Biomedical Engineering Reference
In-Depth Information
22.1
Introduction
22.1.1
Saliva—A miracle biofluid?
Diagnostic tests based on biological fluids in general utilize blood, cerebrospinal fluid, perito-
neal fluid, drainage fluid, urine, feces, and seldomly use esoteric fluids such as saliva, sweat, and
tear. One may even say that saliva's popularity has suffered because it lacks “the drama of blood”,
the “sincerity of sweat,” and the “emotional appeal of tears”
[1]
. With regard to obtaining sufficient
sample volumes for clinical biochemical analysis, sweat and tears pose sample volume issues and
urine lacks the wider acceptance by patients due to privacy issues. Therefore, saliva by default
becomes the biological fluid of interest.
Human saliva offers several advantages over traditional blood-based biochemical assays for
clinical diagnostics due to its noninvasiveness and stress-free sample collection, ease and multiple
sampling opportunities, reduced need for sample preprocessing, minimal risk of contracting infec-
tious organisms such as human immunodeficiency virus (HIV) and hepatitis-B virus (HEP-B), and
it is an ideal biofluid for developing countries in the world due to cost-effective sample collection
and processing
[2
4]
. In addition, saliva is an ideal biological fluid for performing clinical assays
in neonates and in the elderly due to its noninvasive properties and ease of collection. The question
that comes to mind then is why are there no saliva-based tests at the doctor's office or in use at the
clinical pathology laboratories to date? The answer is that the translation and advancement of saliva
diagnostics is hindered by two major obstacles: the analyte concentration in saliva is typically 100
th
to 1000
th
fold less than in blood, therefore requiring sensitive detection technologies to discern the
diagnostic wealth of knowledge trapped within a saliva sample, and up until now the dearth of
available technologies for sample collection and processing.
Human saliva mirrors the body's health and well-being, and most of the biomolecules that are
present in blood or urine can also be found in salivary secretions
[5]
. A recent study by Yan et al.
[6]
compared the human salivary proteome to the plasma proteome by using a peptide fractionation
method coupled to a cation exchange and mass spectrometry (MS) technique and revealed a total
of 3020 proteins in plasma, 597 (
20%) of which were also found in human saliva. This highlights
the clinical usefulness of saliva for disease detection. When using a hexapeptide library to compress
the dynamic range of proteins present in saliva (i.e., to enrich low abundant proteins), Bandhakavi
et al.
[7]
identified 2340 salivary proteins using a single analysis platform. In contrast to the plasma
proteome, in which 99% of the total protein content is made up of only 22 abundant proteins
[8]
,
the 20 most abundant proteins in human whole saliva (WS) constitute only 40% of the protein con-
tent
[8]
This implies that it should be feasible to detect biomolecules of clinical sensitivity and
specificity in saliva with ease as compared to blood.
Saliva is a clinically informative biofluid that may be useful for early disease detection, disease
prognosis, and risk stratification as well as monitoring treatment response in patients facilitating
easy clinical management of diseases. However, most of the current attempts to discern biomolecules
in saliva that are suitable for clinical applications (i.e., technologies with high sensitivity and high
specificity) are in their infancy, and have not yet been translated from a research laboratory to the
clinic. As an example, researchers have developed rapid immunoassays to measure salivary
C-reactive protein (CRP) levels (an acute inflammation marker that is also associated with the devel-
opment of ischemic heart disease (IHD)
[9,10]
), to detect coronary events at an early stage
[11
B
13]
.
