Comparative review of glycated albumin detection from conventional colorimetric assays to Raman spectroscopy, surface-enhanced Raman scattering, and surface plasmon resonance.

Albumin is the most abundant protein in plasma, and has a high susceptibility to non-enzymatic glycation. This results in the production of glycated albumin (GA). It indicates short-term glycemic status (2-3 weeks). Unlike hemoglobin A1c (HbA1c), GA is not affected by red blood cell lifespan, making it a reliable glycemia marker in conditions such as hemoglobinopathies, pregnancy, and renal diseases. Traditional colorimetric assays, such as nitro blue tetrazolium (NBT), have low specificity due to interference from other reducing agents. This review compares conventional detection with three emerging optical techniques. Raman spectroscopy (RS) and surface-enhanced Raman spectroscopy (SERS) provide reagent-free detection of GA. RS detects chemical and structural changes in albumin from changes in Raman scattering of molecular vibrations, particularly shifts in amide I and III vibrational bands. SERS magnifies these signals from localized electromagnetic fields at metallic nanoparticle spots. Also, surface plasmon resonance (SPR) detects changes in refractive index in GA after binding to a sensor surface using boronic acid derivatives and kinetic analysis. This comparative review explains how glycation of albumin, both qualitatively and quantitatively, can be measured by conventional versus RS, SERS, and SPR as better diagnostic tools.