Multi-Channel Optical Measurement Instrument

• US 20090021728A1
• Filed: 06/20/2008
• Published: 01/22/2009
• Est. Priority Date: 06/21/2007
• Status: Active Grant

• Current Assignee: Gen-Probe Incorporated (Hologic Incorporated)
• Original Assignee: Gen-Probe Incorporated (Hologic Incorporated)
• Inventors: Li, Haitao, Heinz, Robert E.
• Granted Patent: US 9,458,451 B2
• Time in Patent Office: Days
• US Class Current: 356/244
• CPC Class Codes: B01F 2101/23 Mixing of laboratory samples e.g. in preparation of analysing or testing properties of materials
• CPC Class Codes: B01F 2101/33 Mixing compost ingredients or organic waste
• CPC Class Codes: B01F 23/59 Mixing systems, i.e. flow charts or diagrams
• CPC Class Codes: B01F 31/00 Mixers with shaking, oscillating, or vibrating mechanisms
• CPC Class Codes: B01F 31/31 using receptacles with deformable parts, e.g. membranes, to which a motion is imparted
• CPC Class Codes: B01F 31/65 the materials to be mixed being directly submitted to a pulsating movement, e.g. by means of an oscillating piston or air column
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01F 35/2131 Colour or luminescence
• CPC Class Codes: B01L 2200/0621 Control of the sequence of chambers filled or emptied
• CPC Class Codes: B01L 2200/0647 Handling flowable solids, e.g. microscopic beads, cells, particles
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2200/0689 Sealing
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2200/14 Process control and prevention of errors
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/123 Flexible; Elastomeric
• 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 2300/1883 : using thermal insulation
• CPC Class Codes: B01L 2400/0457 : passive flow or gravitation
• CPC Class Codes: B01L 2400/0478 : pistons
• CPC Class Codes: B01L 2400/0481 : squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0655 : pinch valves
• CPC Class Codes: B01L 2400/0677 : phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers
• CPC Class Codes: B01L 3/502 : with fluid transport, e.g. in multi-compartment structures centrifugal-type cuvettes G01N21/07; analysis by separation into components G01N30/00; automatic analysers G01N35/00
• CPC Class Codes: B01L 3/502715 : characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/50273 : characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502761 : specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: B01L 3/505 : flexible containers not provided for above
• 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 7/525 : with physical movement of samples between temperature zones
• CPC Class Codes: C12N 15/1006 : by means of a solid support carrier, e.g. particles, polymers
• CPC Class Codes: C12Q 1/6806 : Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay C12Q1/6804 takes precedence
• CPC Class Codes: C12Q 1/6844 : Nucleic acid amplification reactions
• CPC Class Codes: G01N 1/44 : Sample treatment involving radiation, e.g. heat
• CPC Class Codes: G01N 2021/6419 : Excitation at two or more wavelengths
• CPC Class Codes: G01N 2021/6421 : Measuring at two or more wavelengths
• CPC Class Codes: G01N 2021/6432 : Quenching
• CPC Class Codes: G01N 2021/6439 : with indicators, stains, dyes, tags, labels, marks
• CPC Class Codes: G01N 2021/6463 : Optics
• CPC Class Codes: G01N 2035/00544 : using fluid flow
• CPC Class Codes: G01N 21/01 : Arrangements or apparatus for facilitating the optical investigation
• 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: G01N 21/645 : Specially adapted constructive features of fluorimeters
• CPC Class Codes: G01N 2201/0627 : Use of several LED's for spectral resolution
• CPC Class Codes: G01N 35/0098 : involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation magnetic particles used in immunoassays G01N33/54326; magnetic separation in general B03C
• CPC Class Codes: Y10T 137/0391 : Affecting flow by the addition of material or energy
• CPC Class Codes: Y10T 436/143333 : Saccharide [e.g., DNA, etc.]
• CPC Class Codes: Y10T 436/25 : including sample preparation
• CPC Class Codes: Y10T 436/255 : including use of a solid sorbent, semipermeable membrane, or liquid extraction

Abstract

A receptacle having a plurality of interconnected chambers arranged to permit multiple process steps or processes to be performed independently or simultaneously. The receptacles are manufactured to separate liquid from dried reagents and to maintain the stability of the dried reagents. An immiscible liquid, such as an oil, is included to control loading of process materials, facilitate mixing and reconstitution of dried reagents, limit evaporation, control heating of reaction materials, concentrate solid support materials to prevent clogging of fluid connections, provide minimum volumes for fluid transfers, and to prevent process materials from sticking to chamber surfaces. The receptacles can be adapted for use in systems having a processing instrument that includes an actuator system for selectively moving fluid substances between chambers and a detector. The actuator system can be arranged to concentrate an analyte present in a sample. The detector can be used to detect an optical signal emitted by the contents of the receptacle.

