Claims
- 1. A multi-analyte diagnostic system for use with a computer comprising:
a flow analyzer including a substantially co-planar optical assembly having at least one light source and at least one optical detector, said flow analyzer being communicatable with the computer; and a memory medium readable by the computer and storing computer instructions, the instructions including:
processing a biological sample using said flow analyzer, and determining a presence and quantity of at least one analyte of interest in the biological sample substantially simultaneously to said processing step.
- 2. The multi-analyte diagnostic system according to claim 1, wherein said at least one light source includes a plurality of light sources and said at least one optical detector includes a plurality of optical detectors, said plurality of light sources including overlapping focal regions.
- 3. The multi-analyte diagnostic system according to claim 2, wherein said plurality of light sources includes a plurality of laser diodes emitting continuing wave light.
- 4. The diagnostic system according to claim 3, wherein said plurality of laser diodes includes laser diodes emitting a plurality of wavelengths of continuous wave light.
- 5. The diagnostic system according to claim 2, wherein said flow analyzer includes a cuvette having a flat air-to-glass interface.
- 6. The diagnostic system according to claim 5, wherein said cuvette includes a neck-up region having a hexagonal cross-section, said at least one light source including two light sources, each emitting respective two distinct wavelengths of light, said at least one optical detector including four optical detectors.
- 7. The diagnostic system according to claim 2, wherein said flow analyzer includes one of a multi-pass filter and a plurality of bandpass filters coupled in parallel to said at least one optical detector via a respective multi-mode cable.
- 8. The diagnostic system according to claim 7, wherein said flow analyzer includes, for each band-pass filter, an amplifying photo-detector and an analog-to-digital converter connected in series thereto.
- 9. The diagnostic system according to claim 8, wherein said amplifying photo-detector includes one of a photomultiplier tube, an avalanche photo-diode, and a p-i-n photo-diode.
- 10. The diagnostic system according to claim 8, wherein said flow analyzer includes for each band-pass filter, an inverting amplifier in series with a low pass Nyquist filter, connected between said amplifying photo-detector and said analog-to-digital converter.
- 11. The diagnostic system according to claim 7, further comprising a digital interface board connectable to the computer and to said flow analyzer.
- 12. The diagnostic system according to claim 11, wherein said digital interface board including a microcontroller in communication with said flow cytometer, and a digital signal processor in communication with said micro controller and each analog-to-digital converter.
- 13. The diagnostic system according to claim 12, wherein said analog-to-digital converter includes a circular memory buffer having a first movable pointer, a second movable pointer, and a plurality of storage positions, said first pointer pointing to an oldest storage position into which new sample data may be stored, said second pointer pointing to a storage position from which said digital signal processor analyzes old sample data stored therein.
- 14. The diagnostic system according to claim 13 wherein said flow analyzer includes a cuvette, a sample pump communicating with said microcontroller and connected to said cuvette, and a sheath fluid reservoir communicating with said microcontroller and connected to said cuvette.
- 15. The diagnostic system according to claim 14, wherein said flow analyzer includes a waste receptacle, said microcontroller upon assay completion, communicating with said sample pump to one of halt sample fluid flow and to divert any remaining sample to said waste receptacle, and communicating with said sheath fluid reservoir to one of halt sheath fluid flow and divert any remaining sheath fluid to said waste receptacle.
- 16. The diagnostic system according to claim 8, wherein said flow analyzer includes a single-filter light path from each optical detector to each amplifying photo-detector.
- 17. The diagnostic system according to claim 1, further comprising at least one of a vertically and horizontally moveable platform, wherein said flow analyzer includes a vertically moveable aspirator, said platform cooperating with said aspirator.
- 18. The diagnostic system according to claim 17, wherein said platform supports one of a microtiter plate and said flow analyzer.
- 19. The diagnostic system according to claim 1, wherein said flow analyzer includes an aspirator moveable in vertical and horizontal directions.
