Cartridge for diagnostic testing

• US 10,261,047 B2
• Filed: 06/29/2018
• Issued: 04/16/2019
• Est. Priority Date: 07/25/2011
• Status: Active Grant

• Current Assignee: Proxim Diagnostics Corporation
• Original Assignee: Proxim Diagnostics Corporation
• Inventors: Briman, Mikhail
• Primary Examiner(s): Gordon, Brian R
• Application Number:
  US16/023,759
• Publication Number:
  US 20180313788A1
• Time in Patent Office: 291 Days
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0672 Integrated piercing tool
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/0883 Serpentine channels
• CPC Class Codes: B01L 2300/161 Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
• CPC Class Codes: B01L 2400/0478 pistons
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0638 membrane valves, flap valves
• CPC Class Codes: B01L 2400/0655 pinch valves
• CPC Class Codes: B01L 2400/0683 mechanically breaking a wall or membrane within a channel or chamber
• CPC Class Codes: B01L 2400/0694 vents used to stop and induce flow, backpressure valves
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502707 characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: G01N 2333/4712 Muscle proteins, e.g. myosin, actin, protein
• CPC Class Codes: G01N 27/3272 Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels optical biosensors G01N33/52
• CPC Class Codes: G01N 27/48 using polarography, i.e. measuring changes in current under a slowly-varying voltage
• CPC Class Codes: G01N 27/49 Systems involving the determination of the current at a single specific value, or small range of values, of applied voltage for producing selective measurement of one or more particular ionic species
• CPC Class Codes: G01N 2800/324 : Coronary artery diseases, e.g. angina pectoris, myocardial infarction
• CPC Class Codes: G01N 33/5438 : Electrodes
• CPC Class Codes: G01N 33/6893 : related to diseases not provided for elsewhere

Abstract

The present invention relates to a cartridge for conducting diagnostic assays. The cartridge consists of an assembly of components that are easily assembled. The cartridge provides means for receiving a patient sample, precisely controlling fluid introduction, onboard storage of assay fluid and conducting different assay protocols and detection of a plurality of analytes. Methods of use for the cartridge are described. The disclosed invention is suitable for point of care environments or any place where rapid, ultrasensitive testing is required.

Claims

1. A method of detecting a concentration of Troponin in a whole blood sample, the method comprising:

inserting a diagnostic cartridge containing the whole blood sample in a sample chamber into a reader, the diagnostic cartridge having Troponin reporter antibody amended with an enzyme label in the sample chamber and/or in a detection channel; and

operating the reader to

move the sample out of the sample chamber into the detection channel and across an electrode array in the detection channel, a first electrode of the electrode array having affixed thereon an anti-Troponin capture antibody,

move the sample out of the detection channel,

move a wash liquid from a first reservoir in the cartridge into the detection channel,

move the wash liquid out of the detection channel, and

move a substrate solution out of a second reservoir into the detection channel, the substrate solution comprising a component reactive with the enzyme amended to the reporter antibody; and

detect a reaction between the Troponin reporter antibody amended with enzyme and the substrate solution to measure the concentration of Troponin in the whole blood sample with a limit of detection of 3 pg/mL.

2. The method of claim 1 wherein the sample chamber has Troponin reporter antibody amended with the enzyme label deposited therein prior to the inserting step.

3. The method of claim 1 wherein the step of operating the reader to move the sample out of the sample chamber into the detection channel comprises operating the reader to move the sample into the detection channel from a first point of the detection channel on a first side of the electrodes, and wherein the step of operating the reader to move the substrate solution comprises operating the reader to move the substrate solution into the detection channel from a second point of the detection channel on a second side of the electrodes.

4. The method of claim 1 further comprising repeating the steps of operating the reader to move wash liquid into the detection channel and out of the detection channel prior to the step of operating the reader to move the substrate solution.

5. The method of claim 1 further comprising operating the reader to move air into the detection channel as the wash liquid is moved out of the detection channel.

6. The method of claim 1 further comprising operating the reader to move wash liquid out of the detection channel into a waste compartment in the cartridge.

7. The method of claim 1 wherein the step of operating the reader to move the wash liquid comprises operating the reader to move the wash liquid out of the first reservoir and into a reagent channel and from the reagent channel into the detection channel.

8. The method of claim 7 wherein a volume of wash liquid in the first reservoir is equal to or less than a volume of the reagent channel.

9. The method of claim 8 wherein the step of operating the reader to move the wash liquid comprises operating the reader to move a portion of the volume of wash liquid from the reagent channel into the detection channel.

