Optical lens system and method for microfluidic devices

• US 8,512,640 B2
• Filed: 10/05/2011
• Issued: 08/20/2013
• Est. Priority Date: 06/07/2004
• Status: Active Grant

• Current Assignee: Standard Biotools Incorporated
• Original Assignee: Fluidigm Corporation
• Inventors: Unger, Marc A., Facer, Geoffrey Richard, Clerkson, Barry, Cesar, Christopher G., Switz, Neil
• Primary Examiner(s): CHOI, WILLIAM C
• Application Number:
  US13/253,703
• Publication Number:
  US 20120264226A1
• Time in Patent Office: 685 Days
• Field of Search: 359/642, 204/602, 204/603, 422/68.1, 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 one or more selected fluorescence indications from a microfluidic device including an array of closed reaction chambers, the apparatus comprising:

a thermal controller thermally coupled to the array of closed reaction chambers of the microfluidic device, the thermal controller adapted to thermally cycle the array of closed reaction chambers;

an imaging path coupled to the array of thermally cycling closed reaction chambers in the microfluidic device, the imaging path providing for transmission of one or more fluorescent emission signals derived from one or more samples in the array of closed reaction chambers in the microfluidic device, each of the closed reaction chambers in the array of closed reaction chambers having a chamber size, the chamber size being characterized by an actual spatial dimension normal to the imaging path;

an optical lens system coupled to the imaging path, the optical lens system being adapted to transmit the one or more fluorescent signals derived from the one or more samples in the array of closed reaction chambers in the microfluidic device, wherein the optical lens system is adapted to reduce a size of the actual spatial dimension to a reduced size less than the size of the actual spatial dimension; and

a multi-pixel detector coupled to the optical lens system and adapted to receive the one or more fluorescent signals transmitted from the optical lens system.

2. The apparatus of claim 1 wherein a ratio of the reduced size to the actual spatial dimension is characterized by a ratio of less than 0.9.

3. The apparatus of claim 2 wherein the ratio is less than 0.5.

4. The apparatus of claim 1 wherein the microfluidic device is characterized by a microfluidic dimension and the optical lens system is adapted to provide an image of the microfluidic device that is a smaller size than the microfluidic dimension and adapted to transmit the one or more fluorescent emission signals derived from the one or more samples in the array of closed reaction chambers in the microfluidic device at the smaller size.

5. The apparatus of claim 4 wherein the microfluidic dimension is about 30.7 mm by about 30.7 mm or greater.

6. The apparatus of claim 1 wherein the array of closed reaction chambers comprises more than 96 closed reaction chambers.

7. The apparatus of claim 1 further comprising a thermal controller coupled to the microfluidic device.

8. The apparatus of claim 1 wherein each of the closed reaction chambers in the array of closed reaction chambers is characterized by a volume of about 100 nanoliters or less.

9. The apparatus of claim 8 wherein each of the closed reaction chambers in the array of closed reaction chambers is characterized by a volume of about 10 nanoliters or less.

10. The apparatus of claim 1 wherein the array of closed reaction chambers is characterized by an array density of 250 sites per cm2 or greater.

11. The apparatus of claim 10 wherein the array of closed reaction chambers is characterized by an array density of 500 sites per cm2 or greater.

12. The apparatus of claim 1 wherein the multi-pixel detector has at least 2048 pixels by 2048 pixels.

13. The apparatus of claim 1 wherein the multi-pixel detector includes a plurality of pixels for each closed reaction chamber in the array of closed reaction chambers.

14. A method of imaging one or more selected fluorescence indications from a microfluidic device including an array of closed reaction chambers, the method comprising:

thermally cycling the array of closed reaction chambers with a thermal controller;

transmitting one or more fluorescent emission signals derived from one or more samples in the array of thermally cycling closed reaction chambers in the microfluidic device, wherein the one or more fluorescent emission signals are transmitted along an imaging path coupled to the array of closed reaction chambers in the microfluidic device, wherein each of the closed reaction chambers in the array of closed reaction chambers has a chamber size, the chamber size being characterized by an actual spatial dimension normal to the imaging path;

transmitting the one or more fluorescent emission signals derived from the one or more samples in the array of closed reaction chambers in the microfluidic device via an optical lens system coupled to the imaging path, wherein the optical lens system is adapted to reduce a size of the actual spatial dimension to a reduced size less than the size of the actual spatial dimension; and

receiving the one or more fluorescent emission signals transmitted via the optical lens system at a multi-pixel detector.

15. The method of claim 14 wherein a ratio of the reduced size to the actual spatial dimension is characterized by a ratio of less than 0.5.

16. The method of claim 14 wherein the microfluidic device is characterized by a microfluidic dimension and the method further comprises:

providing, via the optical lens system, an image of the microfluidic device that is a smaller size than the microfluidic dimension; and

transmitting, via the optical lens system, the one or more fluorescent emission signals derived from the one or more samples in the array of closed reaction chambers in the microfluidic device at the smaller size.

17. The method of claim 16 wherein the microfluidic dimension is about 30.7 mm by about 30.7 mm or greater.

18. The method of claim 14 wherein the array of closed reaction chambers comprises more than 96 closed reaction chambers.

19. The method of claim 14 wherein each of the closed reaction chambers in the array of closed reaction chambers is characterized by a volume of about 100 nanoliters or less.

20. The method of claim 14 wherein the multi-pixel detector includes a plurality of pixels for each closed reaction chamber in the array of closed reaction chambers.