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1. WO2020141463 - SYSTEMS AND METHODS FOR ANALYZING A FLUID SAMPLE

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[ EN ]

Claims

What is claimed is:

1. A method of analyzing a fluid sample, the method comprising:

performing a particle-based immunoassay on a fluid sample that is flowing through a channel; and

performing image analysis of the flowing fluid sample to analyze dynamics of aggregation of the particles within the flowing fluid sample to determine a concentration of a target analyte in the fluid sample.

2. The method of claim 1, wherein performing image analysis comprises obtaining a plurality of different images, wherein dynamics of formation of the one or more first aggregates is analyzed in each image.

3. The method of claim 2, wherein performing image analysis comprises obtaining a vertical scan along a height of the channel.

4. The method of claim 1, wherein dynamics of formation of aggregation comprises at least one selected from the group consisting of rate of formation of the one or more aggregates, size of the one or more aggregates, and a combination thereof.

5. The method of claim 1, wherein performing the particle-based immunoassay on the fluid sample further comprises:

providing a first plurality of particles, wherein each particle of the first plurality of particles comprises a first antibody that is specific to a first target analyte and the first plurality of particles and the first target analyte will bind each other, via the first antibody, to form one or more first aggregates; and

providing a second plurality of particles, wherein the second plurality of particles comprise an optical characteristic that is different from the first plurality of particles, each particle of the second plurality of particles comprises a second antibody that is specific to the second target analyte, and the second plurality of particles and the second target will bind each other, via the second antibody, to form one or more second aggregates.

6. The method of claim 5, wherein performing image analysis of the flowing fluid sample further comprises:

imaging the flowing incubated fluid sample to capture dynamics of formation of the one or more first aggregates and one or more second aggregates; and

analyzing the dynamics of formation of the one or more first aggregates and the one or more second aggregates to determine a concentration of the first target analyte in the fluid sample and the second target analyte in the fluid sample..

7. The method of claim 1, wherein the fluid sample comprises intact cells and the method is conducted in the presence of the intact cells.

8. The method of claim 7, wherein the image analysis excludes the intact cells that are present in the imaged fluid sample.

9. The method of claim 8, wherein the intact cells are excluded by a technique comprising: processing an image of intact cells to produce a background threshold;

processing an image of the fluid sample comprising the intact cells and one or more aggregates; and

normalizing the image of the fluid sample against the background threshold, thereby excluding intact cells from the image analysis of the fluid sample.

10. The method of claim 1, wherein the performing step comprises:

providing a cartridge;

introducing the fluid sample comprising a first target analyte into a reservoir of the cartridge, the reservoir comprising a first reagent;

incubating the fluid sample with the first reagent;

flowing the fluid sample into a second reservoir of the cartridge comprising a first plurality of particles, wherein each particle of the first plurality of particles comprises a first antibody that is specific to the first target analyte and the first plurality of particles and the first target analyte will bind each other, via the first antibody, to form one or more first aggregates; flowing the fluid sample and first plurality of particles through a channel in the cartridge; imaging the flowing fluid sample to capture dynamics of formation of the one or more first aggregates; and

analyzing the dynamics of formation of the one or more first aggregates to determine a concentration of the first target analyte in the fluid sample.

11. A method of analyzing a fluid sample, the method comprising:

incubating a fluid sample comprising a first target analyte and a first plurality of particles, wherein each particle of the first plurality of particles comprises a first antibody that is specific to the first target analyte and the first plurality of particles and the first target analyte will bind each other, via the first antibody, to form one or more first aggregates;

flowing the incubated fluid sample through a channel;

imaging the flowing incubated fluid sample to capture dynamics of formation of the one or more first aggregates; and

analyzing the dynamics of formation of the one or more first aggregates to determine a concentration of the first target analyte in the fluid sample.

12. The method of claim 11, wherein imaging comprises obtaining a plurality of different images, wherein dynamics of formation of the one or more first aggregates is analyzed in each image.

13. The method of claim 11, wherein imaging comprises obtaining a vertical scan along a height of the channel.

14. The method of claim 11, wherein dynamics of formation of the one or more aggregates comprises at least one selected from the group consisting of rate of formation of the one or more aggregates, size of the one or more aggregates, and a combination thereof.

15. The method of claim 11, wherein the fluid sample comprises a second target analyte and the incubating step further comprises a second plurality of particles, wherein the second plurality of particles comprise an optical characteristic that is different from the first plurality of particles, each particle of the second plurality of particles comprises a second antibody that is specific to the second target analyte, and the second plurality of particles and the second target will bind each other, via the second antibody, to form one or more second aggregates.

