Multiplexed biological analyzer planar array apparatus and methods

• US 7,910,356 B2
• Filed: 02/01/2006
• Issued: 03/22/2011
• Est. Priority Date: 02/01/2005
• Status: Active Grant

• Current Assignee: Purdue Research Foundation (Purdue University)
• Original Assignee: Purdue Research Foundation (Purdue University)
• Inventors: Varma, Manoj, Peng, Leilei, Nolte, David D., Regnier, Fred E.
• Primary Examiner(s): YANG, NELSON C
• Application Number:
  US11/345,477
• Publication Number:
  US 20070003925A1
• Time in Patent Office: 1,875 Days
• Field of Search: 422/82.05, 422/82.09, 422/64, 436/45, 436/165, 436/518, 356/73
• US Class Current: 435/288.7
• CPC Class Codes: C12Q 1/6837 using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: G01N 33/543 with an insoluble carrier for immobilising immunochemicals

Abstract

A planar array having plurality of biological recognition molecules including at least two types of biological recognition molecules distributed about a substrate is disclosed. A first type of biological recognition molecules is distributed according to a first frequency and a second type of biological recognition molecules is distributed according to a second frequency. Another planar array having a plurality of biological recognition molecules including at least two kinds of biological recognition molecules is disclosed. The recognition molecules are distributed about a substrate with first kind of biological recognition molecules distributed at a first height or depth relative to a surface of the substrate and a second kind of biological recognition molecules distributed at a second height or depth relative to the surface. An apparatus including a surface normal interferometry platform including a scanning pathway and a plurality of analyzer molecules adapted to detect the presence or absence of a plurality of target analytes is also disclosed. The plurality of analyzer molecules are distributed about the scanning pathway according to a multiplexing scheme. A method including multiplexing a plurality of kinds of capture molecules about a detection pathway is further disclosed. The method also includes contacting a biological sample to the array, detecting the presence or absence of binding of the plurality of kinds of capture molecules and a plurality of target analytes using interferometry.

Claims

1. A method for determining the presence or absence of biological material in a sample comprising:

multiplexing a plurality of kinds of capture molecules about a detection pathway on a planar array, comprising the steps of;

distributing a first kind of capture molecule along the detection pathway at a first spatial frequency,

interspersing a second kind of capture molecule among the first kind of capture molecule along the detection pathway at a second spatial frequency, and

interspersing a third kind of capture molecule among the first and second kinds of capture molecules along the detection pathway at a third spatial frequency, each of the first, second and third spatial frequency being different from the other of the first, second and third spatial frequencies;

contacting a biological sample to the planar array;

scanning the planar array along the detection pathway with a scanning beam traveling over the plurality of kinds of capture molecules to produce a reflected beam containing information from the plurality of kinds of capture molecules; and

detecting the presence or absence of binding of the plurality of kinds of capture molecules and a plurality of target analytes using interferometry and by demultiplexing the reflected beam containing information from the plurality of kinds of capture molecules to determine information of a particular capture molecule.

2. The method of claim 1 wherein the detecting further comprises detecting a first binding using a first wavelength of laser light and a second binding using a second wavelength of laser light.

3. The method of claim 1 wherein the detection pathway is defined along a surface of a bio-optical disk.

4. The method of claim 1 further comprising rotating the pathway in connection with the detecting.

5. The method of claim 1 wherein the detecting uses self-referencing phase quadrature interferometry.

6. The method of claim 1 further comprising demultiplexing information of a particular capture molecule and a particular target analyte in connection with the detecting.

7. The method of claim 1 wherein the first kind of capture molecule is adapted to selectively bind a first type of target analyte.

8. The method of claim 1 wherein the plurality of kinds of capture molecules are selected from at least one of binding cells, viruses, bacteria, toxins, peptides, DNA fragments and antibodies.

16. The method of claim 1, wherein the first kind of capture molecules are disposed at a first height relative to the planar array and the second kind of capture molecules are disposed at a second height relative to the planar array, the first height being different from the second height;

and wherein the detecting step further comprises;

detecting a first binding using a first wavelength of light, the first height being tuned to produce a phase quadrature condition for the first wavelength of light; and

detecting a second binding using a second wavelength of light, the second height being tuned to produce a phase quadrature condition for the second wavelength of light.

17. The method of claim 1, wherein the multiplexing is frequency-domain multiplexing, wavelength domain multiplexing or code-division multiplexing.

9. A method for determining the presence or absence of a plurality of target analytes in a biological sample comprising:

obtaining a substrate having a surface with a detection pathway with a first type of biological recognition molecule and a second type of biological recognition molecule frequency-domain multiplexed, wavelength domain multiplexed or code-division multiplexed thereabout, the first type of biological recognition molecule being distributed at a first spatial frequency and the second type of biological recognition molecule being interspersed with the first type of biological recognition molecule along the detection pathway and being distributed at a second spatial frequency, the second spatial frequency being different from the first spatial frequency;

exposing the surface of the substrate to the biological sample;

directing a probe laser beam at the surface of the substrate;

scanning the probe laser beam across at least the detection pathway; and

detecting binding of the first type of biological recognition molecule to at least one of the target analytes using a first wavelength of laser light and binding of the second type of biological recognition molecule to at least another one of the target analytes using a second wavelength of laser light.

10. The method of claim 9 wherein the detection pathway is defined along a surface of a bio-optical disk.

11. The method of claim 9 further comprising rotating the detection pathway to detect the binding of the first and second types of biological recognition molecules.

12. The method of claim 9 wherein the detection step includes an interferometric detection process.

13. The method of claim 12 wherein the interferometric detection process includes a self-referencing phase quadrature interferometric process.

14. The method of claim 9 further comprising demultiplexing information of a particular biological recognition molecule and a particular target analyte in connection with the detection step.

15. The method of claim 9 wherein the biological recognition molecules are selected from at least one of binding cells, viruses, bacteria, toxins, peptides, DNA fragments and antibodies.

18. The method of claim 9, wherein the first type of biological recognition molecule is positioned at a first height relative to the surface of the substrate, and the second type of biological recognition molecule is positioned at a second height relative to the surface of the substrate, the first height being different from the second height.

19. A method for determining the presence or absence of biological material in a sample comprising:

multiplexing a plurality of kinds of capture molecules about a detection pathway on a planar array comprising the steps of;

distributing a first kind of capture molecule along the detection pathway at a first spatial frequency,

interspersing a second kind of capture molecule among the first kind of capture molecule along the detection pathway at a second spatial frequency, and

interspersing a third kind of capture molecule among the first and second kinds of capture molecules along the detection pathway at a third spatial frequency, each of the first, second and third spatial frequency being different from the other of the first, second and third spatial frequencies;

contacting a biological sample to the planar array;

scanning the planar array along the detection pathway with a scanning beam traveling over the plurality of kinds of capture molecules to produce a reflected beam containing information from the plurality of kinds of capture molecules; and

detecting the presence or absence of binding of the plurality of kinds of capture molecules and a plurality of target analytes using interferometry and by demultiplexing the reflected beam containing information from the plurality of kinds of capture molecules to determine information of a particular capture molecule, wherein the demultiplexing the reflected beam comprises using the first, second and third spatial frequencies to detect the presence or absence of binding of the first, second and third kinds of capture molecules, respectively, with the plurality of target analytes.