DEVICE FOR RAPID DIAGNOSTIC TESTS TO DETECT ANTIGENS WITH IMPROVED SENSITIVITY

• US 20170212108A1
• Filed: 01/09/2017
• Published: 07/27/2017
• Est. Priority Date: 01/25/2016
• Status: Active Grant

• Current Assignee: General Electric Company, Tokitae LLC (Intellectual Ventures LLC)
• Original Assignee: General Electric Company, Tokitae LLC (Intellectual Ventures LLC)
• Inventors: Cate, David, Rosen, Matthew F., Li, Bing, Moore, David Roger, Misner, Matthew Jeremiah, Nichols, Kevin Paul Flood
• Granted Patent: US 10,983,119 B2
• Time in Patent Office: Days
• CPC Class Codes: G01N 33/54386 Analytical elements
• CPC Class Codes: G01N 33/54388 based on lateral flow
• CPC Class Codes: G01N 33/558 using diffusion or migration of antigen or antibody immunochromatographic test strips G01N33/54387

Abstract

A rapid diagnostic testing device for testing of a biological sample is provided. The device comprises a channeled construct, at least one lateral flow unit, and a cassette housing. The channeled construct is configured to receive a biological sample to form at least partially purified biological sample. The lateral flow unit is at least partially disposed in the cassette housing. The lateral flow unit comprises: a sample receiving zone, a conjugate zone and a detection zone. The sample receiving zone is operatively coupled to the channeled construct for receiving the partially purified biological sample comprising at least one analyte. The conjugate zone comprising a conjugate particle to bind the analyte is disposed adjacent to the first side of the sample receiving zone. The detection zone is disposed adjacent to the second side of the sample receiving zone and comprises at least one binding agent for detecting the analyte.

Claims

1. A rapid diagnostic testing device for rapid diagnostic testing of a biological sample, comprising:

a channeled construct configured to receive at least a portion of the biological sample for rapid separation of one or more undesired components from the biological sample to form at least partially purified biological sample;

at least one lateral flow unit operatively coupled to the channeled construct, wherein the lateral flow unit comprises;

a sample receiving zone operatively coupled to the channeled construct for receiving the partially purified biological sample from the channeled construct, wherein the partially purified biological sample comprises at least one analyte, and wherein the sample receiving zone comprises a first side and a second side;

a conjugate zone disposed adjacent to the first side of the sample receiving zone, wherein the conjugate zone comprises a conjugate particle for binding with the analyte; and

a detection zone disposed adjacent to the second side of the sample receiving zone, wherein the detection zone comprises at least one binding agent for detecting the analyte by capturing the analyte; and

a cassette housing comprising a sample well, a plurality of rib structure, a first surface and a second surface, wherein the lateral flow unit is at least partially disposed in the cassette housing.

2. The rapid diagnostic testing device of claim 1, wherein the biological sample comprises blood, feces, sweat, saliva, mucous, milk, urine, semen, serum, plasma, sputum, tears, vaginal fluid, or tissue.

3. A rapid diagnostic testing device for rapid diagnostic testing of a blood sample, comprising:

a channeled construct configured to receive at least a portion of the blood sample for rapid separation of blood cells and plasma from the blood sample;

at least one lateral flow unit operatively coupled to the channeled construct, wherein the lateral flow unit comprises;

a sample receiving zone operatively coupled to the channeled construct for receiving at least a portion of the plasma from the channeled construct, wherein the portion of the plasma comprises an analyte, and wherein the sample receiving zone comprises a first side and a second side;

a conjugate zone disposed adjacent to the first side of the sample receiving zone, wherein the conjugate zone comprises a conjugate particle for binding with the analyte; and

a detection zone disposed adjacent to the second side of the sample receiving zone, wherein the detection zone comprises at least one binding agent for detecting the analyte by capturing the analyte; and

a cassette housing comprising a sample well, a plurality of rib structure, a first surface and a second surface, wherein the lateral flow unit is at least partially disposed in the cassette housing.

4. The rapid diagnostic testing device of claim 3, wherein the channeled construct is disposed vertically relative to the at least one lateral flow unit.

5. The rapid diagnostic testing device of claim 3, wherein the detection zone comprises a test region and wherein the binding agent is deposited thereon.

6. The rapid diagnostic testing device of claim 3, wherein the binding agent is a primary antibody, a labeled primary antibody, a secondary antibody, or a labeled secondary antibody.

7. The rapid diagnostic testing device of claim 3, wherein the conjugate particle comprises a secondary antibody.

8. The rapid diagnostic testing device of claim 3, wherein the analyte is selected from a malarial biomarker, an influenza biomarker, a cardiac biomarker, a tumor biomarker, or combinations thereof.

