Analytical capability of Raman spectroscopy to detect biochemical changes in red blood cell membrane disorders

Detection of RBC membrane disorders with currently available modalities, such as osmotic fragility test (OFT), EMA binding test, ektacytometry, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), and next-generation sequencing (NGS), has been challenging as they either lack biochemical inferences or are complex in nature. Raman spectroscopy, a highly analytical method known to produce molecular fingerprints, has proven potential in extracting biochemical information from single individual cells. Recent advancements in membrane-targeted Raman measurements using excitation spots of donut and line intensity profiles can transform lab-on-chip Raman-activated cell sorting methods into a potential technique for RBC membrane disorder diagnosis. We, therefore, conjecture that Raman spectroscopy can be a strong contender as a diagnostic modality in RBC membranopathies. In this comprehensive review, we have attempted to encompass the disorder-specific molecular defects, present diagnostic modalities, and their limitations, and explored the translational possibility of Raman spectroscopy as a diagnostic tool for membranopathies.