1. A hybridoma cell, having the designation HAPC 1555 having been deposited under ATCC accession number PTA-2658.
2. A monoclonal antibody produced by a hybridoma cell HAPC 1555 having been deposited under ATCC accession number PTA-2658.
3. A binding fragment of the monoclonal antibody produced by hybridoma cell HAPC 1555 having been deposited under ATCC accession number PTA-2658, said binding segment capable of binding activated protein C with high selectivity over protein C.
4. The binding fragment of claim 3, comprising an Fab portion of said antibody.
5. An assay for assessing the concentration of activated protein C comprising testing a human plasma sample suspected of containing a quantity of activated protein C for binding to an antibody or portion thereof having high specificity for binding to activated protein C, said antibody produced by hybridoma cell HAPC 1555 having been deposited under ATCC accession number PTA-2658.
6. An assay for the detection of activated protein C in a patient plasma sample, comprising:
binding an antibody produced by hybridoma cell HAPC 1555, said cell having been deposited under ATCC accession number PTA 2658, or a binding fragment of said antibody, to a solid support to form a surface-bound antibody,
contacting said surface-bound antibody with a patient plasma sample in a reaction zone;
incubating said reaction zone under conditions effective for binding activated protein C from said patient plasma sample to said surface-bound antibody;
washing said reaction zone to remove unbound reactants; and
testing said reaction zone for bound activated protein C.
7. The assay of claim 6, wherein said patient plasma sample is prepared with a reversible active site inhibitor of activated protein C.
8. The assay of claim 7, wherein said patient plasma sample is about 20 mM benzamidine, 2 units per ml heparin, and 10 mM calcium.
9. The assay of claim 6, wherein said solid support comprises a surface suitable for binding antibodies with sufficient affinity so that reactants can be introduced to said reaction zone comprising said surface-bound antibody and removed without removal of said surface-bound antibody.
10. The assay of claim 9, wherein said solid support is selected from microtiter plates, hollow fibers, affinity resins and beads.
11. The assay of claim 7, wherein said solid support comprises a surface suitable for binding antibodies with sufficient affinity so that reactants can be introduced to said reaction zone comprising said surface-bound antibody and removed without removal of said surface-bound antibody.
12. The assay of claim 11, wherein said solid support is selected from microtiter plates, hollow fibers, affinity resins and beads.
13. The assay of claim 8, wherein said solid support comprises a surface suitable for binding antibodies with sufficient affinity so that reactants can be introduced to said reaction zone comprising said surface-bound antibody and removed without removal of said surface-bound antibody.
14. The assay of claim 13, wherein said solid support is selected from microtiter plates, hollow fibers, affinity resins and beads.
15. The assay of claim 5, wherein said reaction zone is tested for bound activated protein C by providing a saturating amount of substrate for activated protein C to said reaction zone and detecting the activity of activated protein C by monitoring any product formed which is indicative of the action of activated protein C on said substrate.
16. The assay of claim 15, wherein said substrate is chromogenic, and said product is spectrophotometrically measured.
17. The assay of claim 15, wherein said substrate is fluorogenic, and said product is monitored with a fluorescence detection instrument.
18. The assay of claim 6, wherein said reaction zone is tested for bound activated protein C by providing a saturating amount of substrate for activated protein C to said reaction zone and detecting the activity of activated protein C by monitoring any product formed which is indicative of the action of activated protein C on said substrate.
19. The assay of claim 18, wherein said substrate is chromogenic, and said product is spectrophotometrically measured.
20. The assay of claim 18, wherein said substrate is fluorogenic, and said product is monitored with a fluorescence detection instrument.
21. The assay of claim 7, wherein said reaction zone is tested for bound activated protein C by providing a saturating amount of substrate for activated protein C to said reaction zone and detecting the activity of activated protein C by monitoring any product formed which is indicative of the action of activated protein C on said substrate.
22. The assay of claim 21, wherein said substrate is chromogenic, and said product is spectrophotometrically measured.
23. The assay of claim 21, wherein said substrate is fluorogemc, and said product is monitored with a fluorescence detection instrument.
