WO2000045164A1 - Station de travail robotique - Google Patents

Station de travail robotique Download PDF

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Publication number
WO2000045164A1
WO2000045164A1 PCT/US2000/002122 US0002122W WO0045164A1 WO 2000045164 A1 WO2000045164 A1 WO 2000045164A1 US 0002122 W US0002122 W US 0002122W WO 0045164 A1 WO0045164 A1 WO 0045164A1
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WO
WIPO (PCT)
Prior art keywords
tool
workstation
deck
tools
wells
Prior art date
Application number
PCT/US2000/002122
Other languages
English (en)
Inventor
Scott P. Hunicke-Smith
Omar Medeiros
Robert Guettler
Carl Buice
Nancy Bergsteinsson
Keith Batchelder
Original Assignee
Genomic Instrumentation Services, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Genomic Instrumentation Services, Inc. filed Critical Genomic Instrumentation Services, Inc.
Priority to AU26331/00A priority Critical patent/AU2633100A/en
Publication of WO2000045164A1 publication Critical patent/WO2000045164A1/fr

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02—Burettes; Pipettes
    • B01L3/021—Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids
    • B01L3/0217—Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids of the plunger pump type
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B04—CENTRIFUGAL APPARATUS OR MACHINES FOR CARRYING-OUT PHYSICAL OR CHEMICAL PROCESSES
    • B04B—CENTRIFUGES
    • B04B5/00—Other centrifuges
    • B04B5/04—Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers
    • B04B5/0407—Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers for liquids contained in receptacles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B04—CENTRIFUGAL APPARATUS OR MACHINES FOR CARRYING-OUT PHYSICAL OR CHEMICAL PROCESSES
    • B04B—CENTRIFUGES
    • B04B5/00—Other centrifuges
    • B04B5/10—Centrifuges combined with other apparatus, e.g. electrostatic separators; Sets or systems of several centrifuges
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B04—CENTRIFUGAL APPARATUS OR MACHINES FOR CARRYING-OUT PHYSICAL OR CHEMICAL PROCESSES
    • B04B—CENTRIFUGES
    • B04B9/00—Drives specially designed for centrifuges; Arrangement or disposition of transmission gearing; Suspending or balancing rotary bowls
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/0099—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor comprising robots or similar manipulators
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/028—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations having reaction cells in the form of microtitration plates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/0068—Means for controlling the apparatus of the process
    • B01J2219/00686—Automatic
    • B01J2219/00691—Automatic using robots
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0409—Moving fluids with specific forces or mechanical means specific forces centrifugal forces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B04—CENTRIFUGAL APPARATUS OR MACHINES FOR CARRYING-OUT PHYSICAL OR CHEMICAL PROCESSES
    • B04B—CENTRIFUGES
    • B04B11/00—Feeding, charging, or discharging bowls
    • B04B11/04—Periodical feeding or discharging; Control arrangements therefor
    • B04B2011/046—Loading, unloading, manipulating sample containers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N2035/00465—Separating and mixing arrangements
    • G01N2035/00495—Centrifuges
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1065—Multiple transfer devices
    • G01N35/1067—Multiple transfer devices for transfer to or from containers having different spacing

