Chip-Based Flow Cytometer Type Systems for Analyzing Fluorescently Tagged Particles

• US 20070269345A1
• Filed: 05/17/2007
• Published: 11/22/2007
• Est. Priority Date: 05/17/2006
• Status: Active Grant

• Current Assignee: Luminex Corporation (DiaSorin S.p.A.)
• Original Assignee: Luminex Corporation (DiaSorin S.p.A.)
• Inventors: Deicher, William R., Carrano, John C., Schilffarth, Adam Richard, Phillips, Jesse C.
• Granted Patent: US 9,810,707 B2
• Time in Patent Office: Days
• US Class Current: 422/73
• CPC Class Codes: G01N 15/1459 the analysis being performed on a sample stream
• CPC Class Codes: G01N 15/1484 microstructural devices
• CPC Class Codes: G01N 2021/6439 with indicators, stains, dyes, tags, labels, marks
• 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: G01N 35/1095 for supplying the samples to flow-through analysers for a specific analyser see relevant groups, e.g. under G01N15/00, G01N21/00, G01N27/00, G01N30/00, H01J49/00

Abstract

Portable systems for processing and analyzing biological or environmental samples as well as different configurations of chip-based flow cytometers are provided. The portable systems include an automated assay preparation module configured to process a sample into a fluid assay with fluorescently tagged particles and a microfluidic analysis module coupled to the fluid assay module, wherein the microfluidic analysis module includes a chip-based flow cytometer.

Claims

1. A portable system for processing and analyzing biological or environmental samples, comprising:

an automated assay preparation module configured to process a sample into a fluid assay with fluorescently tagged particles; and

a microfluidic analysis module coupled to the automated assay preparation module, wherein the microfluidic analysis module comprises a chip-based flow cytometer.

2. The portable system of claim 1, wherein the chip-based flow cytometer comprises:

a first input conduit for receiving the fluid assay;

a second distinct conduit for receiving a sheath fluid; and

a fluid flow chamber coupled to the first and second input conduits, wherein the fluid flow chamber is configured to generate a fluid stream with the sample fluid confined within the sheath fluid.

3. The portable system of claim 2, wherein the fluid flow chamber is configured to generate a fluid stream with the sample fluid having a first dimension of up to approximately 80 microns in a vertical direction perpendicular to the flow of the fluid stream and a second dimension of up to approximately 25 microns in a horizontal direction perpendicular to the flow of the fluid stream.

4. The portable system of claim 2, wherein the chip-based flow cytometer further comprises:

a channel coupled to the fluid flow chamber for routing the fluid stream through the flow cytometer;

an illumination subsystem comprising a light source system and an optical system collectively configured to direct light toward an interrogation region of the channel; and

a measurement subsystem comprising a collection system configured to gather fluorescence emitted from the fluorescently tagged particles and further comprising an examination system for analyzing the collected fluorescence.

5. The portable system of claim 4, wherein the first conduit, second conduit, fluid flow chamber, channel, and at least some optics of the collection system are fixedly arranged within a substrate.

6. The portable system of claim 5, wherein the illumination subsystem and the measurement subsystem are fixedly arranged relative to each other and the substrate.

7. The portable system of claim 4, wherein the collection system comprises an aspherical mirror to direct light emitted from the fluorescently tagged particles to a detector of the collection system.

8. The portable system of claim 4, wherein the assay preparation module is configured to process a sample into a fluid assay with fluorescently tagged magnetic particles, and wherein the flow cytometer comprises a means for inducing a magnetic field along at least a portion of the channel such that the fluorescently tagged magnetic particles flow within a predetermined region of the fluid stream.

9. The portable system of claim 4, wherein the channel, light source system, and optical system are arranged perpendicular to each other.

10. The portable system of claim 4, wherein the light source system is configured such that individual light sources within the light source system direct light at different spots within the interrogation region, and wherein the collection system is configured such that the fluorescent light emitted from the fluorescently tagged particles at each of the different spots is collected by a different detector of the collection system.

11. The portable system of claim 10, wherein at least one of the individual light sources emits light within a different wavelength range than another of the individual light sources.

12. The portable system of claim 10, wherein the collection system comprises a different set of collection optics to direct the light emitted at each of the different spots to a different detector of the collection system.

