The Use Of Raman Spectroscopy And Microfluidics In Determining The Biochemical Progression From Barrett’s Oesophagus To Oesophageal Adenocarcinoma

Oesophageal adenocarcinoma (OAC) is a highly aggressive cancer, often arising from
Barrett's oesophagus (BO), a condition where the normal squamous epithelium is replaced by intestinal-like columnar epithelium due to chronic acid and bile reflux. Disease progression typically follows a continuum from non-dysplastic BO to dysplasia, eventually leading to OAC. Identifying the biochemical and mechanical changes at each stage is crucial for early diagnosis and intervention. This study utilised advanced single-cell techniques, including Raman spectroscopy and deformation cytometry, to characterise these changes and develop novel diagnostic tools.

Single-cell Raman spectroscopy, a non-invasive biophysical technique, was applied to detect biochemical signatures in healthy oesophageal tissue, non-dysplastic and dysplastic BO, and OAC. This revealed distinct spectral features linked to lipid, protein, and nucleic acid content, reflecting cellular changes during disease progression. For instance, cancerous cells exhibited increased nucleic acid content, indicating higher metabolic activity, while dysplastic cells displayed early alterations in lipid profiles. These biochemical variations highlight potential biomarkers for early detection of oesophageal malignancies.

To complement the biochemical profiling, deformation cytometry was used to measure the mechanical properties of individual cells with microfluidic devices. This revealed significant decreases in cell stiffness in dysplastic and cancerous cells compared to healthy and nondysplastic BO cells, likely due to cytoskeletal remodelling, a hallmark of tumour progression and metastasis. By integrating Raman spectral data with mechanical measurements, this study created a multi-modal framework capable of accurately distinguishing disease stages.

The microfluidic platforms facilitated high-throughput single-cell analysis, enabling rapid,
automated measurement of biochemical and mechanical properties while improving
reproducibility. This system also allowed real-time monitoring of cellular changes,
demonstrating potential applications for time-sensitive studies like drug response
evaluations. Together, these findings highlight the promise of combining Raman
spectroscopy and deformation cytometry as diagnostic tools for early cancer detection and clinical applications.