosed herein, including, but not limited to, tests that involve nucleic acid amplification reactions. Various nucleic acid amplification reactions are known and can be used to determine the presence of target nucleic acids in accordance with the modalities disclosed herein. Nucleic acid amplification methods may include but are not limited to: polymerase chain reaction (PCR), strand displacement amplification (SDA), e.g. multiple displacement amplification (MDA), loop-mediated isothermal amplification (LAMP), ligase chain reaction (LCR), immunoamplification, and various transcription-based amplification procedures, including transcription-mediated amplification (TMA), nucleic acid sequence-based amplification (NASBA), replication-independent sequences (3Sr), and amplification by scroll circle. See, for example, Mullis, “Process for Amplifying, Detecting, and/or Cloning Nucleic Acid Sequences,” US Patent No. 4,683;195; Walker, “Strand Displacement Amplification”, US Patent No. 5,455,166; Dean et al., “Multiple displacement amplification”, US Patent No. 6,977,148; Notomi et al., “Process for Synthesizing Nucleic Acid', US Patent No. 6,410,278; Landegren et al., US Patent No. 4,988,617, “Method of detecting a nucleotide change in nucleic acids”; Birkenmeyer, “Amplification of Target Nucleic Acids Using Gap Filling Ligase Chain Reaction”, US Patent No. 5,427,930; Cashman, "Blocked-Polymerase Polynucleotide Immunoassay Method and Kit", US Patent No. 5,849,478; Kacian et al., "Nucleic Acid Sequence Amplification Methods", US Patent No. 5,399,491; Malek et al., "Enhanced Nucleic Acid Amplification Process", US Patent No. 5,130,238; Lizardi et al., BioTechnology, 6: 1197 (1988); Lizardi et al., US Patent No. 5,854,033, “Rolling circle reporter replication systems”. In some embodiments, two or more of the listed nucleic acid amplification methods are performed, for example, in sequence.
    [0049] As discussed above, in some embodiments, fractions of a sample are transferred to a vessel with reagents for a test. For example, in some embodiments, samples are transferred to a vessel that contains a “master mix” for a test or reaction, such as an amplification reaction or the like. The "master mix" may include any or all of the components necessary for a reaction, including but not limited to enzymes, oligonucleotides, probes, salts, deoxynucleotide triphosphates, which comprise a polymerase enzyme and various nucleotides. In some embodiments, the master mix further comprises hybridization probes with detectable clusters, wherein the probes hybridize specifically to target nucleic acids (and/or positively control target nucleic acid sequences). In some embodiments, a master mixture is provided at a higher concentration than will be used in a reaction. In some embodiments, a master mixture is provided in lyophilized form and reconstituted at a higher concentration than will be used in the reaction. In some embodiments, a master mixture includes reactants at a concentration of at least about 2x the reaction concentration, for example, 2x, 2.5x, 3x, 4x, 5x, 6x, 7x, 8x, 9x, 10x, 15x, 20x, 25x, 40x, 50x, 100x, 200x, 250x or 500x.
    [0050] In some embodiments, the master mix may be in the form of one or more lyophilized granules, as stored in a reagent tube on the test strip, and the method may further include reconstituting a reagent granule with liquid, for example, a fraction of a sample as described above in this document to create a reaction/reagent mixture solution suitable for processing, eg testing.
    [0051] In some embodiments, a “master mix” is included in a vessel with identifying indicia, such as a barcode, RFID code, or the like, that provide identifying information about the reagents contained therein, for example, evidence identifying that the vessel contains reagents for the detection of a specific targeted analyte. Instruments and Systems
    [0052] Also proposed in this document is a system for performing an automated assay, the system comprising an automated instrument configured to receive and process multiple specimens or samples in accordance with one or more assay workflows described herein above.
    [0053] The system may also include a processor; a storage space; and a program to run an automated assay. For example, the program may include instructions for an automated instrument configured to receive and process multiple samples in accordance with one or more assay workflows as described in this document. The program may include instructions for receiving and processing multiple samples according to one or more workflows, where samples are arranged on multiple test strips; automatically transferring a first fraction of each sample to respective first several reagent vessels for a first test; performing the first test to determine the presence of a first targeted analyte; automatically transferring a second fraction of the samples, or a selected subset of the samples, to respective second vessels with reagents for a second test; and performing a second test on the second fraction of the samples, or selected subset of samples, to determine the presence of a second target analyte.
    [0054] Automated instruments that can run multiple assay protocols at the same time are known to those skilled in the art and include, among others, BD MAX® (Becton Dickinson and Co., Franklin Lakes, NJ), VIPER® (Becton Dickinson and Co. ., Franklin Lakes, NJ), VIPER LT® (Becton Dickinson and Co., Franklin Lakes, NJ), SMARTCYLCER® (Cepheid, Sunnyvale, CA), ABI PRISM 7700® (Applied Biosystems, Foster City, CA), ROTOR- GENE™ (Corbett Research, Sydney, Australia), LIGHTCYCLER® (Roche Diagnostics Corp, Indianapolis, IN), ICYCLER® (BioRad Laboratories, Hercules, CA), IMX4000® (Stratagene, La Jolla, CA), Timed PCR System Real CFX96™ (Bio-Rad Laboratories Inc) and the like. Exemplary discussions of typical automated instruments for use with the methods proposed herein can be found, for example, in US Patent No. 8,133,671, which is incorporated herein by reference in its entirety.
    [0055] It will be appreciated that the methods and systems described in this document may apply to instruments with 2, 3, 4 or more workstations, where at least two of the workstations are supported by a service resource in ordinary. For example, an instrument with four workstations and a single pipette head could still be controlled on the basis of compatibility by the two-index concept described in this document.
