Method and system for efficient collection and storage of experimental data

• US 7,467,153 B2
• Filed: 08/27/2003
• Issued: 12/16/2008
• Est. Priority Date: 11/13/1998
• Status: Expired due to Term

• Current Assignee: Cellomics Incorporated (Thermo Fisher Scientific Incorporated)
• Original Assignee: Cellomics Incorporated (Thermo Fisher Scientific Incorporated)
• Inventors: McKenna, Brian, Dunlay, Terry, Boyce, Keith, Glick, Phillip
• Primary Examiner(s): ALAM, SHAHID AL
• Application Number:
  US10/649,323
• Publication Number:
  US 20040139103A1
• Time in Patent Office: 1,938 Days
• Field of Search: 707/10, 707/200, 707/101, 707/102, 707/104.1, 709/203, 709/218, 382/131, 382/128, 382/164, 600/416
• US Class Current: 1/1
• CPC Class Codes: G01N 15/1433 using image recognition
• CPC Class Codes: G01N 2015/1477 Multiparameters
• CPC Class Codes: G01N 2015/1497 Particle shape
• CPC Class Codes: G01N 2035/00158 Elements containing microarrays, i.e. "biochip"
• CPC Class Codes: G06V 20/69 Microscopic objects, e.g. biological cells or cellular parts

Abstract

Methods and system for efficient collection and storage of experimental data allow experimental data from high-throughput, feature-rich data collection systems, such as high-throughput cell data collection systems to be efficiently collected, stored, managed and displayed. The methods and system can be used, for example, for storing, managing, and displaying cell image data and cell feature data collected from microplates including multiple wells and a variety of bio-chips in which an experimental compound has been applied to a population of cells. The methods and system provide a flexible and scalable repository of experimental data including multiple databases at multiple locations including pass-through databases that can be easily managed and allows cell data to be analyzed, manipulated and archived. The methods and system may improve the identification, selection, validation and screening of new drug compounds that have been applied to populations of cells.

Claims

1. A method of collecting experimental data comprising the steps of:

initializing a container using configuration information, the container having a plurality of subcontainers disposed therein or thereon, each subcontainer having a biological specimen disposed within or on the subcontainer;

storing the configuration information used for the container in a container database;

repeating steps (a)-(g) for desired sub-containers in the container;

(a) selecting an individual sub-container in the container,

(b) collecting a plurality of image data from the biological specimen disposed within or on the sub-container,

(c) storing the plurality of image data in an image database,

(d) collecting a plurality of feature data from the image data,

(e) storing the plurality of feature data in a feature database,

(f) calculating a plurality of sub-container summary data using the plurality of image data and the plurality of feature data collected from the biological specimen disposed within or on the sub-container, and

(g) storing the plurality of sub-container summary data in a sub-container database;

calculating a plurality of container summary data using the plurality of sub-container summary data from the sub-container database; and

storing the plurality of container summary data in the container database.

2. A computer readable medium having stored therein instructions for causing a central processing unit to execute the method of claim 1.

3. The method of claim 1 wherein the biological specimen disposed within or on each subcontainer comprises cells treated with an experimental compound.

4. The method of claim 1 wherein the container comprises a microplate, and each subcontainer comprises a well disposed within the microplate.

5. The method of claim 1 wherein the container database comprises microplate data, the sub-container database comprises well data, the image database comprises photographic image data and the feature database comprises cell feature data.

6. The method of claim 1 wherein the step of collecting a plurality of feature data from the image data comprises collecting any of:

size, shape, intensity, texture, location, area, perimeter, shape factor, equivalent diameter, length, width, integrated fluorescence intensity, mean fluorescence intensity, variance, skewness, kurtosis, minimum fluorescence intensity, maximum fluorescence intensity, geometric center, an X-coordinate of a geometric center or a Y-coordinate of a geometric center for cells.

7. The method of claim 1 wherein the step of calculating a plurality of sub-container summary data comprises calculating any of:

sizes, shapes, intensities, textures, locations, nucleus area, spot count, aggregate spot area, average spot area, minimum spot area, maximum spot area, aggregate spot intensity, average spot intensity, minimum spot intensit intensity, maximum spot intensity, normalized average spot intensity, normalized spot count, number of nuclei, nucleus aggregate intensity dye area, dye aggregate intensity, nucleus intensity, cytoplasm intensity, difference between nucleus intensity and cytoplasm intensity, nucleus area, cell count, nucleus box-fill ration, nucleus perimeter squared area or nucleus height/width ratio.

8. The method of claim 1 wherein the step of calculating a plurality of container summary data comprises calculating any of:

mean size, mean shape, mean intensity, mean texture, locations of cells, number of cells, number of valid fields, standard deviation of nucleus area, mean spot count, standard deviation of spot count, mean aggregate spot area, standard deviation of aggregate spot area, mean average spot area, standard deviation of average spot area, mean nucleus area, mean nucleus aggregate intensity, standard deviation of nucleus intensity, mean dye area, standard deviation of dye area, mean dye aggregate intensity, standard deviation of aggregate dye intensity, mean of minimum spot area, standard deviation of minimum spot area, mean of maximum spot area, standard deviation of maximum spot area, mean aggregate spot intensity, standard deviation of aggregate spot intensity, mean average spot intensity, nuclei intensities, cytoplasm intensities, difference between nuclei intensities and cytoplasm intensities, nuclei areas, nuclei box-fill ratios, nuclei perimeter squared areas, nucleus height/width ratios, well cell counts.

9. The method of claim 1 wherein the container comprises a bio-chip and each subcontainer comprises a micro-gel disposed on the bio-chip.

10. The method of claim 1 further comprising:

storing the container database data and the sub-container database data in a second database on a shared database;

storing the image database and the feature database data in a plurality of third databases on a shared database file server; and

creating links in a first database to the second database and the plurality of third databases, wherein the first database includes links to the second database and the plurality of third databases but does not include any data collected from the container, and wherein the first database is used by a display application to view data collected from a container.

11. The method of claim 10 wherein the shared database includes faster access local storage.

12. The method of claim 10 wherein the shared database file server includes slower access remote storage.

13. The method of claim 1 wherein each biological specimen comprises one or more cells.

14. The method of claim 1 wherein the container comprises a DNA array.

15. The method of claim 1 wherein the container comprises a chip based array or a bio-chip based array.

16. A method of collecting experimental data comprising:

storing information about a container in a container database, the container having a plurality of subcontainers disposed therein or thereon, each subcontainer having a biological specimen disposed within or on the subcontainer;

performing steps (a)-(f) for each sub-container;

(a) collecting image data from the biological specimen disposed within or on the subcontainer,

(b) storing the image data from the biological specimen in an image database,

(c) determining feature data for the biological specimen from the image data,

(d) storing the feature data for the biological specimen in a feature database,

(e) calculating sub-container summary data using the image data and the feature data associated with the biological specimen disposed within or on the sub-container, and

(f) storing the sub-container summary data in a sub-container database;

calculating container summary data using the sub-container summary data for each sub-container associated with the container; and

storing the container summary data in the container database.

17. A computer readable medium having stored therein instructions for causing a central processing unit to execute the method of claim 16.

18. The method of claim 16 wherein the container comprises a microplate, and each subcontainer comprises a well.

19. The method of claim 16 wherein each biological specimen comprises one or more cells.