专利摘要:
An analytical system for treating an analyte, said system comprising a) a first position comprising a first receptacle containing a liquid sample comprising an analyte, a second receptacle for containing a liquid sample, a rack containing pipette tips, and a first treatment head for transferring a liquid sample from the first receptacle to a second receptacle, b) a second position comprising a station for receiving said second receptacle, and a rack receiving station for receiving said rack, c) a transfer system for transferring the same. second receptacle and the rack containing pipette tips between the first position and the second position.
公开号:FR3020140A1
申请号:FR1553101
申请日:2015-04-10
公开日:2015-10-23
发明作者:Renato Belz；Andreas Gisler；Robert Huesler；Rolf Knobel；Christian Thalmann
申请人:F Hoffmann La Roche AG；
IPC主号:

专利说明:

[0001] BACKGROUND The present invention relates to an automated analytical system and an automated method for separating and detecting an analyte, as well as to an automated analytical instrument. Analytical systems used in the diagnostics field require sample processing comprising analytes to be analyzed.
[0002] Such treatment involves transferring containers, or samples and liquid reagents from one container to another. For superior performance, simultaneous treatment is often performed using multiple consumables, such as pipette tips and multiwell plates. Especially with systems for nucleic acid analysis, reuse of pipette tips may be limited due to contamination. General Description The present invention relates to an analytical apparatus. The terms "analytical apparatus" (400) and "analyzer" (400) and "analytical instrument" (400) are used interchangeably. An analytical system includes an analyzer. An analyzer includes one or more modules or cells. The said modules or cells comprise stations for carrying out the treatment and / or analysis of an analyte.
[0003] The invention also relates to a method for isolating and analyzing an analyte that may be present in a fluid sample. Preferably, said method comprises the automated steps of a) transferring said fluid sample from a sample container into a treatment container with a pipette tip of a first type; b) combining together a solid support material and said fluid sample in a well of said treatment vessel for a period of time and under conditions sufficient to allow said analyte to be immobilized on the solid support material; c) isolating the solid support material from another material present in the fluid sample in a separation station; d) and purifying the analyte in the separation station by separating the fluid sample from the solid support material and washing the materials one or more times with a wash buffer. In addition, the present invention relates to consumables that are optimized for use in automated analytical systems.
[0004] Legends of Figures Figure 1 shows a view of an assembled rack loaded with pipette tips. Figure 2 shows a view of a rack without loaded pipettes.
[0005] Figure 3 shows a cross-section through the longer side walls of the rack loaded with two types of pipette tips. Figure 4 shows a perspective view of the upper side of the lower rack. Figure 5 shows a perspective view of the lower portion of the lower rack zo. Figure 6 shows a perspective view of the upper side of the insertion rack. Figure 7 shows a perspective view of the lower portion of the insertion rack. Figure 8 shows a perspective view of the upper side of the upper rack. Figure 9 shows a perspective view of the lower portion of the upper rack. Figure 10 shows a partial cross-sectional view through the rack 30 assembled with loaded pipette tips. Figure 11 shows a partial cross-sectional view through the assembled rack without loaded pipette tips.
[0006] Figure 12 shows a perspective view of the upper rack loaded with pipette tips, with details of the first type of tips resting on the through holes. Figure 13 shows a perspective view of the upper rack loaded with pipette tips, with details of the second type of tips resting on the through-hole rim. Figure 14 a) shows a perspective view of the first and second types of pipette tips. B) shows a pipette needle. Figure 15 shows a detailed perspective view of the alignment of the positioning elements on the bottom of the treatment head and the positioning elements on the top of the upper rack for alignment of the treatment head with the first type of treatment. pipette tips. Figure 16 shows a detailed perspective view of the engagement of the positioning elements on the bottom of the treatment head and the positioning elements on the top of the upper rack. Figure 17 shows a detailed perspective view of the engagement of the positioning elements on the bottom of the treatment head and the positioning elements on the top of the upper rack for alignment of the treatment head with the second type of pipette tips. Figure 18 shows a detailed perspective view of the treatment head after engagement of the second type of pipette tips. Figure 19 shows a perspective view of the positioning elements on a side wall of the rack and on the treatment board for initial positioning of the rack inside the analyzer. Figure 20 shows a perspective view of the engagement of locating members on a side wall of the rack and on the treatment board for initial positioning of the rack within the analyzer. Figure 21 shows a detailed cross-sectional view of the bottom of a chamber for receiving the second type of pipette tips in the insertion rack and the ridge between two chambers of the lower rack. Figure 22 shows a detailed cross-sectional view of the bottom of the chambers of the lower rack.
[0007] Figure 23 shows a cross-sectional view of the interaction site between the upper rack and the insert rack with a second type of pipette tip inserted into a through hole. Figure 24 shows a cross-sectional view of the interaction site between the upper rack and the insert rack without a second type of pipette tip inserted into a through hole. Figure 25 Partial view of a second embodiment of the bit rack. Figure 26 shows a perspective view of the treatment plate.
[0008] Figure 27 shows a perspective view of the treatment plate viewed from the opposite angle. Figure 28 shows a top view of the treatment plate. Figure 29 shows a cross-sectional view along the longer side of the treatment plate.
[0009] Figure 30 shows a partial view of the cross-sectional view. Figure 31 shows a perspective view of the longer side of the treatment plate. Figure 32 shows a perspective view of the bottom of the treatment plate. Figure 33 shows a more vertical perspective view of the bottom of the treatment plate. Figure 34 shows the fit of the smaller magnets of the first preferred embodiment of the separation station with the containers of the treatment plate. Figure 35 shows a horizontal cross-sectional view of the central region of the treatment plate and containers. Figure 36 shows the adjustment of the treatment plate in a receiving station of the treatment plate (for example the magnetic separation station), with the locking mechanism disengaged. Figure 37 shows the adjustment of the treatment plate in a receiving station of the treatment plate (for example the magnetic separation station), with the locking mechanism engaged. Figure 38 shows a schematic drawing of an analyzer comprising different stations, modules or cells.
[0010] Figures 39 a) to d) show different views of the second embodiment of the magnetic separation station. Figs. 40 (a) to (c) show a view of the first embodiment of the magnetic separation station containing the treatment plate, with the first type of magnets in the highest Z position and the second type of magnet. magnets in the lowest Z position. Figures 41 (a) to (c) show a view of the first embodiment of the magnetic separation station containing the treatment plate, with the first type of magnets in the highest Z position and the second type of magnets in the highest Z position. Figures 42 (a) to (c) show a view of the first embodiment of the magnetic separation station containing the treatment plate, with the first type of magnets in the lowest position Z and the second type of magnets in the highest Z position.
[0011] Figures 43 (a) to (c) show a view of the first embodiment of the magnetic separation station containing the treatment plate, with the first type of magnets in the lowest position Z and the second type of magnets in the lowest Z position. Figures 44 a) to d) show the plate AD and the frame with the sealing sheet in storage position (a), with the cover (b) raised, during the rotation of the cover (c) and in the closed position waterproof (d). Figure 45 a) shows a sectional side view of the plate AD and the frame in the closed position; b) shows a sealing sheet with two layers and the top of the cover comprising a frame.
[0012] Figures 46 a) and b) show side and top sectional views of a corner of the plate AD and the frame in the storage position. Figures 46 (c) to (d) show side and top side views of a corner of the plate AD and the frame in the closed position. Figures 47 a) and b) show the adjustment of the plate AD in a receiving station of the plate AD with the locking mechanism disengaged (a) or engaged (b). Figure 48 shows the interaction of a tip rack with the gripping fingers. The locking of the gripper prevents movement in the X and Y directions (see drawing on the right).
[0013] Figure 49 shows the interaction between the manipulator and a multiwell plate. The gripping fingers interlock with apertures on the multi-well plate resulting in an interlocking gripping.
[0014] Figures 50 a) and b) show the manipulator connected to a robotic arm, and attachment and release of the consumable by the gripping fingers. c) shows that the manipulator interacts with different consumables with the same interface. Figure 51 is a schematic drawing of an embodiment of an analyzer with stackers that specifically recognize certain consumables. Figure 52 shows a schematic drawing of a hardware architecture with processes from consumable media to different modules, and between different modules (shown by arrows); and different modules to the waste holder. Figure 53 shows a schematic view of systems with modules with predefined process timers and a transport module that is either linear (a)) or circular (b)). c) shows a preferred system with a module of a first type, two modules of a second type and four modules 20 of a third type. Figure 54 shows a schematic front view of an analytical apparatus according to the invention. Figure 55 shows a top view (a) and a side view (b) of the pneumatic lock. Figure 56 shows a perspective view of an analytical apparatus of the present invention with front walls. Description of Preferred Embodiments Analytical Apparatus and Method for Isolating and Analyzing an Analyte A method of isolating and analyzing an analyte that may be present in a fluid sample is disclosed. The method comprises the automated steps of a) transferring said fluid sample from a sample container to a treatment container with a pipette tip; b) combining together a solid support material and said fluid sample in a well of said treatment vessel for a period of time and under conditions sufficient to allow said analyte to be immobilized on the solid support material; c) isolating the solid support material from another material present in the fluid sample in a separation station; d) and purifying the analyte in the separation station by separating the fluid sample from the solid support material and washing the materials one or more times with a wash buffer. Preferably, said pipette tip used in step a) is reused after step a).
[0015] In a preferred embodiment, said pipette tip is a pipette tip of a first type, and said pipette tip of a first type is stored in a rack including pipette tips of a first type and tips. pipettes of a second type. Preferably, said pipette tips of a first type and a second type are stored in said rack at least between one use for pipetting. In a preferred embodiment of the method described above, step a) comprises a1) engaging pipette tips of a first type which are contained in a rack in a first position with a first treatment head. ; a2) transferring said fluid sample from a sample container to a treatment container with pipette tips of a first type engaged with a first treatment head; a3) placing said pipette tips in said rack and disengaging said pipette tips from said treatment head; a4) transporting said rack comprising said pipette tips and said process container to second positions; a5) engaging said pipette tips of a first type which are contained in said rack with a second treatment head at said second position.
[0016] Preferably, the treatment container comprises more than one receptacle. More preferably, the treatment vessel is a multiwell plate. The method preferably further comprises the step of e) reacting said purified analyte with reagents necessary to obtain a detectable signal.
[0017] The reuse of pipette tips results in a reduction of disposable consumables used in the analytical process and cost reductions. In a preferred embodiment, the wash in step d) comprises aspirating and dispensing the wash buffer with a treatment head engaged with the pipette tips. The term "receptacle" as used herein refers to a single container (or tube) or tube included in a multiple tube unit, or to a well (or container) of a multi-well plate. The term "container" is understood to mean a single container or a single container in a multiple tube unit, a multiwell plate or a multiple tube unit or a well of a multiwell plate. In a preferred embodiment, the reaction comprises generating a detectable signal. More preferably, the method further comprises the step of detecting a detectable signal. The term "analyte" as used herein may be any type of biomolecule that is of interest for detection, and the detection thereof is indicative of a diagnostic state of an organism. The organism may be animal or, more preferably, human. Preferred analytes are proteins, polypeptides, antibodies or nucleic acids. More preferably, the analyte is a nucleic acid.
[0018] The term "reaction" as used herein refers to any type of chemical reaction of the analyte with reagents that is necessary to obtain a detectable signal. Preferably, said reaction comprises amplification. Amplification can be understood as any type of signal enhancement. Thus, an amplification may be a conversion of a molecule by an enzyme, wherein said enzyme is coupled to or bound to the analyte, resulting in a detectable signal, in which more signal molecules are formed than analyte molecules present . Such a non-limiting example is a formation of a chemiluminescent dye, for example using an ECL. The term amplification further refers to nucleic acid amplification, if the analyte is a nucleic acid. This includes linear, isothermal and exponential amplifications. Non-limiting examples of nucleic acid amplification methods are TMA, SDA, NASBA, PCR, including real-time PCR. Such methods are well known to those skilled in the art. The term "solid support" as used herein refers to any type of solid support to which the analyte is capable of binding, either directly by adsorption or indirectly and specifically. Indirect binding may be a binding of an analyte to an immobilized antibody on the solid support, or a binding of a label to a label binding compound, for example the binding of 6xHis tags to a Ni chelate. When the analyte is a nucleic acid, such indirect binding is preferably by binding to a capture nucleic acid probe that is homologous to a target sequence of the nucleic acid of interest. Thus, by using capture probes fixed on a solid support, a target analyte, preferably a target nucleic acid, can be separated from a non-target material, preferably a non-target nucleic acid. Such a capture probe is immobilized on the solid support. The solid support material may be a polymer, or a polymer composition. Other types of solid support material include magnetic silica particles, metal particles, and the like. A preferred direct link of nucleic acid to silica particles is in the presence of chaotropic compounds. Such binding may also be referred to as direct binding, as opposed to the indirect binding described above. Preferably, the solid supports are silica particles that comprise a magnetic or magnetizable material. A "separation station" is understood as a station where an analyte is separated from a solid support.
[0019] In a preferred embodiment of the method described above, the transport of said rack comprising said pipette tips and said treatment container to a second position is between a first separate cell of an analytical instrument and a second separate cell. , preferably a processing cell, of said analytical system. Preferably, the rack includes independent chambers for receiving pipette tips. In a preferred embodiment, the first type of pipette tips is reused for washing in step d). In a preferred embodiment, the rack further includes a second type of pipette tips. Further preferred is a method as described above, wherein between step d) and step e) the analyte is eluted from the magnetic particles. A preferred embodiment comprises transferring the analyte from said treatment vessel, which is preferably a multi-well plate, to a reaction vessel, which is preferably a multi-well plate, with said second type of mouthpiece. pipettes. An analytical system for isolating an analyte is exposed, said system comprising a) a first position comprising a first receptacle containing a liquid sample comprising an analyte, a second receptacle for containing a liquid sample, a rack containing pipette tips, and a first treatment head for transferring a liquid sample from the first receptacle to a second receptacle, b) a second position comprising a station for receiving said second receptacle, and a rack receiving station for receiving said rack, c) a system transfer device for transferring the second receptacle and the rack containing pipette tips between the first position and the second position.
[0020] Preferably, the positions are separate cells. The rack transferred by said transfer system includes pipette tips which are used in the first position. In a preferred embodiment, the first receptacle is a sample container and the second receptacle is a treatment container. Also preferred is a process vessel which is a multiwell vessel. Preferred embodiments of said stations are described below. In the analytical system described herein, the transport system preferably transfers the receptacle and the rack from the first position to the second, separate position. Preferably, the second separate position includes a magnetic separation station. The analytical system further preferably comprises an amplification station. The preferred system transport system comprises a manipulator constructed and arranged to grip and transport said rack and said process container from a first to a second position in the system. Other preferred manipulators are shown here. The system is preferably fully automated. An automated analyzer for isolating and analyzing an analyte comprising a plurality of stations disposed within said analyzer is also disclosed. The plurality of stations comprises a sample dispensing station disposed at a first location. Preferably, said sample dispensing station is constructed and arranged to dispense a liquid sample comprising an analyte from a sample container into a treatment container with pipette tips contained in a rack. Further preferred sample dispensing stations are stations comprising a sample container, a process container and a liquid dispensing unit. Said liquid distribution unit is preferably a treatment device. The automated analyzer further includes a separation station disposed at a second location. Preferably, said separation station is constructed and arranged to receive said treatment container containing said liquid sample and said rack containing pipette tips used in the sample dispensing station and to separate an analyte from another material present in the dispensing station. the liquid sample. Another preferred embodiment of a separation station is a separation station comprising moving magnets. The automated analyzer further comprises a reaction station disposed at a third location, wherein said reaction station is constructed and arranged to analyze said analyte to obtain a detectable signal. Another preferred embodiment of a reaction station is a station comprising an incubator. Preferably, said incubator is a temperature-controlled incubator. More preferably, said incubator is maintained at a constant temperature. Another preferred embodiment of an incubator is a thermal cycler block. Preferably, a detector for detecting the detectable signal is integrally connected to the reaction station, more preferably to the incubator as described above. A preferred detector comprises a nucleic acid quantization system for periodic measurement and quantitation. More preferably, the detector further comprises a nucleic acid detection system that detects the signal and ensures the presence or absence of the nucleic acid in the reaction receptacle based on a signal above the nucleic acid. a threshold level is detected or not. Alternatively, the automated analyzer further comprises a detection station. The automated analyzer further includes a transport mechanism. The transport mechanism includes a manipulator for handling consumables. Such a manipulator preferably carries a consumable between stations. In one embodiment, said transport mechanism is constructed and arranged to transport said sample container and said rack from said sample dispensing station to said separation station. Other preferred embodiments of the automated analyzer described herein are individual or combined features set forth herein.