- 20. The diagnostic system according to claim 1, wherein said processing instruction includes exposing a pooled population of subsets of particles to the biological sample, the particles in each subset having (i) at least one classification parameter that distinguishes the particles of one subset from those of another subset, and (ii) a reactant specific for each of the at least one analyte of interest, said processing instruction further including passing the exposed pooled population of subsets of particles through an examination zone.
- 21. The diagnostic system according to claim 1, wherein said determining instruction includes assessing the identify and quantity of each analyte of interest, if present, in the sample by substantially contemporaneously (i) collecting data relating to at least one characteristic classification parameter, including data on fluorescence emission intensities, (ii) collecting data relating to a presence or absence of a complex formed between the reactant and an analyte of interest specific to the reactant, (iii) classifying, without relying exclusively, if at all, on differences in particle size, each particle according to its subset, and (iv) quantifying an amount of complex associated with each subset.
- 22. The diagnostic system according to claim 20, wherein said determining instruction includes assessing the identify and quantity of each analyte of interest, if present, in the sample by substantially contemporaneously (i) collecting data relating to the at least one characteristic classification parameter, including bead subset data on fluorescence emission intensities, (ii) collecting data relating to a presence or absence of a complex formed between the reactant and an analyte of interest specific to the reactant, (iii) classifying, without relying exclusively, if at all, on differences in bead size, each bead according to its subset, and (iv) quantifying an amount of complex associated with each subset.
- 23. The diagnostic system according to claim 22, wherein said step (ii) of collecting data relating to a presence or absence of a complex includes collecting analyte data on fluorescence emission intensities.
- 24. The diagnostic system according to claim 23, wherein the bead subset data and the analyte data exhibit spectral overlap, and wherein said classifying step (iii) includes reducing the spectral overlap sufficiently to identify said each bead according to its subset.
- 25. The diagnostic system according to claim 1, further comprising a circular memory buffer communicatable with said flow analyzer.
- 26. The diagnostic system according to claim 25, wherein said circular memory buffer includes a first movable pointer in operation, pointing to a storage position available for storing new data, and a second movable pointer, in operation, pointing to a storage position having unanalyzed data.
- 27. A cuvette holder comprising:
a cuvette holder top including a viewing groove along one of a diameter and a width of said cuvette holder top.
- 28. The cuvette holder according to claim 27, further comprising a cuvette holder base for cooperating with said cuvette holder top to hold a cuvette.
- 29. A computer program product comprising:
a memory medium; a computer program stored on said memory medium, said computer program containing instructions for:
a) processing a biological sample through a flow analyzer, the biological sample including a pooled population of bead subsets, each bead subset having at least one characteristic classification parameter, the at least one characteristic classification parameter including at least one characteristic fluorescence emission intensity; b) collecting, substantially contemporaneously to said processing step, data related to the at least one characteristic classification parameter including bead subset data on fluorescence emission intensities; c) collecting substantially contemporaneously to said processing step, data related to a presence or absence of an analyte of interest, including analyte data on fluorescence emission intensities, the bead subset data and the analyte data exhibiting spectral overlap; and d) reducing, substantially contemporaneously to said processing step, the spectral overlap sufficiently to identify each bead according to its subset.
- 30. The computer program product according to claim 29, wherein said computer program further comprises instructions for:
e) determining, substantially contemporaneously to said processing step, an identity and quantity of at least one analyte of interest in the biological sample.
- 31. The computer program product according to claim 29, wherein said computer program further comprises instructions for providing at least one of a simplex analysis application module and a multiplexed analysis application module.
- 32. The computer program product according to claim 29, wherein said computer program further comprises instructions for providing at least one of:
a main menu; a results table; a system monitor; a dot plot display including at least one of a density dot plot and a decaying dot ploy; a histogram tab; an optical amplifier control tab; a color compensation control tab; and a doublet discriminator control tab.
