Trends in Analytical Chemistry, Vol. 45, 2013 In the news
In the news
NEMS sensors with high-speed GC detect chemicals
The GCAP small-scale multi-gasanalyzer uses high-speed gaschromatography (GC) techniquescombined with ultrasensitivenanoelectromechanical system(NEMS) for chemical detection inindustrial and petrochemicalapplications, including processmonitoring and environmentalcontrol (Fig. 1).
Analytical Pixels Technology(APIX) designed, assembled andtested the device, which is based onnano-scale silicon componentslicensed from the CEA-Leti and theCalifornia Institute of Technology(Caltech). The silicon componentsare manufactured in Leti’sadvanced semiconductor facility inGrenoble and system assembly and
Figure 1. Prototype GCAP-S system utilizing GC+sub-system with a micro-mechanical six-port valelectronics; and (d) a typical analysis of natural g
0165-9936/$ - see front matter doi:10.1016/j.trac.2013
test are performed in APIX’s facilityin Grenoble.
‘‘GCAP’s very flexible, versatilearchitecture, based on high-densitysilicon columns and sensors, meansGCAP can be configured to performin a number of different modes,including conventional, multi-dimensional or concurrentanalysis,’’ said APIX co-founderPierre Puget. ‘‘This makes it theideal tool for research laboratories,advanced gas analysis, and complexapplications, such as biomedicalscreening.
‘‘One of GCAP’s key features isits ability to work with a number ofdifferent carrier gases,’’ he said.‘‘This is made possible by the ex-treme sensitivity of the silicon
NEMS technology developed by APIX and partneve, a silicon microfabricated GC column, and aas using the system.
.02.001
nano-scale sensors at the heart ofthe system.’’
In particular, the ability of GCAPto work with scrubbed air as acarrier gas in lieu of expensive,cumbersome bottled gases allowseasy in-situ deployment, nearlyreal-time analysis, and a significantreduction in operating costs.
Other major features of GCAPinclude its ability to:� separate and quantify precisely
individual molecules amonghundreds of interfering substances,depending on architectural con-figurations;
� limit detection for mostchemical compounds below 1parts-per-million without pre-concentration and in the
rs. Shown are: (a) the system, (b) the analyticalNEMS resonator array; (c) the NEMS control
v
In the news Trends in Analytical Chemistry, Vol. 45, 2013
TrAC’s Top 10 citedarticles publishedsince 2008*
1.Aptamer-based biosensors
by S. Song, L. Wang, J. Li, C. Fan and
J. Zhao
Trends Anal. Chem. 27 (2008) 108.
2.Ambient desorption ionization
mass spectrometry
by A. Venter, M. Nefliu and R. Graham
Cooks
Trends Anal. Chem. 27 (2008) 284.
3.Green Analytical Chemistry
by S. Armenta, S. Garrigues and M. de la
Guardia
Trends Anal. Chem. 27 (2008) 497.
4.Liquid-phase microextraction
by A, Sarafraz-Yazdi and A. Amiri
Trends Anal. Chem. 29 (2010) 1.
5.Biomolecule-nanoparticle hybrids
for electrochemical biosensors
by S. Guo and S. Dong
Trends Anal. Chem. 28 (2009) 96.
6.Carbon nanostructures as sorbent
parts-per-billion range with pre-concentration;
� reduce the volume of analyterequired to less than 10 lL, andthe volume of carrier gas to lessthan 1 mL; and,
� analyze most chemicals in lessthan 1 min.
The performance of GCAP hasbeen demonstrated with alkanes,permanent gases, volatile organiccompounds and other materials.
Contact:Philippe AndreucciAnalytical Pixels Technology (APIX)Minatec Center for NanotechnologiesInnovationGrenoble, FranceTel: +33 4 38 78 63 24E-mail: [email protected]
materials in analytical processes
by M. Valcarcel, M. Cardenas, B.M.
Simonet, Y. Moliner-Martı and R. Lucena
Trends Anal. Chem. 27 (2008) 34.
7.Functionalized carbon nanotubes
and nanofibers for biosensing
applications
by J. Wang and Y. Lin
Trends Anal. Chem. 27 (2008) 619.