[0021] In a preferred embodiment, the analytical apparatus (400) comprises at least one module (401) for treating an analyte, said processing comprising pipetting a liquid. The treatment module (401) comprises: a) a treatment head (35) for engagement with pipette tips (3, 4), said treatment head (35) comprising positioning elements (36) arranged in the lower surface (61) of said treatment head (35), b) a tip rack (60, 70) containing pipette tips (3, 4), wherein said tip rack (60, 70) comprises positioning elements (31, 32, 33, 34) adapted to mechanically engage with the positioning elements (36) on the treatment head (35). In a preferred embodiment of the analytical apparatus (400) described above, said processing module (401) is a module for isolation and purification of an analyte. Thus, the term "treatment" as used herein is understood to refer to isolation and / or separation and / or capture and / or purification of an analyte. Preferably, said apparatus (400) comprises a module for preparing processing samples (402). Preferably, said apparatus (400) comprises a module for amplification of said analyte (403). In a preferred embodiment, said apparatus further comprises a module (404) for transferring amplification reagents from a storage receptacle to a receptacle comprising a purified analyte. Other preferred embodiments of said apparatus are as described above and hereinafter.
[0022] An automated analyzer (400) for use in a nucleic acid-based amplification reaction is also disclosed. The analyzer includes a plurality of modules (401, 402, 403). A module is a processing module disposed at a first location within the analyzer constructed and arranged to separate a nucleic acid from another material in a sample. Said processing module comprises a separation device as described herein. The analyzer further comprises an amplification module arranged and arranged at a second location within the analyzer. The amplification module comprises a temperature-controlled incubator for incubating the contents of at least one receptacle, preferably a multi-well plate comprising the separated nucleic acid and one or more amplification reagents to produce a product. indicative amplification of the target nucleic acid in the sample.
[0023] An analytical system comprising a holding station and a set of multiwell plates as described herein is another preferred embodiment of the analytical system set forth herein. Preferably, said set of multiwell plates is fixed in said holding station.
[0024] Preferably, said multi-well plate comprises a base with a rim that includes recesses, wherein a positioning and fixing member, preferably a locking clip (Figures 47a) and b), on said holding station is in contact said recesses, wherein said contact exerts a downward pressure on the base of the multiwell plate, thereby securing the multiwell plate in the holding station. Other preferred embodiments of the analytical system include individual or combined features described herein. In addition, an analytical instrument is exposed, comprising: - a processing module for isolating and purifying an analyte comprising a holding station (470) for containing a rack comprising pipette tips, said rack comprising at least one recess located on a sidewall of the rack, and at least one recess located on a second opposite side wall of said rack, wherein said holding station comprises a fastener, preferably a locking clip, and wherein said fastener, preferably a clip of interlocking with said recess by exerting a force against the bottom of said recess; and - a module (403) for analyzing said purified analyte by reacting said analyte with reagents necessary to obtain a detectable signal. The analytical instrument preferably further comprises a liquid handling module (404, 500). Other embodiments and preferred embodiments of the analytical instrument are described herein, either separately or as combinations of embodiments. Preferred embodiments of analyzers are shown in FIGS. 38 and 51. The analytical instrument disclosed herein preferably further comprises a sealing station (410). The sealing station (410) is preferably located in the processing module (401). The terms "module" and "cell" are used interchangeably herein. End Rack A end rack is exposed. Such tip racks include pipette tips. Tip racks are commonly used in analytical systems to provide pipette tips for pipetting liquids into the system. Such tips are disposable, but can be reused at least once. The end rack includes independent chambers for receiving pipette tips. A preferred rack is exposed to contain pipette tips. The rack includes independent chambers for receiving at least one first type of pipette tips and a second type of pipette tips. In one embodiment, said rack comprises more than one part. In another embodiment, said rack is a rack integrated in one part. Preferably, the volume of the first type of pipette tips is at least 1 ml and the volume of the second type of pipette tips is less than 1 ml.
[0025] More preferably, the volume of the first type of pipette tips is between 1m1 and 1.5ml, and the volume of the second type of pipette tips is between 10μl and 600μl. Preferably, the first type of pipette tips and the second type of pipette tips are stored in said rack in alternate rows. In one embodiment, the rack comprises 48 pipette tips of a first type and 48 pipette tips of a second type. Other numbers of tips are, however, also covered. The rack may also include more pipette tips of one type than another type.
[0026] In one embodiment, the independent chambers are containers. A three-part rack is exposed to hold pipette tips. The rack includes features that make it particularly suitable for automated systems. Said rack comprises three parts. An upper rack comprises a surface plate, said surface plate comprises through holes with a seat area for inserting pipette tips into said rack. The rack also includes a lower rack. Said lower rack comprises independent chambers for receiving pipette tips of a first type. The third part of said rack and an insertion rack. The insertion rack is inserted into said lower rack. The insertion rack includes chambers for receiving pipette tips of a second type. The upper rack is assembled over said lower rack and said rack. The rack is thus suitable for holding more than one type of pipette tips. This is useful in systems in which different volumes of liquid are pipetted with pipette tips. The rack shown here includes contamination protection to protect individual tips from contaminating each other. Such contamination can occur due to droplets or aerosols. Such protection is of particular importance if pipette tips are in place in the rack after first use, before being reused again. Thus, the rack preferably includes rows of open chambers for holding a second type of pipette tips. More preferably, said open chambers have a bottom. This bottom separates the chamber containing the second type of pipette tips chambers containing the first type of pipette tips. This reduces the risk of contamination between the first and second type of tips.
[0027] In a preferred embodiment, said rows of open chambers for holding pipette tips of a second type are alternated with rows of independent chambers for receiving said pipette tips of a first type. Preferably, the inner surface of the independent chambers in the lower rack for receiving said pipette tips of a first type is larger than the inner surface of the through holes for inserting the pipette tips. In a preferred embodiment, a wall located on the inside of the side walls of the independent chambers of the lower rack to hold pipette tips of a first type extends from the bottom of the bottom rack to below the top of the bottom rack. side wall of the independent chambers of the lower rack. Preferred embodiments described above and hereinafter relate to a rack comprising pipette tips of a first type, more preferably further comprising a second type of pipette tips. Other preferred embodiments of any tip rack discussed herein include features described above and below without limitation to a specific embodiment by combination with any of the embodiments set forth herein. A first embodiment of an exemplary rack (60) (Figures 1 and 2) comprises multiple parts. An upper rack (1), a lower rack (2) and an insertion rack (14) are assembled into a rack for holding and reusing tips (4). In a preferred embodiment, a first type of ferrules (4) and a second type of ferrules (3) are contained in said rack (60). In a preferred embodiment, tips (4) for sampling, isolating and purifying an analyte and tips (3) for transferring the eluted analyte are contained in a rack according to the invention. Most preferably, the rack (60) contains elongated end caps with a large volume (4) and short endpieces with a small volume (3). Preferred embodiments of the three parts of the racks are described below.
[0028] Upper Rack (1) The upper rack (1) includes a frame (50) and a surface plate (51) located within said frame (50) (Figure 9, Figure 10). Said surface plate (51) comprises through holes (23, 25) (Figure 4). On the lower side (62) of said plate (51), partition walls (16) and separating lamellae (18) are located between the through holes (23, 25). They provide additional protection against contamination between the tips (3, 4) and provide additional stability to the upper rack (1). Some partition walls (16) also include a recess (13). Said recess (13) allows the partition walls (15) of the insertion rack (14) to engage with the partition walls (16) of the upper rack (1) in an overlapping manner for sealing against horizontally projected drops in the event of bubble explosion during handling of tips with tips (4). Preferably, separating lamellae (18) with a recess (13) alternate with separating lamellae (18) without recess. Lower rack (2) The lower rack (2) has two long side walls (52) opposite each other, and two short side walls (53) opposite one of the other. other (Figures 5 and 6). Each short side wall (53) is in contact with the two long side walls (52) to form a frame.
[0029] The interior space defined by said sidewalls (52) and (53) comprises chambers (19) which are formed by inner dividing walls (54) with a ridge (9) and perpendicular to said walls (54) and second walls (55). The chambers (19) include bottoms (21) which are preferably rounded.
[0030] The lower rack (2) includes, on the outside of the walls (52) and (53) stacker guide members (6) and (7) which, preferably, are also hardware identifiers. Insert rack (14) The rack (14) has two long front walls (56) and two short side walls (57). Chambers (24) are formed by partition walls (15) which are arranged parallel to the short side walls (57) (Figure 7, Figure 8). These chambers (24) have bottoms (58) and can receive the second type of end pieces (3). Between each chamber (24), there is a passageway (17) for a first type of end pieces (4) which extends inside the chambers (19) of the lower rack (2). The chambers (24) preferably include stabilizing ribs (41). The insertion rack (14) preferably includes additional stabilizing ribs (42, 43). Combination Bit Rack The multiple part construction of the rack (60) has several advantages. One advantage is that endpieces (4) having an elongated shape for pipeting large volumes can be stored in tightly packed independent chambers (19). The tips (4) thus require a limited space in a horizontal plane for storage, while being able to contain large volumes of liquid. Views of a preferred embodiment are shown in Figures 1 to 24. As a further advantage, the inner horizontal sectional area of the endpiece chambers (4) is larger than the cross-sectional area. through holes in the seat area (22) (Figure 3). This results in a prevention of capillary forces that can lead to a transport of liquid between the chambers (19). Yet another advantage of the construction of the bit rack (60) is that the inner walls (54) of the chambers (19) are not continuous from the bottom (21) of the chamber (21) to the seat area (22). ) (Figure 3). Thus, the transport of liquid from the bottom (21) of the chamber (21) to the seat area (22) and, thus, contamination, is prevented. This makes possible reuse of the pipette tips (4). In addition, the chambers (19) include a wall (5) located on the inner surface (65) (Figure 24). Said wall (5) preferably covers only a portion of the height of the chamber (19). More preferably, said wall (5) extends from above the bottom (21) of the chamber (19) to below the edge (9) of the inner surface (65) of walls (54). ) of the lower rack (2). Said wall (5) further prevents capillary effects in the chamber (19). Yet another advantage of constructing the bit rack (60) is that two different types of tips can be stored therein (Figure 3). In the present preferred embodiment, a second type of ferrules (3) is stored in the ferrule (60) of ferrules. The second type of tip is shorter than the first type of tip, and is used to pipette smaller amounts of liquid than those pipetted by the first type of pipette tip. In the present preferred example, the second type of ferrules are stored in chambers (24) within the insertion rack (14) which are located at a higher level than chambers (19) and are hermetically separated. rooms (19), but are open inside a row of rooms (24. An advantage of this construction is that it saves space, and with the rooms (24) in the insertion rack, there is more space available to prevent contamination, for example by capillary force, between the chambers (19) of the first type of tips (4) In a preferred embodiment, only the first type of end pieces (4) is reused, while the second type of end pieces (3) is used only once, and the insertion rack also has ridges (8) on the bottom of the end pieces. chambers (24) (Figure 3) These ridges (8) prevent splashing of liquid, which can be caused by liquid bubbles forming on the tip end of the pipette tip (4) and exploding at the edge height (8) do not pass into the adjacent chambers (19). The lower rack (2) comprises, at the top of the walls (54) between chambers (19), an edge (9). The edge (9) has the same function as the edge (8). The edge (9) and the edge (8) are not in contact with each other (Figure 23). This prevents hair effects. When stored in the rack (60), the tips (3, 4) rest on the seating area (22, 26) of a through hole (25, 23) (Figure 13, Figure 14). The through holes (25, 23) are located on a seat area (22, 26). Preferably, the seating area (22) of the through holes (25) is raised relative to the seating area (26) of the through holes (23) of the first type of end pieces (4). This has the advantage that when the first type of end pieces (4) is either returned to the rack or reengaged for reuse, in the case where liquid from the first type of end pieces (4) is in contact with the seat area (22) of the through hole (25), the liquid can not rise from the lower seat area (22) to the upper seat area (26), thereby preventing contamination of the second type of end caps (3). Preferably, additional capillary channels (40) separate adjacent through holes (23) at the lower seat area (22) and discharge any liquid in contact with the lower seating area (22) or through holes (23). ) (Figures 4, 9, 13, 14). This prevents contamination of neighboring through holes (23, 25). An additional advantage of the capillary channels (40) is that the liquid is spread over a larger area and can evaporate more rapidly.
[0031] In a preferred embodiment, the pipette tips include a receiving edge (27, 28) that contacts the seating areas (22, 26) of the through holes (23, 25) when the pipette tip (3 , 4) is housed in the rack (60) (Figure 15, Figure 16). More preferably, the second type of ferrules (3) have a receiving edge (27) shorter than the first type of ferrules (4). The difference in height between the receiving edges (27) and (28) is equal to the difference in height of the rim of the through holes (23) and (25). This has the advantage that all pipette tips (3, 4) are at the same level for engagement with the treatment head (35), but at the same time, the second type of pipette tips (3) can be housed on a higher level on the rack to prevent contamination by a liquid from the first type of tips (4). In addition, this allows a visual check of the correct assembly of the first and second type of pipette tips (3, 4) in the rack (60), since the upper surface of the tips (3, 4) housed in the wrong position would be a level lower or higher than that of the end pieces (3,4) properly housed. The receiving edges (27, 28) on the tip (3, 4) do not include a continuous circumferential seat base (59) for contact with the rim of the through hole (23, 25). The seat base (59) has only occasional sites of contact with the seating areas (22, 26). An advantage is that a smaller amount of material is used for the bit (3, 4) and that the bit (3, 4) can be produced with higher precision and with fewer stresses. The reduced contact area between the nozzle (3, 4) and the seat area (22, 26) has the additional advantage that the electrostatic charge of the tips (3, 4) is reduced. The end pieces (3, 4) are matted in the region of the shaft (29) with a surface roughness of 0.8 to 1.6 μm, and polished in the region of the tip end (30). The matted surface of the shaft (29) allows droplets of liquid to rest on the surface and evaporate faster. Thus, when the tip (4) is inserted into the through hole (23, 25), no liquid or less liquid can be wiped if the tip (4) comes into contact with the seat area (22, 26). ), and thus the risk of contamination is reduced. The polished tip end (30) causes droplets of liquid to remain on the tip end (30) in the manner of a bead and are wiped from the tip end (30) when the mouthpiece (4) springs from a liquid. The tip end (30) thus remains without hooked liquid. The upper rack (1) preferably comprises a first type of positioning element (10) (Figure 21, Figure 22) and a second type of positioning element (31, 32, 33, 34) (Figure 17, Figure 18 ). The first type of positioning elements (10) allow approximate positioning of the rack (60) with respect to a processing head (35), while the second type of positioning elements (31, 32, 33, 34) allows precise positioning of said rack (60) relative to the treatment head (35). The approximate positioning by the first type of positioning element (10) ensures that the second type of positioning elements (31, 33) or (32, 34) are aligned with counter positioning elements (36) on the treatment head (35). The advantage of the two types of positioning elements is that the positioning of the rack (60) and the treatment head (35) for engagement of the end pieces is fast and accurate.
[0032] The second type of positioning elements (31, 33) or (32, 34) are preferably located on the upper surface (also called surface plate) (51) of the rack (60) (Figures 17 to 20). The counter-positioning elements (36) are preferably located on the bottom surface (61) of the treatment head (35).
[0033] In a preferred embodiment, the positioning elements (31, 33) engage with the counter positioning elements (36) on the treatment head (35) to align the first type of pipette tips (4). with the interface on the treatment head (35) (Figure 17, Figure 18). Alternatively, the positioning elements (32, 34) engage with the counter elements (36) on the treatment head (35) to align the second type of pipette tips (3) with the interface (67) of the treatment head (35) (Figure 19, Figure 20). In a preferred embodiment, the positioning members are openings (31, 32, 33, 34) in the upper surface (51) of the rack (60), preferably located in opposite corners of the upper surface (51) of the rack (Figure 1). The counter positioning elements, in this preferred embodiment, on the bottom surface (61) of the treatment head (35) are rods (36) located in corresponding corners of the treatment head (35). The openings (31, 32, 33, 34) and the rods (36) are constructed in such a way that the rods (36) can engage with the openings (31, 32 or 33, 34) for precise alignment of the rack (60) and the treatment head (35). Thus, the tip (3, 4) and the interface (67) on the treatment head (35) for engagement of the tips (3, 4) are precisely aligned, and the interface of the treatment head (35). ) can engage the mouthpiece (3, 4). In a more preferred embodiment, two of the openings (31, 32) have a circular cross-section for precise positioning in a horizontal plane. The openings (33, 34) have an elongate shape for compensation of manufacturing tolerances. This is advantageous because the rack (60) can be precisely positioned without overhang with the treatment head (35). The footprint of the rack preferably includes a length and width of the base corresponding essentially to the ANSI SBS footprint format. More preferably, the length is 127.76 mm ± 0.25 mm, and the width is 85.48 mm ± 0.25 mm. The rack 30 (60) includes form locking members (38) for interacting with a manipulator (500). The rack (60) can be grabbed, transported and positioned quickly and securely at high speed while maintaining the correct orientation and position.