Claims

1. A detector for detecting an optical signal that may be indicative of the presence, amount, or state of one or more analytes in a sample, where the detector comprises:

one or more excitation channels, each adapted to direct an excitation signal of a prescribed excitation optical characteristic toward the sample, each excitation channel comprising;

a light emitting element adapted to emit excitation light and excitation optical elements defining an excitation optical path having an excitation optic axis and constructed and arranged to transmit at least a portion of the light emitted by the light-emitting element having the prescribed excitation optical characteristic toward the sample;

one or more emission channels, each adapted to receive an emission signal from the sample, each emission channel comprising;

emission optical elements defining an emission optical path having an emission optic axis and constructed and arranged to transmit at least a portion of any light emitted by the sample having a prescribed emission optical characteristic and a light-detecting element and associated circuitry adapted to detect light transmitted by the emission optical elements and to convert the detected light to an electronic signal indicative of at least one of the presence and strength of the detected light,

wherein the light-emitting and light detecting elements are operably connected to a single circuit board; and

one or more optic elements constructed and arranged to receive an excitation signal from each excitation channel and direct at least a portion of each excitation signal at a prescribed location and to receive emission signals emitted from the sample at the prescribed location and to direct at least a portion of the received emission signals into each emission channel,

provided that the detector does not include a reflective element for redirecting all light impinging on the reflective element in a direction different from an incidence direction of the impinging light, and

further provided that the detector does not include a light characteristic separating element for redirecting a portion of the light impinging on the separating element having a first light characteristic in a direction different from an incidence direction of the impinging light and for transmitting a portion of the light impinging on the separating element having a second light characteristic.

2. The detector of claim 1, wherein the excitation optic axis of each excitation channel and the emission optic axis of each emission channel are parallel to one another throughout their extents.

3. The detector of claim 1, wherein the one or more optic elements are constructed and arranged to (1) receive an excitation signal from each excitation channel and direct at least a portion of the excitation signal at a prescribed location on a container within which the sample is processed, and (2) receive an emission signal emitted from the sample within the container and to direct at least a portion of the received emission signals into each emission channel.

4. The detector of claim 1, comprising two or more excitation channels and two or more emission channels.

5. The detector of claim 1, wherein the one or more optic elements consists of a single, undivided lens.

6. A detector for detecting an optical signal from a sample that may be indicative of the presence, amount, or state of one or more analytes in the sample, the detector comprising:

one or more excitation channels, each adapted to direct an excitation signal of a prescribed excitation wavelength or range of excitation wavelengths toward the sample, and each excitation channel comprising;

a light emitting element adapted to emit excitation light; and

excitation optical elements defining an excitation optical path having an excitation optic axis, the excitation optical elements being constructed and arranged to transmit at least a portion of the light emitted by the light-emitting element having the prescribed excitation wavelength or range of excitation wavelengths toward the sample;

one or more emission channels, each adapted to receive an emission signal from the sample and detect an emission signal having a prescribed emission wavelength or range of emission wavelengths, and each emission channel comprising;

emission optical elements defining an emission optical path having an emission optic axis, the emission optical elements being constructed and arranged to transmit at least a portion of any light emitted by the sample having the prescribed emission wavelength or range of emission wavelengths; and

a light-detecting element adapted to detect light transmitted by the emission optical elements and to convert the detected light to an electronic signal indicative of at least one of the presence and strength of the detected light,

wherein the excitation and emission optic axes are parallel to one another throughout their extents; and

an optic lens constructed and arranged with respect to the excitation and emission channels to (1) direct excitation light transmitted by each excitation channel and impinging on a different portion of the optic lens at a prescribed location and (2) receive emission signals emitted by the sample at the prescribed location and to direct at least a portion of the received emission signals into each emission channel.

7. The detector of claim 6, wherein the optic lens comprises a solid, undivided lens.

8. The detector of claim 6, comprising no lens other than the optic lens outside of the excitation and emission channels.

9. The detector of claim 6, wherein the optic lens is constructed and arranged with respect to the excitation and emission channels to (1) direct excitation light transmitted by each excitation channel and impinging on a different portion of the optic lens at a prescribed location of a container within which the sample is processed and (2) receive emission signals emitted by the sample from within the container and to direct at least a portion of the received emission signals into each of the emission channels.

10. The detector of claim 6, wherein the light emitting element comprises a light-emitting diode.

11. The detector of claim 6, comprising two excitation channels and two emission channels.

12. The detector of claim 6, wherein the excitation optical elements of each excitation channel comprise a lens and an excitation filter constructed and arranged to transmit only light having the prescribed excitation wavelength or range of excitation wavelengths.

