Fluorescence detector for microfluidic diagnostic system

• US 8,883,490 B2
• Filed: 11/14/2007
• Issued: 11/11/2014
• Est. Priority Date: 03/24/2006
• Status: Active Grant

• Current Assignee: HandyLab Incorporated (Becton, Dickinson & Co)
• Original Assignee: HandyLab Incorporated (Becton, Dickinson & Co)
• Inventors: Handique, Kalyan, Brahmasandra, Sundaresh N.
• Primary Examiner(s): BOWERS, NATHAN ANDREW
• Application Number:
  US11/940,321
• Publication Number:
  US 20080149840A1
• Time in Patent Office: 2,554 Days
• Field of Search: 435/288.7, 435/287.2, 435/288.3, 435/288.5, 435/808
• US Class Current: 435/288.7
• CPC Class Codes: B01L 2200/025 Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/0684 Venting, avoiding backpressure, avoid gas bubbles
• CPC Class Codes: B01L 2300/021 Identification, e.g. bar codes
• CPC Class Codes: B01L 2300/022 Transponder chips
• CPC Class Codes: B01L 2300/045 whereby the whole cover is slidable
• CPC Class Codes: B01L 2300/046 Function or devices integrated in the closure
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2300/1805 Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2300/1838 using fluid heat transfer medium
• CPC Class Codes: B01L 2300/1861 using radiation
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/502723 characterised by venting arrangements
• CPC Class Codes: B01L 3/502738 characterised by integrated valves microvalves F16K99/0001
• 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: B01L 9/527 for microfluidic devices, e.g. used for lab-on-a-chip
• CPC Class Codes: C12Q 1/686 Polymerase chain reaction [PCR]
• CPC Class Codes: C12Q 2565/629 being a microfluidic device
• CPC Class Codes: G01N 2021/6419 : Excitation at two or more wavelengths
• CPC Class Codes: G01N 21/6428 : Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: Y02A 90/10 : Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation
• CPC Class Codes: Y10S 435/808 : Optical sensing apparatus

Abstract

The present technology provides for an fluorescent detector that is configured to detect light emitted for a probe characteristic of a polynucleotide. The polynucleotide is undergoing amplification in a microfluidic channel with which the detector is in optical communication. The detector is configured to detect minute quantities of polynucleotide, such as would be contained in a microfluidic volume. The detector can also be multiplexed to permit multiple concurrent measurements on multiple polynucleotides concurrently.

Claims

1. A diagnostic apparatus, comprising:

a microfluidic cartridge comprising a plurality of separate microfluidic channels readable from a first side of the cartridge, the channels aligned adjacent to one another in the cartridge and each comprising an amplification chamber containing one or more polynucleotides, wherein the amplification chambers of a first and a second adjacent microfluidic channel are aligned co-axially along a first axis; and

a scanning read head comprised of a plurality of detector units, the detector units arranged as a plurality of pairs of first and second detector units aligned collinearly in a direction parallel to the first axis and in a direction transverse to the direction of motion of the scanning read head over the microfluidic cartridge, and wherein each of the first detector units of the pairs are aligned collinearly in a direction parallel to the direction of motion of the scanning read head, wherein each of the plurality of detector units comprises;

a light source configured to emit light toward an amplification chamber of the cartridge containing polynucleotides; and

a photodiode configured to collect light emitted from a probe associated with a polynucleotide in an amplification chamber of the cartridge, the light source and photodiode located on the first side of the cartridge and each having a linear optical pathway to the cartridge.

2. The apparatus of claim 1 wherein the plurality of microfluidic channels are in a removable microfluidic cartridge disposed within a receiving bay in the apparatus.

3. The apparatus of claim 1, further comprising a processor coupled to the scanning read head and configured to receive an amplified signal from the plurality of detector units and transmit a diagnostic result to a user.

4. The apparatus of claim 1, wherein the plurality of detector units each comprise a bandpass-filtered diode that selectively emits light in the absorption band of the probe and a bandpass filtered photodiode that selectively detects light in the emission band of the probe.

5. The apparatus of claim 1, wherein the plurality of detector units are each configured to independently detect a plurality of probes at a plurality of different locations, wherein each probe corresponds to a polynucleotide probe or a fragment thereof.

6. The apparatus of claim 1, further comprising a contact heat source configured to be thermally coupled to the plurality of microfluidic channels, whereby the plurality of microfluidic channels are selectively heated to amplify the one or more polynucleotides therein.

7. The apparatus of claim 2, further comprising a lid at the receiving bay, the lid being operable to at least partially exclude ambient light from the receiving bay.

8. The apparatus of claim 7, wherein the plurality of detector units are housed in the lid.

9. The apparatus of claim 1, wherein an aperture is disposed between each of the plurality of detector units and the respective plurality of microfluidic channels.

10. The apparatus of claim 1, wherein the scanning read head comprised of the plurality of detector units is mounted on a movable assembly that permits the one or more detector units to scan across the plurality of microfluidic channels.

11. The apparatus of claim 1, wherein the optical pathway of the light source and the optical pathway of the photodiode are oriented 43 degrees from each other.

12. The apparatus of claim 1, wherein each of the plurality of detector units is configured to detect a different range of wavelengths.

13. The apparatus of claim 1, wherein at least two of the plurality of detector units is configured to detect the same range of wavelengths.

14. The apparatus of claim 10, wherein the plurality of detector units are arranged on the moveable assembly such that when a first one of the detectors is positioned in optical contact with any of the microfluidic channels, a different one of the detectors is not in optical communication with any of the microfluidic channels.

15. The apparatus of claim 10, wherein the plurality of detector units are configured to detect the presence of the one or more polynucleotides in multiple microfluidic channels simultaneously.

16. The apparatus of claim 1, wherein the scanning read head is comprised of a plurality of optical blocks, each optical block being comprised of two detector units, wherein the two detectors in each optical block are aligned collinearly in a direction transverse to the direction of motion of the scanning read head.

17. The apparatus of claim 16, wherein the plurality of optical blocks are stacked back-to-back in a direction parallel to the direction of motion of the scanning read head.

18. The apparatus of claim 16, wherein the two detector units in an optical block each emit and detect the same color.

19. The apparatus of claim 16, wherein the two detector units in an optical block each emit and detect a different color.

20. The apparatus of claim 16, wherein the two detector units in an optical block are each in optical communication with different of the plurality of microfluidic channels.

21. The apparatus of claim 16, wherein the two detector units in an optical block are each in optical communication with the same microfluidic channel of the plurality of microfluidic channels.

22. The apparatus of claim 21, wherein the two detector units in an optical block are each in optical communication with the different portions of the same microfluidic channel of the plurality of microfluidic channels.

23. The apparatus of claim 1, wherein the light source and the photodiode of a detector have non-overlapping optical pathways to the microfluidic channels.

24. The apparatus of claim 16, wherein the two detector units in an optical block comprise a said pair of first and second detector units.

25. The apparatus of claim 1, wherein each of the first detector units detects a different color.

26. The apparatus of claim 1, wherein each of the second detector units detects a different color.

27. The apparatus of claim 1, wherein the first and second detector units that are aligned collinearly are each in optical communication with different of the plurality of microfluidic channels.