Method and system for evaluation of signals received from spatially modulated excitation and emission to accurately determine particle positions and distances

• US 20080183418A1
• 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, Bassler, Michael, Schmidt, Oliver
• Granted Patent: US 9,164,037 B2
• Time in Patent Office: Days
• US Class Current: 702/150
• CPC Class Codes: G01N 2015/1027 Determining speed or velocity of a particle
• CPC Class Codes: G01N 2015/1486 Counting the particles
• CPC Class Codes: G01N 21/6408 with measurement of decay time, time resolved fluorescence
• CPC Class Codes: G01N 21/6458 Fluorescence microscopy fluorescence microscopes per se G02B21/0076 and G02B21/16
• CPC Class Codes: G06F 2111/10 Numerical modelling
• CPC Class Codes: G16B 5/00 ICT specially adapted for modelling or simulations in systems biology, e.g. gene-regulatory networks, protein interaction networks or metabolic networks
• CPC Class Codes: G16H 50/20 for computer-aided diagnosis, e.g. based on medical expert systems

Abstract

A method is provided for extracting the position of a particle, e.g., a moving or stationary particle that is excited or is emitting light. The method includes, among other steps, detecting and recording a signal based on, for example, the movement of the particle, a correlation step to eliminate noise and to create a transformed signal, a matching or fitting step to match the transformed signal to a fit function and an extracting or determining step to determine the position of the particle from the fit function. In one form, at least two particle positions are detected so that the distance between the subject particles can be determined.

Claims

1. A method for determining a position of a particle comprising:

detecting a particle based on a spatial modulation;

recording a time modulated signal based on the detecting of the particle;

applying a correlation routine to the time modulated signal to generate a transformed signal;

applying a fit function to the transformed signal; and

,

extracting the position of the particle based on the applying of the fit function.

2. The method as set forth in claim 1, wherein the applying of the correlation routine comprises applying a test function to the recorded signal and integrating the recorded signal over time.

3. The method as set forth in claim 1 wherein two positions are detected in order to calculate the distance between both positions.

4. The method as set forth in claim 1 wherein the particle is a DNA sequencing tag and the detecting is based on an optical bar code read out.

5. The method as set forth in claim 1 wherein the particle is disposed on a bio-chip.

6. The method as set forth in claim 1 wherein the fit function is a triangle.

7. A method to determine a position of at least one particle comprising:

detecting a particle based on a spatial modulation;

recording a time modulated signal based on the detecting of the particle;

calculating a sliding integral over time on the recorded signal;

applying a fit function to the sliding integral to obtain an estimated position of the particle;

calculating a correlation signal;

calculating a derivative signal of the correlation signal;

determining a maximum and a minimum of the derivative signal based on the estimated position of the particle; and

,

determining a zero transition to determine a calculated position of the particle.

8. The method as set forth in claim 7 wherein the fit function is a triangle.

9. The method as set forth in claim 8 further comprising determining the slope of flanks of the triangle to determine if multiple particles are present.

10. The method as set forth in claim 8 further comprising integrating the triangle to determine if multiple particles are present.

11. The method as set forth in claim 7 wherein the determining comprises determining multiple maximums and minimums to determine the positions of multiple particles.

12. The method as set forth in claim 7 wherein the method is applied in two dimensions to determine a location of the particle.

13. The method as set forth in claim 7 further comprising the use of least squares fitting of a measured signal to determine the positions of multiple particles that are within a predetermined distance from one another.

14. The method as set forth in claim 7 wherein the time modulated signal is based on a detected optical signal.

15. The method as set forth in claim 14 whereby the optical signal is a light signal.

16. The method as set forth in claim 7 wherein the time modulated signal is based on a detected non-optical signal.

17. The method as set forth in claim 7 wherein the correlation signal is based on a chirp signal.

18. The method as set forth in claim 7 wherein the time modulated signal is periodic.

19. The method as set forth in claim 7 wherein the time modulated signal is based on a known signal.

20. A system for determining a position of a particle comprising:

means for detecting a particle;

means for recording a signal based on the detecting;

means for applying a correlation routine to the signal to generate a transformed signal;

means for applying a fit function to the transformed signal; and

,

means for extracting the position of the particle based on the applying of the fit function.

21. The system as set forth in claim 20, wherein the means for applying of the correlation routine comprises means for applying a test function to the recorded signal and means for integrating the recorded signal over time.

22. The system as set forth in claim 20 wherein the particle is a DNA sequencing tag.

23. The system as set forth in claim 20 wherein the particle is disposed on a bio-chip.

24. The system as set forth in claim 20 wherein the fit function is a triangle.

25. A system to determine a position of at least one particle comprising:

means for detecting a particle;

means for recording a signal based on the detecting;

means for calculating a sliding integral over time on the recorded signal;

means for applying a fit function to the sliding integral to obtain an estimated position of the particle;

means for calculating a correlation signal;

means for calculating a derivative signal of the correlation signal;

means for determining a maximum and a minimum of the derivative signal based on the estimated position of the particle; and

,

means for determining a zero transition to determine a calculated position of the particle.