Combinatorial synthesis system

A method for synthesizing a library of compounds on a microfluidic device, the method comprising:

• (a) providing a microfluidic device comprising a plurality of fluid flow channels defined by an elastomeric layer and a solid support such that the flow channels comprise an elastomeric portion and a solid support portion, wherein the solid support comprises a reactive functional group attached to the inner surface of the flow channels for attaching a reactive reagent thereto;
• (b) producing a solid-support bound compound by introducing a reactive reagent into the fluid flow channels under conditions sufficient to covalently attach at least a portion of the first reactive reagent to the reactive functional group;
• (c) modifying the solid support-bound compound by introducing another reactive reagent into the fluid flow channels under conditions sufficient to react the solid-support bound compound with the reactive reagent;
• and
• (d) optionally repeating step (c), thereby obtaining the library of compounds, and wherein the reactive agent introduced in steps (b)–(d) is introduced by providing a laminar flow of a sheath fluid in between the reactive agent and the elastomeric layer portion of the fluid flow channels, wherein the sheath fluid is compatible with the elastomeric layer.

A method for synthesizing a library of compounds on a microfluidic device, the method comprising:

• (a) positioning a solid support and an elastomeric layer having a plurality of recesses formed therein with respect to one another to form a first plurality of flow channels, wherein the solid support comprises a plurality of reactive functional groups for attaching a reactive reagent thereto that are attached to an inner surface of at least some of the first flow channels;
• (b) producing a solid-support bound compound by introducing a first reactive reagent into one or more of the fluid flow channels under conditions sufficient to covalently attach at least a portion of the first reactive reagent to the reactive functional group;
• (c) repositioning the elastomeric layer with respect to the solid support to form a second plurality of flow channels defined by the solid support and the recesses in the elastomeric layer such that the second flow channels intersect the first flow channels;
• (d) modifying the solid support-bound compound by introducing a second reactive reagent into one or more of the second fluid flow channels under conditions sufficient to react, the solid-support bound compound with the second reactive reagent.

A method for synthesizing a library of compounds on a microfluidic device, the method comprising:

• (a) providing a microfluidic device comprising (i) a first solid support comprising a plurality of microfluidic flow channels formed therein, wherein a reactive functional group for attaching a reactive reagent thereto is attached to a surface of each of the flow channels, (ii) a second solid support comprising a plurality of control channels formed therein;
• and (iii) an elastomeric layer sandwiched between the first and second solid support and disposed such that the flow channels and the control channels are separated by different segments of the elastomeric layer, wherein each elastomeric segment is deflectable into or retractable from the fluid flow channel that it overlays in response to an actuation force applied to one of the control channels;
• (b) producing a solid-support bound compound by introducing a reactive reagent into the fluid flow channels under conditions sufficient to covalently attach at least a portion of the first reactive reagent to the reactive functional group;
• (c) modifying the solid support-bound compound by introducing another reactive reagent into the fluid flow channels under conditions sufficient to react the solid-support bound compound with the reactive reagent;
• and
• (d) optionally repeating step (c), thereby obtaining the library of compounds.