Methods and devices for generating chemical and gaseous gradients in microfluidic platforms
Disclosed herein are devices, methods and compositions for making and using microfluidic devices comprising making a microfluid device comprising one or more channels; and coating at least a portion of an interior surface of at least one channel, wherein one or more gradients are formed by simultaneously introducing into the device a first cellular culture media composition having a certain concentration of a gas, an active agent or both and a second composition having a concentration of a gas, an active agent or both that is/are different from that of the first composition. Such devices are used to investigate cellular responses to physiological states and active agents.
1. A microfluidic device, comprising:
a glass or polymethylmethacrylate substrate; and
a layer of polydimethylsiloxane (PDMS) on and bonded to the substrate, the layer of PDMS comprising at least one reservoir having an inner wall of PDMS, the reservoir comprising:
at least two media inlets;
at least one cell chamber;
at least one cell inlet connected to the cell chamber;
at least one serpentine mixing channel network from the at least two media inlets to the cell chamber; and
at least one media outlet connected to the cell chamber;
wherein
the at least one serpentine mixing channel network is configured to provide a media gradient across the cell chamber, and
the inner PDMS wall of the at least one serpentine mixing channel network is coated with a glass substance that inhibits diffusion of a gas within the channel network.
2. The device of claim 1 , further comprising an oxygen sensor on the substrate adjacent to the cell chamber.
3. The device of claim 2 , wherein the oxygen sensor comprises a platinum(II) octaethylporphyrin ketone (PtOEPK)-based sensor layer.
4. The device of claim 2 , further comprising a PDMS membrane on the oxygen sensor.
5. A method of growing or maintaining cells under parallel or opposing gradients of gases, active agents, or both in a microfluidic device according to claim 1 , comprising:
introducing cells into the microfluidic device through the at least one cell inlet;
providing a first cellular culture media composition comprising a first certain concentration of a first gas, a first active agent, or both to a first media inlet of the at least two media inlets;
providing a second cellular culture media composition different from the first cellular culture media composition comprising a second certain concentration of a second gas, a second active agent, or both to a second media inlet of the at least two media inlets;
allowing the cells to grow or be maintained in the microfluidic device in a cellular culture media gradient composition; and
evaluating the cells across the cellular culture media gradient.
6. The method of claim 5 , wherein the cells comprise cancer cells.
7. The method of claim 6 , wherein the first and second cellular culture media compositions comprise anticancer drugs.
8. A kit, comprising: the microfluidic device of claim 1 ; and instructions for: introducing cells into the microfluidic device; providing a first cellular culture media composition comprising a first certain concentration of a first gas, a first active agent, or both; providing a second cellular culture media composition comprising a second certain concentration of a second gas, a second active agent, or both, wherein the second cellular culture media composition is different from the first cellular culture media composition; and allowing the cells to grow or be maintained in the microfluidic device.