Optical sensing of albumin in human serum and urine-A historical review of the transition from classical dye-binding assays to advanced technologies.

Human serum albumin (HSA) is the most abundant protein in human plasma playing essential roles in transporting various biomolecules, metal ions, therapeutic agents, and metabolites. Additionally, it is crucial for maintaining oncotic pressure, scavenging free radicals, and preventing protein aggregation. Accurate quantification of HSA is vital for diagnosing various conditions, including hypertension, diabetes mellitus (DM), liver disorders, and renal diseases. While prevalent in clinical laboratories, traditional dye-binding methods have notable limitations: they can be time-consuming, lack sensitivity, and may suffer from interference from other serum components. These methods often require complex sample preparation and do not readily lend themselves to rapid or point-of-care testing (POCT). Consequently, there is a pressing need for innovative techniques that are rapid, cost-effective, and user-friendly. This review explores various dyes utilized for HSA determination, categorized into groups such as sulfonphthaleins, phenolphthaleins, azo dyes, etc., and provides a historical overview of the limitations of these methods. We critically assess the pros and cons of traditional dye-binding assays and emphasize the potential of emerging technologies, including microfluidic systems, smartphone-based detection, and nanopaper sensors, to address these gaps and enhance the efficiency and accessibility of HSA quantification in clinical settings.