Definitions

  • the present invention relates to robotic workstations for chemical and biological synthesis, analysis and sample processing.
  • Robotic workstations are becoming increasingly important, as there is an explosive increase in biological and chemical research.
  • Modern research and clinical laboratory procedures include biological and chemical analysis of specimen substances that require extensive fluid manipulations.
  • Standard fluid transfer and manipulative techniques include pipetting, diluting, dispensing, aspirating and plate washing.
  • Most tools and robots are dedicated to the performance of one kind of operation.
  • many areas of art are such that there are multiple manipulative steps, often of short duration, which must be performed in quick succession in order to achieve a given result.
  • chemical synthesis often requires multiple steps of heating, mixing, pipetting and centrifugation, each of which may be required within a very few minutes. It has simply been impractical to stop and change tools for each operation.
  • Zymark produces a similar instrument, which it discloses in U.S. Patent No. 4,510,684, issued in April 1985. It discloses a robotic system for manipulating a series of discrete devices used in the field of analytical chemistry. It teaches the use of a robotic arm to open, contact and manipulate discrete laboratory devices in an emulation of manual methods on conventional laboratory instruments. However, the operations of the instrument are discrete and are not integrated into an intelligent coordinated system.
  • Several systems have been built which accommodate a variety of tools from different vendors and interface the tools by using robotic arms.
  • One such system was created by the MIT Whitehead Genome Center and is called the Sequatron II. This system connects a wide variety of tools and instruments from different vendors to form an automated lab. However, it requires a great deal of reconfiguration and modification to the software, tools, and instruments for the system to be used for other applications.
  • High-throughput screening is developing in two important directions: ever larger machines and picoliter miniaturization. What is needed is a cost-effective robotic workstation on which a variety of tools and instruments can function simultaneously resulting in more efficient and effective high-throughput sample processing. Moreover, this robotic workstation should be flexible and capable of modification to meet the scientist's specific needs. Such a system makes the most effective and efficient use of expensive laboratory space.
  • the apparatus includes a. a base on which the robotic workstation is arranged; b. at least two tools, each tool being arranged so that it may be used simultaneously with another tool for sample processing; c. a computer means to run the workstation; d. a means to move at least one tool vertically along a mounting column; e. a means to move microwell plates and at least one tool horizontally; whereby the vertically moved tool interacts with the horizontally moved microwell plate or tool.
  • the tools of the workstation are selected from the following: 1-, 8-, 12-, 96-, 384-, and 1536-well pipetters and larger; thermocycler; arrayable centrifuge; pressure filtration station for filter bottom plates; spectrophotometer; fluorimeter; incubator for special gases; incubator for temperature control; gridder or microarrayer; shaker/ agitator for mixing or suspension; plaque or colony picking device; sample injector for off- instrument analysis; magnet for attraction of magnetic particles; electrophoresis unit; temperature control for deck plates; feedback sensors; bulk reagent dispenser; solid phase extractor; wash station; high performance liquid chromatography; gravimetric analysis apparatus; microplate cassette; and re-arrayer.
  • the workstation has a centrally located column to accommodate at least one centrally mounted tool block, to which the vertically moving tool is attached.
  • the workstation's means to move the tool block vertically is a motor.
  • the workstation's means to move the tool block is a lead screw and stepper motor.
  • the workstation's means to move tools horizontally is a rotary deck powered by a motor that can be a D/C motor.
  • the workstation preferably includes a server arm, which is programmed to move microwell plates on the deck or between adjacent decks.
  • An automated method of processing samples contained in microwell plates includes the following steps: a.
  • an apparatus with a deck to accommodate at least one sample plate and at least one tool, a means for moving the deck, at least one mounting column accommodating at least one tool each, and each mounting column equipped with a means for moving tools, and a computer means to operate the apparatus; b. placing at least one sample plate on a deck; c. moving the deck to precisely position the sample plate and the tools, such tools being programmed to be capable of operating simultaneously to perform their respective functions; and d. removing the plates after the tools have performed respective functions on the samples contained therein.
  • An automated method of preparing cells for cell sorting includes the following steps: a. providing an apparatus with a deck to accommodate at least two sample plates, an array centrifuge, a pipetter, a wash station, and a bulk reagent dispenser; a means for moving the deck; at least one mounting column accommodating at least one tool each, each mounting column equipped with a means for moving the tools, and a computer means to operate the apparatus; b. placing at least one sample plate on a deck; c. moving the deck to precisely position the sample plate and the tools, such tools being programmed to be capable of operating simultaneously to perform their respective functions; and d. removing the plates after the tools have performed respective functions on the samples contained therein.
  • An automated method of performing solid phase extraction with a robotic work station has the following steps: a. providing a workstation with a deck to accommodate at least one sample plate, a microarray centrifuge, a server arm, microwell plates, and baskets for microwell plates and filter plates; a means for moving the deck; at least one mounting column on which are mounted a pipetter, a bulk reagent dispenser, and pressure station; at least one means for moving the column-mounted tools; and a computer with software modified to run the tools for the solid phase extraction; b. placing a sample plate with a plurality of wells containing a combination of growth media, bacteria and phage with cloned DNA onto the deck; c.
  • Another embodiment is a robotic workstation for automated cell preparation for sorting cells.
  • the workstation has a base on which the robotic workstation is arranged, an array centrifuge, a pipetter, a wash station, a bulk reagent dispenser, a server arm, each tool being arranged so that it may be used simultaneously with another tool for sample processing, a computer means to run the workstation; a means to move at least one tool vertically, a means to move microwell plates and at least one tool horizontally, whereby the vertically moved tool can interact with the horizontally moved microwell plate or tool.
