Multicompartment layered and stackable microfluidic bioreactors and applications of same
In certain aspects of the invention, a stackable device includes multiple elements stacked sequentially. A chamber is formed in each of the elements or between adjacent two of the elements, and each chamber is in fluid communication with an input channel and an output channel. The chambers are aligned with each other, and adjacent two chambers are separated from each other by a membrane. In certain aspects of the invention, a system includes at least one stackable device, each stackable device having multiple chambers; and at least one of a perfusion controller, a microformulator, and a microclinical analyzer in fluid communication with the at least one stackable device. In other aspects of the invention, the use of four microformulators, electrodes and an impedance analyzer can measure the impedance spectrum of each barrier in a multi-transwell plate.
1. A planar layered device, comprising:
a top planar layer; and
a bottom planar layer stacked together,
wherein the top planar layer comprises a top base having an upper surface and a lower surface, a top cover covering the upper surface of the top base, and a top membrane attached to the lower surface of the top base, the top base has a top through hole formed therein, the top through hole is sealed by the top cover and the top membrane to form a top chamber, and the top chamber is in fluid communication with a first input channel and a first output channel located in the top base;
wherein the bottom planar layer comprises a bottom base having an upper surface and a lower surface, and a bottom substrate attached to the lower surface of the bottom base, the bottom base has a bottom through hole formed therein, the bottom through hole is sealed by the top membrane and the bottom substrate to form a bottom chamber, and the bottom chamber is in fluid communication with a second input channel and a second output channel located in the bottom base; and
wherein the top chamber and the bottom chamber correspond to each other and are separated by the top membrane.
2. The planar layered device of claim 1 , further comprising at least one middle planar layer disposed between the top planar layer and the bottom planar layer, wherein the at least one middle planner layer comprises a middle base having an upper surface and a lower surface, the top membrane is disposed between the lower surface of the top base and the upper surface of the middle base, a middle membrane is disposed between the lower surface of the middle base and the upper surface of the bottom base, the middle base has a middle through hole formed therein, the middle through hole is sealed by the top membrane and the middle membrane to form a middle chamber, and the middle chamber is in fluid communication with a third input channel and a third output channel located in the middle base.
3. The planar layered device of claim 2 , wherein the first input channel and the first output channel are recessed from the lower surface of the top base, the second input channel and the second output channel are recessed from the lower surface of the bottom base, and the third input channel and the third output channel are recessed from the lower surface of the middle base.
4. The planar layered device of claim 2 , wherein the at least one middle planar layer comprises a plurality of middle planar layers.
5. The planar layered device of claim 2 , wherein a thickness of the top membrane and the middle membrane is in a range of about 5-20 μm, a height of the top chamber, the middle chamber and the bottom chamber is in a range of about 50-150 μm.
6. The planar layered device of claim 2 , wherein the top chamber, the middle chamber and the bottom chamber are aligned sequentially with each other, the top membrane is porous or a portion of the top membrane corresponding to the top chamber and the middle chamber is porous, and the middle membrane is porous or a portion of the middle membrane corresponding to the middle chamber and the bottom chamber is porous.
7. The planar layered device of claim 2 , wherein each of the top planar layer, the middle planar layer and the bottom planar layer further comprises sidewalls surrounding the top base, the middle base or the bottom base.
8. The planar layered device of claim 1 , further comprising a top cell layer disposed between a bottom surface of the top chamber and the top membrane, and a bottom cell layer disposed between the top membrane and an upper surface of the bottom chamber.
9. The planar layered device of claim 8 , wherein the top cell layer comprises brain astrocytes and pericytes, and the bottom cell layer comprises brain microvascular cells.
10. The planar layered device of claim 1 , wherein the top cover and the bottom substrate are made of glass.