Two-dimensional and three-dimensional microarray cell cultures using elastomeric assembly substrates
The invention provides a method for preparing an ordered cell-containing microarray, and a system for preparing an ordered cell-containing microarray.
1 . A method for preparing an ordered microarray, the method comprising process (A) or process (B):
(A) (i) providing an elastomeric substrate,
(ii) modifying a surface of the elastomeric substrate thereby producing a surface-modified elastomeric substrate,
(iii) spraying a composition onto the surface-modified elastomeric substrate thereby producing a disordered microarray, and
(iv) applying a strain to the disordered microarray thereby producing the ordered microarray; or
(B) (i) providing an elastomeric substrate,
(ii) modifying a surface of the elastomeric substrate thereby producing a surface-modified elastomeric substrate,
(iii) applying a strain to the surface-modified elastomeric substrate thereby producing a strained surface-modified elastomeric substrate,
(iv) spraying a composition onto the strained surface-modified elastomeric substrate thereby producing a disordered microarray, and
(v) relaxing the disordered microarray thereby producing the ordered microarray.
2 . The method of claim 1 , wherein modifying the surface of the elastomeric substrate of step (ii) of process (A) or step (ii) of process (B) comprises masking the elastomeric substrate and chemically modifying at least a portion of the surface of the elastomeric substrate thereby producing the surface-modified elastomeric substrate.
3 . The method of claim 2 , wherein the step of chemically modifying at least a portion of the surface of the elastomeric substrate provides at least a portion of the surface of the elastomeric substrate that enables assembly of a disordered microarray into an ordered microarray by hydrophobicity contrast and is capable of attachment of a chemical moiety by chemically, thermally, and/or photolytically treating the surface-modified elastomeric substrate in the ordered microarray.
4 . The method of claim 2 , wherein the step of chemically modifying at least a portion of the surface of the elastomeric substrate comprises oxidizing the surface.
5 . The method of claim 2 , wherein the step of chemically modifying at least a portion of the surface of the elastomeric substrate comprises attaching to the surface of the elastomeric substrate a peptide-based adhesion promoter, a small molecule adhesion promoter, a (meth)acrylate-containing compound, a (meth)acrylamide-containing compound, a polyethylene glycol-containing compound, a fluorocarbon, a NHS-ester-containing compound, a maleimide-containing compound, an azide-containing compound, an alkyne-containing compound, or any combination thereof.
6 . The method of claim 2 , wherein the composition is a cell-containing composition, the disordered microarray is a disordered cell-containing microarray, and the ordered microarray is an ordered cell-containing microarray.
7 . The method of claim 6 , wherein the step of chemically modifying at least a portion of the surface of the elastomeric substrate provides at least a portion of the surface of the elastomeric substrate that enables assembly of a disordered cell-containing microarray into an ordered cell containing microarray by hydrophobicity contrast and promotes cell adhesion or is capable of attachment of a chemical moiety by chemically, thermally, and/or photolytically treating the surface-modified elastomeric substrate in the ordered cell-containing microarray.
8 . The method of claim 1 , wherein the composition is sprayed at a pressure of about 5 kPa to about 100 kPa.
9 . The method of claim 1 , wherein the composition is sprayed at a flow rate of about 10 μLmin −1 to 100 μLmin −1 .
10 . The method of claim 1 , wherein the composition is sprayed at a distance of about 1 cm to about 20 cm from the surface-modified elastomeric substrate or the strained surface-modified elastomeric substrate.
11 . The method of claim 1 , wherein applying the strain to the disordered microarray of step (iv) of process (A) or the surface-modified elastomeric substrate of step (iii) of process (B) comprises stretching the elastomeric substrate uniaxially, biaxially, or omnidirectionally.
12 . The method of claim 1 , wherein the composition is a cell-containing composition, the disordered microarray is a disordered cell-containing microarray, and the ordered microarray is an ordered cell-containing microarray.
13 . The method of claim 12 , wherein the method further comprises
attaching the cell-containing composition to the surface-modified elastomeric substrate in the ordered cell-containing microarray by chemically, thermally, and/or photolytically treating the surface-modified elastomeric substrate in the ordered cell-containing microarray.
14 . The method of claim 12 , wherein the method further comprises
transferring the ordered cell-containing microarray to a cell culture media and inducing and/or sustaining growth of a cell.
15 . The method of claim 12 , wherein the cell-containing composition comprises somatic cells, stem cells, or a combination thereof.
16 . The method of claim 1 , wherein the elastomeric substrate comprises a silane-based material.