8.Fate and toxicity of emerging
pollutants, their metabolites and
transformation products in the
aquatic environment
by M.I. Farre, S. Perez, L. Kantiani and
D. Barcelo
Trends Anal. Chem. 27 (2008) 991.
9.Bioactive paper provides a low-
cost platform for diagnostics
by R. Pelton
Trends Anal. Chem. 28 (2009) 925.
10. Quantitative metabolomics using
NMR
by D.S. Wishart
Trends Anal. Chem. 27 (2008) 228.
* Extracted from SciVerse Scopus, 15
February 2013
Cocaine biosensorshows promise
Biosensing nanotechnology looksset to improve after an interna-tional team of researchers hasadapted natural mechanisms todetect specific molecules, such ascocaine, more accurately andquickly [1].
As a result, their work maygreatly facilitate rapid screening –that is, taking less than 5 min – ofmany drugs, infectious diseases andcancers.
Professor Alexis Vallee-Belisle ofthe University of Montreal Depart-ment of Chemistry worked withProfessor Francesco Ricci of theUniversity of Rome Tor Vergata andProfessor Kevin W. Plaxco of theUniversity of California at SantaBarbara towards a new generationof screening tests.
‘‘Nature is a continuing source ofinspiration for developing newtechnologies,’’ said Prof. Ricci,senior author of the study. ‘‘Many
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scientists are currently working todevelop biosensor technology todetect – directly in the bloodstreamand in seconds – drug, disease andcancer molecules.’’
‘‘The most recent rapid andeasy-to-use biosensors developed byscientists to determine the levels ofvarious molecules, such as drugsand disease markers in the blood,only do so when the molecule ispresent in a certain concentration,called the concentration window,’’added Prof. Vallee-Belisle. ‘‘Belowor above this window, currentbiosensors lose much of theiraccuracy.’’
To overcome this limitation, theinternational team looked atnature.
‘‘In cells, living organisms oftenuse inhibitor or activator moleculesto program automatically thesensitivity of their receptors(sensors), which are able to identifythe precise amount of thousands ofmolecules in seconds,’’ explainedProf. Vallee-Belisle. ‘‘We thereforedecided to adapt these inhibition,activation and sequestration mecha-nisms to improve the efficiency ofartificial biosensors.’’
The researchers put their idea tothe test by using an existing cocainebiosensor and revising its design sothat it would respond to a series ofinhibitor molecules (Fig. 2). Theywere able to adapt the biosensor torespond optimally even with a largeconcentration window.
‘‘What is fascinating,’’ saidAlessandro Porchetta, a doctoralstudent at the University of Rome,‘‘is that we were successful incontrolling the interactions of thissystem by mimicking mechanismsthat occur naturally.’’
‘‘Besides the obvious applicationsin biosensor design, I think thiswork will pave the way for importantapplications related to the adminis-tration of cancer-targeting drugs,an area of increasing importance,’’
said Prof. Plaxco. ‘‘The ability toregulate accurately biosensor ornanomachine activities will greatlyincrease their efficiency.’’
Figure 2. The research team used an existing cocaine biosensor (in green) and revised its design to react to a series of inhibitor molecules (inblue). They were able to adapt the biosensor to respond optimally even within a large concentration window.
Trends in Analytical Chemistry, Vol. 45, 2013 In the news
Contact:Professor Francesco RicciDipartimento di Scienze e TecnologieChimicheUniversity of Rome, ItalyE-mail: [email protected]
Reference[1] A. Porchetta, A. Vallee-Belisle, K.W.
Plaxco, F. Ricci, J. Am. Chem. Soc. 134
(2012) 20601.
Mobile measuresmercury contamination
A sheet that changes color in thepresence of water contaminatedwith mercury can be photographedon site with a mobile phone toquantify the concentration of thisextremely toxic metal [1].
Mercury contamination is a pro-blem that particularly affects de-veloping countries. It poses a risk topublic health since it accumulatesin the brain and the kidneys caus-
ing long term neurological illnesses.It is emitted from industrial andmining waste, especially small-scalegold mining.
A team at the University ofBurgos, Spain, developed the tech-nique to detect the presence ofmercury in water in a cheap, quickand in-situ way, explained JoseMiguel Garcıa, one of the authors ofthe study.