    [0056] As used in this document, the terms “storage space”, “storage device”, “storage” and the like refer to any medium, device or media for storing information. Storage may include, but is not limited to, a disk drive device, such as a hard disk drive, floppy disk, optical disk, or magnetic optical disk, memory, such as RAM or ROM chips, and any other media used to record or store data. In some embodiments, a storage space connects to a processor, which sends information to be written to the storage space after acquiring it. In specific embodiments, data is acquired by a system and written to a storage space. In other embodiments, data is acquired by a system and the information is first processed and then this processed information is recorded in a storage space.
    [0057] The files and programs proposed in this document can be in any suitable programming language. In certain embodiments, ADF uses XML as a mechanism for formatting files. Furthermore, in certain embodiments, ADF uses Python as a scripting language to provide a mechanism for executing result logic using common technologies available in the instrument. It will be appreciated that any suitable file format and programming language can be used with the methods and systems proposed in this document. In certain embodiments, files may be encrypted to protect against the use of counterfeit reagents and to control specific parameter details in assay operations.
    [0058] As used in this document, an "input" may include, for example, data received through a keyboard, pen, mouse, speech recognition system or other device capable of transmitting information from the user to the computer. The input device may also be a touchscreen associated with the display medium, in which case the user responds to commands on the display medium by touching the screen. The user can enter textual information through an input device such as a keyboard or touch screen.
    [0059] The modalities disclosed in this document are operational with many different general purpose or specific computing system environments or configurations. Examples of well-known computing systems, environments and/or configurations that may be suitable for use with the invention include, but are not limited to, microcontrollers, personal computers, server computers, handheld devices, portable devices or laptops, multiprocessor systems, microprocessor-based systems, consumer programmed electronic components, network PCs, personal computers, mainframe computers, distributed computing environments that include any of the above systems or devices, among others.
    [0060] As used in this document, “instructions” refers to computer-implemented steps to process information in the system. Instructions can be implemented in software, firmware or hardware and include any type of programmed step performed by system components.
    [0061] A “microprocessor” or “processor” can be any general purpose microprocessor with one or more cores, such as a Pentium® processor, an Intel® Core™ processor, an 8051 processor, a MIPS® processor, or an ALPHA processor. ®. Furthermore, the microprocessor may be any conventional purpose-built microprocessor, such as a digital signal processor or a video processor. “Processor” may also refer to, but are not limited to, microcontrollers, field programmable gate arrays (FPGAs), application-specific integrated circuits (ASICs), complex programmable logic devices (CPLDs), programmable logic arrays (PLAs), microprocessors or other similar processing devices.
    [0062] The system consists of several modules as discussed in detail in this document. As those skilled in the art will appreciate, each of the modules comprises various subroutines, procedures, definition instructions, and macros. Each of the methods is usually compiled separately and linked to the same executable program. Therefore, the following description of each of the modules is for convenience purposes when describing the functionality of the preferred system. Therefore, the processes executed by each of the modules can be arbitrarily redistributed to one of the other modules, combined in the same module, or made available, for example, in a library of sharable dynamic links.
    [0063] Certain system modes can be used against various operating systems such as SNOW LEOPARD®, iOS®, LINUX, UNIX or MICROSOFT WINDOWS®.
    [0064] Certain system modes can be written in any conventional programming language such as Assembly, C, C++, BASIC, Pascal or Java, and run on a conventional operating system.
    [0065] Additionally, modules and instructions can be stored on one or more programmable storage devices, such as FLASH drives, CD-ROMs, hard drives, and DVDs. One embodiment includes a programmable storage device with instructions stored on it.
    [0066] In some embodiments of the above system, the system further comprises a device for reading identification indicia on reagent packs, for example, on test strips, vessels containing reagents, as well as identification indicia present in vessels containing samples or copies. It will be appreciated that any device suitable for reading identification indicia can be used in the systems proposed in this document. Similarly, it is possible to use any identification indicia that are compatible with the device in the instrument. Examples include barcodes, QR codes, RFID tags, color codes, and the like. In typical embodiments, the device may be a bar code reader and the identifying indicia may comprise a bar code. Exemplary Reflective Essays
    [0067] By way of another example, after a positive MRSA assay, a reflective assay for vancomycin resistance determinants, Panton-Valentine leukocidin (PVL) determinants or to classify MRSA by spa typing, or by typing test of the mec chromosome of the staphylococcal cassette (SCCmec), can be performed on specimens whose result for MRSA was positive. Suitable tests for vancomycin resistance determinants, Panton-Valentine leukocidin (PVL) determinants or to classify MRSA by spa typing, or the SCCmec test are known in the art, as exemplified by Mak et al., J. Clin. Microbiol. (2009) 12:4136; Reischl et al., Eur. J. Clin. Microbiol. Infect. Dis. (2007) 26: 131 to 135; Narukawa et al., Tohoku J. Exp. Med. (2009) 218: 207 to 213; Chongtrakool et al., Antimicrob. Agents Chemother. (2006) 50: 1001 to 1012; each of which is incorporated herein by reference in full.
    [0068] By way of another example, using a specimen of stool from patients with acute diarrhea first tested for Clostridium difficile, a reflex assay could be performed on positives to determine the toxin subtype or negatives to test for the presence of an organism. different causer. The reverse is also true when stool specimens tested for an enteric panel can be mirrored to a test for the presence of Clostridium difficile. Suitable tests for the presence of Clostridium difficile and for toxin subtypes are known in the art, as exemplified by Kvach et al., J. Clin. Microbiol. (2010) 48: 109 to 114; and Northey et al., J. Med. Microbe. (2005) 54: 543 to 547; each of which is incorporated herein by reference in full.
    [0069] By way of another example, using a specimen cerebrospinal fluid from patients with high fever, the specimens or specimens can first be tested for a viral infection using a complete nucleic acid test and a second test can be performed on the negative to look for bacterial targets. Suitable tests for viral and bacterial infections are known in the art, as exemplified by Mahoney et al., J. Clin. Microbiol. (2007) 45: 2965 to 2970 and Melendez et al., Clin. Microbiol. Infect. (2010) 16: 1762 to 1769; each of which is incorporated herein by reference in full.
