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1/10/2019 Volatile Organic Compounds (VOC) as non-invasive biomarkers for a range of diseases.

VOC biomarkers
The measurement of the volatile organic compounds (VOCs)
produced by the body's metabolic activity is a powerful approach
to monitoring health and diagnosing disease

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A real-time chemical snapshot of the body's


metabolism

Volatile organic compounds (VOCs) are gaseous molecules that can be sampled
quickly and non-invasively from breath. They can originate either from within
the body (endogenous VOCs) or from external sources such as diet, prescription
drugs and environmental exposure (exogenous VOCs). With over 1,000 VOCs
present in breath, they are a rich source of information regarding the overall
state of health of individuals. In particular, since the production of endogenous
VOCs is linked directly to metabolic activity in the body, particular patterns of
these VOCs can be biomarkers characteristic of specific disease processes, while
measuring the levels of exogenous VOCs in breath can be used to determine
how drugs are being processed within the body, or to measure exposure to
potentially harmful compounds in the environment, such as benzene. And if

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1/10/2019 Volatile Organic Compounds (VOC) as non-invasive biomarkers for a range of diseases.

there are particular metabolic pathways we are interested in, we can use
isotope-marked
 compounds where, for instance, a 12C atom is replaced by a
heavier 13C one. We can then determine whether the molecule is being broken
down by looking for decay products, such as CO2, containing the heavier
isotope (i.e. 13CO2).

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1/10/2019 Volatile Organic Compounds (VOC) as non-invasive biomarkers for a range of diseases.

Metabolomics vs Genomics

Over the past two decades, a great deal of research has focused on genomics.
While this science has made significant advances, it has not yet delivered on its
full potential to help us understand and cure diseases. Genes serve as the
blueprint for an organism’s biological functions, but it is rare that a single
mutation will result in disease. In most circumstances, a disease is the result of
multiple genetic attributes interacting with environmental factors, diet and
lifestyle choices, microbiome differences and metabolic responses. When an
organism’s biological systems are altered by disease, genetic mutations, or
environmental factors, the profile of metabolites produced by these systems also
changes. This response makes metabolites excellent candidates for biomarkers
for early detection of disease, differentiating related disease states, and
monitoring toxicities and other drug interactions.

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1/10/2019 Volatile Organic Compounds (VOC) as non-invasive biomarkers for a range of diseases.

VOCs in Cancer and the


Warburg Effect
In the case of cancer, the growth of
each tumour is driven by
accumulating genetic changes in
bodily cells. These changes are small
and variable but have a large
uniform downstream effects: cells
escape the immune system and
grow in an unchecked manner.
These effects are therefore reflected
by cellular metabolism at a much
larger scale. As metabolites are the
end-product of cellular activity they
are actively excreted into the
extracellular space. Furthermore,
tumor effects such as immune system
activation, weight loss and increased
oxidative stress all contribute to

changes in the body’s metabolic
signature.

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1/10/2019 Volatile Organic Compounds (VOC) as non-invasive biomarkers for a range of diseases.

One particularly notable metabolic


 change associated with cancer is the
Warburg effect, with a hugely
increased glycolysis rate in
cancerous cells. This leads to
significantly raised levels of
metabolites such as lactate and
fumarate, noticeably altering the
VOC profile in breath.

VOC biomarkers in
Inflammatory Disease
VOC biomarkers are also of use
across a range of inflammatory
disease. In asthma, for example,
various VOCs, such as dodecane,

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1/10/2019 Volatile Organic Compounds (VOC) as non-invasive biomarkers for a range of diseases.

cyclohexane and 2-butanone, reflect


airway
 inflammation, and can be
used to differentiate between
different asthma phenotypes.
Patients with inflammatory bowel
disease (IBD), meanwhile, have been
found to have elevated levels of
ester, indole and short-chain fatty
acids, likely due to dysbiosis of
microbiota. Changes of the VOC
profile of this kind have allowed 
Owlstone’s FAIMS technology to be
used to detect IBD, and to
differentiate between patients
suffering from Crohn’s disease and
those suffering from ulcerative
colitis.

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healthcare providers $1.5B

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1/10/2019 Volatile Organic Compounds (VOC) as non-invasive biomarkers for a range of diseases.

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