9. The rapid diagnostic testing device of claim 8, wherein the analyte is a malarial biomarker histidine rich protein II (HRP 2).

10. The rapid diagnostic testing device of claim 8, wherein the analyte is a cardiac biomarker CK-MB.

11. The rapid diagnostic testing device of claim 3, wherein the sample receiving zone and the conjugate zone comprises a common substrate.

12. The rapid diagnostic testing device of claim 11, wherein the conjugate particle of the conjugate zone is present at one end of the common substrate and the sample receiving zone is present at another end of the common substrate.

13. The rapid diagnostic testing device of claim 3, wherein the sample receiving zone, the conjugate zone, and the detection zone comprises a common substrate.

14. The rapid diagnostic testing device of claim 3, wherein the lateral flow unit comprises glass fiber, nitrocellulose membrane, quartz, or combinations thereof.

15. The rapid diagnostic testing device of claim 3, wherein the detection zone is present on a nitrocellulose membrane.

16. The rapid diagnostic testing device of claim 3, wherein the lateral flow unit further comprises a buffer reservoir disposed adjacent to the conjugate zone.

18. The rapid diagnostic testing device of claim 3, wherein a volume of the blood sample is in a range from about 25 μ

L to about 200 μ

L.

19. The rapid diagnostic testing device of claim 3, wherein the channeled construct comprises a size exclusion separation element.

23. The rapid diagnostic testing device of claim 3, wherein the sample well of the cassette housing comprises at least one wall, a first aperture, and a second aperture, and wherein the wall along with the first and second apertures forms a channel, and wherein the second aperture includes a flange.

24. The rapid diagnostic testing device of claim 23, wherein the channeled construct is disposed on the lateral flow unit to form a gap between the second aperture and the channeled construct, such that the flange of the second aperture is positioned to contact the channeled construct.

25. The rapid diagnostic testing device of claim 24, wherein the plurality of rib structures comprises a series of first rib structures extending from the first surface of the cassette housing, and a series of second rib structures extending from the second surface of the cassette housing.

26. The rapid diagnostic testing device of claim 25, wherein the series of first rib structure is positioned adjacent to the sample well such that a gap is formed between the first rib structure and the sample well, and wherein the series of second rib structure is positioned such that the second rib structure is in contact with the channeled construct.

27. The rapid diagnostic testing device of claim 25, wherein the series of second rib structure is positioned to form a gap between the second rib structure and the channeled construct, and to form a gap between the second rib structures and the lateral-flow unit.

17. The rapid diagnostic testing device of claim Error! Reference source not found.6, wherein the buffer reservoir comprises a non-lytic buffer, a buffer with a surfactant concentration of less than about 0.01 mM, or a combination thereof.

20. The rapid diagnostic testing device of claim Error! Reference source not found.9, wherein the size exclusion separation element is a porous membrane having a first surface and a second surface, wherein the first surface of the porous membrane is substantially planar with a raised edge surrounding the first surface of the porous membrane.

21. The rapid diagnostic testing device of claim 20, wherein the porous membrane comprises an asymmetric distribution of pores.

22. The rapid diagnostic testing device of claim 20, wherein at least a portion of the second surface of the porous membrane of the channeled construct is in contact with the sample receiving zone of the lateral flow unit.

28. A rapid diagnostic testing device for rapid diagnostic testing of a blood sample, comprising:

a channeled construct configured to receive at least a portion of the blood sample for rapid separation of blood cells and plasma from the blood sample;

at least one lateral flow unit operatively coupled to the channeled construct, wherein the channeled construct is vertically disposed relative to the at least one lateral flow unit and wherein the lateral flow unit comprises;

a sample receiving zone operatively coupled to the channeled construct for receiving at least a portion of the plasma from the channeled construct, wherein the portion of the plasma comprises an antigen selected from a malarial biomarker HRP2, a cardiac biomarker CK-MB, or a combination thereof, and wherein the sample receiving zone comprises a first side and a second side,

a conjugate zone disposed adjacent to the first side of the sample receiving zone, wherein the conjugate zone comprises an antibody for binding with the antigen to form an antigen-antibody complex; and

a detection zone disposed adjacent to the second side of the sample receiving zone, wherein the detection zone comprises a test region comprising a secondary antibody, wherein the secondary antibody disposed on the test region for detecting the antigen by capturing the antigen-antibody complex; and

a cassette housing comprising a sample well and a plurality of rib structure;

wherein the lateral flow unit is at least partially disposed in the cassette housing.