    [0070] By way of another example, using saliva specimens, the specimens or specimens may first be tested for Mycobacterium tuberculosis complex (MTBC) and for rifampicin resistance. If positive, a reflex test for Isoniazid and Fluroquinolone resistance can be performed to determine whether the strain is MDR or XDR. Suitable tests for resistance to MTBC, rifampicin, isoniazid and fluoroquinolone are known in the art, as per the examples of Somoskovi et al., J. Clin. Microbiol. (2003) 41: 2822 to 2826; Saribas et al., J. Clin. Microbiol. (2003) 41: 816 to 818; Rindi et al., J. Microbiol. Methods (2003) 55: 797 to 800; Ip et al., J. Clin. Microbiol. (2006) 4: 970 to 975; each of which is incorporated herein by reference in full.
    [0071] By way of another example, using bronchoalveolar aspirates in ICU patients, an initial KPC/OXA/NDM carbapenemase screening is performed. If negatives are found, a VIM/IMP screening is performed. Tests suitable for the detection of KPC/OXA/NDM and for the screening of VIM/IMP are known in the art, as per the examples of Nordmann et al., Clin. Microbiol. Infect. (2002) 8: 321 to 331; and Monteiro et al., J. Antimicrob. Chemother. (2012); each of which is incorporated herein by reference in full.
    [0072] By way of another example, using a sample, and after an identification by Gram lineage or by maldi, an assay can be performed on a panel of resistance markers for a Gram-positive panel (if Gram positive) or a Gram negative panel (if Gram negative). In this case, the reflexive strategy described takes place after another system or test for identification. Tests suitable for both Gram-positive and Gram-negative screening are known in the art, as exemplified by Carroll et al., J. Clin. Microbiol. (2000) 5: 1753 to 1757; which is incorporated herein by reference in its entirety.
    [0073] As another example, using food samples or environmental samples, a screening for Listeria spp. If positives are identified, a specific reflex assay for L. monocytogenes can be performed. Suitable tests to detect Listeria spp. and L. monocytogenes are known in the art, as exemplified by Bubert A. App. Environ. Microbiol. (1999) 10: 4688 to 4692; and Borucki et al., J. Clin. Microbiol. (2003) 41: 5537 to 5540; each of which is incorporated herein by reference in full.
    [0074] By way of another example, using water samples or pharmaceutical environment samples, a TVC assay can be performed. If the initial assay is positive, a reflective assay can be performed by Gram-positive or Gram-negative or a specific assay for E. coli or enterococci or bacillus. Tests suitable for CVT and for Gram-positive and Gram-negative screening are known in the art, as exemplified by Ereveeval et al., J. Clin. Microbiol. (2003) 41: 5466 to 5472; and Carroll et al., J. Clin. Microbiol. (2000) 5: 1753 to 1757; each of which is incorporated herein by reference in full.
    [0075] Another exemplary modality refers to testing specimens from patients with or suspected of having cystic fibrosis. For example, a first test can be performed on samples or specimens from a patient to test for the presence of target analytes, e.g., target nucleic acid sequences, associated with Psuedomonas aeruginosa and/or Burkholderia cepacia. Non-limiting examples of assays for the detection of P. aeruginosa and/or B. cepacia that can be used in the embodiments disclosed herein include, for example, those described in Spilker et al. (2004), J. Clin. Microbiol. 42(5): 2074 to 2079, and Vonberg et al, (2006), J. Med. microbiol. 55 (Pt. 6): 721 to 727. In the case of samples that test positive for any pathogen, reflex tests for determinants of antibiotic resistance can be performed, for example, tests to determine target nucleic acids indicative of the presence of tetracycline, nalidixic acid , norfloacin, chloramphenicol, ciprofloxacin or the like.
    [0076] It will be understood that the above list is only intended to give examples of the methods and systems proposed in this document and that any suitable reflective test can be performed based on the result of an initial test. EXAMPLES
    [0077] Having described the present invention in general terms, a broader understanding may be gained with reference to certain specific examples given in this document for purposes of elucidation only, and in no way limiting. EXAMPLE 1 SAMPLE IDENTIFICATION FOR REFLECTIVE ANALYSIS
    [0078] This example describes the identification of samples for reflective analysis at the end of a PCR using an automated instrument for sample preparation, processing and analysis. A panel of 12 biological specimens, each in a different test tube, is processed to obtain respective solution samples containing isolated nucleic acids. Each test strip includes a tube for cell lysis, indicated by “Reaction Tube” in Figure 1. The test strip also includes positions for three other tubes, indicated by positions 1, 2 and 3 in Figure 1. At position 3, there is a conical tube configured to contain the final extracted nucleic acid solution, or sample solution that includes isolated nucleic acids. As illustrated in Figure 1, the test strip also comprises further reservoir positions therein for containing extraction solutions, a reject chamber for containing residual liquid, and various sheaths for containing disposable pipettes. The test strip is also configured with identifying indicia, such as a bar code on one end of the strip.
