Method and system implementing spatially modulated excitation or emission for particle characterization with enhanced sensitivity

• US 20080181827A1
• Filed: 01/26/2007
• Published: 07/31/2008
• Est. Priority Date: 01/26/2007
• Status: Active Grant

• Current Assignee: Xerox Corporation (Xerox Holdings Corp.)
• Original Assignee: Palo Alto Research Center, Inc. (Xerox Holdings Corp.)
• Inventors: Kiesel, Peter, Johnson, Noble M., Bassler, Michael, Schmidt, Oliver
• Granted Patent: US 8,821,799 B2
• Time in Patent Office: Days
• US Class Current: 422/119
• CPC Class Codes: G01N 15/1427 with the synchronisation of components, a time gate for operation of components, or suppression of particle coincidences
• CPC Class Codes: G01N 15/147 the analysis being performed on a sample stream
• CPC Class Codes: G01N 2015/1447 Spatial selection
• CPC Class Codes: G01N 2015/1454 using phase shift or interference, e.g. for improving contrast
• CPC Class Codes: G01N 21/6486 Measuring fluorescence of biological material, e.g. DNA, RNA, cells G01N21/6428 takes precedence
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]
• CPC Class Codes: Y10T 436/17 Nitrogen containing

Abstract

A method and system for using spatially modulated excitation/emission and relative movement between a particle (cell, molecule, aerosol, . . . ) and an excitation/emission pattern are provided. In at least one form, an interference pattern of the excitation light with submicron periodicity perpendicular to the particle flow is used. As the particle moves along the pattern, emission is modulated according to the speed of the particle and the periodicity of the stripe pattern. A single detector, which records the emission over a couple of stripes, can be used. The signal is recorded with a fast detector read-out in order to capture the “blinking” of the particles while they are moving through the excitation pattern. This concept enables light detection with high signal-to-noise ratio and high spatial resolution without the need of expensive and bulky optics.

Claims

1. A method for characterizing particles, the method comprising:

generating a spatially modulated excitation region;

creating relative movement between a particle and the excitation region, the particle being excited upon exposure to the excitation region to obtain a time modulated signal; and

,

recording the modulated signal.

2. The method as set forth in claim 1 wherein the excitation region includes an excitation pattern.

3. The method as set forth in claim 1 wherein the time modulated signal is caused by light emission from the particle.

4. The method as set forth in claim 1 wherein the excitation region comprises interference stripes.

5. The method as set forth in claim 1 wherein the excitation region is generated by at least one of a shadow mask and a lens array.

6. The method as set forth in claim 1 wherein the excitation pattern is generated by chemo-luminescence.

7. The method as set forth in claim 1 further comprising at least one of determining a location of the particle based on the signal, counting particles based on the signal, and sorting particles based on the signal.

8. The method as set forth in claim 1 wherein the detecting comprises detecting with a pixilated detector.

9. The method as set forth in claim 1 wherein the particle is a portion of a DNA molecule or a molecule attached to the DNA molecule and the signal is used to determine DNA sequencing.

10. The method as set forth in claim 1 wherein the detecting comprises using a spectrometer to receive the fluorescent spectrum of the fluorescing analyte.

11. The method as set forth in claim 1 wherein the generating of the excitation region comprises generating a spatially modulated pattern based on at least one of geometry, electric or magnetic field, fluorescence quenching, analyte concentration, density, and acoustic standing wave.

12. The method as set forth in claim 1 wherein the generating of the excitation pattern comprises generating a spatially modulated region based on environment.

13. The method as set forth in claim 1 wherein the generating, creating and recording is conducted in two-dimensions to locate the particle.

14. A method for characterizing particles comprising;

moving a particle within a channel;

providing an environment along the channel which causes the particle to create a time modulated signal; and

,

detecting and evaluating the time modulated signal.

15. The method as set forth in claim 14 wherein the environment comprises an optical element and the particle emits light detected by the optical element.

16. The method as set forth in claim 15 wherein the optical element is operative to modulate the signal obtained from the particle as a function of a position of a particle.

17. The method as set forth in claim 15 further comprising moving the optical element.

18. The method as set forth in claim 15 wherein the optical element is one of a shadow mask and a micro-lens array.

19. The method as set forth in claim 14 further comprising at least one of determining a location of the particle based on the signal, counting particles based on the signal, and sorting particles based on the signal.

20. The method as set forth in claim 14 wherein the detecting comprises detecting with a pixilated detector.

21. The method as set forth in claim 14 wherein the particle is a portion of a DNA molecule or a molecule attached to the DNA molecule and the signal is used to determine DNA sequencing.

22. The method as set forth in claim 14 wherein the detecting comprises using a spectrometer to receive a fluorescent spectrum of the particle.

23. The method as set forth in claim 15 wherein the optical element is operative to pattern the light based on at least one of geometry, electric or magnetic field, fluorescence quenching, particle concentration, density, and acoustic standing wave.

25. The system as set forth in claim 23 further comprising at least one of a means for determining a location of the particle based on the signal a means for counting particles based on the signal, and means for sorting particles based on the signal.

24. A system for characterizing particles comprising:

means for generating a spatially modulated excitation region;

means for providing relative movement between a particle and the region, the particle being excited upon exposure to the excitation area to obtain a time modulated signal;

means for recording the modulated signal.

26. A system for characterizing particles comprising;

a channel;

a means for moving a particle within the channel;

an environment along the channel operative to cause the particle to create time modulated signal; and

,

a detection system to record and evaluate the time modulated signal.

27. The system as set forth in claim 26 wherein the environment comprises an optical element.

28. The system as set forth in claim 26 further comprising an anti-resonant waveguide operative to cause the particle to emit light.

29. The system as set forth in claim 26 further comprising at least one of a means for determining a location of the fluorescent analyte based on the signal, a means for counting particles based on the signal, and a means for sorting particles based on the signal.

30. The system as set forth in claim 26 wherein the environment allows for a two-dimensional evaluation.