Optical lens system and method for microfluidic devices

• US 7,588,672 B2
• Filed: 12/10/2007
• Issued: 09/15/2009
• Est. Priority Date: 06/07/2004
• Status: Active Grant

• Current Assignee: Standard Biotools Incorporated
• Original Assignee: Fluidigm Corporation
• Inventors: Unger, Marc A., Switz, Neil, Clerkson, Barry, Cesar, Christopher G., Facer, Geoffrey Richard
• Primary Examiner(s): Choi; William C
• Application Number:
  US11/953,538
• Publication Number:
  US 20080088952A1
• Time in Patent Office: 645 Days
• Field of Search: 359/642, 204/602, 204/603, 422/68.1
• US Class Current: 204/603
• CPC Class Codes: B01J 2219/00576 fluorophore
• CPC Class Codes: B01J 2219/00704 integrated with the reactor apparatus
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 7/52 with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: C12Q 1/686 Polymerase chain reaction [PCR]
• CPC Class Codes: G01N 2021/6421 Measuring at two or more wavelengths
• CPC Class Codes: G01N 21/64 Fluorescence; Phosphorescence
• CPC Class Codes: G01N 21/6452 Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G01N 21/6456 Spatial resolved fluorescence measurements; Imaging
• CPC Class Codes: G01N 21/6486 Measuring fluorescence of biological material, e.g. DNA, RNA, cells G01N21/6428 takes precedence
• CPC Class Codes: G01N 21/75 Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated systems in which material is burnt in a flame or plasma G01N21/72, G01N21/73
• CPC Class Codes: G01N 21/8483 Investigating reagent band test-element handling not specific to a test method G01N33/4875; analytical elements specific to chemical analysis of biological material G01N33/52; autometer with reagent band G01N35/04
• CPC Class Codes: G01N 2201/061 Sources
• CPC Class Codes: G01N 27/44721 by optical means
• CPC Class Codes: G02B 21/16 adapted for ultraviolet illumination ; Fluorescence microscopes G02B21/0076 takes precedence
• CPC Class Codes: G02B 21/36 arranged for photographic purposes or projection purposes G02B21/18 takes precedenceor digital imaging or video purposes including associated control and data processing arrangements image data processing per se G06T

Abstract

An apparatus for imaging one or more selected fluorescence indications from a microfluidic device. The apparatus includes an imaging path coupled to least one chamber in at least one microfluidic device. The imaging path provides for transmission of one or more fluorescent emission signals derived from one or more samples in the at least one chamber of the at least one microfluidic device. The chamber has a chamber size, the chamber size being characterized by an actual spatial dimension normal to the imaging path. The apparatus also includes an optical lens system coupled to the imaging path. The optical lens system is adapted to transmit the one or more fluorescent signals associated with the chamber.

Claims

1. An apparatus for imaging a microfluidic device comprising a plurality of processing sites, the apparatus comprising:

an illumination system coupled to the microfluidic device and adapted to illuminate the microfluidic device with electromagnetic radiation, wherein the microfluidic device is characterized by a device dimension about 30.7 mm by about 30.7 mm or greater, the device dimension including the plurality of processing sites;

an imaging system coupled to the microfluidic device and adapted to simultaneously receive electromagnetic radiation emitted from the plurality of processing sites; and

a detector coupled to the imaging system and characterized by a detection area less than the device dimension.

2. The apparatus of claim 1 wherein the plurality of processing sites comprise a plurality of closed reaction chambers.

3. The apparatus of claim 2 wherein the plurality of closed reaction chambers comprises more than 96 closed reaction chambers.

4. The apparatus of claim 2 wherein the plurality of closed reaction chambers comprise a reaction density of about 250 reactions in fluidic isolation per square cm of area or greater.

5. The apparatus of claim 1 wherein the electromagnetic radiation emitted from the plurality of processing sites is a fluorescent signal.

6. The apparatus of claim 5 further comprising a thermal controller coupled the microfluidic device.

7. The apparatus of claim 6 wherein the plurality of processing sites are characterized by a volume of about 100 nanoliters or less.

8. The apparatus of claim 7 wherein the plurality of processing sites are characterized by a volume of about 10 nanoliters or less.

9. The apparatus of claim 7 wherein the plurality of processing sites are characterized by an array density of 250 sites per cm² or greater.

10. The apparatus of claim 7 wherein the plurality of processing sites are characterized by an array density of 500 sites per cm² or greater.

11. The apparatus of claim 1 wherein the plurality of processing sites are adapted to support protein crystallization processes.

12. The apparatus of claim 1 wherein the electromagnetic radiation is optical radiation.

13. The apparatus of claim 1 wherein the detection area includes a pixel region having at least 2048 pixels by 2048 pixels.

