SYNTHETIC MICROFLUIDIC SYSTEMS FOR HYPOXIA
A cell culture device can include: an internal chamber configured for an internal cell culture that has at least one port coupled to a perfusion modulating device capable of modulating perfusion in the internal chamber; at least one fluid channel bordering the internal chamber that is configured for a channel cell culture that has at least one port coupled to a perfusion modulating device capable of modulating perfusion in the fluid channel; and a wall separating the internal chamber and at least one fluid channel having gaps that fluidly couple the internal chamber with the at least one fluid channel, wherein the perfusion modulating device causes reduced fluid flow. The internal chamber can include a first cell type and the at least one fluid channel includes a second cell type. The first cell type has an ischemic zone in the middle, a non-ischemic zone adjacent with the at least one fluid channel, and a border zone between the ischemic zone and non-ischemic zone. In one aspect, the internal chamber and at least one fluid channel are modeled from physiological features. In one aspect, the internal chamber and at least one fluid channel are modeled from idealized features.
1 . A cell culture device comprising:
an internal chamber configured for an internal cell culture that has at least one port coupled to a perfusion modulating system capable of modulating perfusion in the internal chamber;
at least one fluid channel bordering the internal chamber that is configured for a channel cell culture that has at least one port coupled to the perfusion modulating system capable of modulating perfusion in the fluid channel; and
a wall separating the internal chamber and at least one fluid channel having gaps that fluidly couple the internal chamber with the at least one fluid channel,
wherein the perfusion modulating system causes reduced fluid flow in the internal chamber and/or at least one fluid channel.
2 . The cell culture device of claim 1 , wherein the perfusion modulating system includes a pump.
3 . The cell culture device of claim 2 , wherein the internal chamber includes a first cell type and the at least one fluid channel includes a second cell type.
4 . The cell culture device of claim 3 , wherein the first cell type has an ischemic zone in the middle, a non-ischemic zone adjacent with the at least one fluid channel, and a border zone between the ischemic zone and non-ischemic zone
5 . The cell culture device of claim 1 , wherein the internal chamber and at least one fluid channel are modeled from physiological features.
6 . The cell culture device of claim 1 , wherein the internal chamber and at least one fluid channel are modeled from idealized features.
7 . A cell culture system comprising:
the device of claim 1 ; and
the perfusion modulating system coupled to the port of the internal chamber and/or to the port of the at least one fluidic channel.
8 . A method of inducing ischemia, the method comprising:
providing the device of claim 1 having a first cell culture in the internal chamber and a second cell culture in the at least one fluid channel;
modulating perfusion in the internal chamber with the perfusion modulating device; and
assaying for ischemia in the first cell culture.
9 . The method of claim 8 , comprising: modulating perfusion in the at least one fluid channel.
10 . The method of claim 8 , comprising varying flow rate and duration of fluid flow in the at least one fluid channel so as to vary perfusion in the internal chamber.
11 . The method of claim 8 , comprising introducing a chemical, biological and/or physical insult to the first cell culture in the internal chamber.
12 . The method of claim 8 , comprising inducing gradients of hypoxia in the internal chamber.
13 . The method of claim 8 , comprising inducing hypoxia in tissue cells (e.g. myocytes, neurons, nephrons, or hepatocytes) in the internal chamber.
14 . The method of claim 8 , comprising screening therapeutics on hypoxic cells in the first cell culture in the internal chamber.
15 . The method of claim 8 , comprising characterizing viability, pH, hypoxia, or biomarkers in cells in the first cell culture in the internal chamber.
16 . The method of claim 8 , comprising regenerating cells the internal chamber.
17 . The method of claim 8 , comprising visualizing cells in the first cell culture in the internal chamber.
18 . The method of claim 8 , comprising simulating a myocardial infarct in the first cell culture of myocytes in the internal chamber.
19 . The method of claim 8 , comprising modulating nutrient levels in the internal chamber sufficient to induce varying (low, moderate, high) levels of ischemia.
20 . The method of claim 19 , comprising modulating nutrient levels in the internal chamber and at least one fluid channel sufficient to induced moderate to severe ischemia.