High throughput system for performing assays using electrochemiluminescence including consumable shaking apparatus

Abstract

To perform assays on a solid phase to measure the level of analyte in a sample.SOLUTION: A system for performing assays on a solid phase to measure the level of analyte in a sample may perform immunoassays using electrochemiluminescence (ECL) including a counterbalanced orbital shaking apparatus for assaying consumables.SELECTED DRAWING: Figure 10(a)

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This international application claims priority to a provisional application entitled "Consumable Shaking Apparatus", filed on April 6, 2015, having serial number 62 / 143,557, and another provisional patent application entitled "Throughput System for Performing Assays Using Electrochemiluminescence Including a Consumable Shaking Apparatus", filed on March 22, 2016, having serial number 62 / 311,752, both of which are incorporated by reference in their entireties.

[0002] The present invention relates to a system for performing immunoassays using electrochemiluminescence (ECL). [Background technology]

[0003] The use of binding assays on solid phases is a common technique for measuring the levels of analytes in samples. There are many types of natural and synthetic binding reagents (e.g., antibodies, nucleic acids, aptamers, receptors, ligands, etc.), solid phases (e.g., the surface of a vessel or well or the surface of a microparticle), and assay formats (direct binding, sandwich, competitive, etc.) known in the art of solid phase binding assays. One specific example showing the format of a typical processing step of a solid phase binding assay is the sandwich immunoassay that uses two antibodies directed against the target analyte, one of which is immobilized on the solid phase and the other of which carries a label detectable through some detection technique (e.g., using fluorescence, chemiluminescence, electrochemiluminescence, absorbance, or oxygen activity measurements). When the solid phase is the surface of a well in a multi-well plate, conventional steps in this format may include: (i) adding a sample to the well, followed by incubation to allow the analyte in the sample to be collected by the immobilized antibody in the well, (ii) adding a labeled detection antibody to the well, followed by incubation to allow the detection antibody to bind to the collected analyte to form a labeled "sandwich" complex on the solid phase, and (iii) measuring the label present in the sandwich complex on the solid phase.

[0004] Optionally, the wells may be washed before or after any step to remove any unbound material before the addition of a new method. During the incubation step, the plate may be vibrated to reduce time and improve the productivity of the binding reaction. One exemplary detection technique that may be used to measure the label during the measurement step is electrochemiluminescence (ECL) detection, which uses a label such as a derivative of ruthenium tris-bipyridine that emits light when near oxidation or reduction of an electrode under suitable chemical conditions (see, e.g., U.S. Patent No. 6,808,939, which is incorporated herein by reference in its entirety). Instruments and consumables designed to perform binding assays in multi-well formats with ECL detection have been described (see, e.g., U.S. Patent No. 7,842,246, which is incorporated herein by reference in its entirety). The '246 patent describes a method for detecting antibodies or This application describes a multi-well consumable having electrodes attached within the wells that are used as a solid phase support for arrays of antibodies or antibodies. Formation of label complexes at the electrodes is measured by applying a voltage to the electrodes and measuring the composite ECL signal. An ECL lead buffer, such as a buffer containing tripropylamine or another tertiary amine (see, e.g., U.S. Pat. No. 6,919,173, incorporated herein by reference in its entirety), is added to the wells prior to applying the voltage to provide chemical conditions conducive to efficient ECL generation. Several alternative procedures have been described for performing ECL assays, including procedures with an additional step during which harvested antibodies from a lysate are immobilized (see, e.g., U.S. Patent Application Publication No. 20140256588, which is incorporated herein by reference in its entirety), and procedures in which the measurement step prior to the ECL measurement includes an amplification step (see, e.g., U.S. Patent Application Publication No. 20140272939, which is incorporated herein by reference in its entirety).

[0005] In certain circumstances, ECL electrodes or other solid phases may be treated with materials ("blocking agents" or "blocking reagents") that prevent non-specific binding of analytes or analytical reagents. This treatment may be performed as a separate "blocking" step, or the blocking reagent may be included in a buffer or diluent used during other steps of the analytical procedure. Examples of useful blocking reagents include proteins (e.g., serum albumins and immunoglobulins), nucleic acids, polyethylene oxide, polypropylene oxide, block copolymers of polyethylene oxide and polypropylene oxide, polyethyleneimines, and detergents or surfactants (e.g., the classes of non-ionic detergents / surfactants known by the trade names Brij, Triton, Tween, Thesit, Lubrol, Genapol, Pluronic, Tetronic, F108, Span).

[0006] To date, the steps of an ECL immunoassay have been accomplished by various individual machines. For example, washing of multi-well plates is performed by a plate washing machine, pipetting of samples and reagents into multi-well plates is performed by a mechanized pipetting machine with many pipette tips, agitation of samples and antibodies is performed by a mechanical shaker, and excitation of analyte-antibody complexes and detection of emitted light are performed by a plate reading machine. However, there remains a need in the art for an overall system that integrates all these individual machines into a single interconnected system that improves efficiency, provides the ability to wash multiple pipette tips on the fly, and provides thermal control to meet the operating temperature range of reagents and / or samples. Summary of the Invention

[0007] One embodiment of the present invention relates to a method of operating an ECL immunoassay system with multiple assay trays, where each plate is completely processed before the next tray is processed, and the plate incubation period divided by the processing period of each tray is equal to the number of trays processed.

[0008] Another aspect of the invention relates to a method of operating an ECL immunoassay system comprising a pipette dispenser, a plurality of multi-well plates adapted to store ECL complexes attached to electrodes contained in the multi-well plates, an incubator, and an ECL reader. a. removing a single multiwell plate from a shelf; b. optionally, washing the single multiwell plate; c. depositing samples to be tested into wells in the single multi-well plate; d. depositing at least one reagent to form a complex with the analyte in the sample; e. Optionally, washing the single multi-well tray to remove any remaining specimens; f. placing the washed single multi-well plate into an incubator; g. Repeating steps (a)-(f) with another single multi-well plate until the incubator is filled, wherein the duration of the incubation is determined by the time the incubator is filled. and repeating the steps of: h. Placing the fully incubated multi-well plate into an ECL reader. Step (h) is repeated until all incubated plates are placed in the ECL reader. The number of multiwell plates stored in the incubator is equal to the incubation period divided by the time to complete steps (a)-(f).

[0009] Another aspect of the invention relates to an ECL immunoassay system comprising a housing enclosing a pipette dispenser, a plurality of multi-well trays adapted to hold ECL complexes attached to electrodes contained in the trays, an incubator, an ECL reader, and a cooler. The cooler is disposed near a rear surface of the housing, the housing further comprising a flow plenum directing airflow from the cooler to a front surface of the housing. In one embodiment, the flow plenum is disposed near a top surface of the housing. In another embodiment, the flow plenum is disposed near a bottom surface of the housing.

[0010] The upper flow plenum is a space between the upper surface and a second upper surface disposed below the upper surface. The second upper surface includes at least one inlet opening near a cooler and at least one exhaust opening front surface. The cooler can be one or more thermoelectric coolers.

[0011] Another aspect of the invention relates to a pipette tip cleaning system comprising at least one chimney defining an opening adapted to receive at least one pipette tip, a gap between the at least one pipette tip and the at least one chimney being substantially constant, the at least one chimney being in fluid communication with a cleaning fluid, the cleaning fluid being pumped through the gap to clean the exterior of the at least one pipette. A level sensor may be attached to a side wall of the housing of the device. A flow restrictor may be disposed between the at least one chimney and a manifold in fluid communication with the cleaning fluid.

[0012] Yet another aspect of the present invention is a method for cleaning a pipette tip, comprising the steps of: (a) multiple steps of washing the inside of the pipette tip including aspirating incrementally increasing volumes of a washing solution of progressively cleaner water; (b) multiple steps of cleaning the exterior of the pipette tip with the same cleaning solution; The method relates to a method in which a pipette tip is placed near a gap of constant thickness to control the flow of wash fluid. The method may further comprise washing the pipette tip in a dissolving solution of water and bleach prior to steps (a) and (b).The method may include physical inactivation of the pipette tip to minimize carryover of the sample being tested and / or one or more reagent(s).

[0013] The present invention further relates to a counterbalanced analytical consumable vibration apparatus comprising (a) an orbital vibrator assembly comprising a horizontal orbital platform, and (b) an analytical consumable storage assembly disposed on the platform. The storage assembly comprises (i) a shelving subassembly comprising a set of a plurality of vertically arranged storage units, each storage unit sized to receive a consumable and including a consumable locking mechanism, and (ii) a counterweight disposed within the storage assembly at a height corresponding to the center of mass of the storage assembly and the orbital platform. The apparatus further comprises a rotation axis extending vertically from the vibrator assembly to the storage assembly, the counterweight being operatively connected to the rotation axis.

[0014] The present invention further relates to a counterbalanced analytical consumable vibration device comprising (a) an orbital vibrator assembly comprising a horizontal orbital platform, and (b) an analytical consumable storage assembly disposed on the platform. The storage assembly comprises (i) a shelving subassembly comprising a set of a plurality of vertically arranged storage units, each storage unit sized to receive a consumable and equipped with a consumable locking mechanism, and (ii) two or more counterweights disposed within the storage assembly, one counterweight disposed above and another counterweight disposed symmetrically below a height corresponding to the center of mass of the storage assembly and the orbital platform. The device further comprises a rotation shaft extending vertically from the vibrator assembly to the storage assembly, the two or more counterweights being operatively connected to the rotation shaft. Alternatively, the device comprises two or more rotation shafts in operative communication with a timing belt, each rotation shaft being connected to a counterweight.

[0015] Another aspect of the invention is a method of operating an analytical system for analyzing a batch of analytical plates, comprising the steps of: (i) each plate in the batch is subjected to a series of different treatment cycles of length N; (ii) the series of different treatment cycles for a given plate in the batch are separated by an incubation period of at least Y time; (iii) each of the series of different processing cycles is performed sequentially on the plates in the batch; (iv) The number of plates in the batch is less than or equal to Y / N.

[0016] Another aspect of the invention further provides a method of operating an analytical system for analyzing a sequence of analytical plates, comprising the steps of: (i) each plate in the batch is subjected to a series of different treatment cycles of length N; (ii) at least one of said series of cycles is an alternating cycle divided into a pre-incubation subcycle of length A and a post-incubation subcycle of length B, where A+B=N, and in a given plate, the completion of the subcycle of length A and the start of the subcycle of length B are separated by an incubation time that is a multiple of time N; (iii) (a) identifying a first plate in the sequence that has not undergone a pre-incubation subcycle and performing said pre-incubation subcycle thereon or if no plate is available for pre-incubation processing and then idling for a time A; (b) performing alternating cycles in the sequence of plates by identifying the first plate in the sequence that has completed incubation but has not undergone a post-incubation subcycle and performing said post-incubation subcycle thereon or when no plate is available for post-incubation processing and then idling for a time B; (iv) Repeating step (iii) until all plates in the sequence have undergone pre-incubation and post-incubation subcycles.

[0017] The assay system may include a plate handling robot, a processing deck, a plate hotel (or shelf), a pipette dispenser, a plate washer, a vibrating incubator, and a plate reader. The assay plate may include electrodes for performing ECL measurements, and the plate reader is an ECL reader.