13. A system for analyzing a fluid sample, comprising:

a channel for routing a fluid sample comprising magnetic particles through the system;

a means for inducing a magnetic field along at least a portion of the channel such that the magnetic particles flow within a predetermined region of the fluid sample;

an illumination subsystem comprising a light source system and an optical system collectively configured to direct light toward an interrogation region of the channel; and

a measurement subsystem comprising a collection system configured to gather fluorescence emitted from the magnetic particles and further comprising an examination system for analyzing the collected fluorescence.

14. The system of claim 13, wherein the means for inducing the magnetic field comprises a solenoid coil wrapped around the fluid channel.

15. The system of claim 13, further comprising

a first input conduit for receiving the fluid sample;

a second distinct conduit for receiving a sheath fluid; and

a fluid flow chamber coupled to the first and second input conduits, wherein the fluid flow chamber is configured to confine the sample fluid within the sheath fluid, and wherein the fluid flow chamber is further coupled to the channel such that the channel receives the amalgamated fluids.

16. The system of claim 15, wherein the means for inducing the magnetic field is configured to induce the magnetic field along a portion of the channel extending between the fluid flow chamber and through the interrogation region.

17. The system of claim 15, wherein the fluid flow chamber is configured to narrow the diameter of the sample fluid from the input conduit by less than a factor of 10.

18. A chip-based flow cytometer, comprising:

a first input conduit for receiving a fluid sample comprising fluorescently tagged particles;

a second distinct conduit for receiving a sheath fluid;

a fluid flow chamber coupled to the first and second input conduits, wherein the fluid flow chamber is configured to generate a fluid stream with the sample fluid confined within the sheath fluid, and wherein the confined sample fluid comprises a diameter a first dimension of up to approximately 80 microns in a vertical direction perpendicular to the flow of the fluid stream and a second dimension of up to approximately 25 microns in a horizontal direction perpendicular to the flow of the fluid stream;

a channel coupled to the fluid flow chamber for routing the fluid stream through the flow cytometer;

an illumination subsystem comprising a light source system and an optical system collectively configured to direct light toward an interrogation region of the channel; and

a measurement subsystem comprising a collection system configured to gather fluorescence emitted from the fluorescently tagged particles and further comprising an examination system for analyzing the collected fluorescence.

19. The chip-based flow cytometer of claim 18, wherein the first conduit, second conduit, fluid flow chamber, channel, and at least some optics of the collection system are fixedly arranged within a substrate.

20. The chip-based flow cytometer of claim 19, wherein the illumination subsystem and the measurement subsystem are fixedly arranged relative to each other and the substrate.

21. A system for analyzing a fluid sample, comprising:

a channel for routing a fluid sample comprising fluorescently tagged particles through the system;

an illumination subsystem comprising a light source system and an optical system collectively configured to direct light toward an interrogation region of the channel; and

a measurement subsystem comprising an aspherical mirror configured to gather fluorescence emitted from the fluorescently tagged particles and further comprising an examination system for analyzing the collected fluorescence.

22. The system of claim 21, wherein the aspherical mirror is coated with an anti-reflective coating.

23. The system of claim 22, wherein the anti-reflective coating is configured to reflect fluorescent emissions and not scattered light.

24. The system of claim 22, wherein the anti-reflective coating is configured to reflect scattered light and fluorescent emissions.

25. A chip-based flow cytometer, comprising:

a channel for routing a fluid sample comprising fluorescently tagged particles through the flow cytometer;

an illumination subsystem comprising a light source system and an optical system collectively configured such that individual light sources within the light source system direct light toward different spots within the interrogation region; and

a measurement subsystem comprising a collection system configured such that the fluorescent light emitted from the fluorescently tagged particles at each of the different spots is collected by a different detector of the collection system and further comprising an examination system for analyzing the collected fluorescence.

26. The chip-based flow cytometer of claim 25, wherein light source system comprises more than 3 different light sources.

27. The portable system of claim 25, wherein at least one of the individual light sources emits light within a different wavelength range than another of the individual light sources.

28. The portable system of claim 25, wherein the collection system comprises a different set of collection optics to direct the light emitted at each of the different spots to a different detector of the collection system.