Programmable liquid, gel and biohybrid compartments and methods of use

Abstract

Nano- to microscale liquid coacervate particles are provided. The liquid coacervate particles are produced by a process including stimulating a population of liquid droplets containing one or a mixture of components to induce a phase separation point of a first component, and maintaining stimulation at the phase separation point to form a coacervate domain of the first component within each of the droplets to form the liquid coacervate particles. The self-assembled nano, meso, micro and macro liquid coacervate particles and related coated substrates can have utility in drug delivery, bioanalytical systems, controlled cell culture, tissue engineering, biomanufacturing and drug discovery.

The invention claimed is: 
     
         1 . A method for making nano- to microscale liquid coacervate particles, the method comprising:
 stimulating a population of droplets including a solution of one or a mixture of components, wherein the stimulation induces a phase separation point of a first component; and   maintaining stimulation at the phase separation point to form a coacervate domain of the first component within each of the droplets, wherein liquid coacervate particles are formed.   
     
     
         2 . The method of  claim 1 , wherein the population of droplets are formed using one or a combination of mechanical agitation, sonication, or microfluidics. 
     
     
         3 . The method of  claim 1 , wherein the population of droplets are aqueous droplets formed by sonication of the solution in oil or microfluidics of the solution in oil. 
     
     
         4 . The method of  claim 1 , wherein the liquid coacervate particles are reversibly formed by cessation of stimulation followed by re-stimulation and re-maintaining stimulation. 
     
     
         5 . The method of  claim 1 , wherein the first component includes a polymer. 
     
     
         6 . The method of  claim 5 , wherein the polymer includes a polypeptide. 
     
     
         7 . The method of  claim 6 , wherein the polypeptide includes at least a portion of an elastin-like polypeptide (ELP). 
     
     
         8 . The method of  claim 1 , wherein the one or a mixture of components includes: a polymer, a synthetic polymer, a hydrophilic polymer, a hydrophobic polymer, an amphiphilic polymer, an amphiphilic diblock polymer, a protein, a nucleic acid, an epoxy, or a polysaccharide, and combinations thereof. 
     
     
         9 . The method of  claim 1 , wherein the stimulating includes: addition or removal of one or more of the components, evaporation of the droplets, controlled diffusion of one or more of the components, electrostatic quenching of one or more of the components, inducing a reaction of one or more of the components, isomerization of one or more of the components, crosslinking of one or more of the component, or crystallization of one or more of the components, and combinations thereof. 
     
     
         10 . A method for coating a substrate, the method comprising:
 stimulating a solution of one or a mixture of components, wherein a substrate is immersed within the solution, wherein the stimulation induces a phase separation point of a first component;   maintaining stimulation at the phase separation point to form a degree of a coacervate domain of the first component on a surface of the substrate based on a wetting property of the substrate; and   repeating the stimulating and maintaining for one or more additional components in the mixture to form a coacervate domain of the additional component.   
     
     
         11 . The method of  claim 10 , wherein the solution is aqueous. 
     
     
         12 . The method of  claim 10 , wherein the first component and the additional component(s) include polymers. 
     
     
         13 . The method of  claim 12 , wherein the polymers include polypeptides. 
     
     
         14 . The method of  claim 13 , wherein the polypeptides include at least a portion of an elastin-like polypeptide (ELP). 
     
     
         15 . The method of  claim 10 , wherein the first component and the additional component(s) have similar phase separation points and a blended alloy coacervate domain is formed on the surface of the substrate. 
     
     
         16 . The method of  claim 10 , wherein the substrate includes one or more of a medical device, a stent, a vascular graft, a catheter, a biosensor, a drug reservoir or a cell culture substrate. 
     
     
         17 . A nano- to microscale liquid coacervate particle composition produced by a process comprising:
 stimulating a population of droplets including a solution of one or a mixture of components, wherein the stimulation induces a phase separation point of a first component;   maintaining stimulation at the phase separation point to form a coacervate domain of the first component within each of the droplets, wherein liquid coacervate particles are formed; and   optionally repeating the stimulating and maintaining for the one or more additional components in the mixture to form a coacervate domain of the additional component within each of the droplets.   
     
     
         18 . The liquid coacervate particle of  claim 17 , wherein the process further comprises stabilizing at least an outermost coacervate domain within each of the droplets to form capsule structures, wherein the outermost coacervate domain remains consolidated upon cessation of stimulation at the phase separation point for the outermost coacervate domain. 
     
     
         19 . The liquid coacervate particle of  claim 18 , wherein stabilizing includes formation of cross-links by one or a combination of covalent coordination, ionic interaction, disulfide bonds, or hydrogen bonds. 
     
     
         20 . The liquid coacervate particle of  claim 17 , wherein the first component and the additional components include polymers. 
     
     
         21 . The liquid coacervate particle of  claim 20 , wherein the polymers include polypeptides. 
     
     
         22 . The liquid coacervate particle of  claim 21 , wherein the polypeptides include at least a portion of an elastin-like polypeptide (ELP). 
     
     
         23 . The liquid coacervate particle of  claim 17 , wherein the first component and the additional component(s) have similar phase separation points and a blended alloy coacervate domain is formed. 
     
     
         24 . The liquid coacervate particle of  claim 17 , wherein the population of droplets are aqueous droplets.