The method involves placing thefine sheet created by the researchersin the water for 5 min. If it turnsred, this signals the presence ofmercury.
‘‘Changes can be seen by thenaked eye,’’ said Garcıa, ‘‘and any-one, even if they have no previousknowledge, can find out whether awater source is contaminated withmercury above determined limits.’’
In addition, if they take a photo-graph of the sheet with a digitalcamera, like those in mobile phones,they can find out the concentration ofthe metal. Ther mobile phone needsonly image-treatment software (for
which the research team used theopen access GIMP program) to see thecolor coordinates (Fig. 3). The resultis then compared with referencevalues.
The membrane contains a fluor-escent organic compound calledrhodamine, which acts as a mercurysensor.
‘‘Rhodamine is insoluble inwater,’’ said Garcıa. ‘‘But wechemically fix it to a hydrophilicpolymer structure in such a waythat, when put into water, it swellsand the sensory molecules are forcedto remain in the aqueous mediumand interact with mercury.’’
The exact composition of the sheetcan be adjusted to the desiredparameters. More specifically, theresearchers have calibrated the sheetso that it changes color when limitsestablished by the EnvironmentalProtection Agency (EPA) of the USAare exceeded – that is, 2 ppb (parts perbillion) of divalent mercury [Hg(II)]in water destined for humanconsumption.
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Figure 3. The mobile detects the differences in the color of various membranes submerged inwaters with varying mercury concentrations (Credit: J.M. Garcıa et al. [1]).
In the news Trends in Analytical Chemistry, Vol. 45, 2013
Having also developed a methodfor other chemicals, such as iron orcyanide, the researchers believethat the water drunk in Spain ‘‘is ofexcellent quality due to highly effi-cient controls.’’
The technique could be used fordetecting mercury in certain spillsand for studying its presence in fish.
A recent study by the United Na-tions Environment Program (UNEP)demonstrated that a large part ofhuman exposure to this toxicmetal is due to consumption ofcontaminated fish. Named theGlobal Mercury Assessment 2013, theUNEP report analyzed for the firsttime the mercury released into therivers and lakes around the wholeworld. The small-scale extraction ofgold and the combustion of coal forelectricity generation seem to be be-hind the increase in the emissions ofdeveloping countries.
As for the sea, in the past cen-tury, the quantity of mercury hasdoubled in the first 100 m of thesurface of the Earth’s oceans. Con-centrations in deep water have alsoincreased by up to 25%.
To stop the global contaminationby mercury, in January, more than140 countries came together inGeneva and approved the start-up ofthe Minamata Convention, an in-ternational binding regulation bear-ing the name of the Japanese citywhere hundreds of people died inthe 1950s due to mercury poison-ing.
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Contact:Jose M. GarcıaCatedratico de Quımica OrganicaFacultad de CienciasUniversidad de Burgos, SpainTel.: +34 947258085E-mail: [email protected]
Reference[1] H.E. Kaoutit, P. Estevez, F.C. Garcıa,
F. Serna, J.M. Garcıa, Anal. Methods 5
(2013) 54.
Protein filmed whileunfolding
Researchers have succeeded in‘‘filming’’ the complex process ofprotein folding for the first time [1].
Alzheimer’s, Parkinson’s andHuntington’s Chorea are all causedby misfolded proteins that forminsoluble clumps in the brains ofaffected patients and, finally,destroy their nerve cells. One of themost important questions in thebiological sciences and medicine is‘‘How do proteins – the tools ofliving cells – achieve or lose theirthree-dimensional structure?’’
Only if their amino-acid chainsare correctly folded can proteinsperform their tasks properly. But ithas been nearly impossible to in-vestigate how they fold. With heatand pressure, proteins easily losetheir shape – and therefore theirfunction. However, the inter-mediate forms that occur in the
course of protein folding are muchtoo transient to observe.
Scientists tackling this problemwere based at the Max Planck In-stitute for Biophysical Chemistry(MPIbpc) and the German Center forNeurodegenerative Diseases (DZNE)in Gottingen, together with theircolleagues at the Polish Academy ofSciences in Warsaw and at theUniversity of Warsaw. They ren-dered visible – at atomic resolution –how a protein progressively ‘‘losesits shape’’. In doing so, they pinnedtheir hopes on low temperatures.
