M34 - Raman Spectroscopy at an Electrochemical Interface: Investigating the Effectiveness of Surface Modifications for N-Glycan Detection

In fifteen words or less, explain the significance of this contribution (Novel Aspect).: Combines orthogonal techniques; Raman spectroscopy provides new and underexplored opportunities in electrochemical biosensor development.

Abstract Text:

Accurate detection of cancer, along with the effective monitoring of treatment response, remain a critical challenge in oncology. Altered N-glycosylation, including changes in the structure and expression levels, is strongly associated with cancer progression and has been widely reported. The detection of N-glycans present on cancer cell surfaces therefore presents a promising approach for cancer diagnostics and drug treatment response monitoring.

Owing to their rapid detection, high sensitivity, low-cost, and ease-of-use, electrochemical biosensors offer an attractive alternative to conventional diagnostic techniques. However, designing stable biosensor interfaces capable of reliably detecting whole cancer cells and distinguishing between subtle phenotypic changes remains difficult. Here, an electrochemical biosensor has been designed for the detection of N-glycans present on the surface of cancer cells. Based on a modified gold screen-printed electrode, a stable and biocompatible chitosan layer is used to immobilise Concanavalin A (Con A) – a mannose-specific lectin. Mannose is an integral building block of the N-glycan structure and its affinity for Con A enables selective binding. As levels of mannose can vary at the cell membrane between cell types, differentiation of cell lines and disease state can be achieved.

This work combines the analytical capabilities of electrochemical impedance spectroscopy with the characterisation strengths of Raman spectroscopy. The developed sensor provides distinct impedance responses for different cancer cell lines based on variations in their glycosylation profiles and demonstrates a detection limit which rivals more complex electrochemical biosensors reported in literature. To validate the electrochemical results, Raman microscopy was employed to characterise the interface with and without modification, and following cell incubation. Raman spectroscopy offers the critical advantage of allowing the sensor surface to remain hydrated throughout characterisation, avoiding the need for drying steps required by techniques such as SEM or FTIR.

The addition of Raman spectroscopy within the development workflow of an electrochemical device provides invaluable information, enabling in situ analysis without interfering with biosensor performance. This strategy supports the broader goal of integrating surface characterisation with real-time biosensing under biologically relevant conditions.