[go: up one dir, main page]

WO2005009202A2 - Identification automatique de bioagents - Google Patents

Identification automatique de bioagents Download PDF

Info

Publication number
WO2005009202A2
WO2005009202A2 PCT/US2004/015123 US2004015123W WO2005009202A2 WO 2005009202 A2 WO2005009202 A2 WO 2005009202A2 US 2004015123 W US2004015123 W US 2004015123W WO 2005009202 A2 WO2005009202 A2 WO 2005009202A2
Authority
WO
WIPO (PCT)
Prior art keywords
deck
bioagent
protocol
mass
sample
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2004/015123
Other languages
English (en)
Other versions
WO2005009202A3 (fr
Inventor
John Mcneil
David Ecker
Steven A. Hofstadler
Lawrence Blyn
Isaac Gesser
Lendell L. Cummins
Alan Goates
Jared J. Drader
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Ionis Pharmaceuticals Inc
Original Assignee
Isis Pharmaceuticals Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Isis Pharmaceuticals Inc filed Critical Isis Pharmaceuticals Inc
Publication of WO2005009202A2 publication Critical patent/WO2005009202A2/fr
Publication of WO2005009202A3 publication Critical patent/WO2005009202A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00584—Control arrangements for automatic analysers
    • G01N35/0092—Scheduling
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6844—Nucleic acid amplification reactions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples

Definitions

  • the present invention relates generally to the field of investigational bioinf ormatics and more particularly to devices and methods for identifying bioagents.
  • PCR polymerase chain reaction
  • Detection and data analysis then convert the hybridization event into an analytical result.
  • Mass spectrometry provides detailed information about the molecules being analyzed, including high mass accuracy. It is also a process that can be easily automated. Low-resolution MS may be unreliable when used to detect some known agents, if their spectral lines are sufficiently weak or sufficiently close to those from other living organisms in the sample. DNA chips with specific probes can only determine the presence or absence of specifically anticipated organisms. Because there are hundreds of thousands of species of benign bacteria, some very similar in sequence to threat organisms, even arrays with 10,000 probes lack the breadth needed to detect a particular organism.
  • Antibodies face more severe diversity limitations than do arrays. If antibodies are designed against highly conserved targets to increase diversity, the false alarm problem will dominate, again because threat organisms are very similar to benign ones. Antibodies are only capable of detecting known agents in relatively uncluttered environments.
  • Co-owned US Patent Application Publication 20030082539 Al describes a method of identifying an unknown bioagent using a database of known bioagents.
  • the nucleic acid from the unknown bioagent is first contacted with at least one pair of "intelligent" oligonucleotide primers that hybridize to sequences of the nucleic acid that flank a variable nucleic acid sequence of the bioagent.
  • an amplification product of this variable nucleic acid sequence is made.
  • the molecular mass of this amplification product is determined using mass spectroscopy techniques. This molecular mass is compared to the molecular mass of known bioagents within the database to identify the unknown bioagent.
  • the present invention enables automated rapid identification of unknown bioagents using a self-contained device coupled to a system executive module.
  • the device preferably includes two decks separated by an airlock, and in addition includes a storage area for storing reagents and filter plates for use in identifying bioagents.
  • a programmable robot assembly isolates and purifies DNA from the bioagent in the first deck, preparing the sample for amplification through a polymerase chain reaction (PCR).
  • the first deck is preferably maintained at a higher atmospheric pressure than the area external to the device, while the second deck is maintained at a lower atmospheric pressure than the external area; the pressure differential avoids contamination of the sample prior to amplification.
  • PCR can be carried out using several PCR plates, and samples can be transferred to, for example, a 384-well tray. After washing and eluting of the sample in the second deck, the molecular mass of the sample is determined by mass spectroscopy.
  • the system is preferably designed so that the second deck may operate without the first deck in the case where the laboratory has an alternative procedure for isolating and purifying DNA from the bioagent, and preparing the sample for amplification through a polymerase chain reaction (PCR).
  • the present invention also includes a system executive for controlling operation of the self-contained device.
  • the system executive provides a user interface (UI) for receiving analysis requests, and includes logic for performing resource management, job scheduling and additional drill-down analysis.
  • the system executive is also in communication with a database of catalogued bioagents, which in one embodiment forms part of the device, and in alternative embodiments is located remotely. Using the database of bioagents and their known masses, the system executive either identifies the exact bioagent (or its nearest known relative, if it is a new organism not in the database) using the amplicon mass determined through mass spectroscopy (MS), or alternatively determines that a drill-down analysis is required to further differentiate the sample from among multiple candidates within a related group.
  • MS mass spectroscopy
  • the system executive automatically chooses an appropriate set of amplification primers and instructs the device to repeat the PCR process with the second set of primers, obtaining a second identification through MS.
  • This second amplicon mass is then matched once again against catalogued bioagents in the database, and the previously unresolved bioagent sample is identified with a higher degree of precision.
  • the present invention makes bioagent identification more accessible to treatment and detection centers, enabling a more rapid response than is attainable using conventional technology.
  • the present invention includes alerting capability for automatically notifying authorities that a bioagent associated with a high threat level has been identified.
  • FIG. 1 is a block diagram illustrating basic components of a device in accordance with an embodiment of the present invention.
  • Fig. 2 is a block diagram illustrating a system executive in accordance with an embodiment of the present invention.
  • Fig. 3 is a flowchart illustrating a method for identifying a bioagent in accordance with an embodiment of the present invention.
  • Fig.4 is a block diagram illustrating a layout of a device in accordance with an embodiment of the present invention.
  • Fig.5 is a flowchart illustrating a method for performing DNA isolation in accordance with an embodiment of the present invention.
  • FIG. 6 is a flowchart illustrating a method for performing PCR preparation in accordance with an embodiment of the present invention.
  • FIG. 7 is a flowchart illustrating a method for archiving a sample in accordance with an embodiment of the present invention.
  • FIG. 8 is a flowchart illustrating a method for performing PCR in accordance with an embodiment of the present invention.
  • Fig. 9 is a flowchart illustrating a method for performing plate transfers in accordance with an embodiment of the present invention.
  • Fig. 10 is a flowchart illustrating a method for performing an initial rinse in accordance with an embodiment of the present invention.
  • FIG. 11 is a flowchart illustrating a method for performing a NH 4 HC0 3 wash in accordance with an embodiment of the present invention.
  • Fig. 12 is a flowchart illustrating a method for performing a 50% methanol wash in accordance with an embodiment of the present invention.
  • FIG. 13 is a flowchart illustrating a method for performing production elution in accordance with an embodiment of the present invention.
  • Fig. 14 is a flowchart illustrating a method for performing sample injection in accordance with an embodiment of the present invention.
  • the figures depict preferred embodiments of the present invention for purposes of illustration only. One skilled in the art will readily recognize from the following discussion that alternative embodiments of the structures and methods illustrated herein may be employed without departing from the principles of the invention described herein.
  • Fig. 1 illustrates a device 100 for performing bioagent detection in accordance with a preferred embodiment of the present invention.
  • Device 100 includes two decks, Deck A 102 and Deck B 104, separated by an airlock 106.
  • Samples are received from storage area 408 at Deck A, where their DNA is isolated and purified, and the samples are then prepared for PCR, and sent through airlock 106 to Deck B.
  • Deck B they are thermocycled, which performs PCR on the sample.
  • Amplified DNA is then purified, and the amplified and purified samples are then injected into a mass spectrometer for identification.
  • system executive kOO Also shown in Fig. 1 is system executive kOO, further described next with reference to Fig. 2.
  • Purified in this context, means separated from at least one or more components present in the amplified sample.
  • FIG. 2 illustrates a block diagram of system executive kOO in accordance with an embodiment of the present invention.
  • System executive kOO provides logic for operation of device 100, preferably from the receiving of an initial analysis request through to providing a response to the request. Typically, this involves receiving a request from a user through a user interface, determining resource requirements and scheduling for satisfying the request, instructing the device 100 to actually perform the required operations, analyzing the results, and reporting the results to the user.
  • system executive kOO includes a UI 202; an analysis request controller 204; a sample state controller 206; analysis plans database 210; a waiting-for-resources queue 208; a protocol resource allocator 212; a ready queue 214; scheduling controller 216; active queue 218; device controller 220; analysis server 222; resource manager 224; and drill- down PCR logic 226.
  • UI 202 provides an interface for communicating with system executive kOO.
  • UI 202 may be implemented in a variety of ways, and in a preferred embodiment includes a Simple Object Access Protocol (SOAP) interface, which provides for accessing the UI 202 through XML in a platform-independent fashion.
  • SOAP Simple Object Access Protocol
  • UI 202 can be implemented through well-understood interfaces such as HTML, Java, and the like.
  • a requestor rovides a request to system executive 100
  • UI 202 calls analysis request controller (ARC) 204.
  • ARC 204 determines based on requestor input what type of identification is being requested. For example, the requestor may wish to know which family of bacteria a particular sample is suspected to contain. Alternatively, the requestor may want to know the specific strain of a virus suspected to be present in a sample.
  • ARC 204 preferably provides the requestor with a hierarchical view of options for specifying the type of analysis desired, and preferably displays only those options that system 100 can provide depending on available devices, resources and the incoming sample type. ARC 204 passes properly formulated requests to sample state controller 206.
  • Sample state controller 206 uses the request received from ARC 204 to determine an appropriate analysis plan.
  • An analysis plan includes a selection of protocols to be performed on the sample in order to obtain an appropriate response to the request.
  • Sample state controller 206 preferably includes a mapping from request types to analysis plans.
  • analysis plans are stored in an analysis plan database 210, though any suitable data structure can be used, as will be appreciated by those of skill in the art.