[0034] The term "substantially corresponding to ANSI SBS floor space format" means that the base of any consumable may have cut-out sections, for example, cut corners. Thus, the surface geometry of different types of consumables with an ANSI SBS footprint format may be different. However, the base of any consumable fits into a station that has a receiving portion corresponding to the ANSI SBS footprint format. The rack (60) includes one or more hardware identifiers (39), wherein said hardware identifiers (39) form an integral part of the consumable. The rack (60) further includes stacker guide members (6, 7). Said hardware identifiers (39) and stacker guide members (6, 7) include ridges and / or recesses on the sidewalls of the consumables, wherein said edge and / or recess pattern is unique for a specific type consumable, preferably the rack (60). Stack guiding members (6, 7) and hardware identifiers (39) ensure that the user can load the rack only in the appropriate stacker position of an analytical instrument (46). The rack (60) also includes recesses (37) in the side wall of the upper rack (1). The recesses (37) comprise a bottom wall (48) and side walls (49). The rack (60) is positioned within an opening in an analytical instrument (46). When the rack (60) is positioned, the bottom wall (48) of the recess (37) is in contact with the surface of the processing stage (47) of the analytical instrument (46). Said recesses (37) engage with counter elements on an analytical instrument (46) to hold the rack (60) in the instrument. This allows additional stabilization of the rack (60) within the analytical instrument (46). The insertion rack (14) includes an outer centering surface (11) that interacts with an internal centering surface (12) on the upper rack (1) to allow centering during assembly of the rack (60) ( Figures 11, 12, Figures 25 to 26). The upper rack (1) and the lower rack (2) are secured during assembly, preferably by a snap fit (44) located on one or the other of two opposite side walls (63, 64) of the frame the upper rack (1) and a detent groove (45) on one or the other of two corresponding opposite side walls of the lower rack (2).
[0035] A second embodiment of an exemplary rack is a one-piece integrated end rack (70) comprising an upper surface (71), two opposite short side walls (72) and two opposite long side walls (73). (Figure 25). The tip rack includes containers (74, 75) for holding pipette tips (3, 4). Said containers (74, 75) comprise an open top (76) and a closed bottom (77). Any container (74, 75) may contain a mouthpiece (3, 4). The footprint of the rack (70) preferably includes a length and width of the base substantially corresponding to the ANSI SBS footprint format. More preferably, the length is 127.76mm ± 0.25mm, and the width is 85.48mm ± 0.25mm. Preferred embodiments of said second embodiment include hardware identifiers (6, 7, 39), indentations (37) for engaging with counter elements on an analytical instrument for containing the rack in the instrument as well as it is described for the first embodiment of said rack. Preferred embodiments also include positioning elements (31, 32, 33, 34, 10) as described for the first embodiment of the rack (60). Positioning of the Treatment Head and End Rack Analytical systems used in the field of diagnostics require the processing of specimens to be analyzed. Such treatment involves the transfer of containers, or liquid samples and reagents from one container to another. For greater efficiency, simultaneous processing is often performed with processing devices that allow handling multiple consumables simultaneously. The commitment of the processing device and consumables requires proper alignment.
[0036] US 6,846,456 discloses a dosing workstation. A treatment head (400) is aligned with pipette tips (362) or receptacles (262) that are contained in racks (302) or (202) by engagement of rods (408), (410) located on the treatment head (400) with guide holes (510), (512) located on guide supports (500). The guide supports and the racks are separately mounted on a base structure (100). The disadvantage of the prior art is that a multitude of positions has an influence on the alignment of the processing device and the consumable. Positioning inaccuracies caused by imprecise fabrication or mounting of the positioning members or guide supports with the positioning members or racks (302), (202) can degrade the accuracy of alignment of the processing device and the consumable. A positioning method for aligning a rack and a processing device is also disclosed. The positioning method comprises aligning at least two locating elements located on the bottom surface of said treatment device with at least two locating elements located on the upper surface of said rack, and mechanically engaging said locating members on the processing device with the positioning elements of the rack. Treatment devices are preferably related to pipetting. Such treatment heads are well known in the art. Preferably, said consumable is a tip shop comprising pipette tips, and said processing device is a process head including an interface for engagement with pipette tips. The pipette tips are preferably arranged in a two-dimensional array in said pipette rack. Engagement of the positioning elements on the treatment device and positioning elements on the consumable may cause the interface of the treatment device to interact and engage with the pipette tips. A "rack" is understood to be any type of device used in an analytical system that contains a sample, a device that contains a consumable that is constructed and arranged to contain a sample. The rack has an upper surface and four side walls, in which two side walls are parallel and opposite to one another. Optionally, the rack also has a bottom surface. A consumable is understood to be a device that is recurrently introduced into the analytical system for use in an analytical test. A consumable can be used once before being replaced, or it can be used multiple times. In a preferred embodiment, said rack contains containers. The containers may contain a sample for use in an analytical system. Said sample is understood to refer to a sample to be processed in an analytical system, or as a reagent for use in an analytical system. Alternatively, said containers are pipette tips for aspirating and dispensing liquids. Said liquids may be samples or reagents as defined above. Thus, said rack may be a rack of pipette tips. Preferred embodiments of said pipette tip rack include integrally formed racks or racks having more than one portion, as shown in Figure 25 or 1. A multipart rack is described herein. as a preferred but non-limiting example. In another preferred embodiment, the rack is a multiwell plate comprising containers integrally attached to said rack. A processing device is any type of device used in an analytical system that is involved in processing a sample during an analytical test, and that requires alignment with a sample device. A preferred embodiment of a treatment device is a treatment head. A treatment head is understood to be a device that engages with pipette tips. The device includes an interface that can engage with said pipette tips. Preferably, said interface comprises cones. However, other interfaces known in the art are also included. In other embodiments, said processing device may also include devices for grasping consumables. Preferred embodiments of interfaces are cones, cylindrical interfaces, or interfaces with O-rings. Positioning elements are understood to be elements located on the processing device and on the rack. Said elements are constructed and arranged in such a way that positioning elements on the processing device can interact with positioning elements on the rack, thereby mechanically engaging the processing device and the rack. The treatment head preferably comprises a number of interfaces equal to the number of pipette tips of a first type. The treatment head can selectively engage with pipette tips of a first type or pipette tips of a second type. To achieve this, at least two positioning elements on the bit rack engage with at least two positioning elements on the treatment head, so that the treatment head engages with pipette tips only. of a first type or with pipette tips of a second type. Selective engagement with pipette tips of different types can also be accomplished with a tip rack that includes more than two types of pipette tips simply by selecting the appropriate number of positioning elements on the bit rack. . Preferably, a positioning member on the rack in one corner has a shape and the second positioning member on the rack which is mounted on the opposite corner diagonally of said upper surface of said bit rack has a second form. More preferably, the first form is a circular cross section and the second form is an elongated shape. The advantages of this embodiment are described further below. In order to achieve a more reliable positioning, the method may also include a first positioning step, wherein the positioning elements on the bottom surface of said processing device and the positioning elements on the upper surface of said rack are aligned. . Preferably, the first positioning is achieved by engagement of said positioning member with a notch. Other preferred embodiments of the method set forth herein are described above and hereinafter.
[0037] In a preferred embodiment of the method of positioning described above, said tip rack (60, 70) includes alternating rows of pipette tips of a first type (4) and pipette tips. a second type (3).
[0038] Preferably, said treatment head (35) comprises a number of interfaces (67) equal to the number of pipette tips of a first type (4). The interfaces (67) may be tapered or cylindrical, and may preferably include an O-ring. More preferably, at least two locating members (31, 32, 33, 34) on the end tray (60, 70) engage with at least two locating members (36) on the treatment head (35). such that the treatment head (35) engages only with pipette tips of a first type (4) or with pipette tips of a second type (3), still more preferably said method further comprises a first positioning step, wherein the positioning elements (36) located on the bottom surface (61) of said processing device (35) and the positioning elements (31, 32, 33, 34) located on an upper surface (66) of said rack (60, 70) is aligned, More preferably said first positioning is achieved by engagement of a positioning member (10) with a notch (20). more preferred embodiment, said positioning elements (36) on the dispo The processing elements are pins, and said locating members (31,32,33,34) on the upper surface (66) of said rack are openings which are dimensioned to engage with the pins. In a most preferred embodiment, the end rack (60, 70) includes four locating members (31, 32, 33, 34) and the processing head (35) comprises two locating members (36). In a preferred embodiment of the method described above, said positioning elements (31, 32, 33, 34) are located in opposite diagonal corners of said treatment device (35) or said rack (60, 70). However, other locations may be considered which lead to a similar result. Preferably, the tip rack (60, 70) includes an equal number of first pipette tips (4) and second pipette tips (3). Most preferably, a positioning member (31, 32) on the rack (60, 70) in a corner is a circular opening, and the corresponding second positioning member (33, 34) on the rack which is mounted on the Diagonally opposite corner of the upper surface of said end rack (60, 70) is an oval opening. Manipulator A process for isolating and treating an analyte that may be present in a fluid sample is disclosed. The method comprises the automated steps of: a) providing a fluid sample in a multiwell vessel at a first station; b) combining together a solid support material and said fluid sample in a well of said multi-well container for a time and under conditions sufficient to allow said analyte to be immobilized on the solid support material; c) isolating the solid support material from another material present in the fluid sample in a separation station; d) and purifying the analyte in the separation station by separating the fluid sample from the solid support material and washing the materials one or more times with a wash buffer; wherein said multiwell vessel is contacted by a manipulator and wherein said multiwell vessel is transported between stations by said manipulator, wherein said contact between said manipulator and said multiwell vessel is a form lock contact . Preferably, said multiwell vessel is a multiwell plate. Preferably, the method further comprises the step of analyzing the purified analyte in an assay station. More preferably, the analysis is performed in a second multiwell plate. Even more preferably, said second multiwell plate is contacted with at least one manipulator, preferably a manipulator, and transported between stations, wherein said contact between said manipulator and said multiwell vessel is a form-locking contact. In addition, the manipulator preferably transports the multi-well container between two stations, or between three stations. Said stations are preferably a storage station and / or a sample station and / or a separation station and / or a holding station and / or a sealing station and / or an analysis station and / or a detection station. In a preferred embodiment, the method further comprises the step of predicting pipette tips in a tip rack, wherein said tip rack is contacted by at least one manipulator and transported between stations, wherein said contact between said at least one manipulator and said tip rack container is a form-locking contact. One of the stations is preferably a storage station. Other favorite stations are the stations described here.
[0039] In a preferred embodiment, said analysis station is an amplification station. Preferably, the amplification station is an amplification and detection station. Preferably, the method further comprises the step of combining said purified nucleic acid with reagents sufficient to amplify said analyte in a container of a multiwell plate, wherein said multiwell plate is contained in a holding station. In a more preferred embodiment, a manipulator transports a multiwell vessel from a holding station to an airlock (460), and a second manipulator transports said multiwell plate from said airlock to said station. amplification, wherein the two manipulators interact with said multiwell plate by a shape-locking interaction. In a preferred embodiment, said manipulator comprises gripping fingers, wherein said gripping fingers fit into a recess of the multi-well plate, wherein said fit is a form lock (Figure 48, 49). ). A system for purifying and analyzing an analyte is further disclosed comprising a process cell comprising a separation station for separating an analyte included in a container from a multiwell plate of a solid support material. Preferably, said separation station is constructed and arranged to separate an analyte included in a container from a multiwell plate of a solid support material. The system further comprises an assay cell comprising an assay station, wherein said station comprises an incubator for treating said analyte to generate a signal indicative of the presence or absence of said analyte. In addition, the system comprises more than one consumable including openings, wherein at least one opening is located on a side wall of the consumable and at least one opening is located on the opposite side wall of the consumable. A gripper system comprising at least one manipulator is also included in the system, wherein said at least one manipulator comprises at least one gripper finger on one side of the manipulator, and at least one gripper finger on the opposite side of the manipulator. Said gripping fingers interact with said openings on the consumables and wherein said interaction is a form locking interaction. Preferably, the system described above further comprises a sample cell constructed and arranged to transfer a liquid sample from a sample container to a multi-well container. In a preferred embodiment, the multiwell vessel is transported between cells with said gripper system. In another preferred embodiment, the multiwell vessel is transported from said sample cell to said analysis cell. Preferred consumables are described here. Preferably, said more than one consumable includes a multiwell plate and a bit rack.
[0040] A preferred manipulator (500) includes a central portion (500a) that is connected to a robotic arm (502). The central portion (500a) comprises, on two opposite sides, gripping fingers (501). The gripping fingers (501) are movable. When engaging with a consumable (60, 70, 101, 301, 302) comprising shape-locking members (38, 106, 507, 309), as described above, the fingers grippers (501) connect with the consumable (60, 70, 101, 301, 302). The gripping fingers (501) are moved to the consumable (60, 70, 101, 301, 302) in the X direction, lock with the form locking members (38, 106, 507, 309), until the gripping fingers (501) reach a stop. In this position, a form-locking position between the manipulator (500) and the consumable (60, 70, 101, 301, 302) exists. The manipulator (500) connected to the robotic arm (502) can move the consumable (60, 70, 101, 301, 302) from one position to a second position. To release the consumable (60, 70, 101, 301, 302), the gripping fingers (501) move away from the consumable (60, 70, 101, 301, 302). Preferably, the manipulator includes spring-loaded pins (506). Said pins (506) are forced away from the consumable (60, 70, 101, 301, 302) when the manipulator (500) is pushed onto the consumable (60, 70, 101, 301, 302). In this position, the gripping fingers (501) can interact with the form locking members (38, 106, 507, 309) of the consumable (60, 70, 101, 301, 302). When the manipulator (500) is pressed onto the consumable (60, 70, 101, 301, 302), the gripping fingers (501) can move away from the interlocking members (38, 106, 507, 309) consumable (60, 70, 101, 301, 302) (Figure 50a). The manipulator (500) also includes pins (507) which are located on the sides of the multiwell plate when the manipulator (500) is moved downward on the consumable (60, 70, 101, 301, 302) before clinging. These pins (507) guide the consumable (60, 70, 101, 301, 302) to the correct position for gripping. In addition, said pins (507) prevent the consumable (60, 70, 101, 301, 302) from jamming with the manipulator (500) when the gripping fingers (501) move away from the consumable (60, 70 , 101, 301, 302) (Figure 50b).
[0041] Preferably, said form-locking members (38, 106, 507, 309) are openings (38, 106, 507, 309) in the sidewalls of the consumable, more preferably the long side of the consumable (60, 70, 101, 301, 302). Preferably, two openings (38, 106, 507, 309) are located on one side wall and two openings (38, 106, 507, 309) are located on an opposite side wall. Multi-Well Plate / Treatment Plate A multi-well plate for charging or separating an analyte is exposed. Multiwell plates are preferably used in analytical systems. They allow parallel separation and analysis or storage of multiple samples. Multiwell plates can be optimized for maximum fluid recovery, or maximum heat transfer. An improved multiwell plate for optimal use in an automated analytical system is provided. The multiwell plate is optimized to incubate or separate an analyte in an automated analyzer. Preferably, the multiwell plate is constructed and arranged to engage a magnetic device and / or heater. Said multiwell plate comprises: - an upper surface comprising multiple containers with openings at the top arranged in rows. The containers comprise an upper part, a central part and a bottom part. The upper portion is joined to the upper surface of the multiwell plate and has two longer sides and two shorter sides. The central portion has a substantially rectangular cross-section with two longer sides and two shorter sides; two opposing shorter sidewalls and two opposing longer sidewalls and a base, wherein said base comprises an opening constructed and arranged to contact the multiwell plate in contact with said magnetic device and / or a device of heating. In a preferred embodiment of the multiwell plate, adjacent containers in a row are joined on the longer side of said nearly rectangular shape. Preferably, the multiwell plate comprises a continuous space which is located between adjacent rows of containers. Said continuous space is constructed and arranged to receive a magnetic device in the form of a plate. In a preferred embodiment, the bottom portion of the containers comprises a spherical bottom. In a more preferred embodiment, the bottom portion of said containers comprises a conical portion located between said central portion and said spherical bottom. In a preferred embodiment, the upper surface comprises ribs, wherein said ribs surround the openings of the containers. Preferably, a shorter side of said upper portion of the containers comprises a recess, said recess including a curved surface extending from the rib to the interior of the container. In addition, in a preferred embodiment, the containers comprise a rounded inner shape.
[0042] For attachment to the treatment or incubation stations, the base preferably comprises a rim comprising recesses. Locking clips on a station of an analyzer may engage with said recesses to secure the plate to a station.
[0043] In a preferred embodiment, the containers comprise a substantially constant wall thickness. The treatment plate (101) is preferably a one-component plate. Its upper surface (110) comprises multiple containers (103) (Figure 28, Figure 29). Each container has an opening (108) at the top and is closed at the lower end (112). The upper surface (110) includes ribs (104) that are preferably elevated relative to the top surface (110) and surround the openings (108) of the containers (103). This avoids contaminating the contents of the containers (103) with droplets of liquid that may fall on the upper surface (110) of the plate (101). Views of a preferred treatment plate are shown in Figures 26-37.
