Process Modules for Automated Biological Systems

Abstract

The process module 120 of the biological laboratory system includes a housing 102, a work deck 330 disposed within the housing 102, a plurality of work deck plate slots for receiving cell culture plates 160, a liquid handling robot 340 having at least one pipette for aspirating liquid medium, and a first transfer interface 134 communicating with a first storage module 124 for storing the cell culture plates 160, wherein the work deck 330 is movable to a plurality of work positions, wherein at one work position the cell culture plate 160 is positioned below an operating point of the liquid handling robot 340, and at another work position the cell culture plate 160 is aligned with the first transfer interface 134 for transferring the cell culture plate 160 between the outside of the housing 102 and the work deck plate slot 110. The first transfer interface 134 or the second interface 130 can be carried in conjunction with a second storage module 100, 122 for storing labware 300 or liquid materials, and in another working position, a plate with labware 300 or liquid materials carried by one working deck plate slot 110 is aligned with the first or second transfer interface 130, 134 to transfer the labware 300 or liquid materials with the plate between the outside of the housing and the working deck plate slot 110.

Description

[Technical Field]

[0001] The present invention relates to a process module for a biological laboratory system, comprising a housing and a work deck disposed within the housing, the work deck having a work deck plate slot for receiving a cell culture plate, a liquid handling robot having at least one pipette for aspirating a liquid medium, and a first transfer interface associated with a first storage module for storing the cell culture plate, the work deck being movable to a plurality of work positions, in one work position the cell culture plate is positioned below an operating point of the liquid handling robot, and in another work position the cell culture plate is aligned with the first transfer interface for transferring the cell culture plate between the outside of the housing and the work deck plate slot.

[0002] The invention further relates to the use of the single well plate in a biological laboratory system for maintaining cell cultures or to the plate. [Background technology]

[0003] An automated biological laboratory system is disclosed in US Pat. No. 6,233,999.

[0004] Patent Document 2 discloses a machine for automatically filling a plurality of microplates in a biological laboratory system.

[0005] An automated chemical or biological sample analyzer is disclosed in US Pat. No. 5,623,999.

[0006] A sample rack transport device for automated chemical analysis is disclosed in US Pat. No. 5,649,999.

[0007] Patent document 5 shows a system for facilitating biological communication between two or more cell culture devices. A fluid collection device has a tip that engages with an output port or an input port of the fluidic device. Multiple fluidic devices are stored on a carousel.

[0008] US Pat. No. 6,449,649 shows a cell culture device including an incubator for accommodating culture containers in a closed system.

[0009] Patent Document 7 shows an automated cell culture operator having a storage device for storing cell cultures and labware, and a robotic arm capable of three-dimensional movement for handling microplates and labware.

[0010] Patent Document 8 discloses an automatic culture system equipped with a transfer means for transferring a microplate for automatic maintenance.

[0011] US Pat. No. 5,629,499 discloses an automated robotic system for the maintenance of microcell cultures.

[0012] Other microfluidic cell culture systems are known from US Pat. Nos. 5,629,299, 5,729,410, 5,729,429 or 5,729,429.

[0013] Cell culture requires advanced techniques, but is labor-intensive and complicated, resulting in high labor costs. Furthermore, the workflow is difficult and complex, and can take weeks, resulting in low reproducibility. Therefore, attempts are being made to automate cell culture.

[0014] Cells are cultured in plasticware (flasks, round dishes, bottles, multiwell plates) in an incubator. The typical procedure for passaging cells includes: preheating the medium, PBS, and trypsin (stored in the refrigerator) stored in the refrigerator; defrosting special additives such as fetal bovine serum (FBS) and growth factors stored in the freezer; preparing new plasticware (new plates, serological pipettes, and pipette tips); transferring the cells from the incubator to a flow hood (i.e., under sterile conditions, but preferably with minimal time outside the incubator); checking the cells under a microscope; washing the cells with PBS; removing and suspending the cells with trypsin, taking an aliquot, and counting the cell concentration on a microscope counting slide; adding the appropriate amount of cells and any medium; and returning the cells to the incubator. Large-volume liquid transfers are performed with a serological pipette, and small volumes are performed with a micropipette with disposable pipette tips.

[0015] There are existing systems for automating cell biology. These systems consist of various pieces of lab equipment (liquid handlers, automated incubators, refrigerators, etc.) from various vendors in various formats that are not generally designed to work together. These are often assembled by bolting the equipment to a table or other machine bed, which is then integrated with a 3D robotic arm. US Pat. No. 5,699,499 discloses a storage device for cell cultures that includes a carousel with radially arranged plate slots, each level of the carousel having a door for accessing the plate slots. US Patent No. 5,949,999 discloses a storage unit having a housing defining a storage compartment made up of annular shelves. A modular chemical analysis device is disclosed in US Pat. No. 5,629,999. Patent Document 16 discloses an automatic biochemical analyzer that is composed of a process module equipped with a turntable and a plurality of storage modules. An analytical device equipped with rubber is disclosed in US Pat. No. 5,649,999. US Pat. No. 5,629,499 discloses an automated diagnostic analyzer. US Pat. No. 5,629,999 discloses a cryogenic storage system with two storage modules. US Pat. No. 5,629,499 discloses a modular sample repository. US Pat. No. 5,699,499 discloses an automated micro-well plate handling device for removing micro-well plates from a stack. US Pat. No. 5,699,499 discloses an automated storage device with a cylindrical rack having a center well in which a robot is positioned. US Pat. No. 5,623,663 discloses a carrier for carrying bottles for other labware. US Pat. No. 5,629,493 discloses a liquid handling system for biological cell culture. Patent Document 25 discloses a robot handling device equipped with a gripper arm having a protrusion. US Pat. No. 5,649,499 discloses an incubator with a robotic handling device. US Pat. No. 5,627,493 discloses a robotic handling device for opening bottles. US Pat. No. 5,629,493 discloses an apparatus for culturing cells using a pipetting device. Patent Document 29 discloses a robot system. US Pat. No. 5,699,499 discloses a bottle decapper. [Prior art documents] [Patent documents]

[0016] [Patent Document 1] Chinese Patent No. 104777321 [Patent Document 2] U.S. Patent No. 6,360,792 [Patent Document 3] U.S. Patent No. 7,670,553 [Patent Document 4] Japanese Patent Application Publication No. 1-1189561 [Patent Document 5] US Patent Application Publication No. 2016 / 0145555 [Patent Document 6] US Patent Application Publication No. 2018 / 0044624 [Patent Document 7] U.S. Patent No. 7,883,887 [Patent Document 8] US Patent Application Publication No. 2016 / 0201022 [Patent Document 9] U.S. Patent No. 8,652,829 [Patent Document 10] U.S. Patent No. 9,388,374 [Patent Document 11] US Patent Application Publication No. 2017 / 0145366 [Patent Document 12] U.S. Patent No. 9,057,715 [Patent Document 13] WO 03 / 008103 [Patent Document 14] WO 93 / 03891 [Patent Document 15] European Patent Application Publication No. 2 068 155 [Patent Document 16] U.S. Patent No. 6,146,592 [Patent Document 17] European Patent Application Publication No. 3 229 028 [Patent Document 18] US Patent Application Publication No. 2014 / 0273242 [Patent Document 19] US Patent Application Publication No. 2018 / 0202908 [Patent Document 20] International Publication No. 2011 / 047710 [Patent Document 21] U.S. Patent Application Publication No. 2007 / 0059205 [Patent Document 22] European Patent No. 1 573 340 [Patent Document 23] European Patent Application Publication No. 1 900 806 [Patent Document 24] EP 2 733 196 [Patent Document 25] Japanese Patent Application Laid-Open No. 2009-291869 [Patent Document 26] Japanese Patent Publication No. 2004-166558 [Patent Document 27] US Patent Application Publication No. 2017 / 036833 [Patent Document 28] European Patent Application Publication No. 3 078 736 [Patent Document 29] US Patent Application Publication No. 2005 / 0058574 [Patent Document 30] International Publication No. 2016 / 130964 Summary of the Invention [Problem to be solved by the invention]

[0017] It is an object of the present invention to provide a processing module for use in a biological laboratory system that can operate fully automated over extended periods of time.

[0018] A further object of the present invention is to modify the labware used in the process modules. The present invention provides a solution to the above-mentioned problems. [Means for solving the problem]

[0019] The process module of the present invention is characterized in that the first transfer interface or the second transfer interface is associated with a second storage module for storing labware or liquid materials, wherein in another working position, a plate with labware or liquid materials loaded in one of the working deck plate slots is aligned with the first or second transfer interface for transferring the plate with labware or liquid materials between the outside of the housing and the working deck plate slot. The method includes the following steps: transferring a cell culture plate from outside the housing to one of the work deck plate slots via at least one transfer interface; transferring the plate loaded with labware or liquid material from outside the housing to another work deck plate slot via at least one transfer interface; moving the working deck to another position; aspirating the liquid medium from the plate using a liquid handling robot; and / or grabbing the labware from the plate loaded with labware; applying liquid medium to the cell culture plate by using labware; moving the work deck to another work location; Ejecting the cell culture plate through the at least one transfer interface. The following functions can be optionally realized: A process module for a biological laboratory system is provided, which has the following: housing; a work deck within the housing, the work deck having at least one plate slot for holding a microplate or labware; a liquid handling robot positioned above the work deck; the work deck is movable, and in particular rotatable, to position the work deck plate slot below an operating point of the liquid handling device; The plate slot is for transferring microplates or labware between the outside of the housing and the work deck plate slot in one horizontal plane. transfer It is alignable with the interface. This allows processing of biological systems to be carried out in one module, and plates or labware that have completed processing can be transported out of the module from the turntable or work deck, or onto the work deck when processing is required. Preferably, the liquid handling robot is a pipetting robot, which allows for the transfer of liquids between and within labware on the work deck. Preferably, the process module further includes a microscope, a capper / decapper robot, or a lidder / delidder robot, located above the work deck. This allows all processing to be performed in one module without having to move processed plates to another module for inspection or media to another module for decapping. This not only reduces robot movement time, but also reduces processing time, preventing sample spoilage due to delays. Preferably, the working deck plate slots are arranged radially relative to the central axis of rotation of the working deck, so that when the working deck is rotated, the plate slots are always in the same position at each rotation step, ensuring that various robots (such as pipetting robots) are consistently positioned relative to different plate slots as the working deck rotates. Preferably, the work deck plate slot is recessed into the surface of the work deck. Similar to the aforementioned channel, the recess prevents the plate or labware from rotating or moving on the work deck during processing. Preferably, the work deck plate slot has alignment means located on the outer edge of the work deck, which defines a width of the plate slot entrance that decreases as the distance to the center of the module decreases. This allows plates to be quickly aligned without risk of collision when they are brought into the plate slot. Preferably, the work deck is adapted to provide a location for manipulation of the plate slots by a liquid handling robot or to accommodate the work deck plate slots. transfer The plate slots are mechanically indexed to one or more positions to provide a position for alignment with the interface. The indexing is such that when the work deck is rotated, the plate slots transfer Ensure it stops in a position aligned with the interface or in a processing position below or in front of the robotic device. Preferably, the system comprises a further module with a rotatable carousel having at least one storage plate slot, the storage plate slot comprising: transfer The interface and work deck plate slots are radially alignable with each other, allowing the additional modules to feed and discharge the process modules. The additional modules may also be used to connect common access points between the process modules and the additional modules for transferring labware or plates. transfer It has a plate slot that aligns with the interface. Preferably, a storage plate slot, transferThe interface and work deck plate slots are in the same horizontal plane, and the transfer of microplates or labware between the storage plate slots and the work deck plate slots is via a single linear motion, which ensures that the robotic movement does not require vertical movement (or horizontal movement if the modules are stacked), and that plates can be moved from the storage module to a process module slot, or vice versa, in a single motion. Preferably, the rotatable carousel is housed in an incubator module, a refrigerator module, a freezer module, or a plasticware storage module. Preferably, the work deck has a work deck plate slot. transfer It is mechanically indexed to one or more positions to provide positions for alignment with the interface and carousel plate slots. In a further embodiment, a method of operating a process module is provided, the method comprising the steps of: Rotate the work deck in the process module to align the plate slot with the transfer radially aligning with the interface; Rotate the carousel of an adjacent module that has a carousel plate slot to transfer Radially aligned with the interface, transfer transferring the microplate or labware from the process module to an adjacent module or vice versa through an interface; The contents of the carousel plate slot or plate slots transfer transferring the plate through an interface to a radially aligned plate slot; rotating the working deck in the module to a position where the working deck plate slot is located below the liquid handling device; operating the liquid handling device to process the contents of the plate slot; and Rotating the work deck to position an additional plate slot on the work deck below the liquid handling device transfer Interface. This allows for the transfer of labware from the storage module to the process module, the processing of media within the labware, and the transfer of labware from the process module to the storage module. Preferably, the transfer of the carousel plate slot or contents of the plate slot is accomplished via linear horizontal movement of a grabber of a robotic handling device mounted on an adjacent module. Preferably, the grabber is positioned from the center of the adjacent module to the center of the adjacent module. transfer It is restricted to a single horizontal and vertical extension in the direction of the interface. In a further embodiment, there is provided a module for processing biological material, the module comprising: Pipetting robots; Inspection tools; and a turntable having a first retention slot for holding a process material support and a second retention slot for holding a cell culture support; The cell culture carrier is processed on a turntable; and The turntable is rotatable to allow a pipetting robot and an inspection tool access to the first and second retention slots. The turntable makes it extremely easy to compact the process module (effectively a cube, approximately 80cm 2The turntable has a footprint of 100 micrometers (approximately 100 micrometers). This is because the turntable is a very compact mechanism for moving plates in and out of the working area of ​​the pipetting robot. This is also advantageous when all or most of the process functions are located in a single module. This means that the system has an integrated process module surrounded by storage for less required functions. Preferably, the first and second holding slots are the same size. This ensures a uniform system and labware. Preferably, the process material is a liquid. Preferably, the process material carrier is a microplate or labware with the same footprint as a microplate. Standardized sizes allow the same plate slots or handling devices to be used for all items within the module and system. Preferably, the inspection tool is a microscope, which allows analysis of the cell culture supports within the module. This allows for determination of whether a process is complete without removing the plate or labware from the module. Preferably, the module is constructed of a sealed housing. Preferably, the module is equipped with a means for circulating filtered air. This ensures that clean air is always supplied within the module, and the flow ensures that emissions from any one vessel do not affect other vessels. Preferably, the module includes a storage module for inserting and removing microplates or labware having the same footprint as a microplate into and out of the module. transfer The process module or the system including the process module may have a control unit as a computer including software for operating the disclosed process module, and the handling robot is electrically driven.

[0020] The present invention provides a novel use for single-well plates. A single-well plate has a rectangular, flat, horizontal bottom and four vertical walls. The four vertical walls surround a single well. Each well provides a liquid volume. This type of single-well plate is used in the aforementioned biological laboratory system as a reservoir for liquid medium used to maintain cell cultures. The liquid is handled by a robot, which has at least one pipette for aspirating the liquid medium and applying it to cell cultures stored in the cell culture plate. The sealed storage well may be sealed airtight or at least liquid-tight by a film attached to or near the upper edge of the well or the entire plate. The well forms a growth area for biological materials the size of a microplate.