[0018] The processing cycle is as follows: a. using the robot to move a single assay plate of the batch from a hotel or incubator to a deck; b. using the robot to move sample or reagent plates from a hotel or incubator to the deck; c. using a pipettor to transfer samples or reagents from the sample or reagent plate on the deck to the analysis plate on the deck; d. using the plate washer to wash the wells of the assay plate on the deck; e. using the robot to deliver the assay plate on the deck to the hotel or incubator; f. using the robot to deliver the analysis plate to the plate reader.

[0019] The different process cycles may comprise at least one of: (i) a sample addition cycle, (ii) a detection reagent addition cycle, (iii) a plate reading cycle, and (iv) a blocking cycle. The process cycle may further comprise a step of incubating the sample or the assay reagent plate, the incubation time being less than time N.

[0020] At least one of the processing cycles may be an alternating cycle divided into a pre-incubation subcycle of length A and a post-incubation subcycle of length B, where A+B=N, and in a given plate, the completion of the subcycle of length A and the start of the subcycle of length B are separated by an incubation time that is a multiple of time N. The alternating cycles in the batch of plates may be: (i) identifying a first plate in the batch that has not undergone a pre-incubation subcycle and performing said pre-incubation subcycle thereon or when no plates are available for pre-incubation processing and then idling for a time A; (ii) identifying the first plate in the batch that has completed incubation but has not undergone a post-incubation subcycle and performing said post-incubation subcycle thereon or when no plate is available for post-incubation processing and then idling for a period of time B; (iii) This can be performed by repeating step (ii) until all plates in the batch have undergone pre-incubation and post-incubation subcycles.

[0021] In the accompanying drawings, which form a part of and are to be read together with the specification, like reference numerals are used to refer to like parts in the various drawings, and in which: [Brief description of the drawings]

[0022] [Figure 1] FIG. 1 is a schematic diagram showing an exemplary redox ECL reaction in an immunoassay. [Diagram 2] FIG. 1 is a front view of an ECL immunoassay system of the present invention. [Diagram 3] FIG. 3 is a top view of the system of FIG. 2. [Figure 4] FIG. 13 is a perspective view of a pipette tip for cleaning the manifold. [Diagram 5] 5 is a cross-sectional view of multiple chimneys in the cleaning manifold of FIG. 4 with exemplary pipette tips. [Figure 6] FIG. 5 is an enlarged view of the cleaning manifold of FIG. [Figure 7] FIG. 4 is a perspective view of the housing of the system of FIGS. 2 and 3 with elements of the flow plenum not shown for clarity. [Figure 8] FIG. 8 is an enlarged view of the flow deflection plate shown in FIG. [Figure 9(a)] 1 is a flow chart of an exemplary method for operating the system of the present invention. [Figure 9(b)] 1 is a flow chart of an exemplary method for operating the system of the present invention. [Figure 10(a)] FIG. 2 is a perspective front view showing a detailed view of the vibration device with portions of the housing removed to show the internal mechanisms. [Figure 10(b)-(c)]Figure 10(b) is a perspective front view showing a detailed view of the vibration device with the housing removed to show the internal mechanism, and Figure 10(c) is an enlarged view of the upper eccentric mount and counterbalance shown in Figure 10(b). [Figure 10(d)] FIG. 13 is a top view of the drive mechanism and bottom eccentric mount. [Figure 11(a)] FIG. 11(c)-(i) shows detailed views of a storage assembly including various alternative configurations of sets of vertically arranged storage units within the storage assembly. [Figure 11(b)] FIG. 11(c)-(i) shows detailed views of a storage assembly including various alternative configurations of sets of vertically arranged storage units within the storage assembly. [Figure 11(c)] FIG. 11(c)-(i) shows detailed views of a storage assembly including various alternative configurations of sets of vertically arranged storage units within the storage assembly. [Figure 11(d)] FIG. 11(c)-(i) shows detailed views of a storage assembly including various alternative configurations of sets of vertically arranged storage units within the storage assembly. [Figure 11(e)] FIG. 11(c)-(i) shows detailed views of a storage assembly including various alternative configurations of sets of vertically arranged storage units within the storage assembly. [Figure 11(f)] FIG. 11(c)-(i) shows detailed views of a storage assembly including various alternative configurations of sets of vertically arranged storage units within the storage assembly. [Figure 11(g)] FIG. 11(c)-(i) shows detailed views of a storage assembly including various alternative configurations of sets of vertically arranged storage units within the storage assembly. [Figure 11(h)] FIG. 11(c)-(i) shows detailed views of a storage assembly including various alternative configurations of sets of vertically arranged storage units within the storage assembly. [Figure 11(i)] FIG. 11(c)-(i) shows detailed views of a storage assembly including various alternative configurations of sets of vertically arranged storage units within the storage assembly. [Figure 12(a)]13 illustrates an alternative configuration for a set of vertically arranged storage units within a storage assembly and the placement of a counterbalance within the storage assembly for the set of storage assemblies. [Figure 12(b)] 13 illustrates an alternative configuration for a set of vertically arranged storage units within a storage assembly and the placement of a counterbalance within the storage assembly for the set of storage assemblies. [Figure 13(a)] FIG. 13(b) shows a partial view of a microtiter plate, illustrating one embodiment of a locking mechanism used in the storage unit of the device. [Figure 13(b)] FIG. 13(b) shows a partial view of a microtiter plate, illustrating one embodiment of a locking mechanism used in the storage unit of the device. [Figure 13(c)] FIG. 13(b) shows a partial view of a microtiter plate, illustrating one embodiment of a locking mechanism used in the storage unit of the device. [Figure 13(d)] FIG. 13(b) shows a partial view of a microtiter plate, illustrating one embodiment of a locking mechanism used in the storage unit of the device. [Figure 14(a)] 1 illustrates an embodiment of a vibration device with an internal air flow path. [Figure 14(b)] 1 illustrates an embodiment of a vibration device with an internal air flow path. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0023] Unless otherwise defined herein, certain technical terms used in connection with the present invention shall have the meanings commonly understood by those of ordinary skill in the art. The words "tray" and "plate" are used interchangeably herein. The words "hotel" and "shelve(s)" are used interchangeably herein. Further, unless otherwise required by context, singular words include plurals and plural words include the singular. The articles "a" and "an" refer to one or more of the grammatical objects of the article. As used herein, "an element" means one element or more than one element.

[0024] One embodiment of the present invention relates to a system 10 as shown in Figures 2 and 3. The system 10 is a fully automated system that handles preferably all steps of a solid phase binding assay (e.g., ECL immunoassay) as described above, and is preferably capable of handling multiple multi-well plates 4. The system is particularly well adapted to perform ECL-based solid phase binding assays, as described below, but one skilled in the art may adapt the system to perform other assay formats and / or detection techniques with similar processing steps by appropriate selection of plate reader components and assay consumables and reagents. All necessary and optional machinery is contained within a housing or enclosure 12, along with samples, reagents, buffers, washing and cleaning solutions, electronics, and waste storage. Preferably, the enclosure 12 is supported by caster wheels to provide mobility to the system 10.

[0025] As best seen in FIG. 2, the housing 12 has an upper compartment 14 and a lower compartment 16. The upper compartment 14 encloses the machine, samples and reagents. The lower compartment 16 stores electronics 18, which may include a computer, and input / output devices including interfaces for controlling the machine and receiving data and communications from the machine, and a graphical user interface for technicians and other users to select a suitable protocol from a list of predefined protocols and WiFi for remote communication with other users. The lower compartment 16 stores a cleaning solution including pure water with or without surfactant or soap, and further stores a container 20 for storing waste or used water, described below.

[0026] The upper compartment 14 houses a number of equipment and machines mounted on the floor or deck 15, including, but not limited to, a shelf 22, also known as a hotel 22, sized and dimensioned to store multiple trays containing samples or reagents or to be used in an analytical process, a barcode reader 24 (not shown) located below the shelf 22, and a robotic arm 26 designed to transport the trays and their lids (if applicable) to other machines and return them to the shelf 22. The upper compartment 14 further includes a shaker and incubator 28, a plate washer 30 designed to wash materials removed from the wells of a multi-well analytical plate, a multi-channel pipettor 32 for transporting liquids to the wells of a multi-well analytical plate, and a pipette tip washing manifold 34 for cleaning pipette tips from the pipettor 32 after each use. The upper compartment 14 further houses a tray / plate reader 36, a thermoelectric cooler 38, which is a solid-state cooler, and the plate reader 36 is preferably an ECL plate reader for performing measurements based on the ECL reaction as shown in FIG. 1. Alternatively, other formats of plate readers (such as absorbance, fluorescence or chemiluminescence based plate readers) can be used to perform assays using other detection techniques.

[0027] Further attached to the deck 15 is a pipette deck 40, which in this embodiment includes four chambers sized and dimensioned to hold four trays and a gantry 42, which supports the multi-channel pipettor 32 for movement along the deck 15 in three dimensions. The pipette tip washing manifold 34 preferably includes two manifolds 34a and 34b, each including a number of chimneys corresponding to the number of pipette tips used. Preferably, one manifold contains water with a small amount of surfactant as described above in connection with the blocking reagent, and the other manifold contains pure water as further described below.

[0028] Before the analytical system 10 is started, the plates to be used in the analytical process are placed on the shelves 22. The plate is placed on the plate. Any multi-well plate can be used as long as the plate is sized and dimensioned to operate with the machine. Preferably, the shape and dimensions of the plate are consistent with established standards for analytical plates, such as those set by the Society for Laboratory Automation and Screening (SLAS), and the plate handling components (such as plate washers, pipettors, readers, robotic arms, etc.) are configured to process plates conforming to the same standards. To allow high-throughput parallel processing of multiple samples, the analytical plate 4 used to perform the analytical reactions is preferably a multi-well plate. Preferably, the number and configuration of wells follow established standards, such as 24-well, 96-well, 384-well, and 1536-well formats (most preferably, 96-well plate format), although any well configuration is possible. To perform ECL-based assays, analytical plates such as those described in U.S. Pat. No. 7,842,246 can be used. Highest throughput can be achieved by using components that simultaneously process all wells in the plate at the same time. For example, to process a 96-well assay plate, the system 10 preferably includes a 96-channel pipettor and a 96-channel plate washer.

[0029] In addition to the assay plate, other plates may be loaded that provide samples to be tested or reagents used in the assay, such as assay diluent, detection reagents, lead buffer (e.g., TPA lysate), blocking agent, and tip washing reagent (e.g., bleach lysate). These plates may preferably have a multi-well format with the same well density as the assay plate. The use of multi-well plates is preferred when it is desired to deliver different samples or reagents to different wells of the assay plate. Reagents or samples to be delivered to all wells of the plate may also be provided in multi-well plates, or they may be provided in a plate with a single large well (i.e., reagent reservoir). Preferably, the wells of the plates used for samples and / or reagents may be conical or round-bottomed wells to reduce wasted volume. The plates may be sized so that the volume of liquid is sufficient for one assay plate, or multiple assay plates (e.g., by using well plates with a higher volume depth). Plates that store samples and reagents are placed in predetermined positions on the shelves 22. These positions are preselected when defining the procedure so that the robotic arm 26 knows where to return to after extracting a plate or tank. The robotic arm 26 is controlled by a computer stored in the lower compartment 16, which also contains the software for operating the system 10.