  • sample state controller 206 inserts the protocols into waiting-for- resources queue 208.
  • Waiting-for-resources queue 208 is a queue that holds protocols that are to be executed, but have required input resources not yet allocated. Protocols remain in the waiting-for-resources queue 208 until moved to ready queue 214 by protocol resource allocator 212 or cancelled, e.g., by a user request.
  • Protocol resource allocator 212 periodically examines the waiting-for- resources queue 208 to see which protocols are awaiting scheduling.
  • a protocol includes a list of resources and associated amounts required by the protocol. Resources are various materials and reagents required for processing and can include, for example, disposable pipette tips, microtiter filter plates, plates of amplified DNA, and data files.
  • the protocol resource allocator determines whether sufficient amounts of required resources are available to allow a protocol to run. As resources required by a protocol become available, they are reserved for the protocol. When a protocol has all required resources reserved for it, the protocol resource allocator 212 moves the protocol to the ready queue 214. Protocol resource allocator 212 knows which resources are available to assign to protocols by communicating with resource manager 224. Resources are marked reserved in the resource manager as they are assigned to specific protocols.
  • Protocols are preferably either testing protocols or analysis protocols.
  • a testing protocol specifies operations to be performed on the sample by device 100, e.g., by equipment located on Deck A 102 and Deck B 104.
  • An analysis protocol specifies an analysis to be performed by analysis server 222. While examples of resources in a testing protocol include PCR plates, dispensing tips, etc., a resource in an analysis protocol can be anything that must be supplied to analysis server 222 to perform the analysis, such as a data file including results from mass spectroscopy testing.
  • Resource manager 224 maintains an inventory of which resources are available for use in device 100.
  • resource manager 224 receives a notification from device controller 220.
  • resources are identified by bar codes, and resource manager 224 includes logic to determine a particular resource type associated with a particular bar code received from device controller 220.
  • the notification received from device controller 220 is the bar code of the added resource.
  • resource manager 224 updates its inventory list to include the newly added resource.
  • resource manager 224 decrements its inventory list to exclude the allocated resource.
  • Ready queue 214 includes protocols that have been assigned specific resources and are waiting to run.
  • Scheduling controller 216 periodically examines the ready queue 214 for protocols, and when it finds a protocol sends it to either device controller 220 in the case of a testing protocol, or to analysis server 222 in the case of an analysis protocol.
  • Scheduling controller 216 also preferably puts a copy of the protocol in active queue 218 so that system executive kOO maintains a real-time record of which protocols are currently being run.
  • Device controller 220 receives a testing protocol from scheduling controller 216 and performs the operations specified in the protocol as described further below. Device controller 220 reports the results of the operations to schedule controller 216. Typically, an analysis protocol in waiting-for-resources queue 208 will be run upon indication that a testing protocol has been completed (for example, because the test data produced by the test protocol is a resource for the analysis protocol). Analysis server 222 reports the results of the analysis to scheduling controller 216, which in turn reports back to sample state controller 206. Sample state 206 then either returns a response to the requestor via UI 202, or else determines according to drill-down logic 226 that additional analysis is required. Methods by which analysis server 222 identifies a bioagent from BCS data are further described in co-owned US Application 20030082539 Al.
  • a requestor is preferably able to specify a type of identification to be performed on the sample. If the type of identification is of a more general nature, such as identifying a bacterial family to which the sample belongs, the initial set of protocols using intelligent primers may be sufficient to provide a response to the request. However, where a more specific identification has been requested, and, for example, different strains of an organism have very similar or identical base composition sequences, it is useful to perform an additional drill-down analysis by performing a second set of PCR reactions using more focused primers followed by an additional round of mass spectroscopy. For example, Bacillus anthracis can be distinguished from Bacillus cereus and Badllus thuringiensis using the primer 16S 971 1062 . Additional primer pairs that produce unique base composition signatures are described in co-owned US Patent Application 20030082539 Al.
  • sample state controller 206 When sample state controller 206 receives the results of the initial analysis from analysis server 222 (via scheduling controller 216), it compares the results obtained with the request received from the requestor. If the results are sufficient to respond to the request, then the response is forwarded through UI 202 to the requestor. If the results are not spedfic enough to respond to the request, sample state controller 206 uses drill-down logic 226 to automatically select an appropriate pair of primers for performing additional PCR. Protocols for performing the additional PCR, associated mass spectroscopy, and analysis are determined and forwarded to waiting-for-resources queue 208. The protocols are run as described above, results are received from analysis server 222, and once again evaluated by sample state controller 206. As will be appreciated by those of skill in the art, the drill-down process can be automatically repeated if needed to provide even more focused results.
  • Fig. 3 provides a flowchart illustrating a method of operation of system executive kOO in one embodiment of the present invention.
  • System executive kOO receives 302 a request from a requestor and selects 304 an appropriate analysis plan from its store 210 of analysis plans based on the request. Protocols associated with the analysis plans are placed 306 into a waiting-for-resources queue. Protocol resource aUocator 212 inspects the waiting-for-resources queue 208 and allocates 308 resources to protocols in the queue as the resources become available. Once all resources required for a process have been aUocated, the protocol is moved 310 from waiting-for-resources queue 208 to ready queue 214.
  • scheduling controller 216 sends 314 the protocol to device controller 220 for execution, and receives 316 the results back from device controller 220 upon termination.
  • the protocol is sent 318 to analysis server 222 for analysis, and the results of the analysis are received 320 back from the server 222 upon completion of the analysis. Results received either from device controller 220 or analysis server 222 are then forwarded 322 to sample state controller 206. If 324 the results satisfy the request, then system kOO reports 326 the results to the requestor.
  • drill-down PCR logic 226 is used to select 328 new primers, and appropriate protocols are placed 306 once again in the waiting-for-resources queue 208 so that drUl-down PCR analysis can be completed.
  • device controller 220 receives testing protocols to be run from scheduling controller 216.
  • Device controller 220 executes the testing protocols by operating the components of device 100 to perform the functions described in the protocols.
  • Fig. 4 provides a more detailed view of the surface of device 100 in one embodiment. Those of skill in the art will appreciate that the particular arrangement Ulustrated in Fig. 4 is not the only arrangement possible, and the actual placing of components can be changed without departing from the spirit of the present invention.
  • Fig. 4 indudes Deck A 102, Deck B 104, and storage area 110.
  • Deck A 102 includes a storage robot 402 for deUvering resources to Deck A 102 from storage 110 and returning the resources to storage 110 on demand. Note that as ulustrated, resources always make their way through Deck A 102 even if going to Deck B 104, and resources preferably never return to storage from Deck B 104. This arrangements prevents contamination of anything in Deck A 102, where un-amplified samples reside, with amplified DNA from Deck B 104.
  • Deck A 102 also includes a conveyor 404 for transporting objects; a gantry pickup point 406, which is an area of Deck A 102 accessible to a gantry of robot 408; robot 408 which is responsible for implementing the various testing protocols by moving resources and samples from one location to another, and for operating the testing components; and a heat sealer 410 for sealing plates. Also shown is airlock 108, which separates storage area 110 from Deck A 102.
  • Deck B 104 includes a plate shaker (not shown); a centrifuge 414; thermocyclers 416; a 96-channel pipette 418; a heat sealer 420; a manifold liquid dispenser 422; an autosampler 424; and mass spectrometers 426. Also shown is airlock 106, which separates Deck A 102 and Deck B 104, aUowing different atmospheric pressures to exist on each deck. The operation of the various components of device 100 is now described further.
  • Fig. 5 there is shown a flow chart illustrating the operation of device 100 and its constituent components as it carries out DNA isolation in accordance with an embodiment of the present invention.
  • an initial setup function is performed by an operator prior to use of the device, which indudes stocking 502 the device with an initial inventory of resources.
  • operator intervention is preferably required only to replenish resources that have been consumed, or to add new samples to be processed.
  • the initial setup includes loading of various reagents, tips for transferring Uquid between plates, filling of the reagent storage reservoir with elution buffer, and washing the buffers.
  • DNA isolation can begin.
  • a sample containing the bioagent to be identified is located on a sample source plate.
  • the sample source plate is placed 504 on conveyer belt 404 by storage robot 402, and passed from storage location 408 to Deck A 102 through airlock 108 for transport 506 to gantry pickup point 406.
  • gantry pickup point 406 is a location from which the robotic handler that moves materials between stations on Deck A can retrieve an object.
  • a filter plate is presented 508 by storage robot 402.
  • the sample source plate has preferably reached gantry pickup point 406 and is now transported 510 to the robot 408, and the filter plate now reaches gantry pickup point 406.