[0044] The footprint of the treatment plate (101) preferably includes a length and width of the base corresponding to the ANSI SBS floor space format. More preferably, the length is 127.76 mm ± 0.25 mm, and the width is 85.48 mm ± 0.25 mm. Thus, the plate (101) has two shorter side walls (109) in opposition and two longer side walls (118) in opposition. The treatment plate (101) includes shape-lock elements (106) for interacting with a manipulator (500). The treatment plate (101) can be gripped, transported and positioned quickly and safely at high speed while maintaining the correct orientation and position. Preferably, the interlocking elements (106) for gripping are located within the upper central portion, preferably the upper central third of the treatment plate (101). This has the advantage that a potential distortion of the processing plate (101) has only a minor effect on the form locking elements (106) and that the handling of the plate (101) is more robust. The treatment plate (101) preferably comprises hardware identifiers (102) and (115). The hardware identifiers (102) and (115) are unique to the processing plate (101) and different from the hardware identifiers of other consumables used in the same system. The hardware identifiers (102, 115) preferably include ridges (119) and / or recesses (125) on the sidewalls of the consumables, wherein said edge pattern (119) and / or recess (125) is unique. for a specific type of consumable, preferably the treatment plate (101). This unique pattern is also called here a unique "surface geometry". The hardware identifiers (102, 115) ensure that the user can load the process plate (101) only in the appropriate stack position of an analytical instrument (126) in the correct orientation. On the sides of the treatment plate (101), guiding elements (116) and (117) are included (Figure 33). They prevent a cantilever of the treatment plate (101). The guide members (116,117) allow the user to load the treatment plates (101) with the guide members (116,117) in a stack in an analytical instrument which is then transferred vertically into the chamber. instrument in a stacker without cantilever plates.
[0045] The central portion (120) of the containers (103) has an almost rectangular cross section (Figure 30, Figure 31). They are separated along the longer side (118) of the almost rectangular shape by a common wall (113) (Figure 37). The row of containers (103) thus formed has the advantage that, despite the limited space available, they have a large volume, preferably 4 ml. Another advantage is that because of the essentially constant wall thickness, the production is very economical. Another advantage is that the containers (103) reinforce each other and thus a high stability of the shape can be obtained. Between the rows (123) of the containers (103), a continuous space (121) is located (Figure 31, Figure 35). The space (121) can accommodate magnets (122) or heaters (128) (Figure 36, Figure 38). These magnets (122, 127) and these heaters (128) are preferably solid devices. Thus, magnetic particles (216) included in the liquids (215) which may be contained in the containers (103) may be separated from the liquid (215) by exerting a magnetic field on the containers (103) when the magnets (122) 127) are brought near the containers (103). Alternatively, the contents of the containers (103) may be incubated at a controlled high temperature when the treatment plate (101) is placed on the heater (128). Since the magnets (122, 127) or the heaters (128) can be full, a high energy density can be attained. The nearly rectangular shape of the central portion (120) of the containers (103) (Figure 36, Figure 37) also optimizes the contact between the container wall (109) and a flat-shaped magnet (122) or heater. (128) optimizing the contact area between the container (103) and the magnet (122) or the heater (128), thereby improving energy transfer into the container (103). In the conical bottom area (111) of the containers, the space (121) is even more pronounced and can accommodate additional magnets (127). The combination of large magnets (122) in the upper zone and smaller magnets (127) in the conical zone of the vessels (3) allows the separation of magnetic particles (216) in large or small volumes of liquid (215). Small magnets (127) thus facilitate the sequestration of magnetic particles (216) during pipetting of the eluate.
[0046] This allows the eluate to be pipetted with minimal loss by reducing the dead volume of the magnetic particle pellet (216). In addition, the presence of magnetic particles (216) in the transferred eluate is minimized. At the upper end of the containers (103), one of the shorter sidewalls (109) of the container (103) comprises a reagent inlet channel (105) extending to the circumferential rib (104). ) (Figure 32, Figure 30). The reagents are pipetted onto the reagent inlet channel (105) and evacuate from the channel (105) into the vessel (103). Thus, any contact between the needle (80) or pipette tip (3, 4) and the liquid contained in the container is prevented.
[0047] In addition, splashing as a result of the liquid being directly transferred to another liquid (215) contained in the containers (103), which may be the cause of contamination of the needle (80) or the tip ( 3, 4) or adjacent containers (103) are prevented. Sequential pipetting on the reagent inlet channel (105) small volumes of reagent is followed by the larger volume of another reagent ensures that reagents that are added in small amounts are completely transferred to the container ( 103). Thus, pipetting small volumes of reagents is possible without loss of accuracy of the test to be performed. On the inside, on the bottom of the containers (111, 112), the shape becomes conical (111) and ends with a spherical bottom (112) (Figure 34). The inner shape of the container (114), including the rectangular central portion (120), is rounded. The combination of the spherical bottom (112), the rounded inner shape (114), the conical portion (111) and the refined surface of the vessels (103) leads to favorable fluidities that facilitate efficient separation and purification of analytes in the treatment plate (101). The spherical bottom (112) allows substantially complete use of the separated eluate and a reduction in dead volume and reduces the transfer of reagents or cross-contamination of the samples. The rim on the base (129) of the treatment plate (101) includes recesses (107) for engagement with the locking clips (124) on the treatment station (201) or the heater (128) or the analytical instrument (126) (Figure 28, Figure 38, Figure 39). Engagement of the locking clips (124) with the recesses (107) allows positioning and attachment of the treatment plate (101) to the treatment station (201). The presence of the recesses (107) allows the locking force to act on the treatment plate (101) almost vertically at the base (129). Thus, only small forces acting on the side can appear. This reduces the occurrence of a stress and thus the deformation of the treatment plate (101). The vertical locking forces can also neutralize any deformations of the treatment plate (101), resulting in more accurate positioning of the spherical bottoms (111) within the treatment station (201). Generally speaking, the precise interface between the treatment plate (101) and the treatment station (201) or the heating device (128) inside an analyzer (126) reduces the dead volumes and reduces also the risk of cross-contamination of the samples.
[0048] Separation station A device for separating an analyte bound to magnetic particles in a liquid contained in a container is exposed. The device comprises a multiwell plate comprising containers with an opening at the top surface of the multiwell plate and a closed bottom. The containers comprise an upper part, a central part and a bottom part, in which the upper part is joined to the upper surface of the multiwell plate and preferably comprises two longer sides and two shorter sides. The central portion has a substantially rectangular cross-section with two longer sides, wherein said containers are aligned in rows. A continuous space is located between two adjacent rows for selective contact with at least one magnet mounted on a fastener with the side walls in at least two Z positions. The device further comprises a magnetic separation station comprising at least one fixation. The attachment comprises at least one magnet generating a magnetic field. A movable mechanism is present which vertically displaces said at least one fastening device comprising at least one magnet at least between a first and a second position relative to the containers of the multiwell plate. Preferably, said at least two Z positions of the containers comprise the side walls and the bottom portion of said containers. The magnetic field of said at least one magnet preferably drives the magnetic particles to an interior surface of the container adjacent to said at least one magnet when said at least one magnet is in said first position. The effect of said magnetic field is less when said at least one magnet is in said second position than when said at least one magnet is in said first position. Preferably, the fixing device comprising said at least one magnet comprises a frame. The containers have preferred features as described in the Multiwell plate / treatment plate section.
[0049] Such a preferred feature is that at least a portion of said containers has a substantially rectangular cross-section orthogonal to the axis of said containers.
[0050] In said first position, said at least one magnet is adjacent to said portion of said containers. Adjacent means either in close proximity to exert a magnetic field on the contents of the container, or in physical contact with the container. The separation station includes a frame for receiving the multiwell plate, and locking clips for securing the multiwell plate. Preferably, the separation station comprises two types of magnets. This preferred embodiment is described further below. A second preferred embodiment is described below, which comprises a spring which exerts pressure on the frame comprising the magnets, so that the magnets are pressed against the receptacles of the multiwell plate. The first magnets are preferably constructed and arranged to interact with containers of a multiwell plate to exert a magnetic field on a large volume of liquid comprising magnetic particles contained in said containers. Such second magnets are preferably constructed and arranged to interact with containers of a multiwell plate to exert a magnetic field on a small volume of liquid comprising magnetic particles contained in said containers. Said first and second magnets may be moved to different Z positions. A method of isolating and purifying an analyte, preferably a nucleic acid, is exposed. The method includes the steps of binding an analyte to magnetic particles in a container of a multiwell plate. The container comprises an upper opening, a central portion and a bottom portion. The bonded material is then separated from the unbound material contained in a liquid when the major part of the liquid is located above the section where the conical portion of the container is replaced by the central portion with the rectangular shape, moving a magnet of a second position to a first position and, in said first position, applying a magnetic field to the central portion and, optionally, further applying a magnetic field to the bottom portion of said container. The magnetic particles may be optionally washed with a wash solution. A small volume of liquid, in which most of the liquid is located below the section where the conical portion of the container is replaced by the central portion with the rectangular shape, is separated from said magnetic particles by selectively applying a magnetic field to the bottom portion of said container.
[0051] The method described above preferably further comprises between steps c) and d) the step of eluting said nucleic acid. Preferably, the method comprises the step of transferring said eluate from said multiwell plate to a second multiwell plate. In another preferred embodiment, in step b), a first type of magnet is moved from a second position to a first position to apply a magnetic field to a central portion of the container, and, optionally, a second type of magnet is moved to the bottom portion of the container to apply a magnetic field. More preferably, a magnet is moved to the central portion of the container for step b), and the magnet is moved to the bottom portion of said container in a third position for elution of said nucleic acid. A magnetic separation station for separating an analyte bound to magnetic particles is exposed, said separation station comprising first magnets which are constructed and arranged to interact with containers of a multiwell plate to exert a magnetic field on a large volume of liquid comprising magnetic particles contained in said containers, and second magnets constructed and arranged to interact with containers of a multi-well plate to exert a magnetic field on a small volume of liquid comprising magnetic particles contained in said containers, and wherein said first and second magnets can be moved to different Z positions. Preferred embodiments of the magnetic separation station are described herein.
[0052] A first preferred embodiment of a separation station (201) is described below. The first preferred embodiment of said separation station (201) comprises at least two types of magnets (202, 203). The first long type of magnet (202) is constructed and arranged to fit into the space (121) of the treatment plate (101). The magnet (202) thus exerts a magnetic field on the liquid (215) in the container (103) so as to sequester magnetic particles (216) on the inside of the container wall. This allows the separation of the magnetic particles (216) and any material bound thereto and the liquid (215) within the container (103) when a large volume of liquid (215) is present. The magnet (202) has an elongate structure and is constructed and arranged to interact with the substantially rectangular central portion (120) of the container. Thus, the magnet (202) is used when the bulk of the liquid (215) is located above the section where the conical portion (111) of the container (103) is replaced by the central portion (120) with the rectangular shape. As shown in Figure 40, the preferred construction of the magnets (202) includes fasteners (204, 204a) including magnets (202) which fit into the gap (121) between the rows of containers (103) in the treatment plate (101). Another preferred embodiment of magnets (202) includes magnets (202) provided on fasteners (204, 204a). The magnets (203) of the preferred separation station (201) are smaller, and can interact with the conical portion (111) of the container (103). This is shown in Figure 41 (a). The magnets (203) are preferably arranged on a base (205) which can be moved into the space (121) of the treatment plate (101). Each magnet (202, 203) is preferably constructed to interact with two containers (103) in two adjacent rows. In a preferred embodiment, the treatment plate (101) has 6 rows of 8 containers (103). A separation station (201) that can interact with the preferred treatment plate (101) has three fasteners (204, 204a) including magnets (202) and four bases (205) including magnets (203). An embodiment is also included, wherein the separation station has four magnetic fasteners (204, 204a) including magnets (202) and three magnetic bases (205) including magnets (203).
[0053] The magnets (202, 203) are movable. The separation station (201) includes a mechanism for moving the fasteners (204, 204a) and the bases (205). All fasteners (204, 204a) are interconnected by a base (217) and are thereby moved in a coordinated manner. All the magnets (203) are joined to a base (218) and are thus moved in a coordinated manner. The mechanism for moving the magnetic plates (202) and (203) is constructed and arranged to move the two types of magnetic plates (202) and (203) to a total of four end positions. In Figures 40a-c, the magnets (203) are located near the conical portion of the containers (103) of the treatment plate (101). This is the highest position of the magnets (203) and the separation position. In this Figure, the magnets (202) are located in the lowest position. They are not involved in separation when in this position. In Figures 41a-c the magnets (202) and (203) are in their lowest positions. None of the magnets are in a separation position. Therefore, in this position, no separation of magnetic particles of liquid can take place. Figures 42a-c show a position in which the magnets (202) are located in the space (121) of the treatment plate (101). This is the highest Z position of the magnets (202). In this Figure, the magnets (203) are also located in the highest Z position. They exert a magnetic field on the liquid in the conical zone of the containers (103). Thus, the two magnets are in a separation position. The highest Z position of the magnets (202) and (203) is different. Figures 43a-c show a position in which the magnets (202) are located in the space (121) of the treatment plate (101). This is the highest position of the magnets (202) and the separation position. In this Figure, the magnets (203) are located in the lowest position. They are not involved in separation when in this position. In the preferred embodiment shown in Figures 40-43, the base (207) of the magnets (202) is connected to a positioning gear (206). The base (217) includes a bottom end (207) that is in flexible contact with a connecting member (208) by a movable member (209). The movable member is constructed and arranged to move the connecting member (208) along a rail (212) from one side to the other. The movable member (209) is attached to the connecting member (208) with a pin (220). The connecting member (208) is attached to the positioning gear (206) by a screw (210). The connection element (208) is also connected to an axis (211). Said connecting element (208) is preferably a rectangular plate. When the positioning gear (206) moves eccentrically about an axis (211) so that the screw (210) moves from a point above the eccentric axis to a point below the eccentric axis, the movable member (209) and the bottom end (207) of the base (204) with the magnets (202) attached thereto are moved from the position higher up to the lowest position. The base (218) is mounted on a bottom portion (219) and is connected at its lower end with a pin (213) to a movable member (214), which is preferably a gear wheel, which interacts with the wheel positioning gear (206). When the positioning gear (206) rotates about the axis (211), the gear (214) moves along the positioning gear (206). If the toothed wheel (214) is located on a section of the positioning gear (206) where the distance from the axis (211) is short, the magnets (203) are at their lowest position. If the toothed wheel (214) is located on a section of the positioning gear (206) where the distance from the axis (211) is maximum, the magnets (203) are at their highest position. Thus, in the preferred embodiment of the first embodiment of the separation station, the location of the magnets (203) is controlled by the shape of the positioning gear (206). As the movable member (209) moves along the central upper or lower rounded portion (212a) of the rail (212), the small type of magnets (203) is moved up and down. When the movable member (209) is located on the side (212b) of the bottom end (207) and moves up or down, the magnets (202) are moved up or down .
[0054] The positioning gear can be rotated by any motor (224). In a preferred embodiment, a spring (225) is attached to the base (222) of the separation station and the base (218) of the magnets (203) to ensure that the magnets (203) are moved to the position the lowest when they are moved down. The term "spindle" as used herein refers to any fastener, including screws or pins.
[0055] In a second preferred embodiment, the separation station (230) comprises at least one fixing device (231) comprising at least one magnet (232), preferably a number of magnets equal to a number of containers (103) in one row (123). Preferably, the separation station (230) comprises a number of securing devices (231) equal to the number of rows (123) of the multiwell plate (101) described above. More preferably, six fasteners (231) are mounted on the separation station (230). At least one magnet (232) is mounted on a fastener (231). Preferably, the number of magnets (232) is equal to the number of containers (103) in a row (123). More preferably, eight magnets (232) are mounted on a fastener (231). Preferably, a type of magnet (232) is included on said attachment device (231). More preferably, the magnet (232) is mounted on one side that is oriented toward the containers with which the magnet interacts. The fastener (231) is mounted on a base (233). Preferably, said frame is flexible. The base (233) includes springs (234) mounted thereon. The number of springs (234) is at least one spring per fixing device (231) mounted on said base (233). The base further includes a chamfer (236) which limits the movement of the spring and, consequently, the fastener (231) including the magnets (232). Preferably, any one of said springs (234) is constructed and arranged to interact with a fastener (231). More preferably, said spring (234) is a rocker spring. Said interaction controls the horizontal movement of the fastening devices (231). In addition, the separation station (230) comprises a frame (235). The base (233) with the fasteners (231) is connected to the frame (235) by a movable device as described above for the magnets (232) of the first embodiment. Preferably, said base (233) and said attachment device (231) are constructed and arranged to move vertically (in the Z direction).
