Hybrid linear actuator controlled hydraulic cell stretching

• US 10,640,742 B2
• Filed: 09/25/2015
• Issued: 05/05/2020
• Est. Priority Date: 09/25/2014
• Status: Active Grant

• Current Assignee: Board of Supervisors of Louisiana State University and Agricultural and Mechanical College, Board of Supervisors of Louisiana State University Agricultural & Mechanical College (Louisiana State University System)
• Original Assignee: Board of Supervisors of Louisiana State University Agricultural & Mechanical College (Louisiana State University System)
• Inventors: McCarthy, Kevin John, Wassenhove-McCarthy, Deborah Jane
• Primary Examiner(s): Hurst, Jonathan M
• Application Number:
  US14/865,464
• Publication Number:
  US 20160089673A1
• Time in Patent Office: 1,684 Days
• CPC Class Codes: C12M 23/12 Well or multiwell plates C12M25/04 takes precedence
• CPC Class Codes: C12M 23/16 Microfluidic devices; Capillary tubes integrated microfluidic structures B01L3/5027; microreactors B01J19/0093
• CPC Class Codes: C12M 25/04 in combination with well or multiwell plates, i.e. culture inserts
• CPC Class Codes: C12M 35/04 Mechanical means, e.g. sonic waves, stretching forces, pressure or shear stimuli
• CPC Class Codes: C12M 41/48 Automatic or computerized control automatic analysis G01N35/00
• CPC Class Codes: C12M 43/00 Combinations of bioreactors or fermenters with other apparatus
• CPC Class Codes: C12M 47/00 Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass filters in general B01D24/00 - B01D41/00

Abstract

A hydraulic cell stretching device comprising a source of variable pressured hydraulic fluid hydraulically coupled to a flexing chamber. The flexing chamber has at least one cell well. The cell well has a membrane subjected to the variable pressured hydraulic fluid.

Claims

1. A hydraulic cell stretching device comprising:

a source of variable pressured hydraulic fluid hydraulically coupled to a flexing chamber;

the flexing chamber having at least one cell well;

the at least one cell well having a membrane subjected to the variable pressured hydraulic fluid, wherein the membrane carries a cell culture to be subjected to cell stretching;

each cell well having multiple hydraulic openings to allow hydraulic fluid into or out of each of the at least one cell well;

a hydraulic circuit including a fluid delivery path leading to the at least one cell well and a separate fluid return path leading from the at least one cell well;

one of a one-way check valve and a gate valve positioned along the fluid delivery path;

one of another one-way check valve and another gate valve positioned along the fluid return path;

wherein a plurality of cell wells are positioned in a single baseplate;

wherein a first column of the plurality of wells are fluidically connected to one another and experience a first hydraulic pressure from a first independently operated drive module; and

wherein a second column of the plurality of cell wells are fluidically connected to one another but are fluidically separate from the cell wells of the first column and wherein the second column of the plurality of cell wells simultaneously experience a second hydraulic pressure from a second independently operated drive module distinct from the first independently operated drive module at the same time as the first column of the plurality of cell wells experiences the first hydraulic pressure.

2. The device of claim 1 wherein the source of source of variable pressured hydraulic fluid includes a linear actuator coupled to a piston and cylinder assembly.

3. The device of claim 2 wherein the linear actuator is an electro-mechanical actuator powered by a stepper motor.

4. The device of claim 3 wherein the stepper motor allows fine gradations of linear travel of an actuator rod per step such that the membrane may repeatablely flex at a maximum length of 15 microns.

5. The device of claim 3 further comprising a linear encoder.

6. The device of claim 5 wherein the linear encoder includes a sensor, transducer or readhead paired with a scale that encodes position and provides feedback to a computer controller with regard to precise positioning of one of the actuator rod, the length of piston strokes, the speed of piston strokes and the number of piston strokes per minute.

