Abstract: Provided are methods and systems for characterizing a biomolecular parameter of a polynucleotide. A polynucleotide of interest from a sample comprising a heterogeneous mixture of polynucleotides is concentrated and provided to a first fluid compartment of a solid-state nanopore. An electric potential is established across the solid-state nanopore to force the polynucleotide of interest from a first fluid compartment to a second fluid compartment via the nanopore. A passage parameter output is monitored during passage of the polynucleotide of interest through the nanopore, wherein the passage parameter output depends on the biomolecular parameter status of the polynucleotide of interest. In this manner, the methods and systems are compatible with a wide range of applications, including epigenetic modifications to DNA indicative of a disease state such as cancer, in an integrated, reliable and low cost system.