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WO2002093139A2 - Dispositif de deplacement de plaque pour collecte de donnees de cristallisation - Google Patents

Dispositif de deplacement de plaque pour collecte de donnees de cristallisation Download PDF

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Publication number
WO2002093139A2
WO2002093139A2 PCT/US2002/015048 US0215048W WO02093139A2 WO 2002093139 A2 WO2002093139 A2 WO 2002093139A2 US 0215048 W US0215048 W US 0215048W WO 02093139 A2 WO02093139 A2 WO 02093139A2
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WO
WIPO (PCT)
Prior art keywords
crystallization
microscope
plate
plate mover
mover
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2002/015048
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English (en)
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WO2002093139A3 (fr
Inventor
Lansing J. Stewart
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Emerald Biostructures Inc
Original Assignee
Emerald Biostructures 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 Emerald Biostructures Inc filed Critical Emerald Biostructures Inc
Priority to AU2002305563A priority Critical patent/AU2002305563A1/en
Publication of WO2002093139A2 publication Critical patent/WO2002093139A2/fr
Publication of WO2002093139A3 publication Critical patent/WO2002093139A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/24—Base structure
    • G02B21/26—Stages; Adjusting means therefor

Definitions

  • the present invention is a plate mover used in data collection, and in particular the collection of crystallization trials results.
  • Macromolecular x-ray crystallography is an essential aspect of modern drug discovery and molecular biology.
  • biological macromolecules such as proteins, nucleic acids, and their various complexes
  • the enormous value of three-dimensional information has led to a growing demand for innovative products in the area of protein crystallization, which is currently the major rate limiting step in x-ray structure determination.
  • One of the first and most important steps of the x-ray crystal structure determination of a target macromolecule is to grow large, well diffracting crystals with the macromolecule.
  • crystal growth has become a rate limiting step in the structure determination process.
  • Vapor diffusion is the most widely used technique for crystallization in modern macromolecular x-ray crystallography, i this technique, a small volume of the macromolecule sample is mixed with an approximately equal volume of a crystallization solution.
  • the resulting drop of liquid (containing macromolecule and dilute crystallization solution) is sealed in a chamber with a much larger reservoir volume of the crystallization solution.
  • the drop is kept separate from the reservoir, either by hanging from a glass cover slip or by sitting on a tiny pedestal. Over time, the crystallization drop and the reservoir solutions equilibrate via vapor diffusion of the volatile species. Supersaturating concentrations of the macromolecule are achieved, resulting in crystallization in the drop when the appropriate reservoir solution is used.
  • Macromolecular crystallization is a hyperdimensional phenomena, dependent on a host of experimental parameters including pH, temperature, and the concentration of salts, macromolecules, and the particular precipitating agent (of which there are hundreds).
  • the ability to rapidly and easily generate many crystallization trials is important in determining the right conditions for crystallization.
  • the present invention provides a hands-free apparatus to move a crystallization plate across the field of view of a microscope with minimal user intervention.
  • the plate mover is an integrated stage mover and stereo microscope which moves crystallization plates through the microscope field of view.
  • a digital camera attached to the microscope can capture images of crystallization results as the crystallization plate is moved through the field of vision of the microscope.
  • the stereo microscope of at least one embodiment of the present invention provides 3-D information that a 2-D video screen cannot duplicate. This is important in crystallization because the user is not looking at a 2- D slide, but rather is looking at 3-D drops of solution. These drops are often a few millimeters thick.
  • the stereo microscope provides the user an unmatched ability to observe and recognize crystal formation within these drops.
  • To manufacture a plate mover with a standard off-the-shelf microscope the microscope is cut in half so that the phototube portion is separated from the base portion. Holes may then be tapped into the microscope parts so that they can be mounted on a specially-designed plinth.
