Measuring multi-analyte samples using an in-line flow cell

• US 9,110,050 B2
• Filed: 06/09/2014
• Issued: 08/18/2015
• Est. Priority Date: 02/04/2010
• Status: Active Grant

• Current Assignee: Bio-Rad Laboratories Incorporated
• Original Assignee: Bio-Rad Laboratories Incorporated
• Inventors: Likuski, Robert K., Prestigiacomo, Anthony F., Le, Tong, Kramer, Kurt D., Bartling, Donald J.
• Primary Examiner(s): Nagpaul, Jyoti
• Application Number:
  US14/300,164
• Publication Number:
  US 20150027207A1
• Time in Patent Office: 435 Days
• Field of Search: 422500-504, 436/180
• US Class Current: 1/1
• CPC Class Codes: G01N 1/28 Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Qmounting specimens on microscopic slides G02B21/34; means for supporting the objects or the materials to be analysed in electron microscopes H01J37/20 ; laboratory gas handling apparatus B01L5/00
• CPC Class Codes: G01N 15/06 Investigating concentration of particle suspensions by weighing G01N5/00; investigating sedimentation of particle suspensions G01N15/04; investigating individual particles G01N15/10
• CPC Class Codes: G01N 15/075 by optical means
• CPC Class Codes: G01N 21/6486 Measuring fluorescence of biological material, e.g. DNA, RNA, cells G01N21/6428 takes precedence
• CPC Class Codes: G01N 30/06 Preparation
• CPC Class Codes: G01N 33/4915 using flow cells flow cytometry G01N15/14
• CPC Class Codes: G01N 35/00 Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
• 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
• CPC Class Codes: G01N 35/1097 characterised by the valves valves in general F16K
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

Methods and systems for analyzing ratios of analytes within a flowing sample are provided. The flowing sample can be processed in real-time to determine a time interval over which a predetermined amount of a group of analytes passes by a fixed point in a flow cell. The predetermined amount can be routed to a sample container for future processing. The sample can comprise diluted blood and the analytes can comprise a component of hemoglobin, such as A1c, and the total amount of hemoglobin, of which the predetermined amount is metered.

Claims

1. A method for measuring analytes in a sample, the method comprising:

flowing a sample containing analytes through a detector;

measuring a measurand of the analytes passing through the detector;

determining a time interval over which the measurand reaches a predetermined quantity of mass, wherein measuring the measurand comprises performing a real-time integration of the measurand over the time interval;

forming a sample plug based on the time interval over which the measurand reaches the predetermined quantity of mass; and

diverting a portion of the flowing sample containing the sample plug to a sample volume.

2. The method of claim 1, wherein the measurand has a linear relationship with analyte concentration.

3. The method of claim 2, wherein the measurand is based on light absorbance of analyte.

4. The method of claim 1, wherein the time interval is pre-determined.

5. The method of claim 1, wherein the time interval starts at a first time point that is determined by a first measured threshold of the measurand.

6. The method of claim 5, wherein the sample is flowed into a waste output before the first time point.

7. The method of claim 6, wherein the first time point is the basis to switch at least one valve for diverting the portion of the flowing sample from the waste output to the sample volume.

8. The method of claim 1, wherein the time interval ends at a second time point that is determined by a second measured threshold of the measurand.

9. The method of claim 8, wherein the second threshold is determined by a calibration of a second threshold from a previous sample such that the second threshold is at or closer to a desired value.

10. The method of claim 1, wherein the sample comprises a blood dilution.

11. The method of claim 10, wherein the analyte of the blood dilution is a type of hemoglobin.

12. The method of claim 11, wherein the type of hemoglobin is one of A1c, labile A1c, carbamylated A1c, E, D, S, or C.

13. The method of claim 1, wherein measuring a measurand of the analytes passing through the detector comprises determining an average amount of the analytes passing through the detector over the time interval to completely fill the sample volume.

14. The method of claim 13, further comprising:

determining a total amount of the analytes within the sample container from the average concentration.

15. The method of claim 13, further comprising:

injecting a portion of the sample container containing a desired amount of the analytes to a detector device.

16. The method of claim 1, further comprising controlling the flowing sample to flow at a low pressure through the detector.

17. The method of claim 1, wherein the predetermined quantity of mass is based on a fixed mass of hemoglobin.

18. The method of claim 1, wherein the sample volume is a part of the injector of an HPLC system.

19. The method of claim 1, wherein the sample volume is a part of a reaction chamber for an immune-assay system.