Chip-based flow cytometer type systems for analyzing fluorescently tagged particles

Patent metadata

Field	Value
Publication number	US-9810707-B2
Application number	US-75000007-A
Country	US
Kind code	B2
Filing date	May 17, 2007
Priority date	May 17, 2006
Publication date	Nov 7, 2017
Grant date	Nov 7, 2017

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.

First claim

What is claimed is:

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 having:
a first input conduit for receiving the fluid assay;
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 fluid assay confined within the sheath fluid;
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;
a measurement subsystem comprising:
a collection system comprising collection optics configured to gather fluorescence emitted from the fluorescently tagged particles; and
an examination system for analyzing the collected fluorescence;

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

2. The portable system of claim 1 , wherein the fluid flow chamber is configured to generate a fluid stream with the fluid assay 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.

3. The portable system of claim 1 , wherein the illumination subsystem is fixedly arranged relative to the substrate.

4. The portable system of claim 1 , wherein the collection system comprises an aspherical mirror to direct light emitted from the fluorescently tagged particles to a detector of the collection system.

5. The portable system of claim 1 , 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.

6. The portable system of claim 1 , wherein the light source system is configured to direct light toward the interrogation region of the channel in a direction which is perpendicular to a direction from which the collection optics of the collection system are configured to gather fluorescence emitted from the fluorescently tagged particles.

7. The portable system of claim 1 , wherein at least one of the individual light sources emits light within a different wavelength range than another of the individual light sources.

8. The portable system of claim 1 , 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.

9. The portable system of claim 1 , wherein the substrate is configured to be not removable from the system.

10. 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 having:
a substrate configured to be non-removable with an embedded channel for routing the fluid assay 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 comprising collection optics configured to gather fluorescence emitted from the fluorescently tagged particles; and
an examination system coupled for analyzing the collected fluorescence, 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 the chip-based flow cytometer further 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 having the fluid assay confined within the sheath fluid.

12. The portable system of claim 11 , wherein the fluid flow chamber is configured to generate the fluid stream with the fluid assay 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.

13. The portable system of claim 11 , wherein the first conduit, second conduit, fluid flow chamber and at least some collection optics of the collection system are fixedly arranged upon or within the non-removable substrate.

14. The portable system of claim 10 , wherein the illumination subsystem is fixedly arranged relative to the non-removable substrate.

15. The portable system of claim 10 , wherein the collection system comprises an aspherical mirror to direct light emitted from the fluorescently tagged particles to a detector of the collection system.

16. The portable system of claim 10 , wherein the assay preparation module is configured to process the 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 assay.

17. The portable system of claim 10 , wherein the light source system is configured to direct light toward the interrogation region of the channel in a direction which is perpendicular to a direction from which the collection optics of the collection system are configured to gather fluorescence emitted from the fluorescently tagged particles.

18. 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.

19. 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

Assignees

• Schilffarth Adam Richard
• Deicher William R
• Carrano John C
• Phillips Jesse C
• Luminex Corp

Inventors

• Schilffarth Adam Richard
• Deicher William R
• Carrano John C
• Phillips Jesse C

Classifications

• G01N35/0098

  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 title

• G01N2021/6439

  with indicators, stains, dyes, tags, labels, marks · CPC title

• G01N15/1459

  the analysis being performed on a sample stream · CPC title

• G01N15/1484

  microstructural devices · CPC title

• G01N35/1095 Primary

  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) · CPC title