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Portable Raman Spectroscopy for Biomedical Diagnostics and Trace Analysis

Technical notes | 2020 | MetrohmInstrumentation
RAMAN Spectroscopy
Industries
Clinical Research
Manufacturer
Metrohm

Summary

Significance of the Topic


Raman spectroscopy has emerged as a powerful tool for molecular fingerprinting in biomedical diagnostics, enabling near real-time and minimally invasive analysis at the point of care. Its sensitivity to chemical changes associated with disease makes it highly valuable for early detection and monitoring. Surface Enhanced Raman Spectroscopy (SERS) further extends capability to trace-level detection through signal enhancements up to 10^6, supporting applications that demand high sensitivity and low detection limits.

Study Objectives and Overview


The purpose of the work is to demonstrate the utility of a portable Raman system for diverse biomedical and trace analysis tasks. Key application areas include:
  • Biopsy analysis for tissue abnormality assessment
  • Cytology at the single-cell level
  • Drug efficacy monitoring
  • Detection of biomarkers for early-stage diseases such as cancer or tuberculosis
  • Guidance of surgical targets and treatment follow-up
A focus is placed on integrating SERS substrates to achieve enhanced sensitivity for trace analysis.

Methodology and Instrumentation


The spectral regions of interest correspond to characteristic molecular vibrations in biological samples. Important regions include:
  • 4000–2500 cm–1 for X–H stretching modes (e.g. C–H)
  • 2500–2000 cm–1 for triple bonds (e.g. N≡C)
  • 2000–1500 cm–1 for double bonds (e.g. C=C, N=C)
  • 1500–600 cm–1 for complex fingerprint patterns (e.g. C–O, C–N)
Instrumentation employed:
  • i-Raman Prime 785S portable spectrometer (also available with 532 or 1064 nm excitation)
  • Lab-grade trigger probe for consistent sampling
  • Video microscope with XYZ stage for precise targeting
  • BWIQ quantitative analysis software for data processing
  • SERS substrates (e.g. TacPac-P™) to achieve up to 10^6 signal enhancement

Main Results and Discussion


The portable i-Raman system reliably captures Raman signatures of lipids, fatty acids and proteins in tissue specimens. Key findings include:
  • Clear differentiation of healthy versus diseased tissue based on spectral features in the fingerprint region
  • SERS-enabled detection of trace biomarkers at sub-micromolar concentrations
  • High reproducibility of spectra when using the lab-grade probe and controlled sampling environment
The enhanced sensitivity of the SERS substrates allows for rapid, label-free screening of minute sample volumes, supporting early disease detection and therapeutic monitoring.

Benefits and Practical Applications of the Method


  • Point-of-care capability for near real-time decision making
  • Minimally invasive sampling with fiber-optic probes
  • Label-free detection reduces sample preparation time and cost
  • Wide spectral coverage supports identification of diverse molecular species
  • Trace-level sensitivity via SERS expands applications in biomarker discovery and environmental monitoring

Future Trends and Potential Applications


  • Integration with machine learning for automated spectral classification
  • Development of multiplexed SERS substrates targeting multiple analytes simultaneously
  • Miniaturization and wearable Raman probes for continuous health monitoring
  • Remote and in situ diagnostics in resource-limited settings
  • Advanced chemometric methods to deconvolute complex biological spectra

Conclusion


Portable Raman spectroscopy, especially when combined with SERS, offers a versatile platform for rapid, sensitive and minimally invasive biomedical diagnostics and trace analysis. The i-Raman Prime system, together with tailored SERS substrates and advanced software, enables reliable detection of molecular markers across a range of applications from tissue biopsy to cytology and biomarker screening. Continued advancements in instrumentation and data analysis will extend its reach into novel diagnostic and monitoring scenarios.
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