1. In a drill string that extends along an axis from an uphole direction to a downhole direction, a torque converter comprising:
upper and lower cylindrical string parts, each comprising an uphole end and a downhole end;
helical spring elements operatively connecting the downhole end of the upper cylindrical string part to the uphole end of the lower cylindrical string part;
wherein the helical spring elements limit otherwise free relative axial and counter-rotational movement of the upper and lower cylindrical string parts with respect to each other;
wherein relative counter-rotational movement of the upper and lower cylindrical parts in a first direction causes the helical spring elements to contract along the axis, and thus move the lower cylindrical string part in the uphole direction;
wherein relative counter-rotational movement of the upper and lower cylindrical parts in a second, opposite direction causes the helical spring elements to expand along the axis, and thus move the lower cylindrical string part in the downhole direction; and
wherein a predetermined amount of torque applied to the drill string during drill string operation causes relative counter-rotational movement of the upper and lower cylindrical parts in the first direction and thus results in movement of the lower cylindrical string part in the uphole direction.
2. The torque converter according to claim 1, comprising at least one guide element disposed between the upper and lower cylindrical string parts.
3. The torque converter according to claim 1, comprising at least one seal disposed between the upper and lower cylindrical string parts.
4. The torque converter according to claim 1, comprising a drill string having a downhole end and a drill bit operably connected to the downhole end, and wherein the torque converter is incorporated into a drill string such that relative rotation movement of the upper and lower cylindrical parts causes the drill bit to retract in the uphole direction away from a drilling surface.
5. A method of operating the torque converter of claim 4 comprising the step of operating the drill string until a predetermined amount of torque is applied to the helical spring elements to thus retract the drill bit in the uphole direction away form the drilling device.
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. A device for monitoring leukocyte migration including a housing defining:
a plurality of chambers therein, each of the plurality of chambers including:
a first well region including at least one first well;
a second well region including at least one second well; and
a channel region including at least one channel connecting the first well region and the second well region with one another, the at least one channel including at least one leukocyte migration mediator, or endothelial cells disposed therein,
wherein at least one of the plurality of chambers on the one hand, and the first well regions and the second well regions of respective ones of the plurality of chambers on the other hand, are disposed relative to one another to match a pitch of a standard microtiter plate.
2. The device of claim 1, wherein the at least one leukocyte migration mediator comprises a leukocyte capture mediator, a leukocyte rolling mediator, a leukocyte arrest mediator, a leukocyte transmigration mediator, or any combination thereof.
3. The device of claim 2, wherein the leukocyte capture mediator is a selectin or a selectin-binding ligand.
4. The device of claim 2, wherein the leukocyte rolling mediator is a selectin or a selectin binding ligand.
5. The device of claim 2, wherein the leukocyte arrest mediator is an integrin binding ligand.
6. The device of claim 2, wherein the leukocyte transmigration mediator is PECAM-1 or JAM.
7. The device of claim 1, wherein the at least one leukocyte migration mediator comprises a first leukocyte migration mediator and a second leukocyte migration mediator, the first leukocyte migration mediator and the second leukocyte migration mediator being different from one another.
8. The device of claim 7, wherein the first leukocyte migration mediator comprises a leukocyte rolling mediator and the second leukocyte migration mediator comprises a leukocyte arrest mediator.
9. The device of claim 1, further comprising a chemokine disposed in the at least one channel.
10. The device of claim 1, wherein the housing comprises:
a support member; and
a top member mounted to the support member,
wherein the support member and the top member are configured such that they together define the plurality of chambers.
11. The device of claim 10, wherein the top member is in conformal contact with the support member.
12. The device of claim 1, wherein at least one of the plurality of chambers on the one hand, and the first well regions and the second well regions of respective ones of the plurality of chambers, on the other hand are disposed relative to one another to match a pitch of a 24-well microtiter plate, a 96-well microtiter plate, a 384-well microtiter plate, a 768-well microtiter plate or a 1536-well microtiter plate.
13. The device of claim 1, wherein the at least one channel comprises a plurality of rectilinear, parallel channels.
14. The device of claim 1, wherein the second well region is horizontally offset with respect to the first well region in a test orientation of the device.
15. The device of claim 1, wherein the channel region is configured for supporting physiological shear flow therealong.
16. The device of claim 15, wherein the channel region is configured for supporting physiological shear flow by hydrostatic pressure.
17. A system comprising the device of claim 1, further comprising a video camera operatively linked to the device for viewing the at least one channel.
18. A kit for monitoring leukocyte migration comprising:
a device including a housing defining a plurality of chambers therein, each of the plurality of chambers including:
a first well region including at least one first well;
a second well region including at least one second well; and
a channel region including at least one channel connecting the first well region and the second well region with one another,
wherein at least one of the plurality of chambers on the one hand, and the first well regions and the second well regions of the respective ones of the plurality of chambers on the other hand, are disposed relative to one another to match a pitch of a standard microtiter plate; and a first leukocyte migration mediator or endothelial cells.
19. The kit of claim 18, further comprising an inhibitor or promoter of leukocyte migration.
20. The kit of claim 18, further comprising a second leukocyte migration mediator, wherein the first leukocyte migration mediator and the second leukocyte migration mediator are different from one another.
21. A device for monitoring leukocyte migration comprising:
a housing;
means associated with the housing for defining a plurality of chambers in the housing, each of the plurality of chambers including:
an inlet means for receiving a sample comprising leukocytes;
an outlet means in flow communication with the inlet means for receiving the sample comprising leukocytes from the inlet means; and
connection means connecting the inlet means and the outlet means to one another, the connection means including at least one leukocyte migration mediator, or endothelial cells disposed therein,
wherein at least one of the plurality of chambers on the one hand, and the inlet means and the outlet means on the other hand, are disposed relative to one another to match a pitch of a standard microtiter plate.
