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.

1 .- 20 . (canceled) 
     
     
         21 . A method for bulk synthesis of monodisperse, tunable contrast acoustic particles, the method comprising:
 a) agitating in an acidic aqueous solution varying ratios of one of a di-functional, a tri-functional, and a tetra-functional siloxane monomer under conditions sufficient to allow for hydrolysis and the formation of oligomers; and   b) adding a catalyst and continuing to agitate the solution under alkaline pH conditions sufficient to allow for a condensation reaction and formation of 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 siloxane monomers used.   
     
     
         22 . The method of  claim 21 , further comprising removing a majority of the large non-uniform oligomers from the smaller hydrolyzed oligomers after step (a). 
     
     
         23 . The method of  claim 21 , wherein the siloxane monomer comprises a conjugative group such that the group is available for covalent modification in the formed monodisperse particles. 
     
     
         24 . The method of  claim 23 , wherein the conjugative group comprises a vinyl, carboxylate, hydroxyl, epoxide, sulfhydryl, amide, acrylate, thiol, or amine. 
     
     
         25 . The method of  claim 24 , wherein the conjugative group comprises a vinyl group. 
     
     
         26 . The method of  claim 23 , wherein the conjugative group is covalently modified with a moiety for binding to a target of interest. 
     
     
         27 . The method of  claim 26 , wherein the target of interest comprises one of a cell, a protein, a virus, a receptor, an antibody, an antigen, a drug, and a metabolite. 
     
     
         28 . The method of  claim 21 , further comprising washing the particles. 
     
     
         29 . The method of  claim 21 , further comprising heating the solution to about 150° C. for a length of time sufficient to harden the particles. 
     
     
         30 . The method of  claim 21 , wherein the ratio of the tetra-functional to the di-functional siloxane monomer is one of 1:100, about 1:10, about 1:20, or about 1:4. 
     
     
         31 . The method of  claim 21 , wherein the di-functional siloxane monomer is a dimethoxydimethylsilane (DMODMS) or a vinylmethyldimethoxysilane (VMDMOS). 
     
     
         32 . The method of  claim 21 , wherein the tri-functional siloxane monomer is a trimethoxymethylsilane (TMOMS) or a vinyltrimethoxysilane (VTMOS). 
     
     
         33 . The method of  claim 21 , wherein the tetra-functional siloxane monomer is a trimethoxysilane (TMOS) or a (3-Aminopropyl)trimethoxysilane (AmTMOS). 
     
     
         34 . The method of  claim 21 , wherein the catalyst is ammonium hydroxide. 
     
     
         35 . The method of  claim 21 , wherein the monodisperse particles range in size from about 0.5 μm to about 5 μm. 
     
     
         36 . A monodisperse, acoustic contrast particle according to  claim 21 . 
     
     
         37 . A method for acoustic-mediated bioanalysis comprising:
 exposing a fluid sample suspected of containing a target of interest to a plurality of monodisperse, acoustic contrast particles according to  claim 21 , wherein the siloxane monomer comprises a conjugative group, and wherein the conjugative group is covalently modified with a moiety for binding to a target of interest, 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.