Gold standard diagnosis

Duncan Graham of the Centre for Molecular Nanometrology at the University of Strathclyde, and colleagues in the Division of Cancer Sciences and Molecular Pathology at the University of Glasgow, have combined surface-enhanced resonance Raman scattering (SERRS) spectroscopy with a biological test called ELISA to improve accuracy, lower detection limits and make testing for early prostate cancer less invasive and less expensive.¹ 

ELISA, or enzyme-linked immunosorbent assay, is widely used in medical diagnostics, biomedical research and in environmental studies. The technique involves tagging an enzyme with a marker, usually a fluorescent molecule known as a chromophore, and attaching this to an antibody that will recognise the target compound. In this case the target is prostate specific antigen, a protein present in blood serum of men with prostate cancer. If the antigen is present in the sample, the antibody binds to it, which activates the enzyme and this in turn triggers the chromophore. Fluorescence spectroscopy is used to detect the characteristic fluorescence signal and prove that the antigen is present. However, fluorescence spectroscopy in ELISA can only detect one marker molecule at a time because trying to detect more than one would lead to a confusing spectrum with many overlapping signals caused by chromophores used for different targets. 

SERRS, in contrast, requires no fluorescence marker and instead uses gold nanoparticles conjugated to the enzyme-antibody probe to enhance the weak but relatively sharp Raman spectral lines produced when the antigen is bound by the antibody. This means SERRS coupled with ELISA could in theory be used to detect several antigens at once. 

Graham's team has demonstrated that commercially available gold nanoparticles can be used in a SERRS-ELISA test to detect the prostate specific antigen at picograms per millilitre (10^-12 g ml^-1) levels in a patient's serum sample. 'The [current] technique is amenable over a wide range of concentrations and lends itself to future multiplex analysis', the researchers explain. They add that single-molecule detection is also possible and SERRS is more reliable and cheaper compared with many other techniques. 

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