16. The method of claim 15, further comprising:

imaging the flowing incubated fluid sample to capture dynamics of formation of the one or more second aggregates; and

analyzing the dynamics of formation of the one or more second aggregates to determine a concentration of the second target analyte in the fluid sample.

17. The method of claim 11, wherein the fluid sample comprises intact cells and the method is conducted in the presence of the intact cells.

18. The method of claim 17, wherein the analyzing excludes the intact cells that are present in the imaged fluid sample.

19. The method of claim 18, wherein the intact cells are excluded by a technique comprising: processing an image of intact cells to produce a background threshold;

processing an image of the fluid sample comprising the intact cells and one or more first aggregates; and

normalizing the image of the fluid sample against the background threshold, thereby excluding intact cells from the analysis of the fluid sample.

20. The method of claim 11, wherein the fluid sample is whole blood and the target is selected from the group consisting of a c-reactive protein, HbAlC, PCT, BNP, and a combination thereof.

21. A method for analyzing a fluid sample, the method comprising;

providing a fluidic device comprising a first portion configured for performing a complete blood count assay and a second portion for performing an immunoassay;

performing the complete blood count assay in the first portion of the fluidic device to obtain a hematocrit; and

performing the immunoassay in the second portion of the fluidic device, wherein the obtained hematocrit is used in the analysis of results of the immunoassay.

22. The method of claim 21, wherein the immunoassay is performed using image analysis to analyze dynamics of formation of aggregates in the fluid sample.

23. The method of claim 22, wherein the immunoassay is performed on whole blood comprising intact cells.

24. The method of claim 23, wherein the immunoassay is performed without lysing the intact cells.

25. The method of claim 23, wherein the image analysis excludes the intact cells that are present in the imaged fluid sample.

26. The method of claim 25, wherein the intact cells are excluded by a technique comprising: processing an image of intact cells to produce a background threshold;

processing an image of the fluid sample comprising the intact cells and one or more aggregates; and

normalizing the image of the fluid sample against the background threshold, thereby excluding intact cells from the image analysis of the fluid sample.

27. The method of claim 22, wherein the immunoassay is performed on a flowing fluid sample.

28. The method of claim 21, wherein the wherein the fluidic device is a cartridge that is configured to be operably coupled to an analytical instrument.

29. The method of claim 28, wherein cartridge is pre-loaded with reagents for each of the complete blood count assay and the immunoassay.

30. The method of claim 21, wherein the immunoassay is performed to determine a

concentration of a target analyte in the fluid sample, wherein the target analyte is at least one selected from the group consisting of a c-reactive protein, HbAlC, PCT, BNP, and a

combination thereof.

31. A fluid cartridge comprising:

one or more reservoirs comprising a reagent for an immunoassay and a first plurality of particles, wherein each particle of the first plurality of particles comprises a first antibody that is specific to a first target analyte in a fluid sample;

a seal between the one or more reservoirs; and

a first channel operably coupled to the one or more reservoirs to receive and flow fluid from the one or more reservoirs.

32. The fluid cartridge of claim 31, wherein the one or more reservoirs further comprise magnetic particles.

33. The fluid cartridge of claim 31, wherein at least one of the one or more reservoirs comprises a deformable cover that can be deformed into one or more pre-threshold and post-threshold configurations, and the seal is configured to burst only when the deformable cover is in one of the plurality of post-threshold configurations.

34. The fluid cartridge of claim 31, wherein the cartridge further comprises a first reservoir comprising an immunoassay buffer, a second reservoir comprising the first plurality of particles that is fluidically coupled to the first reservoir, and at least a third reservoir associated with an inlet that is different from an inlet to the first reservoir and the second reservoir.

35. The fluid cartridge of claim 34, wherein the third reservoir comprises one or more reagents for performing a complete blood count assay.

36. The fluid cartridge of claim 35, further comprising a second channel operably coupled to the third reservoir to receive and flow fluid from the third reservoir.

37. The fluid cartridge of claim 36, wherein the cartridge is configured such that the first channel and the second channel are coupled to a common junction that is downstream from the first, second, and third reservoirs.

38. The fluid cartridge of claim 37, wherein the cartridge is configured such that when fluid flow through the first channel arrives at the common junction, the fluid flow from the first channel displaces and reverses the fluid flow from the second channel.

39. The fluid cartridge of claim 38, further comprising a third channel coupled to the common junction.

40. The fluid cartridge of claim 39, wherein the cartridge is configured to be operably coupled to an analytical instrument configured to perform image analysis on fluid sample flowing through the third channel.