3D micro-scale engineered tissue model systems

• US 7,763,456 B2
• Filed: 09/28/2007
• Issued: 07/27/2010
• Est. Priority Date: 09/28/2006
• Status: Expired due to Fees

• Current Assignee: Washington University In St Louis
• Original Assignee: University of Washington
• Inventors: Li, Wei, Wang, Hai
• Primary Examiner(s): Prouty; Rebecca E.
• Assistant Examiner(s): Martin; Paul C.
• Application Number:
  US11/864,698
• Publication Number:
  US 20080102478A1
• Time in Patent Office: 1,033 Days
• Field of Search: None
• US Class Current: 435/288.5
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/069 Absorbents; Gels to retain a fluid
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502753 characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation separation in general B01D; microapparatus for analysis using electrophoresis G01N27/44791; sample preparation G01N1/28
• CPC Class Codes: C12M 23/16 Microfluidic devices; Capillary tubes integrated microfluidic structures B01L3/5027; microreactors B01J19/0093
• CPC Class Codes: C12M 25/14 Scaffolds; Matrices in general C12N5/0068
• CPC Class Codes: C12M 35/08 Chemical, biochemical or biological means, e.g. plasma jet, co-culture

Abstract

A polymeric chip having at least one three-dimensional porous scaffold, a microfluidic channel inlet to the porous scaffold, and a microfluidic channel outlet from the porous scaffold. In one embodiment, the polymeric chip has two three-dimensional porous scaffolds: one scaffold comprises liver cells and the other scaffold comprises cancer cells. The chip can be used as a multi-organ tissue model system.

Claims

1. A polymeric chip, comprising,

at least one porous scaffold, wherein the porous scaffold is formed from the polymeric chip and is localized within a portion of the polymeric chip, wherein the porous scaffold includes a first surface and a second surface, and wherein the first surface is opposite from the second surface;

a first microfluidic inlet channel, wherein the first microfluidic inlet channel is in fluid connectivity with the first surface of the porous scaffold; and

a second microfluidic outlet channel, wherein the second microfluidic outlet channel is in fluid connectivity with the second surface of the porous scaffold.

2. The polymeric chip of claim 1, wherein each surface is the area defined by either the upper or lower perimeter of the porous scaffold.

3. The polymeric chip of claim 1, wherein the porous scaffold has a pore size from about 50 μ

m to about 200 μ

m.

4. The polymeric chip of claim 1, wherein the porous scaffold comprises a plurality of living cells.

5. The polymeric chip of claim 1, wherein the chip comprises polymethyl methacrylate, polystyrene, poly(lactic acid), or poly(lactic/glycolic acid).

6. A polymeric chip, comprising:

two or more porous scaffolds, wherein each porous scaffold is formed from the polymeric chip and is localized within a portion of the polymeric chip, wherein each porous scaffold includes a first surface and a second surface, and wherein the first surface is opposite to the second surface;

a first microfluidic inlet channel, wherein the first microfluidic inlet channel is in fluid connectivity with the first surface of each porous scaffold; and

a second microfluidic outlet channel, wherein the second microfluidic outlet channel is in fluid connectivity with the second surface of at least one porous scaffold.

7. The polymeric chip of claim 6, wherein the second microfluidic outlet channel is in fluid connectivity to the second surface of each porous scaffold.

8. The polymeric chip of claim 6, further comprising a third microfluidic outlet channel, wherein the third microfluidic outlet channel is in fluidic connectivity to the second surface of at least one porous scaffold.

9. The polymeric chip of claim 6, wherein each porous scaffold comprises a 3-dimensional volume comprising pores having an averages size from about 50 μ

m to about 200 μ

m.

10. The polymeric chip of claim 6, wherein each porous scaffold comprises living cells.

11. The polymeric chip of claim 6, wherein a first porous scaffold comprises liver cells and a second porous scaffold comprises cancer cells.

12. A polymeric chip, comprising,

at least one porous scaffold, wherein the porous scaffold is formed from the polymeric chip and is localized within a portion of the polymeric chip, wherein the porous scaffold includes a first surface and a second surface, wherein the first surface is opposite from the second surface, and wherein the porous scaffold includes a well having a bottom surface surrounded by upright walls and formed within the porous scaffold;

a first microfluidic inlet channel, wherein the first microfluidic inlet channel is in fluid connectivity with the first surface of the porous scaffold; and

a second microfluidic outlet channel, wherein the second microfluidic outlet channel is in fluid connectivity with the second surface of the porous scaffold.

13. A method for providing an assay solution, comprising,

(a) providing a polymeric chip, comprising,

a first porous scaffold in the chip;

a second porous scaffold in the chip, which is separated from the first porous scaffold, wherein the first porous scaffold and the second porous scaffold are formed from the polymeric chip and are localized within a portion of the polymeric chip;

a first microfluidic channel connecting the first porous scaffold to the second porous scaffold;

a second microfluidic channel inlet to the first porous scaffold; and

a third microfluidic channel outlet from the second porous scaffold;

(b) seeding a plurality of first living cells in the first porous scaffold to provide a first cell culture;

(c) seeding a plurality of second living cells in the second porous scaffold to provide a second cell culture;

(d) dissolving a compound in a cell culture medium to provide a liquid medium;

(e) flowing the liquid medium sequentially through the second microfluidic channel inlet, the first cell culture, the first microfluidic channel, the second cell culture, and the third microfluidic channel outlet to provide an assay solution.

14. The method of claim 13, wherein the first cell culture comprises liver cells and the second cell culture comprises cancer cells.

15. The method of claim 14, further comprising analyzing the second cell culture to determine the inhibitory activity of the compound on the cancer cells.

16. The method of claim 15, further comprising analyzing the assay solution.

17. A method for providing an assay solution, comprising,

(a) providing a polymeric chip, comprising:

at least one porous scaffold, wherein the porous scaffold is formed from the polymeric chip and is localized within a portion of the polymeric chip, wherein the porous scaffold includes a first surface and a second surface, and wherein the first surface is opposite from the second surface;

a first microfluidic inlet channel, wherein the first microfluidic inlet channel is in fluid connectivity with the first surface of the porous scaffold; and

a second microfluidic outlet channel, wherein the second microfluidic outlet channel is in fluid connectivity to the second surface of the porous scaffold;

(b) seeding a plurality of living cells in the porous scaffold to provide a cell culture;

(c) dissolving a compound in a cell culture medium to provide a liquid medium;

(d) flowing the liquid medium through the first microfluidic inlet channel, the cell culture, and the second microfluidic outlet channel to provide an assay solution.

18. The method of claim 17, wherein the cell culture comprises liver cells.

19. The method of claim 17, wherein the cell culture comprises cancer cells.

20. The method of claim 17, wherein the cell culture comprises both stromal cells and cancer cells.

21. The method of claim 17, further comprising analyzing the cell culture to determine the inhibitory activity of the compound on the cells.