Analytical test cartridge; and, methods

• US 7,569,393 B2
• Filed: 06/28/2002
• Issued: 08/04/2009
• Est. Priority Date: 06/28/2002
• Status: Active Grant

• Current Assignee: Easydx Inc.
• Original Assignee: International Technidyne Corporation (Sphingotec GMBH)
• Inventors: Sin, Kee Van
• Primary Examiner(s): ALEXANDER, LYLE
• Application Number:
  US10/185,201
• Publication Number:
  US 20040002161A1
• Time in Patent Office: 2,594 Days
• Field of Search: 422 61- 62, 422/67, 422/68.1, 422/73, 422/100, 422103-104, 436/43, 436 50- 51, 436/69, 436/165
• US Class Current: 436/51
• CPC Class Codes: G01N 33/4915 using flow cells flow cytometry G01N15/14
• CPC Class Codes: Y10T 436/115831 Condition or time responsive
• CPC Class Codes: Y10T 436/116664 with automated titrator
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]
• CPC Class Codes: Y10T 436/144444 Glucose
• CPC Class Codes: Y10T 436/171538 Urea or blood urea nitrogen
• CPC Class Codes: Y10T 436/193333 In aqueous solution
• CPC Class Codes: Y10T 436/201666 Carboxylic acid
• CPC Class Codes: Y10T 436/204998 Inorganic carbon compounds
• CPC Class Codes: Y10T 436/209163 Dissolved or trace oxygen or oxygen content of a sealed environment
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

An analytical test cartridge is provided. The analytical test cartridge can be used for medical analyses of liquid samples removed from a patient, for example blood. The analytical test cartridge is configured to provide for titration experiments. An example of a titration experiment that can be performed with the arrangement, is titration of heparin with protamine. Methods of assembly and use are provided.

Claims

1. A sample analysis cartridge comprising:

(a) a liquid sample inlet;

(b) a main flow channel in fluid flow communication with the inlet;

(c) a titration cell arrangement including;

at least two titration spins located off of and in fluid flow communication with the main flow channel; and

, a titration cell in each spur separated from the main flow channel;

(d) a titration sensor arrangement including a sensor positioned in each titration cell in the titration cell arrangement; and

(e) a titration agent positioned in each titration cell of the titration cell arrangement, with a different amount of titration agent in at least two of the titration cells.

2. A sample analysis cartridge according to claim 1 including:

(a) an electrical conductor arrangement positioned to provide operational electrical communication from the sensor arrangement to an analytical measurement device, when the cartridge is operably connected to the analytical measurement device.

3. A sample analysis cartridge according to claim 1 including:

(a) a secondary flow channel providing fluid flow communication between the main flow channel and the titration cell arrangement.

4. A sample analysis cartridge according to claim 1 wherein:

(a) the titration cell arrangement includes at least four titration spurs, each of which includes a titration cell; and

(b) a different amount of titration agent is positioned in at least four of the titration cells.

5. A sample analysis cartridge according to claim 1 including:

(a) a spur waste changer;

(i) each titration spur being configured for fluid flow communication from the main flow channel, eventually through a selected titration cell and to the spur waste chamber.

6. A sample analysis cartridge according to claim 1 wherein:

(a) each titration spur is a capillary spur.

7. A sample analysis cartridge according to claim 1 wherein:

(a) a selected set of titration cells, including more than one of said titration cells, comprises a selected analyte titration set of titration cells;

(i) each cell in the selected analyte titration set of titration cells includes a titrating agent for a selected analyte; and

(ii) an amount of titrating agent for the selected analyte in selected ones of the capillary spurs in the selected analyte titration set, differs adequately to generate a selected analyte titration calculation based upon operation of said electrochemical sensor arrangement.

8. A sample analysis cartridge according to claim 7 wherein:

(a) the titrating agent for the selected analyte is a titrating agent for heparin.

9. A sample analysis cartridge according to claim 8 wherein:

(a) the titrating agent is protamine.

10. A sample analysis cartridge according to claim 9 wherein;

(a) each capillary spur of the selected analyte titration set defines a titration cell volume within 5% of a selected titration cell volume.

11. A sample analysis cartridge according to claim 1 comprising:

(a) a base structure defining a cartridge perimeter area of no mare than 100 sq. cm.

12. A sample analysis cartridge according to claim 11 having:

(a) a total sample volume in the main flow channel and the titration spurs of no more than 100 microliters.

13. A sample analysis cartridge according to claim 12 having:

(a) a titration cell volume, of each titration cell, of no more than 2.5 μ

l.

14. A sample analysis cartridge according to claim 12 including:

(a) a single reference electrode, for all sensor located in the titration cells;

the single reference electrode being positioned in the main flow channel.

15. A sample analysis cartridge according to claim 14 including:

(a) at least one analytical sensor electrode positioned in the main flow channel.

16. A sample analysis cartridge according to claim 12 including:

(a) a main flow channel waste reservoir;

(i) said main flow conduit being positioned in fluid flow communication between said liquid sample injection port and said main channel waste reservoir.

17. A method of defining an analyte presence in a liquid sample;

said method including steps of;

(a) directing a liquid sample into a plurality of spurs located off of and in fluid flow communication with a single main flow channel, each spur leading to one or more of a plurality of titration cells containing sensors;

(b) titrating at least one of a selected analyte and a selected reagent in the liquid sample to a different degree in selected ones of the plurality of cells; and

(c) calculating an amount of an analyte in the liquid sample based on a titration analysis determined by the step of titrating.

18. A method according to claim 17 wherein:

(a) said step of titrating comprises titrating heparin in a blood sample.

19. A method according to claim 17 wherein:

(a) said step of directing comprises directing a liquid sample into an analytical sample cartridge having a total perimeter area of no more than 100 sq. cm.

20. A method according to claim 19 wherein:

(a) said step of calculating comprises calculating on a basis of titration measurements taken in at least six different cells at different amounts of titration.

21. A method according to claim 17 wherein:

(a) said step of titrating comprises titrating heparin, in blood, with protamine.