Method and apparatus for continuous automated perfusion system harvesting from in-situ filtration probe

• US 10,214,716 B2
• Filed: 05/09/2016
• Issued: 02/26/2019
• Est. Priority Date: 05/08/2015
• Status: Active Grant

• Current Assignee: Flownamics Analytical Instruments Incorporated
• Original Assignee: Flownamics Analytical Instruments Incorporated
• Inventors: Biksacky, Michael
• Primary Examiner(s): West, Paul
• Assistant Examiner(s): Shabman, Mark A
• Application Number:
  US15/149,910
• Publication Number:
  US 20160326481A1
• Time in Patent Office: 1,023 Days
• Field of Search: None
• CPC Class Codes: C12M 29/04 Filters; Permeable or porous membranes or plates, e.g. dialysis
• CPC Class Codes: C12M 29/10 Perfusion
• CPC Class Codes: C12M 41/00 Means for regulation, monitoring, measurement or control, e.g. flow regulation controlling or regulating chemical, physical or physicochemical processes B01J19/0006; heating or cooling apparatus for laboratory use B01L7/00; electro optical investigation of individual particles, flow cytometers G01N15/14; automatic analysis G01N35/00; controlling or regulating in general G06N
• CPC Class Codes: G01F 1/708 Measuring the time taken to traverse a fixed distance
• CPC Class Codes: G01F 15/003 using electromagnetic, electric or electronic means G01F15/002, G01F15/02 take precedence
• CPC Class Codes: G01F 15/005 Valves valves in general F16K
• CPC Class Codes: G01F 23/22 by measuring physical variables, other than linear dimensions, pressure or weight, dependent on the level to be measured, e.g. by difference of heat transfer of steam or water involving the use of floats G01F23/30
• CPC Class Codes: G01F 25/10 of flowmeters
• CPC Class Codes: G01P 5/18 by measuring the time taken to traverse a fixed distance

Abstract

An apparatus and method for determining fluid flow (e.g., sterile media flow, filtrate flow, etc.) through tubing is provided. The apparatus includes an air source, a flow valve, a first sensor, a second sensor, and a media tubing section extending between the first sensor and the second sensor. In operation, air from the air source is introduced by the flow valve into a fluid flow to create a lead line of fluid immediately following the introduced air. As the lead line of fluid passes each sensor, the sensors are used to determine a time between when the lead line passes the first sensor and the second sensor and that determined elapsed time is used, along with a determined volume of the media tubing section to determine the rate of flow of the fluid flow.

Claims

1. A method for monitoring flow, the method comprising:

setting an interval during which a pump is run to introduce a flow of sterile media into a reactor;

running the pump to introduce the flow of sterile media into the reactor;

introducing an amount of air into the flow of sterile media flowing into the reactor;

sensing, with a first sensor, a first time when a lead line of the flow of sterile media following the amount of air reaches the first sensor;

sensing, with a second sensor, a second time when the lead line of the flow of sterile media reaches the second sensor;

using the first time and the second time to determine a flow rate for the flow of sterile media; and

adjusting the interval during which the pump is run based on the determined flow rate for the flow of sterile media.

2. The method of claim 1, wherein the first time and second time are used to determine a flow rate for the flow of sterile media in the tubing by determining an elapsed time between the first time and the second time and comparing a volume of flow of sterile media in the tubing between the first sensor and the second sensor relative to the elapsed time.

3. The method of claim 2, wherein the volume of flow of sterile media is determined from an interior volume of tubing extending between the first sensor and the second sensor.

4. The method of claim 1, wherein the amount of air is introduced into the flow of sterile media through a dual pinch valve.

5. A method for monitoring flow, the method comprising:

running a pump to provide a media flow from a reactor into a tubing;

introducing an amount of air into the media flow;

sensing, with a first sensor, a first time when a lead line of the media flow in the tubing following the amount of air reaches the first sensor;

sensing, with a second sensor, a second time when the lead line of the media flow in the tubing reaches the second sensor;

using the first time and the second time to determine a flow rate for the media flow; and

calibrating, recalibrating or controlling the pump based on the determined flow rate for the media flow from the reactor into tubing and a predefined flow rate of media flow from the reactor into tubing.

6. The method of claim 5, further comprising calibrating, recalibrating or controlling the pump to adjust or compensate when the determined flow rate is less than the predefined flow rate.

7. The method of claim 5, wherein the calibration, recalibration, or control of the pump comprises adjusting an interval during which the pump is run to provide the media flow from the reactor into the tubing.

8. The method of claim 5, further comprising setting a pump interval during which the pump runs to create the media flow from the reactor into the tubing and adjusting the pump interval based on the determined flow rate to obtain a desired volume of media flow from the reactor.

9. A method for monitoring flow, the method comprising:

introducing an amount of air into a fluid flow;

sensing, with a first sensor, a first time when a lead line of the fluid flow following the amount of air reaches the first sensor;

sensing, with a second sensor, a second time when the lead line of the fluid flow reaches the second sensor; and

using the first time and the second time to determine a flow rate for the fluid flow;

introducing an amount of air into a filtrate flow in filtrate tubing running from the reactor;

sensing, with a third sensor, a third time when a lead line of the filtrate flow following the amount of air introduced in the filtrate tubing in reaches the third sensor;

sensing, with a fourth sensor, a fourth time when the lead line of the filtrate flow following the amount of air introduced in the filtrate tubing in reaches the fourth sensor; and

using the third time and the fourth time to determine a flow rate for the filtrate flow in the filtrate tubing.

10. The method of claim 9, further comprising adjusting the flow rate for the fluid flow to be closer to a predetermined flow rate of fluid flow.

11. The method of claim 10, further comprising adjusting the flow rate for the filtrate flow to be closer to a predetermined flow rate of fluid flow.

12. The method of claim 9, further comprising adjusting the flow rate for the filtrate flow to be closer to a predetermined flow rate of fluid flow.