14. An apparatus for imaging a microfluidic device comprising more than 96 closed reaction chambers, the apparatus comprising:

an illumination system coupled to the microfluidic device and adapted to illuminate the microfluidic device with electromagnetic radiation, wherein the microfluidic device is characterized by a device dimension including the more than 96 closed reaction chambers;

an imaging system coupled to the microfluidic device and adapted to simultaneously receive electromagnetic radiation emitted from the more than 96 closed reaction chambers; and

a detector coupled to the imaging system and characterized by a detection area less than the device dimension.

15. The apparatus of claim 14 wherein the more than 96 closed reaction chambers comprise a reaction density between about 250 and 1,000 reactions in fluidic isolation per cm².

16. The apparatus of claim 15 wherein the more than 96 closed reaction chambers comprise a reaction density between about 1,000 and 2,500 reactions in fluidic isolation per cm².

17. The apparatus of claim 16 wherein the more than 96 closed reaction chambers comprise a reaction density of 2,500 reactions in fluidic isolation per square cm of area or greater.

18. The apparatus of claim 14 wherein the electromagnetic radiation emitted from the more than 96 closed reaction chambers is a fluorescent signal.

19. The apparatus of claim 14 wherein the more than 96 closed reaction chambers are adapted to support protein crystallization processes.

20. The apparatus of claim 14 wherein the more than 96 closed reaction chambers are adapted to support PCR processes.

21. The apparatus of claim 14 wherein the device dimension is about 30.7 mm by about 30.7 mm or greater.

22. An apparatus for imaging a microfluidic device comprising a plurality of processing sites, the apparatus comprising:

an illumination system coupled to the microfluidic device and adapted to illuminate the microfluidic device with electromagnetic radiation, wherein the microfluidic device is characterized by a device dimension including the plurality of processing sites;

an imaging system coupled to the microfluidic device and adapted to simultaneously receive a fluorescent signal emitted from the plurality of processing sites;

a detector coupled to the imaging system and characterized by a detection area less than the device dimension; and

a thermal controller coupled to the microfluidic device.

23. The apparatus of claim 22 wherein the plurality of processing sites are characterized by a volume between about 50 nanoliters and 100 nanoliters.

24. The apparatus of claim 22 wherein the plurality of processing sites are characterized by a volume between about 10 nanoliters and 50 nanoliters.

25. The apparatus of claim 22 wherein the plurality of processing sites are characterized by a volume of about 10 nanoliters or less.

26. The apparatus of claim 22 wherein the plurality of processing sites are characterized by an array density between 250 and 1,000 sites per cm².

27. The apparatus of claim 22 wherein the plurality of processing sites are characterized by an array density between 1,000 and 2,500 sites per cm².

28. The apparatus of claim 22 wherein the plurality of processing sites are characterized by an array density of 2,500 sites per cm² or greater.

29. The apparatus of claim 22 wherein the plurality of processing sites are adapted to support protein crystallization processes.

30. The apparatus of claim 22 wherein the plurality of processing sites are adapted to support PCR processes.

31. An apparatus for imaging a microfluidic device comprising a plurality of processing sites, the apparatus comprising:

an illumination system coupled to the microfluidic device and adapted to illuminate the microfluidic device with electromagnetic radiation, wherein the microfluidic device is characterized by a device dimension including the plurality of processing sites;

an imaging system coupled to the microfluidic device and adapted to simultaneously receive electromagnetic radiation emitted from the plurality of processing sites; and

a detector coupled to the imaging system and characterized by a detection area including a pixel region having at least 2048 pixels by 2048 pixels, wherein the detection area is less than the device dimension.

32. The apparatus of claim 31 wherein the electromagnetic radiation emitted from the plurality of processing sites is a fluorescent signal.

33. The apparatus of claim 31 wherein the plurality of processing sites are adapted to support PCR processes.

34. The apparatus of claim 31 wherein the plurality of processing sites are characterized by a volume between about 50 nanoliters and 100 nanoliters.

35. The apparatus of claim 31 wherein the plurality of processing sites are characterized by a volume between about 10 nanoliters and 50 nanoliters.

36. The apparatus of claim 31 wherein the plurality of processing sites are characterized by a volume of about 10 nanoliters or less.

37. The apparatus of claim 31 wherein the plurality of processing sites are characterized by an array density between 250 and 1,000 sites per cm².

38. The apparatus of claim 31 wherein the plurality of processing sites are characterized by an array density between 1,000 and 2,500 sites per cm².

39. The apparatus of claim 31 wherein the plurality of processing sites are characterized by an array density of 2,500 sites per cm² or greater.

40. The apparatus of claim 31 further comprising a thermal controller coupled to the microfluidic device.