In clinical practice, one objective is to obtain diagnostic
information while minimizing the invasiveness of the
tests and the pain for the patients. To this end, tests based on
the interaction of light with readily available biofluids including
blood, urine, or saliva are highly desirable. In this review
we examine the state of the art regarding the use of surfaceenhanced
Raman spectroscopy (SERS) to investigate
biofluids, focusing on diagnostic applications. First, a critical
evaluation of the experimental aspects involved in the collection
of SERS spectra is presented; different substrate types are
introduced, with a clear distinction between colloidal and noncolloidal
metal nanostructures. Then the effect of the excitation
wavelength is discussed, along with anomalous bands
and artifacts which might affect SERS spectra of biofluids.
The central part of the review examines the literature available
on the SERS spectra of blood, plasma, serum, urine, saliva,
tears, and semen. Finally, diagnostic applications are critically
discussed in the context of the published evidence; this section
clearly reveals that SERS of biofluids is most promising as a
rapid, cheap, and non-invasive tool for mass screening for
cancer.