‘‘If a protein is slowly cooled down,its intermediate forms accumulate inlarger quantities than in commonlyused denaturation methods, such asheat, pressure or urea,’’ saidProfessor Markus Zweckstetter,MPIbpc and DZNE. ‘‘We hoped thatthese quantities would be sufficientto examine the intermediate formswith nuclear magnetic resonance(NMR) spectroscopy.’’
As research object, Prof. Zweck-stetter’s team chose a key protein fortoxin production in Enterococcusfaecalis, a pathogen frequentlyencountered in hospitals where itparticularly jeopardizes those pa-tients with a weak immune system.But that is not the only reason whythe so-called CylR2 protein isinteresting. Some time ago,researchers working with StefanBecker at the MPIbpc succeeded inelucidating its structure. Its three-dimensional shape makes CylR2 aparticular promising candidate forthe scientists’ approach.
ClyR2 is a relatively small proteincomposed of two identical sub-units, which gave a great chance tobe able to visualize the individualstages of its unfolding process in thetest tube.
Stefan Becker’s group at MPIbpcundertook the first step – to prepare asufficient amount of the protein in thelaboratory. Subsequently, the proteinwas cooled successively from 25�C to -16�C and its intermediate forms ex-amined with NMR spectroscopy.
Figure 4. ‘‘Snapshot’’ of the unfolding of the CylR2 protein from Enterococcus faecalis. If theprotein is cooled from 25�C to -16�C, it successively breaks down into its two identical sub-units. The latter are initially stable, but, at –16�C, they form an unstable, dynamic proteinform, which plays a key role in folding (ª Zweckstetter, Max Planck Institute for BiophysicalChemistry & German Center for Neurodegenerative Diseases).
Trends in Analytical Chemistry, Vol. 45, 2013 In the news
The resulting ‘‘film clip’’ showedat atomic resolution how the pro-tein gradually unfolds (Fig. 4).
‘‘We clearly see how the CylR2protein ultimately splits into its twosub-units,’’ said Prof. Zweckstetter.‘‘The individual sub-unit is initially re-latively stable. With further cooling,the protein continues to unfold and, at-16�C, it is extremely unstable anddynamic. This unstable protein formprovides the seed for folding and canalso be the ‘trigger’ for misfolding.’’
The scientists’ findings may helpto gain deeper insights into howproteins assume their spatial struc-ture and why intermediate forms ofcertain proteins misfold in the eventof illness.
Contact:Prof. Dr. Markus ZweckstetterMax Planck Institute for BiophysicalChemistryGottingen, GermanyTel.: +49 551 201 2220E-mail: [email protected]
Reference[1] M. Jaremko, L. Jaremko, H.-Y. Kim, M.-K.
Cho, C.D. Schwieters, K. Giller, S. Becker,
M. Zweckstetter, Nature Chem. Biol.
(2013) (DOI: 10.1038/nchembio.1181).
Drugs cause fishybehavior
Anxiety-moderating drugs thatreach waterways in wastewatercreate fearless and asocial fish thateat more quickly than normalfish, and these behavioral changescan have serious ecological con-sequences, according to researchersat Umea University, Sweden [1].
Many drugs leave our bodiesunaffected, and residues from themare therefore found in wastewater.Low concentrations of drugs areoften found downstream from sew-age-treatment plants.
The researchers (Fig. 5)examined how perch behaved whenthey were exposed to anxiety-moderating drug Oxazepam. Thechanges were obvious in drug con-centrations corresponding to thosefound in waters in densely popu-lated areas in Sweden.
‘‘Normally, perch are shy andhunt in schools,’’ explained ecolo-gist Tomas Brodin, lead author ofthe article. ‘‘This is a known strat-egy for survival and growth. Butthose who swam in Oxazepambecame considerably bolder.’’
The drug made the fish braverand less social. This meant thatthey left their schools to look forfood on their own, a behavior thatcan be risky, as school formation isa key defense against being eatenby predatory fish.
The perch also ate more quickly.Since fish fulfill an important func-tion in many aquatic environments,changes in eating behavior canseriously disturb the ecological bal-ance.