[0030] To start the system 10, the operator selects a procedure from a list of procedures to be performed. The procedure is selected in part based on the type of analysis to be performed. Exemplary analysis types are described below. The robotic arm 26 preferably checks whether the plates and tanks are placed where they are supposed to be, and whether a particular plate, such as a plate / tank containing a sample or antibody reagent, has a lid to minimize evaporation. Preferably, all plates and tanks have a bottom surface of substantially the same size so that they can all fit snugly into the tray pipette deck 40. The operation computer can notify the operator if a tray or tank is misplaced or if a lid is missing. Each plate 4 or tank placed on the shelf 22 preferably has a barcode, as best shown in FIG. 1. The barcode reader 24 can read these barcodes and communicate to the operation computer whether the correct tray or tank has been placed on the shelf 22. After this check, the robotic arm 26 may pull one or more trays, such as assay plate 4, a sample plate containing the sample to be tested and / or a reagent plate (e.g., a plate containing diluents, blocking agents, or detection reagents such as antibodies labeled with ECL labels) and place the plate on the plate pipette deck 40. Optionally, the assay plate may be transferred to a plate washer and washed before being placed on the deck 40.

[0031] Thus, the multi-channel pipettor 34 may perform multiple preselected operations according to a selected sequence. In one possible sequence, the pipettor 34 uses 96 pipette tips to aspirate detection reagents from wells of a reagent plate and dispense the same predefined volumes into wells of an assay plate with antibodies immobilized on the surface of each well (e.g., an ECL assay plate with antibodies immobilized on electrodes in each well). The pipettor then uses a similar process to transfer each predefined volume of sample from the wells of the sample plate to the wells of the assay plate. The robotic arm 26 can place the assay plate with samples and detection reagents into the shaker / incubator 28 to mix the samples and detection reagents while incubating the same. During the period when the plate is incubating, additional plates can be processed in succession using the same set of operations.

[0032] After the samples and detection reagents have been fully incubated, the robotic arm 26 removes the tray from the shaker / incubator 28 and transports it to the plate washer 30. The plate washer 30 has a pair of tubes for each well. One tube dispenses wash fluid from a container 20 stored in the lower compartment 16 into the well, while the other tube aspirates the same well and discards the used fluid into a waste container 20 also stored in the lower compartment 16. Preferably, the elevation of the aspirator tube is lower than that of the discharge tube. As mentioned above, one purpose of the wash plate 4 is to remove any analytes or detection reagents that are not attached to the wells, as well as any components of the sample that may interfere with the analytical measurement.

[0033] While the plate is on the washer, the robotic arm 26 moves a reagent tank containing buffer from the shelf 22 to the deck 40. After the plate is washed, the robotic arm 26 carries the washed plate to the deck 40 where the pipettor 34 transfers the lead buffer from the reagent tank to the plate. The robotic arm 26 then moves the plate to the reader 36 where the analytical measurement is performed (e.g., in the case of an ECL measurement, by the reader 36 applying a voltage to electrodes in the wells to initiate the ECL reaction described above). Results are obtained by the reader 36 and transferred to an operating computer stored in the lower compartment 16. Upon completion, the robotic arm 16 returns the plate to the shelf 14.

[0034] It should be noted that the present invention is not limited to the steps described above, as the system 10 can perform any procedure including any number of steps in any sequence involving the machines and equipment described above.

[0035] Depending on the procedure selected, the pipettor 32 may be used to perform multiple pipetting steps on each of the multiple plates being run. An inventive aspect of the present invention is the use of a pipettor using disposable pipette tips, where the tips are cleaned between certain operations being run and replaced less frequently, such as between runs. An additional inventive aspect relates to a subsystem used to clean the tips, which has been selected to maintain high processing throughput while also providing negligible cross-contamination of certain cleaning procedures, reagents, and samples. In one embodiment of the present invention, the pipette tips are cleaned between each cycle of operations being performed on an assay plate (as defined below) to prevent cross-contamination of wells in different assay plates. In some procedures, it may be preferable to clean the pipette tips between operations in one cycle, especially when the sequence of pipetting steps provides the possibility of cross-contamination of sample or reagent plates. Forms of carryover thus include sample carryover and reagent carryover. The tip cleaning process of the present invention allows tip cleaning to be performed in less than 90 seconds (preferably less than 60 seconds) while achieving effective carryover of less than 10 ppm, preferably less than 1 ppm, or less than 0.1 ppm, preferably less than 0.01 ppm or less than 0.001 ppm. , where effective carryover is the amount of lysate 1 transferred to lysate 2 after the two lysates are numbered (1 then 2) pipetted using the same pipette tip. Effective carryover can be determined, for example, by comparison of test analytical conditions (using a cleaned, used pipette tip) to control analytical conditions using an unused (unused) pipette tip for each sample. The control conditions can include running a control sample 1 where a predetermined amount of lysate 1 is spiked into lysate 2. The control conditions can also include running a control sample 2 where lysate 2 is spiked with but not spiked with lysate 1. The results of lysate 2 under test analytical conditions are compared to the analytical signal, e.g., the difference in analyte concentration between control sample 1 and control sample 2 under control conditions, to determine effective carryover. See also Weibel et al., J.Lab.Automation 15:369-378 (2010). One of ordinary skill in the art will understand how to adapt the method of measuring carryover to different analytical platforms and automation systems.

[0036] In one embodiment of the invention, carryover of protein analytes from a first sample to a subsequent sample pipetted with the same tip is preferably less than 1 ppm when the analytes are measured by immunoassay, in another embodiment of the invention, carryover of nuclear analytes from a first sample pipetted with the same tip to a subsequent sample analyzed by nucleic acid hybridization or amplification analysis is less than 1 ppm.

[0037] To minimize effective carryover, the tip cleaning procedure preferably comprises (i) one or more cleaning steps to physically remove materials at the tip that may lead to inaccurate analytical results, and (ii) a deactivation step in which the tip is exposed to deactivating conditions or reagents (e.g., lysis solutions) that inactivate any such materials to reduce and eliminate their ability to affect analytical results even if they are not completely removed by the cleaning steps. The deactivation step may include treatment of the tip with liquids (e.g., using chemical oxidizing agents such as bleach or hydrogen peroxide, acids or bases such as HCl or NaOH lysis solutions, cross-linking agents such as formaldehyde, and / or alkylating agents such as ethylene oxide) by heat, electromagnetic radiation (e.g., using UV light to deactivate nucleic acids in samples or reagents), and / or gas or liquid chemical reactants that react with materials that may cause carryover effects. Preferably, the deactivation step comprises treatment of the pipette tip with a bleach solution. These conditions and reagents significantly reduce the effective carryover of protein or nucleic acid analytes when pipetting a series of samples with the same disposable pipette tip. Using the tip cleaning procedure of the present invention, a disposable tip may be used to process 20 or more samples, preferably 100 or more samples, before requiring replacement with an unused tip.

[0038] One embodiment of the tip washing procedure of the present invention uses the following steps: To clean the pipette tips 33, the robotic arm 26 removes the deactivating reagent tank (e.g., a tank containing a bleach solution as described below) from the shelf 22 and safely places it on the plate pipette deck 40. Referring to Figures 4-6, the pipette tip washing manifold 34 preferably has two manifolds for physically washing the pipette tips. The first manifold 34a preferably uses a mixture of water and a surfactant to wash the pipette tips, and the second manifold 34b preferably uses pure water. Both manifolds have multiple chimneys 44 that fit the number of pipette tips 33 in the pipettor 32. The pipettor 32 is supported by a gantry 42 and is movable in three directions for moving along the deck 15. In one embodiment, the pipettor 32 is positioned across either manifold 34a or 34b and is positioned such that the pipette tip 33 is positioned between the chimneys 44; in other words, the pipette tip 33 is misaligned with the opening of the chimney 44. The contents inside any remaining pipette tip 33 are then expelled into the manifold without getting in and contaminating the chimney 44. Thus, the pipettor 32 is positioned above the bleach solution tank. and inserted into the bleach solution. A first volume of bleach solution is aspirated into the pipette tip. Preferably, this first volume is larger than the volume of any preceding sample or reagent(s), so that the bleach solution moves to a sufficient height inside the pipette tip 33 to overlap the previous height of the sample or reagent(s). The bleach solution is then expelled from the pipette tip 33. The bleach solution may be reused multiple times, for example 10 times, until a fresh tank of bleach solution is needed. Optionally, the step associated with treatment with bleach (i.e., the inactivation step) may be omitted in favor of pipetting steps where the effect of analytical carryover may be small.

[0039] Thus, the pipettor 32 is moved to a position above the first manifold 34a, with the pipette tip 33 aligned directly above the chimney 44. As best shown in FIG. 5, the pipettor 32 submerges the pipette tip 33 into the chimney 44, but maintains a gap 46 between the tip 33 and the chimney 44. A cleaning solution with some surfactant from a container located below the lower section 16 is pumped from the bottom into the chimney 44 through the conduit 48 and the manifold 50 to be distributed into the chimney 44. Optionally, a flow restrictor 51 is placed upstream of each chimney 44 to ensure uniform flow of fluid from the lower manifold 50 into the gap 46. The flow restrictor can be a narrowed section. A second volume of water and surfactant is aspirated into the pipette tip 34, where the second volume is greater than the first volume. Additional water and surfactant is pumped through the gap 46 to wash the outside of the pipette tip 33. To maximize this outer water flow, gap 46 preferably has a certain clearance. In other words, the outer shape or surface of pipette tip 33 conforms to the inner surface of chimney 44 to maintain a certain clearance between tip 33 and chimney 44. Preferably, this clearance is between 0.25 mm and 1 mm, and more preferably, between 0.5 mm and 0.75 mm.

[0040] After being washed with the surfactant solution in the first manifold 34a, the pipettor 32 moves the pipette tip 33 to the second manifold 34b and the same wash is repeated with pure water. A third volume of pure water is aspirated into the pipette tip 33, where the third volume is greater than the second volume. In one example, the first volume is approximately 75 ml, the second volume is approximately 100 ml, and the third volume is approximately 125 ml.

[0041] To clean the pipette tip 33, both the inside and the outside of the pipette tip should be cleaned. For internal cleaning, the amount of aspirated volume in each cleaning step should be progressively larger with progressively "cleaner" dissolving liquids, i.e. closer to clean water. For example, as described above, the aspirated volume increases progressively from the first volume to the third volume, and from the bleach solution to the soapy dissolving liquid (with surfactants) to pure water. Alternatively, the bleach solution can be omitted. The cleaning is separated into at least two tanks (34a, 34b): a coarse cleaning in tank 34a and a fine cleaning in tank 34b. Within each tank, the contaminants are effectively removed by repeated cleaning cycles, i.e. preferably using directional flow. For external cleaning, the pipette tip 33 is placed near the narrow gap 46 to obtain a larger shear force from the flow from the manifold 50. A flow restriction 51 can be placed upstream of the gap 46 to control and increase the flow through the gap.

[0042] This washing step allows disposable pipette tips to be reused within system 10. Unused disposable pipette tips are loaded into pipettor 32 at the start of each run and can be used throughout the run, remaining there until the completion of the run.