  • the workstation has a base on which the robotic workstation is arranged, an array centrifuge, a wash station, a bulk reagent dispenser, a server arm, each tool being arranged so that it may be used simultaneously with another tool for sample processing, a computer means to run the workstation, a means to move at least one tool vertically along a mounting column, a means to move microwell plates and at least one tool horizontally, whereby the vertically moved tool interacts with the horizontally moved microwell plate or tool.
  • Figure 1 is an overview of the robotic workstation with a pipetter, a wash station and a bulk reagent dispenser.
  • Figure 2 shows a cross section of the workstation.
  • Figure 3 shows a cross section of the workstation.
  • Figure 4 shows an overview of the robotic workstation with a pipetter, an array centrifuge, and a bulk reagent dispenser.
  • One of the best ways to achieve reduced cost and increased flexibility for the researcher is to provide a workstation that may be customized at the factory for a variety of particular applications.
  • the key to the new workstation is a platform that accommodates a variety of tools or instruments appropriate to different applications and new tools and software adapted for each application.
  • a scientist orders a "customized" workstation in which the platform is combined with the desired combination of tools, instruments, and software to meet the particular needs. In this way, costs are minimized because a significant fraction of the machine is unchanged from application to application, allowing for lower production costs of all machines.
  • Each researcher receives a workstation suited to the desired applications, increasing flexibility.
  • an automated workstation for chemical and biological synthesis and analysis. It provides great flexibility and functionality in a relatively small space. Modular tools are attached to a central column, which powered by a stepper motor, move the tools vertically to permit performance of a variety of functions on sample plates or other tools or instruments.
  • the sample plates and other tools or instruments are precisely positioned on a rotary deck.
  • the rotary deck is moved radially in the horizontal plane by a DC motor that has precise control to move tools attached thereto within relatively tight tolerances.
  • a remote computer controls the workstation with software tailored to fit the scientist's particular needs.
  • the workstation has a base 20, preferably made from light-weight non- corrosive material such as anodized aluminum, into which are machined a plurality of holes 22. These holes 22 permit the base 20 to be bolted to a work surface and accommodate leveling screws 24 to adjust for an angled surface. The holes also allow for the attachment of additional tools on the sides and/or corners of the apparatus. For example, a group of holes 22 can be used to bolt on a robotic arm.
  • the side support 30 is attached to the base 20. Shown in Figure 1 is one support 30. However, the supports can be any convenient number, which sufficiently stabilizes the entire apparatus but does not interfere with operator access to the deck and internal workings of the apparatus.
  • the first end 32 of each support 30 is attached to the base.
  • the second end 34 of the support 30 can optionally be attached to a cross bar 40 which also connects to the central support 50 via central column 52.
  • This combination of base, supports, cross bar and contact of the central column with the base and the cross bar stabilizes the apparatus.
  • the central support 50 accommodates at least one track 54 in which modular tool mount block 56 moves vertically. The vertical movement is powered by a lead screw (not shown in Figure 1) and stepper motor 58.
  • the modular tool block 56 carries a variety of tools, including a pipetter 102, a wash station 104, or a bulk reagent dispenser 106. Other optional tools are listed below. Also shown in Figure 1 is the rotary deck 60 that revolves around the central column 50.
  • the deck 60 has one or more locations with specially shaped holes 62 which can accommodate microwell plates and deck locations with mounting holes 64. Additionally, the deck 60 has a variety of mounting locations to accommodate various tools or instruments. Horizontal movement of the deck 60 is powered by a deck motor 100, which is adjacent to the central support 50. The entire workstation is controlled by a remote computer (not shown) with software programmed to control the particular tools provided in the configuration of the workstation.
  • Figure 2 is a cross sectional view of the workstation, cutting through the center of the side supports 30 and the central column 52.
  • the deck 60 is seen in cross section.
  • the modular tool mount block 56 is shown in profile with its relation to lead screw 57 and stepper motor 58.
  • Figure 3 is a cross section of the workstation perpendicular to the plane shown in Figure 2.
  • Slide ring 92 sits on the deck bearing plate 90 and contacts slide ring bearing 94.
  • the deck motor 100 has a pinion gear (not shown) which actuates the slide ring 92 on the deck for precise motion to precisely align the deck 60 with a variety of tools and instruments.
  • the electronics box 116 which contains all of the electronic circuitry to run the robotic workstation.
  • Figure 4 one possible configuration of a set of tools and instruments is displayed.
  • a modular tool block 56 is attached to the central column 50 by a modular tool block 56.
  • a bulk reagent dispenser 106 is also attached to the central column 50 by a modular tool block 56.
  • a wash station 104 is nestled into one of the specially shaped holes 62.
  • a microarray centrifuge 108 is attached to the rotary deck 60 at a deck location 64.
  • the modular tool block 56 is powered by a lead screw and stepper motor 58 which moves the pipetter 102 in a precise vertical motion to interact with the microwell plates 110, wash station and microarray centrifuge 108 on the rotary deck 60.
  • This configuration allows for a variety of centrifugation-based biological and chemical protocols to be run efficiently on one automated workstation. This is much more cost effective than purchasing each tool or instrument separately and manually or even robotically connecting them together.
  • the workstation of Figure 4 can be used to process cells prior to cell sorting and in a variety of other procedures.
  • the robotic workstation can accommodate many tools, instruments, and applications.
  • a brief list of tools includes, but is not limited to, the following:
  • a pipetter generally has a plurality of needles to aspirate from and deliver samples into multiwell plates.
  • the needles are anchored in a sample volume block and a needle guide assembly comprising a needle guide shaft, compression spring and needle guide plate, which are attached to the sample volume block and control the spacing of the needles.