    [0079] User positions an extraction tube at position 1 and a master mix for detection and/or identification of methicillin-resistant Staphylococcus aureus (MRSA) and S. aureus (including methicillin-sensitive S. aureus), e.g. BD GENEOHM™ StaphSR™ Assay Reagents (Becton Dickinson, Franklin Lakes, NJ) at position 2 of each of the 12 test strips. Each specimen is automatically processed with lysis buffer in the reaction tube, and a fraction of the resulting liquid is automatically transferred to the extraction tube, where bead-based nucleic acid extraction is performed using the extraction solutions, and the solution sample. The final extracted nucleic acid solution is transferred to the conical tube at position 3. The total volume of the extracted nucleic acid solution sample in the conical tube of each test strip is 25 μl. A 12.5 µl aliquot of the extracted nucleic acid solution is automatically pipetted into the adjacent Master Mix tube to reconstitute the StaphSR™ Master Mix. The master mix is transferred to a reaction cartridge for PCR analysis. After PCR, 6 of the 12 samples are indicated as positive for MRSA or S. aureus, identified as candidates for mupirocin resistance, and therefore are selected for reanalysis as defined in the examples below. EXAMPLE 2 MANUAL TRANSFER OF EXTRACTED NUCLEIC ACIDS SOLUTION TO NEW TEST STRIP AND AUTOMATIC TRANSFER TO A NEW MASTER MIX TUBE FOR REFLECTIVE PCR ANALYSIS
    [0080] Sample preparation and processing using PCR analysis for the presence of MRSA and S. aureus is performed as described above in Example 1. Each of the 6 used test strips corresponding to the identified samples for reflective analysis for resistance to mupirocin are repositioned in rows 1 to 6 of a new shelf. New test strips are placed in rows 1 to 6 of a different shelf. An additional 15 μl of elution buffer is added to the extracted nucleic acid solution remaining on each test strip associated with positive samples based on the StaphSR™ test performed in Example 1 above. A fraction of the residual or remaining sample containing isolated nucleic acids obtained from the specimen is transferred to position 3 of a new test strip. The user places a master mix for PCR analysis of mupirocin resistance at position 2 of each of the 6 new test strips. A 12.5 µl aliquot of the extracted nucleic acid solution is automatically transferred by pipette to the adjacent new master mix tube to reconstitute the master mix for PCR analysis for mupirocin resistance using a new pipette located on the new test strip.
    [0081] Reflective PCR analysis indicates that a subset of samples selected for reflective testing are positive for mupirocin resistance. EXAMPLE 3 AUTOMATIC TRANSFER OF EXTRACTED NUCLEIC ACIDS SOLUTION TO A NEW MASTER MIX TUBE IN A NEW TEST STRIP FOR REFLECTIVE PCR ANALYSIS
    [0082] Sample processing and testing using the StaphSR™ assay is performed as described above in Example 1. Each of the 6 used test strips corresponding to samples identified for reflective analysis for mupirocin resistance are repositioned in rows 1 through 6 from a new shelf. New test strips are placed in rows 1 to 6 of a different shelf. An additional 15 μl of elution buffer is added to the extracted nucleic acid solution remaining on each test strip in rows 1 through 6. A 12.5 µl aliquot of the extracted nucleic acid solution is automatically pipetted into a master mix tube on the corresponding new test strip to reconstitute the master mix for PCR analysis for resistance to mupirocin using a new pipette situated on the new test strip.
    [0083] Reflective PCR analysis indicates that a subset of samples selected for reflective testing are positive for mupirocin resistance. EXAMPLE 4 AUTOMATIC TRANSFER OF EXTRACTED NUCLEIC ACIDS SOLUTION TO A NEW MASTER MIX TUBE ON THE SAME TEST STRIP FOR REFLECTIVE PCR ANALYSIS
    [0084] PCR processing and analysis for MRSA is performed as described above in Example 1, except that a 4-notch strip is used, as illustrated in Figure 2. More specifically, the 4-notch strip is configured so that similar to the test strip used in Examples 1 to 3, but comprises an extra position (the “4 position”) for the optional positioning of an extra master mix tube. For each of the 6 samples identified for reflective analysis for mupirocin resistance, an additional 15 μl of elution buffer is added to the extracted nucleic acid solution remaining on each test strip. The user places a master mix for PCR analysis for mupirocin resistance at position 4 of each of the 6 test strips identified for reflective analysis. A 12.5 μl aliquot of the extracted nucleic acid solution is automatically pipetted into the master mix tube at position 4 to reconstitute the master mix for PCR analysis for mupirocin resistance using a new pipette situated on the new test strip . Nucleic acid amplification is performed as described above.
    [0085] Reflective PCR analysis indicates that a subset of samples selected for reflective testing are positive for mupirocin resistance.
    [0086] It should be borne in mind that the present invention is not limited to the specific embodiments described, as these may, of course, vary. It should also be borne in mind that the terminology used herein is for the purpose of describing specific embodiments only without the intent of limiting the invention.
    [0087] Unless otherwise indicated, all technical and scientific terms used in this document have the same meaning commonly recognized by those skilled in the art to which the modalities pertain. While any methods and materials similar or equivalent to those described herein may also be used in practice or testing the embodiments, preferred methods and materials are described herein.
    [0088] The term “comprise”, as used in this document, is synonymous with “include”, “contain” or “characterized by”, is inclusive and open, and does not exclude additional elements or methodical steps not mentioned.
    [0089] It is also worth noting that, as used in this Descriptive Report and in the attached Claims, the singular forms "um", "a", "o" and "a" include their plural inflections, unless the context clearly dictates the contrary. Thus, for example, a reference to "a method" includes various methods of the type and equivalents thereof known to those skilled in the art, and so on.
    [0090] All references cited in this document, including, but not limited to, published and unpublished applications, patents and literature references, are hereby incorporated in their entirety by reference and hereby constitute part of this Descriptive Report. To the extent that publications and patents or patent applications incorporated by reference contradict the disclosure contained in this Specification Report, it is intended that this supersede and/or take precedence over any such contradictory material.
    [0091] The steps of a method or algorithm described in this document with respect to the modalities disclosed in this document can be implemented directly in hardware, in a software module executed by a processor or in a combination of both. A software module may reside in RAM memory, flash memory, ROM memory, EPROM memory, EEPROM memory, registers, a hard disk drive, a removable disk, a CD-ROM or any other form of storage medium known in the art. An exemplary storage medium may be coupled to the processor so that it can read information from the storage medium or write information to the storage medium. Alternatively, the storage medium may be integral to the processor. The processor and storage medium can reside in an ASIC. The ASIC can reside on a user terminal. Alternatively, the processor and storage medium can reside as separate components on a user terminal.
