Chemical reaction monitor

• US 20040219063A1
• Filed: 01/21/2004
• Published: 11/04/2004
• Est. Priority Date: 01/21/2003
• Status: Active Grant

• Current Assignee: Illumina Incorporated
• Original Assignee: Illumina Incorporated
• Inventors: Kotseroglou, Theo, Lebl, Michal, Fambro, Steven P., Heiner, David Louis
• Granted Patent: US 7,887,752 B2
• Time in Patent Office: Days
• US Class Current: 422/68.1
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/0036 Nozzles
• CPC Class Codes: B01J 2219/00414 using suction
• CPC Class Codes: B01J 2219/00421 using centrifugation
• CPC Class Codes: B01J 2219/00423 using filtration, e.g. through porous frits
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00587 High throughput processes
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00675 In-situ synthesis on the substrate
• CPC Class Codes: B01J 2219/00689 using computers
• CPC Class Codes: B01J 2219/00693 Means for quality control
• CPC Class Codes: B01J 2219/00698 Measurement and control of process parameters
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C40B 40/06 Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/10 Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 50/14 Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: Y10T 436/115831 : Condition or time responsive

Abstract

An apparatus for parallel monitoring of a plurality of chemical reactions, each chemical reaction occurring within a respective one of a plurality of wells. The apparatus includes a lighting device for illuminating the plurality of wells, the lighting device having an light emitting diode (LED) array, a camera device configured to obtain images of the plurality of wells and saving the images to an image storage location, the camera device having a charge couple device (CCD) capable of imaging the plurality of wells simultaneously, a viewing program for viewing one or more of the saved images, and an analyzing program for opening each saved image and geometrically registering each saved image in order to determine a specific value corresponding to each one of the chemical reactions at the time the image was obtained, the analyzing program saving the specific values to an analysis results storage location. A method of utilizing the apparatus is also disclosed.

Claims

1. A chemical reaction monitoring system for parallel monitoring of a plurality of chemical reactions, each chemical reaction occurring within a respective one of a plurality of wells, said system comprising:

a lighting device for illuminating the plurality of wells;

a camera device configured to obtain a fresh image of the plurality of wells and saving said fresh image to an image storage location;

a graphical user interface program for viewing said saved fresh image; and

an analyzer program for accessing said saved fresh image, geometrically registering said saved fresh image in order to determine a specific value corresponding to each one of the chemical reactions within each well at the time the image was obtained, and saving said specific values to an analysis results storage location.

2. The chemical reaction monitoring system of claim 1, wherein the chemical reaction is oligonucleotide synthesis.

3. The chemical reaction monitoring system of claim 1, wherein said plurality of wells comprises a multi-well plate.

4. The chemical reaction monitoring system of claim 1, wherein said lighting device comprises a light emitting diode (LED) array.

5. The chemical reaction monitoring system of claim 4, wherein said LED array includes a first array and a second array positioned on either side of a multi-well plate-viewing window.

6. The chemical reaction monitoring system of claim 4, wherein said LED array includes a single array positioned pivotally mounted on one side of a multi-well plate-viewing window.

7. The chemical reaction monitoring system of claim 1, wherein said camera device comprises a charge couple device (CCD) capable of imaging the plurality of wells simultaneously.

8. The chemical reaction monitoring system of claim 1, wherein said analyzer program processes said fresh image and said specific values comprise a processed image.

9. A chemical synthesis system comprising:

(a) a sample holder placed to support a plurality of wells;

(b) a liquid dispenser placed to dispense a liquid sample to said plurality of wells;

(c) a liquid removal device placed to remove said liquid sample from said plurality of wells;

(d) a lighting device for illuminating said plurality of wells;

(e) a camera device configured to obtain a fresh image of said plurality of wells and save said fresh image to an image storage location; and

(f) a computer system configured to;

(i) access said saved fresh image;

(ii) determine a specific value corresponding to each one of the chemical reactions within each well at the time the image was obtained; and

(iii) communicate a representation of said specific values to a graphical user interface.

10. The system of claim 9, wherein said computer system is further configured to write said specific values to a data storage location.

11. The system of claim 9, wherein said representation comprises a warning message if said specific values are within a pre-defined range of failure.

12. The system of claim 9, wherein said liquid removal device comprises a centrifuge rotor for orbiting said plurality of wells about an axis of rotation.

13. The system of claim 9, wherein said liquid removal device comprises a liquid aspirating tube.

14. The system of claim 9, wherein the chemical reaction is oligonucleotide synthesis.

15. The system of claim 9, wherein said plurality of wells comprises a multi-well plate.

16. The system of claim 9, wherein said lighting device comprises a light emitting diode (LED) array.

17. The system of claim 14, wherein said LED array includes a first array and a second array positioned on either side of a multi-well plate-viewing window.

18. The system of claim 14, wherein said LED array includes a single array positioned pivotally mounted on one side of a multi-well plate-viewing window.

19. The system of claim 9, wherein said camera device comprises a charge couple device (CCD) capable of imaging the plurality of wells simultaneously.

21. The method of claim 19, wherein step (e) further comprises communicating a representation of said specific values to a graphical user interface.

23. The method of claim 19, wherein step (c) further comprises removing said liquid from said plurality of wells after obtaining said fresh image.

24. The method of claim 19, wherein removing said liquid comprises centrifugation or aspiration.

25. The method of claim 19, wherein said polymer comprises a polynucleotide and said monomeric precursor comprises a nucleoside.

26. The method of claim 19, wherein said plurality of wells comprises a multi-well plate.

27. The method of claim 19, wherein step (c) further comprises illuminating said plurality of wells with a light emitting diode (LED) array.

28. The method of claim 19, wherein said fresh image is obtained with a charge couple device (CCD) capable of imaging the plurality of wells simultaneously.

20. A method for synthesizing a plurality of different polymers comprising:

(a) providing a plurality of wells containing support-bound monomeric or oligomeric precursors of said polymers;

(b) dispensing a liquid comprising second monomeric precursors of said polymers to said plurality of wells under conditions for forming an intermediate in which the support-bound monomeric or oligomeric precursors are bound to the second monomeric precursors;

(c) obtaining a fresh image of said plurality of wells and saving said fresh image to an image storage location;

(d) executing commands in a computer system to access said saved fresh image, geometrically register said saved fresh image in order to determine a specific value corresponding to each one of the chemical reactions within each well at the time the image was obtained, and save said specific values to an analysis results storage location; and

(e) if said specific values are within a pre-defined passing range then repeating steps (a) through (d) and if said specific values are within a pre-defined failing range then at least temporarily preventing repetition of steps (a) through (d) for at least one of the wells in said plurality of wells.

22. The method of claim 20, further comprising:

(f) if said specific values are within a pre-defined failing range and repetition of steps (a) through (d) is temporarily prevented for at least one of the wells in said plurality of wells then receiving a command from said graphical user interface to repeat steps (a) through (d).