Biosensors for biological or chemical analysis and systems and methods for same

• US 8,906,320 B1
• Filed: 03/15/2013
• Issued: 12/09/2014
• Est. Priority Date: 04/16/2012
• Status: Active Grant

• Current Assignee: Illumina Incorporated
• Original Assignee: Illumina Incorporated
• Inventors: Eltoukhy, Helmy A., Kain, Robert C., Feng, Wenyi, Pratt, Mark, Hirschbein, Bernard, Sabounchi, Poorya
• Primary Examiner(s): Marschel, Ardin
• Application Number:
  US13/833,619
• Time in Patent Office: 634 Days
• Field of Search: 422/417, 422/68.1, 435/283.1
• US Class Current: 422/417
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/168 Specific optical properties, e.g. reflective coatings
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: C12Q 1/6874 involving nucleic acid arrays, e.g. sequencing by hybridisation
• CPC Class Codes: G01N 15/1404 Handling flow, e.g. hydrodynamic focusing
• CPC Class Codes: G01N 15/1434 Optical arrangements
• CPC Class Codes: G01N 21/6486 Measuring fluorescence of biological material, e.g. DNA, RNA, cells G01N21/6428 takes precedence
• CPC Class Codes: G01N 33/6875 Nucleoproteins
• CPC Class Codes: G06F 16/214 Database migration support

Abstract

A biosensor is provided including a detection device and a flow cell mounted to the detection device. The detection device has a detector surface with a plurality of reaction sites. The detection device also includes a filter layer that is configured to at least one of (a) filter unwanted excitation light signals; (b) direct emission signals from a designated reaction site toward one or more associated light detectors that are configured to detect the emission signals from the designated reaction site; or (c) block or prevent detection of crosstalk emission signals from adjacent reaction sites.

Claims

1. A biosensor comprising:

a flow cell;

a detection device comprising a plurality of stacked layers and having a detector surface configured to support reaction sites, the stacked layers including a filter layer and a solid-state imager coupled to the filter layer, the filter layer comprising filter walls and a light-absorbing material that is deposited between adjacent filter walls, the light-absorbing material configured to prevent transmission of excitation light and permit transmission of emission signals, wherein the adjacent filter walls define a detection path therebetween through the corresponding light-absorbing material toward the solid-state imager, the filter walls configured to reflect the emission signals;

wherein the flow cell is mounted to the detector surface and defines a flow channel between at least one surface of the flow cell and the detection device, the at least one surface of the flow cell comprising a material that permits transmission of the excitation light.

2. The biosensor of claim 1, wherein the solid-state imager includes a CMOS image sensor comprising an array of light detectors that are configured to detect the emission signals.

3. The biosensor of claim 2, wherein each of the light detectors has only a single pixel and wherein a ratio of the pixels to the detection paths defined by the filter walls is substantially one-to-one.

4. The biosensor of claim 1, wherein a length of the detection path is less than 10 microns.

5. The biosensor of claim 1, wherein the filter walls substantially define an image area along the detector surface, the reaction site being located within the image area and having a site area that is less than the image area.

6. The biosensor of claim 1, wherein the stacked layers are formed in a layer by layer manner using integrated circuit processing technologies.

7. The biosensor of claim 1, wherein the filter walls include first and second interior portions, the first interior portion extending in a direction from the reaction sites toward the solid-state imager, the second interior portion extending in a direction from the first interior portion toward the solid-state imager, wherein the first and second interior portions have different reflectivity.

8. The biosensor of claim 1, wherein the filter walls include first and second interior portions, the first interior portion extending in a direction from the reaction sites toward the solid-state imager, the second interior portion extending in a direction from the first interior portion toward the solid-state imager, wherein the second interior portion is configured to attenuate the emission signals from the reaction sites more than the first interior portion.

9. The biosensor of claim 1, wherein the detection path has a width that decreases as the detection path extends in a direction from the reaction sites toward the solid-state imager.

10. The biosensor of claim 1, wherein a ratio between a height of the filter walls and a width of the detection path that extends between the adjacent filter walls is at least 2.5:

1.

11. The biosensor of claim 1, wherein the reaction sites include discrete metal regions on the detector surface.

12. The biosensor of claim 1, wherein the reaction sites include discrete clusters of nucleic acids.