Acoustically Responsive Particles

Abstract

Acoustically responsive particles and methods are provided for their use. Methods are provided for making and using tunable, monodisperse acoustically responsive particles and negative contrast acoustic particles, wherein the particles can contain a functional group available for covalent modification.

What is claimed is: 
     
         1 . A method for bulk synthesis of monodisperse, tunable contrast acoustic particles, the method comprising:
 agitating in an acidic aqueous solution, varying ratios of a di-functional, a tri-functional, and a tetra-functional monomer under conditions sufficient to allow for hydrolysis; and   adding a catalyst and continuing to agitate the solution under alkaline pH conditions sufficient to allow for a condensation reaction and formation of acoustic contrast particles with a narrow size distribution; monodisperse acoustic contrast particles,   wherein the tunable acoustic contrast of the monodisperse particles formed is based on the ratios of the di-functional, tri-functional, and tetra-functional monomers used.   
     
     
         2 . The method of  claim 1  wherein the di-functional, a tri- functional, and a tetra-functional monomers form two, three, or four siloxane bonds, respectively. 
     
     
         3 . The method of  claim 1  further comprising removing a majority of the larger non-uniform oligomers from the hydrolyzed monomers. 
     
     
         4 . The method of  claim 2 , wherein the monomer comprises a conjugative group that is available for covalent modification in the formed monodisperse particles. 
     
     
         5 . The method of  claim 4 , wherein the conjugative group comprises a vinyl, carboxylate, hydroxyl, epoxide, sulfhydryl, amide, acrylate, thiol, or amine. 
     
     
         6 . The method of  claim 4 , wherein the conjugative group comprises a vinyl group. 
     
     
         7 . The method of  claim 1 , wherein the ratio of the tetra-functional to the di-functional monomer is between 1:1000 and 1:2. 
     
     
         8 . The method of  claim 1 , wherein the di-functional monomer is a dimethoxydimethylsilane (DMODMS) or a vinylmethyldimethoxysilane (VMDMOS). 
     
     
         9 . The method of  claim 1 , wherein the tri-functional monomer is a trimethoxymethylsilane (TMOMS), a vinyltrimethoxysilane (VTMOS), or a (3-aminopropyl)trimethoxysilane (AmTMOS). 
     
     
         10 . The method of  claim 1 , wherein the tetra-functional monomer is a tetramethoxysilane (TMOS, a.k.a. tetramethyl orthosilicate) or a tetraethoxysilane (TEOS, a.k.a. tetraethyl orthosilicate). 
     
     
         11 . The method of  claim 1 , wherein the catalyst is ammonium hydroxide or triethylamine. 
     
     
         12 . The method of  claim 1 , wherein the monodisperse particles range in size from about 0.5 μm to about 5 μm. 
     
     
         13 . A monodisperse, acoustic contrast particle formed by the method of  claim 1 . 
     
     
         14 . A monodisperse, acoustic contrast particle formed by the method of  claim 1 , wherein the conjugative group is covalently modified with a moiety for binding to a target of interest. 
     
     
         15 . The monodisperse, acoustic contrast particle of  claim 14 , wherein the target of interest comprises a cell, a protein, a virus, a receptor, an antibody, an antigen, a drug, or a metabolite. 
     
     
         16 . A method for acoustic-mediated bioanalysis comprising:
 exposing a fluid sample suspected of containing a target of interest to a plurality of acoustic contrast particles according to  claim 14  under conditions sufficient that the moiety binds to the target; and   subjecting the fluid sample to acoustic radiation pressure from an acoustic standing wave sufficient within an acoustic focusing chamber to focus the particles to the acoustic antinodes such that the target is separated from other components in the sample.   
     
     
         17 . The method of  claim 3  wherein the monomer comprises a conjugative group that is available for covalent modification in the formed monodisperse particles. 
     
     
         18 . A monodisperse, acoustic contrast particle formed by the method of  claim 3 , wherein the conjugative group is covalently modified with a moiety for binding to a target of interest. 
     
     
         19 . The monodisperse, acoustic contrast particle of  claim 18 , wherein the target of interest comprises a cell, a protein, a virus, a receptor, an antibody, an antigen, a drug, or a metabolite. 
     
     
         20 . A method for acoustic-mediated bioanalysis comprising:
 exposing a fluid sample suspected of containing a target of interest to a plurality of acoustic contrast particles according to  claim 18  under conditions sufficient that the moiety binds to the target; and   subjecting the fluid sample to acoustic radiation pressure from an acoustic standing wave sufficient within an acoustic focusing chamber to focus the particles to the acoustic antinodes such that the target is separated from other components in the sample.