Assay device that analyzes the absorption, metabolism, permeability and/or toxicity of a candidate compound

A method of patterning at least two different cell types in a two-dimensional co-culture configuration comprising:

• a) providing a device having:
• a cell culture support surface;
• and
• a microfluidic system having a removable patterning membrane disposed on the cell culture support surface and a plurality of channels for flowing cells to surfaces exposed within the channels, wherein the channels are in conformal contact with the cell culture support surface and are parallel relative to each other and spaced apart relative to each other;
• b) flowing cells of one tissue type through one set of alternating channels to form multiple rows of contiguous cells of a first tissue type within the channels, wherein the rows are parallel relative to each other and spaced apart relative to each other;
• c) removing the removable microfluidic patterning membrane from the cell culture support to form alternating rows of bare cell culture support contiguous with and parallel relative to the rows of contiguous cells of step (b);
• and
• d) flowing cells of a second tissue type through a second set of alternating channels to the alternating rows of bare cell culture support of step (c), to form rows of contiguous cells of the second tissue type contiguous with the rows of contiguous cells of the first tissue type on the cell culture support.

A method of patterning at least two different cell types in a two-dimensional co-culture configuration comprising:

• a) providing a device having:
• a cell culture support;
• and
• at least one removable membrane disposed on the cell culture support, wherein the membrane forms a stencil pattern on the cell culture support;
• b) applying cells of one tissue type to open areas formed by the stencil pattern, wherein the open areas are spaced apart relative to each other;
• c) removing the at least one removable membrane from the cell culture support to form bare areas of cell culture support;
• and
• d) applying cells of a second tissue type to the bare areas cell culture support.

A method of patterning at least two different cell types in a two-dimensional co-culture configuration comprising:

• a) providing a non-coated cell growth substrate, wherein the substrate has a plurality of patterned electrodes embedded within said substrate and a plurality of electroactive cytophobic self-assembled monolayers (SAMs) patterned onto the cell substrate;
• b) applying cells of a first tissue type to the non-SAM coated cell growth substrate;
• c) desorbing the plurality of electroactive cytophobic SAMs from the cell substrate to form cell adhesive regions in the pattern of the removed SAMs;
• d) activating at least one electrode to form at least one activated region of the cell growth substrate;
• e) applying cells of a second cell type to the at least one activated region of step (d) to form a pattern the cells of the second cell type in at least one activated region, thereby patterning at least two different cell types in a two-dimensional co-culture configuration.

A device comprising:

• a housing defining at least one chamber therein;
• a membrane disposed in the at least one chamber and defining a plurality of micro-orifices, the membrane being configured such that each of the plurality of micro-orifices is adapted to receive a single cell therein, and such that the at least one chamber includes a first region on one side of the membrane, and a second region on another side of the membrane;
• a delivery device in fluid communication with the first region of the at least one chamber, the delivery device being adapted to deliver a fluid to the first region;
• and
• a removal device in fluid communication with the second region of the at least one chamber, the removal device being adapted to remove a fluid from the second region.

A device comprising:

• a housing defining at least one chamber therein;
• a plurality of membranes, each of the membranes defining a plurality of micro-orifices and being configured such that each of the plurality of micro-orifices is adapted to receive a single cell therein, the membranes being disposed in the at least one chamber such that the at least one chamber includes a first region on one side of the membranes, and a second region on another side of the membranes;
• a delivery device in fluid communication with the first region of the at least one chamber, the delivery device being adapted to deliver a fluid to the first region;
• and
• a removal device in fluid communication with the second region of the at least one chamber, the removal device being adapted to remove a fluid from the second region.

A device comprising:

• a housing defining at least one chamber therein;
• a means for controlling fluid flow disposed in the at least one chamber and defining a plurality of micro-orifices, the means for controlling fluid flow being configured such that each of the plurality of micro-orifices is adapted to receive a single cell therein, and such that the at least one chamber includes a first region on one side of the means for controlling fluid flow, and a second region on another side of the means for controlling fluid flow;
• a fluid delivery means in fluid communication with the first region of the at least one chamber, the fluid delivery means being adapted to deliver a fluid to the first region;
• a fluid removal means in fluid communication with the second region of the at least one chamber, the fluid removal means being adapted to remove a fluid from the second region.

A method of analyzing an effect of candidate compound on a cellular coculture, said method comprising:

• a) coculturing at least two different cell types in a two-dimensional coculture device;
• b) contacting at least one cell type with a therapeutically effective dose of at least one test compound for a therapeutically effective time period;
• c) removing at least one analyte of the coculture;
• and
• d) performing an assay on the at least one analyte.