The protein is digested into peptide fragments by proteolytic enzymes.

The mixture is then subjected to paper electrophoresis followed by paper chromatography at 90° to the electrophoresis.

The resulting two-dimensional "fingerprint" reveals that normal hemoglobin HbA and sickle-cell HbS hemoglobin differ by a single peptide fragment.

Further analysis shows a single amino acid change: valine is substituted for glutamic acid at the 6th position of the beta chain.