Method and system for crystallization and X-ray diffraction screening
An integrated fluidic circuit includes a substrate layer and a first structure coupled to the substrate layer and including a plurality of channels. The first structure is configured to provide for flow of one or more materials through the plurality of channels. The integrated fluidic circuit also includes a second structure coupled to the substrate layer. The second structure includes a plurality of control channels configured to receive an actuation pressure. The integrated fluidic circuit is characterized by a thickness of less than 1.5 mm.
1. A method of analyzing one or more crystals in an integrated fluidic circuit having a microchamber disposed in a flow layer and a control layer adjacent the flow layer, the method comprising:
dispensing a sample into a sample port in fluid communication with the microchamber;
transferring the sample through the flow layer to the microchamber;
dispensing a reagent into a reagent port in fluid communication with the microchamber;
mixing the sample and the reagent in the microchamber;
forming the one or more crystals in the microchamber;
irradiating the one or more crystals in the microchamber with an x-ray analysis beam, wherein the x-ray analysis beam passes through:
the one or more crystals in the microchamber present in the flow layer;
through a membrane disposed between the microchamber and the control layer;
through a first portion of the control layer defined by a first material; and
through a second portion of the control layer defined by a second material different from the first material; and
detecting the x-ray analysis beam.
2. The method of claim 1 further comprising excising the microchamber from the integrated fluidic circuit prior to irradiating the one or more crystals in the microchamber with the x-ray analysis beam.
3. The method of claim 1 wherein the sample comprises a macromolecular sample.
4. The method of claim 1 wherein mixing comprises opening an interface valve present in the flow layer and actuated by a pressure change in the control layer.
5. The method of claim 4 wherein mixing further comprises performing a free interface diffusion process.
6. The method of claim 1 further comprising transferring a cryoprotectant into the microchamber prior to irradiating the one or more crystals in the microchamber.
7. The method of claim 1 wherein the flow layer comprises PDMS and the control layer comprises a urethane material.
8. The method of claim 1 wherein the first material comprises an elastomer including silicon and the second material comprises an elastomer substantially free of silicon.
9. The method of claim 8 wherein the elastomer including silicon comprises PDMS and the elastomer substantially free of silicon comprises a urethane material.
10. The method of claim 1 wherein the first material is characterized by a first x-ray scattering cross-section and the second material is characterized by a second x-ray scattering cross-section less than the first x-ray scattering cross-section.
11. The method of claim 1 wherein a control channel is characterized by a height and the first portion of the control layer is characterized by a thickness less than the height.