Optical lens system and method for microfluidic devices

• US 7,906,072 B2
• Filed: 08/10/2009
• Issued: 03/15/2011
• Est. Priority Date: 06/07/2004
• Status: Active Grant

• Current Assignee: Standard Biotools Incorporated
• Original Assignee: Fluidigm Corporation
• Inventors: Unger, Marc A., Clerkson, Barry, Cesar, Christopher G., Facer, Geoffrey Richard, Switz, Neil
• Primary Examiner(s): Choi; William C
• Application Number:
  US12/538,641
• Publication Number:
  US 20090294703A1
• Time in Patent Office: 582 Days
• Field of Search: 359/642, 422/68.1, 422/82.05, 204/602, 204/603, 250/573
• US Class Current: 422/82.05
• 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 fluidic device comprising a plurality of processing sites, the apparatus comprising:

an illumination system coupled to the fluidic device and adapted to illuminate the fluidic device with electromagnetic radiation, wherein the fluidic 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 fluidic device and adapted to receive electromagnetic radiation emitted from the plurality of processing sites;

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

a thermal controller coupled to the fluidic device.

2. The apparatus of claim 1 further comprising an excitation filter disposed along an optical path between the illumination system and the fluidic device.

3. The apparatus of claim 2 wherein the excitation filter is one of several excitation filters disposed in an excitation filter wheel.

4. The apparatus of claim 1 further comprising an emission filter disposed along an optical path between the fluidic device and the multi-pixel detector.

5. The apparatus of claim 4 wherein the emission filter is one of several emission filters disposed in an emission filter wheel.

6. The apparatus of claim 1 wherein the multi-pixel detector includes a plurality of pixels associated with each of the plurality of processing sites.

7. The apparatus of claim 1 wherein the thermal controller is further coupled to a temperature sensor that measures the temperature across the fluidic device.

8. An apparatus for imaging a fluidic device comprising a plurality of processing sites, the apparatus comprising:

an illumination system coupled to the fluidic device and adapted to illuminate the fluidic device with electromagnetic radiation along an illumination path, wherein each of the plurality of processing sites is characterized by an actual spatial dimension normal to the illumination path;

an imaging system coupled to the fluidic device and adapted to receive electromagnetic radiation emitted from the plurality of processing sites along an imaging path; and

a multi-pixel detector coupled to the imaging system along the imaging path, wherein images of the plurality of processing sites are formed on the multi-pixel detector, the images being smaller than the actual spatial dimension.

9. The apparatus of claim 8 wherein the fluidic 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.

10. The apparatus of claim 8 wherein the electromagnetic radiation emitted from the plurality of processing sites comprises a fluorescent signal.

11. The apparatus of claim 8 wherein the plurality of processing sites comprise greater than or equal to 96 processing sites.

12. The apparatus of claim 11 wherein the plurality of processing sites comprise 384 or more processing sites.

13. The apparatus of claim 8 wherein the plurality of processing sites contain reaction volumes greater than or equal to about 0.1 microliters.

14. The apparatus of claim 8 wherein the plurality of processing sites are operable to be sealed in a closed state.

15. The apparatus of claim 8 wherein the illumination system comprises a xenon arc lamp.

16. The apparatus of claim 8 wherein the electromagnetic radiation propagating along the illumination path comprises at least one of electromagnetic radiation at 485 nm, 530 nm, or 580 nm.

17. The apparatus of claim 8 further comprising:

an excitation filter disposed along the illumination path; and

an emission filter disposed along the imaging path.

18. The apparatus of claim 8 wherein the multi-pixel detector comprises at least 2048 pixels by 2048 pixels.

19. An apparatus for imaging a fluidic device comprising a plurality of processing sites, the apparatus comprising:

an illumination system coupled to the fluidic device and adapted to illuminate the fluidic device with electromagnetic radiation along an illumination path, wherein the fluidic device comprises more than 96 processing sites;

an excitation filter disposed along the illumination path;

an imaging system coupled to the fluidic device and adapted to receive fluorescent radiation emitted from the plurality of processing sites; and

a multi-pixel detector coupled to the imaging system.

20. The apparatus of claim 19 further comprising a thermal controller coupled to the fluidic device.

21. The apparatus of claim 19 wherein the excitation filter comprises a filter wheel.

22. The apparatus of claim 19 wherein the fluidic device is characterized by a device dimension about 30.7 mm by about 30.7 mm or greater, the device dimension including the more than 96 processing sites.