  • Another advantage of an embodiment of the present invention is that speech input can be used to direct the movement of the plate/tray, thus providing complete hands-off operation, so that the user can concentrate on his examination of the various solutions.
  • SQL Structured Query Language
  • trial results are presented pictographically, which allows a user to "see” images of rather than read text about the results.
  • Pictographs are highly intuitive and can capture greater than 95 percent of all standard crystallization trial results.
  • the invention plate mover is suitably controlled by a computer having a CPU and a memory, wherein a software application, such as Crystal MonitorTM resides in the computer.
  • Crystal MonitorTM memory is a suitable software application for crystallization results data entry which can use voice recognition commands to enter a crystallization result in a database.
  • the software application can be obtained from Emerald BioStructures, Inc. of Bainbridge Island, Washington.
  • the software is described in U.S. Patent Application No. 09/631,185, filed on August 2, 2000, the specification of which is herein expressly incorporated by reference.
  • Real-time images can be viewed on a computer monitor during operation of the plate mover.
  • an automatic observation feature can cause the plate mover to automatically move the crystallization plate to capture images of crystallization results in a plate with minimal user intervention.
  • a plate mover for use in collecting crystallization data includes a microscope (e.g., a stereo microscope), a translational stage, a memory containing computer program code and a CPU which executes the program code.
  • the translational stage moves a crystallization plate (tray) containing an array of crystallization wells through the microscope's field of view.
  • the CPU controls the translational stage responsive to user input, and is further responsive to crystallization trial data and crystallization result data.
  • Trial data may include information regarding the crystallization conditions to be used in a crystallization trial, including but not limited to, pH, temperature, and the concentration of salts, macromolecules, the particular precipitating agent and so on.
  • Crystallization result data may include crystal type, crystal size, crystal shape, crystal count, etc. hi one embodiment, crystallization trial data, and crystallization results data are stored in a SQL database.
  • a pictograph representing the result appears in a crystallization well as represented in a graphical user interface (GUI).
  • GUI graphical user interface
  • Speech input, keyboard input and cursor/button input may be used to control, through the CPU, the translational stage.
  • the CPU may provide an automatic observation feature in which the plate mover automatically moves the crystallization plate (via the translational stage) to capture images of all crystallization results in the plate with minimal user intervention
  • An embodiment of the invention further comprises a plinth that supports the microscope and translational stage.
  • the plinth itself includes a platform, a phototube mount on which the microscope's phototube is mounted, and a structural member connecting the platform to the mount.
  • the structural member may be a substantially vertical support bar, or a rectangular frame.
  • the base of the microscope is separated from the microscope phototube post, and the base is then mounted onto the plinth platform.
  • the translational stage is then supported by the microscope base.
  • a digital camera may be attached to the microscope to capture images of crystallization results as the plate is moved.
  • the CPU may receive the captured images and store them in a database, which may be the same database in which the crystallization trial data and crystallization results data are stored. Furthermore, the CPU may display the captured images on a computer monitor or other similar display device for viewing, in real time, during operation of the plate mover.
  • An image may be captured in response to a user voice command, or alternatively, in response to a user clicking on (selecting) a representation of the well to be imaged and then clicking on (selecting) a capture command button within a graphical user interface.
  • a foot-controlled focus controller may be provided to allow hands-free focusing of the microscope.
  • the translational stage has a first driver which moves the stage along a first axis, and a second driver which moves the stage along a second axis.
  • the first axis is preferably perpendicular to the second axis.
  • the translational stage may be automatically positioned so that a selected well is centered in the microscope viewing field.