- 33. A computer program product for use with a flow analyzer and a computer, comprising:
a memory medium; a computer program stored on said memory medium, said computer program containing instructions for:
a) processing a biological sample through a flow analyzer, the biological sample including a pooled population of bead subsets, each bead subset having at least one characteristic classification parameter, the at least one characteristic classification parameter including at least one characteristic fluorescence emission intensity; b) collecting, substantially contemporaneously to said processing step, data related to the at least one characteristic classification parameter including bead subset data on fluorescence emission intensities; c) collecting substantially contemporaneously to said processing step, data related to a presence or absence of an analyte of interest, including analyte data on fluorescence emission intensities; and d) determining, substantially contemporaneously to said processing step, an identity and quantity of at least one analyte of interest in the biological sample; an application programming interface library interfacing with the flow analyzer and the computer program, in operation; and a mathematics library communicating with the computer program, in operation.
- 34. The computer program product according to claim 33, wherein said application programming interface library includes at least one of:
a function for initializing a device interface for the flow analyzer; a function for closing a device session with a flow analyzer; a function for loading a map file for distinguishing between the bead subsets; a function for defining bead subsets to be associated with an assay; a function for acquiring bead statistics of a selected bead subset; a function for copying flow analyzer settings into a user-supplied buffer; and a function for changing the flow analyzer settings.
- 35. The computer program product according to claim 33, wherein said computer program includes at least one of:
a function for initiating acquisition of bead statistics for a current sample loaded on the flow analyzer; a function for ending the acquisition of bead statistics; a function for copying most current bead statistics into a user-supplied buffer; and a function for one of returning and displaying data acquisition statistics.
- 36. A multi-analyte analysis or diagnostic method comprising sequential, non-sequential or sequence independent steps:
a) processing a biological sample through a flow analyzer, the biological sample including a pooled population of bead subsets, each bead subset having at least one characteristic classification parameter, the at least one characteristic classification parameter including at least one characteristic fluorescence emission intensity; b) collecting, substantially contemporaneously to said processing step, data related to the at least one characteristic classification parameter including bead subset data on fluorescence emission intensities; c) collecting substantially contemporaneously to said processing step, data related to a presence or absence of an analyte of interest, including analyte data on fluorescence emission intensities, the bead subset data and the analyte data exhibiting spectral overlap; d) reducing, substantially contemporaneously to said processing step, the spectral overlap sufficiently to identify each bead according to its subset; and e) determining, substantially contemporaneously to said processing step, an identity and quantity of at least one analyte of interest in the biological sample.
- 37. An analysis or diagnostic method, comprising the sequential, sequence independent, or non-sequential steps of:
(a) processing a plurality of pooled subsets through an inspection area, each of the plurality of pooled subsets including at least one indication parameter; (b) illuminating, substantially simultaneously and not sequentially, each of the plurality of samples with at least two light beams from at least one source, at substantially the same time; and (c) determining the at least one indication parameter responsive to said illuminating step (b).
- 38. An analysis or diagnostic method according to claim 37, wherein each of said light beams includes continuous wave light.
- 39. A flow cytometer, comprising:
a base section; a plurality of light sources mounted to said base section; a plurality of selectors mounted to said base section; and a sample viewing chamber mounted to said base section and in optical relationship with said plurality of light sources and said plurality of detectors.
- 40. An analysis or diagnostic system, comprising:
an initialization system initializing a device interface for a flow cytometer, including:
a termination system terminating a device session for the flow cytometer; a bead map file system loading a file defining a bead map indicative of an associated bead type; a reset system resetting beads to be used in the analysis or diagnostic system; and a user bead component system used to acquire bead statistics for the beads and the associated bead type; a machine control and monitoring system, responsively coupled to said initialization system, and monitoring and controlling the analysis or diagnostic system, including:
a panel setting system maintaining current flow cytometer settings in a buffer or storage area; and a change panel setting system changing at least one of the current flow cytometer settings responsive to a command; and a sample acquisition and reporting system, responsively coupled to said machine control and monitoring system, collecting data for analysis or diagnosis, including:
a test start system indicating when to begin collecting the data from said machine control and monitoring system; a test stop system indicating when to stop collecting the data from said machine control and monitoring system; a test stop system indicating when to stop collecting the data from said machine control and monitoring system; a test storage system storing the data in another buffer or storage area; and a test query system performing the analysis or diagnosis on the data responsive to a predetermined program or user query.
