Method and system for microfluidic device and imaging thereof

• US 8,808,640 B2
• Filed: 01/31/2013
• Issued: 08/19/2014
• Est. Priority Date: 05/20/2003
• Status: Expired due to Fees

• Current Assignee: Fluidigm Corporation
• Original Assignee: Fluidigm Corporation
• Inventors: Quan, Emerson Chueng, Taylor, Colin Jon, Lee, Michael, Ceasar, Christopher, Harris, Greg, Sun, Gang
• Primary Examiner(s): SIEFKE, SAMUEL P
• Application Number:
  US13/755,754
• Publication Number:
  US 20130266204A1
• Time in Patent Office: 565 Days
• Field of Search: 422/500, 422/68.1
• US Class Current: 422/500
• CPC Class Codes: B01L 2200/025 Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0655 pinch valves
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• CPC Class Codes: B01L 3/502707 characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: G01N 33/00 Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
• CPC Class Codes: Y10T 436/11 Automated chemical analysis

Abstract

A biological substrate, e.g., microfluidic chip. The substrate includes a rigid substrate material, which has a surface region capable of acting as a handle substrate. The substrate also has a deformable fluid layer coupled to the surface region. One or more well regions are formed in a first portion of the deformable fluid layer and are capable of holding a fluid therein. The one or more channel regions are formed in a second portion of the deformable fluid layer and are coupled to one or more of the well regions. An active region is formed in the deformable fluid layer. At least three fiducial markings are formed within the non-active region and disposed in a spatial manner associated with at least one of the well regions. A control layer is coupled to the fluid layer.

Claims

1. A method of processing a deformable microfluidic device having a plurality of chambers each capable of holding a fluid therein and having a plurality of fiducial marks, the method comprising:

identifying at least three fiducial marks of the plurality of fiducial marks that are disposed within a vicinity of one or more chambers of the plurality of chambers;

thereafter

capturing an image of the at least three fiducial marks, where each of the at least three fiducial marks correspond to a design location in an undeformed state of the deformable microfluidic device, and the design locations have a first spatial relationship with respect to each other in a design space, and where each of the at least three fiducial marks are disposed at actual locations in a deformed state of the deformable microfluidic device, and at least one of the at least three fiducial marks has an actual location that is shifted from a corresponding design location such that the actual locations of the at least three fiducial marks have a second spatial relationship with respect to each other in a measurement space that is different from the first spatial relationship; and

generating a mapping between the design space and the measurement space based on the image.

2. The method of claim 1 further comprising:

aligning the deformable microfluidic device to an image acquisition location using the mapping and at least one additional fiducial mark of the plurality of fiducial marks, the at least one additional fiducial mark disposed within the vicinity of the one or more chambers; and

acquiring a second image that includes the at least one additional fiducial mark.

3. The method of claim 2 wherein aligning the deformable microfluidic device comprises acquiring a low-resolution image, normalizing the low-resolution image, and median correcting the low-resolution image.

4. The method of claim 3 wherein aligning the deformable microfluidic device further comprises segmenting the image, performing blob analysis, and translating the deformable microfluidic device in at least one dimension.

5. The method of claim 1 wherein the at least three fiducial marks are portions of one of the plurality of chambers.

6. The method of claim 1 further comprising creating a higher order mapping from the design space to the measurement space based on the mapping and at least one additional fiducial mark of the plurality of fiducial marks.

7. The method of claim 6 wherein the higher order mapping comprises a three dimensional parabolic mapping.

8. The method of claim 1 further comprising:

illuminating the deformable microfluidic device;

capturing an image of the deformable microfluidic device; and

determining values for each of a plurality of portions of the image of the deformable microfluidic device based on illumination intensity of each portion.

9. The method of claim 1 wherein a number of the plurality of chambers in the measurement space is greater than a number of the plurality of fiducial marks in the measurement space.

10. The method of claim 1 wherein the mapping includes a transformation between the design space and the measurement space.

11. A method of processing a deformable microfluidic device having a plurality of chambers each capable of holding a fluid therein and having a plurality of fiducial marks, the method comprising:

identifying at least three fiducial marks of the plurality of fiducial marks that are disposed within a vicinity of one or more chambers of the plurality of chambers;

thereafter

capturing an image of the at least three fiducial marks, where each of the at least three fiducial marks correspond to a design location in an undeformed state of the deformable microfluidic device, and the design locations have a first spatial relationship with respect to each other in a design space, and where each of the at least three fiducial marks are disposed at actual locations in a deformed state of the deformable microfluidic device, and at least one of the at least three fiducial marks has an actual location that is shifted from a corresponding design location such that the actual locations of the at least three fiducial marks have a second spatial relationship with respect to each other in a measurement space that is different from the first spatial relationship;

generating a mapping between the design space and the measurement space based on the image; and

aligning the deformable microfluidic device to an image acquisition location using the mapping.

12. The method of claim 11 wherein aligning the deformable microfluidic device comprises acquiring a low-resolution image, normalizing the low-resolution image, and median correcting the low-resolution image.

13. The method of claim 11 wherein aligning the deformable microfluidic device further comprises segmenting the image, performing blob analysis, and translating the deformable microfluidic device in at least one dimension.

14. The method of claim 11 wherein the at least three fiducial marks are portions of one or more of the plurality of chambers.

15. The method of claim 11 further comprising:

illuminating the deformable microfluidic device;

capturing an image of the deformable microfluidic device; and

determining values for each of a plurality of portions of the image of the deformable microfluidic device based on illumination intensity of each portion.

16. The method of claim 11 further comprising creating a higher order mapping from the design space to the measurement space based on the mapping and at least one additional fiducial mark of the plurality of fiducial marks.

17. The method of claim 11 wherein a number of the plurality of chambers in the measurement space is greater than a number of the plurality of fiducial marks in the measurement space.

18. The method of claim 11 wherein the mapping includes a transformation between the design space and the measurement space.

19. A method of processing a deformable microfluidic device having a plurality of chambers each capable of holding a fluid therein and having a plurality of fiducial marks, the method comprising:

identifying at least three fiducial marks of the plurality of fiducial marks that are disposed within a vicinity of one or more chambers of the plurality of chambers;

thereafter

capturing an image of the at least three fiducial marks, where each of the at least three fiducial marks correspond to a design location in an undeformed state of the deformable microfluidic device, and the design locations have a first spatial relationship with respect to each other in a design space, and where each of the at least three fiducial marks are disposed at actual locations in a deformed state of the deformable microfluidic device, and at least one of the at least three fiducial marks has an actual location that is shifted from a corresponding design location such that the actual locations of the at least three fiducial marks have a second spatial relationship with respect to each other in a measurement space that is different from the first spatial relationship;

generating a mapping between the design space and the measurement space based on the image;

creating a higher order mapping between the design space and the measurement space based on the mapping and at least one additional fiducial mark of the plurality of fiducial marks; and

aligning the deformable microfluidic device to an image acquisition location using the higher order mapping.

20. The method of claim 19 wherein the higher order mapping includes a transformation between the design space and the measurement space.