High-throughput biological screening
A high-throughput flow system includes an array of wells and a separate mechanical tip positioned within each well. Each mechanical tip is separately actuated to impart a shear stress pattern. A separate sleeve may be associated with each tip for maintaining a predetermined distance between the tip and a floor of the tip's corresponding well, with each tip being rotatable within its corresponding sleeve. Alternatively, a separate post may be associated with each tip for maintaining a predetermined distance between the tip and a floor of the tip's corresponding well, with each tip being rotatable about its corresponding post.
1. A high-throughput flow apparatus for use with an array of wells, the apparatus comprising:
an array of mechanical tips each corresponding to one of the wells;
an interface for positioning each tip within its corresponding well;
a separate sleeve mechanically coupled with each tip and extending beyond a distal end thereof, each sleeve thereby being adapted to contact a floor of its corresponding well and to maintain a predetermined distance between its tip and the floor of a testing chamber, wherein the testing chamber is defined by a volume captured within an inner diameter of the sleeve, each tip rotatable within its corresponding sleeve; and
a driver associated with a tip for driving the tip within its respective separate sleeve to impart a shear stress pattern in its corresponding testing chamber.
2. The apparatus of claim 1 , wherein the shear stress pattern mimics a physiological hemodynamic waveform present in the circulatory system of an organism.
3. The apparatus of claim 2 , wherein the physiological hemodynamic waveform comprises at least one of an atheroprotective waveform, an atheroprone waveform, or a waveform that increases stem cell differentiation.
4. The apparatus of claim 2 , wherein the organism is at least one of a human or a mouse.
5. The apparatus of claim 1 , wherein the shear stress pattern comprises at least one of a steady shear stress pattern or an oscillatory shear stress pattern.
6. The apparatus of claim 1 , wherein the shear stress pattern comprises temporal and spatial variations.
7. The apparatus of claim 1 , wherein the shear stress pattern has a magnitude of up to 35 dynes/cm 2 .
8. The apparatus of claim 1 , wherein each tip does not contact a surface of its corresponding well.
9. The apparatus of claim 1 , wherein each of the wells comprises a feature interfacing with a complementary feature of the corresponding mechanical tip for maintaining radial alignment between the tip and an interior wall of the well.
10. The apparatus of claim 1 , wherein a bottom surface of each tip has a flat center and an overall conical shape.
11. The apparatus of claim 1 , wherein the driver comprises a variable-speed precision motor.
12. The apparatus of claim 11 , wherein the variable-speed precision motor is a stepper motor.
13. The apparatus of claim 1 further comprising a carbon dioxide source for regulating a level of carbon dioxide in an environment surrounding the well array.
14. The apparatus of claim 1 further comprising a temperature-controlled fluid bath for the well array.
15. The apparatus of claim 14 further comprising a heater for controlling the temperature of the fluid bath.
16. The apparatus of claim 14 , wherein the fluid bath is maintained at a temperature of approximately 37° C.
17. The apparatus of claim 1 wherein the wells are arranged on a standard microtiter plate or cell culture plate.
18. The apparatus of claim 1 , wherein the driver is associated with at least two tips.
19. The apparatus of claim 1 , wherein a separate driver is associated with each tip.
20. A high-throughput flow apparatus for use with an array of wells, the apparatus comprising:
an array of mechanical tips each corresponding to one of the wells;
an interface for positioning each tip within its corresponding well;
a separate post mechanically coupled with each tip and extending beyond a distal end thereof, each post thereby being adapted to contact a floor of its corresponding well and to maintain a predetermined distance between its tip and the floor of the well, each tip driven independently of its corresponding post; and
a driver associated with a tip for driving the tip around its respective separate post to impart a shear stress pattern in its corresponding well.
21. The apparatus of claim 20 , wherein the shear stress pattern mimics a physiological hemodynamic waveform present in the circulatory system of an organism.
22. The apparatus of claim 21 , wherein the physiological hemodynamic waveform comprises at least one of an atheroprotective waveform, an atheroprone waveform, or a waveform that increases stem cell differentiation.
23. The apparatus of claim 21 , wherein the organism is at least one of a human or a mouse.
24. The apparatus of claim 20 , wherein the shear stress pattern comprises at least one of a steady shear stress pattern or an oscillatory shear stress pattern.
25. The apparatus of claim 20 , wherein the shear stress pattern comprises temporal and spatial variations.
26. The apparatus of claim 20 , wherein the shear stress pattern has a magnitude of up to 35 dynes/cm 2 .
27. The apparatus of claim 20 , wherein each tip does not contact a surface of its corresponding well.
28. The apparatus of claim 20 , wherein each of the wells comprises a feature interfacing with a complementary feature of the corresponding mechanical tip for maintaining radial alignment between the tip and an interior wall of the well.
29. The apparatus of claim 20 , wherein a bottom surface of each tip has a flat center and an overall conical shape.
30. The apparatus of claim 20 , wherein the driver comprises a variable-speed precision motor.
31. The apparatus of claim 29 , wherein the variable-speed precision motor is a stepper motor.
32. The apparatus of claim 20 further comprising a carbon dioxide source for regulating a level of carbon dioxide in an environment surrounding the well array.
33. The apparatus of claim 20 further comprising a temperature-controlled fluid bath for the well array.
34. The apparatus of claim 33 further comprising a heater for controlling the temperature of the fluid bath.
35. The apparatus of claim 33 , wherein the fluid bath is maintained at a temperature of approximately 37° C.
36. The apparatus of claim 20 wherein the wells are arranged on a standard microtiter plate or cell culture plate.
37. The apparatus of claim 20 , wherein the driver is associated with at least two tips.
38. The apparatus of claim 20 , wherein a separate driver is associated with each tip.
39. A high-throughput flow apparatus for use with an array of wells, the apparatus comprising:
an array of mechanical tips each corresponding to one of the wells;
an interface for positioning each tip within its corresponding well;
a separate sleeve associated with each tip and extending a predetermined distance beyond a distal end thereof, each sleeve thereby being adapted to contact a floor of its corresponding well and to maintain the predetermined distance between its tip and the floor of a testing chamber, wherein the testing chamber is defined by a volume captured within an inner diameter of the sleeve, each tip rotatable within its corresponding sleeve; and
a driver associated a tip for driving the tip within its respective separate sleeve to impart a shear stress pattern in its testing chamber.
40. The apparatus of claim 39 , wherein the separate sleeve is mechanically coupled to its respective tip.
41. The apparatus of claim 39 , wherein a bottom surface of each tip has a flat center and an overall conical shape.
42. The apparatus of claim 39 , wherein a separate driver is associated with each tip.
43. A high-throughput flow apparatus for use with an array of wells, the apparatus comprising:
an array of mechanical tips each corresponding to one of the wells;
an interface for positioning each tip within its corresponding well;
a separate post associated with each tip and extending a predetermined distance beyond a distal end thereof, each post thereby being adapted to contact a floor of its corresponding well and to maintain the predetermined distance between its tip and the floor of the well, each tip driven independently of its corresponding post; and
a driver associated a tip for driving the tip around its respective separate post to impart a shear stress pattern in its corresponding well.
44. The apparatus of claim 43 , wherein the separate post is mechanically coupled to its respective tip.
45. The apparatus of claim 43 , wherein a bottom surface of each tip has a flat center and an overall conical shape.
46. The apparatus of claim 43 , wherein a separate driver is associated with each tip.