7. The device of claim 1 wherein the at least one cell well is over 300 cell wells positioned on a single baseplate.

8. The device of claim 1 further comprising a fluidic sensor system arranged along the hydraulic circuit.

9. The device of claim 1 further comprising a plurality of cell wells and one of a delivery manifold distributing hydraulic fluid among the plurality of cell wells and a receiving manifold receiving hydraulic fluid from the plurality of cell wells.

10. The device of claim 1 further comprising at least one one-way check valve along the hydraulic circuit between the source of hydraulic fluid and the at least one cell well.

11. The device of claim 1 further comprising at least one gate valve along the hydraulic circuit between the source of hydraulic fluid and the at least one cell well.

12. The device of claim 1 further comprising a pressure accumulator along the hydraulic circuit between the source of hydraulic fluid and the at least one cell well.

13. The device of claim 1 wherein the flexing chamber includes a first portion that provides a pathway to hydraulic fluid, a second portion that defines the cell well, and the membrane being sandwiched between the first portion and the second portion.

14. The device of claim 13 wherein the first portion has a mounting point recess, the second portion has a mating inset, and the membrane is captively retained between the first portion and the second portion when the inset is brought to mate with the mounting point recess.

15. The device of claim 1 wherein the flexing chamber comprises a single baseplate, the baseplate defining a hydraulic bore within to direct hydraulic fluid to a plurality of cell wells mounted on the baseplate, the baseplate having a hydraulic inlet to receive hydraulic fluid to the hydraulic bore and a hydraulic outlet to discharge hydraulic fluid from the hydraulic bore.

16. A hydraulic cell stretching device comprising:

a source of variable pressured hydraulic fluid hydraulically coupled to a flexing chamber;

the flexing chamber having at least one cell well;

the at least one cell well being elongate, having a length more than two times a width;

the at least one cell well having a membrane subjected to the variable pressured hydraulic fluid such that the membrane carries a cell culture to be subjected to cell stretching;

a hydraulic circuit including a fluid delivery path leading to the at least, one cell well and a separate fluid return path leading from the at least one cell well

one of a one-way check valve and a gate valve positioned along the fluid delivery path;

one of another one-way check valve and another gate valve positioned along the fluid return path;

wherein a plurality of cell wells are positioned in a single baseplate;

wherein a first column of the plurality of cell wells are fluidically connected to one another and experience a first hydraulic pressure from a first independently operated drive module; and

wherein a second column of the plurality of cell wells are fluidically connected to one another but are fluidically separate from the cell wells of the first column and wherein the second column of the plurality of cell wells simultaneously experience a second hydraulic pressure from a second independently operated drive module distinct from the first independently operated drive module at the same time as the first column of the plurality of cell wells experiences the first hydraulic pressure.

17. A fluidic cell stretching device comprising:

a source of variable pressured fluid, fluidically coupled to a flexing chamber;

the flexing chamber having at least one cell well;

each at least one cell well having a fluid input and fluid output that are vertically aligned with one another,

the each at least one cell well having a membrane subjected to the variable pressured fluid, wherein the membrane carries a cell culture to be subjected to cell stretching;

a hydraulic circuit including a fluid delivery path leading to the fluid input and a separate fluid return path leading from the fluid output;

one of a one-way check valve and a gate valve positioned along the fluid delivery path; and

one of another one-way check valve and another gate valve positioned along the fluid return path;

wherein a plurality of cell wells are positioned in a single baseplate;

wherein a first column of the plurality of cell wells are fluidically connected to one another and experience a first hydraulic pressure from a first independently operated drive module; and

wherein a second column of the plurality of cell wells are fluidically connected to one another but are fluidically separate from the cell wells of the first column and wherein the second column of the plurality of cell wells simultaneously experience a second hydraulic pressure from a second independently operated drive module distinct from the first independently operated drive module at the same time as the first column of the plurality of cell wells experiences the first hydraulic pressure.