[0043] Referring to FIG. 6, the first and second manifolds 34a and 34b have a level sensor 52 preferably located in its wall. In one embodiment, the level sensor 52 is a light reflective sensor that emits an IR (infrared) beam toward a transparent window 54, preferably acrylic. The refractive index of the window 54 is close to that of the cleaning liquid, but different from that of air. When air is behind the window 54, the difference between the refractive indexes of the window 54 and the air is high enough to cause more IR to be reflected by the window 54. When the cleaning liquid is behind the window 54, the difference between the refractive indexes of the window 54 and the cleaning liquid is small enough to cause more IR to be transmitted through the window 54. The sensor 52 can detect a higher IR transmission, indicating that the liquid level is at the window 54. This can inform the operation computer to close the pump to stop the flow of the cleaning liquid until the liquid is drained through the drain hole 56. The drain hole 56 is connected to a waste container located in the lower section 16.

[0044] Advantageously, the level sensor 52 can be used to establish a constant fill level in the pipette tip washing manifold 34. The pump can be shut off and the drain hole 56 can be made smaller when the sensor 52 detects that the level reaches the window 54. This fill level is known to the operation computer when waste water droplets adhere to the pipette tip 33 and the pipettor 32 can place the pipette tip 33 away from the chimney 44 and the lower tip 33 at a height above the fill level but sufficient for the waste water droplets to come into contact with the liquid. This allows the waste water droplets to be transferred to this liquid in the washing manifold 34 without touching the pipette tip, which may previously have been used to wash the pipette tip 33 and may contain contaminants.

[0045] According to another aspect of the invention, an advantage of enclosing the machine inside the housing 12 is that the temperature and / or humidity inside the housing 12 can be controlled and evaporation of reagents and other liquids can be minimized. The housing 12 does not need to be sealed from the environment, however, the inside of the upper compartment 14 does not actively exchange air with the outside environment. The upper compartment 14 is enclosed by a top surface, side surfaces, a rear surface and a deck 15. The front surface includes one or more sliding or hinged doors. In some applications, it is desirable to maintain a temperature within the upper compartment 14 between approximately 23° C. and approximately 27° C., and within this temperature range, within ±1° C. at a particular selected, pre-set temperature.

[0046] Referring to FIG. 7, another inventive aspect of the present invention relates to the controlled air flow within the upper section 14. As multiple machines and other objects are present on the deck 15, they disrupt the air flow and redirect it in an uncontrolled manner. The thermoelectric coolers 38 generally take in air inside the upper section 14, cool / warm the air horizontally approximately at their centers, and discharge the air vertically at their tops and bottoms. FIG. 7 shows the housing 12 with the machines and other components removed for clarity. The top surface of the housing 12, indicated by reference numeral 58 in FIG. 2, and the deck 15 are also removed for clarity. Below the top surface 58 of the housing 12, a second top surface 60 is disposed below the top surface 58 to form a flow plenum 62 at the top of the upper section 14. Preferably, the second top surface 60 is spaced a sufficient distance from the top surface 58 to allow the discharge of the air flowing therethrough. The size of the flow plenum 62 can be adjusted to be smaller to speed up the air flow or larger to slow it down. The second upper surface 60 has at least one inlet 64 located near the upper discharge of the thermoelectric cooler 38 and at least one outlet 66 near the front of the upper section 14. As shown, the top discharged air enters the flow plenum 62 at the inlet 64 and flows along the plenum until it reaches the outlet 66 near the front of the upper section where it is forced to flow downward to modify the temperature of the machine before flowing back to the thermoelectric cooler at its suction. Without the flow plenum 62, the flow pattern from the top discharge air would not reach the front of the upper section 14 because the discharge air would bounce off the upper surface 58 to the horizontal suction without traveling to the front of the upper section 14.

[0047] 7 and 8, a sloped flow diverter 68 is positioned directly below the bottom discharge of the thermoelectric cooler 38 to deflect the flow along the deck 15 to direct the air flow to the front of the upper section 14 and then up and back to the horizontal suction of the thermoelectric cooler. In another embodiment, the second flow plenum 62 can have a bottom surface positioned below the deck 15 and an inlet 64 and an outlet 66 provided on the deck 15.

[0048] The deflected airflow at the top and / or bottom of the upper section 14 results in a longer airflow path from the top and bottom discharges of the thermoelectric coolers 38 back to their horizontal central intakes. The longer airflow path provides a more efficient distribution of the airflow through the upper section, reducing temperature gradients within the enclosure to maintain temperature differences within the upper section 14 to within ±1°C.

[0049] procedure The ECL immunoassay system 10 can perform any number of analytical procedures. Preferably, the analytical procedures for processing each plate are broken down into a series of time processing cycles of equal duration, each cycle including the processing of a single plate on the deck 15, and the different cycles performed on each plate can be separated by plate incubation periods. This method can provide extremely high throughput processing while maintaining precise control of the timing of the analytical steps, and greatly simplifies the planning of individual automated operations. As long as each cycle has a duration of N minutes (meaning that the operations or steps within a cycle take less than N minutes) and the incubation time between any two adjacent cycles for a given plate is at least Y minutes, then the system 10 can batch Y / N ​​plates in progress without accessing two plates at the same time, while maintaining constant timing for all analytical procedures and incubation steps on all plates.

[0050] In one embodiment of this "time cycle" method, the individual cycles forming the processing sequence for an analytical procedure are formed by modifying the overall composite step cycle, by removing steps that are not required for steps involving fluid movement in a particular cycle, and by identifying certain volumes to be moved. The modified cycles are feasible within the duration of the overall general cycle and do not require any changes to the overall schedule of the cycle.

[0051] An exemplary flow chart of one general cycle is shown in FIG. 9(a) as there is an opportunity to modify the cycle to generate several analysis-specific cycles. In step 70, the target plate is selected. In step 72, a decision is made of the plate to be washed. If YES, then in step 74, a washing procedure is selected and a washing buffer is selected. After step 74, or if the decision in washing the plate from step 72 is NO, then the procedure proceeds to step 76 where a reagent (or sample) is added. A reagent (or sample) source and a reagent (or sample) volume are selected. Thus, another decision is made in step 78 whether to add a second reagent. If YES, then in step 80, another reagent (or sample) source and volume are selected. After step 80, or if the decision from step 78 is NO, then the procedure proceeds to step 82 where the plate is incubated and agitated. An incubation time and an incubation position, for example, the vibrator 28 or the shelf 22, are selected. A decision is then made in step 84 whether the pipette tip should be washed. If YES, then another decision is made in step 86 whether to wash with an inactivating lysing solution such as bleach. After step 86, or if the decision from step 84 is NO, then the procedure proceeds to step 88, where the plate is placed in Leader 36.

[0052] In one example, an analytical procedure may include the following cycle formed by modifying the general cycle of FIG. 9(a) into the following steps / operations: Cycle 1. Pull the assay plate and blocking reagent reservoir from the shelf 22, add blocking reagent to the plate using the pipettor 32, and place the plate on the shaker 28. Cycle 2. Pull the analysis plate from the shaker 28 and the sample plate from the shelf 22, wash the analysis plate in the plate washer 30, add samples to the plate using the pipettor 32, and place the plate on the shaker 28. Cycle 3. Pull the assay plate from the shaker 28 and the detection reagent tank from the shelf 22, wash the assay plate, add detection reagent to the plate using the pipettor 32, and place the plate on the shaker 28. Cycle 4. Pull the analysis plate from the shaker 28 and the Lead buffer tank from the shelf 22, wash the analysis plate, add Lead buffer to the plate using the pipettor 32, and position the plate in the reader 36 for analysis. In this example, each cycle takes 3 minutes or less to perform, and with an incubation time of 60 minutes in shaker 28, system 10 can then run a batch of 20 multiwell plates without interference between plates.

[0053] In another example, the system may be used to perform procedures that include incubations that are short or of duration comparable to the duration of the cycle, e.g., incubation times in the range of 10 seconds to 6 minutes. This procedure is suitable for performing assays of large numbers of samples with short incubations instead of requiring diluents. Because of the short incubations relative to the cycle length, the incubations may be performed as steps within the cycle. In this case, the plate may remain on the deck (either not vibrated during incubation, or with a pipettor to mix by pipetting up and down), or the plate may be transferred to the vibrator and incubated or returned to the deck within the time frame of a single cycle. In this case, where the incubation time is M multiplied by the cycle time N (i.e., incubation time=M×N), an alternating process may be used that alternates between a pre-incubation processing step (provided in a pre-incubation subcycle of duration A) and a post-incubation processing step (provided in a post-incubation subcycle of duration B), where A+B=N (total time of the individual cycles). In this case, the alternating process processing cycle may comprise (i) processing plates in a batch using a pre-incubation subcycle or if no plates are available (e.g., all plates have already undergone a pre-incubation subcycle), then idling for a time A, and (ii) processing plates in a batch that has completed M×N hours of incubation using a post-incubation subcycle or if no plates are available (e.g., no plates have completed M×N incubation). Using this alternating method, plates can be processed continuously and there is no upper limit to the batch size. If the analytical process comprises an incubation step of time Y as described above for the time cycled method, then the length of the incubation step determines the batch size that can be performed during the procedure.

[0054] In another example, system 10 may be operated as shown in FIG. 9(b). In step 90, system 10 is started, where consumables such as plates, reservoirs, pipette tips, etc. are loaded as described above. In step 92, a procedure is selected by the operator. In step 94, a first single multi-well assay plate is processed, and a first processing run is performed that includes one or more exemplary processing steps (a)-(f). The use of cycles is carried out. a. Remove a single multi-well tray from the shelf; b. Optionally, washing the single multi-well tray; c. depositing samples to be tested into wells in said single multi-well tray; d. depositing at least one reagent into wells in said single multi-well tray; e. Optionally, washing the single multi-well tray to remove any remaining specimens; f. Place an optional cleaned single multi-well tray into the incubator. The first processing cycle is repeated until the incubator is filled with an additional single multi-well analysis tray, as shown in step 96, i.e., (h) steps (a)-(f) are repeated until the incubator is filled with another single multi-well tray. In this example, the incubation period is the total time for the multi-well tray to fill the incubator. After the incubator is filled with the processing tray, step (g), as shown in step 96, the now fully incubated first tray is removed and optionally processed using a second processing cycle 94, which may include one or more steps (a)-(f). The second processing cycle, if used, is then repeated until the incubator is filled with an additional single multi-well tray. Similarly, additional processing cycles 94 may be performed on a batch of plates as required for a particular analysis procedure. The final processing cycle comprises a processing step (h) (shown in FIG. 9b as step 98) in which the analysis tray is transferred to a plate reader (e.g., an ECL tray reader) for analysis. The final cycle is repeated until all analysis trays are placed in the reader and analyzed in step 99. The number of multi-well trays stored in the incubator is equal to the incubation period divided by the time to complete the longest processing time (i.e., steps (a)-(f) and the final cycle, (h)).

[0055] The method shown in Figure 9(b) can be modified by first determining the number of multi-well trays that can be processed and stored in the incubator for the incubation period, then processing the trays by processing steps (a)-(f). The system can process the remaining trays, and after the first tray is fully incubated, the trays are moved to the reader for ECL analysis on a first-in-first-out basis.

[0056] Any number of procedures may be designed by one of ordinary skill in the art based on the teachings herein, and the present invention is not limited to any particular procedure.