    权利要求:
    Claims (24)
    [0001]
    1. Method for Performing Automated Assay on Samples, characterized in that the method comprises: a) providing an automated instrument configured to receive and process samples from said samples for one or more target analytes in accordance with one or more respective streams of rehearsal work; b) provide samples to be tested; c) automatically transferring a first portion of each of said samples to be tested to respective first vessels comprising reagents for a first test for a first target analyte; d) automatically performing the first test on the portion of said samples to determine the presence of a first target analyte in accordance with a first assay workflow; e) selecting a subset of samples from the samples in which the presence of the first target analyte was determined; f) automatically transferring a second part of the subset of samples selected from e) to a second vessel comprising reagents for a second test to determine the presence of a second target analyte different from the first target analyte according to a second flow of assay work, wherein the second vessel comprising reagents for the second test is located on the same test strip as a respective first vessel or is located on a different test strip than the respective first vessel; and g) automatically running the second test on the second part of the selected sample subset.
    [0002]
    2. Method for Performing Automated Assay on Exemplars, according to Claim 1, characterized in that each of the samples comprises a pre-processed solution of nucleic acids isolated from respective copies.
    [0003]
    3. Method for Performing Automated Assay on Samples, according to Claim 2, characterized in that the automated instrument automatically processes the samples to obtain the respective samples comprising isolated nucleic acids.
    [0004]
    4. Method for Performing Automated Testing on Samples, according to Claim 1, characterized in that, for each sample, said sample and said first vessel comprising reagents for a first test are arranged in a first test strip and in that step f) further comprises automatically transferring the second part of the sample to the second vessel comprising reagents for the second test arranged on a second test strip.
    [0005]
    5. Method for Performing Automated Testing on Samples, according to Claim 4, characterized in that step e) further comprises e1) identifying a subset of said first test strips for the second test; and e2) for each first test strip in said subset, providing a corresponding second test strip comprising a vessel comprising reagents for a second test for a second analyte.
    [0006]
    6. Method for Performing Automated Assay on Samples, according to Claim 4 or 5, characterized in that said second test strip comprises at least one pipette tip.
    [0007]
    7. Method for Performing Automated Testing on Specimens, according to Claim 4 or 5, characterized in that it comprises, before step f), adding extra liquid to said sample.
    [0008]
    8. Method for Performing Automated Testing on Samples, according to Claim 1, characterized in that, for each sample, said sample, said first vessel and a receptacle for said second vessel are arranged on a single test strip.
    [0009]
    9. Method for Performing Automated Testing on Samples, according to Claim 8, characterized in that it comprises, prior to step e), the steps of: d1) identifying a subset of said first test strips to test for the second analyte; and d2) for each test strip in said subset, providing the second vessel comprising reagents for the second test in the receptacle.
    [0010]
    10. Method for performing automated testing on specimens, according to any one of claims 8 and 9, characterized in that it comprises, before step f), the step of providing a pipette tip configured to transfer said second part of the sample to the second vessel comprising reagents for the second test.
    [0011]
    11. Method for Performing Automated Assay on Samples according to Claim 10, characterized in that said pipette tip is an unused pipette tip.
    [0012]
    12. Method for Performing Automated Assay on Samples, according to Claim 10, characterized in that said pipette tip is a washed pipette tip.
    [0013]
    13. Method for Performing Automated Testing on Specimens, according to any one of Claims 8 to 12, characterized in that it comprises, before step f), the step of adding extra liquid to said sample.
    [0014]
    14. Method for Performing Automated Testing on Samples, according to any one of Claims 1 to 13, characterized in that said first test or said second test comprises a reaction selected from the group selected by: Polymerase Chain Reaction ( PCR), Transcription-Mediated Amplification (TMA), Oligonucleotide Binding Assay (OLA), Ligase Chain Reaction (LCR), Rolling Circle Amplification (RCA), Strand Shift Amplification (SDA) and a hybridization reaction .
    [0015]
    15. Method for Performing Automated Testing on Samples, according to any one of Claims 1 to 14, characterized in that it further comprises the step of comparing identification indicia on a test strip to a set of stored test-specific identification data on the instrument.
    [0016]
    16. Method for Performing Automated Testing on Species, according to any one of Claims 1 to 15, characterized in that the first test comprises a test for the simultaneous detection of methicillin-resistant Staphylococcus aureus and Staphylococcus aureus and wherein the second test comprises a test for the detection of a mupirocin resistance determinant.
    [0017]
    17. Method for Performing Automated Assay on Species, according to Claim 16, characterized in that the mupirocin resistance determinant comprises the mupA gene.
    [0018]
    18. System for Performing Automated Assays on Samples from Respective Samples, characterized in that the system comprises: an automated instrument configured to receive and process samples according to one or more assay workflows; said instrument comprising test strips; a processor; an information storage capability that stores instructions for execution by the processor, the instructions comprising: a) automatically transferring a first portion of each sample to respective first vessels comprising reagents for a first test; b) performing the first test to determine the presence of a first target analyte in accordance with a first assay workflow; c) automatically transferring a second part of the samples, or a selected subset of the samples, to respective second vessels comprising reagents for a second test, wherein a second vessel of the respective second vessels is located on the same test strip as a respective first vessel or is located on a different test strip than the respective first vessel; and d) performing a second test on the second portion of the samples, or selected subset of samples, to determine the presence of a second target analyte other than the first analyte, in accordance with a second assay workflow.
    [0019]
    19. System for Performing Automated Assay on Samples from Respective Exemplars, according to Claim 18, characterized in that the instructions further comprise instructions for automatically isolating nucleic acid from exemplars in order to obtain respective samples comprising nucleic acids isolated.
    [0020]
    20. System for Performing Automated Testing on Samples from Respective Samples, according to Claim 18, characterized in that, for each sample, said sample and said first vessel comprising reagents for the first test are situated on a first strip of the test strips and wherein step (c) comprises automatically transferring a portion of each of the samples in the selected subset of samples to a respective second master mix tube situated on a second discrete test strip test strip.
    [0021]
    21. System for Performing Automated Testing on Samples from Respective Samples, according to Claim 18, characterized in that, for each sample, said sample, said first vessel and a receptacle for said second vessel are arranged in a single test strip of test strips, said instructions comprising instructions for the steps of: c1) identifying a subset of said first test strips to test for the presence of the second analyte; and c2) for each test strip in said subset, providing a corresponding second vessel comprising reagents for the second test in the receptacle.
