Fluorescence detector for microfluidic diagnostic system

• US 10,695,764 B2
• Filed: 10/27/2017
• Issued: 06/30/2020
• 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 A
• Application Number:
  US15/795,842
• Publication Number:
  US 20180154364A1
• Time in Patent Office: 977 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 method of detecting the presence of one or more polynucleotides in a microfluidic cartridge comprising a plurality of separate microfluidic channels, a first and a second amplification chamber aligned along a first cartridge axis and a third and a fourth amplification chamber aligned along a second cartridge axis substantially parallel to the first cartridge axis, each amplification chamber configured to contain or more polynucleotides, the method comprising:

positioning a scanning read head in a first position relative to the microfluidic cartridge, the scanning read head comprising a first optical detection block and a second optical detection block, the first optical detection block comprising a first detection unit and a second detection unit aligned along a first detection axis, the first detection unit and the second detection unit each comprising a light source and a light detector, wherein, in the first position, the first detection axis of the first optical detection block and the first cartridge axis are substantially coplanar in a first plane perpendicular to a surface of the microfluidic cartridge;

transmitting light using the light source of the first detection unit of the first optical detection block on to the first amplification chamber and transmitting light using the light source of the second detection unit of the first optical detection block on to the second amplification chamber;

receiving, in the light detector of the first detection unit of the first optical detection block, light emitted from the first amplification chamber and receiving, in the light detector of the second detection unit of the first optical detection block, light emitted from the second amplification chamber; and

moving the scanning read head in a direction transverse to the first detection axis to a second position relative to the microfluidic cartridge, wherein, in the second position, the first detection axis of the first optical detection block and the second cartridge axis are substantially coplanar in a second plane perpendicular to the surface of the microfluidic cartridge.

2. The method of claim 1, further comprising, after receiving light emitted from the first amplification chamber and the second amplification chamber, measuring a first frequency of the light emitted from the first amplification chamber, and measuring a second frequency of light different than the first frequency of light emitted from the second amplification chamber.

3. The method of claim 1, further comprising detecting, using the first optical detection block, the presence of one or more polynucleotides in the first amplification chamber and the second amplification chamber simultaneously.

4. The method of claim 1, further comprising, after moving the scanning read head to the second position:

transmitting light using the light source of the first detection unit of the first optical detection block on to the third amplification chamber and transmitting light using the light source of the second detection unit of the first optical detection block on to the fourth amplification chamber; and

receiving, in the light detector of the first detection unit of the first optical detection block, light emitted from the third amplification chamber and receiving, in the light detector of the second detection unit of the first optical detection block, light emitted from the fourth amplification chamber.

5. The method of claim 1, wherein the second optical detection block comprises a third detection unit and a fourth detection unit aligned along a second detection axis, the third detection unit and the fourth detection unit each comprising a light source and a light detector, and wherein, in the first position, the second detection axis of the second optical detection block and the second cartridge axis are substantially coplanar in the second plane perpendicular to a surface of the microfluidic cartridge.

6. The method of claim 5, further comprising detecting, using the first optical detection block and the second optical detection block, the presence of one or more polynucleotides in the first amplification chamber, the second amplification chamber, the third amplification chamber, and the fourth amplification chamber simultaneously.

7. The method of claim 1, wherein each detector unit detects a different range of wavelengths of light.

8. The method of claim 1, wherein each detector unit detects the same range of wavelengths of light.

9. The method of claim 1, wherein the second optical detection block comprises a third detection unit and a fourth detection unit aligned along a second detection axis, and wherein each detector unit is in optical communication with a different amplification chamber in the first position.

10. The method of claim 9, wherein, in the first position, the third detection unit and the fourth detection unit of the second optical detection block are in optical communication with the third amplification chamber and the fourth amplification chamber, respectively, and wherein moving the scanning read head to the second position moves the first detection unit and the second detection unit of the first optical detection block into optical communication with the third amplification chamber and the fourth amplification chamber, respectively.

11. The method of claim 1, further comprising selectively heating the amplification chambers.

12. A method of measuring light emitted from a microfluidic cartridge using a moveable read head comprising a first optical detection block and a second optical detection block, each of the first and the second optical detection blocks comprising a first detection unit and a second detection unit aligned along a detection axis of the optical detection block, the microfluidic cartridge comprising a plurality of separate microfluidic channels, a first and a second amplification chamber aligned along a first cartridge axis and a third and a fourth amplification chamber aligned along a second cartridge axis, each amplification chamber configured to contain or more polynucleotides, the method comprising:

transmitting a first beam of light from the first detection unit of the first optical detection block on to the first amplification chamber and transmitting a second beam of light from the second detection unit of the first optical detection block on to the second amplification chamber;

receiving, in the first detection unit of the first optical detection block, light emitted from the first amplification chamber and receiving, in the second detection unit of the first optical detection block, light emitted from the second amplification chamber; and

moving the first optical detection block transverse to the first cartridge axis to a position where the first beam of light from the first detection unit of the first optical detection block is transmitted to the third amplification chamber but not the first amplification chamber, and the second beam of light from the second detection unit of the first optical detection block is transmitted to the fourth amplification chamber but not the second amplification chamber.

13. The method of claim 12, wherein the first beam of light is transmitted using a light source of the first detection unit of the first optical detection block, and the second beam of light is transmitted using a light source of the second detection unit of the first optical detection block.

14. The method of claim 12, wherein the light emitted from the first amplification chamber is received in a light detector of the first detection unit of the first optical detection block, and the light emitted from the second amplification chamber is received in a light detector of the second detection unit of the first optical detection block.

15. The method of claim 12, wherein the detection axis of the first optical detection block is substantially parallel to the detection axis of the second optical detection block.

16. The method of claim 12, wherein, before moving the first optical detection block, the detection axis of the first optical detection block and the first cartridge axis are aligned in a first plane.

17. The method of claim 16, wherein, before moving the first optical detection block, the detection axis of the second optical detection block and the second cartridge axis are aligned in a second plane that is substantially parallel to the first plane.

18. The method of claim 17, wherein, after moving the first optical detection block, the detection axis of the first optical detection block and the second cartridge axis are aligned in the second plane.

19. The method of claim 18, wherein the first plane and the second plane are substantially perpendicular to a surface of the microfluidic cartridge.

20. The method of claim 12, further comprising detecting, before moving the first optical detection block, the presence of one or more polynucleotides in the first amplification chamber, the second amplification chamber, the third amplification chamber, and the fourth chamber simultaneously using the first optical detection block and the second optical detection block.