13. The detector of claim 6, wherein the light-detecting element comprises a photodiode.

14. The detector of claim 6, wherein the emission optical elements of each emission channel comprise a lens and an emission filter constructed and arranged to transmit only light having the prescribed emission wavelength or range of emission wavelengths.

15. The detector of claim 6, wherein the light emitting elements of the excitation channels and the light detecting elements of the emission channels are mounted on the same plane.

16. The detector of claim 6, further comprising a housing, wherein each of the excitation and emission channels is disposed within a different conduit defined within the housing.

17. The detector of claim 16, comprising two excitation channels and two emission channels and wherein the conduits of the excitation channels and the emission channels are disposed in a circular pattern, with the conduits being spaced by approximately 90°

.

18. The detector of claim 16, further comprising a base including at least one printed circuit board, the housing being mounted to the base and the light emitting elements of the excitation channels and the light detecting elements of the emission channels being operatively connected to the printed circuit board.

19. The detector of claim 6, further comprising ambient light filtering circuitry comprising:

excitation modulation circuitry constructed and arranged to modulate the excitation signal of each excitation channel at a predefined excitation frequency; and

detection circuitry constructed and arranged to identify that portion of the detected light that is substantially at the excitation frequency.

20. The detector of claim 19, comprising two or more excitation channels and wherein the excitation frequency is different for the excitation signal of each excitation channel.

21. The detector of claim 19, comprising two or more excitation channels and wherein the excitation frequency is the same for the excitation signal of each excitation channel.

22. The detector of claim 6, wherein the excitation optical elements and the emission optical elements do not include optic fibers.

23. A detector for detecting optical emissions of two or more different wavelengths or ranges of wavelengths from a sample, wherein emissions of two or more different wavelengths may be indicative of the presence, amount, or state of two or more analytes of interest in the sample, and wherein the emissions are detected without moving components of the detector with respect to the sample, the detector comprising:

two or more excitation channels fixed with respect to the sample and each other, wherein each excitation channel is adapted to direct an excitation signal of a different prescribed excitation wavelength or range of excitation wavelengths toward the sample and each excitation channel comprises;

a light emitting element adapted to emit excitation light; and

excitation optical elements defining an excitation optical path having an excitation optic axis, the excitation optical elements being constructed and arranged to transmit at least a portion of the light emitted by the light-emitting element having the prescribed excitation wavelength or range of excitation wavelengths toward the sample; and

two or more emission channels fixed with respect to the sample, the excitation channels, and each other, wherein each emission channel is adapted to receive and detect an emission signal of a different prescribed emission wavelength or range of emission wavelengths from the sample and each emission channel comprises;

emission optical elements defining an emission optical path having an emission optic axis, the emission optical elements being constructed and arranged to transmit at least a portion of any light emitted by the sample having the prescribed emission wavelength or range of emission wavelengths; and

a light-detecting element adapted to detect light transmitted by the emission optical elements and to convert the detected light to an electronic signal indicative of at least one of the presence and strength of the detected light,

whereby the detector is adapted to direct light having a unique excitation wavelength or range of excitation wavelengths at the sample with each of the excitation channels and detect light having a unique emission wavelength or range of emission wavelengths emitted from the sample with each of the emission channels without moving the excitation channels or the emission channels with respect to the sample or each other.

24. The detector of claim 23, wherein the excitation optical elements are constructed and arranged to transmit at least a portion of the light emitted by the light-emitting element having the prescribed excitation wavelength or range of emission wavelengths toward a container within which the sample is processed, and the emission optical elements are constructed and arranged to transmit at least a portion of any light having the prescribed emission wavelength or range of emission wavelengths emitted by the sample from within the container, and whereby the detector is adapted to direct light having a unique excitation wavelength or range of excitation wavelengths at the container with each of the excitation channels and detect light having a unique emission wavelength or range of emission wavelengths emitted from the container with each of the emission channels without moving the excitation channels or the emission channels with respect to the container or each other.

25. The detector of claim 23, wherein the excitation optic axes of the excitation channels and the emission optic axes of the emission channels are parallel to one another throughout their extents.

26. The detector of claim 23, further comprising an optic lens constructed and arranged with respect to the excitation channels and the emission channels to (1) direct excitation light transmitted by each excitation channel and impinging on a different portion of the optic lens at a prescribed location and (2) receive emission signals emitted by contents of the sample and to direct at least a portion of the received emission signals into each of the emission channels.

27. The detector of claim 23, wherein the light emitting element comprises a light-emitting diode.

28. The detector of claim 23, wherein the excitation optical elements of each excitation channel comprise a lens and an excitation filter constructed and arranged to transmit only light having the prescribed excitation wavelength or range of excitation wavelengths.