  • the selected well may be selected, for example, by voice command, by clicking on an image of a well displayed on a computer monitor using a cursor control device, or by keyboard entry.
  • a joystick or similar controller may be provided for making fine adjustments so that a feature which is not in the center of a well can be viewed. After fine adjustments have been made, a user can click on (select) the representation of the well to move the plate mover back to the center of the well.
  • Fig. 1 shows a schematic of an embodiment of the hardware configuration according to the present invention.
  • Fig. 2 shows a schematic of an embodiment of a platemover according to the present invention.
  • Fig. 3 is a view of the plate mover constructed according to the present invention.
  • Fig. 4 is a view of a plinth with microscope base constructed according to the present invention.
  • Fig. 5 is a view of a plinth constructed according to the present invention.
  • Fig. 6 is a view of a phototube mount constructed according to the present invention.
  • Fig. 7 is a view of a plinth constructed according to the present invention.
  • Fig. 8 is a view of a translational stage used in the present invention.
  • Fig. 9 is a view of a plinth and a microscope base constructed according to the present invention.
  • Fig. 10 is a view of the plinth and structural members constructed according to the present invention.
  • Fig. 11 is a view of the plinth and a translation stage constructed according to the present invention.
  • Fig. 12 is a view of the plinth and phototube constructed according to the present invention.
  • Fig. 13 shows a GUI for a trial observation recording tab for an active session according to the present invention.
  • Fig. 14 shows a GUI for a plate mover builder accordmg to the present invention.
  • Fig. 15 is a view of the plate mover constructed according to the present invention.
  • Fig. 16 shows a GUI for a trial observation recording tab according to the present invention.
  • Fig. 17 shows a GUI for a digital image builder according to the present invention.
  • Figs. 18A - 18E are various views illustrating an alternate embodiment of the present invention using a different microscope from that shown in Fig. 3.
  • Fig. 1 illustrates a typical hardware configuration for implementing the present invention.
  • At least one client computer 10 maybe a stand alone computer, or more preferably, is connected along with a plurality of other client computers 14, 16 and 18 to a network server 12 by a local area network (LAN).
  • the client computers can be laptop or desktop computers (or other computer if desired).
  • the computer 10 includes a cursor control device and a keyboard (not shown).
  • the computer may have a mouse as the cursor control device.
  • Attached to each client computer 10, 14, 16, 18 via suitable interfaces are a number of peripheral devices including (i) a barcode scanner 2, (ii) a crystallization trial observation device, such as a plate mover which includes a microscope 104 and a positioning mechanism for positioning the wells of a crystallization trial tray (plate) for viewing by a user, (iii) a digital camera 108 and (iv) a microphone headset 6.
  • the microphone headset 6 provides audio speech input and audio feedback.
  • a table top microphone and speaker can be used.
  • Fig. 1 also shows a user 8 seated at the viewing microscope 104.
  • the microscope 104 may be fitted with a digital camera 108 for image capture of the crystallization trial data that is also observable through the microscope 104.
  • the user may use the barcode scanner 2 to read a barcode on a crystallization trial tray prior to the tray being mounted on the positioning mechanism. This enables quick and accurate identification of the trial number.
  • the positioning mechanism is an electromechanical mechanism that includes a tray or plate 106 whose position is controlled by x-y transducers 142.
  • the position of the x-y transducers 142 is controlled by client computer 10.
  • the client computer 10 can control the position of the plate 106 so that the desired well 136 can be seen through the microscope 104 and/or photographed by the digital camera 108.
  • Software executing on the client computer 10 creates crystallization trial data for storage in a relational database that, preferably, is stored on the network server 12.
  • the software includes a plurality of graphical user interfaces (GUIs) that provide user interfaces with various database managers which are described in U.S. Patent Application No. 09/631,185, filed on August 1, 2000, incorporated by reference herein.
  • GUIs graphical user interfaces
  • Fig. 3 illustrates a plate mover 100 constructed according to the present invention.
  • the plate mover 100 according to the present invention includes a translational stage mover 102 and stereo microscope 104, which moves a crystallization plate 106 through the microscope field of view.
