1501 Refocus metabolomics

METABOLOMICS IN 2015:
Renton (Ewan McGregor) // Trainspotting
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TABLE OF CONTENTS
Cover article
News
Pages 3-13
01 02
Reflections
Xtandards
Pages 14-17
03
Network News
ure X
Pages 18-20
04
News Flash
a
Pages 21-24
05
Gadgets &
Innovations
Pages 25-33

4
THE OVER-EXAGGERATED HYPE
Metabolomics is often described as the study of “the
complete set of low molecular weight
intermediates, which are context dependent,
varying according to the physiology,
developmental or pathological state of the cell,
tissue, organ or organism”.
In fact, metabolomics is a new term for an old science in
which classical biochemical concepts are investigated.
New and unique to the current research that is being
conducted is the combination with genomics information
and full system biology.

5
The molecules involved in metabolic analysis are
chemically very diverse, consisting of a broad range of
polarities, chemistries and size.
Additionally, metabolites are present at a wide range of
concentrations within a particular sample.
These two facts, next to the large number of metabolites
that have to be detected comprehensively in certain
metabolic experiments, contribute to the major challenges
of performing this type of analyses and studies.
OR NOT?

6
METABOLITE TYPES
Primary metabolite
Directly involved in normal growth,
development and reproduction. Strongly
conserved among species.
Secondary metabolite
Not directly involved in normal growth,
development and reproduction. The
absence of secondary metabolites does
not result in immediate death, rather in
long term impairment of the organism’s
survivability. Secundary metabolites are
often restricted to a narrow set of species
within a phylogenetic group. They often
occur in low concentrations.
There are estimated to be approximately 2.000 primary metabolites in humans with this
number increasing by 10-fold or more if secondary metabolites are considered as well.
“

7
RESEARCH AREAS
Target compound analysis:
Carried out to determine and quantify specific metabolites of
interest in a consistent & accurate manner.
Metabolite profiling:
Used to determine, qualitatively or quantitatively, a group of
related compounds or associated specific metabolic pathways,
such as carbohydrates, amino acids, etc.
Metabolomics:
Comprehensive analysis of the whole metabolome under a given
set of conditions. Carried out quantitatively as well as semi-
quantitatively.
Metabolomic fingerprinting:
Metabolic fingerprinting is not aimed at the identification of
individual compounds but rather at the comparison of patterns or
fingerprints of metabolites and how they change in response of
disease or exposure to toxins.
Indicative
²²²
Accurate, validated & reliable

8
DISCUSSION
Critical to obtaining valid metabolomic data is understanding the question behind a study.
This means knowledge of and/or hypotheses on the metabolic pathways that could be
involved in the particular question under investigation. Once these hypotheses are described
and particular metabolites have been identified, it is much easier to develop analytical
procedures that accurately target these analytes. For example, many secondary metabolites
are easier to analyze by LC/MS methods whereas most primary metabolites can readily be
quantified by GC/MS. In the same respect, it is evenly important to identify the chemical
classes of compounds that should be targeted, because this has a determining influence on the
analytical strategy that is finally opted for.
Metabolomics has to be considered an extension of
classical target-driven analytical chemistry.
“

9
DISCUSSION
The identification of metabolites must always be based on at least two orthogonal physicochemical characteristics,
such as retention index and mass spectrum. Identifications that are based on authentic chemical standards are generally
more trustworthy than annotations based on calculated characteristics. Nevertheless, the metabolome itself is an
unrestricted entity that clearly comprises more than the suite of known compounds to be found in classical textbooks or
that can be purchased from chemical manufacturers. The metabolome cannot be simply computed from reconstructed
biochemical pathways due to enzymatic diversity, substrate ambiguity and variation in regulatory mechanisms. The sheer
complexity of natural products, including isomeric compounds, renders the use of accurate masses and database queries
often insufficient for correct metabolite annotation.
Quality control is important.
This means that short as well as long-term influence of matrix effects is carefully evaluated. Only if quantification of a
range of well-known target metabolites validates a specific analytical protocol, can unbiased analysis be furthered to the
level of metabolomics and comprise novel metabolite signals. QC/QA has to include randomized sample sequences, blank
controls and bracketing samples with external calibration standards.

