Apparatus for the precise positioning of cells

• US 5,108,926 A
• Filed: 09/08/1987
• Issued: 04/28/1992
• Est. Priority Date: 09/08/1987
• Status: Expired due to Term

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Klebe, Robert J.
• Primary Examiner(s): Lacey, David L.
• Assistant Examiner(s): Beisner, William H.
• Application Number:
  US07/094,341
• Time in Patent Office: 1,694 Days
• Field of Search: 435/30, 435/284, 435/285, 435/287, 435/292, 435/293, 435/297, 435/299, 435/300, 435/240.243, 435/240.23, 346/140 R, 118/715, 118/64, 118/313, 401/35, 427/2, 427/4, 600/36, 623/66, 623/15
• US Class Current: 435/286.4
• CPC Class Codes: A61F 2/105 Skin implants, e.g. artificial skin
• CPC Class Codes: B01L 3/0268 using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
• CPC Class Codes: C12M 23/20 Material Coatings immunocoatings C12M25/00
• CPC Class Codes: C12M 33/00 Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus chemical or physical laboratory apparatus in general B01L, devices for taking cell samples A61B10/0045, withdrawing or distributing predetermined quantities of fluid B01L99/00
• CPC Class Codes: C12N 2533/52 Fibronectin; Laminin
• CPC Class Codes: C12N 2535/10 Patterned coating
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06
• CPC Class Codes: G01N 2001/282 with mapping; Identification of areas; Spatial correlated pattern
• CPC Class Codes: G01N 35/109 with two horizontal degrees of freedom

Abstract

Disclosed are apparati for the precise positioning of cells into highly organized tissue structures. In particular, ink jet printers and graphics plotters are modified to allow their use in the preparation of tissue structures which are suitable for use in the treatment of burn patients. Cells are positioned by the use of computer-controlled placement of cell adhesion materials such as fibronectin to a substratum which is suitable for maintaining cell growth, followed by allowing cells to attach to those areas of the substratum where the cell adhesion material has been placed. Alternatively, specific placement of cells onto substrata is obtained by the computer-controlled placement of cells directly. These apparati may be even further modified and improved by providing a controlled biological environment in the area of the substratum, thus providing an integral unit for the production of organized tissues.

Claims

1. A combination tissue culture device and an apparatus for the precise positioning of cell adhesion material on the tissue culture device for the cellular arrangement of tissue cultured thereon, the combination comprising:

(a) a solid support;

(b) a substratum positioned on said solid support and constructed such that it is separable from said solid support and any tissue cultured thereon;

(c) container means containing a cell adhesion material; and

(d) positioning means, connected to the support and in fluid communication with said container means, for positioning said cell adhesion material at selected points within an array on the surface of the substratum.

2. The combination of claim 1 wherein said cell adhesion material is selected from the group consisting of fibronectin, laminin, chondronectin, epinectin, epibolin and uromorulin.

3. The combination of claim 1 wherein the cell adhesion material comprises an antibody having specificity for a cell surface determinant.

4. The combination of claim 1 further comprising a second container means in communication with said positioning means, said second container means containing a biological material to be positioned on said substratum.

5. The combination of claim 1 further comprising means for biologically controlling the environment surrounding the substratum.

6. The combination of claim 1 wherein said substratum is selected from the group consisting of collagen, polylactide, pyrex glass, carnmauba wax, silicone aluminum, polytetrafluoroethylene, polyvinyl acetate, polyvinyl chloride and polystyrene.

7. The combination of claim 1 wherein the substratum comprises collagen in the form of a wafer or sheet.

8. The combination of claim 1 wherein said positioning means comprises:

(a) a housing constructed so as to receive a flow of the cell adhesion material from the container means and depositing the material on the substratum, the housing having at least one metered pore through which the material may flow onto the substratum; and

(b) data processing means for precisely locating the housing at points within the array.

9. The combination of claim 8 wherein the housing has a plurality of metered pores and the positioning means further comprises data processing means for metering the flow of the material through the pores.

10. The combination of claim 9 wherein the housing comprises an ink jet printer or graphics plotter head.

11. The combination of claim 1 wherein the positioning means is movable to selected points with a 2-dimensional array.

12. The combination of claim 1 wherein the positioning means is movable to selected points within a 3-dimensional array.

13. A combination tissue culture device and an appartus for the precise positioning of living cells on a the tissue culture device for the cellular arrangement of tissue cultured thereon, the combination comprising:

(a) a solid support;

(b) a substratum positioned on said solid support and constructed such that it si separable from said solid support and any tissue cultured thereon;

(c) container means containing living cells; and

(d) positioning means, connected to the support and in fluid communication with said container means, for positioning said living cells at selected points within an array on the surface of the substratum.