  • Thermocycler A machine that automates the alternating heat cycles for the process of polymerization chain reaction (PCR). (MJ Research, Watertown, MA; and Perkin Elmer, Foster City, CA)
  • Server Arm A robotic arm utilized for moving sample plates to various destinations.
  • An example of a server arm is the GarconTM: a modular, automated server arm designed to automatically deliver and retrieve microwell plates to and from other processing equipment (GeneMachines, San Carlos, CA).
  • Pressure Filtration Station A positive-pressure device for filter plates. Filter-based preparation systems for nucleic acids have been shown to be useful in a variety of applications. These are commonly implemented using a centrifuge or vacuum filtration. Centrifugation gives excellent results but is classically difficult to automate. Vacuum methods are not capable of generating high enough pressures to filter more viscous solution, and they can cause cross-contamination through foaming or out-gassing of the filtrate. The GeneMachines Pressure Station eliminates these problems and gives you great control in a small package. (GeneMachines, San Carlos, California) 6. Spectrophotometer - An instrument that measures the concentration of a compound that has been dissolved in a solvent.
  • the instrument shines a light through the solution, measures the fraction of the light that is absorbed by the solution, and calculates the concentration from that absorbance value.
  • Fluorimeter An instrument used to measure fluorescence. It generates the wavelength of light required to excite the analyte of interest. The analyte of interest then emits a different wavelength that is measured by the fluorimeter. The emitted light is proportional to the concentration of the analyte being measured. (Amersham Pharmacia Biotech, Buckinghamshire, United Kingdom; and Dynex Laboratories, Farmington Hills, MI) 8.
  • Incubator for Special Gases Controlled environment for microplate incubation featuring control of temperature and atmosphere. Incubation occurs in user-defined atmospheres, for instance, enriched carbon dioxide or oxygen atmospheres, and with controlled humidity. This incubator supports cell growth in a wide variety of cell types. (Beckman Coulter, Palo Alto, CA) 9. Incubator for Temperature Control - An enclosure placed around an instrument for the regulation of temperature. (Fischer Scientific, Pittsburgh, PA and Thermolyne, Dubuque, Iowa).
  • Gridder or Microarrayer An instrument used for arraying nucleic samples by eluting DNA samples onto a solid surface containing complementary DNA.
  • the preferred microarrayer is a high performance, multi-axis microarrayer capable of arraying biological samples from standard 96- or 384-well microwell plates onto a variety of substrates, including glass slides and nylon membranes.
  • the microarrayer incorporates features supporting routine arraying protocols, while providing a flexible, customized platform to meet specific research needs and accommodate future developments. (OmniGridTM, GeneMachines, San Carlos, CA).
  • Shaker/Agitator An instrument that has positions for holding samples and mixes or suspends the samples by a rocking motion.
  • the preferred shaker combines orbital shaking, oxygenation, and incubation in a high-capacity format for bacteria and phage growth. With these unique features, growth in standard 96-microwell plates meets most sequencing needs. (HiGroTM, GeneMachines, San Carlos, CA and New Brunswick Scientific, Edison, NJ).
  • Plaque or colony picker An instrument designed for the picking of isolated plaques and colonies. It has narrow tubes or pins that can pick up plaques and colonies from samples and deposit them to a designated position. A preferred high speed, high throughput picker of plaques and colonies accomplishes 2000 picks per hour and can pick colonies about 0.5 mm in diameter and about 0.5 mm apart. It can be coupled with a robotic arm to automate the entire process. Controlled by user-friendly software with a graphical user interface (GUI), it enables researchers to pick plaques and colonies automatically, saving time and money. (Gel-2-WellTM, GeneMachines, San Carlos,
  • Sample injector for off-instrument analysis A tool that is capable of aspirating samples from one instrument and depositing them on another instrument for analysis. (Beckman Coulter, Palo Alto, CA) 14. Magnet for attraction of magnetic particles - Material which attracts magnetic particles and can help keep samples and instruments in their designated positions. GeneMachines offers this as part of its OmniGridTM microarrayer. One way in which the samples are held in place is through magnetic force. (GeneMachines, San Carlos, CA). 15. Electrophoresis Unit - An instrument that automates the technique for separating molecules based on the differential movement of charged particles through a matrix when subjected to an electric field. (Amersham Pharmacia Biotech, Buckinghamshire, United Kingdom; and BioRad, Hercules, CA)
  • Temperature control for deck plates Individual deck positions may be equipped with temperature control capability. A microplate in a specific position is then cooled or heated in order to keep the samples at the predetermined temperature. This feature maintains plates and their contents at the required temperature prior to their use.
  • Solid phase extractor - Solid-phase extraction is an extraction method that uses a solid phase and a liquid phase to isolate one, or one type, of analyte from a solution. It is usually used to clean up a sample before using a chromatographic or other analytical method to quantitate the amount of analyte(s) in the sample (AutoGen, Framingham, MA).
  • Wash station A liquid container for the cleaning of instruments.
  • GeneMachines offers such an instrument on its RevPrepTM workstation. This wash station has a large well that contains cleaning solution. Other instruments are dipped into the well and cleaned off. The well is automatically drained and refilled before each new instrument is placed in the cleaning solution. (GeneMachines, San Carlos, California).
  • Sample plates would be tared when empty, liquid analyte would be added to plate, dried, and then reweighed with dry analyte in plates. The mass of resulting analyte could be used to monitor process progress. This process could be useful for either a full plate of samples or for independent samples. (Metter, Toledo, Ohio has an instrument similar to the one disclosed). 23. Microplate Cassette - Storage hotels for sample plates. Microwell plates in a variety of densities have greatly improved the sample handling capabilities of high-throughput genomic research labs. Just as tubes were juggled by technicians 10 years ago, microwell plates are being juggled. Now scientists deal with a few dozen plates per day instead of a few dozen tubes.
