Methods and compositions for thiol-acrylate based materials for 3d cell culturing in a microfluidic device

Abstract

Provided are thiol-acrylate hydrogels and tunable cell culture materials including thiol-acrylate hydrogels, and methods of making thereof. Also provided are systems for forming three-dimensional cell culture scaffolds including the materials, and methods of culturing cells, including cancer cells, using thiol-acrylate hydrogels and tunable cell culture materials. The materials herein can be used in microfluidic droplet-generating devices.

What is claimed is: 
     
         1 . A system for 3D cell culture comprising:
 a microfluidic droplet-generating device and a tunable cell culture material comprising a thiol-acrylate hydrogel.   
     
     
         2 . The system of  claim 1 , wherein the microfluidic droplet-generating device comprises a droplet trapping array located below a microfluidic flow channel, wherein the trapping array comprises a plurality of circular traps. 
     
     
         3 . The system of  claim 2 , wherein the circular traps have a diameter of about 70 μm to about 300 μm. 
     
     
         4 . The system of  claim 1 , wherein the thiol-acrylate hydrogel is a product of a reaction between a thiol comprising ethoxylated trimethylolpropane tri (3-mercapto-propionate) (ETTMP), and an acrylate comprising poly(ethylene glycol) diacrylate (PEGDA); and
 wherein the reaction is a base-catalyzed Michael addition occurring at a pH of about 7.6 to 8.2.   
     
     
         5 . The system of  claim 4 , wherein the thiol-acrylate hydrogel and cells are provided to the microfluidic droplet-generating device in an aqueous phase, and the reaction completes polymerization inside a trapping array. 
     
     
         6 . The system of  claim 1 , wherein:
 when a hydrogel weight percent is about 8.5 and a molar ratio is about 1.0, a gelation time is about 150 minutes;   when the hydrogel weight percent is about 8.5 and the molar ratio is about 1.05, the gelation time is about 40 minutes;   when the hydrogel weight percent is about 9 and the molar ratio is about 1.0, the gelation time is about 80 minutes;   when the hydrogel weight percent is about 9 and the molar ratio is about 1.05, the gelation time is about 30 minutes;   when the hydrogel weight percent is about 9.5 and the molar ratio is about 1.0, the gelation time is about 30 minutes; and   when the hydrogel weight percent is about 9.5 and the molar ratio is about 1.05, the gelation time is about 25 minutes.   
     
     
         7 . The system of  claim 3 , wherein the trapping array has about 785 circular traps having a diameter of 70 μm each. 
     
     
         8 . The system of  claim 3 , wherein the trapping array has about 990 circular traps having a diameter of 150 μm each 
     
     
         9 . The system of  claim 3 , wherein the trapping array has about 450 circular traps having a diameter of 300 μm each. 
     
     
         10 . The system of  claim 1 , wherein the microfluidic droplet-generating device comprises a flat layer having two inlets and an outlet, wherein the flat layer is above a bottom PDMS device layer that includes the microfluidic flow channel and the droplet trapping array, such the that the droplet trapping array is provided below the microfluidic flow channel.