IP Library › Granted Patent US 10,174,280
Granted Patent B2
US 10,174,280 · App. 13/858,890 · Granted Jan 8, 2019

Apparatus, system, and method providing fluid flow for cell growth

Inventors: Thomas N. Corso (Groton, NY); Colleen K. Van Pelt (Groton, NY)
Assignee: CorSolutions LLC
C12M41/48C12M41/00
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Quick Facts
Patent No.
US 10,174,280
App. No.
13/858,890
Granted
Jan 8, 2019
Kind
B2
Abstract

An apparatus, system and method providing a fluid flow suitable to grow and maintain living cells in the fluid flow are disclosed. The apparatus includes a fluid displacement apparatus capable of providing at least one of positive and negative displacement of the fluid and configured to indirectly displace the fluid, an in-line flow sensor configured to directly measure the fluid flow, and a feed-back control in communication with the fluid displacement apparatus and the in-line flow sensor, wherein the feed-back control is configured to continuously control the fluid flow in response to the flow sensor measurements.

Claims (34)

1. A method for providing a fluid flow, comprising:

providing a fluid source in a fluidic system;

providing a peristaltic or pneumatic pump apparatus capable of providing at least one of positive and negative displacement of the fluid and configured to indirectly displace the fluid to establish a fluid flow within the system;

providing a flow-through in-line flow sensor configured to directly measure the fluid flow;

providing a feed-back control, comprising a process signal speed faster than about 1 second, in communication with the pump apparatus and the in-line flow sensor, wherein the feed-back control is capable of achieving a fluid flow rate in the range of from about 1 microliters/minute to about 20 milliliters/minute and control the fluid flow in response to the flow sensor measurements;

establishing a desired fluid flow rate through the fluidic system by adjusting the pump apparatus in response to the feed-back control in a manner to maintain the fluid flow at a constant velocity with pulsing less than from about 0.01% to about 20% of the set point for the desired fluid flow rate;

exposing living cells directly in the path of the fluid flow; and

maintaining the desired fluid flow rate to a value suitable to grow and maintain the living cells directly in the path of the fluid flow while preventing exceeding said pulsing by operation of the feed-back control.

2. The method of claim 1 , wherein the fluid flow has a shear stress value between about 0.01 dynes/cm 2 and about 60 dynes/cm 2 .

3. The method of claim 1 , wherein the fluid comprises growth media.

4. The method of claim 1 , wherein establishing a desired fluid flow rate through the fluidic system by adjusting the pump apparatus in response to the feed-back control further comprises generating a system backpressure with the use of a pulse dampener or flow restrictor.

5. The method of claim 1 , wherein the fluid flow rate is maintained by changing the fluid velocity at a rate of from about 0.01 to about 10 dynes per millisecond.

6. The method of claim 1 , wherein the system comprises conduits having an effective circumference ranging from about 6 microns to about 2 centimeters.

7. The method of claim 1 , wherein the fluid flow has flow profile ranging from about 0.2 Hz to about 10 Hz.

8. The method of claim 1 , further comprising collecting a sample of the fluid without disrupting the fluid flow rate following the exposing living cells to the fluid flow.

9. The method of claim 1 , further comprising adjusting the temperature of the fluid following the providing a fluid source.

10. The method of claim 1 , further comprising removing bubbles from the fluid without disrupting the fluid flow rate following the establishing a desired fluid flow rate.

11. The method of claim 1 , wherein the system is capable of maintaining the fluid flow rate and keeping the cells alive for longer than about 12 hours.

12. The method of claim 1 , further comprising selectively trapping bubbles from the fluid without disrupting the fluid flow rate following the establishing the desired fluid flow rate.

13. The method of claim 1 , where the fluid comprises a gas composition having a concentration of at least one of CO 2 , O 2 , and N, further comprising controlling the concentration.

14. The method of claim 1 , where the fluid pH is buffered.

15. The method of claim 1 , wherein the flow sensor is a thermal sensor in contact with an exterior surface of a fluid transporting tube such that the fluid flow avoids direct contact with the sensor.

16. The method of claim 1 , wherein the feed-back control is capable of achieving a fluid flow rate of 0.5 microliters/minute.

17. A method for providing a fluid flow, comprising:

providing a fluid source in a fluidic system;

providing a fluid displacement pump apparatus capable of providing at least one of positive and negative displacement of the fluid and configured to indirectly displace the fluid to establish a fluid flow within the system;

providing a flow-through in-line flow sensor configured to directly measure the fluid flow;

providing a feed-back control, comprising a process signal speed faster than about 1 second, in communication with the apparatus and the in-line flow sensor, wherein the feed-back control is configured to achieve a fluid flow rate in the range of from about 1 microliter/minute to about 20 milliliters/minute and control the fluid flow in response to the flow sensor measurements;

establishing a desired fluid flow rate through the fluidic system by adjusting the fluid displacement apparatus in response to the feed-back control in a manner to maintain the fluid flow at a constant velocity with pulsing less than from about 0.01% to about 20% of the set point for the desired fluid flow rate;

exposing living cells directly in the path of the fluid flow; and

maintaining the desired fluid flow rate to a value suitable to grow and maintain the living cells directly in the path of the fluid flow while preventing exceeding said pulsing by operation of the feed-back control.

18. The method of claim 17 , wherein the pulsing is maintained at less than about 5% of the set point for the desired fluid flow rate.

19. The method of claim 17 , wherein the fluid flow rate set point is in a range of from about 1 microliter/minute to about 1 milliliter/minute.

20. The method of claim 17 , wherein the feed-back control is capable of achieving a fluid flow rate of 0.5 microliters/minute.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 12, 2013
From: VAN PELT, COLLEEN K.; CORSO, THOMAS N.
To: CORSOLUTIONS LLC
Reel/Frame 030596/0705 →
Continuity (2)
Provisional Application 61621279 · Apr 6, 2012
Related Publication 20130266929A1 · Oct 10, 2013
Cited By (1)
US 12,722,122