0
50
100
150
200
250
300
0 25 50 75 100 125 150
Concentration/ppb
Time / seconds
COMPARISON OF SMOKER’S AND NON
SMOKER’S BREATH
Acetone Ethanol Isoprene Acetonitrile
Non smoker Smoker
WHAT CAN WE DO FOR YOU?
Selected-ion Flow Tube MS
SIFT-MS is a dedicated MS technique that uses soft
chemical ionization with three reagent ions in a flow tube.
The technique is particularly well suited for real-time
analysis of volatile compounds (organic as well as
inorganic) without the need for external calibration
(absolute quantification).
We use SIFT-MS in exhaled breath analysis:
 SCAN analysis: biomarker discovery
 SIM analysis: in-situ quantitative analysis of
biomarkers

11
GC/MSMS in full scan/SRM mode
Current state-of-the-art in GC/MSMS technology permits
quantitative target analysis of several hundreds of compounds at
ultratrace levels and with short cycle times.
Typical workflow:
 Extraction/derivatization (methoxyamination + silylation)
 SCAN analysis: untargeted analysis; biomarker discovery
 autoSRM analysis: determination of MS/MS transitions
 SCAN/SRM: discovery & quantitative analysis

Automated Sample Preparation
Sample preparation for metabolomics is tedious, time-consuming and therefore highly prone to variability induced errors.
A suite of modular Lego-type solutions exist that enable full automation of sample preparation prior to GC/MS and LC/MS
analysis.
Solutions include:
 In-vial extraction
 Two-phase derivatization
 Centrifugation
 Filtration
 Solid phase extraction
 …
12

Data analysis
We provide training & consultancy in data analysis for biomarker discovery.
 Design of experiments (DOE)
 Data pre-processing: smoothing, baseline correction, normalization
 Data alignment: peak warping
 Comparative analysis: surface maps, peak matching, peak picking
 Statistical analylis: univariate and multivariate
13
WHAT CAN WE MEAN DO YOU?

SYFT LAB IN THE PICTURE
A couple of weeks ago a new Voice200 Ultra was installed in our laboratory in Breda. The new instrument is not only
equipped with a heated transfer line for standard VOC applications but also with the new swab desorber interface for
introducing semi-volatile components into the instrument. The new Voice200 Ultra combines state-of-the-art SIFT-MS
technology with optimized sample introduction hardware for demanding applications at PPT levels.
These multidisciplinary studies have been initiated
in the wake of the new installation:
 Geographical differentiation of olive oils
 Analysis of residual solvents in contaminated soils
 Direct measurement of printer emissions
 Monitoring of apple sauce production
 Analysis of beer aroma
 Analysis of plant emissions when treated with biocides

PAL ARROW – A NEW TYPE OF SPME ANALYSIS
Since its development by Belardi and Pawliszyn in 1989, Solid Phase
Microextraction (SPME) has become one of the most popular extraction
technologies for environmental, food and health analyses. However, the
technique remained almost unchanged with some significant drawbacks,
such as the limited mechanical stability and small phase volumes of the
fibers. All attempts to overcome these limitations have until now been a
trade-off between versatility and labor-intense handling. With the PAL SPME
Arrow we present a new technology for micro-extraction, offering trace level
sensitivity combined with high mechanical robustness. The PAL SPME
Arrow features an outer diameter of max. 1.5mm, which allows the enclosure
of a large sorption phase volumes with a highly resistant and stabilizing inner
rod. The arrow-shaped tip allows smooth penetration of vial septa and
injector. In contrast to traditional SPME fibers, the Arrow design fully
protects the sorptive material, minimizing adverse influences and loss of
analytes during transfer processes.

PAL HEATEX STIRRER
The efficient mixing of reagents is required for many operations in the
laboratory, like sample homogenization, the dissolving of solids or
liquid/liquid extraction. For the efficient headspace analysis of liquid
samples a rapid exchange between the liquid and the gas phase (headspace)
is required. Often magnetic stirrers are applied to achieve mixing. However,
especially at higher speeds stir bars tend to loose contact to the magnet and
stop turning. This problem is aggravated when solids are added to the sample
liquid which is common practice, e.g. the addition of salts to the liquid to
shift the equilibrium. Furthermore stir bars make autosampling cumbersome
since a bar has to be added to every sample vial manually. Vortex mixers offer
effective stirring, but cannot be used for SPME sampling.
The powerful PAL Heatex Stirrer mixes samples rapidly applying cycloid
shaped mixing pattern without the need for stir bars. For SPME headspace
and immersion sampling the special design (pat. pending) ensures that the
delicate fiber is not damaged.

