Methods and apparatus for analyzing polynucleotide sequences

A method of analyzing a target polynucleotide comprising:

• (a) pretreating the surface of a substrate with a polyelectrolyte multilayer (PEM) to create surface chemistry that facilitates polynucleotide attachment and sequence analysis;
• (b) providing a primed target polynucleotide attached to a surface of a substrate;
• (c) providing a labeled first nucleotides to the attached target polynucleotide under conditions whereby the labeled first nucleotide attaches to the primer, if a complementary nucleotide is present to serve as template in the target polynucleotide;
• (d) determining presence or absence of a signal, the presence of a signal indicating that the labeled first nucleotide was incorporated into the primer, and hence the identity of the complementary base that served as a template in the target polynucleotide;
• (e) repeating steps (c)-(d) with a labeled further nucleotide, the same or different from the first labeled nucleotide, whereby the labeled further nucleotide attaches to the primer or a nucleotide previously incorporated into the primer;
• and
• (f) repeating step (e) until identities of the bases in a portion or all of the target polynucleotide are determined.