24. The assay of claim 8, wherein said reaction zone is tested for bound activated protein C by providing a saturating amount of substrate for activated protein C to said reaction zone and detecting the activity of activated protein C by monitoring any product formed which is indicative of the action of activated protein C on said substrate.
25. The assay of claim 24, wherein said substrate is chromogenic, and said product is spectrophotometrically measured.
26. The assay of claim 24, wherein said substrate is fluorogenic, and said product is monitored with a fluorescence detection instrument.
27. The assay of claim 9, wherein said reaction zone is tested for bound activated protein C by providing a saturating amount of substrate for activated protein C to said reaction zone and detecting the activity of activated protein C by monitoring any product formed which is indicative of the action of activated protein C on said substrate.
28. The assay of claim 27, wherein said substrate is chromogenic, and said product is spectrophotometrically measured.
29. The assay of claim 27, wherein said substrate is fluorogenic, and said product is monitored with a fluorescence detection instrument.
30. The assay of claim 10, wherein said reaction zone is tested for bound activated protein C by providing a saturating amount of substrate for activated protein C to said reaction zone and detecting the activity of activated protein C by monitoring any product formed which is indicative of the action of activated protein C on said substrate.
31. The assay of claim 30, wherein said substrate is chromogenic, and said product is spectrophotometrically measured.
32. The assay of claim 30, wherein said substrate is fluorogenic, and said product is monitored with a fluorescence detection instrument.
33. The assay of claim 11, wherein said reaction zone is tested for bound activated protein C by providing a saturating amount of substrate for activated protein C to said reaction zone and detecting the activity of activated protein C by monitoring any product formed which is indicative of the action of activated protein C on said substrate.
34. The assay of claim 33, wherein said substrate is chromogenic, and said product is spectrophotometrically measured.
35. The assay of claim 33, wherein said substrate is fluorogenic, and said product is monitored with a fluorescence detection instrument.
36. The assay of claim 12, wherein said reaction zone is tested for bound activated protein C by providing a saturating amount of substrate for activated protein C to said reaction zone and detecting the activity of activated protein C by monitoring any product formed which is indicative of the action of activated protein C on said substrate.
37. The assay of claim 36, wherein said substrate is chromogenic, and said product is spectrophotometrically measured.
38. The assay of claim 36, wherein said substrate is fluorogenic, and said product is monitored with a fluorescence detection instrument.
39. The assay of claim 13, wherein said reaction zone is tested for bound activated protein C by providing a saturating amount of substrate for activated protein C to said reaction zone and detecting the activity of activated protein C by monitoring any product formed which is indicative of the action of activated protein C on said substrate.
40. The assay of claim 39, wherein said substrate is chromogenic, and said product is spectrophotometrically measured.
41. The assay of claim 39, wherein said substrate is fluorogenic, and said product is monitored with a fluorescence detection instrument.
42. The assay of claim 14, wherein said reaction zone is tested for bound activated protein C by providing a saturating amount of substrate for activated protein C to said reaction zone and detecting the activity of activated protein C by monitoring any product formed which is indicative of the action of activated protein C on said substrate.
43. The assay of claim 42, wherein said substrate is chromogenic, and said product is spectrophotometrically measured.
44. The assay of claim 42, wherein said substrate is fluorogenic, and said product is monitored with a fluorescence detection instrument.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
What is claimed is:
1. An optical transmission apparatus for externally modulating an optical carrier with an electrical signal for transmission, comprising:
a light source for outputting the optical carrier;
an external optical modulator for modulating the optical carrier outputted from said light source with the electrical signal;
a bias voltage applier for applying a bias voltage to said external optical modulator; and
bias voltage control means for controlling the bias voltage applied by said bias voltage applier to said external optical modulator based on an amount of second order distortion included in an optical signal from the external optical modulator and caused by non-linearity thereof.