  • An elution plate is then presented 516 by storage robot 402 to conveyer 406, just as the filter plate reaches 518 robot 408.
  • Conveyer 406 transports 520 the elution plate to gantry pickup location 406.
  • the gantry then deUvers 522 the elution plate to robot 408.
  • a DNA isolation procedure occurs 524 at robot 408. In a preferred embodiment, this isolation indudes four steps. First, a ceU lysis buffer is added to the sample source plate. Next, the samples are transferred to the filter plate, where the filter media binds the sample. Third, impurities are washed off of the filter using wash buffers, and lastly elution buffer is added to the plate. Purified genomic DNA then elutes onto the elution plate, which is now referred to as a genomic DNA plate.
  • the tip racks are preferably discarded for later removed 526 by an operator.
  • the sample source plate is then moved 528 to and sealed by heat sealer 410.
  • the sample source plate then is moved 530 to a conveyer for transport to a disposal area on Deck B 104.
  • the filter plate is moved 532 to the heat sealer 410 and sealed. Meanwh e, the sample source plate travels 534 to the airlock 106 to Deck B 104 for disposal.
  • the filter plate also travels 536 through airlock 106 to Deck B 104 for disposal.
  • FIG. 6 there is shown a flow chart illustrating a process for preparing samples for PCR in accordance with an embodiment of the present invention.
  • storage robot 402 presents 602 a tip box to the Deck A conveyer 404, which carries 604 the tip box to gantry pickup position 406.
  • Primer plate 1 is presented 606 by storage robot 402 to the conveyer 404, as the pipet tip box is moved 608 to robot 408.
  • Primer plate 1 is then deUvered 610 to plate pickup position 406, and then moved 612 to robot 408 by the gantry.
  • PCR setup then begins 614.
  • PCR setup 614 includes the foUowing steps: first, the sample is aspirated from the first weU of the Genomic DNA plate. Next, the sample is transferred into 16 wells of primer plate 1. This process repeats until primer plate 1 is full. The primer plate is now known as pre-PCR plate 1.
  • Pre-PCR plate 1 is moved 616 to sealer 410, which applies 618 a foil seal to pre-PCR plate 1.
  • the gantry moves 620 the tip box back to the conveyer destined for the Deck B waste area.
  • the sealed pre-PCR plate is then moved 622 to conveyer 404 and also headed toward Deck B 104.
  • a new tip box is presented 624 by storage robot 402, and the above steps 604 to 622 are preferably then repeated 626 for each remaining plate.
  • the genomic DNA plate is re-lided 702 by robot 408, placed 704 on the conveyer 404, and returned 706 to the storage robot 402, which places 708 the genomic DNA plate into storage area 110.
  • a flow chart illustrating a method for thermocycling PCR samples in Deck B of device 100, in accordance with an embodiment of the present invention.
  • Pre-PCR Plate 1 is received 802 through airlock 106 from Deck A 102, after being processed as described above with respect to Fig. 6.
  • Pre-PCR Plate 1 is then transferred 804 to plate shaker 412 and mixed.
  • a PCR Balance plate is transferred 806 to centrifuge 414.
  • a balance plate is a plate that is of equivalent weight to the plate being centrifuged.
  • Pre-PCR Plate 1 is also transferred 808 to centrifuge 414, and spun down 810.
  • Pre-PCR plate 1 is then moved 812 to thermocycler 416, where it preferably undergoes 814 cycling for about 2.5 hours.
  • the PCR Balance plate is then picked up 816 from the centrifuge and returned to storage.
  • Pre-PCR Plates 2-16 are then received in turn through airlock 106 from Deck A, and undergo a thermocycling process similar to pre-PCR Plate 1.
  • the PCR Balance plate is transferred 902 to centrifuge 414. Crude PCR plate 1 is then transferred 904 to centrifuge 414 and spun down 906. Crude PCR plate 1 is then moved 908 to a 96-channel pipette 418, and the PCR Balance plate is returned 910 to storage.
  • a resin slurry source plate is transferred 912 to 96-channel pipette 418, and its lid is removed 914.
  • the resin slurry is resuspended 916 by continuous aspirate dispense, and then transferred 918 to crude PCR plate 1.
  • a filter plate preferably having 384 weUs, is then presented 920 at airlock 106.
  • the resin slurry source plate is reUdded and returned 922 to storage.
  • a binding reaction in crude PCR plate 1 is mixed 924 by continuous aspiration and dispensing, and then transferred 926 to the first well of the filter plate.
  • the needles on 96-channel pipette 418 are then washed 928, the filter plate is moved 930 back to temporary storage, and empty PCR plate 1 is transferred to plate sealer 420 and sealed 932.
  • the sealed empty crude PCR plate 1 is then moved 934 to a solid waste capture area (not shown).
  • the remaining crude PCR plates are then transf erred to the wells of the fUter plate in a similar fashion.
  • the next phase of bioagent detection involves an initial rinse.
  • the filter plate is moved 1002 to manifold dispense system 422. In a preferred embodiment, about 125 »L of water are dispensed 1004 to each well for balance.
  • the resin capture waste balance is moved 1006 to centrifuge 414, and a waste catchplate arrives 1008 at airlock 106 from Deck A 102 and is also moved 1010 to centrifuge 414.
  • the filter plate is then moved to centrifuge 414 and preferably stacked 1012 on top of the waste catchplate.
  • the filter plate and catch plate assembly is then centrifuged 1014, preferably for about 15 seconds.
  • the filter plate is moved 1104 to manifold dispensing system 422 where about 200 »L of NH 4 HCO a is dispensed 1106.
  • the waste catchplate is transferred 1108 to 96-channel pipette 418, where the waste is aspirated off and syringe needles are washed.
  • the empty waste catchplate is then returned 1110 to centrifuge 414.
  • the fUter plate is then returned 1112 to the centrifuge 414, and stacked on top of the waste catchplate.
  • the fUter plate / waste catchplate combination is then spun 1114 on the centrifuge for about 15 seconds. The process is preferably repeated 1116 a second and third time.
  • the filter plate returns 1202 to the manifold dispensing system 422, where receives about 200 »L of MeOH wash.
  • the waste catchplate is again cleaned 1204, and returned 1206 to centrifuge 414.
  • the filter plate also returns 1208 to centrifuge 414, where the filter plate / waste catchplate combination is again washed 1210 for about 15 seconds.
  • this cyde is repeated 1212 twice more, with the final washing being for approximately two minutes.
  • the sample is now ready for elution.
  • the filter plate returns again 1302 to manifold dispensing system 422, where about 25-50 «L of elution buffer is dispensed.
  • the waste catchplate is again cleaned 1304 and returned 1306 to storage, as is the resin capture waste balance.
  • the resin product capture balance is moved 1308 to centrifuge 414, and a product catchplate is deUvered 1310 to Deck B 104 from Deck A 102 via airlock 106 and also placed in centrifuge 414.
  • the fUter plate is moved 1312 to centrifuge 414 and placed on top of the product catchplate, where the combination is spun 1314 for about 2 minutes.
  • Product is then eluted 1316 from the filter plate to the product catchplate.
  • the empty fUter plate is then moved to the Deck B sealer 420 and sealed 1318.
  • the sealed fUter fl4 is then moved 1320 to the solid waste capture area.
  • the product catchplate is moved to the Deck B sealer 420 and sealed 1322 to prevent evaporation.
  • the resin capture balance plate is returned 1324 to storage.
  • the sample is preferably subjected to mass spectroscopy.
  • the sealed product catchplate is moved 1402 to a conveyer and directed to autosampler 424. Samples from the catchplate are sampled 1404 by the autosampler 424 and then sprayed 1406 into mass spectrometer 426. Sampling by autosampler 424 in one embodiment takes approximately 7 hours to complete.
  • the empty product catchplate 424 is then sealed 1408 and moved to solid waste capture fl8.
  • the results of the analysis by mass spectrometer 426 are then made avaUable plO to scheduling controller 216, which proceeds as described above.
  • system kOO can operate autonomously. Handling requests, running test protocols, querying the analysis server, determining whether the results are suffident to fulfill the request, and if they -ire not then automatically selecting a secondary set of primers for performing drill-down — each of these processes is automated in system kOO. This automation enables an additional feature of system kOO, in which bioagents have associated threat levels, and threat levels have corresponding reporting actions. In one embodiment, bioagent threat levels are returned by analysis sever 222 along with the bioagent identification.
  • sample state controller 206 or another module of device 100 includes an assodation between bioagents and threat levels.
  • bioagents associated with terrorist activity may have a corresponding threat level of "very high", while harmless bioagents have a corresponding threat level of "very low”.
  • threat levels differ depending on a geographic origin of the sample, in order to account for bioagents that may be common (and presumably a low threat) in one region, but rare (and thus potentially threatening) in a different region.
  • Sample state controUer 206 preferably includes logic for issuing an alarm, e.g., via UI 202, to appropriate authorities when a bioagent having a threat level above a threshold value is detected.
  • the present invention also relates to an apparatus for performing the operations herein.
  • This apparatus may be specially constructed for the required purposes, or it may comprise a general-purpose computer selectively activated or reconfigured by a computer program stored in the computer.
  • a computer program may be stored in a computer readable storage medium, such as, but is not limited to, any type of disk including floppy disks, optical disks, CD-ROMs, magnetic-optical disks, read-only memories (ROMs), random access memories (RAMs), EPROMs, EEPROMs, magnetic or optical cards, application spedfic integrated circuits (ASICs), or any type of media suitable for storing electronic instructions, and each coupled to a computer system bus.
  • the computers referred to in the specification may indude a single processor or may be architectures employing multiple processor designs for increased computing capability.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Zoology (AREA)
  • Immunology (AREA)
  • Wood Science & Technology (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pathology (AREA)
  • General Physics & Mathematics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

