1. A method for detecting an antibody in a test sample comprising:
(a) contacting the test sample with a first detector to form a first complex comprising the first detector and the antibody, wherein the first detector comprises an Fc-binding molecule conjugated to a first detectable entity;
(b) contacting the first complex with a capture entity immobilized on a test region of a surface, wherein the capture entity is capable of specifically binding to the antibody; and
(c) detecting the presence of a signal from the first detectable entity in the test region, wherein the presence of the signal is indicative of the presence of the antibody in the test sample.
2. The method of claim 1, wherein the first detector is immobilized to a conjugate region of the surface and wherein the conjugate region does not overlap with the test region of the surface.
3. The method of claim 1, wherein the Fc-binding molecule is protein A andor protein G.
4. The method of claim 1, wherein the capture entity is an antigen or antigenic peptide.
5. The method of claim 4, wherein said antigen or antigenic peptide is from an organism selected from the group consisting of heartworm, Ehrlichia canis, Ehrlichia chaffeensis, Ehrlichia ewingii, Borrelia burgdorferi, Borrelia afzelii, Borrelia garinii, Anaplasma phagocytophilum, Anaplasma platys, feline leukemia virus, parvovirus, influenza A strain, influenza B strain, avian influenza virus, respiratory syncytial virus, Legionella, adenovirus, rotavirus, feline immunodeficiency virus, human immunodeficiency virus, and Group A Streptococcus.
6. The method of claim 1, wherein the first detectable entity is a metal nanoparticle, metal nanoshell, fluorophore, or colored latex particle.
7. The method of claim 6, wherein the metallic nanoparticle or metallic nanoshell is selected from the group consisting of gold particles, silver particles, copper particles, platinum particles, cadmium particles, composite particles, gold hollow spheres, gold-coated silica nanoshells, and silica-coated gold shells.
8. The method of claim 1, further comprising contacting the test sample with a second detector, wherein the second detector comprises an antigen or antigenic peptide conjugated to a second detectable entity, said antigen or antigenic peptide being capable of specifically binding to the antibody.
9. The method of claim 8, wherein the first and second detector are immobilized on a conjugate region and wherein the conjugate region does not overlap with the test region of the surface.
10. The method of claim 2 or 9, wherein the conjugate region further comprising a control detector.
11. The method of claim 8, wherein the first and second detectable entities are the same.
12. The method of claim 11 wherein the first and second detectable entities are gold nanoparticles.
13. The method of claim 8, wherein the first and second detectable entities are different.
14. The method of claim 8, wherein the surface is a flow path in a lateral flow assay device, a surface of a microtiter plate or a flow path in an analytical rotor.
15. The method of claim 8, wherein said antigen or antigenic peptide is from an organism selected from the group consisting of heartworm, Ehrlichia canis, Ehrlichia chaffeensis, Ehrlichia ewingii, Borrelia burgdorferi, Borrelia afzelii, Borrelia garinii, Anaplasma phagocytophilum, Anaplasma platys, leukemia virus, parvovirus, influenza A strain, influenza B strain, avian influenza virus, respiratory syncytial virus, Legioneila, adenovirus, rotavirus, feline immunodeficiency virus, human immunodeficiency virus, and Group A Streptococcus.
16. The method of claim 8, wherein the first detector and the second detector are present in a ratio of about 20:1 to about 1:1.
17. The method of claim 16, wherein the first detector comprises an Fc-binding molecule conjugated to a first detectable entity, and wherein the Fc-binding molecule is protein A andor protein G.
18. The method of claim 16, wherein the first detector comprises protein A and protein G each conjugated to a first detectable entity.
19. The method of claim 18, wherein protein A and protein G are present in a ratio of about 10:1 to about 1:10.
20. The method of claim 1, when the surface is a flow path in a lateral flow assay device or a flow path in an analytical rotor.
21. The method of claim 1, wherein the test sample is a bodily fluid, extract of a bodily organ, blood, serum, or plasma.
22. An antibody detection device comprising:
a sample loading region;
a conjugate region, wherein said conjugate region comprises a mobilizable first detector including an Fc-binding molecule conjugated to a first detectable entity; and
a test region, wherein said test region comprises an immobilized capture entity capable of specifically binding to the antibody;
wherein the sample loading region, the conjugate region and the test region are configured so that in operation a liquid sample when loaded into the sample loading region, is in fluid communication with the conjugate region and the test region.
23. The detection device of claim 22, wherein the Fc-binding molecule is protein A andor protein G.
24. The detection device of claim 22, wherein the capture entity is an antigen or antigenic peptide.
25. The detection device of claim 24, wherein said antigen or antigenic peptide is from an organism selected from the group consisting of heartworm, Ehrlichia canis, Ehrlichia chaffeensis, Ehrlichia ewingii, Borrelia burgdorferi, Borrelia afzelii, Borrelia garinii, Anaplasma phagocytophilum, Anaplasma platys, feline leukemia virus, parvovirus, influenza A strain, influenza B strain, avian influenza virus, respiratory syncytial virus, Legionella, adenovirus, rotavirus, feline immunodeficiency virus, human immunodeficiency virus, and Group A Streptococcus.