    [0022]
    22. Method for Performing Reflective Testing on Samples, characterized in that the method comprises: a) providing samples to be tested; b) processing specimens to obtain the respective samples, each sample held in a respective sample vessel; c) transferring a first portion of said samples to be tested from the respective sample vessel to respective first vessels comprising reagents for a first test for a first target analyte; d) automatically performing the first test on the portion of said samples to determine the presence or absence of a first target analyte in accordance with a first assay workflow; e) selecting a subset of samples from the samples in which the presence of the first target analyte was determined for the reflective test; f) automatically transferring a second portion of the selected subset of samples from (e) from the respective sample vessel to a second vessel comprising reagents for a second test to determine the presence or absence of a second target analyte in accordance with a second assay workflow, wherein the second target analyte is different from the first analyte, wherein the second vessel comprising reagents for the second test is arranged on the same test strip as the respective first vessel or is arranged on a test strip. test different from the respective first vessel; and g) automatically running the second test on the second part of the selected sample subset in accordance with a second assay workflow, the second test providing a result indicating, for an individual sample included in the sample subset, the presence of the second target analyte on the copy from which the individual sample was processed.
    [0023]
    23. Method for Performing Reflective Testing on Specimens, according to Claim 22, wherein the first test comprises a test for the simultaneous detection of methicillin-resistant Staphylococcus aureus and Staphylococcus aureus and wherein the second test comprises a test for detection of a mupirocin resistance determinant.
    [0024]
    24. Method for Performing Reflective Testing on Species, according to Claim 23, characterized in that the mupirocin resistance determinant comprises the mupA gene.
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    Gentile2012|Analytical Validation of a Novel Multiplex Gene-Specific LATE-PCR Sepsis Assay for Pathogen Detection in Whole Blood and Pure Culture
    同族专利:
    公开号 | 公开日
    JP6653061B2|2020-02-26|
    US20180246130A1|2018-08-30|
    JP2015514223A|2015-05-18|
    IN2014DN09302A|2015-07-10|
    BR112014025384A2|2017-06-20|
    CN107727874B|2021-03-05|
    AU2013246418B2|2017-02-23|
    JP6832310B2|2021-02-24|
    CN104620112A|2015-05-13|
    AU2017203426C1|2019-10-10|
    CN107727874A|2018-02-23|
    WO2013154734A1|2013-10-17|
    US20210140986A1|2021-05-13|
    CA2869717A1|2013-10-17|
    JP2021092577A|2021-06-17|
    US10782309B2|2020-09-22|
    RU2014140117A|2016-06-10|
    US20150024375A1|2015-01-22|
    RU2627383C2|2017-08-08|
    CN104620112B|2017-11-28|
    JP2018141805A|2018-09-13|
    AU2013246418A1|2014-10-23|
    BR112014025384A8|2019-02-19|
    AU2017203426A1|2017-06-08|
    AU2017203426B2|2019-03-28|
    EP2836846A1|2015-02-18|
    US9958466B2|2018-05-01|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    BE791340A|1972-01-06|1973-03-01|Becton Dickinson Co|NEW METHOD AND APPARATUS FOR TAKING A CULTURE AND IDENTIFYING MICRO-ORGANISMS OF MOODS|
    HU168257B|1973-05-18|1976-03-28|
    US4666850A|1983-10-28|1987-05-19|Becton, Dickinson And Company|Microbial pathogen detecting system and process|
    US4693972A|1984-01-16|1987-09-15|Becton, Dickinson And Company|Composition and method for rapid detection of microorganisms in clinical samples|
    US4618576A|1984-02-27|1986-10-21|Becton Dickinson And Company|Diagnostic test for Streptococcus A|
    US4683195B1|1986-01-30|1990-11-27|Cetus Corp|
    US5849478A|1986-08-14|1998-12-15|Cashman; Daniel P.|Blocked-polymerase polynucleotide immunoassay method and kit|
    US5130238A|1988-06-24|1992-07-14|Cangene Corporation|Enhanced nucleic acid amplification process|
    US4988617A|1988-03-25|1991-01-29|California Institute Of Technology|Method of detecting a nucleotide change in nucleic acids|
    US5091316A|1988-06-09|1992-02-25|Becton, Dickinson And Company|Biological sample collection and transport device|
    US5084005A|1988-07-13|1992-01-28|Becton, Dickinson And Company|Swab for collection of biological samples|
    JPH0623769B2|1988-08-31|1994-03-30|株式会社島津製作所|Automatic analyzer|
    JPH02141861U|1989-04-28|1990-11-29|
    CA2020958C|1989-07-11|2005-01-11|Daniel L. Kacian|Nucleic acid sequence amplification methods|
    US5427930A|1990-01-26|1995-06-27|Abbott Laboratories|Amplification of target nucleic acids using gap filling ligase chain reaction|
    US5700636A|1990-10-19|1997-12-23|Becton Dickinson And Company|Methods for selectively detecting microorganisms associated with vaginal infections in complex biological samples|
    US5455166A|1991-01-31|1995-10-03|Becton, Dickinson And Company|Strand displacement amplification|
    US5646049A|1992-03-27|1997-07-08|Abbott Laboratories|Scheduling operation of an automated analytical system|
    US5747265A|1992-10-30|1998-05-05|T Cell Diagnostics, Inc.|Method for measuring the amount of a cell-associated molecule|
    JP3229498B2|1994-09-21|2001-11-19|シスメックス株式会社|Automatic sample analysis method and apparatus|
    US5854033A|1995-11-21|1998-12-29|Yale University|Rolling circle replication reporter systems|