L'invention concerne un procédé servant à l'identification rapide automatisée de bioagents inconnus au moyen d'un dispositif autonome couplé à un module superviseur. Le dispositif selon l'invention comprend deux plateaux séparés par un sas, ainsi qu'une zone de stockage servant à stocker des réactifs et des plaques filtrantes servant à identifier des bioagents. Un ensemble robot programmable isole et purifie l'ADN provenant du bioagent dans le premier plateau et prépare l'échantillon pour la réaction en chaîne de la polymérase. Le premier plateau est maintenu, de préférence, à une pression atmosphérique supérieure à celle de la zone externe au dispositif alors que le deuxième plateau est maintenu à une pression atmosphérique inférieure à celle de la zone externe afin d'éviter la contamination. Après isolation et purification, l'échantillon est amené à travers le sas au deuxième plateau où il subit la réaction en chaîne de la polymérase. Après lavage et élution de l'échantillon, la masse moléculaire de l'échantillon est déterminée par spectroscopie de masse. Le module superviseur assure le traitement automatisé des requêtes, la planification des travaux, la gestion des ressources et l'analyse en mode descendant.
PCT/US2004/015123 2003-05-12 2004-05-12 Identification automatique de bioagents Ceased WO2005009202A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US47017503P 2003-05-12 2003-05-12
US60/470,175 2003-05-12