[0021] The present invention further relates to the use of such plates and similar plates, which have a transport device for transporting liquid from a supplier to a biological laboratory system and applying the liquid for cell culture maintenance, and a plurality of wells. The top opening of at least one well is sealed with foil. The plate preferably has a microplate footprint. Preferably, the foil is heat-sealed to the upper edge of the wall. Preferably, the sealed top opening of at least one well is covered with a lid. The sealed storage well can be sealed airtight or at least fluid-tight by a film attached to or near the upper edge of the well or the entire plate. The film can have breaking strength or features, such as a score feature that allows a plastic disposable pipette tip to penetrate. These and other features of the invention will now be described in more detail, purely by way of example, with reference to the accompanying drawings, in which: [Brief explanation of the drawings]

[0022] [Figure 1] FIG. 1 shows a schematic plan view of an embodiment of a module. [Figure 2]FIG. 2 shows a schematic plan view of the modules of FIG. 1 formed into a system of modules. [Figure 3A] FIG. 3A shows a schematic plan view of the modules of FIGS. 1 and 2 formed into a system in a different configuration. [Figure 3B] FIG. 3B shows a schematic plan view of the system according to FIG. 3B in a different configuration. [Figure 4A] FIG. 4A shows a schematic plan view of the transfer interface between modules. [Figure 4B] FIG. 4B shows a schematic plan view of the transfer interface between modules. [Figure 4C] FIG. 4C shows a schematic plan view of the transfer interface between modules. [Figure 5] FIG. 5 shows a schematic cross-sectional side view of the plate slots, plates and grippers of the module. [Figure 6] FIG. 6 shows a schematic cross-sectional side view of the transfer interface according to FIGS. 4A, 4B and 4C. [Figure 7A] FIG. 7A shows a schematic plan view of a further embodiment of a transfer interface between modules. [Figure 7B] FIG. 7B shows a schematic plan view of a further embodiment of a transfer interface between modules. [Figure 8] FIG. 8 shows a schematic plan view of a further embodiment of the transfer interface between modules. [Figure 9] 9A and 9B show schematic cross-sectional side views of two vertically stacked modules. [Figure 10] FIG. 10 shows a schematic side view of vertically and horizontally oriented modules. [Figure 11] 11A and 11B show a schematic plan view of a buffer slot between two modules. [Figure 12] 12A-12F show schematic plan views of steps using buffer slots of three modules. [Figure 13] 13A and 13B show schematic side views of labware according to one embodiment. [Figure 14] FIG. 14 shows a schematic plan view of the labware. [Figure 15A] FIG. 15A shows a schematic cross-sectional side view of the storage module and the process module. [Figure 15B] FIG. 15B shows a schematic plan view of the storage module and process module of FIG. 15A. [Figure 16] FIG. 16 shows a schematic side view of the process module and air handler. [Figure 17] FIG. 17 shows a schematic side view of the plate and plate slots. [Figure 18] FIG. 18 shows a schematic plan view of the transfer interface between modules with sensing means. [Figure 19] FIG. 19 shows a schematic plan view of the plate transfer steps between modules. [Figure 20] FIG. 20 shows a schematic plan view of the plate transfer steps between modules. [Figure 21] FIG. 21 shows a schematic plan and side view of a handling device and plate according to one embodiment. [Figure 22] FIG. 22 shows a schematic plan view of the handling device and plate slot of FIG. 21 and further handling devices. [Figure 23] FIG. 23 shows a schematic plan view of the handling device and plate slot of FIG. 21 and further handling devices. [Figure 24] FIG. 24 shows schematic top and side views of labware for use with the handling device of FIG. [Figure 25] FIG. 25 shows a schematic side view of a bottle for use in the handling device of FIG. [Figure 26] FIG. 26 shows a schematic plan and side view of a handling device according to one embodiment. [Figure 27] FIG. 27 shows a schematic top and side view of labware with interfaces for handling with caps and lids. [Figure 28A]FIG. 28A shows a schematic plan view of a system of modules with a central robotic handler according to one embodiment. [Figure 28B] FIG. 28B shows a schematic side view of a system of vertically stacked modules with a central robotic handler according to one embodiment. [Figure 29A] FIG. 29A shows a schematic plan view of the system of FIG. 28A with an additional carousel. [Figure 29B] FIG. 29B shows a schematic side view of the system of FIG. 28B with an additional carousel. [Figure 30] FIG. 30 shows a schematic enlarged side view of the robotic handling system and rack of the module. [Figure 31A] FIG. 31A shows a schematic side view of a rotatable robotic handling device according to one embodiment. [Figure 31B] FIG. 31B shows a schematic side view of a rotatable robotic handling device according to one embodiment. [Figure 32] FIG. 32 shows a schematic side view of a robotic handling device with a magazine rack and modules according to one embodiment. [Figure 33] FIG. 33 shows a schematic plan view of a system of modules and robotic devices on rails according to one embodiment. [Figure 34] FIG. 34 shows a schematic plan view of transferring plates between modules in vertically stacked modules, according to one embodiment. [Figure 35] FIG. 35 shows a plan view similar to FIG. 1 of a further embodiment of the invention. [Figure 36] FIG. 36 shows a single well plate for containing liquid media. [Figure 37] FIG. 37 shows a single well plate for containing liquid media. [Figure 38] FIG. 38 shows two adjacent modules connected with a sealing element 311. [Figure 39]FIG. 39 shows two adjacent modules connected with a sealing element 311. DETAILED DESCRIPTION OF THE INVENTION

[0023] 15A and 15B, there is shown a process module 120 connected to an additional module 100, which may be any of the modules described herein. The process module 120 includes a rotating element 108, or turntable. However, in some process modules 120, the turntable 108 is a single surface and does not include various vertical racks 210. Instead, the top surface of the turntable 108 forms a work deck 330, or at least a portion of the work deck 330. The turntable work deck has multiple slots for labware and is aligned with a functional module (e.g., a liquid handling robot) within the process module, and plates are transferred horizontally onto the turntable work deck from another module. transfer The turntable work deck can be aligned with the interface, thus serving as a very compact, integrated and simple means for transferring plates into the module and between multiple functional elements.

[0024] Within the process module 120 is a liquid handling robot 340. The liquid handler 340 is positioned above the turntable 108. In the illustrated embodiment, the liquid handler 340 does not occupy the entire area above the working deck 330, as shown in FIGS. 15A and 15B. As shown in FIG. 15B, the turntable 108 is rotated so that five plate slots 110 are located below the liquid handler 340. The liquid handler can be configured to have a liquid discharge point for each of the plate slots 110 located below it, or for a selected number as needed. The actual size of the liquid handler can vary depending on the required functionality of the system 99. In a given embodiment, it is positioned to access all of the plate slots 110 on the working deck 330.

[0025] As mentioned above, the turntable 108, and thus the rotating work deck 330, within the process module 120 has radially arranged plate slots 110 that can hold a variety of items, such as cell culture plates 116 and plates containing consumables such as pipette tips and media bottles. While eight slots may be sufficient for a general-purpose cell culture system, the total number of plate slots 110 can be varied as needed, for example, the plate slots 110 can be adapted to hold two or more plates adjacent to each other.

[0026] FIG. 15B shows a microscope positioned in the plate slot 110 of the process module 120 so that the turntable 108 can rotate within it. The microscope has a lens below the plate (to view cells through the bottom of the plate) and a light source, such as a high-power LED array, above the plate. Any location within the work deck 330 where it is desired to scan the plate 116 with the microscope 342 must therefore have a notch to expose the bottom of the plate 116 to the microscope lens. Alternatively, the plate can be lifted from the rotating work deck by a handling means and transferred to the microscope. The microscope can observe or scan the entire plate 116 by moving or scanning in the x and y directions. The turntable 108 indexes the microscope 342 so that it always remains in the same position, ensuring high-quality inspection of the plate and contents below. In the illustration, the microscope 342 is positioned at the location where the plate 116 will be transported to and from the incubator 124. This allows the plate 116 to be transferred to and from the plate slot 110 below the microscope 342 without rotating the turntable 108 of the process module 120, thereby not interrupting other processes occurring on the turntable working deck 330. Other embodiments are possible, for example, the microscope 342 could be located in a different slot on the working deck 330.

[0027] Microscope 342 is typically used to monitor the state of the cells (e.g., confluence) to know the rate at which the cells are growing and when they need to be passaged next or where there are enough cells to start another process. In another embodiment, microscope 342 can also detect the pH of the medium (carrying a dye that acts as a pH indicator) and / or detect gross microbial contamination (making the medium acidic (more yellow) and cloudy).

[0028] In another embodiment, the microscope 342 is indexed to the turntable 108 or positioned to view an area larger than the area of ​​the required plate 116 or plate slot 110 and is programmed to ignore features outside this field of view or use them to compensate for misalignment in the plate 116.

[0029] An optional decapper robot 344 is shown positioned above the plate slot 110 when the turntable 108 is rotated into position. The decapper 344 decaps the vials 321 and bottles 323. Vials 321 and bottles 323 that need to be decapped have their plate slot 110 rotated by the turntable 108 to a decap position below the decapper 344. The turntable 108 can then rotate the decapped plate slot 110 into a position required for the liquid handler 340 (e.g., a pipetting robot).

[0030] An optional delidder station 346 is also shown, providing for deliding plates 116, e.g., cell culture plates. In the art, consumables such as pipette tip boxes and pipette tip stacks, or plates such as microplate reservoirs, are housed on the deck of a liquid handler. In the system described herein, it is desirable for the process module to have random access to a wide range of consumables that a human might use in a laboratory. To this end, the process module is interfaced with an automated incubator, automated refrigerator, and automated plasticware storage, allowing for flexible movement of consumables or cell culture plates into and out of the process module as needed. To achieve this, a system for opening and closing the lids of the pipette tip boxes and microplate reservoirs is desirable. In the art, pipette tip box lids are adapted for human use, hinged to the box, and somewhat flexible, typically made of a polymer such as polypropylene. Microplate reservoir lids, if present, also have somewhat flexible polymer lids. Pipette tip boxes or other labware (such as microplate reservoirs) can also be de-lidded with the de-lidder if they have lids that can be handled by the de-lidder. Such lids are known in the art for cell culture plates and are generally made of materials such as polycarbonate, which require rigidity. It is also advantageous for these lids to be glossy, as is known in the art. By rotating the turntable 108, the de-lidder 346 can be positioned over one of the plate slots 110 containing the plate whose lid needs to be removed.

[0031] 15B, an exemplary process module 120 may be configured with one microscope 342, one de-lidder 346, and one de-capper 344, all mounted on the work deck 330. Other configurations are possible depending on the needs of the system. For example, more than one microscope 342 may be required, or a configuration may not require a de-capper 344.

[0032] As an example, the work deck 330 holds cell culture plates 116 in plate slots 110, racks with vials 320 (e.g., vials containing reagents or growth factors) and bottles 322 (e.g., bottles containing cell culture medium or trypsin), and a pipette tip box 324 with two different sizes of pipette tips. The work deck 330 may be stationary while the liquid handler 340 transfers liquids, or it may rotate to conveniently present various dishes and other consumables to the liquid handler 340 at various times. Additionally, other items, such as cell culture plates 116, may be located below the microscope 342, delidder 346, or decapper 344. If the mechanisms for the microscope 342, delidder 346, and decapper 344 were located above the plate slots 110 on the work deck 330, in most cases this would prevent the liquid handler 340 from reaching the items in those plate slots 110. Items in the plate slot 110 below the microscope 342, delidder 346 or decapper 344 can be exposed to the liquid handler 340 when required by rotating the work deck 330.

[0033] The turntable 108 for the work deck 330 has eight radially arranged plate slots 110 for cell culture plates 116 having a SLAS (Society for Laboratory Automation and Screening) microplate footprint and can be small, e.g., less than 80 cm in diameter. This allows the process module 120, or other modules 100 having similarly sized turntables, to be compact and easily pass through doors, such as laboratory clean room doors. This generally makes installation of the system 99 simple, fast, and economical, since the modules can be assembled in a factory and then assembled on-site.

[0034] 15B, a carousel 108 with a rack system 210, such as the carousel 108 of the incubator 124 shown in FIG. 15B, can be positioned adjacent to the work deck 330 of the process module 120, thereby allowing labware 300, such as cell culture plates 116, to be transferred by a simple horizontal movement from the plate slots 110 of the carousel 108 of the incubator 124 to the plate slots 110 of the work deck 330. A robotic device 160 for transferring the plates 116 can be provided within the incubator 124.

[0035] An external solid waste receptacle 348 equipped with a robotic grabber 160 is provided in association with the process module 120. Solid waste from the process module 120 (e.g., used cell culture plates, empty pipette tip boxes, empty bottles) can be transferred to the solid waste receptacle 348. The solid waste receptacle 348 does not need to be the size of the module 100 and can have a smaller capacity, perhaps requiring its contents to be emptied into bags and transported outside the laboratory. A sealing means 311 formed by a piece of pipe connects the modules 100, 120 airtight. The sealing means 311 can be used to rigidly connect the two modules 100, 120.

[0036] 16 is a schematic diagram of the air flow through process module 124. An air handler 350 is provided, which is located above process module 124 to conserve floor space. However, air handler 350 may be installed in other locations as appropriate in a given system 99. The air handler supplies clean air 352 to process module 124, which is routed across (i.e., horizontally) process module 124 to an exhaust where the exhaust air 354 is returned to air handler 350.

[0037] Preferably, HEPA-filtered air is blown into and through the process module 124. Directing the air horizontally minimizes particle fallout into open cell culture plates 116 or reagent vials or bottles. HEPA air can be recirculated through the system 99 via a HEPA filter as a way to reduce particulates and reduce exhaust air from the system 99. Recirculating air may be preferable for processing steps where exhausting air into the room is undesirable, such as in systems handling lentiviruses. It may also be preferable not to recirculate air in a given system.

[0038] In one embodiment, the process module 124 further comprises some means for periodic sterilization, such as hydrogen peroxide vapor, ozone, ethylene oxide, or UV light, such as a UV LED, arranged to irradiate the surfaces of interest.

[0039] FIG. 17 shows two versions of a plate slot 110. In one version, a plate 116 or other labware 300 rests within a channel or trough 156 formed by slot sides 152 and a bottom 154 that is generally perpendicular to the slot sides 152. As mentioned above, the plate 116 or other labware 300 has a footprint 360 that is wider than the width of the plate 116 or other labware 300 itself. This can be used to allow a grabber 164 to slide within the trough 156. However, in the channel 156 shown in the plate slot 110 on the right side of FIG. 17, the slot sides 152 have a wider portion at the bottom of the channel 156 and a narrower portion at the opening of the channel 156. In this situation, the width of the trough is such that footprint 360 is wider than the narrow portions (but can fit between the wide portions), and plate 116 is vertically constrained within plate slot 110. This allows for alignment of labware 300 and prevents it from falling or getting lost.

[0040] Such a configuration may be particularly useful, for example, in locations on the work deck 330 of the process module 120. If the grabbers 164, and thus the gripper fingers 168, do not extend down the sides of the plate 116 within the slot 110, then either additional grooves in the channel walls (e.g., FIG. 5) or grooves 370 in the labware (FIG. 19A) are required to accommodate the gripper fingers. Alternatively, a robotic handling device 160 is required. This can be achieved by a gripper handling the front side of the plate 116, or by the plate 116 being pushed in and out of the plate slot 110.

[0041] Chamfers 362 are provided on the upper edges of the slot sides 152 at the openings of the channels 156. These chamfers 362 can assist in vertically aligning the plates 116 placed in the plate slots 110. The features described above, such as the chamfers 362 and slot sides 152, which provide various widths for the channels 156, can be combined with the features of FIG. 5, such as the grooves 166 in the sides.

[0042] 18, the end of the plate slot 110 is provided with an engagement means 362. The engagement means 362 is activated or otherwise triggered by the placement of the plate 116 to indicate the presence of the plate 116 within the slot 110. In one embodiment, the engagement means 362 is a spring that retracts into the wall of the plate slot 110 when the plate 116 is present. This activates a proximity or pressure switch, which notifies the control system that a plate is present or properly positioned within the plate slot 110.

