Bioassay system including optical detection apparatuses, and method for detecting biomolecules

• US 7,811,810 B2
• Filed: 07/09/2009
• Issued: 10/12/2010
• Est. Priority Date: 10/25/2007
• Status: Active Grant

• Current Assignee: Industrial Technology Research Institute
• Original Assignee: Industrial Technology Research Institute
• Inventors: Chu, Chang-Sheng, Chung, Shuang-Chao, Fan, Chih-Hsun, Chu, Cheng-Wei, Li, Yu-Tang, Chiou, Chung-Fan
• Primary Examiner(s): Lam; Ann Y
• Application Number:
  US12/500,567
• Publication Number:
  US 20090311774A1
• Time in Patent Office: 460 Days
• Field of Search: None
• US Class Current: 435/287.2
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00576 fluorophore
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00704 integrated with the reactor apparatus
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C40B 60/04 Integrated apparatus specially adapted for both screening libraries and identifying library members
• CPC Class Codes: C40B 60/12 for screening libraries

Abstract

A bioassay system is disclosed. The bioassay system may include a plurality of optical detection apparatuses, each of which includes a substrate having a light detector, and a linker site formed over the light detector, the linker site being treated to affix the biomolecule to the linker site. The linker site is proximate to the light detector and is spaced apart from the light detector by a distance of less than or equal to 100 micrometers. The light detector collects light emitted from the biomolecule within a solid angle of greater than or equal to 0.8 SI steridian. The optical detection apparatus may further include an excitation light source formed over the substrate so as to provide a light source for exciting a fluorophore attached to the biomolecule.

Claims

1. An apparatus for identifying a single biomolecule, comprising:

a substrate having a light detector, the substrate being configured to detect light emitted from the biomolecule;

a blind sheet over the substrate, the blind sheet including a pinhole having a diameter;

a filter layer provided between the blind sheet and the substrate and provided under the pinhole, the filter layer being non-planar and configured to filter the light emitted from the biomolecule; and

a linker site provided proximate to the pinhole, the linker site being treated to position the biomolecule proximate to the pinhole.

2. The apparatus of claim 1, where the light detector is chosen from one of a charged-coupled device, CMOS sensor, or photodiode.

3. The apparatus of claim 1, wherein non-planar comprises one of curved, spherical, elliptical, or bowed.

4. The apparatus of claim 1, wherein the pinhole has a diameter of less than or equal to about 1,000 nanometers.

5. The apparatus of claim 1, wherein the pinhole has a diameter of less than or equal to about 200 nanometers.

14. The apparatus of claim 1, wherein the light passes through the non-planar filter at an orthogonal angle.

6. An apparatus for identifying a single biomolecule, comprising:

a substrate having a light detector, the substrate being configured to detect light emitted from the biomolecule;

a light emitting layer formed over the filter layer, wherein the light emitting layer includes a cavity;

a filter layer provided between the cavity and the substrate and under a pinhole, the filter layer being non-planar and configured to filter the light emitted from the biomolecule; and

a linker site provided proximate to the cavity and the pinhole, the linker site being treated to position the biomolecule proximate to the pinhole.

7. The apparatus of claim 6, wherein the light passes through the non-planar filter at an orthogonal angle.

8. The apparatus of claim 6, wherein the light emitting layer emits light from an excitation light source to the linker site through the cavity along a horizontal direction parallel to a surface of the light detector.

9. The apparatus of claim 6, further comprising:

a blind sheet over the substrate, the blind sheet including the pinhole having a diameter.

10. The apparatus of claim 6, wherein non-planar comprises one of curved, spherical, elliptical, or bowed.

11. The apparatus of claim 6, wherein the pinhole has a diameter of less than or equal to about 1,000 nanometers.

12. The apparatus of claim 6, wherein the pinhole has a diameter of less than or equal to about 200 nanometers.

13. The apparatus of claim 8, wherein the excitation light source is chosen from a light emitting diode (LED), an organic light emitting diode (OLED), a polymer light emitting diode (PLED), and a laser diode (LD).

15. An apparatus for identifying biomolecules, comprising:

a substrate having a light detector;

a blind sheet proximate to the filter layer, the blind sheet including an array of pinholes; and

a filter layer formed under the array of pinholes, wherein a filter-layer structure provided under each of at least some of the pinholes is non-planar;

a linker site formed proximate to each pinhole, the linker site being treated to affix the biomolecule to the linker site.

16. The apparatus of claim 15, where the light detector is chosen from one of a charged-coupled device, CMOS sensor, or photodiode.

17. The apparatus of claim 15, wherein non-planar comprises one of curved, spherical, elliptical, or bowed.

18. The apparatus of claim 15, wherein each pinhole has a diameter of less than or equal to about 1,000 nanometers.

19. The apparatus of claim 15, wherein each pinhole has a diameter of less than or equal to about 200 nanometers.

20. A method for identifying a single biomolecule, comprising:

attaching the biomolecule to a linker site, the linker site being provided proximate to a pinhole formed on a blind sheet, the pinhole having a diameter;

filtering a light emitted from the biomolecule by a filter layer, the filter layer

(i) being provided between the blind sheet and a substrate having a light detector,

(ii) being provided under the pinhole, and

(iii) being non-planar; and

using a light detector to detect the light passing through the filter layer.