Ultrasound molecular sensors and uses thereof
The present invention relates to the use of polymers as contrast agents for ultrasounds. The idea is to have a molecular imprint in the polymer that is specific for a given molecule or analyte. When that molecule binds to the polymer it induces a conformational change that results in an increase in the ultrasound signal, referred to as a target-bound state. The method can also be used for example for quantitative measurements of analytes.
1. A method for ultrasound contrast enhancement, comprising:
providing an ultrasound molecular sensor consisting of a hydrogel polymer with one or more target binding sites for binding one or more target molecules, said ultrasound molecular sensor having target-bound and target-unbound states wherein binding of said one or more target molecules to said ultrasound molecular sensor causes a modulation in one or more frequencies of an ultrasound signal; contacting said ultrasound molecular sensor with said one or more target molecules to produce ultrasound molecular sensor in the target-bound state; and obtaining an ultrasound signal of the target-bound ultrasound molecular sensor at one or more ultrasound frequencies wherein the signal comprises a modulation indicative of the presence of at least one target molecule.
2. The method as claimed in claim 1 wherein the modulation is selected from a relative intensity value of two or more frequencies and a shift in one or more frequencies.
3. The method as claimed in claim 1 wherein the one or more frequencies comprise anharmonic frequencies.
4. The method as claimed in claim 1 , further comprising quantifying the one or more target molecule.
5. The method as claimed in claim 4 wherein the quantifying comprises: establishing a standard curve using signal amplitude of at least one frequency characteristic of the presence of the target molecule; or establishing a linear combination of signal amplitude at multiple frequencies that correlates with concentration of the target molecule.
6. The method as claimed in claim 1 wherein the target molecule binding sites are selected from an aptamer, antibody, variable regions of antibody, receptor, nucleic acids, protein or part thereof, carbohydrates, molecular imprints and combinations thereof.
7. The method as claimed in claim 1 wherein two or more target molecules are simultaneously detected.
8. The method as claimed in claim 7 wherein two or more ultrasound molecular sensors are used to detect the target molecules.
9. The method as claimed in claim 1 wherein said detection is performed in a sample obtained from a subject and said sample is a blood sample.
10. The method as claimed in claim 1 further comprising administering the ultrasound molecular sensor to a subject and wherein the detection of the target molecule is performed in situ.
11. The method as claimed in claim 10 wherein said administration is selected from either of enteral and parenteral.
12. The method as claimed in claim 1 , wherein the hydrogel polymer is selected from polyacrylamide, cellulose and alginate.
13. The method as claimed in claim 1 wherein the hydrogel polymer is selected from isopropylacrilimide (NIPA), hydroxypropyl cellulose (HPC) and carboxymethyl cellulose (CMC).