Publications (2)

Publication Number Publication Date
WO2005009202A2 true WO2005009202A2 (fr) 2005-02-03
WO2005009202A3 WO2005009202A3 (fr) 2005-11-10

Family

ID=34102619

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2004/015123 Ceased WO2005009202A2 (fr) 2003-05-12 2004-05-12 Identification automatique de bioagents

Country Status (1)

Country Link
WO (1) WO2005009202A2 (fr)

Cited By (43)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7956175B2 (en) 2003-09-11 2011-06-07 Ibis Biosciences, Inc. Compositions for use in identification of bacteria
EP2333559A1 (fr) * 2009-12-10 2011-06-15 F. Hoffmann-La Roche AG Procédé de séparation et de détection d'un analyte
US7964343B2 (en) 2003-05-13 2011-06-21 Ibis Biosciences, Inc. Method for rapid purification of nucleic acids for subsequent analysis by mass spectrometry by solution capture
US8017322B2 (en) 2001-03-02 2011-09-13 Ibis Biosciences, Inc. Method for rapid detection and identification of bioagents
US8026084B2 (en) 2005-07-21 2011-09-27 Ibis Biosciences, Inc. Methods for rapid identification and quantitation of nucleic acid variants
EP2333560A3 (fr) * 2009-12-10 2011-10-05 F. Hoffmann-La Roche AG Procédé de séparation et de détection d'un analyte
US8046171B2 (en) 2003-04-18 2011-10-25 Ibis Biosciences, Inc. Methods and apparatus for genetic evaluation
US8057993B2 (en) 2003-04-26 2011-11-15 Ibis Biosciences, Inc. Methods for identification of coronaviruses
US8071309B2 (en) 2002-12-06 2011-12-06 Ibis Biosciences, Inc. Methods for rapid identification of pathogens in humans and animals
US8073627B2 (en) 2001-06-26 2011-12-06 Ibis Biosciences, Inc. System for indentification of pathogens
US8084207B2 (en) 2005-03-03 2011-12-27 Ibis Bioscience, Inc. Compositions for use in identification of papillomavirus
EP2402764A1 (fr) * 2010-06-29 2012-01-04 F. Hoffmann-La Roche AG Distribution d'échantillons
US8097416B2 (en) 2003-09-11 2012-01-17 Ibis Biosciences, Inc. Methods for identification of sepsis-causing bacteria
US8119336B2 (en) 2004-03-03 2012-02-21 Ibis Biosciences, Inc. Compositions for use in identification of alphaviruses
US8148163B2 (en) 2008-09-16 2012-04-03 Ibis Biosciences, Inc. Sample processing units, systems, and related methods
US8158936B2 (en) 2009-02-12 2012-04-17 Ibis Biosciences, Inc. Ionization probe assemblies
US8158354B2 (en) 2003-05-13 2012-04-17 Ibis Biosciences, Inc. Methods for rapid purification of nucleic acids for subsequent analysis by mass spectrometry by solution capture
US8163895B2 (en) 2003-12-05 2012-04-24 Ibis Biosciences, Inc. Compositions for use in identification of orthopoxviruses
US8173957B2 (en) 2004-05-24 2012-05-08 Ibis Biosciences, Inc. Mass spectrometry with selective ion filtration by digital thresholding
US8182992B2 (en) 2005-03-03 2012-05-22 Ibis Biosciences, Inc. Compositions for use in identification of adventitious viruses
US8187814B2 (en) 2004-02-18 2012-05-29 Ibis Biosciences, Inc. Methods for concurrent identification and quantification of an unknown bioagent
US8214154B2 (en) 2001-03-02 2012-07-03 Ibis Biosciences, Inc. Systems for rapid identification of pathogens in humans and animals
WO2012058559A3 (fr) * 2010-10-29 2012-09-07 Thermo Fisher Scientific Oy Agencement pour un système automatisé de préparation et d'analyse d'échantillons
US8268565B2 (en) 2001-03-02 2012-09-18 Ibis Biosciences, Inc. Methods for identifying bioagents
US8298760B2 (en) 2001-06-26 2012-10-30 Ibis Bioscience, Inc. Secondary structure defining database and methods for determining identity and geographic origin of an unknown bioagent thereby
US8407010B2 (en) 2004-05-25 2013-03-26 Ibis Biosciences, Inc. Methods for rapid forensic analysis of mitochondrial DNA
US8534447B2 (en) 2008-09-16 2013-09-17 Ibis Biosciences, Inc. Microplate handling systems and related computer program products and methods
US8546082B2 (en) 2003-09-11 2013-10-01 Ibis Biosciences, Inc. Methods for identification of sepsis-causing bacteria
US8550694B2 (en) 2008-09-16 2013-10-08 Ibis Biosciences, Inc. Mixing cartridges, mixing stations, and related kits, systems, and methods
US8563250B2 (en) 2001-03-02 2013-10-22 Ibis Biosciences, Inc. Methods for identifying bioagents
US8871471B2 (en) 2007-02-23 2014-10-28 Ibis Biosciences, Inc. Methods for rapid forensic DNA analysis
US8950604B2 (en) 2009-07-17 2015-02-10 Ibis Biosciences, Inc. Lift and mount apparatus
US9149473B2 (en) 2006-09-14 2015-10-06 Ibis Biosciences, Inc. Targeted whole genome amplification method for identification of pathogens
US9194877B2 (en) 2009-07-17 2015-11-24 Ibis Biosciences, Inc. Systems for bioagent indentification
EP2943116A4 (fr) * 2013-01-09 2016-09-07 Siemens Healthcare Diagnostics Distribution de réactif pour l'optimisation de débit
US9598724B2 (en) 2007-06-01 2017-03-21 Ibis Biosciences, Inc. Methods and compositions for multiple displacement amplification of nucleic acids
AU2015261711B2 (en) * 2010-10-29 2017-11-09 Thermo Fisher Scientific Oy Automated system for sample preparation and analysis
US9873906B2 (en) 2004-07-14 2018-01-23 Ibis Biosciences, Inc. Methods for repairing degraded DNA
US9890408B2 (en) 2009-10-15 2018-02-13 Ibis Biosciences, Inc. Multiple displacement amplification
WO2021145771A1 (fr) 2020-01-17 2021-07-22 In Ovo Holding B.V Dispositif de détermination de caractéristiques d'œufs
WO2021257041A1 (fr) * 2020-06-19 2021-12-23 Intecro Roboti̇k Otomasyon Arge Mühendi̇sli̇k Maki̇ne Sanayi̇ Ve Ti̇caret Anoni̇m Şi̇rketi̇ Unité de mécanisme robotisé destinée à être utilisée dans des tests et analyses diagnostiques in vitro
WO2022010348A1 (fr) 2020-07-05 2022-01-13 In Ovo Holding B.V. Procédé et dispositif de détermination d'œuf
CN114369529A (zh) * 2020-10-19 2022-04-19 成都瀚辰光翼生物工程有限公司 基因检测设备

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7321828B2 (en) * 1998-04-13 2008-01-22 Isis Pharmaceuticals, Inc. System of components for preparing oligonucleotides
US6856914B1 (en) * 1999-11-19 2005-02-15 The University Of British Columbia Method, apparatus, media and signals for identifying associated cell signaling proteins
CA2423552A1 (fr) * 2000-10-13 2002-04-18 Irm Llc Systeme de traitement a haut rendement et procede d'utilisation