[0043] Alternatively, the engagement means 362 may be a recess, a press fit, or a spring that engages the labware 300. The engagement means 362 can provide feedback (e.g., read by the motor driving the gripper 164) when the means 362 is initially engaged by the labware 300 and further feedback when the labware 300 is fully engaged in the plate slot 110. Producing such a signal as a function of the position of the plate 116 within the slot 110 can be accomplished by various means, such as an impedance strip, or by proximity sensors located at the front and rear ends of the plate 116 that are triggered by contact with the engagement means 362. Alternatively, variations in the shape of the plate 116 from front to rear can result in different forces being applied to the engagement means 362. For example, the plate can be narrower at the front, and therefore the engagement means 362 will retract less than wider portions of the plate 116, which will retract the engagement means 362 more. This requires consistent alignment of the plate 116 and therefore corresponding engagement means 362 may be provided at the entrance to the plate slot 110.

[0044] A sample process will now be described with reference to Figure 19 and its sub-figures A, B and C. Here, the replacement of nutrient medium in a cell culture plate 116 will be described.

[0045] While the cells are growing, the cell culture plate 116 containing nutrient medium resides in the incubator 124. Due to waste accumulation or nutrient deficiency, the medium needs to be changed. In FIG. 19A , the plate 116 is transferred to the work deck 330 along with pipette tips 324 and new medium (which may be in a deep-well plate 364, or alternatively in a bottle in an adapter rack or in a bottle with a microplate footprint). The associated plate 116 with cells is then removed from the plate slot 110 of the plate hotel / rack 210 in the carousel 108 by the robotic device 160. The vertical movement of the robotic device 160 and the rotation of the carousel 108 present the correct plate 116 to the robotic device 160, which then removes the plate 116 from the plate slot 110. The robotic device 160 then moves vertically to align with the door 130 of the incubator 324, which is aligned with a slot in the rotating work deck 330. The carousel 108 / rotating work deck 330 rotates to align the target plate slot 110 on the rotating deck 330 (i.e., where the plate 116 will be transferred) with the door 130 of the incubator 324, and the robotic device 160 then horizontally transfers the plate 116 to the target plate slot 110 on the rotating work deck 330. The plate 116 is then de-lidded, for example, by rotating the rotating work deck 330 until it is aligned with the de-lidder station 346, which then removes and stores the lid.

[0046] Pipette tips 324 and cell culture media (in deep well plates 364) are transferred in a similar manner from another storage 122 to a target plate slot 110 on the rotating work deck 330 by vertical movement of the robotic device 160, rotation of the carousel 108, and alignment of the associated target plate slot 110 on the work deck 330 with the door 130 of the associated storage 122. In Figure 19B, all necessary materials, i.e., plate 116, media, and tips, are present in the process module 120.

[0047] The liquid handling robot 340 picks up a new, disposable, sterile pipette tip 324. Disposable pipette tips are used to prevent the medium and cells from becoming contaminated with microorganisms or excess chemicals from previous pipetting steps. The liquid handler aspirates the used medium from the plate and disposes of it as waste. The pipette tip 324 is then discarded, and a new pipette tip 324 is picked up. The liquid handler 340 then aspirates fresh medium from a reservoir (e.g., a deep-well plate) and dispenses it into the plate with the cells. The plate can be a single-well or multi-well plate, in which case the pipette dispenses into a row of wells, repeating this process until all wells are filled with fresh medium. Re-lid the plate 116 with fresh medium: The rotating work deck 330 is rotated until the plate 116 is aligned with the delidder 346 containing the lid that was removed from the plate 116, which re-lids the plate 116 and returns the plate 116 to the incubator 124. If no longer needed, the medium and pipette tips are returned to storage 122.

[0048] FIG. 19C shows the plate 116, pipette tips 324, and deep well plate 364 returned to their original positions in the system 99.

[0049] An exemplary sample process will now be described further with reference to Figures 20A, B, and C. Cells are typically passaged when they are, for example, 80% confluent. In this example process, the following are transferred to the rotating work deck 330: 1. Usually, a plate containing nearly confluent cells is used. A box of 2.1 ml pipette tips 324. The tips may preferably be wide bore tips. 3. Deep well plate 364 containing PBS (phosphate buffered saline) + EDTA (or equivalent reagent) 4. Deep-well plate containing trypsin (or equivalent reagent) 5. Deep-well plate 364 with fresh medium 6. Two new plates for transferring cells 116

[0050] The initial position of the materials is shown in Figure 20A. The liquid may optionally be preheated by transferring the plate 116 to the incubator 124 for a suitable period of time. This may be achieved by transferring the plate 116 from storage 122 to the rotating work deck 330, and then from the rotating work deck 330 to the incubator 124, as previously described.

[0051] 20B, once the required material is on the rotating work deck 330 and the lid of the associated plate 116 is removed, the liquid handling head 340 picks up a new pipette tip 324 and aspirates the old medium from the passing plate 116. The medium is discarded into the liquid waste 366.

[0052] Residual medium (including serum) is then washed away. Liquid handler 340 picks up a new pipette tip, aspirates PBS, and pipettes it into the wells of plate 116. The PBS is then removed and discarded. Repeating this rinse can further reduce the amount of residual medium and serum.

[0053] Next, trypsin is added. Note that in Figure 20B, multiple plates are below a diagonally oriented delidder apparatus 346. Because the delidder apparatus 346 is not fixed to the rotating work deck 330, the decapper 344 and delidder 346 remain in fixed positions as the deck rotates. Also, a diagonal position may be inconvenient for the pipetting head. Therefore, in this example, the rotating work deck 330 can be rotated to present the plates 116 in a convenient orientation and position.

[0054] After the liquid handler 340 picks up a new pipette tip, it rotates the work deck 330, causing the liquid handler 340 to aspirate the (usually minimal) amount of trypsin needed for the associated plate. The work deck 330 is then rotated again, returning the plate 116 containing the cells to a position where the pipetting head can easily pipette, and trypsin is added to the wells of the plate. The plate is then incubated for several minutes to allow the trypsin to detach the cells. In some methods, the plate is incubated at room temperature, which can be achieved by placing it on the rotating work deck 330. In other methods, the plate is incubated at 37°C while the cells are detaching, which can be achieved by returning the plate to the incubator 124. Various methods can be used to select the trypsin incubation time; for example, the incubation time can be predicted based on past results with a given cell line. Alternatively, automated microscopy can be used to monitor cell detachment.

[0055] Once the cells are sufficiently detached, the liquid handler 340 adds medium, typically containing serum, to quench the trypsin (by rotating the work deck 330 as necessary, as described above for trypsin). Alternatively, modified trypsins and similar reagents are known in the art that do not require serum quenching. The liquid handler picks up a new pipette tip, aspirates the required amount of medium, and pipettes it into the well containing the detached cells. The detached cells are resuspended (to reduce shear stress on the cells), for example by gently pipetting up and down using a wide-bore pipette tip.

[0056] The required number of cells are then transferred to two fresh plates 116 to achieve a target confluence of the newly seeded plates, for example 20% confluence.

[0057] Various methods can be used to determine the volume of cell mixture to be transferred. For example, cells can be counted using an automated cell counter, or cell number can be estimated based on confluency immediately prior to passaging. In either case, the pipetting head aspirates the required volume of cell suspension (containing the desired number of cells) and seeds the cells into a fresh plate. The wells of the new plate are replenished with new medium, as needed, to ensure the correct volume of medium per well. The newly seeded plate is then re-lidded and returned to the incubator. The old plate is discarded, and the medium, PBS, and trypsin can be returned to the plate hotel storage location on the associated carousel 108, as shown in Figure 20C.

[0058] In the handling strategy briefly described, all necessary materials (fresh plates, PBS, trypsin, media, pipette tips) are loaded onto the rotating work deck 330 at the beginning of the process. Other movement sequences are possible. For example, preheated liquids may be loaded onto the work deck 330 only when needed.

[0059] As discussed above, there is a need for automated equipment that can handle more complete and integrated workflows. Currently, there is a need to create equipment that can handle a wide variety of traditional, human-optimized labware that is difficult for automated systems to handle. Provided here is a labware set and method for its use that enables end-to-end automation of complex cell culture workflows using essentially only labware that conforms to the SLAS microplate footprint, thereby adapting the workflow to a format that can be easily handled by automated equipment. Also provided is a universal format for handling the labware set, including robotic handlers, racks, and slots, as well as storage that conforms to this format.

[0060] As mentioned above, labware having a footprint compatible with the microplate footprint 116 will be grasped by the grabber arm 164, and more particularly by the gripper fingers 168. Thus, a standardized form of plate 116 is used for one robotic device 160 to access all storage modules (i.e., refrigerator 128, freezer 126, plasticware and room temperature reagents 122, etc.). Microplates or microtiter plates 116 are often used in cell culture processes.

[0061] The terms "microplate" and "plate" are used interchangeably herein to mean "labware with an SBS / SLAS microplate footprint," which consists of a set of labware including microplates, microplate reservoirs, single-well cell culture plates, multi-well cell culture plates, microtiter plates, bottles, pipette tip boxes, vial and / or bottle adapter racks, all of which use the same bottom footprint and can therefore be manipulated within module 100 by the same robotic device handler 160. Furthermore, all of this labware can have the microplate bottom footprint and are interchangeable.

[0062] Referring to FIG. 13A, a set of labware 300 is arranged in a rack 310. The rack 310 is arranged as two vertical stands 314 with rack rails 312 positioned between the two vertical stands 314 and extending slightly into the interior region of the rack 310. Because these rack rails 312 extend only a portion of the interior region, when a plate 116 is placed on the rails 312, it interacts with only a portion of the plate 116 (or labware) and does not limit its height because it does not extend across the rack stands 314. The gripper fingers 164 can still interact with the plate 116 and other labware 300 as they grip the top of the rack rails 312, as will be described in more detail below with reference to FIG. 13B.

[0063] 13A shows a microplate 116 (or the like) seated on rails 312 of a rack 310. Also shown is a vial plate 320 mounted on the rails 312. However, in this embodiment, the vials 321 of the vial plate 320 extend beyond the height of the next rail 312 placed above it. The vials 321 can extend beyond the height of the next rail 312 because the rails 312 do not extend into the interior region of the rack 310 more than far enough for the footprint of the plate 116 or vial plate 320 to be placed on the rails 312.

[0064] The vertical stands 314 can be arranged so that each column forms a row of racks 310 side by side, with rails 312 extending from both sides of the vertical stands 314. This allows each vertical stand 314 to form part of a rack 310 in an additional rack 310, thereby achieving a compact rack 310. In this arrangement, the robotic device 160 needs to be able to move not only in a single horizontal dimension, i.e., toward and away from the rack 310, but also in a second horizontal dimension, left and right, and thus in the z-axis and y-axis, to access adjacent racks 310. When racks 210 are arranged on the carousel 108, one vertical stand 314 cannot be used for two racks 210 because the racks are arranged radially.

[0065] A bottle tray 322 is shown in FIG. 13A , where the footprint of a microplate 116 is provided with a tray suitable for holding multiple bottles 323. Like the vial plate 320, the bottles 323 are shown extending beyond the height of the rails 312 above them. This is possible because the rails 312 extend into the interior area of ​​the rack 310 only far enough to support the microplate footprint and are therefore not height-limiting. A pipette tip tray 324 is also shown, and like the other examples, the footprint of a microplate 116 can be accommodated in a rack 310 with a pipette rack capable of holding multiple pipettes while the height between the rails 312 is shorter than the height of the pipette tip tray 324.

[0066] Two examples of large bottles 326, 327 are shown in FIG. 13A. The large bottles 326, 327 are manufactured to have the same footprint as the plate 116 or trays 322, 324. Therefore, the bottles are not placed on a microtiter footprint rack, as is the case with other labware 330. The base of the bottle 326 has an extension 328 that is wider than the width between the rails 312 but narrower than the width between adjacent vertical stands 314 of the rack 310, so that the bottles 326, 327 are suspended by the rack's rails. A bottle that is narrower than the width between the two rails 312 extends from the extension 328. The bottle 327 also has an upper extension 329 that reaches between the rails 312 of the rack 310 so that it can be suspended by the rails 312. However, the upper extension 329 is positioned midway up the bottle so that the bottle 327 can extend in both directions (i.e., up and down) from the extension 329. As such, bottle 329 can be placed on a higher rail 312 and extend upward while hanging downward. This contrasts with bottle 326, which has an extension 328 at its base that extends upward relative to the height of rack 310. This allows bottle 326 to be placed on the lowest rail 312 of rack 310 and pass through the rail 312 above.

[0067] The extensions 328, 329 and / or bottles 326, 327 can be shaped to have a horizontally circular cross section, i.e., to form the outline of a circle when viewed from above, allowing even conventionally shaped bottles to be held on the rail 312. Alternatively, the extensions 328, 329 can have flat sides extending along the length of the rail 312, thereby providing a larger support area for hanging the bottles 326, 327. The bottles can be circular or similarly shaped with flat sides, in which case the more rectangular shaped bottles (when viewed from above) can be more space efficient and are often used in cell culture work.

[0068] This provides a versatile racking solution, eliminating the need for specially sized plate slots 110 for various types of labware, and instead, plate slots 110 are universally sized to accommodate many types of labware. Additionally, in some embodiments, plate slots 110 do not need to be specially sized for specific heights, and instead, plate slots 110 can accommodate items of labware 300 that are taller than the set of rails 312, because the set of rails 312 does not extend into the height of plate slots 110 and, therefore, racks 210, 310.

[0069] The racks 210, 310 described above are located on the carousel 108. In some cases, a rack 210 can be completely removed from the carousel 108 and a new rack 210, 310 can be loaded. This allows a new set of plasticware 300 or plates 116 to be pre-loaded and replaced in the rack. Access to the racks 210, 310 can be achieved through a user-accessible door. The door height should be the same as the height of the rack 210, 310 being removed or placed in the module 100. To avoid contamination of the module or environmental changes, rack 210, 310 exchange can be performed in conjunction with a load lock. In some cases, only the module 100 used for plasticware storage or room temperature storage is accessible for rack 210, 310 exchange.

[0070] The carousel 108 has been described in the singular for each module 100. However, multiple rotating disks can be provided to form a carousel that holds the racks 210, 310. For example, a lower turntable and an upper turntable can have spaces between them for the racks 210, 310 to seat. In some embodiments, rows of plate slots 110 are seated on separate carousels 108 that rotate independently within the same module 100.

[0071] When researchers culture large numbers of cells, they use a large number of flasks. On the other hand, plates are used when users need multi-well plates to perform multiple cultures or experiments in parallel. Single-well plates, like T75 flasks, have a large liquid surface area, e.g., 77 cm. 2 Single-well plates can be provided with a liquid surface area of ​​100 μm. Single-well plates are inconvenient and unusual for humans to use, but can be used by robotic devices 160. This simplifies mechanical handling in automated systems.

[0072] Figure 13B shows a set of labware 300 as shown in Figure 13A. However, gripper fingers 168 are shown interacting with various pieces of labware 300. In the case of plate 116, gripper fingers 168 grip each side of plate 116 (except for the footprint that rests on rails 312). Because it is the sides of the plate that are gripped, gripper fingers 168 do not encroach on the area above (or below) plate 116. This does not restrict the height of the plate or contents; the only height limitation is the height of the rack 310 (or module 100) in which labware 300 is intended to be placed, or the height of the rack 310 (or module 100) through which labware 300 is intended to pass. transfer Interface 133、 It can be 134cm high.

[0073] For vial plate 320, bottle tray 322, pipette tip tray 324, and large bottle 326, gripper fingers 168 all grip labware 300 above a footprint that rests on rails 312. It is worth noting that when placed on rack 310, there is enough space between vertical stand 314 and the sides of plate 116 or other portions of labware 300 to allow gripper fingers 168 to fit. This is because the footprint of labware 300 (extensions 328, 329 in the case of large bottles 326, 327) is wider than the width between the sides of labware 300. In the case of large bottle 327, because extension 329 rests on rails 312, the gripper fingers can instead grip bottle 327 at a lower level than extension 329.