[0057] Description of System 10 Components The machinery and equipment, particularly as shown in Figures 2 and 3 and described above, may be specially designed or commercially purchased. The shelf 22 is preferably specially designed for the intended use. The barcode reader 24 may be a commercial off-the-shelf component. The robotic arm 26 may also be a commercial off-the-shelf component. The plate washer 30 may also be a commercial off-the-shelf component, available from Biotek, Inc. The reader 36 may also be a commercial off-the-shelf component, available from Meso Scale Diagnostics, Inc. as the MESO QuickPlex SQ 120 Reader. This reader is described and claimed in commonly owned pre-grant U.S. Patent Application Publication US2014 / 0191109, which is incorporated herein by reference in its entirety. The multi-channel pipettor 32 and thermoelectric cooler 38 may also be commercial off-the-shelf components. The pipette wash manifold 34 may be specially designed or purchased and modified to improve wash effectiveness. The gantry 42 is preferably designed specifically for the system 10.

[0058] The vibrator 28 may be a commercial off-the-shelf component; however, in the embodiment of the system 10 described above, the vibrator 28 is inventive and is a "Consumable" component. This disclosure is set forth and claimed in commonly owned provisional application entitled "Polymer Shaking Apparatus" filed April 6, 2015, and having Serial No. 62 / 143,557, which is incorporated herein by reference in its entirety. The relevant portions of this prior provisional application are reproduced below.

[0059] The vibrator and incubation apparatus 28 is shown in Figures 10(a)-1(d). The apparatus includes an orbital vibrator assembly (101) including a horizontal track platform (102) and an analytical consumables storage assembly (103) disposed on the platform (102). The storage assembly (103) includes a shelving subassembly (104) and a counterweight (105) disposed within the storage assembly at a height or plane that substantially corresponds to the center of mass of the track components of the apparatus, i.e., the storage assembly and the track platform. The shelving subassembly includes a set of a plurality of vertically aligned storage units. The apparatus shown in Figures 10(a)-1(b) includes a set of four vertically aligned storage units (106-109). Each storage unit (110) is sized to accommodate an analytical consumable (111) and includes a locking mechanism (112) for securing the consumable within the storage unit and ensuring that each consumable placed within a subassembly experiences the same trajectory of vibrational momentum, speed and direction.

[0060] Examples of analytical consumables suitable for use with the present invention include, but are not limited to, vials, flasks, beakers, analytical cartridges and cassettes, microtiter plates, e.g., multi-well plates, slides, analytical chips, lateral flow devices (e.g., strip tests), flow-through devices (e.g., dot blots), solid supports for biological reagents, and the like. In certain embodiments, the test sites in the analytical consumable are defined by compartments in the analytical consumable, e.g., wells, chambers, channel flow cells, and the like. In certain embodiments, the analytical consumable is a microtiter plate, e.g., with 6, 24, 96, 384, or 1536 wells. More particularly, the analytical consumable is a 96-well microtiter plate.

[0061] 10(a) and 1(d), the orbital shaker assembly 101 includes a rotating shaft (113) that extends in a vertical Z-axis from the orbital shaker assembly (101) to the analytical consumables storage assembly (103). A counterweight (105) is operatively connected to the shaft (113) at or near the center of mass plane or a plane containing the center of mass of the analytical consumables storage assembly (103). An upper eccentric (115) is operatively connected to the top of the rotating shaft (113) and to a chassis or surface of the analytical consumables storage assembly (103) which will be described in more detail below.

[0062] Referring to FIG. 10(d), the orbital shaker assembly (101) comprises a drive motor (121) connected to the rotating shafts (113), (123) and (125) by a belt (127). Preferably, the belt (127) is grooved or is a timing belt. One or more pulleys (129) are arranged to ensure that the shafts are driven at substantially the same rotational speed. The shafts (123 and 125) are operatively connected to a first bottom eccentric (131) and a second bottom eccentric (133). The bottom eccentrics (131, 133) are operatively connected to a horizontal track (102) supporting the assembly (103) and are operatively connected directly to the assembly (103), and the top eccentric (115) is attached to the chassis or to a surface of the analytical consumable storage assembly (103) as described above. The axially extending axial direction of the axially extending axial assembly (103) is connected to act at or near a plane containing the center of mass of the axially extending axial assembly (103).

[0063] The eccentrics (115, 131 and 133) are cylindrical components disposed around the rotating shaft (113, 123 and 125 respectively) and having inner and outer diameters (125 and 137 respectively) that do not share the same centerline. The rotating shaft is received within the inner diameter of the eccentrics, which in turn are received within ball bearing receivers in the horizontal track (102) that supports the analytical consumable storage assembly (103) and / or within ball bearing receivers adapted to receive the upper eccentric (115) as best shown in FIG. 10(a). The distance between the centerlines of the inner and outer diameters of the eccentrics determines the orbit radius of the device. For example, in the embodiment shown in FIG. 10(c), the distance between the centerlines of the inner and outer diameters is 2 mm, and thus the orbit radius is 2 mm, although this configuration may be adjusted without departing from the spirit or scope of the invention. In one embodiment, all rotating parts (eg, motor, drive shaft, and counterweight) rotate at the same speed and in the same direction.

[0064] In another embodiment, at least two bottom eccentrics (131 and 133) are attached to the horizontal track mount (102) to minimize, and preferably prevent, the analytical consumable storage assembly (103) from rotating about a single axis of rotation. Preferably, the top eccentric (115) is used to minimize or prevent the shaft (113) from orbiting, where the shaft (113) should primarily or only rotate. Additional bottom and top eccentrics may be used. To help ensure that the entire analytical consumable storage assembly (103) orbits uniformly about a vertical axis, similarly sized eccentrics are used at the bottom mounting plate and at the top of the shaft (113) to mechanically restrain the shaft vertically. To minimize vibration, all eccentrics preferably rotate in phase with each other. Preferably, the shafts (113, 131 and 133) connecting the eccentrics to the drive pulleys rotated by the belt (127) have a single axis of rotation.

[0065] In yet another embodiment, the eccentric rotates and the storage assembly orbits, but preferably does not rotate. The rotational positions of the eccentrics about the axes of their shafts correspond to the orbital positions of the storage assembly about its central axis. The upper eccentric (115) is preferably positioned approximately 180° out of phase with the counterweight (105). The counterweight (105), provided to minimize undesirable turbulence, or tendency to "walk", as best shown in FIG. 10(c), has an adjustable component 106 that can be moved toward or away from the rotating shaft (113) to increase or decrease the angular thrust of the counterweight. In one non-limiting example, the mass of the analytical consumable storage assembly (103) is approximately 5,000 grams and the mass of the counterweight (105) is approximately 412 grams.

[0066] The system spring constant (K) of the analytical consumable storage assembly (103) is preferably substantially high so that the resonant frequency is:

number

[0067] Detailed drawings of the shelving subassembly (104) are shown in Figures 11(a)-(c). The shelving assembly includes a housing (201) having a top (202), a rear (203), left and right housing walls, which may be double walls (204 and 205, respectively), and a set of multiple vertically aligned storage units. Two sets of vertically aligned storage units are shown in Figures 11(a)-(b) (206 and 207, respectively). The storage units within a set are stacked in an aligned fashion (e.g., 208-209), each storage unit including an entry opening (210) and a door configured to seal the opening (211).

[0068] The shelving subassembly comprises an array of sets of vertically arranged storage units. The array may be linear, circular, or polygonal. In one embodiment, the array is an M×N linear array of vertically arranged sets of storage units, where M and N are integers. One embodiment of a linear array is shown in FIGS. 11(a)-(b), which includes two sets of storage units (206 and 207, respectively) adjacent to each other in the subassembly forming a 2×1 array. Alternative configurations of linear arrays are shown in FIGS. 11(d)-(f), which show a 2×2 array (2(d)), a 3×3 array (2(e)), and a 4×4 array (2(f)). Additionally, the array may be polygonal or circular, as shown in FIGS. 11(g)-(i). Where the array is polygonal, it may be a regular polygon, for example a triangle, pentagon, hexagon, heptagon, octagon, nonagon, decagon, or dodecagon, as shown in Figures 11(g) and 11(h), where X is an integer from 1 to 7. Alternatively, the array is circular, as shown in Figure 11(i). In the embodiment shown in Figures 11(g)-(i), the array comprises a set of 360° / P store units, where P is an integer, arranged within the shelving subassembly about a central axis (212-214, respectively).

[0069] Each shelving subassembly may contain up to 100 individual storage units, preferably up to 40 individual storage units, and more preferably up to 24 individual storage units. Those skilled in the art will readily appreciate that numerous configurations of sets of storage units in the shelving subassemblies may be configured that vary the number of sets, as well as the number of vertically arranged storage units in a given set or collection of sets, so long as the apparatus includes sufficient counterweights located within the storage assemblies at an elevation corresponding to the combined center of mass of the storage assemblies and the track. In certain embodiments, each adjacent set of storage units that share adjacent walls (215, e.g., 206 and 207) includes the same number of storage units.

[0070] As shown in Figures 12(a)-(b), the device may include two or more counterweights, where the counterweights are evenly distributed such that the resulting center of mass of the counterweights coincides with the combined center of mass of the orbiting components. As mentioned above, a single counterweight may be positioned to coincide with the center of mass of the orbiting components. In the embodiment shown in Figure 12(a), two or more counterweights (301 and 302, respectively) are in operative communication with the axis of rotation (303). Preferably, the counterweights (301, 302) are symmetrically positioned above and below the center of mass plane of the system shown in Figure 12(b). Alternatively, as shown in Figure 12(b), a first counterweight (304) is in operative communication with a corresponding first rotating shaft (305) and a second counterweight (306) is in operative communication with a corresponding second rotating shaft (307), where each shaft is driven by a timing belt (308) such that each rotating shaft is driven in unison by the orbital oscillator assembly. Preferably, the counterweights (304, 306) are located at or near the center of mass plane of the actuation system shown in Figure 12(b).

[0071] Any suitable orbital vibration mechanism may be used in the device, the disclosure of which is incorporated herein by reference. As described in U.S. Patent No. 5,558,437, which is incorporated by reference herein, conventional vibratory mechanisms may drive a platform in an orbital motion and include one or more vertical shafts driven by a motor with an offset or a crank at the top end of the top shaft such that the axis of the upper shaft moves in a cycle with a radius determined by the offset of the shafts, i.e., by a crank throw. The upper shaft or shafts are connected to the underside of the platform through bearings to decouple from the rotational motion between the upper shaft or shafts and the platform. In compound shaft mechanisms, rotation of the platform is generally prevented by a four bar coupling mechanism of the shafts. In single shaft mechanisms of the platform, rotation of the platform is generally prevented by connecting an additional coupling or a mating coupling between the platform and the base.

[0072] As mentioned above, each storage unit is sized to accommodate an analytical consumable, e.g., a microtiter plate, and includes a locking mechanism for securing the consumable within the storage unit. An exemplary plate locking mechanism is shown in Figures 13(a)-(d) that is configured to receive and engage an exemplary plate disposed on the storage unit platform (401) (or a consumable having the same footprint and external physical form such as a multiwell / microtiter plate configured for use in an apparatus as described herein). The plate has at least a first, second, third, and fourth side, the first and third sides being substantially parallel to one another, and the second and fourth sides being substantially parallel to one another. The outer edge of the plate includes a skirt (402) that surrounds the walls of the plate and is of a lower height than the walls of the plate, in accordance with standard design conventions for multiwell / microtiter plates (a close-up view is shown in Figure 13(b)). The plate locking mechanism is designed to press the outer edge of the skirt against two corresponding physical stops on the plate platform on two orthogonal sides of the plate, and for repeatability applies a downward physical force at a defined location on the top of the plate skirt to hold the plate fixed.