    JP3558898B2|1998-11-05|2004-08-25|株式会社日立製作所|Automatic analyzer and automatic analysis method|
    EP2045337B1|1998-11-09|2011-08-24|Eiken Kagaku Kabushiki Kaisha|Process for synthesizing nucleic acid|
    DE19937187A1|1999-08-06|2001-03-01|Qiagen Gmbh|Automated protein purification in multiwell format through vacuum filtration|
    EP2322666A3|1999-09-28|2011-08-10|Geneohm Sciences Canada, Inc.|Highly conserved gene and its use to generate species-specific, genus-specific, family-specific, group-specific and universal nucleic acid probes for microorganisms.|
    US6602718B1|2000-11-08|2003-08-05|Becton, Dickinson And Company|Method and device for collecting and stabilizing a biological sample|
    WO2002056030A2|2000-11-08|2002-07-18|Becton Dickinson Co|Method and device for collecting and stabilizing a biological sample|
    US7270959B2|2001-07-25|2007-09-18|Oakville Hong Kong Company Limited|Specimen collection container|
    US6977148B2|2001-10-15|2005-12-20|Qiagen Gmbh|Multiple displacement amplification|
    JP4532264B2|2002-05-17|2010-08-25|ベクトン・ディキンソン・アンド・カンパニー|Automatic system, automatic processing method, and automatic nucleic acid extraction method|
    EP1508024A1|2002-05-20|2005-02-23|Northrop Grumman Corporation|Automatic point source biological agent detection system|
    US20040176705A1|2003-03-04|2004-09-09|Stevens Timothy A.|Cartridge having an integrated collection element for point of care system|
    EP1619947A4|2003-05-01|2006-05-31|Replidyne Inc|Antibacterial methods and compositions|
    US7381370B2|2003-07-18|2008-06-03|Dade Behring Inc.|Automated multi-detector analyzer|
    CN1826218B|2003-07-18|2010-09-22|Dade白令公司|Automated multi-detector analyzer|
    US8852862B2|2004-05-03|2014-10-07|Handylab, Inc.|Method for processing polynucleotide-containing samples|
    US20060004526A1|2004-07-01|2006-01-05|Ambion, Inc.|System and method for processing results of a complex genetic test|
    US7662562B2|2004-08-10|2010-02-16|Becton, Dickinson And Company|Method for rapid identification of microorganisms|
    JP2006084351A|2004-09-16|2006-03-30|Denka Seiken Co Ltd|Specimen suspension liquid composition, kit and test method|
    JP2006125868A|2004-10-26|2006-05-18|Arkray Inc|Cartridge for automatic measurement, and measuring method|
    US20060292647A1|2004-12-03|2006-12-28|Green Lawrence R|Reflex supplemental testing - A rapid, efficient and highly accurate method to identify subjects with an infection, disease or other condition|
    US20080124738A1|2005-03-01|2008-05-29|Pritest, Inc|Compositions and methods of testing for tuberculosis and mycobacterium infection|
    US20060246423A1|2005-02-10|2006-11-02|Adelson Martin E|Method and kit for the collection and maintenance of the detectability of a plurality of microbiological species in a single gynecological sample|
    WO2006116010A2|2005-04-21|2006-11-02|Advandx, Inc.|Detection of virulence markers of staphylococci|
    GB0601302D0|2006-01-23|2006-03-01|Semikhodskii Andrei|Diagnostic methods and apparatus|
    US8133671B2|2007-07-13|2012-03-13|Handylab, Inc.|Integrated apparatus for performing nucleic acid extraction and diagnostic testing on multiple biological samples|
    US7998708B2|2006-03-24|2011-08-16|Handylab, Inc.|Microfluidic system for amplifying and detecting polynucleotides in parallel|
    US8097419B2|2006-09-12|2012-01-17|Longhorn Vaccines & Diagnostics Llc|Compositions and method for rapid, real-time detection of influenza A virus swine 2009|
    US20090098527A1|2006-09-12|2009-04-16|Fischer Gerald W|Biological organism identification product and methods|
    US7989185B2|2006-11-29|2011-08-02|The Board Of Trustees Of The Leland Stanford Junior University|Rapid, informative diagnostic assay for influenza viruses including H5N1|
    US9372191B2|2006-12-08|2016-06-21|Alere Switzerland Gmbh|Methods and devices for detecting methicillin resistant Staphylococcus aureus|
    JP5431644B2|2006-12-28|2014-03-05|シスメックス株式会社|Examination method of respiratory infection|
    US7748283B2|2007-02-16|2010-07-06|Whatman, Inc.|Controlled transfer biological sample collection devices and methods of using such devices|
    US20090137047A1|2007-03-02|2009-05-28|John Frederick Regan|Automated Diagnostic Kiosk for Diagnosing Diseases|
    TWI329742B|2007-05-11|2010-09-01|Animal Health Res Inst Council Of Agriculture|
    US8182763B2|2007-07-13|2012-05-22|Handylab, Inc.|Rack for sample tubes and reagent holders|
    EP3741869A1|2007-07-13|2020-11-25|Handylab, Inc.|Polynucleotide capture materials and methods of using same|
    US8080645B2|2007-10-01|2011-12-20|Longhorn Vaccines & Diagnostics Llc|Biological specimen collection/transport compositions and methods|
    EP3020832A1|2007-10-01|2016-05-18|Longhorn Vaccines and Diagnostics, LLC|Biological specimen collection and transport system and methods of use|
    WO2009049007A2|2007-10-10|2009-04-16|Magellan Biosciences, Inc.|Compositions, methods and systems for rapid identification of pathogenic nucleic acids|
    KR101056251B1|2007-10-26|2011-08-11|주식회사 하이닉스반도체|Patterning method of semiconductor device|
    WO2009082747A1|2007-12-24|2009-07-02|Zeus Scientific, Inc.|Methods and compositions including diagnostic kits for the detection of staphylococcus aureus|
    WO2009098485A1|2008-02-07|2009-08-13|Forensic Sciences Service Ltd|Improvements in and relating to analysis|
    US8802370B2|2008-05-23|2014-08-12|Strand Diagnostics, Llc|Method and apparatus to minimize diagnostic and other errors due to transposition of biological specimens among subjects|