  • GeneMachines provides Microwell CassettesTM that organize microwell plate transfer, storage, and presentation (GeneMachines, San Carlos, CA). 24. Re-Arraver - Re-arrayers efficiently rearrange or subtract identified libraries with maximum format flexibility. An available re-arrayer provides a 24-pin pneumatic head and autoloader, which enable full rearrangement of a library, selection of specific target wells for analysis, or replication. Libraries can be rearrayed on 96- and 384-well plates. (FlexysTM, Genomic Solutions, Ann Arbor, MI).
  • the robotic workstation stands alone without any side supports.
  • the robotic workstation has tools or instruments attached to the base around the perimeter of the rotary deck to perform biological or chemical protocols.
  • the workstation has one or more mounting columns supporting the rotary deck located on the periphery of the deck instead of centrally located.
  • the workstation has an oblong deck that moves back and forth. Instead of a central column on which tools move vertically, the workstation has columns along one or both sides of the deck to accommodate tools and instruments. It is convenient to locate the tools along one side and at least one server arm on the opposite side.
  • a server arm is provided in conjunction with the robotic workstation.
  • the server arm contacts the microwell plates and moves them to various locations on the robotic workstation or to adjacent workstations.
  • a chain of workstations can thus be linked with server arms, creating a fully automated chemical and biological laboratory for scientists.
  • any machinable metals are utilized as material for the robotic workstation.
  • Examples include stainless steel and aluminum.
  • the computer controlling the robotic work station and its various tools and instruments is located on the rotary deck or on the base.
  • the workstation has a heater positioned in the center or along a side or corner, which rapidly heats up the wells in the sample plate.
  • Incubation may be performed at any temperature that facilitates the chemical reactions, typically between 4° and 40° C, more commonly between 15° and 40° C. Incubation periods are likewise selected for optimal binding but also minimized to facilitate rapid, high- throughput screening.
  • Another embodiment provides a method of preparing cells for cell sorting utilizing a customized robotic workstation.
  • Another embodiment provides a method of performing automated solid phase extractions utilizing a customized robotic workstation.
  • Example 1 One configuration of the robotic workstation is customized for the preparation of cells for cell sorting. Before cell sorting based on fluorescent-activated compounds, the desired cells need to be labeled with a fluorescent tag, such as a labeled antibody.
  • the robotic configuration suitable for such cell preparation is illustrated in Figure 4 and combines the following tools and instruments: 1) an array centrifuge 108, 2) a pipetter 102, 3) a wash station 104, and 4) a bulk reagent dispenser 106. LabVIEWTM Software (LTR Publishing, Inc., Dallas, TX) is programmed to run this configuration of the robotic workstation.
  • a pipetter 102 is attached to the central column 50 by a modular tool block 56.
  • Microwell plates 110 are nestled into deck locations with specially shaped holes 62 therein.
  • Each well of a first microwell plate 1 10 contains a different cell sample or a control.
  • a second microwell plate (not shown) contains antibodies in a plurality of its wells.
  • the rotary deck 60 powered by the deck motor 100 revolves and carries the first microwell plate 110 containing the cells, until the plate is precisely aligned underneath the pipetter 102.
  • the pipetter 102 is lowered by lead screw 57 attached to stepper motor 58 toward the rotary deck 60, and it aspirates the cells from the microwell plate 110.
  • the pipetter 102 moves vertically to its original position while the second microwell plate containing the test antibodies is then moved on the rotary deck until it is precisely aligned beneath the pipetter 102.
  • the pipetter 102 moves vertically towards the rotary deck 60 and dispenses the cells into the plurality of wells. The combinations of cells and antibodies then incubate in the second microwell plate.
  • a bulk reagent dispenser 106 is also attached to the central column 50 via a modular tool mount block 56. Vertical motion of the bulk reagent dispenser 106 is powered by a lead screw 57 and stepper motor 58.
  • the microwell plate 110 containing the combination of antibodies and cells is moved horizontally on the rotary deck 60 until it is precisely aligned with the bulk reagent dispenser 106.
  • the bulk reagent dispenser 106 moves vertically towards the rotary deck 60 and deposits wash solution into the plurality of wells of the microwell plate 110. Then the bulk reagent dispenser 106 moves back up to its original position, as the second microwell plate containing the combination of solutions is horizontally moved until it precisely aligns with the pipetter 102.
  • the pipetter 102 moves vertically and aspirates the combined solutions.
  • An array centrifuge 108 with a plurality of wells is located on the rotary deck 60.
  • the rotary deck 60 powered by the deck motor 100, revolves and places the array centrifuge 108 in a position precisely below the pipetter 102.
  • the pipetter 102 moves down and dispenses the diluted, incubated combinations into a plurality of wells in the microarray centrifuge 108. While the pipetter moves up, the array centrifuge 108 is actuated, and the centrifugal force forms a supernatant and a cell pellet in each well.
  • the pipetter 102 is then vertically moved to aspirate the supernatant from the plurality of wells of the microarray centrifuge.
  • the pipetter 102 moves vertically back to its original position.
  • a wash station 104 occupies position 62 on the rotary deck 60.
  • the rotary deck 60 is then moved in a horizontal direction until the wash station is precisely positioned below the pipetter 102.
  • the pipetter 102 is then vertically moved towards the wash station 104 and dispenses the supernatant into it and washes the pipettes as well, by aspirating and dispensing repeatedly.
  • the pipetter 102 is then vertically moved back to its original position.
  • the array centrifuge 108 is vertically moved until it is precisely aligned with the bulk reagent dispenser 106.
  • the bulk reagent dispenser 106 moves vertically and deposits wash reagent into the plurality of wells of the array centrifuge 108.
  • the array centrifuge 106 resuspends the cell pellet by rapid changes in its rotational velocity.
  • the array centrifuge 108 then centrifuges the mixture once again to separate a supernatant and a cell pellet. As the array centrifuge slows down, the deck moves to align the array centrifuge with the pipetter 102.
  • the supernatant is removed by the pipetter 102 and dispensed into the wash station 104, and then the bulk reagent dispenser 106 adds more wash reagent into the array centrifuge 108.
  • the addition of a wash, resuspension of the cell pellet, centrifugation and removal of a supernatant is repeated three times. After the completion of these steps, a clean cell pellet remains in the array centrifuge 108.