[0056] The multiwell plate (101) described above is inserted into the separation station (230). The fastening device (231) comprising the magnets (232) is moved vertically. Any fixing device (231) is thus moved in a space (121) between two rows (123) of containers (103). Vertical movement brings the magnets (232) mounted on a fastener (231) into contact with the containers (103). The Z position is chosen according to the volume of liquid (215) inside the containers (103). For large volumes, the magnets (232) are in contact with the containers (103) in a central position (120) where the containers (103) are of almost rectangular shape. For small volumes of liquid (215) where most of the liquid (215) is located below the central portion (120) of the containers (103), the magnets (232) are preferably in contact with the conical portion ( 111) containers (103). A spring is attached to the base (233) of any frame (231) (Figures 39 a), b)). The spring presses the magnets (232) against the containers (103). This ensures contact between the magnets (232) and the containers (103) during the magnetic separation. Preferably, the magnet (232) is in contact with the container (103) on the side wall (109) below the inlet (105). This has the advantage that liquid that is added by pipetting flows over the sequestered magnetic particles and ensures that the particles are resuspended and all samples in all containers are treated identically. This embodiment is particularly adapted for separating a liquid (215) contained in a multiwell plate (101) as described above from magnetic particles (216) when different levels of liquid (215) are contained in the containers. (103) of said multiwell plate (101). AD plate and chassis For amplification and detection, multiwell plates are commonly used. Such plaques are particularly useful in automated analytical systems that include an amplification station for amplifying nucleic acid analytes.
[0057] In order to prevent contamination between the wells before, during and after the amplification reaction, the reaction vessels in which the amplification takes place are sealed. One common way of sealing multi-well amplification plates is to place a sealing film on the plate and connect it to the plate by gluing or heat sealing. An improved automated method for isolating and amplifying a nucleic acid, an improved multiwell plate with a sealing film and an improved automated analytical system are set forth herein. A method for isolating and amplifying a nucleic acid analyte that may be present in a fluid sample is disclosed. The method comprises separating said nucleic acid analyte from another material present in said fluid sample in a first container. Preferably, said first container is contained in a first multiwell plate. A second multiwell plate is provided. This second multi-well plate includes a cover that includes a frame and a sealing film. The lid is lifted and then the separated analyte in the first container is transferred to a well of the second multiwell plate. The cover comprising said sealing film is placed on the second multi-well plate. Then, the second multi-well plate is sealed with the sealing film. Once the second multiwell plate is sealed, the analyte is amplified in the presence of amplification reagents that have been added prior to closure in said second multiwell plate. In a preferred embodiment, in step b), the lid is present on the second multi-well plate in a first position, said first position preventing contact between the sealing film and the multi-well plate; and in step e), the cover is placed on said second multi-well plate in a second position, wherein said second position promotes contact between said sealing film and said multi-well plate.
[0058] In a preferred embodiment of the method described above, the lid is rotated 180 °.
[0059] Preferably, the frame comprises support ribs, more preferably four support ribs, and the multi-well plate includes corresponding recesses, more preferably four corresponding recesses, wherein said recesses are positioned such that the frame support ribs are not aligned with the recesses in the first position of the lid on the multiwell plate, and that the support ribs are aligned with the recesses in the second position of the lid on the multiwell plate.
[0060] In said second position, the frame support ribs are preferably located within the recesses of the multiwell plate. In a preferred embodiment of the process described herein, the seal in step f) is a heat seal. Other preferred embodiments of the process are described above or hereinafter. A multi-well plate assembly comprising a multi-well plate and a cover is exposed, wherein said cover comprises a frame and a sealing film attached to said frame, wherein in a first position of said cover on said well plate multiple, a separation distance is located between said sealing film and the upper surface of said multiwell plate, and in a second position, the sealing film is in contact with said upper surface of the multiwell plate . Preferably, the frame comprises support ribs and the multi-well plate comprises apertures, wherein, in said first position, the support ribs are in a location different from the apertures, and in said second position, said support ribs and said openings are aligned. In a preferred embodiment of the multiwell plate assembly described herein, the upper surface of said multiwell plate includes heating flanges, and in said second position, the sealing film is in contact with the heating flanges. . Preferably, the sealing film is attached to the frame by a heat seal process. More preferably, the sealing film is attached to the upper surface of the frame. In a preferred embodiment, the sealing film comprises a polymer. Preferably, the sealing film comprises at least two layers having different melting points. More preferably, the sealing film comprises two layers having different melting points, wherein the layer having the lowest melting point is oriented towards the multiwell plate. Other preferred embodiments of the process are described above or hereinafter. An analytical system comprising a holding station and a multiwell plate as described herein is also disclosed, wherein said multiwell plate is secured in said holding station. Preferably, the analytical system further comprises a sealing station for heat sealing the sealing film included in the frame to the multiwell plate.
[0061] Preferably, the multi-well plate comprises a base with a rim that includes recesses, wherein a positioning and fixing member on said holding station is in contact with said recesses, wherein said contact exerts a downward pressure on the base of the multiwell plate, thus securing the multiwell plate in the holding station. The multi-well plate example with a frame includes a multiwell plate (300) that includes a plurality of containers (312).
[0062] The containers (312) are integrally formed on the upper surface (326) of the multiwell plate (300). On the upper surface (326), each container (312) is surrounded by a raised heating rim (311). The lid (302) comprises a frame (302b) comprising a polymer (314) and a film (303) comprising a polymer. The film (303) is attached to the frame (302b) 302 0140 52 by a heat sealing process. Preferably, the film (303) is sealed to the upper surface (302a), more preferably by heat sealing. The multiwell plate (300) comprises two long sidewalls (323, 324) which are opposed to each other, and two short sidewalls (319, 320) which are opposed to each other . The frame (302b) includes two long side walls (328, 327) which are oppositely located to one another and two short side walls (321, 322) which are oppositely located to each other. other. The preferred film (303) comprises two layers (314, 315) having different melting points. A layer (311) has a lower melting point. This layer (311) is oriented toward the multiwell plate (301) with the heating flanges (310, 311) and the frame surface (302a) (302b). During heat sealing, heat is transferred through the more stable layer (310) having the higher melting point to the layer (311) having the lower melting point. The layer (311) is thus heated and melted. The upper layer (310) is not melted during heat sealing. This minimizes the risk of film leakage (303) (Figure 45 (b)). The multiwell plate (301) and the lid (302) are assembled in pairs (300) for delivery. On the inside (316) of the upper surface (317), the frame (302b) comprises support ribs (318). Two support ribs (318) are located along a first side wall (321) of the frame (302b), and two support ribs (318) are located along a second side wall (322) opposite to the first side wall (319). Preferably, said side walls are the short side walls of the frame (302b). The edge of the upper surface (313) of the multiwell plate (301) includes openings (308). Said openings (308) are located along side walls (319, 320) corresponding to the side walls (321, 322) of the frame where the support ribs (318) are located. In the assembly / delivery position of the lid (302) relative to the multiwell plate (301) (Figure 44a), the openings (308) are positioned in such a manner that they are not aligned with the ribs support (318). Thus, when the cover (302) is placed on the multiwell plate (301), the support ribs (318) rest on the upper surface (313) of the multiwell plate (301) (Figure 46a)). This prevents the film (303) from being in contact with the heating flanges (310, 311) and thus prevents the film (303) from being scratched, which otherwise could be caused by slippage of a plate multi-well plate (300) on the film surface of a second multi-well plate (300) which could degrade the optical and mechanical properties of the film (303) during transport, storage and loading. When the microwell plate (301) with the lid (302) is used in an analytical instrument (126), the lid (302) is lifted for addition of purified analyte and reagents. When all reagents are added to the containers (312), the lid (302) is rotated 180 ° and placed on the multi-well plate (301) (Figures 44 (b) and (c)). The openings (308) on the top of the multiwell plate (301) and the support ribs (318) on the chassis (302b) are aligned by the 180 ° rotation. Thus, when placed on the multiwell plate (301), the film (303) is brought into contact with the heating ledges (311) surrounding the containers (312) of the multiwell plate (301) and heat may be applied to seal the containers (312) with the film (303) (Figure 44d), Figure 45 (a)).
[0063] The micro-well plate (301) and the lid (302) both include a length and width of the base corresponding to the ANSI SBS floor space format. More preferably, the length is 127.76 mm ± 0.25 mm, and the width is 85.48 mm ± 0.25 mm. They include openings (304) on the plate (301) and openings (309) on the cover (302) that are constructed and arranged to be gripped by a manipulator (500), either in pairs or individually. Thus, it is possible to grip and transport the assembled plate and frame (300), or only the cover (302) or only the plate (301).
[0064] The multiwell plate (301) includes a base (325) surrounding the bottom of the sidewalls (319-322) of the plate (301). The base (325) includes recesses (306). These recesses (306) may interact with a positioning and securing member (124a) on a holding station (330) of the analyzer (126), as described above for the Treatment Plate. The interaction between the positioning and fixing member (124a) and the recess (306) positions and secures the plate (301). This keeps the plate (301) attached to the holding station (330) while handling the cover (302) independently of the plate (301). Fixing the plate (301) also leads to a maximum contact area between the plate (301) and the holding station (330). This equates potential differences in static charge between the holding station (330) and the plate (301). Finally, the attachment also ensures that the containers (312) are all at the same height, allowing for more accurate pipetting. The frame (302b) includes a recess (307). This recess is located at the lower end of the chassis side (302b). This recess is preferably located at a position different from that of the openings (304).
[0065] Preferably, two recesses (307) are located on one side of the frame (302), and two recesses (307) are located on the opposite side of the frame (302b). Most preferably, said recesses (307) are located in the same position as the recesses (306) on the multiwell plate (301). The recesses (307) ensure that when the plate (301) is secured by engagement of fasteners (124a) and recesses (306), only the multi-well plate (301) is secured, not the cover (302). . Analytical system with hardware coding of consumables An analytical system (440) comprising an automated analytical apparatus (400) for isolating and / or analyzing an analyte is disclosed. An "analyte" as used herein refers to any type of analyte of interest. Preferred analytes are polypeptides or nucleic acids. More preferably, the analyte is a nucleic acid. The analytical system (440) further comprises more than one type of consumables (60, 70, 101, 301, 302), wherein said consumables (60, 70, 101, 301, 302) have substantially the same footprint. and wherein any type of consumables (60, 70, 101, 301, 302) comprises a single surface geometry (601). In addition, the system also includes a system comprising specific recognition elements for distinguishing said different consumables, wherein any one of said recognition elements comprises a unique surface geometry complementary to a unique surface geometry of a specific type. consumable.
[0066] Preferably, said system for distinguishing said different consumables (60, 70, 101, 301, 302) is constructed and arranged to specifically recognize said unique surface geometry (601). The analytical system (440) discussed herein is preferably a system (440) comprising a module (401) for isolating and / or purifying an analyte. More preferably, the system (440) further comprises a module (403) for analyzing said analyte to obtain a detectable signal. The detectable signal can be detected in the same module (401, 402, 403) or, alternatively, in a separate module. The term "module" as used herein refers to any spatially defined location within the analyzer (400). Two modules (401, 403) may be separated by walls, or may be in an open relationship. Any module (401, 402, 403) may be autonomously controlled, or control of the module (401, 402, 403) may be shared with other modules. Preferably, all modules are centrally controlled. The transfer between modules (401, 402, 403) can be manual, but it is preferably automated. Thus, a number of different embodiments of automated (400) analyzers are covered by this disclosure.
[0067] Consumables (60, 70) with substantially identical bulk footprint are plastic consumables for storing other consumables, such as pipette tips or single tubes, or for holding reagents and samples, or consumables ( 101, 301, 302) containing reaction mixtures in which the treatment or analysis of the analyte is carried out. Preferred embodiments of such consumables are racks (60, 70) or multiwell plates (101, 301, 302). Different types of multiwell plates (101, 301, 302) with identical floor space may be preferably used in the system (440). Such preferred types of multiwell plates (101, 301, 302) are multiwell plates for storing samples and reagents, multiwell plates for isolating and analyzing an analyte, and / or multiwell plates. to react an analyte to obtain a detectable signal. In a preferred embodiment, the analyte is a nucleic acid, the reaction may be any type of nucleic acid amplification known to those skilled in the art. Preferably, said consumables (60, 70, 101, 301, 302) comprise at least one end tray (60, 70) and one multiwell plate (101, 301). Preferably, said footprint includes a length and width of the base corresponding to the ANSI SBS footprint format. More preferably, the length is 127.76 mm ± 0.25 mm, and the width is 85.48 mm ± 0.25 mm. The term "surface geometry" refers to the surface structure, preferably sidewalls of the consumables (60, 70, 101, 301, 302). The surface geometry preferably comprises material identifiers (39, 7, 6, 117, 118, 116, 102, 119, 115, 125, 305), more preferably integrally formed recesses and / or ridges. in the surface of a consumable (60, 70, 101, 301, 302). Preferably, any one of all types of consumables (60, 70, 101, 301, 302) with said footprint includes a single surface geometry (601). A "single surface geometry" means a surface geometry (601) as described above which is unique for one type of consumable (60, 70, 101, 301, 302) and is substantially different from the geometries other consumables (60, 70, 101, 301, 302), so that the consumable (60, 70, 101, 301, 302) is specifically recognized by the recognition system (450) of the analytical system (440). In a preferred embodiment, the system includes stackers (600a, b) for stacking multiple consumables (60, 70, 101, 301, 302) of a type, wherein any one of said stackers (600a, 600b) , b) comprises recognition elements for a type of consumable (60, 70, 101, 301, 302). The term "stacker" as used herein refers to the setting zone in the analytical system for a specific consumable (60, 70, 101, 301, 302). Multiple consumables (60, 70, 101, 301, 302) of a specific type are stacked in the stacker (600 a, b). Individual consumables (60, 70, 101, 301, 302) of a type are then recovered from the stacker (600 a, b) within the system (440) and automatically transported to the module (401, 402, 403 ) in which they are used, by a conveyor or, preferably by a manipulator (500) connected to a robotic arm (502). Thus, due to the unique surface geometry (601) of the consumable (60, 70, 101, 301, 302), a specific type of consumable (60, 70, 101, 301, 302) can only be loaded into a stacker (600 a, b) specific. This prevents the user from loading the erroneous consumable (60, 70, 101, 301, 302) in a specific stacker (600 a, b), even if the consumables (60, 70, 101, 301, 302 ) have the same footprint. In a preferred embodiment, more than two different types of consumables (60, 70, 101, 301, 302) with the same footprint are included in the system (440). In a more preferred embodiment, more than three different types of consumables (60, 70, 101, 301, 302) with the same footprint are included in the system (440). Consumables (60, 70, 101, 301, 302) are preferably selected from the group consisting of a tip rack (60, 70), a multi-well plate (101) for sample preparation, a plate multi-well (302) for amplification and / or detection, a reagent cassette holder, a tube holder, etc. A method is also provided for recognizing the identity of a consumable (60, 70, 101, 301, 302) within an analyzer (400) as described above. The method includes providing a type of consumable (60, 70, 101, 301, 302), wherein said one consumable type (60, 70, 101, 301, 302) comprises a surface geometry (601). unique. The method further comprises the interaction of said one consumable type (60, 70, 101, 301, 302) comprises a single surface geometry (601) with a stacker (600 a, b) including recognition elements (602) specific for said single surface geometry (601). The consumable (60, 70, 101, 301, 302) is then identified when the unique surface geometry (601) is engaged by the recognition elements (602). The term "recognition elements" as used herein refers to elements such as a guide (602) mounted on the inside of a stacker (600 a, b) which fits specifically with the geometry surface area (601) of a type of consumable (60, 70, 101, 301, 302). The analyzer (400), the preferred consumables (60, 70, 101, 301, 302) and stacker (600 a, b) are as defined above. Finally, a consumable (60, 70, 101, 301, 302) is also provided, comprising a unique surface geometry (601) constructed and arranged to allow a stacker (600 a, b) to specifically identify the type of consumable ( 60, 70, 101, 301, 302). Preferred embodiments of the consumable (60, 70, 101, 301, 302), the stacker (600 a, b) and the surface geometry (601) are as described above.
[0068] A schematic drawing of an exemplary analytical system (440) is shown in Figure 51. The recognition of the surface geometry (601) by the stacker (600 a, b) is shown in Figure 51. The inner surface the stacker (600a, b) comprises recognition elements (602). It is constructed and arranged to engage with the surface geometry (601) of the consumable (60, 70, 101, 301, 302) and, thus, the type of consumable (60, 70, 101, 301, 302 ) is specifically recognized and the erroneous type of consumable (60, 70, 101, 301, 302) is avoided. In a preferred embodiment, more than one type of multiwell plate is used in the analytical system (440), preferably at different stages of the analytical method. Thus, different types of multiwell plates (101, 301, 302) have different surface geometries that are unique for each type of multiwell plate (101, 301, 302). Each type of multiwell plate (101, 301, 302) is specifically recognized by its unique surface geometry (601). System with spatial separation A new process and a new system with improved prevention of contamination are exposed. In preferred embodiments, the protection against contamination can be further improved by combining the claimed method with any of the known contamination methods described above. In one aspect of the method described above, said first cell comprises a first air pressure, and said second cell comprises a second air pressure, wherein said first air pressure is greater than said second air pressure. . In a preferred embodiment of the method, outside air entering said first cell is filtered. Air filtering reduces the risk of contaminants entering the analyzer. Preferably, the filters are HEPA filters. Preferably, said first and second cells are separated by a wall. The separation of cells by walls further reduces the risk of potential contaminants passing from one cell to another. In one aspect of the present process, the purified analyte is transferred from said first cell to said second cell through an airlock located between said first and second cells. Preferably, the airlock includes a door on the side of the first cell and a door on the side of the second cell. In the state of rest of the airlock, the two doors are in the closed position. The door on the side of the first cell opens when a plate must pass from the first cell into the second cell. The plate is then placed on a movable plate holder. Said movable plate holder is then passed through the airlock. The door on the side of the first cell closes. Then the door on the side of the second cell opens. The plate on the plate holder passes to the end of the lock, and a manipulator then removes the plate from the plate holder of the lock. In a preferred embodiment of the method described above, said purified analyte is included in a reaction vessel. In one aspect of the present process, said reaction vessel is sealed prior to analysis of said analyte. Especially in the preferred field of nucleic acid analysis, the assay involves the multiplication of the target nucleic acid by amplification. Thus, during the analysis process and following the analysis, the reaction vessels comprise large amounts of the target nucleic acid (acids), which may be a potential source of contamination. Sealing the reaction vessels, preferably with a film, more preferably by heat sealing said reaction vessels with a film, further reduces the risk of potential contamination of samples and purified nucleic acids prior to analysis. Preferably, the reaction vessel is sealed prior to transporting said first cell to said second cell. The effect of preventing contamination by sealing is then optimal. In one aspect of the present process, an additional step includes transferring a sample from a sample container to a multi-well plate in a third cell, wherein said third cell comprises a separate air stream. of said first and said second cell and wherein said step precedes the steps implemented in the first cell. Preferably, the first cell is a processing cell as described herein, the second cell is an analytical cell as described herein and the third cell is a sample cell as described herein. In a preferred embodiment of the method, a first manipulator transfers said reaction vessel from said first cell to said airlock, and a second manipulator transfers said reaction vessel from said airlock to said second cell. Preferred embodiments of cells are described below. An automated analytical apparatus for the treatment of an analyte is also disclosed, comprising a process cell comprising a separation device for isolating and purifying said analyte, wherein said process cell has a first air stream; an analytical cell for analyzing said analyte contained in a reaction vessel, wherein said analytical cell has a second air stream; a transfer system for transferring a container comprising said purified analyte from the process cell to the analytical cell; wherein said first air stream in said process cell and said second air stream are separated. In one aspect, said first cell comprises a first air pressure and said second cell comprises a second air pressure, wherein said first air pressure is greater than said second air pressure. The advantages of this aspect are as described above. In a preferred embodiment of the present method, an airlock is located between said processing cell and said analytical cell. The advantages of said embodiment are as described above.