[0074] The system described above handles cell culture plates 116, liquid media (typically contained in bottles 323, 326, 327), liquid additives (such as growth factors) contained in, for example, 2 ml vials 321, sample plates 116 (for storing samples taken from cells), pipette tips (contained in pipette tip box 324), etc. These different objects can be handled differently in the same system 99 using robotic devices 160. This allows for a highly autonomous automated cell culture system 99 capable of withstanding long-term operation.

[0075] 3A and 3B, a process module 120 is shown in which various labware 300 is shown on the work deck of the carousel 108 in accordance with the above description. It is notable that because the plate slots 110 are the same size and configuration throughout the system 99, such as those on the work deck of the carousel 108, all labware (e.g., plasticware) 300, including vials 321, bottles 323, 326, 327, and pipette tip boxes 324, are handled by the same gripper fingers 168, are housed in the same types of racks 210, 310 and carousel 108, and are seated in the same types of docks 110 on the rotating work deck.

[0076] Vials typically contain 0.2-2 ml of liquid. They are often screw-capped, but other methods are possible. Vials can be cryovials, with caps ranging from 0.2 to 2 ml.

[0077] Because pipette tips occupy a large amount of space and because the system 99 uses such a large number of pipette tips, they are typically stored in space-saving stacks (magazines). However, it is advantageous to have a variety of tip types available, such as 10 μl, 100 μl, and 1 ml tips. Additionally, it may be advantageous to have other tip types, such as 100 μl and 1 ml wide-bore tips, or aerosol-resistant versions of those tips. If multiple tip boxes 324 were preloaded on the deck or if there were magazines for the boxes, this flexibility would require multiple slots 110 and magazines. This may require a large or complex deck. Therefore, while handling tips in a single box 324 may appear to use a large amount of limited space, it actually simplifies the system, increasing flexibility and reducing downtime, thereby improving system 99 availability. It also requires fewer personnel to replace tips as needed. Variations of these embodiments can be employed depending on the requirements of the system 99.

[0078] 14 shows plan views of different trays or plates 116 for different functions, for example, on the left is shown a bottle tray 322 with four defined areas for bottles 323, and on the right is shown a vial plate 320 with 48 slots for vials 321. However, the central tray 325 shows a combination of slots or areas so that bottles or vials can be accommodated on a single tray 325. Various combinations for the trays 325 can be provided depending on the requirements of the system 99.

[0079] Various labware 300 may have computer readable means, such as barcodes, RFID, NFC chips, etc., to record tray or plate types and configurations on the system. A reader may be present on the robotic device 160 to detect tray or plate selection.

[0080] Cell culture plates typically require 10–15 ml of medium. This medium is typically pipetted from 100–500 ml bottles using a 15–20 ml serological pipette. Serological pipettes were originally designed for manual use and are typically made of rigid polymers such as polycarbonate. Their inner diameter is widest at the center of the body length and narrows at the tip, and the end where they connect to the mechanism that applies air pressure to aspirate or dispense liquid is also narrow. This traditionally required automated systems to handle bottles and serological pipettes, resulting in complex and prone to malfunctioning robots. While conventional pipetting robots are mature and reliable, their heads typically only handle volumes up to 1 ml, requiring long pipetting steps to transfer 10–15 ml of medium. Pipetting robots typically have a piston and often operate with air exchange. Disposable pipette tips are used; they are somewhat compliant and typically made of polymers such as polypropylene, which sealably attach to the outside of the pipette's "cone." The pipette tip has a significantly larger inner diameter where it attaches to the pipette cone.

[0081] It should also be noted that deep-well plates 116 can be used as medium storage containers instead of bottles 323, 326, and 327. The use of deep-well plates in this system facilitates handling by the automated robotic system 99. Furthermore, deep-well plates 116 can be sealed with film (to prevent liquid leakage during shipping), which can be broken by a pipette. Alternatively, the plate lid may be sealed or have a gasket. A 96-well plate with 2 ml wells can hold 192 ml of medium, similar to bottles, allowing for efficient use of space. Unlike bottles, deep-well plates, like trough reservoirs, are accessible to multichannel pipette heads. An 8-channel pipette head with 1 ml pipettes can pipette 8 ml at a time from deep-well plates, allowing for two pipetting steps to fill a single-well plate with up to 16 ml of medium. Although filling plates with media using a multichannel pipette head may seem inefficient at first glance, using deep-well plates as large-volume liquid reservoirs and pipetting with a multichannel pipette significantly reduces the mechanical complexity of the automated system and increases system occupancy (i.e., efficient use) due to its space efficiency and flexibility. Single-well plates can be used by robots in place of T75 flasks, which have a culture area of ​​75 cm. 2 Although they are large and useful for maintaining cell stocks, they are preferred by humans and are not suitable for robots. On the other hand, single-well plates exist, but are rarely used because they are difficult for humans to use and easily tip over, spilling the medium. However, single-well plates are suitable for robots and are 75cm in diameter. 2In automated systems, plate heights of 15 mm or less, or even 10 mm or less, can be advantageously used to increase storage density. This is usually a disadvantage for human use, as tilting the plate can easily cause spillage.

[0082] In an example of system use, a user loads the liquids required by the system 99 into the system. The liquids may be transferred from bottles 326, 327 to the deep-well plate (e.g., by an automated liquid handler or dispenser) or may have been provided to the deep-well plate by a supplier, as described above. The user may load the deep-well plate containing media, PBS (Phosphate Buffered Saline), and trypsin into racks 210, 310 in the carousel 108 of the refrigerator 128 of the system 99, for example. When the system 99 is ready to passage cells, the robotic device 160 in the refrigerator 128 retrieves the media, PBS, and trypsin from the racks 210, 310 in the refrigerator 128 and transfers them to empty racks 210, 310 in the incubator 124 to warm for five minutes. After five minutes, the system transfers a box of 1 ml pipette tips 324 and at least one fresh cell culture plate 116 to the work deck 108. The robotic device 160 in the plasticware storage 122 retrieves the tip box 324 from the slot 110 in the carousel 108 and places it over the slot 110 in the work deck 108, which has been rotated to align with the door 130 of the plasticware storage 122, where it then places the tip box 324 and places a fresh tissue culture plate 116 in a similar manner. The work deck 108 then rotates to align the slot 110 that receives the PBS, medium, and trypsin with the door 130 of the incubator 124, and the robotic device 160 in the incubator 124 places those liquids (contained in the deep well plate 116) into the appropriate slot 110 in the turntable 108. The robotic device 160 then places the plate 116 containing the cells that need to be passaged.

[0083] Referring to FIG. 21, an improved interface of the robotic device 160, specifically the interface between the handler or gripper fingers 168 and the plate 116 or other compatible labware 300, is shown.

[0084] Typically, the interface consists of a combination of a handler and a "dock and key" feature on the labware. The feature, for example, a beveled or conical shape, allows the labware to be aligned on the handler during pickup, even offsetting a few millimeters. The handling interface provides a more secure hold on the labware. This feature allows the system to detect and reject labware that does not have a handling interface and is the wrong size.

[0085] FIG. 21A shows a plate 116 having a footprint 360 with a groove 370 extending through its sidewall. In particular, the groove 370 begins at an end of the footprint 360 and extends along the length of the plate 116. In some embodiments, the length of the groove 370 does not exceed half the length of the plate 116, and furthermore, the length is the same as (or longer than) the length of the gripper fingers 168. The groove 370 is closed on the top and bottom surfaces of the footprint 360. However, the groove 370 can be open on the sidewall of the footprint 360 closest to the open side to form a channel. Grooves 370 are also provided on the opposite ends (i.e., across the width of the plate 116). The two grooves 370 are sized so that a pair of gripper fingers 168 can slide along the groove 370 to manipulate the plate 116. The labware 300 other than the plate 116 preferably has a footprint similar or identical to that of the plate 116. Therefore, grooves 370 can be provided on all labware 300.

[0086] The upper and lower surfaces of the grooves 370 limit the vertical movement of the plate 116 relative to the gripper fingers 168. As a result, not only must the gripper fingers 168 rely on horizontal force to manipulate the plate 116, but the plate is also constrained vertically, reducing the likelihood of dropping the plate 116. A pair of identical grooves 370 can be provided from opposite ends of the plate 116, allowing the gripper fingers 168 associated with the robotic device 160 to manipulate the plate 116 from both sides and pass the plate 116 back and forth.

[0087] Alternatively, groove 370 may be enclosed on the sides or open on the bottom. Grooves 370 may also be provided with different shapes, such as square or circular in cross section. This feature may be reversed so that instead of gripper fingers 168 aligning with groove 370, the flanges of labware 300 align with beveled grooves in gripper fingers 168 or rack 210.

[0088] 21B shows a set of gripper fingers 168 having conical or pyramidal protrusions 372 and a plate 116 having corresponding conical or pyramidal indentations 374. The conical protrusions 372 are located on the faces of the gripper fingers 168 that grip against the sides of the plate 116. Corresponding conical or pyramidal indentations 374 are located on the outer edge of the plate 116 opposite the gripper fingers 168. In operation, the gripper fingers 168 extend along a specified length of the plate 116 and close against the plate 116 to grip it. This specified length is such that the indentations 374 and the protrusions 372 are aligned. Small amounts of misalignment between the plate 116 and the gripper fingers 168 are automatically corrected by moving the plate 116 so that the conical or pyramidal protrusions 372 move into the recesses 374 and are properly aligned with the gripper fingers 168.

[0089] A corresponding conical or pyramidal protrusion 372 and a corresponding conical or pyramidal depression 374 are provided on the gripper fingers 168 on the other side of the plate 116. Note that the protrusions 372 and depressions 374 do not have to be horizontally aligned. Providing two different heights for the protrusions and depressions allows, for example, the plate to be handled correctly. Furthermore, if the protrusions 372 and depressions 374 are not horizontally aligned across the width of the plate 116, the plate 116 cannot rotate around the depression. In FIG. 21B , the gripper fingers 168 have two protrusions 372 and depressions 374 located on one side of the end of the gripper fingers 168, i.e., one is located toward the end of the gripper fingers 168 and the other is located at the beginning of the end of the plate 116. On the other side, there is a single protrusion 372 and depression 374 located horizontally between the protrusion 372 and depression 374 of the other gripper finger 168. The conical or pyramidal shape allows for alignment and also aids in gripping not only due to the inward force of the gripper fingers 168 required to hold the plate 116, but also due to the vertical component provided by the conical or pyramidal shape to reduce the chance of the plate being dropped by the robotic device 160.

[0090] Other shapes than cones or pyramids may be used, such as semicircular projections 372 and depressions 374. Any number of projections 372 and depressions 374 may be provided as desired. For example, both gripper fingers 168 may not have projections 372 and depressions 374.

[0091] Referring to Figure 21C, a similar arrangement of protrusions 372 and recesses 374 as in Figure 21B is shown. However, the additional recesses 374 are located on sides of the plate 116 that are inaccessible to the gripper fingers 168 when approaching from one side. Furthermore, the recesses 374 are mirrored both horizontally and vertically. That is, the recesses 374 are positioned so that the plate can be picked up by a robotic device 160 having the protrusions 372 from either side of the plate 116. This allows plates 116 or other labware 300 having such recesses to be handled by two robotic devices 160 simultaneously and to be transferred between robotic devices 160 or modules 100.

[0092] 23 illustrates such a transfer between a pair of robotic devices 160, where two sets of gripper fingers 168 can simultaneously engage the plate 116 to provide a transfer in which positive control of the plate 116 is maintained throughout.

[0093] 22, a dock for labware 300, i.e., plate slot 110, is provided to interact with recess 374 so that robotic device 160 can transfer plate 110. Here, instead of providing protrusion 372 in plate slot 110, feedback means 378 is provided in a position where, when plate 116 is placed in plate slot 110, feedback means 378 extends into recess 374 of plate 116 to provide feedback that plate 116 is fully placed in plate slot 110.

[0094] The feedback means 378 in the plate slot 110 can provide mechanical feedback such as: i) when the labware 300 begins to engage the plate slot 110; ii) when the labware 300 is fully engaged; and iii) when the labware 300 is in the correct orientation and has the correct handling interface. The feedback means can be implemented in a manner similar to that previously described with reference to FIG. 18 , i.e., a contact is triggered when the feedback means 378 is within the recess 374. Alternatively, the feedback can be based on the depression of a spring or other resilient means in the feedback means 378 when depressed by the plate 116 and when within the recess 374.

[0095] The feedback reverses when the operation is reversed, i.e., when the robotic device 160 is removing the labware 300 from the plate slot 110. Each of the plate slots 110 on the work deck 330 or in the rack 210 can have these features. In one embodiment, one or more or all of these features are combined with the engagement means 362 described with reference to FIG. 18 .

[0096] The plate 116 and gripper fingers 168 in FIG. 21C have a single protrusion 372 and indentation 374 on each side of the plate 116. However, additional indentations 374 are provided on the front and rear surfaces 116 of the plate, respectively. Furthermore, a protrusion 372 is provided on a beam 376 of the grabber 162 that extends perpendicularly between and connects the two gripper fingers 168. Such protrusions 372 and indentations 374 further provide alignment for the plate 116. As previously mentioned, the number or shape of both the protrusions 372 and indentations 374 on the beam 376 or gripper fingers 168 is not limited to those described above. In one embodiment, an indentation is provided off-center on each end surface of the plate 116 to limit handling of a plate 116 that is positioned correctly.

[0097] Referring to Figure 21D, protrusions 372 and recesses 374 are shown positioned on the footprint 360 of plate 116. This further reinforces that these protrusions 372 and recesses 374 do not encroach on the interior volume of plate 116 or labware 300, and they have a larger footprint 360 area to aid in handling. For example, given the standardized footprint 360 described above with reference to Figures 13A and 13B, protrusions 372 and recesses 374 are compatible with all of the labware 300 described above.

[0098] Two types of features, grooves 370 and protrusions 372 and recesses 374, can be combined in one interface or plate 116.

[0099] The conical fit of the protrusions 372 and recesses 374 tends to self-align the plate 116 even if it is misaligned by a few millimeters with the gripper fingers 168. Additionally, both of the above-described fitment features (grooves 370 or cones 372, 374) allow the gripper fingers 168 to more securely and reliably hold the plate by preventing the labware 300 from slipping or dropping vertically from the gripper fingers 168. The three recesses 374 in FIGS. 21B and 21C allow for unique orientation of the plate 116. The protrusions 372 and recesses 374 align the plate to the gripper fingers 168 in three dimensions. This can be used as feedback that the plate has been properly oriented.

[0100] Both the grooves 370 and the recesses 374 allow the gripper fingers 168 to determine whether the labware 300 has the correct handling interface. This allows the system to reject labware 300 that does not have the interface, which in turn allows the system 99 to reject labware 300 that is the incorrect size. This increases the reliability of the system and allows it to reject third-party trays that have poor tolerances. This can be used to create a partially closed system, making it easier to control the reliability of the system 99.

[0101] The plate incorporating the grooves 370, protrusions 372 and depressions 374 can still conform to the footprint of a microplate (SLAS plate).

[0102] As mentioned above, the interface of Figures 21A-D can be used with labware 300, not just plate 116. Referring to Figure 24, a bottle tray 322 is shown with protrusions 372 and recesses 374. In particular, it can be seen that bottle tray 322 has recesses 374 that are positioned in footprint 360 of bottle tray 322. Therefore, this can be adapted to any type of labware 300.

[0103] 25, a large bottle 326 having the width of plate 16 is provided. It provides a conical fit of protrusions 372 and recesses 374, and the bottle itself has recesses 374 in the body of the bottle. This allows gripper fingers 168 to grip the sides of bottle 326 without using a tray for the bottle 326 to sit on. In one embodiment, bottle 326 is held in rack 210 which has protrusions 372 to hold it in place.

[0104] Trays, plates, and boxes for vials and pipettes adapted to function with grooves 370 and conical mating interfaces are similarly envisioned.

