Fluent material handling – with receiver or receiver coacting mea – With conveying means to supply successive receivers – Sampler type
Reexamination Certificate
2002-01-25
2003-10-28
Douglas, Steven O. (Department: 3751)
Fluent material handling, with receiver or receiver coacting mea
With conveying means to supply successive receivers
Sampler type
C141S129000, C141S001000, C422S091000, C422S105000, C436S174000, C436S180000
Reexamination Certificate
active
06637473
ABSTRACT:
The present invention relates to automated storage and retrieval devices and methods for using, and in particular to such devices and methods used in conjunction with inspection devices for sequentially inspecting microscopic crystals.
BACKGROUND OF THE INVENTION
The determination of the three dimensional atomic structure of matter is one of the most important areas of pure and applied research. One way in which the three dimensional atomic structure of matter can be determined is through X-ray crystallography. X-ray crystallography utilizes the diffraction of X-rays from crystals in order to determine the precise arrangement of atoms within the crystal. The result may reveal the atomic structure of substances such as metal alloys, deoxyribonucleic acid (DNA), or the structure of proteins.
There are very important benefits to knowing the accurate molecular structure of a protein crystal. For example, once the molecular structure is known, a drug designer can more effectively develop effective therapeutic agents and drugs. However, despite its promises, X-ray crystallography is limited by the fact that it is very difficult to grow successful crystals.
Prior Art Method of Growing Crystals
Protein crystals are commonly grown in the wells of micro-well plates. A micro-well plate is also known as a micro-titer plate or a microplate. Micro-well plates typically come with either 24, 48, 96, 384 or 1536 wells. A 96-well micro-well plate is shown in detail in FIG.
2
. There are a variety of methods in which protein crystals may be grown. Five common ways are summarized below.
Hanging Drop Method
One of the main techniques available for growing crystals, known as the hanging-drop or vapor diffusion method, is a method wherein a drop of a solution containing protein is applied to a glass cover slip and placed upside down in an apparatus such as a vapor diffusion chamber where conditions lead to supersaturation in the protein drop and the initiation of precipitation of the protein crystal.
Sitting Drop Method
Another method is the sitting drop method where the drop sits in a small well adjacent the growing solution instead of hanging over it. This method provides a more stable drop and location.
Aqueous Drop in Oil Method
Another method is the aqueous drop in oil method. The drop is placed in a micro-well and is covered with an oil based solution. The drop stays at the bottom of the well as the crystal grows.
Dialysis Method
In another method referred to as the dialysis method (also called microbatch crystallization), the protein solution is contained within a semi-permeable size exclusion membrane and then placed in a solution of fixed pH and precipitant concentration. As the precipitant diffuses through the membrane into the protein compartment, the solubility of the protein is reduced and crystals may form.
Gel Crystal Growth Method
This method involves the placement of a gel into the end of small diameter glass capillaries. After the solutions have gelled, a protein solution is placed into one end (top) of the capillary and the other end is submerged in a solution of precipitating agent. If the conditions are appropriately selected, crystal growth occurs at a point in the gel where the protein and precipitating agent reach the proper concentrations as the solutions slowly mix by diffusion. Since this is a diffusion limited process, it thus only occurs after an extended period of time. Crystals however, grown by this method are often larger and of higher quality.
Regardless of the method chosen, protein crystal growth is a very delicate and time-consuming process. It can take several days to several months before crystals of sufficient size and quality are grown and ready for x-ray crystallography. The current minimum size that is typically stated is a crystal of at least 50 microns thick by 100 microns in extent. The protein crystal growing environmental conditions need to be rigorously maintained, from the chemistry, to the surrounding air humidity and temperature, cleanliness to prevent contamination, and even lighting conditions. A protein crystallographer working with unknown protein families may only be about 5% successful in growing proper sized quality crystals. With this success rate, for example, a 96-well micro-well plate may only have 5 wells in which good crystals are growing.
Prior Art Inspection of Crystal Growth
Currently, a laboratory technician, or operator, aided by a microscope and a laboratory notebook manually inspects crystals grown in micro-well plates. To inspect a micro-well plate, a laboratory technician dons a clean-room gown suit and enters a cold room in which the crystals are growing. The technician then puts a micro-well plate underneath the microscope and examines each well in the micro-well plate until all of the wells in the micro-well plate have been inspected. The technician then makes a mental judgement as to how he shall classify (also known as “score”) the crystal. For example, the technician may feel that he is observing an image that shows “grainy precipitation” or “ugly precipitation”. Or, he may feel that the image shows “no crystal growth”. The technician then records the classification into a laboratory notebook.
The above system is riddled with opportunities for human error. An operator, manually inspecting a 96-well micro-well plate will take approximately 5 to 20 minutes depending on the skill of the operator and the number of wells that contain interesting features, microcrystals, or crystals. The operator may be subject to physical fatigue, suffer eyestrain, and may be uncomfortably cold in the temperature controlled and generally high humidity room. The operator can be tired and confused and can easily make errors in manually recording data in the notebook. For example, the operator may observe crystal growth at well H
5
(FIG.
2
), but incorrectly record in the notebook that the crystal growth was at well H
6
. Additional transcription errors may occur when the data is transferred to a computer database.
Research efforts are underway to try to solve the above problem, but they are inadequate for the needs of the industry. One such effort is described in Jurisica et al. “Intelligent Decision Support for Protein Crystal Growth”
IBM systems Journal
, Vol. 40, No 2, 2001. Another such effort is described at the Website www.dsitech.com.
Current Problems with Micro-well Plate Storage and Retrieval Procedures
Typically, after a technician has inspected a micro-well plate for crystal growth, the micro-well plate is stored until it is time to inspect it again. The growing of protein crystals in micro-well plates and the accompanying inspection of the micro-well plates for successful crystal growth are procedures that are typically carried out concurrently in large quantities in laboratories. For example, a typical lab at any given moment may have literally thousands of micro-well plates in which protein crystals are attempting to grow. The growth cycle of a protein crystal can be approximately 6 months. During the 6 month time period, a micro-well plate may be inspected up to approximately 12 times. If there are thousands of micro-well plates that require inspection, it can be a very time consuming task to manually move the micro-well plate from its storage location, place it under a microscope, record the results, and then move it back to its appropriate storage location. Moreover, there is tremendous opportunity for a technician to forget where a particular micro-well plate belongs. Or, a technician handling such a large quantity of micro-well plates can easily drop or otherwise damage the micro-well plates he is handling.
What is needed is a better device and method for storing and retrieving trays containing micro-well plates.
SUMMARY OF THE INVENTION
The present invention provides a device and method for the automated storage and retrieval of trays holding subject matter. A plurality of trays is inserted into an access device. A computer system is programmed to control a storage gantry to move the trays between the access device, a s
Adams John A.
Brovold Chritopher T.
Ganz Brian L.
Jewell David W.
Mickley Mandel W.
Douglas Steven O.
RoboDesign International, Inc.
Ross John R.
Ross, III John R.
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