    US20100009351A1|2008-07-11|2010-01-14|Handylab, Inc.|Polynucleotide Capture Materials, and Method of Using Same|
    USD618820S1|2008-07-11|2010-06-29|Handylab, Inc.|Reagent holder|
    JP2010054232A|2008-08-26|2010-03-11|Olympus Corp|Reaction card and automatic analyzing apparatus|
    WO2010039917A2|2008-10-03|2010-04-08|Ibis Biosciences, Inc.|Compositions for use in identification of staphylococcus aureus|
    US8053239B2|2008-10-08|2011-11-08|The Governing Council Of The University Of Toronto|Digital microfluidic method for protein extraction by precipitation from heterogeneous mixtures|
    JPWO2010064628A1|2008-12-05|2012-05-10|オリンパス株式会社|Nucleic acid-containing sample preparation method, sample preparation solution, and nucleic acid analysis method|
    AU2009331083B2|2008-12-25|2016-02-11|Universal Bio Research Co., Ltd.|Method for pretreating specimen and method for assaying biological substance|
    EP2280358B1|2009-07-24|2013-11-20|F.Hoffmann-La Roche Ag|A urine work area manager and a urine work area|
    US8282895B2|2009-09-15|2012-10-09|Qiagen Gaithersburg, Inc.|Reagent cabinet system|
    USD655424S1|2009-11-18|2012-03-06|Becton, Dickinson And Company|Cassette for a medical device|
    EP2536855A4|2010-02-19|2013-07-31|Argylla Technologies|Isolation of biomolecules from biological samples|
    CN107663553A|2010-07-20|2018-02-06|贝克顿·迪金森公司|Method for point of care quick diagnosis test result to be connected with the method based on laboratory|
    WO2012036296A1|2010-09-17|2012-03-22|ユニバーサル・バイオ・リサーチ株式会社|Cartridge and automatic analysis device|
    WO2013020137A1|2011-08-04|2013-02-07|The Regents Of The University Of California|Saliva collection, processing, stabilization, and storage method|
    US8603769B2|2011-10-07|2013-12-10|Becton, Dickinson And Company|Method for direct and rapid identification of microorganisms and antimicrobial susceptibility testing from positive blood cultures|
    BR112014025384B1|2012-04-13|2022-01-25|Becton, Dickinson And Company|System and methods for performing automated assay and reflective testing on samples from the respective specimens|US7829025B2|2001-03-28|2010-11-09|Venture Lending & Leasing Iv, Inc.|Systems and methods for thermal actuation of microfluidic devices|
    US8895311B1|2001-03-28|2014-11-25|Handylab, Inc.|Methods and systems for control of general purpose microfluidic devices|
    EP2402089A1|2003-07-31|2012-01-04|Handylab, Inc.|Processing particle-containing samples|
    US8852862B2|2004-05-03|2014-10-07|Handylab, Inc.|Method for processing polynucleotide-containing samples|
    US9186677B2|2007-07-13|2015-11-17|Handylab, Inc.|Integrated apparatus for performing nucleic acid extraction and diagnostic testing on multiple biological samples|
    US8883490B2|2006-03-24|2014-11-11|Handylab, Inc.|Fluorescence detector for microfluidic diagnostic system|
    WO2007112114A2|2006-03-24|2007-10-04|Handylab, Inc.|Integrated system for processing microfluidic samples, and method of using same|
    US8105783B2|2007-07-13|2012-01-31|Handylab, Inc.|Microfluidic cartridge|
    US10900066B2|2006-03-24|2021-01-26|Handylab, Inc.|Microfluidic system for amplifying and detecting polynucleotides in parallel|
    US7998708B2|2006-03-24|2011-08-16|Handylab, Inc.|Microfluidic system for amplifying and detecting polynucleotides in parallel|
    WO2008061165A2|2006-11-14|2008-05-22|Handylab, Inc.|Microfluidic cartridge and method of making same|
    US8182763B2|2007-07-13|2012-05-22|Handylab, Inc.|Rack for sample tubes and reagent holders|
    US8287820B2|2007-07-13|2012-10-16|Handylab, Inc.|Automated pipetting apparatus having a combined liquid pump and pipette head system|
    EP3741869A1|2007-07-13|2020-11-25|Handylab, Inc.|Polynucleotide capture materials and methods of using same|
    WO2012142516A1|2011-04-15|2012-10-18|Becton, Dickinson And Company|Scanning real-time microfluidic thermo-cycler and methods for synchronized thermocycling and scanning optical detection|
    USD692162S1|2011-09-30|2013-10-22|Becton, Dickinson And Company|Single piece reagent holder|
    RU2658773C2|2012-02-03|2018-06-22|Бектон, Дикинсон Энд Компани|System and method of implementation of automated assays on plurality of biological samples|
    BR112014025384B1|2012-04-13|2022-01-25|Becton, Dickinson And Company|System and methods for performing automated assay and reflective testing on samples from the respective specimens|
    JP6771903B2|2016-02-29|2020-10-21|シスメックス株式会社|Specimen pretreatment device, sample pretreatment cartridge and sample pretreatment method|
    US11255762B1|2020-08-11|2022-02-22|Specialty DiagnosticLaboratories, Inc.|Method and system for classifying sample data for robotically extracted samples|
    法律状态:
    2018-12-04| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|
    2019-11-19| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|
    2021-06-22| B07A| Application suspended after technical examination (opinion) [chapter 7.1 patent gazette]|
    2021-12-28| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|
    2022-01-25| B16A| Patent or certificate of addition of invention granted [chapter 16.1 patent gazette]|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 13/03/2013, OBSERVADAS AS CONDICOES LEGAIS. |
    优先权:
    申请号 | 申请日 | 专利标题
    US201261624198P| true| 2012-04-13|2012-04-13|
    US61/624,198|2012-04-13|
    PCT/US2013/031072|WO2013154734A1|2012-04-13|2013-03-13|Reflex testing of samples using residual materials from a prior test|
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