Cited By (88)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9416424B2 (en) 2001-03-02 2016-08-16 Ibis Biosciences, Inc. Methods for rapid identification of pathogens in humans and animals
US8214154B2 (en) 2001-03-02 2012-07-03 Ibis Biosciences, Inc. Systems for rapid identification of pathogens in humans and animals
US8265878B2 (en) 2001-03-02 2012-09-11 Ibis Bioscience, Inc. Method for rapid detection and identification of bioagents
US9752184B2 (en) 2001-03-02 2017-09-05 Ibis Biosciences, Inc. Methods for rapid forensic analysis of mitochondrial DNA and characterization of mitochondrial DNA heteroplasmy
US8268565B2 (en) 2001-03-02 2012-09-18 Ibis Biosciences, Inc. Methods for identifying bioagents
US8563250B2 (en) 2001-03-02 2013-10-22 Ibis Biosciences, Inc. Methods for identifying bioagents
US8017322B2 (en) 2001-03-02 2011-09-13 Ibis Biosciences, Inc. Method for rapid detection and identification of bioagents
US8017743B2 (en) 2001-03-02 2011-09-13 Ibis Bioscience, Inc. Method for rapid detection and identification of bioagents
US8017358B2 (en) 2001-03-02 2011-09-13 Ibis Biosciences, Inc. Method for rapid detection and identification of bioagents
US8815513B2 (en) 2001-03-02 2014-08-26 Ibis Biosciences, Inc. Method for rapid detection and identification of bioagents in epidemiological and forensic investigations
US8802372B2 (en) 2001-03-02 2014-08-12 Ibis Biosciences, Inc. Methods for rapid forensic analysis of mitochondrial DNA and characterization of mitochondrial DNA heteroplasmy
US8298760B2 (en) 2001-06-26 2012-10-30 Ibis Bioscience, Inc. Secondary structure defining database and methods for determining identity and geographic origin of an unknown bioagent thereby
US8380442B2 (en) 2001-06-26 2013-02-19 Ibis Bioscience, Inc. Secondary structure defining database and methods for determining identity and geographic origin of an unknown bioagent thereby
US8073627B2 (en) 2001-06-26 2011-12-06 Ibis Biosciences, Inc. System for indentification of pathogens
US8921047B2 (en) 2001-06-26 2014-12-30 Ibis Biosciences, Inc. Secondary structure defining database and methods for determining identity and geographic origin of an unknown bioagent thereby
US8071309B2 (en) 2002-12-06 2011-12-06 Ibis Biosciences, Inc. Methods for rapid identification of pathogens in humans and animals
US8822156B2 (en) 2002-12-06 2014-09-02 Ibis Biosciences, Inc. Methods for rapid identification of pathogens in humans and animals
US9725771B2 (en) 2002-12-06 2017-08-08 Ibis Biosciences, Inc. Methods for rapid identification of pathogens in humans and animals
US8046171B2 (en) 2003-04-18 2011-10-25 Ibis Biosciences, Inc. Methods and apparatus for genetic evaluation
US8057993B2 (en) 2003-04-26 2011-11-15 Ibis Biosciences, Inc. Methods for identification of coronaviruses
US8158354B2 (en) 2003-05-13 2012-04-17 Ibis Biosciences, Inc. Methods for rapid purification of nucleic acids for subsequent analysis by mass spectrometry by solution capture
US8476415B2 (en) 2003-05-13 2013-07-02 Ibis Biosciences, Inc. Methods for rapid purification of nucleic acids for subsequent analysis by mass spectrometry by solution capture
US7964343B2 (en) 2003-05-13 2011-06-21 Ibis Biosciences, Inc. Method for rapid purification of nucleic acids for subsequent analysis by mass spectrometry by solution capture
US8097416B2 (en) 2003-09-11 2012-01-17 Ibis Biosciences, Inc. Methods for identification of sepsis-causing bacteria
US8546082B2 (en) 2003-09-11 2013-10-01 Ibis Biosciences, Inc. Methods for identification of sepsis-causing bacteria
US7956175B2 (en) 2003-09-11 2011-06-07 Ibis Biosciences, Inc. Compositions for use in identification of bacteria
US8013142B2 (en) 2003-09-11 2011-09-06 Ibis Biosciences, Inc. Compositions for use in identification of bacteria
US8163895B2 (en) 2003-12-05 2012-04-24 Ibis Biosciences, Inc. Compositions for use in identification of orthopoxviruses
US8187814B2 (en) 2004-02-18 2012-05-29 Ibis Biosciences, Inc. Methods for concurrent identification and quantification of an unknown bioagent
US9447462B2 (en) 2004-02-18 2016-09-20 Ibis Biosciences, Inc. Methods for concurrent identification and quantification of an unknown bioagent
US8119336B2 (en) 2004-03-03 2012-02-21 Ibis Biosciences, Inc. Compositions for use in identification of alphaviruses
US8173957B2 (en) 2004-05-24 2012-05-08 Ibis Biosciences, Inc. Mass spectrometry with selective ion filtration by digital thresholding
US8987660B2 (en) 2004-05-24 2015-03-24 Ibis Biosciences, Inc. Mass spectrometry with selective ion filtration by digital thresholding
US9449802B2 (en) 2004-05-24 2016-09-20 Ibis Biosciences, Inc. Mass spectrometry with selective ion filtration by digital thresholding
US8407010B2 (en) 2004-05-25 2013-03-26 Ibis Biosciences, Inc. Methods for rapid forensic analysis of mitochondrial DNA
US9873906B2 (en) 2004-07-14 2018-01-23 Ibis Biosciences, Inc. Methods for repairing degraded DNA
US8182992B2 (en) 2005-03-03 2012-05-22 Ibis Biosciences, Inc. Compositions for use in identification of adventitious viruses
US8084207B2 (en) 2005-03-03 2011-12-27 Ibis Bioscience, Inc. Compositions for use in identification of papillomavirus
US8551738B2 (en) 2005-07-21 2013-10-08 Ibis Biosciences, Inc. Systems and methods for rapid identification of nucleic acid variants
US8026084B2 (en) 2005-07-21 2011-09-27 Ibis Biosciences, Inc. Methods for rapid identification and quantitation of nucleic acid variants
US9149473B2 (en) 2006-09-14 2015-10-06 Ibis Biosciences, Inc. Targeted whole genome amplification method for identification of pathogens
US8871471B2 (en) 2007-02-23 2014-10-28 Ibis Biosciences, Inc. Methods for rapid forensic DNA analysis
US9598724B2 (en) 2007-06-01 2017-03-21 Ibis Biosciences, Inc. Methods and compositions for multiple displacement amplification of nucleic acids
US9023655B2 (en) 2008-09-16 2015-05-05 Ibis Biosciences, Inc. Sample processing units, systems, and related methods
US8550694B2 (en) 2008-09-16 2013-10-08 Ibis Biosciences, Inc. Mixing cartridges, mixing stations, and related kits, systems, and methods
US8148163B2 (en) 2008-09-16 2012-04-03 Ibis Biosciences, Inc. Sample processing units, systems, and related methods
US8609430B2 (en) 2008-09-16 2013-12-17 Ibis Biosciences, Inc. Sample processing units, systems, and related methods
US9027730B2 (en) 2008-09-16 2015-05-12 Ibis Biosciences, Inc. Microplate handling systems and related computer program products and methods
US8534447B2 (en) 2008-09-16 2013-09-17 Ibis Biosciences, Inc. Microplate handling systems and related computer program products and methods
US8252599B2 (en) 2008-09-16 2012-08-28 Ibis Biosciences, Inc. Sample processing units, systems, and related methods
US8796617B2 (en) 2009-02-12 2014-08-05 Ibis Biosciences, Inc. Ionization probe assemblies
US8158936B2 (en) 2009-02-12 2012-04-17 Ibis Biosciences, Inc. Ionization probe assemblies
US9165740B2 (en) 2009-02-12 2015-10-20 Ibis Biosciences, Inc. Ionization probe assemblies
US8950604B2 (en) 2009-07-17 2015-02-10 Ibis Biosciences, Inc. Lift and mount apparatus
US9194877B2 (en) 2009-07-17 2015-11-24 Ibis Biosciences, Inc. Systems for bioagent indentification
US9890408B2 (en) 2009-10-15 2018-02-13 Ibis Biosciences, Inc. Multiple displacement amplification
US8476015B2 (en) 2009-12-10 2013-07-02 Roche Molecular Systems, Inc. Method for separating and detecting an analyte
US9365895B2 (en) 2009-12-10 2016-06-14 Roche Molecular Systems, Inc. Amplification system with spatial separation
US8530229B2 (en) 2009-12-10 2013-09-10 Roche Molecular Systems, Inc. Amplification system with spatial separation
US10351843B2 (en) 2009-12-10 2019-07-16 Roche Molecular Systems, Inc. System for separating and detecting an analyte
US8809039B2 (en) 2009-12-10 2014-08-19 Roche Molecular Systems, Inc. Amplification system with spatial separation
JP2016033518A (ja) * 2009-12-10 2016-03-10 エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ 分析対象物を分離して検出する方法
US9315801B2 (en) 2009-12-10 2016-04-19 Roche Molecular Systems, Inc. Method for separating and detecting an analyte
CN102141572A (zh) * 2009-12-10 2011-08-03 霍夫曼-拉罗奇有限公司 具有空间分离的放大系统
EP2333560A3 (fr) * 2009-12-10 2011-10-05 F. Hoffmann-La Roche AG Procédé de séparation et de détection d'un analyte
JP2011123067A (ja) * 2009-12-10 2011-06-23 F Hoffmann La Roche Ag 空間的分離による増幅システム
EP2333559A1 (fr) * 2009-12-10 2011-06-15 F. Hoffmann-La Roche AG Procédé de séparation et de détection d'un analyte
US8772036B2 (en) 2010-06-29 2014-07-08 Roche Molecular Systems, Inc. Automated method for sample distribution and isolation of an analyte with a solid support
US9383379B2 (en) 2010-06-29 2016-07-05 Roche Molecular Systems, Inc. Sample distribution in a method for isolating analytes in fluid samples in an automated system
JP2012013697A (ja) * 2010-06-29 2012-01-19 F. Hoffmann-La Roche Ag サンプルの分配
EP2402764A1 (fr) * 2010-06-29 2012-01-04 F. Hoffmann-La Roche AG Distribution d'échantillons
US9383378B2 (en) 2010-06-29 2016-07-05 Roche Molecular Systems, Inc. Sample distribution in an analytical system for processing an analyte
US9236236B2 (en) 2010-10-29 2016-01-12 Thermo Fisher Scientific Oy System layout for an automated system for sample preparation and analysis
CN105911196B (zh) * 2010-10-29 2019-04-23 恩姆菲舍尔科技公司 用于样品制备和分析的自动化系统的系统布局
AU2015261711B2 (en) * 2010-10-29 2017-11-09 Thermo Fisher Scientific Oy Automated system for sample preparation and analysis
CN105911196A (zh) * 2010-10-29 2016-08-31 恩姆菲舍尔科技公司 用于样品制备和分析的自动化系统的系统布局
WO2012058559A3 (fr) * 2010-10-29 2012-09-07 Thermo Fisher Scientific Oy Agencement pour un système automatisé de préparation et d'analyse d'échantillons
US10088460B2 (en) 2010-10-29 2018-10-02 Thermo Fisher Scientific Oy Automated system for sample preparation and analysis
US10739321B2 (en) 2010-10-29 2020-08-11 Thermo Fisher Scientific Oy Automated system for sample preparation and analysis
US10557835B2 (en) 2010-10-29 2020-02-11 Thermo Fisher Scientific Oy Automated system for sample preparation and analysis
US9000360B2 (en) 2010-10-29 2015-04-07 Thermo Fisher Scientific Oy System layout for an automated system for sample preparation and analysis
EP2943116A4 (fr) * 2013-01-09 2016-09-07 Siemens Healthcare Diagnostics Distribution de réactif pour l'optimisation de débit
US10139422B2 (en) 2013-01-09 2018-11-27 Siemens Healthcare Diagnostics Inc. Throughput optimizing reagent distribution
WO2021145771A1 (fr) 2020-01-17 2021-07-22 In Ovo Holding B.V Dispositif de détermination de caractéristiques d'œufs
WO2021257041A1 (fr) * 2020-06-19 2021-12-23 Intecro Roboti̇k Otomasyon Arge Mühendi̇sli̇k Maki̇ne Sanayi̇ Ve Ti̇caret Anoni̇m Şi̇rketi̇ Unité de mécanisme robotisé destinée à être utilisée dans des tests et analyses diagnostiques in vitro
WO2022010348A1 (fr) 2020-07-05 2022-01-13 In Ovo Holding B.V. Procédé et dispositif de détermination d'œuf
CN114369529A (zh) * 2020-10-19 2022-04-19 成都瀚辰光翼生物工程有限公司 基因检测设备
CN114369529B (zh) * 2020-10-19 2023-06-16 成都瀚辰光翼生物工程有限公司 基因检测设备