[0069] In one aspect of the present method, said automated analytical apparatus further comprises a sample cell for transferring samples from a sample container to a treatment container. In a preferred embodiment, said apparatus comprises partition walls located between said cells. The advantages of said embodiment are as described above. Preferably, said sample cell comprises a filter for filtering air entering said sample cell. In one aspect of the apparatus, seals are included in the upper housing of said treatment cell.
[0070] In a preferred embodiment, said reaction vessel is covered or sealed. In one aspect of the apparatus, said transfer system includes a first manipulator for transferring said reaction vessel from said treatment cell to said airlock, and a second manipulator for transferring said reaction vessel from said airlock to said analytical cell. .
[0071] A preferred embodiment of the apparatus is an automated nucleic acid analyzer comprising a processing cell for a sample preparation and an amplification cell.
[0072] Advantages and effects of said embodiments and aspects are as described above. Figure 54 shows a preferred embodiment of an apparatus. The apparatus (700) includes a first cell (702), a second cell (703), and a third cell (701). Preferred embodiments of the cells are a sample cell (701) for delivering samples to be analyzed, a processing cell (702) for isolating and purifying an analyte, and an amplification / detection cell (703) for amplifying and detecting a nucleic acid analyte. The sample cell (701) and the process cell (702) include filters (730), preferably HEPA filters, for passing air through the apparatus. The sample cell (701) has an air flow (741) and an air pressure (751), and the treatment cell (702) has an air flow (742) and an air pressure ( 752), and the amplification cell (703) has an airflow (743) and an air pressure (753). Preferably the air pressures (751) and (752) are substantially the same. The air pressure (752) is greater than the air pressure (753), which prevents air from passing from the amplification cell (703) to the treatment cell (702). The walls (731) to (734) are located between the three cells (701) to (703). An airlock (710) is located between the processing cell (702) and the amplification cell (703).
[0073] Figure 55 shows a side view (a) and a top view (b) of the lock (710). The airlock (710) has a main body (723) and sidewalls (713) and a door (711) on the side of the treatment cell (702) and a second door (712) on the side of the airframe. amplification (703). The doors (711), (712) are movably attached to the main body by hinges (716). Inside the lock (710), a movable carriage (714) is mounted. The carriage (714) comprises a plate holder (720). On the carriage, at least one learning bolt (721), preferably more than one training bolt (721), is mounted. The training bolt (721) serves as an orientation for the manipulator when the manipulator is in the process of engaging the plate on the plate holder (720) or moving the plate on the plate holder (720). The carriage also includes notches (721) that provide space for the gripping fingers of the gripper system. The lock (710) also includes seals (719) for proper closure of the doors (711), (712). The main body (723) also comprises, at each end, a mechanical stop (718) for the doors (711) and (712). There is also a motor (715) attached to the main body (723) to move the carriage (714). Figure 56 shows a preferred apparatus. The apparatus comprises, on the front side, walls (761) and (762). The walls are movable to allow access to the cells (701), (702) for the manipulator system (704). Preferably, the walls (761, 762) consist of a film. They can be moved up and down. The apparatus further includes outer sidewalls (735). Preferred embodiments of the apparatuses, methods and systems are those described below, which further include the features described above. Other preferred features of the apparatus are preferred embodiments described below.
[0074] Hardware Architecture An analytical apparatus (400) for isolating and analyzing at least one analyte is also provided, comprising (i) at least one module (401) for receiving and dispensing a sample to be analyzed, (ii) at least one module (402) ) to isolate said analyte to be analyzed, (iii) at least one module (403) for analyzing said analyte, wherein said modules (i) to (iii) are arranged along an axis. In a preferred embodiment, said modules are arranged along an axis X.
[0075] In a second embodiment, said modules are arranged along a vertical axis. Said modules can also be arranged along a Y or Z axis. The axis can also be partially circular. The apparatus further comprises at least one transport module (480) for transferring consumables (60, 70, 101, 301, 302), wherein said at least one transport module (480) is arranged parallel to said axis ahead of modules (i) to (iii). The at least one transport module (480) preferably comprises a manipulator (500) as described below. The apparatus (400) comprises at least one consumable holder (600), wherein said at least one consumable holder (600) is arranged along said axis in front of the modules (i) to (iii). In a preferred embodiment, said consumable holder (600) is a stacker (600). The stacker (600) preferably includes recognition elements for recognizing consumables (60, 70, 101, 301, 302). Preferably, said stacker (600) is arranged below said transport module (480). The terms "analytical apparatus" (400) and "analyzer" (400) and "analytical instrument" (400) are used interchangeably.
[0076] Other preferred embodiments of said stacker (600) and said analytical apparatus (400) and said analytical system (440) are described below.
[0077] The modules (401, 402, 403) of the analytical apparatus (400) are preferably attached to neighboring modules (401, 402, 403). In one embodiment, the modules (401, 402, 403) are attached to one another using fasteners, preferably screws. In another embodiment, the modules (401, 402, 403) are fixedly mounted in frames, and the neighboring module frames are attached to each other, preferably by fasteners, more preferably by screws. . In a preferred embodiment of the apparatus described above, said module (403) for analyzing said analyte comprises a thermal cycler. In a more preferred embodiment, the apparatus comprises at least two modules (403) for analyzing said analyte, wherein said at least two modules (403) for analyzing said analyte are mounted on two vertical levels. Other preferred embodiments of said module for analyzing said analyte include modules for detecting chemical reactions or modules for detecting antibody binding to antigens. Other preferred embodiments of said module for analyzing said analyte are described below. The analytical apparatus (400) described above, in a preferred embodiment, comprises more than two consumable holders (600). Preferably, at least one consumable holder is a consumable waste holder (650). The analytical apparatus as described above comprises, in a preferred embodiment, a module for preparing at least one reaction mixture for analyzing said at least one analyte, wherein said module is arranged between the module (ii) and the module (iii). An analytic system (440) is also exposed. An analytical system (440) includes an analytical apparatus (400) as described herein. An analytical apparatus (400) comprises one or more modules or cells (401, 402, 403). The said modules or cells comprise stations for performing the treatment and / or analysis of an analyte. Preferably, said apparatus and said system are automated. More preferably, the consumables are loaded manually. One embodiment of the apparatus is shown schematically in Figure 52. The arrangement of all the modules of the apparatus facilitates the loading of consumables into the apparatus by the user. The device and individual modules are also more easily accessible for maintenance than existing analytical devices. The arrangement of the transport module along the same axis as the modules also makes it possible to optimize the footprint of the entire apparatus and the system because the transport module is used to load the consumables into the system. device, as well as for the transfer of consumables between the different modules and the waste holder. An automated method for isolating and analyzing at least one analyte is further disclosed, comprising the steps of a) receiving a sample contained in a sample container in a first module for receiving and dispensing samples, b) transporting a sample. first consumable of a consumable holder up to said first module for receiving and dispensing samples with a transport module, c) dispensing said sample into receptacles of a first consumable for isolating an analyte included in said sample, d) transport said first consumable for isolating an analyte included in said sample with said transport module of said first module for receiving and dispensing samples to a second module for isolating the analyte included in said sample, e) isolating said analyte in said second module to isolate the analyte, f) analyzing said analyte in a third module to analyze an analyte.
[0078] The term "dispense" as used herein refers to the aspiration of a sample from a sample container, and the subsequent dispensing into containers for containing a liquid. Preferred embodiments of said container are described hereinafter and above, with reference to the preferred embodiments of the analytical apparatus. In a preferred embodiment of the method described above, said analyte is transported by the transport module of said second module to isolate the analyte to said third module to analyze an analyte.
[0079] In another preferred embodiment of the automated method described above, the isolated analyte is transferred from said first consumable to isolate an analyte included in said sample to a second consumable to analyze said analyte. Preferred embodiments of said second consumable are described below. The automated method further includes a preferred embodiment wherein said second consumable for analyzing said analyte is transferred by the second module transfer module to isolate the analyte 30 to the third module to analyze an analyte. More preferably, the transfer module comprises at least two transfer devices (500), in which a transfer device transfers consumables from the consumable holder to module (i) or (ii), from module (i) to to the module (ii) and the module (ii) up to an interface between the module (ii) and the module (iii), and the module (i), the module (ii) or the interface up to a waste holder of consumables; and the second transfer device transfers the consumables between the interface and the module (iii). Preferably, the transfer module comprises two transfer devices. In a preferred embodiment, said method further comprises between steps c) and f) the step of preparing reaction mixtures for analyzing said at least one analyte. The flow of transported consumables is shown with arrows in Figures 52 a) to c). Other preferred embodiments are described below. Workflow Timing A method and system for isolating and analyzing an analyte in an automated analyzer is also disclosed, including the steps of supplying a liquid sample comprising said analyte to a sample container. treatment in a module of a first type; transferring said liquid sample comprising said analyte to a module of a second type; isolating and purifying said analyte in said process vessel in said module of a second type; transferring said purified analyte to a module of a third type; analyzing said analyte in said module of a third type by reacting said analyte with reagents necessary to obtain a detectable signal. The timer for the transfer and processing in any one module of a type is predefined, and said timer in any one module of a type is the same for any analyte that is isolated and analyzed. In addition, the timing of any type of module may be independent of the timing of any other type of module. Thus, the modules can operate autonomously. The advantage of the method and system is that the predefined timeout of any one module of a type allows optimization of the overall workflow timeout and provides high efficiency optimized for analytical testing. The predefined module timeout starts the analytic process, starting with sample distribution, only if, at the end of a module's workflow, a next type of module for the next step in the analytic process is available. Thus, for example, the isolation and purification of the analyte is only initiated if, at the end of the isolation and purification process, a module for analyzing the isolated and purified analyte is available. Thus, in a preferred embodiment, said analyzer comprises at least two modules of a third type. In a preferred embodiment of the method described above, a first analyte is isolated and analyzed in said automated analyzer, and a second analyte isolated and analyzed in said automated analyzer, wherein said first and second analytes are isolated and analyzed. in parallel, wherein said first analyte is analyzed in one of said modules of a third type, and said second analyte is analyzed in a second of said modules of a third type, and wherein the durations for isolating and analyzing said first and second analytes are identical. Thus, the timing of the analytical tests being done in parallel can be kept identical, so that any analyte is processed and analyzed in the analytical apparatus under identical conditions. This also makes it possible to use more than one module of one type in the automated analyzer while ensuring identical conditions for each test. The possibility of using multiple modules of one type makes it possible to adapt the performance of the analytical apparatus to the needs of the user. In a preferred embodiment, said analyte is a nucleic acid analyte. In other preferred embodiments, the analyte is an antibody, an antigen or a cell. Preferably, said module of a third type is an amplification module.
[0080] In a preferred embodiment of the method described above, said automated analyzer comprises at least two modules of a second type.
[0081] In another preferred embodiment, said analyzer comprises at least four modules of a third type. Preferably, at least 48 samples comprising at least one analyte are isolated and purified in parallel. More preferably, said samples are isolated and purified in 96-well plates in parallel. Most preferably, the samples are analyzed in 96-well plates in at least one module of a third type. In a preferred embodiment of the method described above, at least 192 samples comprising at least one analyte are isolated and purified in parallel in at least two separate modules of a second type, and are analyzed in at least two separate modules. of a third type. The processing time in any of the modules of a third type is identical. Thus, it is possible to isolate and purify analytes in 48-well plates in at least two modules of a second type in parallel, and then analyze the purified samples in at least four modules of a third. type. Preferred embodiments for modules of a first type are sample cells for dispensing a sample comprising an analyte into a treatment container. Sample cells and processing vessels are further described hereinafter. Preferred embodiments for modules of a second type are cells for purifying and isolating an analyte comprising a separation station. Such cells are further described below. Preferred embodiments of modules of a third type are analytical modules, more preferably cells for amplifying an analyte which is a target nucleic acid. Preferred embodiments of such cells include temperature-controlled incubators, more preferably thermal cyclers.
[0082] Since the time required for analysis of a sample in a module of a third type, preferably an amplification and detection module, is longer, preferably twice as long as the isolation and purification of a sample present in a module of a second type, a maximum efficiency can be obtained using a configuration as shown in Figure 53c) using twice as many modules of a third type than modules of a second type. The preferred workflow in any module is described by the following process steps: - Loading all required consumables via predefined interfaces; - Loading samples via predefined interfaces; - Initiation of a test when all samples to be analyzed and all required consumables are loaded; - Output of the result in the form of processed samples (eg isolated and purified samples) or measured data or monitoring results; - Exit or evacuation of the materials used; - Exit or evacuation of analyzed samples. More preferably, said workflow further comprises, for the module of a second type, the loading of reagents.
[0083] The transfer in the transfer system is manual or automated. Preferably, the transfer is automated. The transfer system transfers consumables and some reagents between modules and storage areas.
[0084] Preferred embodiments of storage areas are described below. Another preferred storage area is a refrigerator. The apparatus used in the method described above preferably comprises a linear transfer module. In another embodiment, it preferably comprises a rotary transfer module. The delay of the transfer module that connects the modules is not critical. This means that manual operations on the system during the process, such as loading with consumables, or loading samples into any of the modules, does not affect the workflow of the system in general. Also, pauses between two types of modules are possible without affecting the workflow in the critical processes (those in modules of a first type, a second type and a third type).
[0085] Preferably, in the method described above, the time for isolation and purification and analysis of any analyte is the same as the time for isolation and purification and analysis of another analyte.
[0086] In a preferred embodiment, the process of providing and isolating and purifying at least one analyte is initiated subject to the availability of a module of a third type when the isolation and purification process and preparing reaction mixtures is completed.
[0087] The method disclosed herein also makes it possible to generate systems comprising multiple analytical devices with said modules, or to connect multiple systems while ensuring that critical workflows remain constant and that any analyte is isolated, purified and processed in the process. system under identical conditions. This improves the accuracy and reliability of the parallel analytical tests. It is also possible, with the claimed method, to introduce pauses that are not critical for the analytical test when the process in a module of one type is completed, and before the workflow of the following type of module fails. be launched.
[0088] However, such breaks are not possible for temporally critical stages. The method and system described above may further comprise a module of a fourth type for preparing reactions for analysis in the module of a third type; and a module of a fifth type for detecting a reaction performed in said module of a third type. Preferably, the analysis of an analyte comprises both of a reaction and a detection in said module of a third type. Other preferred embodiments of the method described above are described herein.