[0073] In the embodiment shown in FIG. 13(a), the plate locking mechanism (403) is perpendicular to the edge of the platform aligned with the plate entry opening of the storage unit (404). The plate locking mechanism comprises a locking member (405) that is biased to lock into position and constitutes two pedals (406 and 407, respectively). Two cleats (408 and 409, respectively) located on the same side as the pedals (406, 407) and cleats (421, 422) located on the opposite side configured to vertically restrain the plate skirt. Referring to FIG. 13(c), a first pedal (406) is adapted to push a first side of the multiwell plate against a first cleat (408) that engages the plate skirt (402). The first cleat (408) engages the plate skirt and provides a hard mechanism limit to the vertical movement of the plate. As the plate is pushed towards the inside of the platform, the second cleats (409) engage the plate skirt, further restricting vertical movement of the plate skirt. When the plate is fully inserted into the platform, as shown in FIG. 13(d), the locking mechanism is fully engaged and the first and second cleats (408, 409), along with the opposing third and fourth cleats (421, 422) engage the plate skirt, limiting vertical movement of the plate. Pedal (407) provides a side bias to the plate and pedal (406) provides a side and rear bias to the plate. In the embodiment shown in FIG. 13(d), the plate is pushed against the rear end of the plate platform (410) opposite the plate entry opening, as well as the side of the platform opposite the locking mechanism (411).

[0074] In accordance with another aspect of the present invention, an optional air flow path (425) is provided within the analytical consumables storage assembly (103), as best seen in Figures 14(a) and 14(b). This air flow path (425) is preferably configured to route between the horizontal track (102) and the lower shelf subassembly (106-109) to allow cooling air to flow through and circulate within the analytical consumables storage assembly (103) and between the preferably vertically aligned storage units (106-109). 4) and a plurality of horizontal air shafts (429) interconnecting the plurality of vertical air shafts (427) between the upper and lower shelf subassemblies 104 and 106. An air exhaust or blower assembly (431) is provided to draw air through this gap. Alternatively, the air exhaust or blower assembly (431) may push air into the air flow path (425). Another optional air shaft may be provided in the space between the upper shelf subassembly 104 and the lower shelf subassembly 104.

[0075] Example 1 The system 10 is designed for ultra-high throughput testing of clinical samples with ECL detection technology, such as that of Meso Scale Diagnostics ("Meso Scale") of Rockville, Md. To achieve high throughput, the system 10 uses multiple tests in a 96-well plate format and can process batches of up to 20 plates. It has a central robotic arm 26 that moves plates between the components that perform the different analytical steps, a channel pipetter 32, a barcode reader, a plate washer 30, a plate shaker 28, and a plate ECL reader 36 from Meso Scale. The system 10 is a standalone, fully automated system. The system 10 is functional and the beta unit is used at Meso Scale.

[0076] Key features of the platform of system 10 include, but are not limited to: 1. Batching of 20 or fewer assay plates (1600 samples + 16 wells per batch, assuming 80 singlicate samples per plate used for calibrators or controls); 2. High throughput of 12,800 samples per day (8 batches of 20 plates per day) 3. All pipetting and washing steps are performed using a 96-channel component capable of simultaneously processing all wells in a plate; 4. The analytical process is carried out in a temperature-controlled enclosure, with all steps precisely synchronized to provide more reproducible and accurate results. A specially designed shaker with 5.20 plate capacity (described in commonly owned provisional application Ser. No. 62 / 143,557, incorporated herein in its entirety) provides fast antibody binding kinetics, with each plate incubated in a separate enclosed chamber within the shaker to prevent evaporation; 6. The ability to perform sample dilutions, 7. The method is simply designed to include one that does not require interleaving of analytical procedures.

[0077] System 10 uses individual off-the-shelf and specially designed components as one fully automated system. The off-the-shelf components include a MESO QuickPlex® SQ 120 Reader (available from Meso Scale), a BioTek® 96-channel plate washer, a Precise Automation® plate handling robot, a barcode reader, and an Apricot Designs™ 96-channel pipetting head. The specially designed platform components include a plate hotel / shelf, a 20-plate vibrating incubator, two pipette tip washing manifolds, a four pipetting plate pipette deck, and a pipetter gantry to support the pipetting head. The deck and all components are housed within an enclosure with a heating / cooling unit that maintains the enclosure at a set temperature (FIGS. 2 and 3).

[0078] The platform reaches ultra-high throughput by using a 96-channel assembly to process an entire 96-well plate at once. This method allows processing operations to be divided into a series of processing cycles separated by incubation periods, where any particular The time associated with a processing cycle is a discrete amount of time, e.g., less than 3 minutes. It is therefore possible to plan each cycle on each plate to be run at 3 minute intervals, simplifying the planning of operations while maintaining strict control over the timing of each cycle. By separating each analysis cycle with a 1 hour binding reaction incubation, a batch of, e.g., 20 plates, can be run while maintaining a 3 minute interval between plates over multiple analysis cycles. The system can be scaled to even higher throughputs.

[0079] By way of non-limiting example, in the case of biological dosimetry (see Example 2), the system 10 performs a single incubation analysis with the following automated analytical processing steps divided into cycles: 1. Sample addition cycle, a. The robot removes plates (with samples), reagent tanks (with detection antibody lysates), and analysis plates (MSD®, Multi-Array plate with capture antibody array, from Meso Scale) from the plate hotel / shelf and places them on the deck; b. The robot lifts the lid from the resource plate to allow pipettor access; c. The pipettor transfers the sample and detection antibody to the wells of the assay plate; d. The robot moves the assay plate to the shaker for a 1 hour incubation; e. The pipette tips are washed using a wash manifold; 2. Plate reading cycle (scheduled for 1 hour after step), a. The robot removes the assay plate from the shaker and places it in the washer; b. The plate washer washes the wells three times with wash buffer to remove the samples; c. The robot moves the assay plate and the reagent tank with lead buffer to the deck; d. The pipettor transfers the Lead Buffer to the wells of the assay plate; e. The robot moves the plate to the MSD SQI20 plate reader for analysis.

[0080] By maintaining a 3 minute interval between plates, it is possible to process 20 plates in a batch with a time to first result of 1 hour and a time to last result of 2 hours while maintaining tight control over the timing of each cycle. Optionally, the binding of sample and detection antibody can be separated into two separate cycles with a 1 hour incubation separated to achieve optimal analytical performance. In this case, the time to first result for a 20 plate batch can be 2 hours and the time to last result can be 3 hours.

[0081] To prepare the system and reagents to perform biodosimetry tests in a batch of 20 plates, the operator follows the steps described below: The lyophilized detection antibody is rehydrated and transferred to the reagent tank. Lead buffer, supplied as a liquid volume reagent, is added to a second reagent reservoir; The freeze-dried calibrators and controllers (supplied with the kit in tubes with the kit) are rehydrated, Samples, controllers, and calibrators are transferred from the tubes to a 96-well resource plate. In a duplicate 2 controller, columns 1 and 2 in the plate are reserved for running a 7-point calibration curve, and columns 3 to 12 are used for 80 samples), This step can be performed manually or for higher throughput by automated sample delivery workstations that exist in many clinical laboratories; The user logs into the system using his or her login credentials, The user selects the analysis type (in this case a biodosimetry test), which defines the analysis procedure settings including dispense volumes, incubation times, etc. The software provides a graphical view that allows the user to add MSD analysis plates, resource plates, and reagent tanks to the plate rack; The system runs a setup routine to take an inventory of all resource plates and all component reagent tanks to verify their location (barcodes are read), the system also verifies that volumetric reagents have been replaced by the user, The system performs the automated biodosimetry analysis procedure (described above), Used analytical plates / tanks are removed from the plate hotel / shelf and Results are calculated by the software and displayed in the touchscreen GUI.

[0082] System 10 can process 20 plates in 2 hours. For maximum throughput, the next set of 20 sample resource plates (including samples, calibrators, and controllers) can be prepared while the current set of 20 plates is being run. The resource plates can be prepared manually, however, a commercial off-the-shelf system for reconstituting samples can be used to complete this task more efficiently and maintain the same throughput as system 10. Automated systems present in many large clinical laboratories can spin blood tubes, uncapped tubes, and pipette plasma samples into predefined layouts into the sample resource plates of system 10. These systems can be further programmed to send calibrators and controllers to the sample resource plates, or the user can perform this task manually once the samples have been processed and added to the resource plates. The software for the system has the capability of communicating with these automated systems to upload the location of each sample (identified by a unique barcode ID) within each resource plate (further identifiable by a unique barcode ID).

[0083] Example 2: Biological dosimetry analysis A detailed description of biodosimetry analyses and algorithms that may be obtained using the apparatus and / or method according to the invention is described in US Patent Application No. 14 / 348,275 (US Publication No. 2014 / 0315742), which is incorporated by reference in its entirety. Included in this application is the use of a panel of six radioactive biomarkers (Flt-3 L, CD20, CD 177, TPO, LBP, salivary amylase) in plasma or blood to estimate individual exposure doses to radiation. This particular panel is described for illustrative purposes. The invention encompasses the use of the apparatus and methods described herein to perform the analysis of any one of these biomarkers alone or in combination with other analytes, or in any combination of two, three, four, or five of these biomarkers, with or without other analytes in the same analytical panel. Specifications for such tests in the system 10 are outlined below. [Table 1] [Table 2]

[0084] Types of Analysis That May Be Performed in System 10 System 10 can be configured to perform any number of assay formats by varying the processing cycle used to process the assay plate (as described above). Although several exemplary examples are provided below for different immunoassay formats, the basic method is clearly applicable to other assay formats, including binding assays using non-antibody based binding reagents (e.g., nucleic acid mix assays). System 10 is specifically designed to perform assays using ECL detection and the Meso Scale (MSD) MULTI-ARRAY®, although the methods are applicable to techniques using other multi-well plate consumables and detection technologies.

[0085] The different assay formats are described by a table listing the process cycles used by system 10 to complete the assay process. Each cycle includes one or more of the following assay steps: (i) using the robotic arm to select the desired plate from a hotel or shaker and moving the plate to a washer for plate washing; The cycle may include a number of steps, (ii) using a robotic arm to move a destination plate to the pipette deck for pipetting, (iii) and (iv) selection of up to two resource / reagent plates including moving the plates from the hotel to the pipette deck and using a pipettor to deliver lysate to the destination plate, (v) a pipette wash step (after each plate undergoing a particular cycle or only after the last plate), (vi) sending the destination plate to an incubation position where incubation can be performed with vibration (i.e., in a shaker) or without vibration (in a plate hotel), and (vii) sending to a plate reader to perform analytical measurements. The table lists which steps are performed in each cycle and identifies the destination and source / reagent plates by their contents, where "capture", "detection" and "sample" refer to the resource / reagent plate containing the capture reagents, detection reagents, or sample, respectively.