[0105] While a pair of gripper fingers has been described above, other embodiments may use additional means for picking the plate, optionally using the protrusions and depressions described above. Referring to FIG. 26 , a plate 116 is provided having a standard microplate footprint 360. The plate 116 may be labware 300, as described above. Instead of active or passive gripper fingers, a robotic handler may have an end effector having a passive handling plate 260 extending beneath the plate 116 to manipulate and move the plate 116. The handling plate 260 is shown extending across the width of the plate 116, approaching the plate 116 from that width. However, other embodiments are contemplated. The handling plate 260 has a protrusion 372 extending upward from the handling plate 260 toward the footprint 360 of the plate 116 when placed thereon. The plate 116 has a corresponding depression 374 and protrusion 372 in its footprint 360.

[0106] The handling plate 260 also has alignment means 262 that allow for alignment of the plate 116 when it is placed on the handling plate 260. These alignment means 262 extend along the preferred position of the plate 116 on the handling plate 260 and are sloped or tapered to encourage the plate 116 to slide into the correct position when placed on the handling plate 260.

[0107] The protrusions 372 and recesses 374 are shown positioned eccentrically relative to the centerline of the plate 116. However, as noted for the gripper fingers, various configurations are possible. For example, the plate 116 could have multiple recesses 374 so that the plate 116 can be picked up by handling plates 260 approaching from different directions. Also, the protrusions 372 and recesses 374 could be reversed. Also, additional protrusions 372 and recesses 374 could be provided.

[0108] The handling width of the handling plate 260 is smaller than that of the plate 116, so by using the handling plate 260, it is possible to transfer Interface 133 The width of the rack 210 and plate slot 110 can be minimized to the width or length of the plate 116. The handling plate 260 also provides a solid base for increasing the stability of the plate loading operation.

[0109] Referring to FIG. 27, a decapper interface built into a bottle or vial is shown. A bottle 326 is provided with a lid 380. The lid 380 has a capping interface 382 on the top surface of the lid 380. The capping interface 382 is a hexagonally shaped recess such that a correspondingly shaped protrusion can interface with (i.e., reside inside) the capping interface 382. This interface provides a rotation lock such that rotating the lid 380 rotates the male protrusion, and vice versa. The use of this protrusion in the decapper 344 provides a more reliable decapping or capping than conventional gripping or unscrewing of a lid without the interface 382.

[0110] Multiple shapes and interfaces can be used for the capping interface 382. Additionally, the decapper can have a female interface and the bottle can have a male interface, which is more common with conventional auto-mating capping processes.

[0111] Vial 321 also has a lid 384 with a recess on its top surface to form a vial capping interface 386. Similar to bottle lid 380, vial capping interface 386 is shown to have a hexagonal shape when viewed from above, allowing a correspondingly shaped protrusion to rotatably lock with vial lid 384, resulting in a reliable capping or decapping process.

[0112] Similar to the bottle 326, various shapes of the capping interface 386 can be used. For example, another polygonal shape can be used to provide a rotation lock.

[0113] The bottle 326 has a bottom interface 388, which includes a recess similar to that of the capping interface 382, ​​extending from the bottom of the bottle to the body of the bottle 326. The bottom interface 388 is hexagonal when viewed from below. This allows a corresponding hexagonal protrusion to fit into the bottom recess and rotatably lock. The vial 321 also has a vial bottom interface 390 identical to the bottom interface 388 of the bottle 326. These bottom interfaces 388, 390 allow the bottle 326 or vial 321 to be rotatably held from below. This allows the desorption machine 344 to be configured to be attached from below, or the protrusion of a plate to restrain the bottle from rotating so that the decapping operation of the bottle or vial lid does not result in rotation of the bottle or vial itself.

[0114] The lower interface can also be used to prevent bottles 326 or vials 321 from tipping or falling as they are moved through the system 99 by placing them on a tray with specific ridges for alignment. This also allows the bottles 326 or vials 321 to be properly positioned on a tray or plate for various robotic handling devices to interact with them.

[0115] If desired, a combination of upper and lower interfaces can be used. The interfaces provided on the upper and lower sides do not have to be the same. However, identical interfaces can be useful for uniform operations. Vials 321 and bottles 326 can have interfaces of the same shape so that they can be handled by the same gripper on the same picking or decapping robot 344.

[0116] Further modifications can be made to the capping interfaces 382, ​​386, such as an undercut interface 390 where the recess in the lid 380, 384 has a narrower opening than the depth of the cap. This allows for an interface with additional vertical locking, such as a protrusion that expands at the distal end when the lid 380, 384 is removed from the bottle 326 or vial 321. This can reduce the risk of the lid 380, 384 being dropped by the gripper of the picking or decapping robot 344.

[0117] The upper or lower interfaces 382, ​​386, 388, 390 are chamfered or beveled to align the grippers of the decapper or picker as they approach the interface. This allows for some tolerance in the positioning of the vial 321 or bottle 326, such as with the tray or plate, or the tray or plate in the plate slot 110 itself. This also helps with machine or robotic tolerances. These features also allow the machine to reject third-party or poorly toleranced labware 300, allowing for more reliable automation, as labware 300 without the correct interface cannot be used with the machine.

[0118] FIG. 1 illustrates a storage module 100 according to one embodiment of the present invention. The storage module 100 has a shell or housing 102 that forms a box with four sides 104. These sides 104 may all be the same length, forming a storage module 100 with a square footprint. Due to the nature of the module and its internal carousel function (discussed in more detail below), equal-length sides 104 are preferred, but in some embodiments, the sides 104 may be of varying lengths, resulting in a rectangular or other polygonal module 100. Having more than four sides 104 is even possible.

[0119] The length 106 of each side 104 can be 70 cm to 80 cm. In particular, the length 106 of each side 104 of each storage module 100 should be 80 cm or less in at least two dimensions. This makes the overall system 99 of modules 100 compact, which is advantageous because these systems are installed in laboratories or clean rooms where floor space is at a premium, and this allows the modules 100 to fit through doors. This also reduces the difficulty and cost of shipping the storage modules 100.

[0120] Within the outer shell 102 is a carousel 108, which is a circular plate that occupies the footprint of the storage module 100. The carousel 108 has tray or plate slots 110 arranged along its radii (i.e., radially). The center of the carousel 108 is open, containing a center well 112. The plate slots 110 are arranged so that their edges all face the center well 112. In the illustration, the center well 112 has eight tray edges 114, thus being octagonal in shape. In some embodiments, the center well 112 has flat tray edges 114 such that it is a polygon with a number of sides equal to the number of plate slots 110. However, in some embodiments, a center well 112 with a circular edge can be used, with the tray edges 114 forming a perimeter around the circular center well 112.

[0121] Plate slots 110 are locations designated to hold plates, trays, or labware. The plates or trays can be process plates, cell culture plates, microtiter or microplates, plates that hold other labware or containers, or labware itself. Plate slots and plates are described in more detail below.

[0122] The carousel 108 can be placed on the floor of the module 100 or can be elevated off the floor.

[0123] The module 100 has a height such that the shell 102 forms a cube (i.e., a cubical shape). The height of the storage module 100 need not be equal to the length 106. However, the height preferably does not exceed the height of the access door, and ideally should be less than the access door for ease of transportation and assembly.

[0124] In a vertical configuration (see Figures 9A and 9B, described in more detail below), the plate slots 110 are stacked vertically so that process plates or other labware can be stacked vertically in the rack 210. Thus, each plate slot 110 has a plate slot above it, forming a rack 210 of plate slots 110. The design of the plate slots 110 can vary, from being placed directly on the carousel 108 to being placed higher (or lower) above the carousel 108, as will be described in more detail below.

[0125] The racks 210 can extend through the height 204 of the storage modules 100, or even below that height when the carousel 108 is elevated. The space within the shell or housing 102 can have clean air inside and is constructed by assembling multiple modules 100 that can lock together, depending on the requirements of each module 100. Thus, the interior is hermetically sealed, eliminating the need for additional, expensive shrouds or installing the storage modules 100 in large, expensive clean air cabinets.

[0126] 2 shows several storage modules 100 in a modular arrangement to form a modular system 99. In particular, an incubator module 124 is shown on the far left, a process module 120 in the center, and a plasticware storage module 122 on the far right. These modules are indicative and not limiting. However, as shown, each module 100 uses the same format, e.g., each includes a carousel 108 with respective plate slots 110 formed therein or thereon.

[0127] Other modules 100, such as a freezer (126; Figure 3A), can be envisioned. Many experimental and culture media contain reagents, such as growth factors, that must be frozen if stored for more than one or two days. This results in a system 99 that prepares media daily or every two days by mixing reagents into a basal medium, with some of the reagents stored frozen within the system. Thus, a freezer module 126 can be provided, allowing the system 99 to store frozen reagents and retrieve and thaw them as needed. Another module 100 in the system is a refrigerator (128; Figure 3A). Many reagents, especially cell culture media, are stored in the refrigerator, and relying solely on the freezer module would make repeated freezing and thawing of reagents cumbersome and even harmful.

[0128] As shown in FIG. 2, this example of a modular system 99 used for cell culture includes a process module 120 and a series of storage compartments, namely, an incubator 124 for cell culture and a plasticware storage compartment 122, such as the module on the right. As mentioned above, other modules may include a refrigerator for storing media, a freezer for storing, for example, growth factors and samples, and a room-temperature reagent storage compartment. A slot 110 is provided configured to receive a set of labware 300 designed to fit into a slot with a microplate footprint. The set 300 may include a tray, an adapter rack for bottles or vials, a box, bottles, or a dish, as described in more detail below with reference to FIGS. 13A and 13B. A plate 116 (e.g., a cell culture plate, an adapter rack, or labware) may be placed in the plate slot 110. The plate 116 may be loaded with a vial or container capable of holding reagents or cell culture media. The plate 116 may be transported between modules 100, such as when the plate 116 is passed from the incubator 124 to the process module 120. The transfer is performed by a specific transfer Interface 133、 It will be held at 134.

[0129] The storage module 100 is configured to allow the module 100 to present or receive plates 116 (or other plasticware). transfer Interface 13 3 It has. transfer Interface 13 3 on the adjacent module 100 transfer Interface 13 3 , allowing the plate 116 to be transferred from one module to another, for example, so that a plate 116 holding vials can be transferred from an incubator 124 to a process module 120. transfer Interface 13 3 The modules 100 may have doors 130 to close access to the modules 100. These doors may open vertically or horizontally, may be sliding doors, and may have multiple panels or be a single door 130. The doors may vary depending on the requirements of the module 100. For example, some doors are pressure resistant or thermally insulated. These transfer Interface 13 3 can be in the same plane (e.g., in a horizontal plane to greatly simplify robot handling). transfer The interface can also be vertical or a variation thereof. Storage modules 100 can be stacked vertically to conserve floor space. This allows for the construction of a system 99 by stacking modules 100 together without the need for gaps or spaces between modules, and therefore without the need for additional processing capabilities to transfer trays 116 or other items between them. It also allows for the system 99 to be upgraded to add more functionality or more capacity by stacking more modules 100. Vertically stacked modules are described in detail with reference to FIG. 9A. They are connected using sealing elements 311 that form a gripper path.

[0130] As mentioned above, module 100 transfer Interface 13 3 and in some embodiments, these transfer The interfaces are hermetically sealed by sealing elements 311 and / or doors, thereby allowing modules 100 to be "connected" together to create a complete system 99 containing clean air, without the need for expensive and bulky housings containing clean air spaces. transfer Interface 13 3 The doors 130 only provide access to adjacent modules 100, instead of passing the plate 116 through to the external space outside the outer shell 102 or housing. To ensure this is maintained, the doors 130, if any, are also hermetically sealed to each other, which also has the advantage of making handling easier.

[0131] 2 also shows a robotic device 160. The robotic device 160 is disposed in the center well 112 of the module 100. The robotic device has a grabber 162 capable of holding a plate 116 from a plate slot 110. The robotic device 160 also has a robotic arm 164 connected to the grabber 162 to enable actuation of the grabber 162 to extend and retract. The robotic arm 164 is telescopic. The grabber 162 can reach the plate 116 holding the plate slot 110 (or the rack 210 of the slot 110) and restrain the plate 116 so that the plate is pulled out of the slot 110 or rack 210 and placed in the slot 110 or rack 2 ... that can move the plate 116 to an adjacent module 100 by actuation of the robotic device 160. transfer Interface 13 32 shows two modules 100 (e.g., incubator 124 and plasticware storage 122) with similar robotic devices 160 with grabbers 162 and doors 130 in the same locations. Not all modules 100 need have robotic devices 160; some modules 100 may rely on robotic devices 160 from adjacent modules to pass or transfer plates 116. Notably, process module 120 is shown without robotic devices 160.

[0132] A robotic device 160 in the center well 112 of a module 100 can pass a plate 116 to a plate slot 110 in another module 100 without intermediate devices such as a robotic arm or conveyor belt. This provides a simpler system 99 by eliminating the intermediate devices. Eliminating the space required for intermediate devices also makes the system 99 more compact, reduces alignment and tolerance stack-up issues, reduces double handling, and facilitates building compact systems that do not require additional external shrouds or clean air housings.

[0133] The robotic device 160 within the center well 112 may have very limited degrees of freedom of movement. It may have only two degrees of freedom: vertically within the well 112 and in relation to the door 130 or transfer Interface 133、 134 or horizontally into slot 110. Carousel 108 can be configured to rotate to allow robotic device 160 access to all of racks 210. Thus, robotic device 160 can: transfer Interface 133、134) and vertically. Alternatively, in some embodiments, the robotic device 160 can rotate and the carousel 108 can be constrained, or a combination of both. The robotic device 100 can be further constrained, such as by running in rails or having a grabber 162 that runs in rails instead of extending the robotic arm 164. This reduces the chance of the robotic device 160 losing alignment. The modular system 99 also allows for modular software with reused code. This is achieved in part by making the storage module 100 a "self-contained vending machine," in the sense that it autonomously provides plates 116 (and other objects) to other modules 100, instead of having an incubator 124 with an automatic door 130 and carousel 108 that a 3D robotic arm reaches.

[0134] 3A and 3B show a plan view of a further system 99 including several modules 100. Multiple modules 100 are arranged horizontally to provide an example complete system 99 constructed from an incubator 124, refrigerator 128, freezer 126, and plasticware storage 122, interfacing with a central process module 120. Each module except the process module is equipped with a robotic device 160 in the center well 112, so no "external" untethered 3D robotic arm is required. All modules 100 are connected by a door 130 or door 140 adjacent to the plate 116. transfer Interface 13 3The process module 120 is centrally located to allow access to each side of the multiple modules 100 (incubator 124, refrigerator 128, freezer 126, and plasticware storage 122). When the extending robotic arm 164 is fixed (so that it cannot rotate), it is pointed towards the door of the process module 120 to allow the plate 116 to enter and exit the process module 120. A service module 138 can be added to provide additional functionality, such as a processor unit, power means, or machine unit for operating the robotic device 160.

[0135] In some embodiments, a module 100 may have a dedicated "load lock" with a door that is externally accessible and not connected to another module 100. This load lock is routinely accessible to personnel. This allows users to interact with the plate slots 110 or racks 210 to exchange consumables, plates containing cells or samples, etc. within the system 99. The load lock may only open to the outside or inside of the module 100 at any time to avoid contamination or changes to environmental conditions inside the module 100. This prevents access to rotating or manipulating machinery when a user accesses the load lock, allowing the system 99 to continue operating without risk of injury. In some embodiments, the load lock may be rotatable to access additional accessible doors or to allow a robotic handler to access the contents placed within the load lock.

[0136] FIG. 3B shows a system with the same modules 100 as FIG. 3A: incubator 124, refrigerator 128, freezer 126, and plasticware storage 122. However, freezer 126 is connected to a refrigerator module 128 that is connected to process module 120. This means that freezer 126 is accessed through refrigerator 128, reducing frosting and temperature cycling within freezer 126. The refrigeration module has been described. However, additional environmental changes between modules 100 are anticipated, such as changes in humidity, temperature, or gas concentrations. Automated or user-controlled controls are provided to control the environment of each module 100.