http://www.ncbi.nlm.nih.gov/pubmed/25549013
IMDO @ VUB PUBLISHES FIRST SIFT-MS ARTICLE
The IMDO group of Prof De Vuyst at VUBrussels has published their first peer reviewed SIFT-MS article. The article
discussed the set-up they have designed for on-line monitoring of fermentation processes. The feasibility of this technique
was demonstrated using the case of the production of ethanol during sourdough fermentation. The potential of SIFT-MS as
an online monitoring device for food fermentations was further demonstrated by the detection of acetoin in certain
sourdough fermentations. This allowed discrimination between sourdough fermentation processes and illustrated the
importance of real-time monitoring of food fermentations.

In their recent publication, Vergeynst, Van Langenhove and Demeestere discuss the use of modern high-
resolution MS for full spectrum trace level analysis of emerging environmental organic contaminants.
Modern HRMS raises the opportunity for post-acquisition suspect screening when no reference standards are a priori
available. When setting up a conventional screening identification train based on successively different identification
criteria including mass error and isotope fit, the false negative rate typically accumulates upon advancing through the
decision tree. The challenge is thus to elaborate a well-balanced screening, in which the different criteria are equally
stringent, leading to a controllable number of false negatives.
Presented is a novel suspect screening approach using liquid-chromatography Orbitrap HRMS. Based on a multivariate
statistical model, the screening takes into account the accurate mass error of the mono isotopic ion and up to three
isotopes, isotope ratios, and a peak/noise filter. As such, for the first time, controlling the overall false negative rate of the
screening algorithm to a desired level (5% in this study) is achieved. Simultaneously, a well-balanced identification
decision is guaranteed taking the different identification criteria as a whole in a holistic statistical approach.
http://pubs.acs.org/doi/abs/10.1021/ac503426k
HIGH-RESOLUTION MS

TRACE DETECTION OF ENDOGENOUS VOC
FOR SEARCH & RESCUE APPLICATIONS
Since Pauling's paper in the 1970s, interest has increased
in volatile organic compounds (VOCs) released from
different bio-fluids, such as skin, breath, blood and urine.
A number of VOCs reflect internal biochemical pathways
occurring in the human body and their chemical pattern
may serve as the chemical platform for tracing human
VOCs. Monitoring endogenous human VOCs is proposed
as an alternative method to the use of canines for search,
rescue and emergency applications. Tracing humans
VOCs requires robust, rapid, reliable and sensitive
analytical instruments. Instrumentation currently used to
study human VOC biomarkers (e.g. GC-MS, PTR-MS,
SIFT-MS, MCC-IMS, FAIMS and sensor based systems)
has significant clinical potential, but has yet to receive
widespread consideration for emergency search
applications.
http://www.sciencedirect.com/science/article/pii/S0165993615000199

Product ion yields for a suite of hydrocarbons associated with motor vehicle exhaust including alkenes, alkanes,
cycloalkanes, and aromatic compounds are reported for a PTR-MS instrument operated at an E/N ratio of 80 and 120 Td.
At 120 Td many of the compounds tested underwent dissociative proton transfer reactions complicating the interpretation
of the vehicle exhaust mass spectrum. However at 80 Td most aromatic and alkene compounds tested yielded M + H
product ions at near 100% yield and alkyl substituted cyclohexanes and C9-C12 branched alkanes yielded M-H ions as the
major product ion. The PTR-MS response factors to dimethyl and trimethyl cyclohexane compounds were about a third of
that expected if they reacted at the collisional rate limit with H3O+. Analysis of gasoline at 80 Td showed that the major
peaks in the mass spectrum could be reasonably accounted for from known hydrocarbon abundance and their product ion
yields, including the alkyl substituted cyclohexane compounds which yielded M-H ions at m/z 97, 111, and 125. Operation
at lower E/N ratios would enable the PTR-MS to measure alkyl substituted cyclohexanes and larger alkane compounds in
urban air at their M-H product ion.
PTR FRAGMENTATION OF GASOLINE

