Point-of-Care with Raman: Detection of cancer, infection, and more

Mar 25, 2024

Article

The medical industry is a new frontier for Raman spectroscopy. In the past few years, Raman has been used in dental and cancer studies, and is now building on this success by extension into Point-of-Care (POC) applications. This article gives an overview of some very new and exciting research into the use of Raman spectroscopy for the detection of cancerous tissue, biomarkers of disease, and pathogens that cause disease.

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Detecting bone infection with a handheld Raman spectrometer
Raman spectroscopy for cancer detection
Traditional Raman spectroscopy in breast cancer assessment
SERS for detection and measurement of pancreatic cancer biomarkers
Rapid, Point-of-Care (POC) assay for femtogram-level detection of COVID-19
Multiplex immunophenotyping of blood and breast cancer cells with Raman spectroscopy
Easy detection of enzymes with the electrochemical-SERS effect

Detecting bone infection with a handheld Raman spectrometer

Complication from infection is a serious issue for the use of human bone grafts in musculoskeletal surgery. Staphylococcus epidermidis and Staphylococcus aureus are the most common culprits in bone-related infections, and treatment of these bacteria is extremely difficult.

Raman spectroscopy for cancer detection

Raman’s «molecular fingerprint» spectra can be sensitive enough to detect the chemical changes that accompany disease. Compact Raman spectrometers can help surgeons assess tumors during surgical procedures for faster decision-making. Application examples for breast cancer and pancreatic cancer are discussed in the following sections.

Traditional Raman spectroscopy in breast cancer assessment

When breast cancer is suspected, one surgery is typically required for biopsy and a second is for removal of malignant tumors. The ability to assess suspect tissues during preliminary surgery permits immediate removal, if required. The benefit to the patient and to the medical industry is inestimable—and research suggests that Raman spectroscopy may be able meet this need for some types of cancer.

Raman spectroscopy is sensitive enough to detect changes in tissue that result from many types of cancer. For example, there are very subtle differences in Raman spectra from healthy breast tissue and malignant tumors. Researchers in the UK used a high-resolution i-Raman laboratory device (Figure 1) and multivariate tools, including PCA, for successful discrimination of healthy and cancerous tissues [2].

SERS for detection and measurement of pancreatic cancer biomarkers

SERS (surface-enhanced Raman spectroscopy) can be a solution when Raman is not ideal for analysis. This may be the case in situations where the target exists in a complex sample matrix, or because of the fluorescence of carbon-based molecules. SERS enhances the Raman signal, but not the competing fluorescence signal. Also, the SERS effect enables sensitive detection of analytes at mg/L levels—sometimes down to µg/L. Finally, SERS peaks are sharp and well-defined, allowing efficient detection and identification of target analytes.

To learn more about SERS, read our previous blog post on this topic.

Raman vs SERS… What’s the Difference?

Pancreatic cancer is deadly, partly because it is hard to diagnose. However, there are some biomarkers that are present at elevated levels in ~75% of positive cases [3]. These can be detected with enzyme-linked immunosorbent assays (ELISA), which measure a variety of biomarkers, including antibodies, antigens, and proteins.

In an emerging technique, an i-Raman laboratory spectrometer was used at the University of Utah for SERS analysis in conjunction with ELISA to detect an antigen associated with pancreatic cancer [2]. The SERS signal was generated from a reporter molecule complexed to both a gold nanoparticle and the target analyte in an otherwise classical lateral-flow or «sandwich» immunoassay (Figure 2). This is an incredibly accurate technique, enabling very sensitive detection – with potential for quantification – of the biomarker of interest.

Rapid, Point-of-Care (POC) assay for femtogram-level detection of COVID-19

Multiplex immunophenotyping of blood and breast cancer cells with Raman spectroscopy

Another study used MIRA DS to evaluate a portable SERS-based ELISA for immunophenotyping of different types of red blood and breast cancer cell surfaces [5]. Distinguishing healthy and diseased cells and detection of multiple biotargets in one sample can support informed treatment of different kinds of breast cancer.

This assay had «specificity, sensitivity, and repeatability for… immunophenotyping in different cell types [using] smaller analysis sample volume as compared to conventional... multiplex immunoassays,» and it was less «labor-intensive and technically straightforward to perform.» The authors praised MIRA’s Orbital Raster Scan for improving the sensitivity of their assay through a larger area of interrogation and spatially averaged measurements.

Traditional multiplexing flow assays can be limited by availability of different colored stains and interpretation of results. They are also associated with a large laboratory footprint. In contrast, this method based on handheld Raman spectroscopy offers the potential for accurate POC results with quick sample-to-result time, multiplexing capability, and a very compact instrument.

Easy detection of enzymes with the electrochemical-SERS effect

Conclusion

Raman technology is truly being utilized in innovative ways. Research groups worldwide are applying its considerable benefits – including sensitivity, trace detection, small form-factor, and fast results – for detecting cancerous tissue, disease biomarkers, and disease-causing pathogens. The findings are incredibly exciting and promising!