Funnel-guided microtissue stacking and manipulation
The invention provides a device and a method for the assembly of an aggregation of adherent cells, particularly a three-dimensional assembly of adherent cells.
1. A device for assembling multi-cellular structures constructed from stacked microtissues, wherein the microtissues have the shape of a toroid, wherein the multi-cellular structures are stacked in a manner to cause openings defined by the multi-cellular structures to substantially align, the device comprising a funnel-guide, the funnel-guide comprising:
(a) a free-fall chamber,
(b) a funnel chamber, comprising a funnel with an angle between 30< <77, and
(c) a stacking chamber, wherein the stacking chamber is square-shaped and has a width and diagonal slightly larger than a toroid diameter,
such that in the operation of the device,
(i) the toroids spontaneously right themselves during free fall to align with openings defined by the multi-cellular structures in the stacking chamber,
(ii) causing the multi-cellular structures in the stacking chamber to be stacked in a manner to cause openings defined by the multi-cellular structures to substantially align,
(iii) such that the stacked microtissues comprise a lumen.
2. The device of claim 1 , wherein the free-fall chamber is at least 10 mm in height.
3. The device of claim 1 , wherein the stacking chamber has a square shape.
4. The device of claim 1 , wherein the stacking chamber is honeycomb-shaped.
5. The device of claim 1 , wherein the stacked microtissues comprising a lumen comprises a stack of at least twenty-five toroids.
6. A device for assembling multi-cellular structures constructed from stacked microtissues, wherein the microtissues have the shape of a honeycomb, wherein the multi-cellular structures are stacked in a manner to cause openings defined by the multi-cellular structures to substantially align, the device comprising a funnel-guide, the funnel-guide comprising:
(a) a free-fall chamber,
(b) a funnel chamber, comprising a funnel with an angle between 30< <77, and
(c) a stacking chamber,
such that in the operation of the device,
(i) the honeycombs spontaneously right themselves during free fall to align with openings defined by the multi-cellular structures in the stacking chamber,
(ii) causing the multi-cellular structures in the stacking chamber to be stacked in a manner to cause openings defined by the multi-cellular structures to substantially align,
(iii) such that the stacked microtissues comprise lumens.
7. The device of claim 6 , wherein the stacked microtissues comprising a lumen comprises a stack of at least five honeycombs.