  • a digital camera 108 is optionally attached to the microscope 104 to capture images of crystallization results as the plate 106 is moved.
  • the plate mover 100 is suitably controlled by a computer having a CPU and a memory wherein a software application for crystallization results data entry, such as CRYSTAL MONITOR resides therein.
  • Real-time images can be viewed on a computer monitor 112 during operation of the plate mover 100.
  • an automatic observation feature can cause the plate mover 100 to automatically move the crystallization plate 106, to capture images of all crystallization results in a plate 106 with minimal user intervention.
  • the plate mover 100 includes (a) a stereo microscope 104, such as Leica Microsystems AG's MS5 stereo microscope shown in Fig. 3, (b) a suitable stage mover 102, such as a Prior Scientific, Lie's XY translational stage, (c) a suitable digital camera 108, such as a Pixera Corporation digital camera, and (d) a plinth 114, suitably made from steel or the like.
  • the plinth 114 suitably holds the translational stage 102 and the microscope 104.
  • a crystallization plate 106 is shown on the translational stage 102.
  • Aluminum plate inserts 118 are constructed according to the present invention to accommodate different crystallization plates 106 and mate with the stage 102.
  • the microscope 104 includes a focus controller 134 which can be attached to foot pedals (not shown) for hands-free focusing.
  • the hands-free focusing controller and hardware is supplied by Prior Scientific, Inc.
  • the translational stage 102 is connected to a power supply (not shown).
  • the power supply can drive a first 120 and second 122 driver, to move the stage 102 in both X and Y directions.
  • the plate inserts 118 are suitably made to mate with the translational stage 102.
  • Fig. 4 illustrates the microscope base 126 and the plinth 114 of Fig. 3.
  • the microscope base 126 has been separated from rest of the microscope 104, for example by sawing, and attached to the plinth 114 by suitable fasteners, such as screws to enable the construction of the plate mover 100.
  • Mounting holes 150 are tapped into the base 126 for attaching the base 126 to the platform 130, and the translational stage 102 (shown in Fig. 3) to the base 126.
  • Fig. 5 illustrates the plinth 114, constructed according to the present invention.
  • the plinth 114 includes a platform 130, a phototube mount 132, and a structural member 134 connecting the platform 130 to the mount 132.
  • a suitable size for the platform 130 is about 16" wide by 18" long. However, other suitable sizes can also be used to provide a steady mount for the translational stage 102 and microscope 104.
  • the structural member 134 is suitably made to accommodate any suitable microscope.
  • a suitable height of the structural member 134 is about 18" high. However, other suitable heights can be used depending on the suitable microscope which is selected.
  • the structural member 134 can be a steel box framed tube.
  • Fig. 6 illustrates a suitable phototube mount 132 constructed according to the present invention.
  • a suitable mount 132 has three apertures disposed at the corners of an imaginary triangle and sized to accommodate the microscope phototube.
  • other fastener configurations are possible, depending on the microscope which is selected.
  • Fig. 7 is a perspective view of the plinth 114 of Fig. 3, constructed according to the present invention.
  • the plinth platform 130 is a rectangularly shaped member. Towards the back end 152 of the platform 130, the structural member 134 is mounted thereon at approximately midway from a first 156 and second 158 lateral sides of the platform 130.
  • the structural member 134 includes a first 160 and a second 162 end wherein the first 160 end has been welded to the platform 130 as described above.
  • the second end 162 includes the microscope mount 132.
  • the microscope mount 132 is constructed so as to suitably hold the microscope phototube.
  • Fig. 8 illustrates the translational stage assembly 102 of Fig. 3.
  • This stage includes a first 120 and a second 122 driver.
  • the first driver 120 can move the stage 164 in a first direction, while the second driver 122 moves the stage 164 in a direction which is perpendicular to the first direction.
  • a suitable translational stage is provided by Prior Scientific, h e.
  • the stage 164 includes an aperture for holding -li ⁇
  • a suitable translational stage measures 17" wide by 17" in length.
  • the microscope base 126 is attached to the plinth mount 132 by suitable fasteners, such as screws through mounting holes 150 in microscope base 126.
