Scaffolded nucleic acid polymer particles and methods of making and using

A method of sequencing a template nucleic acid comprising:

• (a) disposing a particle in a reaction confinement region associated with an electronic-based sensor, wherein the particle includes a non-nucleosidic polymer network and a plurality of template nucleic acids attached to the non-nucleosidic polymer network, the particle having a coefficient of variance of volume of not greater than 15%, wherein the non-nucleosidic polymer network is a polyacrylamide gel, the polymer being permeable to proteins having a size in the range of 50 kilodaltons to 200 kilodaltons;
• (b) performing a polymerase extension reaction on a primer annealed to one or more of the plurality of template nucleic acids to incorporate a nucleotide into the primer;
• and
• (c) detecting a signal output in the electronic-based sensor indicative of the incorporation of the nucleotide into the primer.