[0086] Two-Step Sandwich Immunoassay. In a two-step sandwich immunoassay, the wells of an MSD assay plate (with one capture antibody or an array of capture antibodies immobilized at the bottom of each well) are first incubated with the sample diluted in assay diluent, then with a labeled detection antibody before measurement of the labeled sandwich complex that forms. The procedure includes a blocking cycle as the first cycle as shown, and optionally this cycle can be omitted. One simple variation of this procedure includes an additional cycle (3a) between cycles 3 and 4. This procedure is used when the detection reagent in cycle 3 does not carry a label in a format that can be detected in the reader. Cycle 3a is like cycle 3, except that the source plate 1 includes a labeled second reagent that combines the detection reagent with a label suitable for the reader. The use of a labeled second detection reagent is well known in the art. Specific examples include the use of a labeled anti-specific antibody to detect the antibody detection reagent, or the use of labeled streptavidin to detect the biotin containing detection reagent. [Table 3]

[0087] Sandwich assays include an antibody immobilization step. This procedure is similar to the sandwich assay described above, except that instead of using an assay plate pre-coated with a capture antibody, the assay plate is either uncoated or coated with a common capture reagent such as streptavidin. The procedure therefore includes an additional cycle during which the capture antibody is absorbed to an uncoated plate or captured by binding to a capture reagent (e.g., biotin targeting of immobilized streptavidin in the wells). Cycle 1 is a cycle in which the collection reagents are immobilized at a rate of 1000 μg / ml (by binding of the identified collection antibody). As in the previous table, the blocking cycle can be omitted. The procedure described in the table can be used to stop a single collection reagent per well, or can be used for lysis liquid phase assembly of an array of collected reagents as described in U.S. Published Patent Application No. 20140256588. For example, the wells in an assay plate can each have an immobilized array of different target reagents (e.g., oligonucleotides), and the collection reagents (i.e., the contents of resource plate 1 in cycle 1) can be a mixture of different collection reagents (e.g., oligonucleotide complements to the target substance) that are bound to the different target reagent complements, such that the target reagents and their complements bind when this mixture is incubated in the well, and the different collection reagents are immobilized at different elements of the target reagent array to form the collection reagent array. [Table 4]

[0088] Bridging immunogenicity / serology analysis. In this procedure, antibodies against a particular antigen or drug are identified by their ability to bind two copies of the antigen or drug simultaneously to form a sandwich complex. In the embodiment illustrated in the table, a mix (master mix "mastermix") of antigen conjugated to biotin (or some other binding reagent) and antigen conjugated to a label detectable in the System 10 plate reader (such as an ECL label) is aliquoted into a plate (master mix plate). Sample and acid are transferred into a plate (treatment plate) to dissociate any antibody complexes that may be present in the sample. The acid-treated sample and neutralizing buffer are then combined with the master mix and incubated to allow the formation of a sandwich complex of biotin antigen, antibody of interest, and labeled antigen. The resulting lysate is then transferred to an analysis plate with wells containing immobilized streptavidin (or a suitable binding partner) for the binding reagent conjugated to the antigen and incubated to collect sandwich complexes to the immobilized streptavidin, which can be measured in a plate reader. In some cases, it may be preferable to perform this procedure without acid digestion, in which case the acid in resource plate 1 in cycle 3 may be replaced with a non-acidic diluent buffer, and optionally the neutralization buffer may be omitted or replaced with analysis diluent. Alternatively, cycle 3 may be omitted entirely, and samples may be added directly to the master mix plate in cycle 4 (i.e., resource plate 2 is the sample plate). Since incubations after cycles 1 and 2 occur in the plate hotel, these incubations are not necessary. Note that incubations for subsequent cycles may continue in parallel until a result plate is required in each of cycles 4 and 5. [Table 5]

[0089] Amplified immunoassay. System 10 may be used to perform binding assays that use an amplification step to improve sensitivity. In the above-mentioned two-step immunoassay example, the process may include an additional cycle (3a) between cycles 3 and 4 to prepare or perform the amplification procedure. If the detection reagents include an enzyme label, cycle 3a may include the addition of an enzyme substrate (at resource plate 1) to the analysis plate (destination plate), where modification of the substrate by enzyme reading is detectable by the reader. Alternatively, cycle 3a may be omitted and substrate may be added in cycle 4 from resource plate 1 or 2 just before sending the analysis plate to the reader. If the detection reagents include a nucleic acid label, cycle 3a may include the addition of reagents for amplification of the label from resource plate 1 and / or 2 (e.g., by PCR or isothermal nucleic acid), where amplification is obtained in a subsequent incubation period. The table below describes automated assay steps for performing an amplified binding assay as described in US Published Patent Application No. 20140272939 in the context of an immunoassay using antibodies as analyte binding reagents, however the steps can obviously be applied to assays using other types of binding reagents. Each well of the MSD assay plate has an immobilized capture antibody, i.e., optionally co-immobilized with an immobilization reagent comprising a sequence for immobilizing an oligonucleotide. The procedure includes an optional blocking cycle (cycle 1), followed by a cycle for adding sample to bind the analyte to the capture antibody (cycle 2) and a cycle for adding detection reagent to bind the collected analyte (cycle 3). In this embodiment, In the binding cycle (cycle 3), a binding synthesis is loaded into each well with a ligase and one or more connecting nucleic acid sequences that are linear sequences with regions complementary to the first and second probes, such that when incubated in the presence of one of the complexes of the collection antibody, the analyte, and the first and second detection antibodies, the connecting sequence(s) bind to the first and second probes in the complex to form a circular nucleic acid sequence. If any oligonucleotide immobilization is included, the connecting sequence(s) include a fixed region that matches a region of the fixed sequence (i.e., they are both synthesized to the same complementary sequence). In the amplification cycle (cycle 4), an amplification synthesis is loaded into each well with a DNA polymerase and a labeled detection probe (with a detection sequence that matches a detection region in the connecting sequence(s)). When the amplification compound is incubated in the presence of circular nucleic acid immobilized on the first and second probes, the first probe is elongated by rolling circle amplification and the labeled detection probe immobilizes the elongated entity. The elongated entity also binds to immobilizing reagents, if present. In the read cycle, read buffer is added to the wells and the labeled probe is detected in the reader to measure the presence of the analyte. [Table 6]