26. The detection device of claim 22, wherein the first detectable entity is a metal nanoparticle, metal nanoshell, fluorophore, or colored latex particle.
27. The detection device of claim 26, wherein the metallic nanoparticle or metallic nanoshell is selected from the group consisting of gold particles, silver particles, copper particles, platinum particles, cadmium particles, composite particles, gold hollow spheres, gold-coated silica nanoshells, and silica-coated gold shells.
28. The detection device of claim 22, wherein said device further comprises a control region in fluid communication with a liquid sample when it is loaded to the sample loading region.
29. The detection device of claim 28, wherein said control region comprises an immobilized binding partner capable of specifically binding a control detector.
30. The detection device of claim 29, wherein said first detector comprises protein A or protein G conjugated to a first detectable entity and said immobilized binding partner is an anti-protein A or anti-protein G antibody.
31. The detection device of claim 22, further comprising an absorbent pad positioned downstream of the test region.
32. The detection device of claim 22, wherein said conjugate region is positioned upstream of said sample loading region.
33. The detection device of claim 22, wherein said conjugate region is positioned downstream of said sample loading region.
34. The detection device of claim 22, wherein said sample loading region comprises a blood separator material.
35. The detection device of claim 22, wherein said conjugate region further comprises a mobilizable second detector, wherein the second detector comprises an antigen or antigenic peptide conjugated to a second detectable entity, said antigen or antigenic peptide being capable of specifically binding to the antibody.
36. The detection device of claim 35, wherein the first and second detectable entities are the same.
37. The detection device of claim 36, wherein the first and second detectable entities are gold nanoparticles.
38. The detection device of claim 35, wherein the first and second testable entities are different.
39. The detection device of claim 35, wherein said antigen or antigenic peptide is from an organism selected from the group consisting of heartworm, Ehrlichia canis, Ehrlichia chaffeensis, Ehrlichia ewingii, Borrelia burgdorferi, Borrelia afzelii, Borrelia garinii, Anaplasma phagocytophilum, Anaplasma platys, feline leukemia virus, parvovirus, influenza A strain, influenza B strain, avian influenza virus, respiratory syncytial virus, Legionella, adenovirus, rotavirus, feline immunodeficiency virus, human immunodeficiency virus, and Group A Streptococcus.
40. The detection device of claim 33, wherein the first mobilizable detector and the second mobilizable detector are present in a ratio of about 20:1 to about 1:1.
41. The detection device of claim 40, wherein the first mobilizable detector comprises an Fc-binding molecule conjugated to a first detectable entity, and wherein the Fc-binding molecule is protein A andor protein G.
42. The detection device of claim 40, wherein the first mobilizable detector comprises protein A and protein G each conjugated to a first detectable entity.
43. The detection device of claim 42, wherein protein A and protein G are present in a ratio of about 10:1 to about 1:10.
44. A kit comprising the detection system of claim 22 and instructions for using the system to detect an antibody in a test sample.
45. The kit of claim 44, further comprising a second detector and instructions for combining the second detector with the test sample prior to application to the sample loading region of the detection system, wherein said second detector comprises an antigen or antigenic peptide conjugated to a second detectable entity, said antigen or antigenic peptide being capable of specifically binding to the antibody.
46. The kit of claim 45, wherein the first mobilizable detector and the second detector are present in a ratio of about 20:1 to about 1:1.
47. The kit of claim 46, wherein the first mobilizable detector comprises an Fc-binding molecule conjugated to a first detectable entity, and wherein the Fc-binding molecule is protein A andor protein G.
48. The kit of claim 46, wherein the first detector comprises protein A and protein G each conjugated to a first detectable entity.
49. The kit of claim 48, wherein protein A and protein G are present in a ratio of about 10:1 to about 1:10.
50. A method of detecting an antibody in a test sample comprising applying the test sample to the sample loading region of the detection system of claim 22 and detecting the presence or absence of a signal from the first detectable entity in the test region.
51. The method of claim 50 further comprising combining a second detector with the test sample prior to application to the sample loading region of the detection system, wherein said second detector comprises an antigen or antigenic peptide conjugated to a second detectable entity, said antigen or antigenic peptide being capable of specifically binding to the antibody.
52. The method of claim 51, wherein the second detector is added to the test sample such that it will be present in a ratio of about 20:1 to about 1:1 with the first mobilizable detector.
53. A capture complex comprising a capture entity, an antibody in a test sample, and a first detector, wherein the capture entity binds to the antibody and wherein the first detector comprises a Fc-binding molecule conjugated to a first detectable entity and binds to the Fc region of the antibody.
