Novel droplet-embedded microfibers, and methods and devices for preparing and using same

Abstract

The invention includes microfluidic methods and devices that allow for the continuous production of microfibers with embedded droplets aligned along the length of the fiber at specific positions. The invention allows for formation of single or multiple emulsions within a fiber. The various phases comprised within the fiber can vary in terms of in terms of hydrophobic/hydrophilic character, solid/fluid, or gel crosslink density, which allows for the introduction of heterogeneous microenvironments within the fiber, each of which with distinct solubility characteristics, permeability, and mechanical properties. Various compounds and materials can be encapsulated in the different microcompartments of the fiber for storage and delivery applications, as well as to provide multifunctionality to the fiber structure. The disclosed structures have a broad range of potential applications, for example as engineered substrates with controlled release profiles of multiple compounds for tissue engineering (such as a tissue scaffold, for example) and bioengineering applications.

What is claimed is: 
     
         1 . A microfiber comprising a matrix material;
 wherein the microfiber further comprises a plurality of droplets embedded in the matrix material along a length thereof;   wherein each one of the plurality of droplets independently comprises a single fluid;   wherein each one of the plurality of droplets is insoluble in the matrix material of the microfiber; and   wherein, if the matrix material of the microfiber is hydrophilic, the matrix material is prepared from a precursor using at least one method selected from the group consisting of polymerization, solvent extraction and covalent crosslinking.   
     
     
         2 . The microfiber of  claim 1 , wherein the matrix material has a composition that does not vary substantially along a length of the microfiber. 
     
     
         3 . The microfiber of  claim 1 , wherein the matrix material has a composition that varies along a length of the microfiber. 
     
     
         4 . The microfiber of  claim 1 , wherein each one of the plurality of the droplets has a like composition. 
     
     
         5 . The microfiber of  claim 1 , wherein at least one of the plurality of droplets has a first composition, and at least one other of the plurality of droplets has a second composition, the first composition being different from the second composition. 
     
     
         6 . The microfiber of  claim 1 , wherein the matrix material further comprises at least one agent selected from the group consisting of a cell, tissue, filler, therapeutic drug, chemoattractant, biocide, ion, peptide, protein, nucleic acid, magnetic compound, and detectable probe. 
     
     
         7 . The microfiber of  claim 1 , wherein at least one of the plurality of droplets further comprises at least one agent selected from the group consisting of a cell, tissue, filler, therapeutic drug, chemoattractant, biocide, ion, peptide, protein, nucleic acid, magnetic compound, and detectable probe. 
     
     
         8 . The microfiber of  claim 1 , wherein at least one selected from the group consisting of the matrix material and at least one of the plurality of droplets comprises a magnetic compound. 
     
     
         9 . The microfiber of  claim 1 , wherein the matrix material of the microfiber is hydrophobic and the single fluid of the droplet is hydrophilic. 
     
     
         10 . The microfiber of  claim 1 , wherein the matrix material of the microfiber is hydrophilic and the single fluid of the droplet is hydrophobic. 
     
     
         11 . The microfiber of  claim 1 , wherein the matrix material comprises a first agent and at least one of the plurality of droplets comprises a second agent, the second agent having distinct solubility or distinct chemical compatibility from the first agent. 
     
     
         12 . The microfiber of  claim 1 , wherein the matrix material of the microfiber is biodegradable. 
     
     
         13 . A microfiber comprising a matrix material;
 wherein the microfiber further comprises a plurality of droplets embedded in the matrix material along the length thereof;   wherein each one of the plurality of droplets independently comprises an emulsion comprising a first droplet phase within a second droplet phase; and   wherein the matrix material of the microfiber is insoluble in the second droplet phase of each one of the plurality of droplets.   
     
     
         14 . The microfiber of  claim 13 , wherein the matrix material has a composition that does not vary substantially along a length of the microfiber. 
     