[0090] The present invention is not limited in scope by the specific embodiments described herein. Indeed, various modifications of the present invention in addition to those described herein will become apparent to those skilled in the art from the foregoing description and accompanying drawings. Such modifications are intended to fall within the scope of the appended claims. Various publications have been cited herein, the disclosures of which are incorporated by reference in their entireties. The technical features described herein are listed below. [Technical feature 1] 1. A counterbalanced analytical consumable vibration device comprising: (a) an orbital shaker assembly having a horizontal track platform; (b) an analytical consumable storage assembly disposed on the platform, the storage assembly comprising: (i) a shelving subassembly comprising a set of a plurality of vertically arranged store units, each store unit being dimensioned to receive a consumable item and including a consumable locking mechanism; (ii) The counterbalanced analytical consumable vibrating device comprises either (a) a counterweight disposed within the storage assembly at a height corresponding to the center of mass of the storage assembly and the track, or (b) two or more counterweights disposed within the storage assembly, wherein the combined center of mass of the two or more counterweights is the same as or corresponds to the center of mass of the storage assembly. [Technical feature 2] The apparatus according to technical feature 1, further comprising a rotation axis extending vertically from the vibrator assembly to the storage assembly, and the counterweight(s) are connected to act on the rotation axis. [Technical feature 3] The apparatus according to technical feature 1, wherein the storage assembly is attached to the platform. [Technical feature 4] The apparatus described in technical feature 1, wherein the shelf mounting subassembly comprises a housing including a housing top, a housing rear, and left and right housing walls, and the set of multiple vertically arranged storage units is disposed within the housing, each storage unit including a consumable introduction opening and a door configured to seal the introduction opening. [Technical feature 5] The apparatus of technical feature 4, wherein the shelving subassembly comprises an M×N linear array of sets of vertically arranged storage units, where M and N are integers. [Technical feature 6] The apparatus according to technical feature 5, wherein the array is selected from 2x1, 2x2, 3x3, or 4x4. [Technical feature 7] The apparatus of technical feature 6, wherein the shelving subassembly comprises a 2×1 array of storage units. [Technical feature 8] The apparatus of technical feature 4, wherein the shelving subassembly comprises an annular array of sets of P vertically arranged storage units arranged in the array at increments of 360° / P, where P is an integer. [Technical feature 9] The apparatus according to technical feature 8, wherein the set of vertically arranged storage units are arranged around a central axis in the annular arrangement. [Technical feature 10] The device according to technical feature 4, wherein the consumable is a microtiter plate. [Technical feature 11] 11. The device according to technical feature 10, wherein the microtiter plate is selected from a 6, 24, 96, 384 or 1536 well plate. [Technical feature 12] The device according to technical feature 11, wherein the microtiter plate is a 96-well microtiter plate. [Technical feature 13] 5. The device according to claim 4, wherein the door is spring loaded. [Technical feature 14] 14. The device according to technical feature 13, wherein the door is mounted to act on a door locking mechanism. [Technical feature 15] The apparatus of technical feature 4, wherein the shelving subassembly comprises a polygonal array of sets of P vertically arranged storage units arranged in the array in increments of 360° / P, where P is an integer. [Technical feature 16] 16. The device according to technical feature 15, wherein the array comprises a regular polygon. [Technical feature 17] 17. The apparatus according to technical feature 16, wherein the regular polygon comprises a triangle, a square, a rectangle, a pentagon, a hexagon, a heptagon, an octagon, a nonagon, a decagon, or a dodecagon. [Technical feature 18] The apparatus described in Technical Feature 1, wherein the shelving subassembly comprises at least two vertically arranged storage units. [Technical feature 19] 20. The apparatus of claim 18, wherein the shelving subassembly comprises 20 or less vertically arranged storage units. [Technical feature 20] The apparatus described in Technical Feature 1, wherein the storage assembly comprises a set of two or more vertically arranged storage units. [Technical feature 21] The apparatus described in technical feature 20, wherein the two or more sets of vertically aligned storage units are arranged in the storage assembly around a central axis in an A×B linear array of shelving subassemblies, where A and B are integers. [Technical feature 22] 22. The apparatus according to technical feature 21, wherein the array is selected from 2x1, 2x2, 3x3, or 4x4. [Technical feature 23] 23. The apparatus of technical feature 22, wherein the array comprises a 2×1 array of vertically arranged sets of storage units. [Technical feature 24] 21. The apparatus of technical feature 20, wherein the two or more sets of vertically aligned storage units are arranged within the storage assembly about a central axis in a circular arrangement of 360° / R storage units, where R is an integer number. [Technical feature 25] The apparatus according to technical feature 1, further comprising a plurality of eccentrics orbitally connecting corresponding rotation axes to the horizontal rail. [Technical feature 26] The apparatus according to technical feature 25, further comprising at least one eccentric orbitally connecting another corresponding rotation axis to the analytical consumable storage assembly. [Technical feature 27] 27. The apparatus according to any one of technical features 25 to 26, wherein each eccentric comprises a cylindrical body having inner and outer diameters that do not share the same centerline. [Technical feature 28] The apparatus of technical feature 1, wherein the analytical consumable storage assembly further comprises an internal air flow path fluidly connected to a blower assembly. [Technical feature 29] 1. A method of operating an analytical system for analyzing a batch of analytical plates, comprising the steps of: (i) each plate in the batch is subjected to a series of different treatment cycles of length N; (ii) for a given plate in the batch, the series of different treatment cycles are separated by an incubation period of at least Y time; (iii) each of the series of different processing cycles is performed sequentially on the plates in the batch; (iv) the number of plates in the batch is less than or equal to Y / N. [Technical feature 30] 1. A method of operating an analytical system for analyzing a sequence of analytical plates, comprising the steps of: (i) each plate in the batch is subjected to a series of different treatment cycles of length N; (ii) at least one of said series of cycles is an alternating cycle divided into a pre-incubation subcycle of length A and a post-incubation subcycle of length B, where A+B=N, and in a given plate, the completion of the subcycle of length A and the start of the subcycle of length B are separated by an incubation time that is a multiple of N; (iii) (a) identifying the first plate in the sequence that has not undergone the pre-incubation subcycle and performing the pre-incubation subcycle thereon or when no plate is available for pre-incubation processing and then idling for a time A; (b) performing said alternating cycles in said sequence of plates by identifying said first plate in said sequence that has completed said incubation but has not undergone said post-incubation subcycle and performing said post-incubation subcycle thereon or when no plate is available for post-incubation processing and then idling for a time B; (iv) repeating step (iii) until all of the plates in the sequence have undergone the pre-incubation and post-incubation subcycles. [Technical feature 31] 31. The method according to technical feature 29 or 30, wherein the system comprises a plate handling robot, a processing deck, a plate hotel, a pipette dispenser, a plate washer, a vibrating incubator, and a plate reader. [Technical feature 32] The process cycle comprises the following steps: a. using the robot to move a single assay plate of the batch from the hotel or incubator to the deck; b. using said robot to move sample or reagent plates from said hotel or incubator to said deck; c. using the pipettor to transfer samples or reagents from the sample or reagent plate on the deck to the analysis plate on the deck; d. using the plate washer to wash the wells of the assay plates on the deck; e. using the robot to deliver the assay plates on the deck to the hotel or an incubator; f. The method according to technical feature 31, comprising one or more steps of using the robot to transport the analysis plate to the plate reader. [Technical feature 33] 33. The method according to any one of technical features 31 to 32, wherein the analysis plate is equipped with electrodes for performing ECL measurements and the plate reader is an ECL reader. [Technical feature 34] The different processing cycles include: (i) a sample addition cycle; (ii) a detection reagent addition cycle; (iii) a plate reading cycle. [Technical feature 35] 35. The method according to technical feature 34, wherein the different processing cycles further comprise a shut-off cycle. [Technical feature 36] 33. The method according to technical feature 32, wherein at least one of the processing cycles further comprises a step of incubating an analysis of a sample or a reagent plate, the incubation time being shorter than time N. [Technical feature 37] said series of at least one said cycle is an alternating cycle divided into a pre-incubation subcycle of length A and a post-incubation subcycle of length B, where A+B=N, and in a given plate, the completion of said subcycle of length A and the initiation of said subcycle of length B are separated by an incubation time that is a multiple of time N; The alternating cycles in the batch of plates include: (i) identifying the first plate in the batch that has not undergone the pre-incubation subcycle and performing the pre-incubation subcycle thereon or when no plates are available for pre-incubation processing and then idling for a time A; (ii) identifying the first plate in the batch that has completed the incubation but has not undergone the post-incubation subcycle and performing the post-incubation subcycle thereon or when no plate is available for post-incubation processing and then idling for a time B; (iii) repeating step (ii) until all of the plates in the batch have undergone the pre-incubation and post-incubation subcycles. The method according to any one of technical features 29 to 30, [Technical feature 38] 1. A method of operating an ECL immunoassay system comprising a plurality of assay plates, each plate being completely processed before the next plate is processed, and the incubation period of the plate divided by the processing period of each plate being equal to the number of the plates being processed. [Technical feature 39] 1. A method of operating an ECL immunoassay system, the system comprising a pipette dispenser, a plurality of multiwell plates adapted to store ECL complexes attached to electrodes contained within the multiwell plates, an incubator, and an ECL reader, the method comprising the steps of: a. removing a single multiwell plate from a shelf; b. Optionally, washing the single multi-well plate; c. depositing samples to be tested into the wells in the single multi-well plate; d. depositing at least one reagent to form a complex with an analyte in the sample; e. Optionally, washing the single multi-well plate to remove residual specimens; f. placing the washed single multiwell plate into the incubator; g. Repeating steps a-f with another single multi-well plate until the incubator is filled, the duration of incubation being determined by the time the incubator is filled. the repeating step, wherein the time for filling the multiwell plate with h. placing the fully incubated multiwell plate into the ECL reader. [Technical feature 40] 40. The method according to technical feature 39, wherein step g is repeated until all incubated plates are placed in the ECL reader. [Technical feature 41] 40. The method according to technical feature 39, wherein the number of multi-well plates stored in the incubator is equal to the incubation period divided by the time to complete steps a-f. [Technical feature 42] 1. An ECL immunoassay system comprising: a housing enclosing a pipette dispenser; a plurality of multiwell plates adapted to hold ECL complexes attached to electrodes contained in the plates; an incubator; an ECL reader; and a cooler, the cooler disposed near a rear surface of the housing, the housing further comprising a flow plenum that directs air flow from the cooler to a front surface of the housing. [Technical feature 43] The system described in technical feature 42, wherein the flow plenum is disposed near an upper surface of the housing. [Technical feature 44] The system described in technical feature 42, wherein the flow plenum is disposed near a bottom surface of the housing. [Technical feature 45] 44. The system of technical feature 43, wherein the flow plenum is a space between the upper surface and a second upper surface disposed below the upper surface. [Technical feature 46] 46. ​​The system of claim 45, wherein the second upper surface comprises at least one inlet opening near the cooler and at least one exhaust opening front surface. [Technical feature 47] The system according to technical feature 42, wherein the cooler comprises at least one thermoelectric cooler. 1. An apparatus for cleaning at least one pipette tip, comprising: at least one chimney defining an opening adapted to receive at least one pipette tip; a gap between the at least one pipette tip and the at least one chimney being substantially constant; and the at least one chimney being fluidly connected to a cleaning fluid, the cleaning fluid being pumped through the gap to clean the exterior of the at least one pipette. [Technical feature 49] The apparatus according to technical feature 48, further comprising a level sensor attached to a side wall of the housing of the apparatus. [Technical Features 50] 49. The apparatus of technical feature 48, further comprising a flow restrictor disposed between the at least one chimney and a manifold in fluid communication with the cleaning fluid. [Technical features 51] 1. A method for cleaning a pipette tip, comprising: (a) multiple steps of washing the inside of the pipette tip including aspirating incrementally increasing volumes of a washing solution of progressively cleaner water; (b) multiple steps of washing the exterior of the pipette tip with the same washing solution, wherein the pipette tip is positioned adjacent a gap of constant thickness to control the flow of washing solution. [Technical features 52] The method according to technical feature 51, further comprising the step of washing the pipette tip in a dissolving solution of water and bleach prior to steps (a) and (b). [Technical features 53] The method according to technical feature 51, further comprising a step of minimizing sample or reagent carryover. [Technical feature 54] 54. The method according to technical feature 53, wherein the step of minimizing carryover comprises the steps of (i) at least one washing step to physically remove material at the pipette tip and (ii) an inactivation step. [Technical features 55] 55. The method according to technical feature 54, wherein the inactivation step reduces the ability of the material to affect the analytical result. [Technical Features 56] 56. The method according to technical feature 55, wherein the step of deactivating comprises treating the pipette tip with heat, electromagnetic radiation and / or a chemical reactant that reacts with the material. [Technical Features 57] 56. The method of claim 55, wherein the chemical reactant comprises at least one of a bleaching agent, hydrogen peroxide, an acid or base, a cross-linking agent, or an alkylating agent.

Claims

1. 1. An apparatus for cleaning at least one pipette tip, comprising: at least one chimney defining an opening adapted to receive at least one pipette tip; a gap between the at least one pipette tip and the at least one chimney being substantially constant; the at least one chimney being fluidly connected to a cleaning fluid, the cleaning fluid being pumped through the gap to clean an exterior of the at least one pipette tip.

2. The apparatus of claim 1 , further comprising a level sensor mounted to a side wall of a housing of the apparatus.

3. The apparatus of claim 1 , further comprising a flow restrictor disposed between the at least one chimney and a manifold in fluid communication with the cleaning fluid.

4. 10. The device of claim 1, comprising a plurality of chimneys adapted to accommodate a plurality of pipette tips.

5. The apparatus of claim 1 including at least one manifold having said at least one chimney.

6. 2. The apparatus of claim 1, further comprising an outer shape of the at least one pipette tip that conforms to an inner surface of the at least one chimney to maintain a constant clearance between the at least one pipette tip and the at least one chimney.

7. 1. A method for cleaning a plurality of pipette tips, comprising: (a) multiple steps of washing the inside of the pipette tip including aspirating incrementally increasing volumes of a washing solution of progressively cleaner water; (b) multiple steps of washing the exterior of the multiple pipette tips with the same washing solution, wherein the multiple pipette tips are positioned near a gap of constant thickness to control the flow of washing solution.

8. 8. The method of claim 7, further comprising the step of washing the plurality of pipette tips in a dissolving solution of water and bleach prior to steps (a) and (b).

9. The method of claim 7 further comprising the step of minimizing sample or reagent carryover.

10. 10. The method of claim 9, wherein the step of minimizing carryover comprises (i) at least one washing step that physically removes material in the plurality of pipette tips and (ii) a passivation step.

11. The method of claim 10 , wherein the step of deactivating reduces the ability of the material to affect analytical results.

12. 12. The method of claim 11, wherein the step of deactivating comprises treating the plurality of pipette tips with heat, electromagnetic radiation and / or a chemical reactant that reacts with the material.

13. 13. The method of claim 12, wherein the chemical reactant comprises at least one of a bleaching agent, hydrogen peroxide, an acid or base, a crosslinking agent, or an alkylating agent.

14. The apparatus of claim 5 further comprising two manifolds having a plurality of chimneys.

15. 15. The apparatus of claim 14, further comprising a conduit provided in a bottom portion of at least one of said two manifolds, said cleaning fluid being pumped through said conduit and said bottom portion of at least one of said two manifolds.

16. 8. The method of claim 7, further comprising the step of draining residual contents within the pipette tip into a manifold prior to steps (a) and (b).

17. 17. The method of claim 16, further comprising a plurality of chimneys having the gap of the constant thickness, the plurality of pipette tips being positioned proximate the plurality of chimneys.

18. 20. The method of claim 17, further comprising shifting the positions of the pipette tips so that the pipette tips are positioned between the chimneys prior to discharging residual contents within the pipette tips into a manifold.

19. The method of claim 7 further comprising providing a uniform fluid flow through said gap of constant thickness with a flow restrictor.

20. 8. The method of claim 7, further comprising maintaining the gap of constant thickness adjacent the plurality of pipette tips in a range of 0.25 mm to 1 mm.

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