[0137] Optionally, the process module 120 may not include a robotic device 160 for transferring plates 116. However, other robotic operations may be implemented within the process module 120 for the automated cell culture system 99. The process module 120 may include a liquid handler with a rotating work deck, or "turntable work deck" 108, that interfaces with at least one carousel. Slots on the work deck may accommodate microplates 116 or compatible labware by simple (horizontal linear) transfer from an appropriately positioned carousel 108 and rotation of the turntable work deck and carousel 108. The process module 120 may also include a microscope, other handling modules (vial decapper, vial picker, plate de-lidder), or other functions, as described below with reference to Figures 15A and 15B.

[0138] Plates 116 are microtiter plates or microplates, or other labware with a similar footprint. These plates conform to the Society for Laboratory Automation and Screening (SLAS) standard, which requires microplates to be 85.48 mm wide and 127.76 mm long, although variations and modifications to this are possible.

[0139] Additional tube-picking robotic devices can be provided in refrigerator 128 or freezer 126, for example, to pick frozen tubes from rack 210 while minimizing temperature cycling of other tubes in rack 210. Picking robots can be incorporated into wasted space within rack 210 of refrigerator 128 or freezer 126.

[0140] During operation, one or more source storage plates 116 are removed, for example, from a shelf or rack 210 in the freezer 126, and the desired tubes are removed from the plate 116 and placed in the target plate 116. The source plate 116 is returned to the storage shelf 210, and the target plate 116 with the picked tubes is transferred to the incubator 124 where it is thawed and / or warmed. After sufficient time has passed to reach the target temperature, the plate 116 with the tubes is transferred to the work deck. The process is reversed, with tubes containing unused reagents being returned to the freezer storage 126. Bottles or vials can be thawed or pre-warmed by transferring them to the incubator 124. Additionally, to conserve space on the work deck, a de-lidder can be incorporated into the slots 110 in the racks 210 of the incubator 124.

[0141] A high efficiency particulate air (HEPA) filter can be provided for the incubator 124, and the air within the incubator 124 is recirculated through the filter to reduce particulate matter within the incubator 124. Although not a HEPA air filter, an air filter can also be provided that removes 99.97% of particles 0.3 μm or larger (from the air passing through).

[0142] 4A and 4B, between two rotating carousels 108 of adjacent modules 100 transfer Interface 13 3 4B shows a 6-well tissue culture plate 116 passing through the interface. transfer Interface 13 3 Both modules 100 have a rotating carousel 108. Only a portion of each rotating carousel 108 (i.e., one slot for a plate 116) is shown. One module 100 can be an incubator 124 with a carousel 108 that has racks 210 (also called a plate hotel). transfer Interface 133 The main operation performed in is the movement of the plate 116 between the two modules 100. In some embodiments, the plates generally conform to SLAS size standards, such as cell culture plates 116 (e.g., a 6-well cell culture plate 116 is shown), or other compatible labware. Automatic doors 130 (not shown) are provided between the modules. Some modules may have transfer Interface 13 3 However, for example, if the environments between the modules 100 are different, a door 130 is provided. The two modules 100 are connected by connecting means or fasteners (bolts) 132. transfer Interface 13 3 The fixture 132 is fixed or locked at transfer Interface 13 3, minimizing tolerance stack-up. To ensure that the plate 116 can pass between the modules 100 without collision between the outer shells or housings 102 of the modules 100, the fasteners 132 ensure that the modules 100 are aligned and held or locked in place. Additional fasteners 132 may also be provided so that the modules 100 can be coupled to each other or to other features or modules 100. Thus, transfer Interface 13 3 provides a controlled location where the position of the plate 116 is constrained for delivery of the plate 116. A connecting means or fixture 132 is located near the location where the plate 116 is delivered. In some embodiments, the fixture 132 is transfer Interface 13 3 From the edge of transfer Interface 13 3 This reduces "tolerance build-up," which can affect the alignment of critical parts due to fixture or manufacturing variations or movement during operation. In particular, when fixture 132 is transfer Interface 13 3 The connecting means 132 may be bolts or any other means that constrain or compress the housings of two adjacent modules 100 to hold them firmly together. In some embodiments, interlocking lips or other indexing means are provided to align the modules so that the connection means 132 can be aligned. The carousel 108 may be configured to align, for example, by means of pins 140 and slots 142. transfer Interface 13 3The plate 116 is indexed relative to the plate slots 110 on the carousel 108. Pins 140 are provided in the wall of the module 100. Alignment slots 142 are provided in the carousel 108 where the carousel 108 can receive or hold the plate 116. The plate slots 110 on the carousel 108 are aligned such that the transfer of a plate 116 (or other compatible labware) between two plate slots 110 on the carousel 108 can be accomplished by a simple linear movement from one plate slot 110 to an adjacent plate slot 110 on the other carousel 108. transfer Interface 13 3 The pins 140 can be moved so that the alignment slots 142 are always free to move. Alternatively, the carousel 108 can be aligned when moved to the transfer position and can rotate freely at other times. While a pin 140 and slot 142 are shown, other alignment means, electronic or mechanical, can be provided. For example, the slot and pin positions can be swapped so that the pin 140 is positioned within the carousel 108. Alternatively, the carousel 108 motor can be indexed and stopped at a predetermined index position. Figure 4B shows the movement of a plate from one plate slot 110 to another plate slot 110. transfer Interface 13 3 The plate 116 is shown passing between the modules 100 so that it passes through the plate 116 in the direction indicated by the robotic device 160.

[0143] This movement is driven by the robotic device 160. The carousel 108 rotates and the robotic device 160 moves vertically, and the robotic device 160 then moves the plate 116 from any position within the carousel rack 210 with a combination of highly constrained movement along two constrained axes. transfer Interface 13 3The robotic device 160 moves in three directions: vertically to the appropriate level in the rack, horizontally to remove the plate 160, vertically to the height of the working deck (i.e., plate slot 110) of the carousel 108, and horizontally to place the plate 116 in the plate slot 110 on the carousel 108. More specifically, the robotic device 160 moves horizontally in a direction along a line connecting the two central axes of the center wells 114 of adjacent modules 100. The interfaces / doors 130, 13 3 is positioned on the sidewall of each module so that its widthwise center is on a line connecting the two central axes of the center wells 114 of the adjacent module 100. The robotic device 160 has sufficient horizontal movement to move the plate 116 directly into the slot 110 of the other carousel 108. Not all robotic devices 160 require this degree of horizontal movement, as there may be a robotic device 160 in an adjacent module 100. In such a situation, the robotic device 160 can hand over to a robotic device 160 in the adjacent module 100.

[0144] FIG. 4A shows an additional alignment mechanism 144 to ensure that the plate 116 is properly aligned during transport. transfer Interface 13 3 A chamfer 144 at the end of the plate slot 110 of the carousel 108 opposite the plate slot 110 acts to capture and align the incoming labware 116, even if it is misaligned by a few millimeters. This occurs when the plate 116 collides with the chamfer 144, which tilts toward the plate slot 110, thus allowing the plate 116 to slide and align toward the plate slot 110. Alternatively, the alignment mechanism 146 transfer Interface 13 3 In such a case, the door 130 or the space between the modules may be present in the opening or door 130 itself. transfer Interface 13 34B. In this arrangement, a plate 116 that falls out of alignment during transport will collide with the chamfer 146 and be oriented back into alignment with the plate slot 110.

[0145] FIG. 8 shows the chamfer 146 facing the interior of the module 100. transfer Interface 13 3 are located on the surface of transfer 1 illustrates an alternative embodiment of the interface. Thus, the chamfering increases with increasing distance from the center of the module 100. transfer Interface 13 3 Narrow the width of the mouth. transfer Interface 13 3 This allows for alignment of the plate 116 and / or grabber 164 to enter the mouth of the plate 116. Although not shown, in some embodiments, the plate 116 may be inserted into the plate slot 110, transfer Interface 13 3 , grabber 164, or any other feature that may interact with plate 116. Such alignment features on plate 116 further allow for alignment of plastic instruments passing through module 100 or system 99. A combination of these chamfer locations may be provided on module 100.

[0146] Referring to FIG. 4C, instead of or in addition to providing chamfers 144 on one or more edges of the plate slot 110, transfer Interface 13 3 The wall of the housing may be provided with a recess 148. The recess 148 may be transfer Interface 13 3 From the perspective of transfer Interface 13 3 The recess has a shape extending toward the center of the module 100. The recess provides a space or opening 150 for the plate 116 (between the modules 100). transfer Interface 13 3 The space defined by the plate 116 can be shaped so that the width of the plate 116 is close to that of the plate 116. This allows the side of the plate 116 to transfer Interface 13 3 Such recesses can be present on both modules 100 so that there is an extended area where plates 116 are forced to align within recesses 148. The recesses allow unaligned plates 116 to transfer Interface 13 3 The grabber 164 is configured to slide across the face of the recess 148 until it is aligned to pass through the plate 116. In some cases, the grabber 164 that operates the plate 116 may be wider than the width of the plate 116. In such cases, any alignment means, such as the recess 148, is configured to accommodate the grabber 164 and thus be equal to or slightly larger than the outer width of the grabber 164. In other cases, rails or slots may be provided to guide or support the movement of the grabber 164. In some instances, the grabber 164 may be wider than the width of the plate 116 and grabber 164. transfer Interface 13 3 The slot can be constructed by narrowing the carousel bevel 144 and providing a slot in the interface through which the grabber 164 extends. transfer Interface chamfer 146, and transfer A combination of interface recesses 148 may be provided, all of which function to dynamically align the moving plastic implement with the plate 116 and / or grabber 164.

[0147] Although spaces are shown in the figure to provide clear boundaries between the different modules 100, transfer Interface 13 3 can be adjacent so that they are flush with one another. Further, as noted above, in some embodiments, transfer Interface 13 3At least some of the modules 100 in the automated cell culture system 99 have clean, HEPA filtered air. transfer Interface 13 3 Sealing prevents the intrusion of unfiltered air. Sealing may include ensuring there are no gaps between modules 100 and / or transfer Interface 13 3 Alternatively, this can be achieved by placing a seal around the door 130. Seals can also be provided between the edges of the module 100.

[0148] Opening 150 (between modules 100 transfer Interface 13 3 Openings 150 (in the carousel 108) and plate slots 110 in the carousel 108 are closely positioned and can closely fit plates 116 (e.g., microplates). Together, openings 150 and plate slots 110 form a substantially continuous "race" or "channel" along which plates 116 and / or grabbers 164 of robotic device 160 slide or run, thereby significantly reducing the chance of labware being dropped, lost, or misplaced because the position of the labware is always confined.

[0149] 5 , the plate slot 110 is shown having slot sides 152 extending from a bottom 154 of the plate slot 110. The plate 116 is positioned on the bottom 154 of the plate slot 110 between the slot sides 152. The slot sides limit lateral movement of the plate 116. The end of the plate slot 110 opposite the end of the plate slot 110 in the direction of movement of the plate 116 can be further closed, for example, by a backplate or end stop extending partially or completely between the slot sides 152 to prevent rearward movement of the plate 116. The slot sides 152 include gripper grooves 166 extending along the length of the slot sides 152. The gripper grooves 166 are shaped so that gripper fingers 168 of the grabbers 162 can move along the gripper grooves 166 when the plate 116 is present. A microplate 116 is shown in which grabbers 164, or gripper fingers 168, grasp the plate 116 by surrounding it on either side. This allows the robotic device 160 to pick up and move the plate 116 as needed. In some embodiments, the gripper grooves 166 extend only partially along the length of the slot side portions 152. Corresponding grooves 166 can extend from the opposite edge, allowing the gripper fingers 168 to grasp the plate from either side. Other examples of grabbing mechanisms can be provided. For example, grooves can be provided so that the gripper fingers 168 fit into the plate itself 116 instead of the bottom surface 154 of the plate slot 110, or grooves can be provided in the plate 116 itself so that the gripper fingers 168 enter the plate body.

[0150] 5 has a bottom that is wider than its sides. To accommodate this, the slot sides 152 of the plate slot 110 can have different widths above and below the gripper grooves 166.

[0151] Figure 6 shows transferInterface 13 3 The figure below shows a side cross-sectional view of the transfer Interface 13 3 108. As mentioned above, the plate slots 110 of the carousel 108 have recesses formed by the slot sides 152 so that the plate 116 or other labware, and / or the grabber 164 of the robotic device 160, travel within the channels 156 or troughs or races or rails. In this manner, the plate 116 and grabber 164 are highly confined, making the transfer very reliable. transfer Interface 13 3 This substantially continuous channel 156, formed in the plate slot 110, uses the bottom portion 154 of the plate slot 110 as the floor of the channel 156. The plate 116 or other labware and / or grabber 164 slide within this channel 156. By physically restraining the plate 116 / labware and grabber 164, the channel 156 greatly reduces the chance of labware being dropped or lost, making the system simpler, more reliable, and easier to program.

[0152] 7A and 7B show that the plate 116 in the plate slot 110 of the carousel 108 transfer Interface 13 3 1. The robotic device 160 includes a grabber 164 with gripper fingers 168, ready to move to the adjacent plate slot 110 via the transfer Interface 13 3 1. The robotic arm 162 is actuated to move the grabber 164. transfer Interface 13 3 The width of the gripper fingers 168 is close to that of the gripper fingers 168 to ensure that the plate and grabber 164 fit securely and can be physically restrained and aligned.

[0153] Figure 8 is not based on a carousel transfer Interface 13 3 1 shows an alternative embodiment of the present invention, where the plate slot 110 on the module 100 is a conveyor belt 170. This conveyor 170 is transfer Interface 13 3 through, or transfer Interface 13 3 The robotic device 160 may still be present to deliver or retrieve the plates 116 to or from the conveyor 170. As noted above, the chamfer 146 is also shown, but the chamfer is located on the side facing the interior of the module 100. transfer Interface 13 3 are placed on the surface of the

[0154] The modules 100 can be arranged vertically for added flexibility. Figures 9A and 9B show a system 99 with the modules 100 so arranged. This arrangement facilitates the arrangement of the system 99 by allowing more freedom as to where the modules 100 can be placed in the system 99. For example, it is easy to add more capacity to the system 99 by stacking the plastic labware storage 122 or incubators 124 higher. Stacking the modules 100 vertically allows the system 99 to occupy less floor space.

[0155] As described above, the two modules 100 are arranged so as to be stacked in the vertical direction. Between the modules, there is provided a gap between the horizontally arranged modules 100 shown in FIGS. 4A to 4C. transfer Interface 13 3There is a vertical interface 234 that is very similar to it. The vertical interface 234 is optional and has a door 230 or an opening 231 through which the robot device 160 can move vertically. The module 100 has connecting means or fixing points 232 around the door 230 or the opening 231 to ensure that the vertically stacked modules 100 are securely constrained to each other. The fixing points 232 are arranged near the opening 231 or the door 230 and reduce the tolerance buildup as described with reference to the connecting means 132 in FIGS. 4A - 4C. The airtight seal means 311 can be arranged between the transfer interface 13 3 of two adjacent modules, 234.

[0156] FIGS. 9A and 9B show a plate track 210 in which a plurality of vertically stacked plate slots 110 are arranged. Thus, the rack 210 is formed by the plate slots 110 being formed in layers. Two racks 210 are shown in FIG. 9A, and the rack 210 is arranged on the plate slots 110 around the carousel 108 shown in FIG. 1. For simplicity, the carousel 108 is not shown in FIG. 9A or FIG. 9B. However, the plate track 210 rotates about the axis of rotation of the carousel 108 so that the robot device 160 can access each row of the rack 210. The robot device 160 is rotatably fixed so that it can move only in the horizontal and vertical directions. Thus, to access the plate slots 110 behind the robot device 160, the rack 210 (and thus the carousel 108) is rotated so that the required plate slots 110 face the robot device. Next, the vertical and horizontal movement of the robot device can be executed to access the plate slots 110. In some alternative configurations, the rack 210 can rotate in subgroups so that the layers of the plate slots 110 rotate independently of the plate slots 110 below them. Alternatively, the robot device 160 can rotate and the rack 210 is held stationary.

