Differentially encoded biological analyzer planar array apparatus and methods

• US 20070023643A1
• Filed: 02/01/2006
• Published: 02/01/2007
• Est. Priority Date: 02/01/2005
• Status: Abandoned Application

• Current Assignee: Purdue Research Foundation (The Trustees of Purdue University (d/b/a Purdue University))
• Original Assignee: Purdue Research Foundation (The Trustees of Purdue University (d/b/a Purdue University))
• Inventors: Varma, Manoj, Peng, Leilei, Zhao, Ming, Nolte, David, Regnier, Fred
• Application Number:
  US11/345,566
• Publication Number:
  US 20070023643A1
• Time in Patent Office: Days
• US Class Current: 250/288
• CPC Class Codes: G01N 21/45 using interferometric methods; using Schlieren methods
• CPC Class Codes: G01N 21/553 and using surface plasmons fluorescence excitation G01N21/648; enhanced Raman G01N21/658
• CPC Class Codes: G01N 21/645 Specially adapted constructive features of fluorimeters
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings

Abstract

A method of probing a plurality of analyzer molecules distributed about a detection platform is disclosed. The method includes contacting a test sample to the plurality of analyzer molecules, scanning the plurality of analyzer molecules at a rate relating to a carrier frequency signal, and detecting the presence or absence of a biological molecule based at least in part upon the presence or absence of a signal substantially at a sideband of the carrier frequency signal. A molecule detection platform including a substrate and a plurality of targets positioned about the substrate is also disclosed. Specific analyzer molecules adapted to bind a specific analyte are immobilized about a first set of the targets. Nonspecific analyzer molecules are immobilized about a second set of the targets. The targets positioned about the substrate along at least a segment of a scanning pathway alternate between at least one of the first set and at least one of the second set. A method including providing a substrate for supporting biological analyzer molecules the substrate including at least one scanning pathway is also disclosed. The scanning pathway includes a plurality of scanning targets. Specific biological analyzer molecules adapted to detect a specific target analyte are distributed about a first set of the targets which alternate in groups of at least one with a second set of the targets the second set of the targets not including the specific biological analyzer molecules.

Claims

1. A method of probing a plurality of analyzer molecules distributed about a detection platform comprising:

contacting a test sample to the plurality of analyzer molecules;

scanning the plurality of analyzer molecules at a rate relating to a carrier frequency signal; and

detecting the presence or absence of a biological molecule based at least in part upon the presence or absence of a signal substantially at a sideband of the carrier frequency signal.

2. The method of claim 1 further comprising prescanning the plurality of analyzer molecules before the contacting and improving the detecting based upon a difference between the scanning and the prescanning.

3. The method of claim 1 wherein the sideband is substantially free from overlap with the carrier frequency signal.

4. The method of claim 1 wherein the detecting utilizes self referencing phase quadrature interferometric detection.

5. The method of claim 1 wherein the detection platform is a bio-CD.

6. The method of claim 1 further comprising suppressing the carrier frequency signal.

7. The method of claim 1 wherein the detecting utilizes interferometry and the scanning utilizes a laser beam.

8. The method of claim 1 further comprising detecting the presence or absence of a second biological molecule based at least in part upon the presence or absence of a second signal substantially at a second sideband of the carrier frequency signal.

9. The method of claim 1 wherein the detecting includes detecting a harmonic signal closest to zero frequency.

10. The method of claim 1 wherein the detecting includes detecting a harmonic signal at a frequency greater than that of a harmonic signal closest to zero frequency.

11. The method of claim 1 wherein the detecting includes detecting a signal at or about a fundamental carrier frequency.

12. The method of claim 1 wherein the detecting utilizes fluorescence detection.

13. A molecule detection platform comprising a substrate and a plurality of targets positioned about the substrate wherein specific analyzer molecules adapted to bind a specific analyte are immobilized about a first set of the targets, and nonspecific analyzer molecules are immobilized about a second set of the targets, and the targets positioned about the substrate along at least a first segment of a scanning pathway alternate between at least one of the first set and at least one of the second set.

14. The platform of claim 13 wherein the targets positioned about the substrate alternate along the first segment of the scanning pathway between at least four of the first set and at least four of the second set.

15. The platform of claim 13 wherein the platform is a micro diffraction bio-CD, a phase contrast bio-CD, or an adaptive optics bio-CD.

16. The platform of claim 13 wherein the nonspecific analyzer molecules exhibit nonspecific background binding at least substantially similar to the specific analyzer molecules.

17. The platform of claim 13 wherein the targets are interferometric microstructures.

18. The platform of claim 13 wherein the targets positioned about the substrate along at least a second segment of the scanning pathway adjacent the first segment alternate between at least one of the second set and at least one of the first set in the opposite order as the alternation of the first segment.

19. The platform of claim 13 wherein the targets are substantially contiguous along the segment of a scanning pathway.

20. A method comprising:

providing a substrate for supporting biological analyzer molecules the substrate including at least one scanning pathway, the scanning pathway including a plurality of scanning targets; and

distributing specific biological analyzer molecules adapted to detect a specific target analyte about a first set of the targets which alternate in groups of at least one with a second set of the targets, the second set of the targets not including the specific biological analyzer molecules.

21. The method of claim 20 further comprising distributing nonspecific analyzer molecules about the second set of the targets.

22. The method of claim 20 wherein the first set of the targets alternate in groups of at least four with the second set of the targets.

23. The method of claim 20 further comprising:

contacting a test sample to the molecules;

scanning the plurality of targets at a rate; and

detecting the presence or absence of a biological molecule based at least in part upon the presence or absence of a signal substantially about a frequency offset from a frequency defined by the distribution of the targets and the scanning rate.

24. The method of claim 23 wherein the detecting utilizes fluorescence.

25. The method of claim 23 wherein the substrate is a surface of a bio-CD, and the detecting utilizes phase quadrature interferometric detection