  • suitable spacers 166 are attached to the microscope base 126.
  • the spacers 166 separate the microscope base 126 from the translational stage 102.
  • a suitable material to use as a spacer is brass; however, other suitable metal or synthetic materials may also be used.
  • the placement of the spacers 166 may suitably be determined based on the selected translational stage 102.
  • the translational stage 102 is mounted onto the spacers 166 and attached thereto by suitable fasteners, such as screws.
  • the microscope phototube 170 is attached to the plinth mount 132 by suitable fasteners 172, such as screws.
  • Fig. 13 is a view of a "trial observation recording" dialog window 5400.
  • a user has several options for entering crystallization results data.
  • a user can click on or otherwise select individual results buttons in the crystallization results control panel 5401, or a user can enter data by voice using speech recognition software that forms part of this invention and is more fully described below, hi this regard, a user has the option of enabling speech recognition by checking a speech recognition check box 5402. A user also has the option of hearing the input by checking a feedback checkbox 5404. Speech recognition permits the user to maintain his focus on the microscope 104 and determining crystallization trial results during an observation session. This results in faster crystallization data collection as there is no physical motion required of the user, such as taking focus away from the microscope to write observations in a notebook. The audio feedback confirmation of the speech recognition commands ensures practically complete accuracy of the speech recognition.
  • Selecting an options command button 5406 in the crystallization results control panel 5401 of the trial observation recording dialog window 5400 customizes the voice command settings while an observation session is active.
  • the user may choose to enable the plate mover.
  • the automated plate mover allows precise, reproducible plate translations for recording crystallization observations.
  • the plate mover is controlled by cursor controller clicks over a particular well 5408, selected keyboard keys, or speech recognition.
  • Using the plate mover requires that crystallization trays be appropriately inserted into or mounted on a plate insert which fits into the microscope support structure.
  • software formed in accordance with the present invention comes preloaded with the positions of the trial wells (drop chambers) for all available crystallization trays or plates. New trays and/or plates are definable using the apparatus manager in the manner described in U.S. Patent Application No. 09/631,185.
  • Fig. 14 illustrates an exemplary options dialog window 6400 which can be used to calibrate the plate mover.
  • Calibration requires that a user place the plate insert with the plate or tray in the microscope stage so that a reference hole in the insert is in a predetermined position, i.e., the upper left comer, when the inserted plate is viewed from above. The user manually adjusts the plate mover using a joystick control until the reference hole is in the center of the viewing field of the microscope.
  • the plate calibration options dialog window 6400 also allows a user to test the plate mover by clicking on a run command button 6401.
  • a run command button 6401 When a user selects the run command button 6401, followed by the align coordinates command button 6402, the plate mover is calibrated with pre-defined plate definitions.
  • calibrating the plate mover for one type of plate insert calibrates the mover for all plate inserts.
  • the plate mover can be recalibrated if the plate mover is jarred.
  • the plate mover can be used to view or record crystallization trials by a user opening the trial and checking the plate mover checkbox 5416 in the trial observation recording dialog window 5400 (Fig. 13). Since the type of crystallization plate used in the trial and its dimensions and well positions are stored in the database, selecting on a representation of a well using a cursor control device automatically positions the plate mover so that the selected well is centered in the microscope viewing field.
  • a joystick (not shown) can be used for fine adjustments so that a feature which is not in the center of the well can be viewed.
  • selecting the well representation 5408 returns the plate mover to the center of the corresponding well.
  • the plate mover moves in single well increments using the up, down, left, and right arrow keys of a keyboard.
  • the plate mover can also be moved by voice commands during an active trial observation session. Suitable navigational voice commands are, but are not limited to: Next, Back, Well Left, Well Right, Well Up, Well Down, First Well, and Last Well.
