Most hemoglobins are soluble in a high-molarity phosphate buffer; Hb S is not. The buffer is made up of dibasic and monobasic potassium phophates, saponin, and dithionate. A 1:100 dilution of blood into buffer is made, incubated for 5 minutes, and turbidity is observed against a white background with black lines.
A positive result (A below) is indicated by a turbid solution.
A negative result (B below) is obtained when lines are visible through the solution.
The solubility test should only be used as a screening test as it is not reliable for diagnosing sickle cell disease.