[0157] As will be appreciated from the previous discussion, the module 100 has horizontal transfer Interface 13 3 This horizontal transfer Interface 13 3 are formed at a height in the rack 210 that is the same height as the plate slots 110 of the current module 100 and the required plate slots 110 of the adjacent module 100. transfer Interface 13 3 These plate slots 110 located at the height and rotational position of the module 100 are transfer slots. transfer Interface 13 3 The modules 100 are rotatable on the carousel 108 so as to be aligned with the corresponding transfer slots in adjacent modules 100. In some embodiments, transfer Interface 13 3 Any plate slot 110 on the rack 210 that is horizontally aligned with the rack 210 can function as a transfer slot, and this can include plate slots 110 that are vertically aligned on the rack 210.

[0158] In use, the carousel 108 rotates horizontally to transfer plates from the storage modules 100 (incubators 124, refrigerators 128, freezers 126, plasticware storage 122, load locks, etc.). transfer Interface 13 3 the door of the rack 210 and align the "transfer slot" of the module 100. transfer Interface 13 3 The transfer slot may be empty or may contain a plate 116 to be transferred. transfer Interface 13 3 The receiving transfer slot is indexed to the delivery transfer slot and transfer Interface 13 3 and if a door is present, it is opened, thus allowing access to the transfer slot, door or transferInterface 13 3 , and the receiving transfer slot. If the transfer slot contains a plate 116, the grabber 164 moves horizontally into the transfer slot, engages the plate 116, and then moves along the same axis against the door or transfer Interface (13 in Figure 7) 3 ) and then the grabber 164 releases the plate 116 and retracts into its own center well 112. In some embodiments, any slot in the horizontal row can be used as a transfer slot. In some embodiments, a slot in that horizontal row can be used as a buffer (described below).

[0159] In some embodiments, transfer Interface 13 3 has a height sufficient to pass through a cell culture plate 116, such as a microplate. However, in other embodiments, transfer Interface 13 3 The height of the door 300 is larger to allow for the transfer of taller labware 300 to and from the module 100. The height can be specified by the door 300 opening to the required height depending on the plate 116. In such a case, transfer Interface 13 3 can extend vertically greater than the height of the microplate. More specifically, in some embodiments, the door 130 can be taller in a particular module 100. For example, a refrigerator can have a taller door 130 to accommodate bottles. transfer Interface 13 3 The height will be 4 cm to allow for the transfer of deep well plates, 8 cm to allow for the transfer of bottles, and 10 cm to allow for the transfer of pipette boxes.

[0160] The robotic device 160 is positioned in the center well 112 and can transfer plates 116 or other labware to and from plate slots 110 on racks 210 in another vertically arranged module 100. A vertical rail 172 is provided that appropriately extends the height of the rack 210 to allow the robotic handling device 160 full vertical movement to access all plate slots 110 on the rack 210. The grabber 162 of the robotic device 160 is connected to the rail 172 by an engagement device 174. The engagement device 174 is attached to the rail 172 by runners 176. The runners 176 are vertically disposed at either end of the engagement device 174. The engagement device 174 moves the robotic device 160 vertically along the vertical rail 172 by actuating the runner 176. The actuation means can be a motor. The grabber 162 is attached to the engagement device 174 and moves vertically along the engagement device 174. This allows the grabber 162 to reach all plate slots 110 throughout the height of the rack 210 and is not limited by the height of the engagement device 174. Vertical movement of the grabber 162 can be achieved via a motor or servo mechanism located within the engagement device 174.

[0161] When transitioning from one module 100 to another, the robotic device 160 must transition onto the rails 172 of the other module 100. To accomplish this, the runners 176 disengage from the rails of the module 100 that the robotic device 160 is transitioning to, so that the robotic device is held by the runners 176 on the opposite vertical side of the engagement device 174. The disengaged runners 176 then engage the rails 172 of the module 100 that the robotic device 160 is transitioning to, as shown in FIG. 9B , with continued vertical movement from the runners 176 that the robotic device 160 is still engaged with. Continuing vertical movement releases the other runners 176 to re-engage with the rails 172 of the other module 100. Thus, the robotic device 160 is always held and constrained within at least one module 100 in which at least one runner 176 engages the rails 172.

[0162] Each module 100 can have its own robotic device 160, or alternatively, a single robotic device can be provided to perform operations on both modules 100. When multiple robotic devices 160 are provided, they are constrained to prevent collisions with each other. In some embodiments, the robotic devices 160 move in different horizontal planes. Additionally or alternatively, they operate on different rails 172 or other transport means. When a shared rail 172 is used for multiple robotic devices 160, plates 116 must be passed between the devices to allow access to all plate slots 110 of the modules 100.

[0163] While a specific configuration has been described, other means of transitioning the robotic device 160 are possible. For example, multiple runners 176 could be used, or a single runner that is tall enough to span the interface 234 between modules 100 to ensure that the modules 100 are always engaged with the rail. By providing multiple rails, the robotic device 160 is restrained at multiple points, ensuring better alignment and reducing sagging due to the weight of the plates 116. Alternatively, the rails 172 could be omitted, and instead a vertically extending robotic arm could be used that is fixed at a single point and is not guided by rails or other means to transport the device vertically.

[0164] Thus, the robotic device 160 can engage with alignment and / or indexing features (e.g., rails 172, shelf chamfers, slot and pin features, indexing motors) in other modules 100. The transfer can be downward or upward, but not necessarily both.

[0165] As previously mentioned, the racks 210 are arranged on the carousel 108 so as to rotate, and the robotic device is constrained to horizontal movement in one plane. Thus, vertical movement in one plane and horizontal movement in one plane allows the robotic device to access all plates 116 in the racks 210.

[0166] FIG. 10 shows a schematic diagram of a system in which multiple modules 100 are provided in a vertically and horizontally stacked arrangement. In this configuration, the system 99 is provided with a freezer module 126. The freezer module 126 has a robotic device 160 capable of picking plates 116. The robotic device 160 can be any of the robotic devices described herein. A vial picker can also be provided (described in more detail with reference to FIG. 15B). The freezer module 126 is horizontally connected on its horizontal side to a refrigerator module 128 and a plasticware storage 122. The robotic device 160 can transfer plates 116 (or other plasticware) between these vertically connected modules. The refrigerator module 128 also has a robotic device 160. The robotic device 160 can be any of the robotic devices described herein. The incubator module 124 is stacked vertically on top of the refrigerator module 128. The incubator module 124 and refrigerator module 128 have an interface that allows plates 116 (or other plasticware) to be transferred between them by vertical movement of a robotic device 160. The incubator 124 also has a robotic device 160 for gripping plates. The robotic device 160 can be any of the robotic devices described herein. The incubator 124 can optionally be equipped with a plate de-lidder. The process module 120 is positioned horizontally relative to the incubator module 124. Therefore, the process module 120 is stacked vertically on the freezer module 126. However, there is no interface between the process module 120 and the freezer module 126. The process module 120 may include a microscope, a vial decapper, and a liquid handler. It also includes a turntable / carousel 108. However, in this example, the process module 120 does not include a robotic device 160 for handling the plates 116. Instead, the plates 116 are placed on the carousel 108, and other devices within the module perform the operations. The incubator 124 and the process module 120 interface so that the incubator's robotic device 160 can transfer the plates 116 from the incubator onto the carousel 108 of the process module 120. The process module is horizontally connected and interfaced to a plasticware storage 122. The plasticware storage 122 can also contain reagents at room temperature. Because the freezer 126 and the process module 120 are both connected horizontally to the plasticware storage 122, the plasticware storage 122 is a module that is twice as tall as the other modules 100 in the system 99. For example, the module is approximately 70 cm 3 10 includes a plate-grabbing robotic device 160 that can transfer plates 116 (or other plasticware) to both the process module 120 and the freezer 126.

[0167] As is clear from the above description, the modules 100 have compatible interface formats that allow for stacking of the modules. This is particularly true when the modules are cubic in structure and the larger modules are integral multiples of the cube. In particular, stacking one on top of another storage 122 increases the capacity of the plasticware storage 122. The capacity of the plasticware storage 122 may be limited in some cases. This arrangement therefore allows the system 99 to operate autonomously for extended periods of time without restocking, for example, on weekends or holidays, while maintaining modularity. In some embodiments, the system 99 has the capacity to culture at least 150-200 cell culture plates.

[0168] This requires a refrigerator 128 with a capacity equivalent to approximately 100 plates to store sufficient media and other liquids for unattended operation. Specifically, if each plate requires an average of 10 ml of media every two days, 200 plates require 1,000 ml of media per day. Deep-well plates hold approximately 192 ml of liquid, so a three-day supply of media requires 16 plates (i.e., 3 x 1,000 ml / 192 ml), which requires deep-well plates at least twice the height of cell culture plates. Therefore, the media alone requires the equivalent of 32 plate slots. PBS, trypsin, and other supplies require an additional 40 or more slots. Plasticware storage 122 may require a capacity equivalent to approximately 400 cell culture plates, depending on whether pipette tip boxes are included.

[0169] Processing such a large number of plates therefore places a significant load on the robotics of system 99. The liquid handler 340 (described in more detail below) can be operated near its capacity. This may require minimizing cycle time, which may require minimizing plate transfer time (into and out of process module 120). Because the liquid handler 340 may not be able to operate while a process module 120 is being loaded or unloaded, the robotics 160 can operate sequentially with the liquid handling robot 340. For example, if the robotics 160 were transferring items between the plasticware storage 122 and the process module 120, this could become a bottleneck that reduces effective system performance.

[0170] Furthermore, plate transfer can be a cumbersome problem. Specifically, the robotic device 160 that moves plates 116 into and out of the process module 120 has two-way traffic, meaning that plates "pass" through the robotic device 160 in two different directions: into the process module and out of the process module. This bidirectional traffic can be difficult to handle efficiently, especially for a heavily utilized robotic device 160, and the robotic device 160 can become a bottleneck. Therefore, in some embodiments, the system 99 employs "buffering," i.e., providing a plate slot 110 that is temporarily used for the transfer of labware to and from an adjacent module 100. This plate slot 110 is called a buffer. Furthermore, the movement of plates from the buffer to the process module is fast and short. Furthermore, the traffic is essentially very simple.

[0171] transfer Interface 13 3On the level of the rack 210, i.e., on the transfer slot, which is horizontally at the same level as the module 100, the module 100 has at least one transfer slot or space that serves as a "pass-through" slot. In this case, the robotic device 160 passes the plate 116 through the pass-through slot, transfer Interface 13 3 and can be passed to another module 100. transfer Interface 13 3 If all transport slots at the same level as, are pass-through slots, then they can be used as buffers to provide buffering.

[0172] 11A and 11B, the process module 120's turntable half is loaded. Plates or other labware can be placed in buffer slots 1-3 (see 211, 212, and 213 in FIG. 11A) of a module 100 (e.g., incubator 124) that interfaces with the process module 120. The module's 100 robotic device 160 can pick up a plate 116 from any slot 110 of the module 100 and place it in the appropriate buffer slot 211, 212, or 213 (as previously described, in some embodiments, this is accomplished via a combination of vertical and radial movement of the robotic device 160 in a single plane and rotation of the carousel 108). Referring to FIG. 11B, the plates 116 can be placed in an order that results in the plates being placed in the desired positions on the process module's turntable / carousel 108. This buffering can occur while the process module 120 is operating (e.g., handling liquids).

[0173] Considering the step of loading a process module 120, the carousel 108 of the storage module 100 rotates to, for example, load a buffer / transfer slot 1211 into the process module 120. transfer Interface 13 3The carousel 108 of the process module 120 rotates to move the transfer slot. transfer Interface 13 3 The robotic device 160 of the storage module 100 can then remove the first plate 116 from the transfer slot, which may have the door 130 opened as needed. transfer Interface 13 3 The robotic device 160 then retracts to the center well 112 of the carousel 108 of the storage module 100. The carousel 108 of the storage module 100 then rotates to the next transfer slot, buffer slot 2 212, which contains the next labware to be transferred. transfer Interface 13 3 At the same time, the carousel 108 of the process module 120 rotates to locate the next transfer slot. transfer Interface 13 3 The robotic device 160 then transfers the second plate from the transfer slot to transfer Interface 13 3 , into the transfer slot of the carousel 108 of the process module 120, and then back to the center well 112 of the carousel 108 of the module 100. This operation is repeated once more to transfer the remaining plates. In this example, the carousel 108 of each of the process module 120 and the storage module 100 rotates to the next plate slot 110 on the carousel 108 so that the next operation can begin. Thus, for a carousel 108 with eight plate slots 110 on the horizontal plane, the carousel 108 only needs to rotate one-eighth of a full rotation. This reduces the travel time and, consequently, the time between transfer operations.

[0174] While the above example describes a single module 100 supplying plates to the process module 120, more modules can simultaneously supply the process module 120. In some embodiments, these modules are generally located on opposite sides of the process module 120. This allows each half of the carousel 108 of the process module 120 to be filled (or emptied) at the same time, allowing for the most efficient transfer to the process module 120.

[0175] In the embodiment shown in Figures 12A-12F, two modules 100 are an incubator 124 and a plasticware storage 122. These two modules 100 send the most items to the process module 120. Figure 12A shows the flow of plates 116 using arrows for indication. Furthermore, the unloading and loading of the process module 120 typically occurs continuously without pauses. Typically, each module 100 loads approximately four plates into its buffer, or transfer slot, ready for transfer to the process module 120. Figure 12B shows a starting position where the module 100 is buffered and the process module 120 is full of plates 116. For example, as shown, if the carousel 108 of the process module 120 holds eight plates and the carousel 108 of module 100 has eight buffer positions, the combined capacity of the two modules 100 can buffer up to eight plates 116 in the transfer slots. FIG. 12C illustrates the first transfer of plates 116. In use, one module 100 can buffer more than half of this total number, while the other module 100 can buffer the remainder of the total number depending on the requirements of the system 99. Similarly, each module 100 typically keeps four transfer slots in its buffer empty and ready to receive items from a process module 120. As above, plates 116 can be organized on transfer slot layers as needed in adjacent slots, so that only a series of 1 / 8 rotations are required, as shown in FIG. 12D, where all carousels 108 rotate one slot. The overall unloading of the process module 120 is shown in FIG. 12E, where the module 100 contains a mix of plates unloaded from the process module 120 and plates to be loaded. Next, FIG. 12F illustrates the first step in loading the process module 120.

[0176] Considering a larger system 99, such as that shown in FIG. 10 , plates 116 can be buffered from other modules 100 to a module 100 that interfaces with a process module 120. For example, culture media is typically stored in a refrigerator 128 but is pre-warmed in an incubator 124. Frozen goods may be buffered in the refrigerator 128, the plasticware storage 122, or the incubator 124, as needed. Thus, the system 99 can transfer plates 116 from one module 100 to another module 100 while the process module 120 is running. For example, the refrigerator 128 can be transferred relative to the incubator 124 while the process module 120 is running to minimize cycle time. In this example (not shown), the refrigerator 128 is connected to the plasticware storage 122, which is connected to the incubator 124 to minimize temperature disturbances during transfer. Similarly, as noted elsewhere, it is advantageous for the freezer 126 to interface with the refrigerator 128 and for the system 99 to access the freezer 126 via the refrigerator 128 to minimize temperature disturbances within the freezer 126.

[0177] The plate slot 110 is shown in Figures 11A-12F as having a wider edge facing the center well 112. The orientation of the plate slot 110 can be changed as needed for best efficiency.