54. The capture complex of claim 53, further comprising a second detector, wherein the second detector specifically binds to the variable region of the antibody.
55. The capture complex of claim 53, wherein the capture complex is immobilized on a test region of a surface.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. An apparatus for controlling flow of a fluid into a wellbore tubular from a production zone comprising:
a) a housing connectable to the wellbore tubing adjacent to the production zone and
b) at least one divergent passageway disposed within said housing between:
i) a first opening in the housing for entry of the fluid from the production zone into the divergent passageway, and
ii) a second opening in said housing for exit of the fluid from the divergent passageway and into the bore of the wellbore tubular,
c) the at least one divergent passageway comprising:
i) a throat disposed at the first opening or between the first opening and the second opening, and
ii) a divergent section disposed between the throat and the second opening,
wherein the average angle of divergence in the divergent section is between 2\xb0 and 40\xb0.
2. The apparatus of claim 1 further comprising a convergent section disposed between the first opening and the throat, wherein the average angle of convergence in the convergent section is between 2\xb0 and 60\xb0.
3. The apparatus of claim 1 further comprising a connection for connecting the apparatus to a device in the same flowpath that minimizes the influx of particulate matter into the bore of the wellbore tubular.
4. The apparatus of claim 1, wherein the housing comprises two parts:
a) a first part connectable to the outside of the wellbore tubular and
b) a second part disposed inside the bore of the wellbore tubular,
and wherein the first opening is in the first part and the second opening is in the second part.
5. The apparatus of claim 1, wherein the divergent section is symmetric, asymmetric, straight or curved.
6. The apparatus of claim 1, wherein the divergent section reconnects with the throat enabling fluid to recirculate within the device.
7. The apparatus of claim 1, comprising two or more divergent passageways between the first opening and the second opening.
8. The apparatus of claim 7 wherein the two or more divergent passageways are connected to one another in series.
9. The apparatus of claim 7 wherein the two or more divergent passageways are connected to one another in parallel.
10. The apparatus of claim 7 wherein the two or more divergent passageways are connected to one another in series and in parallel.
11. The apparatus of claim 1 further comprising at least one additional opening in the throat that entrains fluids from the bore of the wellbore tubular.
12. The apparatus of claim 1 further comprising at least one additional opening in the divergent section that recirculates fluid within the apparatus.
13. The apparatus of claim 1 wherein the exit of the fluid from the passageway and into the wellbore tubular is aligned within 60 degrees with the direction of flow in the bore of the wellbore tubular.
14. A method for controlling distributed flow of fluids into a wellbore tubular from a production zone comprising the steps of:
a) connecting at least two flow restriction devices along the length of the wellbore tubular, said at least two flow restriction devices each comprising:
i) a first opening for entry of the fluid from the production zone into the flow restriction device,
ii) a second opening for exit of the fluid from the flow restriction device into the bore of the wellbore tubular,
iii) at least one divergent passageway disposed between the first opening and the second opening, said divergent passageway having a throat disposed at the first opening or between the first opening and the second opening, and a divergent section disposed between the throat and the second opening, and
iv) wherein the average angle of divergence in the divergent section is between 2\xb0 and 40\xb0,
b) inserting the wellbore tubular into the wellbore and to the production zone, and
c) enabling fluid flow from the production zone into the first opening, through the divergent passageway and out the second opening into the bore of the wellbore tubular.
15. The method of claim 14 wherein the connecting of the flow restriction device on the wellbore tubular is connecting the flow restriction device to an outside surface of the wellbore tubular.
16. The method of claim 14 wherein the flow restriction device comprises two parts, a first part and a second part, and the connecting of the flow restriction device on the wellbore tubular is connecting the first part to an outside surface of the wellbore tubular, and connecting the second part to the inside of the wellbore tubular.
17. The method of claim 14 wherein the flow of the production fluid into the wellbore tubular from the production zone through the device is sub-critical, critical (sonicchoked), or super-critical.
18. The apparatus of claim 1, wherein the divergent passageway is made from an insert made from sintered tungsten carbide or similar material that is press-fit, threaded, or connected with a snap ring to the housing.
19. The apparatus of claim 1, wherein the housing is made from stainless steel, or it is coated on the inside surfaces with a material with good erosion and corrosion resistance.
20. An apparatus for controlling flow of a fluid into a wellbore tubular from a production zone comprising:
a) a housing connectable to the wellbore tubing adjacent to the production zone and
b) at least one passageway disposed within said housing, said passageway comprising:
i) a first opening for entry of the fluid from the production zone into the passageway, and
ii) a second opening for exit of the fluid from the passageway and into the bore of the wellbore tubular,
wherein the exit of the fluid from the passageway and into the wellbore tubular is aligned within 60 degrees with the direction of flow in the bore of the wellbore tubular.