- 41. An analysis or diagnostic method, comprising:
initializing a device interface for a flow cytometer, said initializing step including:
terminating a device session for the flow cytometer; loading a bead map file defining a bead map indicative of an associated bead type; resetting beads to be used in the analysis or diagnostic system; and acquiring bead statistics for the beads and the associated bead type; controlling and monitoring an analysis or diagnosis using a machine control and monitoring system, including:
maintaining current flow cytometer settings in a buffer or storage area; and changing at least one of the current flow cytometer settings responsive to a command; and collecting data for analysis or diagnosis, including:
indicating when to begin collecting the data from the machine control and monitoring system; indicating when to stop collecting the data from the machine control and monitoring system; storing the data in another buffer or storage area; and performing the analysis or diagnosis on the data responsive to a predetermined program or user query.
- 42. The multi-analyte diagnostic system according to claim 1, wherein the computer instructions further provides at least one of:
a main menu; a results table; a system monitor; a dot plot display including at least one of a density dot plot and a decaying dot ploy; a histogram tab; an optical amplifier control tab; a color compensation control tab; and a doublet discriminator control tab.
- 43. The cuvette holder according to claim 27, further comprising:
a base frame, said cuvette holder top secured to said base frame; and a stability bracket secured to said base frame and securing a top of the cuvette.
- 44. The diagnostic system according to claim 5, wherein said cuvette includes a substantially flat glass-to-fluid interface.
- 45. The diagnostic system according to claim 44, wherein said cuvette includes a neck region having one of an internal rectangular cross-section and an internal square cross-section.
- 46. A detector apparatus comprising:
a U-block assembly; at least one optical beam splitter; at least one optical detector secured to said U-block assembly; and at least one push-pull assembly adjustably securing said at least one optical beam splitter to said U-block assembly, and directing said at least one optical beam splitter to be sufficiently optically couplable with said at least one optical detector.
- 47. The detector apparatus according to claim 46, wherein said U-block assembly includes one of a unitary and integrated body having an inner portion, said at least one optical beam splitter bordered, in part, by said inner portion of said U-block assembly.
- 48. The detector apparatus according to claim 47, wherein said body of said U-block assembly includes first and second legs, said at least one optical detector secured within said first leg, said at least one push-pull assembly secured within said second leg.
- 49. The detector apparatus according to claim 46, further comprising an optical assembly base frame, and said U-block assembly being secured thereto.
- 50. The detector apparatus according to claim 46, wherein said at least one push-pull assembly includes a screw tap and spring assembly for at least one of pushing a side of said at least one beam splitter toward said at least one optical detector, and pulling another side of said at least one beam splitter away from said at least one optical detector.
- 51. The detector apparatus according to claim 46, wherein said at least one optical beam splitter comprises at least one dichroic mirror.
- 52. The detector apparatus according to claim 51, wherein said at least one dichroic mirror includes a plurality of dichroic mirrors, each dichroic mirror of said plurality of dichroic mirrors directing a respective band of wavelengths of light to a respective optical detector and transmitting a remainder of wavelengths of light therethrough.
- 53. The detector apparatus according to claim 46, further comprising at least one filter, interposed between said at least one optical beam splitter and said at least one optical detector.