     
         15 . The microfiber of  claim 13 , wherein the matrix material has a composition that varies along a length of the microfiber. 
     
     
         16 . The microfiber of  claim 13 , wherein each one of the plurality of the droplets has a like composition. 
     
     
         17 . The microfiber of  claim 13 , wherein at least one of the plurality of droplets has a first composition, and at least one other of the plurality of droplets has a second composition, the first composition being different from the second composition. 
     
     
         18 . The microfiber of  claim 13 , wherein the matrix material further comprises at least one agent selected from the group consisting of a cell, tissue, filler, therapeutic drug, chemoattractant, biocide, ion, peptide, protein, nucleic acid, magnetic compound, and detectable probe. 
     
     
         19 . The microfiber of  claim 13 , wherein at least one of the plurality of droplets further comprises at least one agent selected from the group consisting of a cell, tissue, filler, therapeutic drug, chemoattractant, biocide, ion, peptide, protein, nucleic acid, magnetic compound, and detectable probe. 
     
     
         20 . The microfiber of  claim 13 , wherein at least one selected from the group consisting of the matrix material and at least one of the plurality of droplets comprises a magnetic compound. 
     
     
         21 . The microfiber of  claim 13 , wherein the matrix material of the microfiber is hydrophilic and the second droplet phase of each one of the plurality of droplets is hydrophobic. 
     
     
         22 . The microfiber of  claim 13 , wherein the matrix material of the microfiber is hydrophobic and the second droplet phase of each one of the plurality of droplets is hydrophilic. 
     
     
         23 . The microfiber of  claim 13 , wherein the first droplet phase of at least one of the plurality of droplets comprises a solid. 
     
     
         24 . The microfiber of  claim 13 , wherein within at least one of the plurality of droplets the first droplet phase comprises a first agent and the second droplet phase comprises a second agent, the second agent having at least one property selected from the group consisting of solubility and chemical compatibility that is distinct from that of the first agent. 
     
     
         25 . The microfiber of  claim 13 , wherein the matrix material of the microfiber is biodegradable. 
     
     
         26 . A microfiber comprising an outer matrix material and an inner matrix material;
 wherein the outer matrix material and the inner matrix material span the length of the microfiber;   wherein the inner matrix material is embedded in the outer matrix material;   wherein the microfiber further comprises a plurality of droplets embedded in the inner matrix material along the length thereof; and   wherein the inner matrix material of the microfiber is insoluble in each one of the plurality of droplets and in the outer matrix material.   
     
     
         27 . The microfiber of  claim 26 , wherein the outer and inner matrix materials are coaxially aligned within the microfiber. 
     
     
         28 . The microfiber of  claim 26 , wherein the radius of the inner matrix material is substantially constant along a length of the microfiber. 
     
     
         29 . The microfiber of  claim 26 , wherein the radius of the outer matrix material is substantially constant along a length of the microfiber. 
     
     
         30 . The microfiber of  claim 26 , wherein each one of the plurality of the droplets has a like composition. 
     
     
         31 . The microfiber of  claim 26 , wherein at least one of the plurality of droplets has a first composition, and at least one other of the plurality of droplets has a second composition, the first composition being different from the second composition. 
     
     
         32 . The microfiber of  claim 26 , wherein at least one selected from the group consisting of the outer matrix material and the inner matrix material further comprises at least one agent selected from the group consisting of a cell, tissue, filler, therapeutic drug, chemoattractant, biocide, ion, peptide, protein, nucleic acid, magnetic compound, and detectable probe. 
     
     
         33 . The microfiber of  claim 26 , wherein at least one of the plurality of droplets further comprises at least one agent selected from the group consisting of a cell, tissue, filler, therapeutic drug, chemoattractant, biocide, ion, peptide, protein, nucleic acid, magnetic compound, and detectable probe. 
     
     
         34 . The microfiber of  claim 26 , wherein the outer matrix material is hydrophilic, the inner matrix material is hydrophobic, and each one of the plurality of droplets is hydrophilic. 
     
