Microfluidic tissue model
The present disclosure describes systems and methods for mimicking body tissue and the function thereof. The mimicked body tissue can include kidney tissue, the blood brain barrier, and other tissues. In some implementations, the systems described herein are used to test the impact of controlled factors on the tissue. The controlled factors can include flow rates, shear rates, and test chemicals (e.g., therapeutics and toxins). In some implementations, the system and methods are used to test pharmaceutical and biological therapies, characterize healthy or diseased tissue, and observe phenomena of the tissue in vitro.
1. A culture device comprising:
a first layer having a membrane-adjacent surface and a first microfluidic channel having a recessed surface and two sidewalls defined into the first layer, wherein the two sidewalls connect the recessed surface to the membrane adjacent surface;
a first graduated microfluidic channel defined into the first layer such that a height of the first graduated microfluidic channel is between about ⅛ and about ⅔ of a height of the first microfluidic channel and the first graduated microfluidic channel is in fluid communication with the first microfluidic channel;
a second layer having a membrane-adjacent surface and a second microfluidic channel having a recessed surface and two sidewalls defined into the second layer, wherein the two sidewalls connect the recessed surface to the membrane adjacent surface;
a membrane separating the first microfluidic channel of the first layer from the second microfluidic channel of the second layer and in contact with the membrane-adjacent surfaces of the first and second layers;
a plurality of first electrodes disposed in the first microfluidic channel, wherein the first electrodes cover at least a portion of the recessed surface of the first microfluidic channel; and
a plurality of second electrodes disposed in the second microfluidic channel, wherein the second electrodes cover at least a portion of the recessed surface of the second microfluidic channel.
2. The device of claim 1 , further comprising a second graduated microfluidic channel in fluidic communication with the second microfluidic channel.
3. The device of claim 1 , wherein the first and second electrodes are between about 0.5 μm and about 15 μm thick.
4. The device of claim 2 , wherein a height of the second graduated microfluidic channel is between about ⅛ and about ⅔ of a height of the second microfluidic channel.
5. The device of claim 1 , further comprising a transition channel between an inlet of the first microfluidic channel and the first microfluidic channel, wherein an angle between a wall of the transition channel and the membrane is between about 10 degrees and about 30 degrees.
6. The device of claim 1 , further comprising an imager.
7. The device of claim 1 , further comprising at least one valve to control a fluid flow into the first microfluidic channel and the second microfluidic channel.
8. The device of claim 1 , wherein the first and second electrodes are configured to measure a trans-epithelial electrical resistance across the membrane.
9. The device of claim 1 , wherein the first layer and the second layer comprise a cyclic olefin copolymer.
10. The device of claim 1 , wherein the first electrodes run up one of the sidewalls of the first microfluidic channel and extend across a portion of the membrane-adjacent surface of the first layer, and the second electrodes run up one of the sidewalls of the second microfluidic channel and extend across a portion of the membrane-adjacent surface of the second layer.
11. The device of claim 1 , wherein the first and second electrodes are less than 15 μm thick.