- 54. In a flow analyzer including a pressure sensor and a sheath fluid reservoir, a de-bubbler comprising:
a bottle including an upper portion and a lower portion, said upper portion of said bottle including an inlet operatively connected to the sheath fluid reservoir to receive sheath fluid therefrom, said lower portion of said bottle including an outlet operatively connected to the pressure sensor; and a substantially waterproof vent sealing a top of said bottle and exposing an interior of said bottle to an atmosphere external to said bottle so that, in operation, sheath fluid is output via said outlet substantially free of a gas bubble.
- 55. The de-bubbler according to claim 54, wherein the flow analyzer further includes a sample pump, and wherein the pressure sensor transmits a command to deactivate the sample pump upon sensing a decreased fluid pressure in said de-bubbler.
- 56. A multi-analyte diagnostic system for analyzing a sample fluid for one or more analytes of interest, comprising:
a flow analyzer comprising: a cuvette including, in operation, a fluid core, and including a neck region having a substantially flat glass-to-fluid interface and a substantially flat air-to-glass interface; a first magnification lens optically cooperative with said cuvette and having a magnification power; and a filter and optical amplifier assembly including an entrance aperture, said entrance aperture dimensioned to cooperate with the magnification power to transmit light from the fluid core in said cuvette with substantially no light distortion from at least one of said glass-to-fluid interface and said air-to-glass interface.
- 57. The multi-analyte diagnostic system according to claim 56, wherein said flow analyzer is communicatable with a computer, said multi-analyte diagnostic system further comprising:
a memory medium readable by the computer and storing computer instructions executed by the computer, the computer instructions including: processing the sample fluid using said flow analyzer, and analyzing the sample fluid and determining a presence and quantity of at least one analyte of interest in the sample fluid substantially simultaneously to said processing step.
- 58. The multi-analyte diagnostic system according to claim 56, further comprising a first mirror optically coupled to said first magnification lens and reflecting a first plurality of wavelengths of the light to said entrance aperture, at least one of said first plurality of wavelengths indicative of a presence of at least one analyte of interest in the sample fluid.
- 59. The multi-analyte diagnostic system according to claim 56, wherein said flow analyzer further comprises at least one light source to radiate said cuvette.
- 60. The multi-analyte diagnostic system according to claim 59, wherein said at least one light source includes at least one of a laser diode and a diode pumped laser.
- 61. The multi-analyte diagnostic system according to claim 59,
wherein said cuvette includes upper and lower portions, and wherein said multi-analyte diagnostic system further comprises:
an optical assembly base frame, said first magnification lens, said filter and optical amplifier assembly, and said at least one light source secured to said optical assembly base frame; a cuvette holder secured to said optical assembly base frame and securing a bottom of said cuvette; and a stability bracket secured to said optical assembly base frame and securing a top of said cuvette.
- 62. The multi-analyte diagnostic system according to claim 56, further comprising:
a second magnification lens optically cooperative with said cuvette; at least one optical beam splitter optically cooperative with said second magnification lens; and at least one optical detector identifying at least one particle as belonging to a respective particle subset, and optically cooperative with said at least one optical beam splitter.
- 63. The multi-analyte diagnostic system according to claim 62, further comprising a second mirror optically coupled to said second magnification lens and said at least one beam splitter, and reflecting a second plurality of wavelengths of light to said at least one optical beam splitter, at least one of said second plurality of wavelengths indicative of the identity of the at least one particle.
- 64. The multi-analyte diagnostic system according to claim 62, further comprising a side scatter optically cooperating with said at least one beam splitter and identifying a doublet.
RELATED APPLICATIONS
[0001] This application claims priority to U.S. Provisional Application Serial No. 60/085,381, filed May 14, 1998 and incorporated herein by reference.
Provisional Applications (1)
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Number |
Date |
Country |
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60085381 |
May 1998 |
US |
Continuations (1)
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Number |
Date |
Country |
Parent |
09311115 |
May 1999 |
US |
Child |
10442130 |
May 2003 |
US |