10. The method of claim 1 wherein a volume of reagent in the second reservoir is greater than a volume of the detection channel.

11. The method of claim 1 wherein a second electrode of the electrode array has a Troponin capture antibody affixed thereon.

12. The method of claim 11 wherein a third electrode of the electrode array has an antibody not specific to Troponin affixed thereon.

13. The method of claim 1 wherein the detecting step comprises detecting amperometrically a reaction between the reporter antibody and the substrate solution to measure the concentration of Troponin in the sample with a limit of detection of 3 pg/mL.

14. The method of claim 1 further comprising operating the reader to output a Troponin concentration reading.

15. The method of claim 1 wherein the step of operating the reader to detect a reaction further comprises operating the reader to detect the reaction between the reporter antibody and the substrate solution to measure a concentration of Troponin in the whole blood sample with a linear correlation between Troponin concentration and signal over a concentration range of 0-180 pg/ml of Troponin in whole blood.

16. A cartridge for detecting a concentration of Troponin in a whole blood sample, the cartridge comprising:

a cartridge body adapted to be inserted into a cartridge reader;

a sample chamber within the cartridge body and comprising an opening for depositing a whole blood sample;

a detection channel within the cartridge body and communicating with the sample chamber to receive the whole blood sample from the sample chamber in response to actuation by the cartridge reader;

Troponin reporter antibody amended with an enzyme label disposed in the sample chamber and/or in the detection channel;

an analyte sensor in the detection channel, the analyte sensor comprising an electrode array, a first electrode of the electrode array comprising a sensor electrode having affixed thereon an anti-Troponin capture antibody;

a wash liquid disposed in a first reservoir in the cartridge body and communicating with the detection channel;

a reagent solution disposed in a second reservoir in the cartridge body and communicating with the detection channel; and

a waste compartment in the cartridge body and communicating with the detection channel;

the cartridge being operable by the cartridge reader to detect a reaction between the Troponin reporter antibody as amended with the enzyme and the substrate solution to measure a concentration of Troponin in the whole blood sample with a limit of detection of 3 pg/mL.

17. The cartridge of claim 16 wherein the first reservoir is adapted to receive a motive force from the cartridge reader to move wash liquid from the wash liquid reservoir and into a reagent channel.

18. The cartridge of claim 17 wherein the first reservoir comprises a blister pack, the motive force comprising a compressive force applied to the blister pack by the cartridge reader.

19. The cartridge of claim 17 further comprising an inlet in the cartridge body communicating with the reagent channel and adapted to receive a pneumatic force from the cartridge reader to move a portion of the wash liquid from the reagent channel into the detection channel.

20. The cartridge of claim 17 wherein the wash liquid in the first reservoir has a volume equal to or less than a volume of the reagent channel.

21. The cartridge of claim 16 wherein the second reservoir is adapted to receive a motive force from the cartridge reader to move reagent solution into the detection channel.

22. The cartridge of claim 21 wherein the second reservoir comprises a blister pack, the motive force comprising a compressive force applied to the blister pack by the cartridge reader.

23. The cartridge of claim 16 wherein the reagent solution in the second reservoir has a volume greater than a volume of the detection channel.

24. The cartridge of claim 16 wherein the second reservoir communicates with the detection channel at a first point on a first side of the electrode array and the storage chamber communicates with the detection channel at a second point on a second side of the electrode array.

25. The cartridge of claim 24 wherein the waste compartment communicates with the detection channel on the first side of the electrode array.

26. The cartridge of claim 16 wherein a second electrode of the electrode array has a Troponin capture antibody affixed thereon.

27. The cartridge of claim 26 wherein a third a third electrode of the electrode array has an antibody not specific to Troponin affixed thereon.

28. The cartridge of claim 16 wherein the cartridge is further operable by the cartridge reader to detect the reaction between the reporter antibody and the substrate solution to measure a concentration of Troponin in the whole blood sample with a linear correlation between Troponin concentration and signal over a concentration range of 0-180 pg/ml of Troponin in whole blood.

29. The cartridge of claim 16 further comprising an inlet in the cartridge body communicating with the sample chamber and adapted to receive a pneumatic force from the cartridge reader to move the biological sample from the sample chamber into the detection channel.

30. The cartridge of claim 16 further comprising an inlet in the cartridge body communicating with the reagent channel, the second inlet adapted to receive a pneumatic force from the cartridge reader to move wash liquid from the reagent channel into the detection channel.

31. The cartridge of claim 16 further comprising an inlet in the cartridge body communicating with the detection channel and adapted to receive air from the cartridge reader and to permit the air to flow into the detection channel.