  • the array centrifuge 108 is horizontally moved and precisely aligned with the bulk reagent dispenser 106, and a labeling buffer is deposited into a plurality of wells of the array centrifuge 108.
  • the array centrifuge 108 then resuspends the cell pellet into the labeling buffer by rapid changes in its rotational velocity. This combination of substances is incubated for one hour in the array centrifuge 108, or it can be removed and placed in a microwell plate 110 for the incubation period.
  • the bulk reagent dispenser 106 adds wash reagent to the incubated substance. This incubated substance is then centrifuged. The supernatant is removed by the pipetter 102 and disposed of in the wash station 104. More wash reagent is added to a plurality of the array centrifuge 108 wells; then there is resuspension and then centrifugation. The cycle of adding a wash reagent, resuspending, centrifuging and removing a supernatant is repeated twice.
  • the array centrifuge 108 is then realigned with the bulk reagent dispenser 106 and a re-suspension and fixing solution is added to the wells. This mixture is resuspended. This solution is then removed by the pipetter 102 and placed into an appropriate container for cell sorting.
  • Another inventive configuration of tools and instruments on the robotic workstation can be used to perform automated solid phase extractions (SPE) in an efficient and cost-effective way.
  • This configuration includes 1) a microarray centrifuge, 2) a bulk reagent dispenser, 3) a server arm, 4) microwell plates, and 5) baskets for microwell plates and filter plates.
  • LabVIEWTM Software is programmed to run this particular configuration of the robotic workstation.
  • An example of an automated SPE using this machine is the isolation of DNA for sequencing from bacteriophage M13. By the time that the following procedure takes place, the bacteriophage have multiplied in the E. coli.
  • M13 and its host E. coli cells suspended in a growth media are contained in a plurality of wells of a microwell plate.
  • the microwell plate is placed on the rotary deck of the robotic workstation by a robotic server arm.
  • the rotary deck moves in a horizontal direction until the microwell plate is precisely aligned with the pipetter.
  • the pipetter is vertically moved towards the deck where it aspirates the samples of growth media and cloned DNA from the microwell plate.
  • the pipetter is then vertically moved to its original position.
  • An array centrifuge is located on the rotary deck of the robotic workstation. While the pipetter is moving vertically, the rotary deck moves in a horizontal direction until the array centrifuge is precisely aligned with the pipetter.
  • the pipetter is vertically moved towards the array centrifuge and deposits the samples into a plurality of wells of the array centrifuge.
  • the pipetter is then moved in a vertical direction back to its original location, while the array centrifuge is actuated, and the cells and supernatant containing Ml 3 are separated.
  • the pipetter is vertically moved towards the array centrifuge, the supernatant is aspirated, and the pipetter vertically moves back to its original position.
  • a filter plate with a plurality of wells is also located on the rotary deck. Underneath the filter plate is a basket that hangs from the rotary deck that is designed to accept a microwell plate. While the pipetter moves, the rotary deck moves horizontally until the filter plate is precisely aligned with the pipetter. The pipetter is vertically moved and deposits approximately 300 ⁇ l of the Ml 3 supernatant into a plurality of wells of the filter plate.
  • a bulk reagent dispenser is attached to the central column via a modular tool mount block.
  • the vertical motion of the bulk reagent dispenser is powered by a lead screw and stepper motor.
  • the filter plate is moved horizontally by the rotary deck until it is precisely aligned with the bulk reagent dispenser.
  • the bulk reagent dispenser is vertically moved towards the filter plate and deposits 30 ⁇ L of 20% PEG 8000 in 2.5M NaCl into wells of the filter plate.
  • the bulk reagent dispenser is moved back to its original position.
  • a pressure station is also attached to the central column via a modular tool mount, and its vertical motion is powered by a lead screw and stepper motor. While the reagent dispenser is moving vertically, the rotary deck horizontally moves the filter plate until it is precisely aligned with the pressure station. The pressure station is vertically moved towards the filter plate and exerts air pressure above the filter plate. The air pressure filters the reagent and supernatant and traps the Ml 3 phage in the filter. The pressure station then vertically moves back to its original position, while the filter plate is moved horizontally to precisely align with the bulk reagent dispenser, where the filter is washed twice with 3M NaC10 4 in 70% EtOH to lyse phage and bind DNA to glass.
  • the filter is washed six times with 70% EtOH to remove salts.
  • the bulk reagent dispenser then is returned to its original position. Simultaneously, the filter plate is moved horizontally to precisely align with the pressure station, which dries the filter plate with compressed air. The filter plate is then moved horizontally to precisely align with the bulk reagent dispenser.
  • the bulk reagent dispenser adds 60 ⁇ l of 10 mM Tris-HCl, pH 8.5, containing 1 mM EDTA (TE) to each well and moves back to its original position. The mixture is incubated for two minutes and resuspends the clean DNA.
  • the filter plate is then moved horizontally to precisely align with the pressure station.
  • a robotic server arm then loads a microwell plate into the basket beneath the filter plate such that the wells of the microplate are precisely aligned with the wells of the microwell plate.
  • the pressure station exerts air pressure and elutes the incubated solution into the microwell plate.
  • the purified DNA in TE solution is collected in the wells of the microwell plate.
  • This configuration of tools on the robotic workstation can produce approximately 50 ⁇ l of single stranded DNA per well at approximately 80 ng/ ⁇ l.
  • the disclosed invention can be utilized to perform a great number of different operations in an automated, compact and precise system, which saves money and time.
  • the same space can be adapted for the performance of many different assays and operations.
  • Utilizing equipment that takes up a small amount of space and that can be used for multiple tasks creates a great savings in overhead costs.
  • the automation of so many steps also eliminates operator error and leads to precise results.
  • the Robotic Workstation can isolate plasmid DNA significantly more quickly and cheaply because of the extent of automation and coordination.
  • the inventive workstation is a cost effective apparatus for automating biological and chemical protocols.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Clinical Laboratory Science (AREA)
  • Hematology (AREA)
  • Engineering & Computer Science (AREA)
  • Robotics (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