权利要求:
Claims (7)
[0001]
An analytical system for treating an analyte, said system comprising a) a first position comprising a first receptacle containing a liquid sample comprising an analyte, a second receptacle for holding a liquid sample, a rack containing pipette tips, and a first head of processing for transferring a liquid sample from the first receptacle to a second receptacle, b) a second position comprising a station for receiving said second receptacle, and a rack receiving station for receiving said rack, c) a transfer system for transferring the second receptacle and the rack containing pipette tips between the first position and the second position.
[0002]
The analytical system of claim 1, wherein the positions are separate cells. 20
[0003]
The analytical system of claims 1 to 2, wherein the rack transferred by said transfer system comprises pipette tips which have been used in the first position. 25
[0004]
The analytical system of claims 1 to 3, wherein the first receptacle is a sample container and the second receptacle is a treatment container.
[0005]
The analytical system of claims 1 to 4, wherein said treatment vessel is a multi-well vessel.
[0006]
6. Analytical system according to one of claims 1 to 5, wherein the transport system transfers the receptacle and the rack from the first position to the second separated position.
[0007]
The analytical system of claims 1 to 6, wherein said transport system comprises a manipulator constructed and arranged to grip and transport said rack and said processing container from one to a second location within the system.

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DE112017005675T5|2016-11-11|2019-09-05|Brio Apps Alphasip, S.L.|System for performing chemical, biological and / or medical processes|

