Device and microfluidic system for studying cell cultures
The present invention relates to a novel microfluidic device and a microfluidic system for culturing cell samples based on: one or more culture wells ( 2 ) forming cell housing volumes for three-dimensional cell culture; one or more capillary channels ( 1 ) for circulating cells and/or fluid media, said channels ( 1 ) being connected to the wells ( 2 ) as well perfusion means; and an inlet port ( 3 ) and an outlet port ( 3 ′) for seeding cells and/or for circulating fluid in said channel ( 1 ), said ports ( 3, 3 ′) being connected to the ends of each capillary channel ( 1 ). The novel configuration of the ports ( 3, 3 ′) and their corresponding channels ( 1 ) allows known microfluidic perfusion media to be improved, dispensing with the use of complex elements for injecting the fluid media, such as syringe pumps, for example. The invention also allows two-dimensional and three-dimensional culture studies to be performed simultaneously.
1. A microfluidic device for culturing cell samples comprising:
one or more capillary channels for circulating cells or fluid media, or both, each capillary channel extending between a first end and a second end,
a first inlet port connected to each first end and a second inlet port connected to each second end for seeding cells or for circulating fluid, or both, through the one or more capillary channels,
one or more culture wells forming cell housing volumes for three-dimensional cell culture, wherein the one or more culture wells are formed in the one or more capillary channels such that said one or more capillary channels are connected to the one or more culture wells as culture well perfusion means;
wherein each of the first and second inlet ports have housing volumes for housing a liquid at a level above the level of the one or more capillary channels, such that said liquid exerts pressure at both ends of said one or more capillary channels; and
wherein the device further comprises:
an upper region reservoir for containing fluids above the one or more capillary channels and for accessing the one or more culture wells, providing a two-dimensional cell culture surface adjacent thereto, and
one or more walls confining a perimeter of the upper region reservoir for containing fluids in said upper region reservoir, and
wherein the one or more culture wells are open such that the one or more culture wells are accessible through the upper region reservoir, and
wherein each of the first and second inlet ports of the one or more capillary channels extend also above the upper region, and each of the first and second inlet ports have an opening configured such that a pipette or a fluid connector can be fitted therein.
2. The device according to claim 1 , wherein each of the first and second inlet ports have a housing volume of at least 25 μl.
3. The device according to claim 1 , wherein the one or more capillary channels together with the respective first and second inlet ports, configure a curved trajectory in the device, and a cross-section of the one or more capillary channels has a diameter comprised between 300 and 500 microns.
4. The device according to claim 1 , wherein each capillary channel has two or more culture wells arranged in a row within the capillary channel in which they are formed.
5. The device according to claim 1 , wherein the device is obtained from one or more biocompatible polymeric materials.
6. The device according to claim 1 , wherein each of the one or more culture wells has a diameter larger than the diameter of a section of the capillary channel to which the one or more culture wells are connect.
7. A microfluidic system for studying cell cultures, comprising a device according to claim 1 , in combination with a closure cover for enclosing the upper region of said device.
8. The system according to claim 7 , wherein the closure cover comprises a plurality of fluidic capillary channels, the layout of which coincides with the distribution of the one or more wells of the microfluidic device.
9. The system according to claim 7 , wherein the closure cover comprises a plurality of fluidic inlet and outlet ports connected to each of the one or more capillary channels, wherein the ports comprise housing volumes for housing a liquid at a level different from the level of the one or more capillary channels, said volumes acting like pressure cylinders on said one or more channels.
10. The system according to claim 8 , wherein the closure cover comprises a plurality of fluidic inlet and outlet ports connected to each of the one or more capillary channels, wherein the ports comprise housing volumes for housing a liquid at a level different from the level of the one or more capillary channels, said volumes acting like pressure cylinders on said one or more channels.