Recently, thermally-assisted hydrolysis and methylation followed by gas chromatography–mass spectrometry (THM–GC–
MS) in combination with chemometrics has been used to develop a 20-compound model for fast differentiation of
Mycobacterium tuberculosis (MTB) from Non-tuberculous mycobacteria (NTM) in bacterial cultures. This model provided
better than 95% accuracy. In our current work a hexane/methanol/water extraction followed by a solid phase extraction
(SPE) clean-up procedure was developed for use before THM–GC–MS, to make the test suitable for the identification of
mycobacteria in sputum. The 20 biomarker model had to be adapted since many compounds were also found in the
sputum of non-tuberculosis patients. An algorithm was established based on tuberculostearic acid, hexacosanoic acid and
mycoserosates.
DIRECT DETECTION OF MYCOBACTERIUM
TUBERCULOSIS IN SPUTUM
The detection limit of the method was approximately
1 × 104 bacteria/mL sputum. Sputum specimens from 32
patients from South Africa who were suspected of having
tuberculosis were blindly tested using the new method.
Eight of the nine culture-positive sputum specimens were
detected by the new SPE–THM–GC–MS method,
resulting in a sensitivity of 89%. The specimen that was
missed by the new method was also microscopy negative.

BACTERIA CAN’T CLING TO NEW NANOSURFACE
http://www.futurity.org/bacteria-biofilm-nanopores-838502/
Bacteria can’t stick to a new type of nanoscale surface that could prove useful in food processing, medical, and shipping
industries. The technology uses an electrochemical process called anodization to create nanoscale pores that change the
electrical charge and surface energy of a metal surface, which in turn exerts a repulsive force on bacterial cells and prevents
attachment and biofilm formation. Whereas a sheet of paper is about 100,000 nanometers thick, these pores can be as
small as just 15 nanometers. When the researchers applied the anodization process to aluminum, it created a nanoporous
surface called alumina, which proved effective in preventing surrogates of two well-known pathogens, Escherichia coli
O157:H7 and Listeria monocytogenes, from attaching, according to the study in Biofouling. The study also investigates how
the size of the nanopores changes the repulsive forces on bacteria.
It’s probably one of the lowest-cost possibilities to manufacture a nanostructure on a metallic
surface,” says senior author Carmen Moraru, professor of food science at Cornell University.
“

In this publication the authors present a proof-of-concept demonstration of an all-printed temporary tattoo-based glucose
sensor for noninvasive glycemic monitoring. The sensor represents the first example of an easy-to-wear flexible tattoo-
based epidermal diagnostic device combining reverse iontophoretic extraction of interstitial glucose and an enzyme-based
amperometric biosensor. In-vitro studies reveal the tattoo sensor’s linear response toward physiologically relevant glucose
levels with negligible interferences from common coexisting electroactive species. The iontophoretic-biosensing tattoo
platform is reduced to practice by applying the device on human subjects and monitoring variations in glycemic levels due
to food consumption. Correlation of the sensor response with that of a commercial glucose meter underscores the promise
of the tattoo sensor to detect glucose levels in a noninvasive fashion.
Control on-body experiments demonstrate the
importance of the reverse iontophoresis operation and
validate the sensor specificity. This preliminary
investigation indicates that the tattoo-based
iontophoresis-sensor platform holds considerable
promise for efficient diabetes management and can be
extended toward noninvasive monitoring of other
physiologically relevant analytes present in the
interstitial fluid.
http://pubs.acs.org/doi/abs/10.1021/ac504300n
TATTOO-BASED NONINVASIVE MONITORING

CALL CENTERS REPLACED BY WHATSAPP
Haptik is a mobile messaging assistant from India which enables customers to receive real-time support and information
for over 200 international companies, including American Express, BMW, British Airways and many more. Users begin by
downloading the app to their smartphone or tablet. They then send a query to Haptik via the WhatsApp-style platform and
an assistant will respond within six minutes. The platform’s experts — who specialize in specific areas such as wireless and
telecom or food and delivery — offer a huge range of services from finding a mobile plan, to locating a nearby ATM, to
troubleshooting a customer’s IT problem. Users simply browse the categories in the app to see if Haptik can help with their
particular problem. As more companies come on board, potential services offered will continue to expand.

