SYSTEMS FOR SCREENING PHARMACEUTICAL CHEMICALS

• US 20080038812A1
• Filed: 07/06/2007
• Published: 02/14/2008
• Est. Priority Date: 08/14/2001
• Status: Active Grant

• Current Assignee: Washington University In St Louis
• Original Assignee: Washington University In St Louis
• Inventors: McConnaughey, William, Wakatsuki, Tetsuro, Elson, Elliot
• Granted Patent: US 8,227,240 B2
• Time in Patent Office: Days
• US Class Current: 435/287.1
• CPC Class Codes: C12M 21/08 for producing artificial tissue or for ex-vivo cultivation of tissue prostheses A61F2/00, grafts A61L27/00
• CPC Class Codes: C12M 23/12 Well or multiwell plates C12M25/04 takes precedence
• CPC Class Codes: C12M 25/14 Scaffolds; Matrices in general C12N5/0068
• CPC Class Codes: C12M 41/48 Automatic or computerized control automatic analysis G01N35/00

Abstract

An apparatus for culturing a bio-artificial tissue including a multi-well plate and a scaffold is disclosed herein. Also disclosed is a tissue indentation system that includes a probe, an isometric force transducer, a computer and a computer-controlled motor. A tissue response system is provided and has a well including a scaffold with a bio-artificial tissue suspended on the scaffold and the tissue indentation system.

Claims

1. An apparatus for culturing a bio-artificial tissue, comprising:

a multi-well plate having a plurality of wells therein;

at least one of the wells including a scaffold of a non-porous material;

the scaffold having at least one member with a cross-sectional diameter between about 100 μ

m and about 2.0 mm, and disposed above the bottom of the well.

2. The apparatus of claim 1, further comprising at least one leg for supporting the scaffold above the bottom of the well.

3. The apparatus of claim 1, wherein the scaffold is at least about 0.5 mm above the bottom of the well.

4. The apparatus of claim 1, wherein the scaffold is at least about 1.0 mm above the bottom of the well.

5. The apparatus of claim 1, wherein the scaffold is metal.

6. The apparatus of claim 1, wherein the scaffold is plastic.

7. The apparatus of claim 1, wherein the member is tubular.

8. The apparatus of claim 1, wherein the member has a cross-sectional diameter of about 1.0 mm.

9. The apparatus of claim 1, wherein the scaffold is circular.

10. The apparatus of claim 1, wherein the scaffold includes two parallel, spaced apart members.

11. The apparatus of claim 1, wherein the scaffold is triangular.

12. The apparatus of claim 1, wherein the scaffold is supported by the side of the well.

13. The apparatus of claim 1, wherein the scaffold is attached to the side of the well.

14. A tissue indentation system, comprising:

a probe for exerting a force on a test tissue;

an isometric force transducer, operatively connected to the probe, for receiving a force signal from the probe;

a computer, operatively connected to the transducer, for processing the force signal into a signal corresponding to a tissue indentation; and

a first computer-controlled motor, operatively connected to the probe, for moving the probe relative to the test tissue.

15. The system of claim 14, wherein the first computer-controlled motor moves the probe vertically and horizontally relative to the test tissue.

16. The system of claim 14, wherein the first computer-controlled motor moves the probe vertically relative to the test tissue.

17. The system of claim 14, further comprising a stage for securing the test tissue.

18. The system of claim 17, further comprising a second computer-controlled motor operatively connected to the stage and capable of positioning the test tissue horizontally relative to the probe.

19. The system of claim 14, wherein a response of the test tissue to a test agent is measured by the system.

20. The system of claim 19, wherein the response measured is at least one of contractile force and tissue stiffness.

21. The method of claim 20, wherein tissue stiffness includes at least one of hysteresis, phase lag and dynamic stiffness.

22. The system of claim 14, wherein the test tissue is a bio-artificial tissue.

23. The system of claim 14, wherein the probe is L-shaped.

24. The system of claim 14, wherein the probe has a cross-sectional diameter between 1 μ

m and 1.0 mm.

25. The system of claim 17, further comprising a warming plate connected to the stage for warming the test tissue.

26. The system of claim 14, wherein the isometric force transducer measures a force selected from the group consisting of constant force, linear force, ramp force and sinusoidal force.

27. A tissue response system, comprising:

a well including a scaffold;

a bio-artificial tissue suspended on the scaffold, the well for holding a test agent in contact with the tissue; and

a tissue indentation system including,

a probe for exerting an applied force on the tissue;

an isometric force transducer, operatively connected to the probe, for receiving a force signal corresponding to the applied force;

a computer, operatively connected to the transducer, for processing the force signal into a signal corresponding to a tissue response to the test agent; and

a first computer-controlled motor, operatively connected to the probe, for moving the probe relative to the tissue.

28. The system of claim 27, further comprising a stage for securing the well.

29. The system of claim 28, further comprising a second computer-controlled motor operatively connected to the stage and capable of positioning the well relative to the probe.