29. The detector of claim 23, wherein the light-detecting element comprises a photodiode.

30. The detector of claim 23, wherein the emission optical elements of each emission channel comprise a lens and an emission filter constructed and arranged to transmit only light having the prescribed emission wavelength or range of emission wavelengths.

31. The detector of claim 23, wherein the light emitting elements of the excitation channels and the light detecting elements of the emission channels are mounted on the same plane.

32. The detector of claim 23, further comprising a housing, wherein each of the excitation and emission channels is disposed within a different conduit with the housing.

33. The detector of claim 32, comprising two excitation channels and two emission channels and wherein the conduits of the excitation channels and the emission channels are disposed in a circular pattern, with the conduits being spaced by approximately 90°

.

34. The detector of claim 32, further comprising a base including at least one printed circuit board, the housing being mounted to the base and the light emitting elements of the excitation channels and the light detecting elements of the emission channels being operatively connected to the printed circuit board.

35. The detector of claim 23, further comprising ambient light filtering circuitry comprising:

excitation modulation circuitry constructed and arranged to modulate the excitation signal of each excitation channel at a predefined excitation frequency; and

detection circuitry constructed and arranged to identify that portion of the detected light that is substantially at the excitation frequency.

36. The detector of claim 35, wherein the excitation frequency is different for the excitation signal of each excitation channel.

37. The detector of claim 35, wherein the excitation frequency is the same for the excitation signal of each excitation channel.

38. The detector of claim 23, wherein the excitation optical elements and the emission optical elements do not include optic fibers.

39. A method for detecting an optical signal that may be indicative of the presence, amount, or state of one or more analytes in a sample, wherein the method comprises:

generating a first excitation signal and transmitting a portion of the first excitation signal having a first excitation wavelength or range of excitation wavelengths along a first excitation path;

focusing the first excitation signal at the sample with a first portion of an optic lens; and

directing a portion of a signal emitted by the sample, if any, into a first emission path using a second portion of the optic lens, transmitting light having a first emission wavelength or range of emission wavelengths along the first emission path, and detecting light having the first emission wavelength or range of emission wavelengths;

wherein the first excitation path and the first emission path are parallel to each other throughout their extents.

40. The method of claim 39, wherein the method further comprises:

generating a second excitation signal and transmitting a portion of the second excitation signal having a second excitation wavelength or range of excitation wavelengths along a second excitation path;

focusing the second excitation signal at the sample with a third portion of the optic lens; and

directing a portion of a signal emitted by the sample, if any, into a second emission path using a fourth portion of the optic lens, transmitting light having a second emission wavelength or range of emission wavelengths along the second emission path, and detecting light having the second emission wavelength or range of emission wavelengths,

wherein the first and second excitation paths and the first and second emission paths are parallel to each other throughout their extents.

41. The method of claim 39, wherein focusing the first excitation signal at the sample comprises focusing the first excitation signal at the contents of a container within which the sample is being processed.

42. The method of claim 41, wherein directing a portion of a signal emitted by the sample into a first emission path comprises directing a signal emitted by the sample with the container.

43. The method of claim 39, wherein the optic lens comprises a solid, undivided lens.

44. The method of claim 39, comprising transmitting the first excitation signal along the first excitation path and transmitting light along the first emission path without the use of (1) a reflective element for redirecting all light impinging on the reflective element in a direction different from an incidence direction of the impinging light or (2) a light characteristic separating element for redirecting a portion of the light impinging on the separating element having a first light characteristic in a direction different from an incidence direction of the impinging light and for transmitting a portion of the light impinging on the separating element having a second light characteristic.

45. The method of claim 39, wherein the focusing and directing steps are accomplished without any optic element other than the single lens outside the first excitation path and the first emission path.

46. The method of claim 39, wherein the generating step is performed by a light emitting diode.

47. The method of claim 39, wherein transmitting the portion of the first excitation signal having the first excitation wavelength or range of excitation wavelengths along the first excitation path comprises filtering the first excitation signal to remove wavelengths of the first excitation signal other than the first excitation wavelength or range of excitation wavelengths, and transmitting light having the first emission wavelength or range of emission wavelengths along the first emission path comprises filtering the portion of the emission signal directed into the first emission path to remove wavelengths of the first emission signal other than the first emission wavelength or range of emission wavelengths.

48. The method of claim 39, further comprising modulating the excitation signal at a predefined excitation frequency and identifying that portion of the detected light that is substantially at the excitation frequency.

49. The method of claim 39, wherein transmitting the portion of the first excitation signal having the first excitation wavelength and transmitting light having the first emission wavelength along the first emission path do not include transmitting light along an optic fiber.