[0178] Vertically stacked modules 100 can also have a personnel-accessible door on the exterior of the module 100 through which the system 99 can be restocked, e.g., with fresh labware at a convenient height. Such an exterior door can be located, for example, in plasticware storage 122 or refrigerator 128. Alternatively, there can be a dedicated load lock that is the only module 100 with a personnel-accessible door on a daily basis, through which users can exchange consumables, cell plates, or samples with the system 99.

[0179] Vertical stacking of modules also allows the incubator 124 doors (interface doors 130, 230 or exterior human access doors) to be placed low on the wall, minimizing the escape of warm, moist, CO2-rich air when the doors are opened. Refrigerators 128 and freezers 126 can also be placed low in the system 99, which means that their doors (interface doors 130, 230 or exterior human access doors) can be placed high on the sides, minimizing the escape of cold air from those compartments 126, 128 when the doors are opened.

[0180] Other possible embodiments of the module and interface innovations are not limited to use with carousels, but can be used with conventional robotic arms, gantry robots, etc.

[0181] Referring to FIG. 28A , the robotic device 160 is located at the center 400 of the four modules 100. The arm 160 rotates about a central axis, the grabber 162 translates to move plates 116 in and out of the module 100, and the robotic device 160 moves vertically along the central axis. One of the modules may be a storage unit 122. The storage unit 122 optionally has a full-height vertical door 402 to allow the robotic device 160 to access any level within the internal rack 210. The other doors may also be full-height doors 402. The carousel 108 of the module 100 rotates to access the required plate slot 110. The rotation of the carousel 108 and the vertical movement of the robotic device 160 allow the robotic device to access any plate slot 110 of the module 100. Therefore, by combining the movements of the robot device 110 (rotation around an axis, movement along an axis, translation into and out of the module 100) with the rotation of the carousel 108 or the rotation of the work deck carousel 108 within the process module 124, the robot device 160 can transport any plate 116 to any location within the system 99. This has the advantages of simple movements, easy programming, and simple and reliable hardware.

[0182] The grabber 162 can be mechanically or optically (e.g., using machine vision or optical or magnetic sensors) indexed or aligned to the door 402 or interface 130. The interface 130 can have mechanical alignment features, including features such as chamfers or pin and slot features, as previously described. The grabber 162, or the wrist of the grabber 162, can have a degree of compliance to allow alignment with alignment features such as chamfers. The robotic device 160 can be aligned so that the chamfers (e.g., on the door 402) are not normally contacted as the grabber 162 passes through the door 402, but the grabber 162 only contacts the chamfers if misaligned. Contact with the chamfers can dynamically or mechanically correct misalignment. The chamfers can correct the grabber 162 in the horizontal or vertical plane, or both. Contact with the chamfers can further provide feedback that can be used to correct the alignment of the robotic device 160.

[0183] 28B shows a side view of the robotic device 160 positioned in a center 400 between modules 100, where vertically stacked modules 100 are provided. The robotic device 160 has vertical movement to reach all modules 100 through doors 402 or interfaces 130. The carousel 108 on which the racks 210 or work deck 330 are located can rotate to allow the robotic device 160 to access the required plate slots 110.

[0184] 30, a close-up view of the robotic device 160 interacting with the rack 210 of the module 100 is shown, where the grabber 162 is sized so that it can extend into the module to grasp the associated labware 300.

[0185] For example, the system 99 described above in FIG. 28 can have a standardized interface, as previously mentioned. The system 99 can have a rotating work deck 330, as previously described. The system 99 can have a standardized set of labware 300, and all labware 300 can be handled in the same way. The system 99 can use the previously described method of enabling complex workflows to be performed autonomously by the system 99 using only the complete set of labware 300 described, in the form of SLAS microplates 116. All of these features can be used alone or in combination to enable simple and reliable handling by a single robotic device 160 in the center 400 of a module 100. Using these features in combination, the system can achieve a mean time between failures of more than 30,000 or even more than 60,000 plate transfer or movement events. "Mean time between failures" refers to the arithmetic average of the number of plate transfers or movements between failures, where one failure is an error that shuts down the system until a human can correct the problem.

[0186] Alternatively, a more flexible robotic arm, such as a six-axis arm, can be used. Machine vision can be used to enhance the system and increase reliability. The system 99 can be positioned horizontally on one level. The robotic device 160 can run on rails that index to the door 402 or interface 130.

[0187] 29A and 29B, the robotic device 160 may again be located at a center 400 with modules surrounding the robotic device 160. However, the robotic device 160 may be an arm 406 that pops a turntable 404 also located at the center 400. The arm 406 may transfer plates 116 horizontally between the plate slots 110 of the modules 100 and the turntable 404. The arm 406 may also rotate about a central axis to access other modules 100. The arm moves vertically along the central axis. The turntable 404 also moves up and down and rotates. Vertical rails 408 may be present to support the robotic device 160, maintain alignment, and for connecting or indexing to doors or interfaces.

[0188] In the embodiment of FIGS. 29A and 29B, the turntable 404 can function as a temporary storage or magazine from which the plates 116 can be transferred to the carousel 108 within the process module 124.

[0189] 31A and 31B, a turntable 404 may be handed over to a process module 124. There may also be two turntables 404, one in the process module 124 where work is being performed and a second that can be loaded while the first is working. The turntables 404 can then be swapped.

[0190] FIG. 32 shows a robotic device 160 with a magazine 410, which is a vertical rack. The robotic device 160 collects plates 116 and other labware 300 for the next workflow into the magazine 410 and then transfers them from the magazine 410 to the process module 124. This avoids delays as the robotic device 160 moves between various modules 100 and the process module 124 one item at a time. The robotic device 160 may also have two magazines 410. It may load the next item to be loaded into the process module 124 into one magazine 410, then unload from the process module 124 into the second magazine 410, reload the process module 124 from the first magazine 410, and then unload from the second magazine 410 into the associated module 100.

[0191] 33, the modules 100 may be arranged in two opposing rows. They may be accessed by a robotic device 160 that moves between them on rails 412 or similar fixed tracks, such as a gantry. The robotic device 160 may, for example, mechanically or optically index to a door 402 or interface 130 on a module 100, and the robotic device 160 may move to the door 402 or interface 130 on a fixed rail or by moving to the door 402 or interface 130.

[0192] 33, it may be desirable to avoid one or more of a heavy robotic device 160, a long travel distance and therefore a long rail 412, and / or a fast travel speed, as these may make the system vulnerable to deviations from tolerances. While robots are inherently very precise, the mechanisms and fixtures that secure and align the robot to the module can flex, distort, or shift, causing misalignment.

[0193] The module 100 need not be limited to the use of a carousel 108, but instead may use a module 100 with a rectangularly arranged rack 210, with access to the rack 210 being via a vial rail or carousel system. A rectangularly arranged rack is more space efficient and denser than a carousel 108.

[0194] Thus, the described system 99 can use a robotic device 160 located outside of the module 100. This is made practical by the simplified handling previously described (movement along limited axes, horizontal movement, fixed interface, single plastic instrument handling format, etc.). The robotic device 160 can interface to an interface 130 on the module 100; for example, a grabber 162 can index or align with the door 402. The robotic device 160 can travel on rails 412, which are fixed to the interface 130. The module 100 can have a fixed interface format.

[0195] Referring to FIG. 34, the operation sequence is shown as viewed from left to right. A module 100 is provided, having a rack 210 with plate slots 110. Stacked vertically on the module 100 are process modules 124. A robotic device 160 moves between modules 100 on rails 172, as described above with reference to FIGS. 9A and 9B. However, the process module 124 does not have a rack 210 because its space is occupied by a liquid handler, decapping machine, etc. Therefore, the process module 124 has a carousel 108 with a working deck 330. Similar to the center well 112 described above, a central portion of the working deck 330 is left unoccupied to allow the robotic device 160 to partially pass through to deliver labware 300 and plates 116 to the working deck 330. As shown in the sequence of figures, the robotic handler 160 can partially pass through the process module 124 and deliver the plate 116 to the target plate slot 110 on the work deck 330, thus enabling vertical delivery of the plate 116 and labware 300. This reduces the space required in the process module 124 for movement of the plate 116, as the rails 172 required for vertical movement may not be present.

[0196] While the above examples show modules implemented as rotating features (such as a carousel with a plate hotel), those skilled in the art will understand that the features and principles described can also be applied to other types of modules and transports.

[0197] FIG. 35 shows an alternative arrangement similar to that disclosed in FIG.

[0198] The working deck plate slot 110 has windows 111 that open to the top and bottom of the working deck 330. The windows 111 are used for the arms of a gripper (not shown) to lift a plate, such as a cell culture plate 116, from the working deck plate slot 110. The gripper can have a tray with protrusions that fit into recesses on the underside of the plate.

[0199] 35 further illustrates a first transfer interface 133 and a second transfer interface 134 disposed at different positions relative to the housing 102 or the rotatable work deck 330. The first transfer interface 133 can interface with a first storage module (not shown in FIG. 35 but described above). The second transfer interface 134 can interface with a second storage module (not shown in FIG. 35 but disclosed above). One of the storage modules can store cell culture plates 116 as disclosed above. The other storage module can store labware as described above or liquid media for application to the cell culture plates as described above.

[0200] 36 and 37 show a single well plate 301 having a rectangular bottom 302. The single well plate 301 has the microplate footprint described above (width 85.5±1 mm, length 127.8±1 mm).

[0201] The single-well plate 301 has four walls 303 with an upper edge 304. A foil (plastic foil) is sealed to the edge 304, covering the upper opening of the well 307 surrounded by the walls 303. The connection between the foil 305 and the edge 304 is a heat-sealed connection. The plate 301 can be used to transport liquid media from a supplier to a biological laboratory system. The sealed opening of the plate 301 can be covered with a lid 309.

[0202] The foil 305 can be broken by the tip of a pipette of the liquid handler 340 to aspirate the liquid contained within the well 307 .

[0203] 38 and 39 show sealing elements 311 forming a passage for plates moving between one module 100 and another module 120, where one module 100 is a storage module and the other module 120 can be a process module or a storage module 100. The height of the opening 150 formed by the frames 315 and the sealing elements 311 located between the frames 315 can be larger than shown. transfer Interface 133、 The height of 134 is transfer Interface 133、 Just enough to move the microplate through 134. transfer Interface 133、 134 may have a uniform height greater than the height of the bottle or tallest appliance stored in the module 100.

[0204] All these features combine to make labware handling simpler and more reliable, software faster and easier to write and debug, and system software stability – in contrast to the current situation where unstable software is one of the major obstacles.

Claims

1. A biological laboratory system having a process module (120), a first storage module (124), and a second storage module (122), a first carrier (116) carrying biological material such as a cell culture; a second carrier carrying a liquid; a third carrier carrying a pipette tip box (324); all of the first, second, and third carriers in the modules (120, 124, 122) have a footprint the same size as a SLAS-compliant microplate footprint; The process module (120) a housing (102); a work deck (330) disposed within the housing (102) and rotatable between a plurality of work positions, the work deck (330) having a plurality of work deck plate slots (110) including first, second, and third work deck plate slots for receiving the first, second, and third carriers, respectively, the plurality of work deck plate slots (110) being radially disposed about a center of rotation of a single surface of the work deck (330); a liquid handling robot (340) including at least one pipette for aspirating liquid; a first transfer interface (133) communicating with the first storage module (124) for storing the first carrier (116); a second transfer interface (134) communicating with the second storage module (122) for storing the second carrier and the third carrier; At a first one of the work positions, the first carrier (116) is located below an operating point of the liquid handling robot (340); At a second one of the work positions, the first carrier (116) is aligned with the first transfer interface (133) for transferring the first carrier (116) between the first storage module (124) disposed outside the housing (102) and the first working deck plate slot (110); at a third one of the work positions, the second or third carrier is aligned with the second transfer interface (134) for transferring the second or third carrier between the second storage module (122) disposed outside the housing (102) and the second or third work deck plate slot (110); the alignment at the second and third positions is radial alignment; and In the biological laboratory system, the movement of the first and second or third carriers at the second and third positions is a linear horizontal movement, the liquid handling robot (340) is capable of accessing a different work deck plate slot (110) of the work deck (330) and grabbing a pipette tip from the pipette tip box (324) on the third carrier disposed in the third work deck plate slot (110); The liquid handling robot (340) further aspirates liquid from the second carrier (116) disposed in the second work deck plate slot (110) using the pipette tip and transfers the liquid to the first carrier (116) disposed in the first work deck plate slot (110).

2. 10. The system of claim 1, further comprising one of a microscope (942), a capper / decapper robot (344), or a lidder / delidder robot (346) positioned above the work deck (330).

3. The system of claim 1 or 2, wherein the first, second, and third working deck plate slots (110) have windows (111) in a surface of the working deck (330).

4. The system of any one of claims 1 to 3, wherein the first, second and third working deck plate slots (110) open to an edge of the working deck (330).

5. 5. The system according to claim 1, wherein the first, second and third working deck plate slots (110) have windows (111) for handling arms to reach recesses (374) on the undersides of the first, second and third carriers disposed in the first, second and third working deck plate slots (110) to lift the first, second and third carriers.

6. 6. The system of claim 1, wherein the first, second, and third working deck plate slots have alignment means provided on the outer edges of the working deck, the alignment means defining widths of the entrances of the first, second, and third working deck plate slots that decrease as the distance to the center of the process module decreases.

7. 7. The system of claim 1, wherein the work deck (330) is positioned at one or more positions to provide positions for operation by the liquid handling robot (340) on the first, second, and third work deck plate slots (110) or to provide positions for aligning the first, second, and third work deck plate slots (110) with the first and second transfer interfaces (133, 134).

8. 10. A method of operating the biological laboratory system of claim 1, comprising: At a second one of the work positions, transferring the first carrier (116) from outside the housing (102) through the first transfer interface (133) into one of the first working deck plate slots (110); At a third one of the work positions, transferring the second carrier carrying a liquid and the third carrier carrying the pipette tip box (324) from outside the housing (102) to the second and third work deck plate slots (110) via the second transfer interface (134), respectively; moving the working deck (330) to another working position; said liquid handling robot (340) accessing different working deck plate slots (110) of said working deck (330); the liquid handling robot (340) grabbing a pipette tip from the pipette tip box (324) on the third carrier disposed in the third work deck plate slot (110); the liquid handling robot (340) aspirating liquid from the second carrier located in the second work deck plate slot (110) using the pipette tip; the liquid handling robot (340) transferring the aspirated liquid using the pipette tip to the first carrier (116) located in the first work deck plate slot (110); moving the working deck (330) to a further working position; and ejecting the first carrier (116) through the first transfer interface (133).

9. 9. The method of claim 8, further comprising one of a microscope (942), a capper / decapper robot (344), or a lidder / delidder robot (346) positioned above the work deck (330).

10. 10. The method of claim 8 or 9, wherein the first, second and third working deck plate slots (110) have windows (111) in a surface of the working deck (330).

11. The method according to any one of claims 8 to 9, wherein the first, second and third working deck plate slots (110) open to an edge of the working deck (330).

12. 12. The method according to any one of claims 8 to 11, wherein the first, second and third working deck plate slots (110) have windows (111) for handling arms to reach recesses (374) on the undersides of the first, second and third carriers located in the first, second and third working deck plate slots (110) to lift the first, second and third carriers.

13. 13. The method of claim 8, wherein the first, second, and third working deck plate slots have alignment means provided on the outer edges of the working deck, the alignment means defining widths of the entrances of the first, second, and third working deck plate slots that decrease as the distance to the center of the process module decreases.

14. 14. The method of claim 8, wherein the work deck (330) is positioned at one or more positions to provide positions for operation by the liquid handling robot (340) on the first, second, and third work deck plate slots (110) or to provide positions for aligning the first, second, and third work deck plate slots (110) with at least one of the transfer interfaces.

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