Image analysis – Applications – Biomedical applications
Reexamination Certificate
1999-02-26
2001-04-10
Johns, Andrew W. (Department: 2621)
Image analysis
Applications
Biomedical applications
Reexamination Certificate
active
06215894
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to the imaging and analysis of experiments performed on microarry biochips. More particularly it relates to the automatic control of microarry scanners and selection of the proper protocols for analysis of the image maps provided by the scanners.
BACKGROUND OF THE INVENTION
Micrroarray biochips are being increasingly used for the performance of large numbers of closely related chemical tests. For example, to ascertain the genetic differences between lung tumors and normal lung tissue one might deposit small samples of different cDNA sequences under a microscope slide and chemically bond them to the glass. ten thousand or more such samples can easily be arrayed as dots on a single microscope slide using mechanical microarraying techniques. Next, sample mRNA is extracted from normal lung tissue and from a lung tumor. The mRNA represents all of the genes expressed in these tissues and the differences in the expression of mRNA between the diseased tissue and the normal tissue can provide insights into the cause of the cancer and perhaps point to possible therapeutic agents as well. The “probe”samples from the two tissues are labeled with different fluorescent dyes. A predetermined amount of each of the two samples is then deposited on each of the microarray dots where they competitively react with the cDNA molecules. The mRNA molecules that correspond to the cDNA strands in the array dots bind to the strands and those that do not are washed away.
The slide is subsequently processed in a scanner that illuminates each of the dots with laser beams whose wavelengths correspond to the fluorescences of the labeling dyes, The fluorescent emissions are sensed and their intensity measured to ascertain for each of the array dots the degree to which the mRNA samples correspond to the respective cDNA sequences. In the experiment outlined above the image scanner separately senses the two fluorescences and thereby provides separate maps of the reactions of the mRNA extracted from the normal and tumorous tissues. The scanner generates an image map of the array, one for each of the fluorescenses. The maps are ultimately analyzed to provide meaningful information to the experimenter.
Microarray biochips are available in a variety of form factors and they may contain one or more different fluorescence labels. The reagents involved in the chemical reactions in the array dots are typically biological samples such as DNA, RNA, peptides, proteins or other organic molecules. The biochips might be used for diagnostics, screening assays, genetics and molecular biology research. They may include, in addition to the test dots, carlibration dots containing known amounts of the fluorescent materials. Scanning of the latter dots thus serves to calibrate the readings obtained from the test dots.
In order to obtain accurate information from the scanning of a biochip array, it is important to know which fluorescence materials have been used, in where the array is located, and the locations of the calibration dots, if any. It is important to know the fluorescent materials in order to use the correct wavelengths in illuminating the dots and to filter the correct wavelengths of the fluorescent omissions. Furthermore, it is advantageous to excite the fluorescenses with a high intensity so as to provide the maximum signal to the fluorescence detector. However, the intensity must be kept below the level at which the flurorescense is saturated or the fluorescent material is degraded and this depends on the particular fluorescent material that is used.
Furthermore, analysis of raw data collected by the scanner must be performed in accordance with protocols that may vary in accordance with experiment parameters. Prior to the present invention entry of the scanning and analysis protocol has been performed manually. This involves significant operator time and, further, is a source of errors in the scanning and analysis procedure.
SUMMARY OF THE INVENTION
In accordance with the invention an identifier corresponding to each experiment is imprinted on the biochip. The identifier is machine readable and, preferably, also human readable. For example, the identifier may be a number with numerals imprinted on the slide along with a bar code representation of the number. The experiment identifier is imprinted on the chip prior to the deposition of the array experiment. A file folder (i.e., “directory”) is opened in a computer system and is logically linked to the array identifier. An operator may enter into that folder the various parameters of the experiment array, e.g., a map of the reagents deposited in the array, identification of the fluorescent tags and the reagents to which they are bonded, and also the locations of any calibration dots on the chip. The operator may also enter into the folder an identification of the scanning and processing protocols to be used in connection with the scanning process. Preferably, however, the system is programmed to retrieve the information from the biochip. The protocols are therefore identified, or even described, in the machine-readable code on the biochip.
Accordingly, when the biochip is subsequently installed in a scanner, the scanner can scan the bar code version of the identifier. The system can then automatically open the requisite file folders and obtain the scanning and analysis protocols. The scanner is then set up to operate in accordance with the retrieved protocol. The resulting image map of the scanned data is stored in one or more files in the chip's file folder. The analysis protocol is subsequently retrieved and the image map processed in accordance with the latter protocol provide an array of output data.
If the system cannot locate an appropriate protocol, either for scanning or processing, it prompts the operator to identify an appropriate stored protocol or to enter a new protocol, if required.
With the foregoing arrangement the requirement for operator intervention is significantly reduced. This speeds up the overall process and, perhaps more important, reduces the probability of error that would be encountered error due to improper entry of scanning and processing protocols.
REFERENCES:
patent: 5849486 (1998-12-01), Heller et al.
patent: 5874219 (1999-02-01), Rava et al.
patent: 5978053 (1999-11-01), Giles et al.
patent: 5991030 (1999-11-01), Yamamoto et al.
patent: 6139831 (2000-10-01), Shivashankar et al.
Achin Ron
Schermer Mack
Zeleny Rolland
Cesari & McKenna LLP
General Scanning, Incorporated
Johns Andrew W.
Nakhjavan Shervin
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