Amino acid (AA) disorders are the main class of inborn errors of metabolism with diverse medical presentations. This paper was aimed to provide a novel and efficient sensor array for the quantification and differentiation of AAs using different pH buffer solutions as sensor elements (SEs) and nanocurcumin (NC) in the role of a marker in biofluids of newborn babies. Amino and carboxyl groups along with the side chain of different AAs in different pH buffer solutions are protonated or deprotonated. This makes each AA molecule an acid (in the role of a proton donor), a hydrogen bonding donor, as well as a polar ion. So that, these differences may permit a profile differentiation-based sensor array for AAs discrimination. Using NC as a marker, the interactions between AA and NC in different pH buffer solutions (mainly involved in acid-base, hydrogen bonding, and π- π stacking interactions) result in absorbance changes, making a discriminate response profile for each AA. The results reveal that AAs can be discriminated successfully at three concentrations levels 10, 25, and 50 μM by linear discrimination analysis (LDA) and hierarchical clustering analysis (HCA). Complex AA mixtures are also capable to be classified. The results show that our sensor array can be potentially employed to the differentiation of AAs in biofluids of healthy and unhealthy newborn babies. It should be noted that the sensor array requires only common and available lab equipment and materials, which can be applied in AAs-related fundamental studies and clinical diagnosis.