     
         35 . The microfiber of  claim 26 , wherein the outer matrix material is hydrophobic, the inner matrix material is hydrophilic, and each one of the plurality of droplets is hydrophobic. 
     
     
         36 . A microfluidic device comprising:
 a first microfluidic duct for delivering a first fluid;   a second microfluidic duct for delivering a second fluid, the second fluid being immiscible with the first fluid, wherein the first microfluidic duct opens into the second microfluidic duct and forms a first fluidic junction therewith;   a third microfluidic duct that is in fluid communication with the first fluidic junction and is wettable by the second fluid;   a fourth microfluidic duct for delivering a third fluid, wherein the third microfluidic duct opens into the fourth microfluidic duct and forms a second fluidic junction therewith; and   an outlet that is in fluid communication with the second fluidic junction.   
     
     
         37 . The microfluidic device of  claim 36 , wherein the first fluidic junction is selected from the group consisting of a flow-focusing junction and a t- junction. 
     
     
         38 . The microfluidic device of  claim 36 , wherein the second fluidic junction is a flow-focusing junction. 
     
     
         39 . The microfluidic device of  claim 36 , wherein the third microfluidic duct is at least partially coated with a polymer that is wettable by the second fluid. 
     
     
         40 . A microfluidic device comprising:
 a first microfluidic duct for delivering a first fluid;   a second microfluidic duct for delivering a second fluid, the second fluid being immiscible with the first fluid,   wherein the first microfluidic duct opens into the second microfluidic duct and forms a first fluidic junction therewith;   a third microfluidic duct that is in fluid communication with the first fluidic junction and is wettable by the second fluid;   a fourth microfluidic duct for delivering a third fluid,   wherein the third microfluidic duct opens into the fourth microfluidic duct and forms a second fluidic junction therewith,   a fifth microfluidic duct that originates from the second fluidic junction and is wettable by the third fluid;   a sixth microfluidic duct for delivering a fourth fluid,   wherein the fifth microfluidic duct opens into the sixth microfluidic duct and forms a third fluidic junction therewith; and   an outlet that is in fluid communication with the third fluidic junction.   
     
     
         41 . The microfluidic device of  claim 40 , wherein the first and second fluidic junctions are independently selected from the group consisting of a flow- focusing junction and a t-junction. 
     
     
         42 . The microfluidic device of  claim 40 , wherein the third fluidic junction is a flow-focusing junction. 
     
     
         43 . The microfluidic device of  claim 40 , wherein the third microfluidic duct is at least partially coated with a polymer that is wettable by the second fluid. 
     
     
         44 . The microfluidic device of  claim 40 , wherein the fifth microfluidic duct is at least partially coated with a polymer that is wettable by the third fluid. 
     
     
         45 . A method of preparing a microfiber, the method comprising the steps of:
 providing the microfluidic device of  claim 36 ;   delivering a first fluid to the first microfluidic duct and a second fluid to the second microfluidic duct, whereby a first emulsion comprising the first fluid into the second fluid is formed within or in the proximity of the first fluidic junction; and   delivering a third fluid to the fourth microfluidic duct, whereby a mixture of the third fluid and the first emulsion is formed within or in the proximity of the second fluidic junction; and   allowing the microfiber to form within or in the proximity of the outlet of the second fluidic junction.   
     
     
         46 . A method of preparing a microfiber, the method comprising the steps of:
 providing the microfluidic device of  claim 40 ;   delivering a first fluid to the first microfluidic duct and a second fluid to the second microfluidic duct, whereby a first emulsion comprising the first fluid within the second fluid is formed within or in the proximity of the first fluidic junction;   delivering a third fluid to the fourth microfluidic duct, whereby a second emulsion comprising the first emulsion within the third fluid is formed within or in the proximity of the second fluidic junction;   delivering a fourth fluid to the sixth microfluidic duct, whereby a mixture of the fourth fluid and the second emulsion is formed; and   allowing the microfiber to form within or in the proximity of the outlet of the third fluidic junction.   
     
