초록 ▼

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

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.

대표청구항 ▼

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 beyo

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; anda 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/cm2. 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; anda 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/cm2. 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; anda 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; anda 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.