Method and apparatus for determining hemocompatibility
Provided herein are techniques for screening materials for hemocompatibility. Hemocompatible materials may be advantageous when incorporated into devices that may come into direct contact with blood or other bodily fluids. Such techniques take advantage of conformational changes in fibrinogen when adsorbed onto certain materials. As a result of conformational changes, the fibrinogen has altered responsiveness to cleavage by thrombin. Accordingly, the products of thrombin cleavage of fibrinogen may be assessed to determine the hemocompatibility of a material.
1. A method of screening a candidate material for hemocompatibility comprising:
(1) contacting a candidate material with fibrinogen;
(2) contacting the candidate material from step (1) with thrombin;
(3) determining a presence or level of a fibrinogen cleavage product from step (2); and
determining if the candidate material is hemocompatible based on the presence or level of the fibrinogen cleavage product.
2. The method of claim 1 , wherein the fibrinogen cleavage product comprises fibrinopeptide A.
3. The method of claim 1 , wherein the fibrinogen cleavage product comprises fibrinopeptide B.
4. The method of claim 1 , wherein determining the presence or level of the fibrinogen cleavage product comprises using an antibody specific for the fibrinogen cleavage product.
5. The method of claim 1 , wherein determining the presence or level of the fibrinogen cleavage product comprises performing an enzyme-linked immunosorbent assay.
6. The method of claim 1 , comprising removing a liquid sample from a receptacle containing the candidate material.
7. The method of claim 6 , wherein determining the presence or level of the fibrinogen cleavage product comprises contacting the liquid sample with an antibody specific for the fibrinogen cleavage product.
8. The method of claim 6 , wherein determining the presence or level of the fibrinogen cleavage product comprises performing an enzyme-linked immunosorbent assay.
9. A method of screening a candidate material a material for hemocompatibility comprising:
(1) adsorbing fibrinogen with a candidate material;
(2) cleaving the fibrinogen from step (1) with thrombin to yield a fibrinogen cleavage product;
determining a presence or level of conformational change in fibrinogen based on a presence or level of the fibrinogen cleavage product from step (2); and
(4) determining if the candidate material is hemocompatible based on the presence or level of conformational change in fibrinogen.
10. The method of claim 9 , wherein the fibrinogen cleavage product comprises fibrinopeptide A.
11. The method of claim 9 , wherein the fibrinogen cleavage product comprises fibrinopeptide B.
12. The method of claim 9 , comprising the additional steps of binding the fibrinogen cleavage product with a signal generator and detecting the signal emitted by the signal generator, wherein the signal generator is associated with a primary or secondary antibody.
13. A high-throughput screening method for hemocompatiblity comprising:
(1) contacting a plurality of candidate materials with fibrinogen;
(2) contacting the plurality of candidate materials from step (1) with thrombin;
(3) determining a presence or level of a fibrinogen cleavage product for each of the plurality of candidate materials from step (2); and
(4) which of the plurality of candidate materials are hemocompatible based on the presence or level of the fibrinogen cleavage product.
14. The method of claim 13 , wherein the fibrinogen cleavage product comprises fibrinopeptide A.
15. The method of claim 13 , wherein the fibrinogen cleavage product comprises fibrinopeptide B.
16. The method of claim 13 , wherein determining the presence or level of the fibrinogen cleavage product comprises performing an enzyme-linked immunosorbent assay.
17. The method of claim 13 , comprising removing a respective liquid sample from a plurality of receptacles each containing a respective candidate material.
18. The method of claim 17 , wherein determining a presence or level of a fibrinogen cleavage product comprises performing an enzyme-linked immunosorbent assay on each liquid sample.
19. The method of claim 13 , wherein the plurality of candidate materials comprises at least 100 materials.
20. A method of making a hemocompatibility medical device comprising:
providing a hemocompatible material, wherein the hemocompatible material is identified by:
(1) contacting a candidate material with fibrinogen;
(2) contacting the candidate material from step (1) with thrombin;
(3) determining a presence or level of a fibrinogen cleavage product from step (2);
and determining if the candidate material is hemocompatible based on the presence or level of the fibrinogen cleavage product; and
(4) forming a medical device from the hemocompatible material identified in step (3).