Fluorescence detector for microfluidic diagnostic system

• US 9,802,199 B2
• Filed: 11/10/2014
• Issued: 10/31/2017
• 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:
  US14/537,517
• Publication Number:
  US 20150133345A1
• Time in Patent Office: 1,086 Days
• 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 a 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 planar surface and a plurality of separate microfluidic channels comprising a first microfluidic channel with a first amplification chamber, a second microfluidic channel with a second amplification chamber, a third microfluidic channel with a third amplification chamber, and fourth microfluidic channel with a fourth amplification chamber;

the microfluidic channels aligned adjacent to each other at a first end of the microfluidic cartridge, the first and the second amplification chambers aligned along a first axis, the third and the fourth amplification chambers aligned along a second axis, wherein the first axis is substantially parallel to the second axis, and each amplification chamber configured to contain one or more polynucleotides; and

a scanning read head comprising a first optical detection block and a second optical detection block, the first optical detection block having a first detection unit and a second detection unit aligned along a first detection axis, the first detection unit configured to measure a particular frequency of light from a particular location, the second detection unit configured to measure a particular frequency of light from a particular location,

wherein in a first position the first detection axis of the first optical detection block and the first axis are coplanar in a first plane perpendicular to the planar surface of the microfluidic cartridge, wherein the scanning read head is configured to travel in a direction transverse to the first detection axis to a second position wherein the first detection axis of the first optical detection block and the second axis are coplanar in a second plane perpendicular to the planar surface of the microfluidic cartridge;

wherein each detection unit comprises

a light source configured to transmit a beam of focused light on to a particular region of the microfluidic cartridge; and

a light detector configured to receive light that is emitted from the particular region of the microfluidic cartridge.

2. The apparatus of claim 1, wherein each amplification chamber is configured to be independently heated through a series of cycles to carry out amplification of nucleotides therein.

3. The apparatus of claim 1, wherein the first optical detection block is configured to detect the presence of the one or more polynucleotides in multiple amplification chambers simultaneously.

4. The apparatus of claim 1, wherein the first and second optical detection blocks are discrete blocks stacked back-to-back as part of the scanning read head.

5. The apparatus of claim 1, wherein the first and second optical detection blocks are part of a single module scanning read head.

6. The apparatus of claim 1, wherein each detector unit is configured to detect a different range of wavelengths.

7. The apparatus of claim 1, wherein each detector unit is configured to detect the same range of wavelengths.

8. The apparatus of claim 1, wherein each detector unit is configured to emit and detect the same color.

9. The apparatus of claim 1, wherein each detector unit is configured to emit and detect a different color.

10. The apparatus of claim 1, wherein each detector unit is in optical communication with a different amplification chamber.

11. The apparatus of claim 1, further comprising a contact heat source configured to be thermally coupled to the first and second amplification chambers, whereby the first and second amplification chambers are selectively heated to amplify the one or more polynucleotides therein.

12. A diagnostic apparatus, comprising:

a planar surface of a microfluidic cartridge, the microfluidic cartridge comprising a plurality of separate microfluidic channels comprising a first microfluidic channel with a first amplification chamber, a second microfluidic channel with a second amplification chamber, a third microfluidic channel with a third amplification chamber, the microfluidic channels aligned adjacent to each other at a first end of the microfluidic cartridge, wherein the first and the second amplification chambers are aligned along a first axis, wherein the third amplification chamber is aligned along a second axis parallel to the first axis, each amplification chamber configured to contain one or more polynucleotides;

an optical detection block having a first detection unit and second detection unit aligned along a detection axis,

wherein the optical detection block is configured to travel in a direction transverse to the detection axis from a first position wherein the detection axis and the first axis are coplanar in a first plane perpendicular to the planar surface to a second position wherein the detection axis and the second axis are coplanar in a second plane perpendicular to the planar surface,

wherein each detection unit comprises

a light source configured to transmit a beam of focused light on to a particular region of the microfluidic cartridge; and

a light detector configured to receive light that is emitted from the particular region of the microfluidic cartridge.

13. The apparatus of claim 12, further comprising a scanning read head comprising a plurality of optical detection blocks.

14. The apparatus of claim 12, further comprising a second optical detection block having a third detection unit aligned along a second detection axis.

15. The apparatus of claim 14, wherein the second detection axis and the first axis are coplanar in a third plane perpendicular to the planar surface when the optical detection block is in the second position.

16. The apparatus of claim 12, further comprising a fourth microfluidic channel with a fourth amplification chamber, the third and the fourth amplification chambers aligned along the second axis.

17. The apparatus of claim 16, further comprising a second optical detection block having a third detection unit and a fourth detection unit aligned along a second detection axis.

18. The apparatus of claim 17, wherein the second detection axis and the first axis are coplanar in a third plane perpendicular to the planar surface when the optical detection block is in the second position.

19. The apparatus of claim 17, further comprising a scanning read head comprising the optical detection block and the second optical detection block, wherein the scanning read head is mounted on a movable assembly that permits the scanning read head to scan across microfluidic cartridge.

20. A diagnostic apparatus, comprising:

a microfluidic cartridge having a planar surface and a plurality of separate microfluidic channels, each channel comprising an amplification chamber, each channel aligned adjacent to each other at a first end of the microfluidic cartridge;

wherein the amplification chambers of a first and a second adjacent microfluidic channel are aligned co-axially along a first axis and wherein the amplification chambers of a third and a fourth adjacent microfluidic channel are aligned co-axially along a second axis, each amplification chamber configured to contain one or more polynucleotides;

a first detection unit aligned along a detection axis, the first detection unit comprising a first light source configured to transmit a beam of focused light on to any of the amplification chambers and a first light detector configured to receive light that is emitted from any of the amplification chambers; and

a second detection unit aligned along the detection axis, the second detection unit comprising a second light source configured to transmit a beam of focused light on to any of the amplification chambers and a second light detector configured to receive light that is emitted from any of the amplification chambers;

wherein in a first position, the detection axis and the first axis lie on a first plane perpendicular to the planar surface of the microfluidic cartridge, and wherein in a second position the detection axis and the second axis lie on a second plane perpendicular to the planar surface of the microfluidic cartridge.

21. The apparatus of claim 20, further comprising a third and fourth detection units aligned along a second detection axis, the third detection unit comprising a third light source configured to transmit a beam of focused light on to any of the amplification chambers and a third light detector configured to receive light that is emitted from any of the amplification chambers, and the fourth detection unit comprising a fourth light source configured to transmit a beam of focused light on to any of the amplification chambers and a fourth light detector configured to receive light that is emitted from any of the amplification chambers.

22. The apparatus of claim 21, wherein in the second position, the second detection axis and the first axis lie on a third plane perpendicular to the planar surface of the microfluidic cartridge.