  • the up, down, left, and right arrow buttons 5405 in the results control panel 5401 (Fig. 13) can be used to move the plate mover during an active observation session.
  • a suitable digital camera 108 is mounted on the microscope phototube 170.
  • a suitable digital camera is made by Pixera Corporation and is attachable to the microscope 104 with a common C- mount.
  • Ancillary equipment such as cables, drivers, controllers, and power supplies can be attached at any stage or microscope, so as to enable the construction of a hands-free crystallization results data collection in combination with a suitable computer executable set of instructions.
  • the digital image camera 108 maybe used to capture digital images of the crystallization results.
  • An observation session must be active in order to take a digital image.
  • an image capture options list is displayed.
  • the image capture options list allows a user to select the pixel resolution of the image to be captured.
  • all images are saved in JPEG format.
  • a 320 by 240 pixel image requires about 200 kB of data storage, and a 1,260 by 960 pixel image requires about 3 MB of data storage.
  • an image is captured by a user clicking on the image and then clicking on a capture command button, or issuing a capture voice command.
  • Several feedback beeps can be emitted, for example, to indicate to a user that the camera is preparing to capture an image. More beeps can be used to denote that a higher resolution image will be captured.
  • a clicking shutter feedback sound can be emitted when the image is taken.
  • Fig. 16 shows a GUI for a trial observation recording tab according to the present invention.
  • the captured image appears in a thumbnail box 6500 in the crystallization results control panel, and an image capture icon 6502 appears in the related well in the trial template.
  • double clicking an image in the thumbnail box 6500 will automatically launch a program that creates a larger size view 6601 of the image as shown in Fig. 17.
  • the image is such that it can then be manipulated by any suitable graphics program and the edited version saved as a result.
  • a pictograph representing the result appears in the crystallization well representation of the GUI.
  • a result crystallization trial data
  • a pictograph representing the result appears in the crystallization well representation of the GUI.
  • up to six different crystallization results plus a comment and a digital image can be entered for a crystallization well during an observation session.
  • the focus is advanced to the next well using the navigation commands - next, back, well right, well left, well up, and well down.
  • Fig. 13 is an example of what the crystallization results might look like.
  • any captured image is viewable during a review of the data produced during an observation session.
  • clicking on the image capture command button 5407 turns on an observed flag for the related well representation 5408, even if no other observations are recorded for that well.
  • Figs. 18A - 18E are various views illustrating an alternate embodiment of the present invention using a different microscope from that shown in Fig. 3.
  • Fig. 18 A illustrates a second suitable stereo microscope 104 for use in the present invention: a Leica LZ12.5 stereo microscope 200.
  • any suitable stereo microscope can be incorporated into the plate mover 100 in accordance with the present invention.
  • FIG. 18B illustrates this microscope as it is purchased "off the shelf.
  • a post 203 on which the phototube holder 205 rides is integral with the base 201.
  • the phototube 207 sits in the phototube holder 205.
  • Fig. 18C illustrates an embodiment of the present invention using this microscope.
  • a plinth comprises a base 211 which provides stability.
  • a rectangular frame 213 supports the phototube mount 215. Note that the post 203 has been severed from the microscope's base, by sawing it off in the case of this particular microscope model. Mounting holes are then tapped into the post 203, which is then attached to the plinth's phototube mount 215. The phototube holder 205 is then attached to the post 203, as normal. The phototube 207 will then sit in the phototube holder 205.
  • This figure shows the camera 209 attached to the phototube 207. Also shown is the translational stage 217, which is attached to the microscope base (not shown), which in turn is mounted to the platform 211.
  • a bar code scanner 252 Also shown in Fig. 18C are a bar code scanner 252 and a joystick 250.
  • Fig. 18D is another view of the invention with the phototube 207 mounted in the phototube holder 205.
  • Fig. 18E is yet another view showing how the post 203 is attached to the phototube mount 215 using, in this embodiment, three fasteners 220.