http://www.wired.com/2015/01/getac-v110/
LAPTOP BUILT FOR MILITARY BEATDOWNS
“Ruggedness” is about more than just surviving stress tests. It’s about performing when there’s every excuse not to, and
that’s just what Getac’s ultra-rugged, nearly indestructible V110 convertible PC does. With an array of essential crunch-
time features and improved performance and functionality over its predecessor, Getac’s V110 is something of a must-have
for anyone whose worksite conditions skew toward the extreme. Weighing just 4.6 pounds (relatively light; rugged
notebooks usually weigh between 7 and 10 pounds), the V110 sports a 11.6-inch display and a full-size mechanical
keyboard. The machine also doubles as a tablet—the touchscreen swivels around and folds down flat. There are many
convertibles out there, but this one’s built to be virtually fail-proof in high-pressure environments. Hard knocks and
occasional drops are dispelled by the magnesium alloy chassis and shock-absorbing rugged polymers and hardened
rubbers. Spills can’t harm it—the ports and modules are all sealed behind hinged door-flaps, and the keyboard is sealed by
a membrane that’s fully waterproof.

http://www.springwise.com/smart-acupuncture-pen-checks-vitamins/
SMART PEN CHECKS VITAMINE LEVELS
Vitastiq allows anyone to track their vitamin and mineral levels through a handheld device and app that blends scientific
data with thousands of years of acupuncture wisdom. The device itself is a consumer-friendly handheld electrode which
enables users to examine their vitamin levels and spot deficiencies before physical symptoms occur. It plugs straight into
the headphone socket of any smartphone and works by sending a small electrical current through acupuncture points on
the user’s body. This may sound painful, but it isn’t. In fact, it’s a standard element of the EAV — electroacupuncture —
methodology, which has been used worldwide for over 20 years.
When people press the Vitastiq against their skin, the data is logged to the user’s smartphone
through the free app, where they can monitor up to 30 changing vitamin and mineral requirements.
An in-app tutorial guides users through the relevant reading spots one at a time to ensure they get
an accurate and complete reading of the body.

http://www.springwise.com/smart-handlebars-haptic-feedback-enable-screen-free-navigation/
SMART HANDLEBARS USE HAPTIC FEEDBACK TO
ENABLE SCREEN-FREE NAVIGATION
The humble bicycle may be one of our oldest forms of transport but it is also one the greenest and most fulfilling ways to
get from A to B. The relative simplicity of its structure has recently made it ripe for additional smart features and add-ons.
We have already seen Merge from New York and COBI from Germany attempt to offer cyclists the “ultimate” bike. Now,
smrtGRiPs is a three-in-one bike upgrade that can make any bike smarter, safer and easier to locate. Users insert a pair of
smrtGRiPs into their handlebars and connect them with their smartphone via bluetooth. Haptic and audible feedback
guide cyclists through their journey safely without the need for screens or taking their eyes off the road. The handlebars
vibrate to indicate left and right turns and separation alerts can inform cycling partners if someone has been left behind.
The connected app can also be used to locate missing bikes in a busy bike rack by making the handlebars ring with the
“ring your ride” feature, and if a bike is stolen the app notifies the crowdGPS network to be on the lookout.

SMART PATCH LAUNCHES CROWDFUNDING
CAMPAIGN
STEMP was designed to solve issues related to thermometers currently on the market, especially those designed for small
children and their parents, who comprise a large share of first-time thermometer consumers. Especially when you have
children that get sick, STEMP is a great way to continuously monitor your child’s temperature continuously by simply
putting the STEMP on with the provided patch. It syncs to your smart phone so you can collect data, see trends, and make
smarter decisions, over hours, days, or even weeks (one charge lasts up to 30 days). You can even share the information
with your healthcare provider in the cloud.

http://www.springwise.com/green-computer-server-heats-homes-free/
GREEN SERVER HEATS HOMES FOR FREE
By turning servers into electrical heaters for homes, Nerdalize does not need the building and expensive cooling equipment
normal datacenters need. Not using a building and cooling systems adds up to about 60% in savings! The beauty of our
idea is that our servers get just as warm as a normal heater, so we can heat the homeowner’s house with them. In return for
allowing us to do that we pay for the homeowner’s heating bill. This way computing users get affordable computing power
and homeowners get a free heating bill.

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1501 Refocus metabolomics

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