L'invention se rapporte à une station de travail robotique conçue pour la mise en oeuvre de processus biologiques et chimiques. Dans une réalisation, l'appareil comporte une base (20) sur laquelle est disposée la station de travail robotique, au moins deux outils conçus chacun de manière à pouvoir être mis en oeuvre simultanément à un autre outil pour le traitement d'échantillons, un ordinateur (116) conçu pour gérer la station de travail, un organe conçu pour déplacer (56) au moins un outil verticalement le long d'une colonne de montage (52), un organe conçu pour déplacer (60) des plaques à microcupules (110) et au moins un outil horizontalement, ledit outil déplacé verticalement interagissant avec la plaque à microcupules (110) ou l'outil déplacé horizontalement. L'invention se rapporte également à des méthodes de laboratoire et à des stations de travail personnalisées pour la mise en oeuvre desdites méthodes.
PCT/US2000/002122 1999-01-29 2000-01-28 Station de travail robotique WO2000045164A1 (fr)

Priority Applications (1)

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AU26331/00A AU2633100A (en) 1999-01-29 2000-01-28 Robotic work station

Applications Claiming Priority (4)

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US11801399P 1999-01-29 1999-01-29
US60/118,013 1999-01-29
US12526399P 1999-03-19 1999-03-19
US60/125,263 1999-03-19

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Cited By (21)

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WO2000049557A2 (fr) * 1999-02-22 2000-08-24 Gentra Systems, Inc. Procede et dispositif destines a la mise en oeuvre par ordinateur de l'isolement de l'acide nucleique
WO2005031313A1 (fr) * 2003-09-24 2005-04-07 Keyneurotek Ag Dispositif et procede permettant l'execution automatisee d'operations de laboratoire
WO2006027163A1 (fr) * 2004-09-03 2006-03-16 Bioplan Consulting Gmbh Installation de traitement d'echantillons microbiologiques
EP1649911A3 (fr) * 2004-10-19 2007-04-11 Agilent Technologies, Inc. Extraction en phase solide
US7340324B2 (en) 1999-10-20 2008-03-04 Qiagen North American Holdings, Inc. Mixing and pouring apparatus and vessel therefor
WO2009061643A1 (fr) * 2007-11-06 2009-05-14 Abbott Laboratories Système de chargement automatique d'un analyseur de laboratoire
WO2009061641A3 (fr) * 2007-11-05 2009-08-27 Abbott Laboratories Analyseur automatisé pour laboratoire clinique
EP2191900A1 (fr) 2008-11-28 2010-06-02 F. Hoffmann-Roche AG Système et précédé pour le traitement d'un fluide contenant des acides nucléiques
US20100273162A1 (en) * 2007-10-17 2010-10-28 Sailaja Chandrapati Rapid detection of microorganisms
US20110201127A1 (en) * 2010-02-12 2011-08-18 George Feilders Independent heating of samples in a sample holder
CN102507923A (zh) * 2011-10-31 2012-06-20 上海裕隆生物科技有限公司 全自动反应系统
CN102507964A (zh) * 2011-10-31 2012-06-20 上海裕隆生物科技有限公司 全自动反应仪
CN102507963A (zh) * 2011-10-31 2012-06-20 上海裕隆生物科技有限公司 全自动反应仪的清洗机构
CN102998473A (zh) * 2012-12-19 2013-03-27 北京利德曼生化股份有限公司 全自动化学发光免疫分析仪
WO2013192514A2 (fr) * 2012-06-21 2013-12-27 Automation Solutions, Inc. Système de distribution de fluide, monte-charge et utilisation associée
CN103712835A (zh) * 2012-09-28 2014-04-09 希森美康株式会社 试料调制装置及细胞分析装置
WO2017027425A1 (fr) * 2015-08-10 2017-02-16 Counsyl, Inc. Système modulaire de manipulation de liquides
CN106834114A (zh) * 2017-02-20 2017-06-13 佛山市金蓝领教育科技有限公司 一种基于pcr应用的自动化检测系统
CN109201133A (zh) * 2018-11-13 2019-01-15 望潮科技（北京）有限公司 一种机械臂实验系统
WO2022037556A1 (fr) * 2020-08-17 2022-02-24 Nanjing GenScript Biotech Co., Ltd. Système intégré automatisé pour la production continue de plasmide à l'échelle industrielle
WO2022169726A1 (fr) * 2021-02-03 2022-08-11 Amgen Inc. Systèmes et approches pour un traitement de médicaments