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  • Physics & Mathematics (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Optics & Photonics (AREA)
  • Crystals, And After-Treatments Of Crystals (AREA)
  • Microscoopes, Condenser (AREA)

Abstract

L'invention concerne un dispositif de déplacement de plaque comprenant un dispositif de déplacement d'étage intégré et un microscope stéréoscopique déplaçant les plaques de cristallisation à travers le champ angulaire du microscope. Une caméra numérique reliée au microscope peut capturer des images des résultats de la cristallisation au fur et à mesure que la plaque de cristallisation est déplacée à travers le champ angulaire du microscope. Le dispositif de déplacement est commandé de manière adaptée par un ordinateur équipé d'une unité centrale et d'une mémoire, une application logicielle, telle que Crystal MonitorTM, étant installée dans l'ordinateur. Crystal MonitorTM est une application logicielle adaptée à la saisie des données relatives aux résultats de la cristallisation, elle permet l'utilisation de commandes par reconnaissance vocale pour entrer les données relatives aux résultats de la cristallisation dans la base de données. Des images en temps réel peuvent être visualisées sur l'écran de l'ordinateur pendant le fonctionnement du dispositif de déplacement de plaque. Dans un mode de réalisation adapté, un élément d'observation automatique entraîne le déplacement automatique de la plaque de cristallisation par le dispositif de déplacement de plaque de manière à capturer des images des résultats de la cristallisation dans une plaque, limitant ainsi les interventions de l'utilisateur.
PCT/US2002/015048 2001-05-11 2002-05-10 Dispositif de deplacement de plaque pour collecte de donnees de cristallisation Ceased WO2002093139A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2002305563A AU2002305563A1 (en) 2001-05-11 2002-05-10 Plate mover for crystallization data collection

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US29046001P 2001-05-11 2001-05-11
US60/290,460 2001-05-11

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WO2002093139A3 WO2002093139A3 (fr) 2003-07-03

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6911056B2 (en) 1999-06-18 2005-06-28 The Regents Of The University Of California Method for diffracting crystals formed by submicroliter crystallization experiments
US7416710B1 (en) 2003-12-31 2008-08-26 Takeda San Diego, Inc. Method and system for performing crystallization trials

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5671086A (en) * 1995-04-18 1997-09-23 The Regents, University Of California Method and apparatus for accurately manipulating an object during microelectrophoresis
EP0819964B1 (fr) * 1996-07-16 2004-02-04 Perkin-Elmer Limited Contrôle de l'ouverture d'un microscope
JP3689584B2 (ja) * 1999-03-31 2005-08-31 サッポロビール株式会社 観察装置の位置設定手段における座標変換方法及び座標変換手段を備える観察装置

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6911056B2 (en) 1999-06-18 2005-06-28 The Regents Of The University Of California Method for diffracting crystals formed by submicroliter crystallization experiments
US6932845B2 (en) 1999-06-18 2005-08-23 The Regents Of The University Of California Method for performing submicroliter crystallization experiments
US6951575B2 (en) 1999-06-18 2005-10-04 The Regents Of The University Of California Method for performing high density submicroliter crystallization experiments
US7001438B2 (en) 1999-06-18 2006-02-21 The Regents Of The University Of California Method for performing submicroliter crystallization experiments with high experiment to experiment precision
US7015041B2 (en) 1999-06-18 2006-03-21 The Regents Of The University Of California Automated method for setting up multiple crystallization experiments in submicroliter volumes
US7416710B1 (en) 2003-12-31 2008-08-26 Takeda San Diego, Inc. Method and system for performing crystallization trials
US7416709B1 (en) 2003-12-31 2008-08-26 Takeda San Diego, Inc. Method for performing crystallization trials
US7431768B1 (en) 2003-12-31 2008-10-07 Takeda San Diego, Inc. System for performing crystallization trials
US7431769B1 (en) 2003-12-31 2008-10-07 Takeda San Diego, Inc. Method for performing crystallization trials
US7435397B1 (en) 2003-12-31 2008-10-14 Takeda San Diego, Inc. System for performing crystallization trials
US7435379B1 (en) 2003-12-31 2008-10-14 Takeda San Diego, Inc. System for performing crystallization trials
US7452419B1 (en) 2003-12-31 2008-11-18 Takeda San Diego, Inc. Method for performing crystallization trials
US7510690B1 (en) 2003-12-31 2009-03-31 Takeda San Diego, Inc. System for performing crystallization trials

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