     
         47 . A system comprising a microfluidic device and first, second and third fluid reservoirs,
 wherein the microfluidic device comprises first, second, third and fourth microfluidic ducts and an outlet,   wherein the first fluid reservoir comprises a first fluid and is in fluid communication with the first microfluidic duct,   wherein the second fluid reservoir comprises a second fluid and is in fluid communication with the second microfluidic duct, the second fluid being immiscible with the first fluid,   wherein the first microfluidic duct opens into the second microfluidic duct and forms a first fluidic junction therewith;   wherein the third microfluidic duct is in fluid communication with the first fluidic junction and is wettable by the second fluid;   wherein the third fluid reservoir comprises a third fluid and is in fluid communication with the fourth microfluidic duct,   wherein the third microfluidic duct opens into the fourth microfluidic duct and forms a second fluidic junction therewith; and   wherein the outlet is in fluid communication with the second fluidic junction.   
     
     
         48 . A system comprising a microfluidic device and first, second, third and fourth fluid reservoirs,
 wherein the microfluidic devices comprises first, second, third, fourth, fifth and sixth microfluidic ducts and an outlet,   wherein the first fluid reservoir comprises a first fluid and is in fluid communication with the first microfluidic duct,   wherein the second fluid reservoir comprises a second fluid and is in fluid communication with the second microfluidic duct, the second fluid being immiscible with the first fluid,   wherein the first microfluidic duct opens into the second microfluidic duct and forms a first fluidic junction therewith;   wherein the third microfluidic duct is in fluid communication with the first fluidic junction and is wettable by the second fluid;   wherein the third fluid reservoir comprises a third fluid and is in fluid communication with the fourth microfluidic duct,   wherein the third microfluidic duct opens into the fourth microfluidic duct and forms a second fluidic junction therewith;   wherein the fifth microfluidic duct originates from the second fluidic junction and is wettable by the third fluid;   wherein the fourth fluid reservoir comprises a fourth fluid and is in fluid communication with the sixth microfluidic duct;   wherein the fifth microfluidic duct opens into the sixth microfluidic duct and forms a third fluidic junction therewith; and   wherein the outlet is in fluid communication with the third fluidic junction.   
     
     
         49 . A method of physically displacing a microfiber, the method comprising applying a magnetic field to a microfiber, wherein the microfiber is at least one selected from the group consisting of:
 (a) a microfiber comprising a matrix material; wherein the microfiber further comprises a plurality of droplets embedded in the matrix material along the length thereof; wherein each one of the plurality of droplets independently comprises a single fluid; wherein the matrix material of the microfiber is insoluble in each one of the plurality of droplets; and wherein at least one selected from the group consisting of the matrix material and at least one of the plurality of droplets comprises a magnetic compound;   (b) a microfiber comprising a matrix material; wherein the microfiber further comprises a plurality of droplets embedded in the matrix material along the length thereof; wherein each one of the plurality of droplets independently comprises an emulsion comprising a first droplet phase within a second droplet phase; wherein the matrix material of the microfiber is insoluble in the second droplet phase of each one of the plurality of droplets; and wherein at least one selected from the group consisting of the matrix material and at least one of the plurality of droplets comprises a magnetic compound;   (c) a microfiber comprising an outer matrix material and an inner matrix material, wherein the outer matrix material and the inner matrix material span the length of the microfiber; wherein the inner matrix material is embedded in the outer matrix material;   wherein the microfiber further comprises a plurality of droplets embedded in the inner matrix material along the length thereof; wherein the inner matrix material of the microfiber is insoluble in each one of the plurality of droplets and in the outer matrix material; and wherein at least one selected from the group consisting of the matrix material and at least one of the plurality of droplets comprises a magnetic compound;   whereby the microfiber is physically displaced.