Also Published As

Publication number Publication date
WO2005009202A3 (fr) 2005-11-10

Similar Documents

Publication Publication Date Title
WO2005009202A2 (fr) Identification automatique de bioagents
AU2021286412B2 (en) High Throughput System for Performing Assays Using Electrochemiluminescence Including A Consumable Shaking Apparatus
US11835533B2 (en) Reflex testing of samples using residual materials from a prior test
EP1188126B1 (fr) Procedes, appareil, articles de fabrication, et interface utilisateur pour effectuer la preparation de dosage biologique et la purification automatisees de macromolecules
US7390458B2 (en) High throughput processing system and method of using
AU2013270739B2 (en) Interfacing apparatus between a laboratory automation system and a platform for handling consumables and liquids in the field of molecular biology
EP2600156B1 (fr) Dispositif d'analyse d'acides nucléiques
KR20050008720A (ko) 표적 핵산 서열의 분리, 증폭 및 검출을 위한 자동화 시스템
CN105188938A (zh) 诊断系统和方法
WO2012012779A2 (fr) Système et procédé comprenant des unités analytiques
EP1612561A1 (fr) Instrument de traitement efficace des dispositifs analytiques
US11022622B2 (en) High-throughput screening system based on multi-manipulators
WO2000008472A2 (fr) Appareil de dosage immunologique automatise muni d'un doigt de ramassage
JP2010002353A (ja) 核酸分析装置，自動分析装置、及び分析方法
JP5846773B2 (ja) サンプルの分配
EP1513948B1 (fr) Systeme de micro-reseau integre et procedes associes
EP1718411B1 (fr) Appareil pour analyser l'interaction entre molecules cibles et sonde
EP1772192B1 (fr) Appareil de traitement biochimique doté d'un mécanisme de transport liquide
US20250341533A1 (en) Fully Automatic Instrument System for Biochemical Assays
Choi et al. Intelligent BioRobot platform for integrated clinical test

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): BW GH GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase