1. A method for generating coated, gas-filled albumin microbubbles for use in affinity isolation or affinity assay comprising:
(a) heating a solution of albumin;
(b) sonicating the heated solution from step (a) to introduce gas into the solution wherein the solution does not contain any andehyde or Cr+++, thereby generating albumin microbubbles that have not been stabilized by crosslinking the albumin with an aldehyde or by treatment with Cr+++;
(c) suspending the albumin microbubbles from step (b) in a buffered solution comprising polyvinyl alcohol; and
(d) coating the microbubbles from step (c) with an affinity molecule.
2. A method for generating affinity-modified gas-filled protein microbubbles for use in affinity isolation or affinity assay comprising:
(a) providing a protein in a solution, wherein the protein is coupled to an affinity molecule;
(b) heating the solution of protein from step (a);
(c) sonicating the heated solution from step (b) to introduce gas into the solution wherein the solution does not contain any andehyde or Cr+++, thereby generating affinity-modified protein microbubbles, wherein the protein microbubbles are not stabilized by fixing by crosslinking the protein with an aldehyde or by treatment with Cr+++; and
(d) suspending the affinity-modified protein microbubbles from step (c) in a buffered solution comprising polyvinyl alcohol.
3. A method for generating coated gas-filled microbubbles for use in affinity isolation or affinity assay comprising:
(a) heating a solution of protein;
(b) sonicating the heated solution from step (a) to introduce gas into the solution to generate protein microbubbles, wherein the protein microbubbles are not stabilized by crosslinking the protein with an aldehyde or by treatment with Cr+++;
(c) suspending the protein microbubbles from step (b) in a buffered solution comprising polyvinyl alcohol; and
(d) coating the microbubbles from step (c) with an affinity molecule.
4. The method of any one of claim 1, 2 or 3, wherein the affinity molecule is selected from the group consisting of a receptor, a ligand, a nucleic acid and an antibody.
5. The method of claim 3, wherein the affinity molecule is biotin.
6. The method of claim 3, wherein the affinity molecule is avidin or streptavidin.
7. The method of any one of claim 1, 2 or 3, wherein the coating comprises covalently coupling the affinity molecule to an amine group on the microbubble.
8. The method of claim 3, wherein the coating comprises covalently coupling the affinity molecule to an epoxy group on the microbubble.
9. The method of any one of claim 1, 2 or 3, wherein the coating comprises coupling the affinity molecule to the microbubble through a heterobifunctional reagent.
10. The method of claim 9 wherein the method further comprises treating microbubbles with the heterobifunctional reagent sulfosuccinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (s-SMCC)) to form s-SMCC microbubbles.
11. The method of claim 10 wherein the method further comprises treating the affinity molecule with n-succinimidyl S-acetylthioacetate (SATA), and the protective acetyl group is removed just prior to reaction with s-SMCC microbubbles.
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. A method of obtaining a fluid sample from an underground formation traversed by a borehole, method comprising:
lowering a tool into the borehole, the tool including at least one perforation mechanism disposed through a sidewall of the tool, and at least one port fluidly connected to a sample container;
creating a first hole through a borehole wall into the formation with the at least one perforation mechanism;
increasing a mobility of formation fluid, wherein the formation fluid is disposed between the borehole wall and the first hole; and obtaining a sample of fluid from the formation, wherein at least one of increasing and obtaining is performed utilizing the first hole.
2. A method according to claim 1, wherein both increasing and obtaining are performed utilizing the first hole.
3. A method according to claim 1, wherein creating the first hole includes drilling the first hole in the borehole wall with a drill bit.
4. A method according to claim 1, wherein increasing the mobility includes engaging at least one of a packer and a pad against the borehole wall.
5. A method according to claim 4, further including heating at least one of the packer and the pad thereby increasing the mobility of the formation.
6. (canceled)
7. A method according to claim 1, wherein increasing the mobility includes activating a heating element disposed in the tool.
8. A method according to claim 1, wherein increasing the mobility includes injecting a fluid into the formation.
9. (canceled)
10. (canceled)
11. A method according to claim 8, further comprising mixing at least two fluids downhole.
12. A method according to claim 1, wherein increasing the mobility includes extending a pipe into the first hole.
13. A method according to claim 12, further comprising heating the pipe.
14. (canceled)
15. A method according to claim 1, further comprising creating a second hole through the borehole wall into the formation.
16. A method according to claim 15, wherein obtaining the sample is performed through utilizing the second hole.
17. A method according to claim 1, further comprising analyzing the sample in the borehole tool.
18. A method according to claim 1, wherein increasing a mobility of the formation fluid includes at least one of generating an acoustic wave, generating electromagnetic radiation, creating an exothermic reaction, and creating in-situ combustion.
19. (canceled)
20. An apparatus for obtaining a sample of formation fluid from a hydrocarbon reservoir traversed by a borehole, apparatus comprising:
at least a first perforation mechanism disposed on a sidewall of a downhole tool, for creating a first hole through a borehole wall into the formation;
a heat source at least partially disposed in the downhole tool, the heat source being adapted for heating a portion of the formation for enhancing the mobility of formation fluid located adjacent the first hole; and
at least one sampling port disposed on a sidewall of the downhole tool, the sampling port being fluidly connected to a container disposed in the downhole tool.
21. An apparatus according to claim 20, wherein the perforation mechanism includes at least one of a drilling mechanism and a perforation gun.
22. (canceled)
23. An apparatus according to claim 20, wherein the heat source includes at least one of a resistive heating element, hot fluid, hot solvent, six induction coil, an exothermic reaction, in-situ combustion and an acoustic wave.
24. An apparatus according to claim 20, further including a sealing element adapted to engage the borehole wall, wherein at least a portion of the sealing element surrounds the sampling port.
25. (canceled)
26. (canceled)
27. An apparatus according to claim 20, further including a second sampling port fluidly connected to a pump, wherein the second port is adapted to receive contaminated formation fluid.
28. An apparatus according to claim 20, wherein at least a portion of the heat source is extendable into the first hole.
29. A system for obtaining a sample of formation fluid from a hydrocarbon reservoir traversed by a borehole, system comprising:
at least one perforation mechanism disposed on a sidewall of a downhole tool, for creating a first hole through a borehole wall into the formation;
an injection port disposed on a sidewall of the downhole tool; the injection port being adapted to inject fluid into the formation for enhancing the mobility of formation fluid located adjacent the first hole; and
a sampling port disposed on a sidewall of the downhole tool, the sampling port being fluidly connected to a container disposed in the downhole tool.
30. An apparatus according to claim 29, wherein one of the at least one perforation mechanism and a second perforation mechanism creates a second hole in the formation hole, wherein the injection port injects fluid into the first hole and the sampling port samples the formation fluid from the second hole.
31. An apparatus according to claim 29, wherein the injection port is fluidly connected to a tank located on the surface.
32. An apparatus according to claim 29, wherein the injection fluid is at least one of air and oxygen for creating an in-situ combustion.
33. A method of obtaining a fluid sample from an underground formation traversed by a borehole, method comprising:
lowering a tool into the borehole, the tool including at least one perforation mechanism disposed through a sidewall of the tool, and at least one port fluidly connected to a sample container;
creating a first hole through a borehole wall into the formation with the at least one perforation mechanism;
creating a second hole through the borehole wall into the formation;
increasing a mobility of formation fluid, wherein the fonnafion fluid is disposed between the first and the second hole; and
obtaining a sample of fluid from the formation, wherein at least one of increasing and obtaining is performed utilizing the first hole.
34. (canceled)