2. The optical transmission apparatus according to claim 1, wherein said bias voltage control means includes:
an optical branching unit for branching the optical signal from said external optical modulator into two optical signals;
an optical-electrical converter for converting one optical signal from said optical branching unit into an electrical signal;
a distortion detector for detecting the amount of second order distortion included in the optical signal from said external optical modulator and caused by the non-linearity thereof by extracting a component in a specific band from the electrical signal provided by said optical-electrical converter and measuring a level of the component; and
a bias voltage control circuit for controlling the bias voltage applied by said bias voltage applier to said external optical modulator so as to minimize the amount of second order distortion detected by said distortion detector.
3. The optical transmission apparatus according to claim 2, wherein said bias voltage control circuit
increases or decreases the bias voltage applied by said bias voltage applier to said external optical modulator, and
determines whether the second order distortion detected by said distortion detector is increased or decreased before and after increasing or decreasing said bias voltage, and further determines, based on a determination result, whether to increase or decrease the bias voltage next time.
4. The optical transmission apparatus according to claim 2, wherein said bias voltage control means further includes
an optical power detector for detecting average optical power of the optical signal from said external optical modulator by measuring electrical power of the electrical signal from said optical-electrical converter, and
said bias voltage control circuit determines, based on the average optical power detected by said optical power detector, whether to increase or decrease the bias voltage applied by said bias voltage applier to said external optical modulator.
5. The optical transmission apparatus according to claim 1, wherein said external optical modulator includes:
two waveguides for branching the optical carrier from said light source into two optical signals for guiding;
an optical coupler for coupling the optical signals guided by said waveguides; and
first and second ports for outputting the two optical signals from said optical coupler, and said bias voltage control means includes:
an optical-electrical converter for converting the optical signal from said second port into an electrical signal;
a distortion detector for detecting an amount of second order distortion included in the optical signal from said second port and caused by non-linearity of said external optical modulator by extracting a component in a specific band from the electrical signal outputted from said optical-electrical converter and measuring a level of the component; and
a bias voltage control circuit for controlling the bias voltage applied by said bias voltage applier to said external optical modulator so that the amount of second order distortion detected by said distortion detector agrees with a previously-stored reference value.
6. The optical transmission apparatus according to claim 5, wherein
when said bias voltage applier applies to said external optical modulator the bias voltage that can minimize an amount of second order distortion included in the optical signal outputted from said first port and caused by non-linearity of said external optical modulator, said bias voltage control circuit stores the minimized amount of second order distortion detected by said distortion detector as said reference value.
7. In an optical transmission apparatus comprising an external optical modulator that modulates an optical carrier from a light source with an electrical signal, a method of controlling a bias voltage applied to the external optical modulator, comprising steps of:
measuring an amount of second order distortion included in an optical signal from said external optical modulator and caused by non-linearity thereof, and
controlling the bias voltage applied to said external optical modulator so as to minimize the amount of second order distortion measured in said distortion measuring step.
8. The bias voltage control method according to claim 7, further comprising a step of detecting average optical power of the optical signal from said external optical modulator, wherein said bias voltage controlling step includes a step of
determining, based on the optical average power detected in said optical power detecting step, whether to increase or decrease the bias voltage applied to said external optical modulator.
9. The bias voltage control method according to claim 7, wherein said external optical modulator includes:
two waveguides for branching the optical carrier from said light source into two optical signals for guiding;
an optical coupler for coupling the optical signals guided by said waveguides; and
first and second ports provided to said optical coupler for outputting the two optical signals, and said bias voltage controlling step includes steps of:
detecting an amount of second order distortion included in the optical signal from said second port and caused by non-linearity of said external optical modulator; and
controlling the bias voltage applied to said external optical modulator so that the amount of second order distortion detected in said distortion detecting step agrees with a previously-stored reference value.
10. The bias voltage control method according to claim 9, wherein said bias voltage control step includes a step of
storing the amount of second order distortion detected in said distortion detecting step as said reference value in an initial state in which the bias voltage is applied to said external optical modulator so as to minimize the amount of second order distortion included in an optical signal outputted from said first port and caused by non-linearity of said external optical modulator.