Polymer backbone element tags
Element tags based on novel metal-polymer conjugates are provided for elemental analysis of analytes, including ICP-MS. A polymer backbone is functionalized to irreversibly bind metals that are selected prior to use by the user. The polymer is further functionalized to attach a linker which allows for attachment to antibodies or other affinity reagents. The polymer format allows attachment of many copies of a given isotope, which linearly improves sensitivity. The metal-polymer conjugate tags enable multiplexed assay in two formats: bulk assay, where the average biomarker distribution in the sample is diagnostic, and single cell format to distinguish a rare (for example a diseased) cell in a complex sample (for example, blood).
1. A method comprising:
providing an isotopic composition comprising multiple lanthanide atoms of a single isotope of a lanthanide;
providing an element tag comprising a linear or branched polymer comprising a plurality of chelating groups, wherein each chelating group is capable of binding at least one of the lanthanide atom of the isotopic composition; and
binding the lanthanide atoms of the isotopic composition to the one or more chelating groups of the element tag;
wherein:
the isotopic composition does not comprise a natural mixture of isotopes, and
the lanthanide atoms are non-radioactive.
2. The method of claim 1 , further comprising providing an additional isotopic composition wherein the additional isotopic composition comprises multiple additional lanthanide atoms of an additional single isotope of a non-radioactive lanthanide that is different from the single isotope of the non-radioactive lanthanide of the isotopic composition.
3. The method of claim 2 , further comprising providing an additional element tag comprising an additional linear or branched polymer comprising a plurality of chelating groups.
4. The method of claim 3 , wherein each chelating group of the linear or branched polymer of the element tag includes at least one lanthanide atom of the isotopic composition, and wherein each additional chelating group of the additional linear or branched polymer of the additional element tag includes at least one additional lanthanide atom of the additional isotropic composition.
5. The method of claim 1 , further comprising:
providing a biomolecule; and
covalently binding the biomolecule to the element tag.