23. The apparatus of claim 19 wherein the excitation filter is operable to pass electromagnetic radiation at about 485 nm.

24. The apparatus of claim 19 wherein the fluorescent radiation propagates along an emission path to the multi-pixel detector, the apparatus further comprising an emission filter disposed along the emission path.

25. The apparatus of claim 24 wherein the emission filter is operable to pass fluorescent radiation at about 519 nm.

26. The apparatus of claim 24 wherein the emission filter is operable to pass fluorescent radiation at about 550 nm.

27. The apparatus of claim 24 wherein the emission filter is operable to pass fluorescent radiation at about 600 nm.

28. The apparatus of claim 24 wherein the emission filter is operable to pass fluorescent radiation associated with at least one of a fluorescein amidite (FAM) dye or a VIC dye.

29. An apparatus for imaging a fluidic device comprising a plurality of processing sites, the apparatus comprising:

an illumination system coupled to the fluidic device and adapted to illuminate the fluidic device with electromagnetic radiation along an illumination path, wherein the fluidic device comprises greater than 96 processing sites and the illumination system comprises a xenon arc lamp;

an excitation filter wheel disposed along the illumination path, wherein the filter wheel is operable to pass electromagnetic radiation at about 485 nm;

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

a multi-pixel detector coupled to the imaging system along an emission path and operable to receive the electromagnetic radiation emitted from the plurality of processing sites;

an emission filter wheel disposed along the emission path, wherein the emission filter is operable to pass fluorescent radiation associated with at least one of a fluorescein amidite (FAM) dye or a VIC dye; and

a thermal controller coupled to the fluidic device.

30. The apparatus of claim 29 wherein the plurality of processing sites are operable to be sealed in a closed state.

31. The apparatus of claim 29 wherein the multi-pixel detector is characterized by a detection area less than the device dimension.

32. The apparatus of claim 29 wherein the multi-pixel detector comprises at least 2048 pixels by 2048 pixels.

33. The apparatus of claim 29 wherein the multi-pixel detector comprises a CCD.

34. The apparatus of claim 29 wherein the thermal controller is further coupled to a temperature sensor operable to measure a temperature associated with the fluidic device.

35. An apparatus for imaging a fluidic device comprising a plurality of processing sites, the apparatus comprising:

an illumination system coupled to the fluidic device and adapted to illuminate the fluidic device with electromagnetic radiation along an illumination path, wherein the fluidic device comprises greater than 96 processing sites;

an excitation filter wheel disposed along the illumination path, wherein the filter wheel is operable to pass electromagnetic radiation at about 485 nm;

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

a multi-pixel detector coupled to the imaging system and operable to receive the electromagnetic radiation along an emission path;

an emission filter wheel disposed along the emission path, wherein the emission filter is operable to pass fluorescent radiation associated with at least one of a fluorescein amidite (FAM) dye or a VIC dye; and

a thermal controller coupled to the fluidic device.

36. The apparatus of claim 35 wherein the multi-pixel detector is characterized by a detection area less than the device dimension.

37. The apparatus of claim 35 wherein the multi-pixel detector comprises at least 2048 pixels by 2048 pixels.

38. The apparatus of claim 35 wherein the multi-pixel detector comprises a CCD.

39. The apparatus of claim 35 wherein the thermal controller is further coupled to a temperature sensor that measures the temperature across the fluidic device.

40. An apparatus for imaging a fluidic device comprising a plurality of processing sites, the apparatus comprising:

an illumination system coupled to the fluidic device and adapted to illuminate the fluidic device with electromagnetic radiation along an illumination path, wherein the fluidic device comprises a plurality of detection sections each having greater than 96 processing sites;

an imaging system coupled to the fluidic device and adapted to receive electromagnetic radiation emitted from the plurality of processing sites in the plurality of detection sections;

a multi-pixel detector coupled to the imaging system, wherein the multi-pixel detector is characterized by a detection area less than the device dimension and wherein the electromagnetic radiation propagates along an emission path from the fluidic device to the multi-pixel detector;

an emission filter disposed along the emission path; and

a thermal controller coupled to the fluidic device.

41. The apparatus of claim 40 wherein the illumination system comprises a laser.

42. The apparatus of claim 40 wherein the multi-pixel detector comprises at least 2048 pixels by 2048 pixels.

43. The apparatus of claim 40 wherein the thermal controller is further coupled to a temperature sensor operable to measure a temperature associated with the fluidic device.