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CN110914447A|2017-01-26|2020-03-24|生物辐射实验室股份有限公司|Assay performance system including aqueous sample stabilization|

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JP6694486B2|2018-03-29|2020-05-13|バイオティクス， インコーポレイテッド|Pipette tip tray with increased rigidity|

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WO2020257672A1|2019-06-19|2020-12-24|Life Technologies Corporation|Reagent container and methods of use|

法律状态:
2015-12-24| PLFP| Fee payment|Year of fee payment: 6 |

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2016-11-17| PLFP| Fee payment|Year of fee payment: 7 |

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2017-11-20| PLFP| Fee payment|Year of fee payment: 8 |

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2018-09-21| PLSC| Publication of the preliminary search report|Effective date: 20180921 |

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2018-11-19| PLFP| Fee payment|Year of fee payment: 9 |

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2019-11-22| PLFP| Fee payment|Year of fee payment: 10 |

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2020-11-19| PLFP| Fee payment|Year of fee payment: 11 |

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2021-11-17| PLFP| Fee payment|Year of fee payment: 12 |

优先权:

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申请号 | 申请日 | 专利标题

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EP09178713|2009-12-10|

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EP09178713.5|2009-12-10|

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EP10158862|2010-03-31|

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EP10158862.2|2010-03-31|

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FR1060289A|FR2953932B1|2009-12-10|2010-12-09|METHOD FOR SEPARATING AND DETECTING AN ANALYTE|

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FR1553101A|FR3020140B1|2009-12-10|2015-04-10|ANALYTICAL SYSTEM FOR PROCESSING AN ANALYTE|FR1553101A| FR3020140B1|2009-12-10|2015-04-10|ANALYTICAL SYSTEM FOR PROCESSING AN ANALYTE|