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CN108579973A (zh) * 2017-12-13 2018-09-28 贵州金银药业有限公司 中药材的快速捣碎装置

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Cited By (35)

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WO2000049557A3 (fr) * 1999-02-22 2001-05-31 Gentra Systems Inc Procede et dispositif destines a la mise en oeuvre par ordinateur de l'isolement de l'acide nucleique
WO2000049557A2 (fr) * 1999-02-22 2000-08-24 Gentra Systems, Inc. Procede et dispositif destines a la mise en oeuvre par ordinateur de l'isolement de l'acide nucleique
US7340324B2 (en) 1999-10-20 2008-03-04 Qiagen North American Holdings, Inc. Mixing and pouring apparatus and vessel therefor
WO2005031313A1 (fr) * 2003-09-24 2005-04-07 Keyneurotek Ag Dispositif et procede permettant l'execution automatisee d'operations de laboratoire
DE10344284A1 (de) * 2003-09-24 2005-05-04 Keyneurotek Ag Vorrichtung und Verfahren zur automatisierten Durchführung von Laborarbeitsschritten
WO2006027163A1 (fr) * 2004-09-03 2006-03-16 Bioplan Consulting Gmbh Installation de traitement d'echantillons microbiologiques
US7563410B2 (en) 2004-10-19 2009-07-21 Agilent Technologies, Inc. Solid phase extraction apparatus and method
EP1649911A3 (fr) * 2004-10-19 2007-04-11 Agilent Technologies, Inc. Extraction en phase solide
US20100273162A1 (en) * 2007-10-17 2010-10-28 Sailaja Chandrapati Rapid detection of microorganisms
US8222048B2 (en) 2007-11-05 2012-07-17 Abbott Laboratories Automated analyzer for clinical laboratory
WO2009061641A3 (fr) * 2007-11-05 2009-08-27 Abbott Laboratories Analyseur automatisé pour laboratoire clinique
EP2305384A1 (fr) * 2007-11-05 2011-04-06 Abbott Laboratories Analyseur automatique pour un laboratoire clinique
US9329194B2 (en) 2007-11-05 2016-05-03 Abbott Laboratories Automated analyzer for clinical laboratory
WO2009061643A1 (fr) * 2007-11-06 2009-05-14 Abbott Laboratories Système de chargement automatique d'un analyseur de laboratoire
US8691149B2 (en) 2007-11-06 2014-04-08 Abbott Laboratories System for automatically loading immunoassay analyzer
EP2191900A1 (fr) 2008-11-28 2010-06-02 F. Hoffmann-Roche AG Système et précédé pour le traitement d'un fluide contenant des acides nucléiques
US8921094B2 (en) 2008-11-28 2014-12-30 Roche Molecular Systems, Inc. System and method for nucleic acids containing fluid processing
US8845983B2 (en) * 2010-02-12 2014-09-30 Scp Science Independent heating of samples in a sample holder
US20110201127A1 (en) * 2010-02-12 2011-08-18 George Feilders Independent heating of samples in a sample holder
US10328432B2 (en) 2010-02-12 2019-06-25 Scp Science Independent heating of samples in a sample holder
CN102507963A (zh) * 2011-10-31 2012-06-20 上海裕隆生物科技有限公司 全自动反应仪的清洗机构
CN102507923B (zh) * 2011-10-31 2014-05-28 曲阜裕隆生物科技有限公司 全自动反应系统
CN102507964A (zh) * 2011-10-31 2012-06-20 上海裕隆生物科技有限公司 全自动反应仪
CN102507923A (zh) * 2011-10-31 2012-06-20 上海裕隆生物科技有限公司 全自动反应系统
WO2013192514A2 (fr) * 2012-06-21 2013-12-27 Automation Solutions, Inc. Système de distribution de fluide, monte-charge et utilisation associée
WO2013192514A3 (fr) * 2012-06-21 2014-02-20 Automation Solutions, Inc. Système de distribution de fluide, monte-charge et utilisation associée
US8968654B2 (en) 2012-06-21 2015-03-03 Automation Solutions, Inc. Fluid delivery system and lift for use in conjunction therewith
CN103712835A (zh) * 2012-09-28 2014-04-09 希森美康株式会社 试料调制装置及细胞分析装置
CN102998473A (zh) * 2012-12-19 2013-03-27 北京利德曼生化股份有限公司 全自动化学发光免疫分析仪
WO2017027425A1 (fr) * 2015-08-10 2017-02-16 Counsyl, Inc. Système modulaire de manipulation de liquides
CN108139420A (zh) * 2015-08-10 2018-06-08 考希尔股份有限公司 模块化液体处理系统
CN106834114A (zh) * 2017-02-20 2017-06-13 佛山市金蓝领教育科技有限公司 一种基于pcr应用的自动化检测系统
CN109201133A (zh) * 2018-11-13 2019-01-15 望潮科技（北京）有限公司 一种机械臂实验系统
WO2022037556A1 (fr) * 2020-08-17 2022-02-24 Nanjing GenScript Biotech Co., Ltd. Système intégré automatisé pour la production continue de plasmide à l'échelle industrielle
WO2022169726A1 (fr) * 2021-02-03 2022-08-11 Amgen Inc. Systèmes et approches pour un traitement de médicaments

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