APPARATUS FOR SELECTIVE EXCITATION OF MICROPARTICLES

• US 20090061505A1
• Filed: 08/28/2007
• Published: 03/05/2009
• Est. Priority Date: 08/28/2007
• Status: Active Grant

• Current Assignee: Rebus Biosystems, Inc.
• Original Assignee: LightSpeed Genomics, Inc.
• Inventors: Ryu, Jekwan, Hong, Stanley S., Park, Jong Buhm
• Granted Patent: US 8,759,077 B2
• Time in Patent Office: Days
• US Class Current: 435/287.200
• 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: B01L 7/52 with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: C12Q 1/6869 Methods for sequencing
• CPC Class Codes: G01N 21/6452 Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G01N 33/54366 Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings

Abstract

Nucleic acid microparticles are sequenced by performing a sequencing reaction on the microparticles using one or more selectively exciting the microparticles in an excitation pattern, optically imaging the microparticles at a resolution insufficient to resolve individual microparticles, and processing the optical images of the microparticles using information on the excitation pattern to determine the presence or absence of the optical signature, which indicates the sequence information of the nucleic acid. An apparatus for optical excitation of the microparticles comprises an optical fiber delivering a first laser beam, and an interference pattern generation module coupled to the optical fiber. The interference pattern generation module splits the first laser beam into second and third laser beams and generates the excitation pattern for selectively exciting the microparticles by interference between the second and third laser beams.

Claims

1. An apparatus for optical excitation of a target, the apparatus comprising:

a laser for generating a first laser beam;

a first optical fiber coupled to receive the first laser beam;

a first interference pattern generation module coupled to the first optical fiber for receiving the first laser beam delivered via the first optical fiber, the first interference pattern generation module splitting the first laser beam into a second laser beam and a third laser beam and configured to generate an excitation pattern for selectively exciting the target by interference between the second laser beam and the third laser beam.

2. The apparatus of claim 1, wherein the first interference pattern generation module comprises:

a beam splitter for splitting the first laser beam into the second laser beam and the third laser beam; and

a mirror reflecting the third laser beam, the mirror being movable within a range to vary an optical path-length of the third laser beam.

3. The apparatus of claim 2, wherein a phase of the third laser beam in relation to a phase of the second laser beam is varied responsive to the optical path-length of the third laser beam being varied within the range.

4. The apparatus of claim 1, wherein the first interference pattern generation module comprises:

a beam splitter for splitting the first laser beam into the second laser beam and the third laser beam; and

a window coupled to the third laser beam and rotating to modulate an optical phase of the third laser beam.

5. The apparatus of claim 4, wherein the window is rotated using a galvanometer.

6. The apparatus of claim 1, further comprising:

a beam splitter splitting the first laser beam into the first laser beam and a fourth laser beam;

a second optical fiber coupled to receive the fourth laser beam;

a second interference pattern generation module coupled to the second optical fiber and for receiving the fourth laser beam delivered via the second optical fiber, the second interference pattern generation module splitting the fourth laser beam into a fifth laser beam and a sixth laser beam and generating the excitation pattern for selectively exciting the target by interference between the second laser beam, the third laser beam, the fifth laser beam and the sixth laser beam.

7. The apparatus of claim 1, wherein an amplitude of the first laser beam is varied.

8. The apparatus of claim 1, wherein the target is a nucleic acid microparticle array.

9. The apparatus of claim 1, wherein the excitation pattern produces rectilinear sampling of a frequency domain.

10. The apparatus of claim 1, wherein the excitation pattern produces non-rectilinear sampling of a frequency domain.

11. A system for sequencing nucleic acid microparticles, the system comprising:

a sequence reaction module configured to apply one or more sequencing reagents to the nucleic acid microparticles;

a selective microparticle excitation module configured to selectively excite the nucleic acid microparticles in an excitation pattern generated by an interference of a plurality of illumination beams onto the nucleic acid microparticles;

an optical imaging module configured to generate one or more optical images of the nucleic acid microparticles at a resolution insufficient to resolve individual microparticles; and

an image processing module configured to process the optical images of the nucleic acid microparticles using information on the excitation pattern and to determine presence or absence of an optical signature, the presence or absence of the optical signature indicating the sequence information of the nucleic acid,

wherein the selective microparticle excitation module comprises;

a laser for generating a first laser beam;

a first optical fiber coupled to receive the first laser beam; and

a first interference pattern generation module coupled to the first optical fiber and for receiving the first laser beam delivered via the first optical fiber, the first interference pattern generation module splitting the first laser beam into a second laser beam and a third laser beam and generating the excitation pattern for selectively exciting the nucleic acid microparticles by interference between the second laser beam and the third laser beam.

12. The system of claim 11, wherein the first interference pattern generation module comprises:

a beam splitter for splitting the first laser beam into the second laser beam and the third laser beam; and

a mirror reflecting the third laser beam, the mirror being movable within a range to vary an optical path-length of the third laser beam.

13. The system of claim 12, wherein a phase of the third laser beam in relation to a phase of the second laser beam is varied responsive to the optical path-length of the third laser beam being varied within the range.

14. The system of claim 11, wherein the first interference pattern generation module comprises:

a beam splitter for splitting the first laser beam into the second laser beam and the third laser beam; and

a window coupled to the third laser beam and rotating to modulate an optical phase of the third laser beam.

15. The system of claim 14, wherein the window is rotated using a galvanometer.

16. The system of claim 11, wherein the selective microparticle excitation module further comprises:

a beam splitter splitting the first laser beam into the first laser beam and a fourth laser beam;

a second optical fiber coupled to receive the fourth laser beam; and

a second interference pattern generation module coupled to the second optical fiber and for receiving the fourth laser beam delivered via the second optical fiber, the second interference pattern generation module splitting the fourth laser beam into a fifth laser beam and a sixth laser beam and generating the excitation pattern for selectively exciting the nucleic acid microparticles by interference between the second laser beam, the third laser beam, the fifth laser beam and the sixth laser beam.

17. The system of claim 11, wherein an amplitude of the first laser beam is varied.

18. The system of claim 11, wherein the excitation pattern produces rectilinear sampling of a frequency domain.

19. The system of claim 11, wherein the excitation pattern produces non-rectilinear sampling of a frequency domain.

20. An apparatus for optical excitation of a target, the apparatus comprising:

a source of coherent electromagnetic radiation for generating a first beam;

an optical fiber coupled to receive the first beam;

an interference pattern generation module coupled to the optical fiber for receiving the first beam delivered via the optical fiber, the interference pattern generation module splitting the first beam into a second beam and a third beam and configured to generate an pattern for selectively exciting the target by interference between the second beam and the third beam.