22. The device of claim 21, wherein:
the support means comprises support member;
the means for defining comprises a support member and a top member,
wherein the support member and the top member are configured such that they together define the plurality of chambers.
23. The device of claim 21, wherein:
the inlet means comprises at least one first well; and
the outlet means comprises at least one second well.
24. A method of monitoring leukocyte migration comprising:
providing a device including a housing defining a plurality of chambers therein, each of the plurality of chambers including:
a first well region including at least one first well;
a second well region including at least one second well; and
a channel region including at least one channel connecting the first well region and the second well region with one another, wherein at least one of the plurality of chambers on the one hand, and the first well regions and the second well regions of the respective ones of the plurality of chambers are disposed relative to one another to match a pitch of a standard microtiter plate;
disposing at least one leukocyte migration mediator, or endothelial cells in the at least one channel;
providing a sample comprising leukocytes in the at least one channel; and
observing the interaction between the leukocytes and the at least one leukocyte migration mediator or the interaction between the leukocytes and the endothelial cells.
25. The method of claim 24, wherein the at least one leukocyte migration mediator comprises a leukocyte capture mediator, a leukocyte rolling mediator, a leukocyte arrest mediator, a leukocyte transmigration mediator or any combination thereof.
26. The method of claim 25, wherein the leukocyte capture mediator is a selectin or selectin binding ligand.
27. The method of claim 25, wherein the leukocyte rolling mediator is a selectin or selectin binding ligand.
28. The method of claim 25, wherein the leukocyte arrest mediator is an integrin binding ligand.
29. The method of claim 24, wherein the at least one leukocyte migration mediator comprise a first leukocyte migration mediator and a second leukocyte migration mediator, the first leukocyte migration mediator and second leukocyte migration mediators being different from one another.
30. The method of claim 29, wherein the first leukocyte migration mediator comprises a leukocyte rolling mediator and the second leukocyte migration mediator comprises a leukocyte arrest mediator.
31. The method of claim 29, further comprising adding at least one inhibitor adapted to inhibit the first leukocyte migration mediator, the second leukocyte migration mediator, or both.
32. The method of claim 29, further comprising adding at least one promoter adapted to promote leukocyte migration mediated by the first leukocyte migration mediator, the second leukocyte migration mediator, or both.
33. The method of claim 24, further comprising adding a test agent to the sample comprising leukocytes.
34. The method of claim 33, wherein the test agent comprises an inhibitor of leukocyte migration or a promoter of migration.
35. The method of claim 24, wherein the housing comprises:
a support member; and
a top member mounted to the support member, wherein the support member and the top member are configured such that they together define the plurality of chambers.
36. The method of claim 24, further comprising providing physiological shear flow along the longitudinal axis of the at least one channel.
37. The method of claim 36, wherein the shear flow is provided by hydrostatic pressure.
38. The method of claim 36, wherein the shear flow has a velocity in the range between about 0.1 dynescm2 to about 20 dynescm2.
39. The method of claim 24, further comprising providing a video camera operatively linked to the device for viewing the at least one channel.
40. The method of claim 24, wherein the video camera is adapted to capture an image during predetermined intervals over a predetermined period of time.
41. The method of claim 24, further comprising determining a rolling velocity of leukocytes.
42. The method of claim 24, wherein the sample of leukocytes are in about 10 microliters to about 100 microliters of media.
43. The method of claim 24, wherein the number of leukocytes in the sample comprising leukocytes is in the range of about 103 to about 106.
44. A method of simulating physiological conditions of a blood vessel in vivo comprising:
providing a device comprising a housing defining a chamber, the chamber including:
a first well region including at least one first well;
a second well region including at least one second well; and
a channel region including at least one channel connecting the first well region and the second well region with one another;
placing a first leukocyte migration mediator adapted to mediate a rolling of a leukocyte in the at least one channel;
placing a second leukocyte migration mediator adapted to an arrest of a leukocyte in the at least one channel;
providing a suspension comprising leukocytes in about 10 microliters to about 100 microliters of media in the at least one channel; and
allowing the suspension comprising leukocytes to flow along the at least one channel.
45. The method of claim 44, wherein the first leukocyte migration mediator is a leukocyte rolling mediator and the second leukocyte migration mediator is a leukocyte arrest mediator.
46. The method of claim 44, wherein the leukocytes flow along the at least one channel under hydrostatic pressure.
47. A method of screening test agents comprising:
providing a device comprising a housing defining a plurality of chambers, each chamber including:
a first well region including at least one first well;
a second well region including at least one second well; and
a channel region including at least one channel connecting the first well region and the second well region with one another, the at least one channel including at least one leukocyte migration mediator, or endothelial cells disposed therein, the first well regions and the second well regions of respective ones of the plurality of chambers are disposed relative to one another to match a pitch of a standard microtiter plate;
providing leukocytes in each of the first well regions of respective ones of the plurality of chambers;
placing at least one of a plurality of test agents in each of the first well regions of respective ones of the plurality of chambers;
observing the interaction between the leukocytes and the at least one leukocyte migration mediator in the presence of the least one of a plurality of test agents.
48. A device for monitoring leukocyte migration including a housing comprising:
a support member; and
a top member, the top member mounted to the support member by being placed in conformal contact with the support member, wherein the support member and the top member are configured such that they together define at least one chamber, the at least one chamber including:
a first well region including at least one first well;
a second well region including at least one second well; and
a channel region including at least one channel connecting the first well region and the second well region with one another, the at least one channel including at least one leukocyte migration mediator disposed therein.
49. The device of claim 48, wherein the at least one chamber includes a plurality of chambers.