‘‘We’re now going to examinewhat consequences this mighthave,’’ said Brodin. ‘‘In waterswhere fish begin to eat more effi-ciently, this can affect the compo-sition of species, for example, andultimately lead to unexpectedeffects, such as increased risk ofalgal blooming.’’
Considerably more drugs withthe same function are found insurface water downstream fromsewage-treatment plants, not onlyin Sweden but also elsewhere inthe world. Moreover, drug use ispredicted to increase. This meansthat previously unknown changesin behavior among fish, withecological consequences as a re-sult, may be a global phenomen-on.
‘‘The solution to the problem isnot to stop medicating ill people butto try to develop sewage-treatmentplants that can capture en-vironmentally-hazardous drugs,’’said environmental chemist JerkerFick.
Contact:Tomas BrodinDepartment of Ecology andEnvironmental ScienceUmea University, SwedenTel.: +46 90 786 56 01E-mail: [email protected]
Reference
[1] T. Brodin, Science (Washington, DC) 339
(2013) 814.
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Figure 5. The study was conducted by an interdisciplinary research team at Umea University, Sweden (from the left): Jerker Fick, Jonatan Kla-minder, Tomas Brodin and Michael Jonsson.
In the news Trends in Analytical Chemistry, Vol. 45, 2013
Nanosensors supportskin-cancer therapy
Figure 6. Eight cantilevers of 500 ım in length are applied for detection of the geneticmutation. (Photo: University of Basel).
A novel diagnostic method analyzesthe ribonucleic acid (RNA) ofmelanoma cancer cells usingnanomechanical sensors, so as todistinguish healthy cells fromcancer cells [1].
Malignant melanoma is themost aggressive type of skin can-cer. In more than half affectedpatients, a particular mutationplays an important role. As thelifespan of the patients carryingthe mutation can be significantlyextended by novel drugs, it is veryimportant to identify those pa-tients reliably. For identification,researchers from the University ofBasel and the Ludwig Institute forCancer Research in Lausanne de-veloped a novel method. Whenmalignant melanoma is detectedearly, the prospects of recovery arevery good, but, at later stages, thechances of survival are reduceddrastically.
In the past few years, novel drugshave been developed to take ad-vantage of the presence of parti-cular genetic mutations related tofast cell growth in tissue. In the case
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of melanoma, the so-called BRAFgene is important, as its mutatedstate leads to uncontrolled cellgrowth. Since only about half ofpatients with malignant melanomashow this mutation, it is importantto identify them so that they canaccess the novel therapy. Takinginto account the negative side ef-fects of the drug, it would be in-appropriate to apply the drug to allpatients.
The teams of Professor ChristophGerber from the Swiss NanoscienceInstitute of the University of Basel
and Donata Rimoldi from theLudwig Institute for Cancer Researchin Lausanne recently developed thenovel diagnostic method that ana-lyzes the RNA of the cancer cellsusing nanomechanical sensors (i.e.microscopically small cantilevers)(Fig. 6). In contrast to other meth-ods, the cantilever approach is sosensitive that DNA does not need tobe amplified or labeled.
The method is based on bindingof molecules to the top surface of acantilever and the related change insurface stress. For this purpose, the
Trends in Analytical Chemistry, Vol. 45, 2013 In the news
cantilevers are first coated with alayer of DNA molecules that canbind mutated RNA from cells. Thebinding process deflects the canti-lever. The bending is measuredusing a laser beam. The molecularinteraction must take place veryclose to the cantilever surface toproduce a signal.
In experiments, the researcherscould show that cells carrying thisgenetic mutation can bedistinguished from others lackingthe mutation. RNA of cells from acell culture was tested in con-centrations similar to those in tissuesamples. Since the researcherscould detect the mutation in RNAstemming from different cell lines,the method works independent ofthe origin of samples.
‘‘The technique can also be ap-plied to other types of cancer thatdepend on mutations in individualgenes, for example in gastro-intestinal tumors and lung can-cer,’’ said lead author FrancoisHuber. ‘‘This shows the wide ap-plication potential in cancer diag-nostics and personalized healthcare.’’
‘‘Only the interdisciplinary ap-proach in medicine, biology andphysics allows us to apply novelnanotechnology methods in medi-cine for the benefit of patients,’’ saidco-author Donata Rimoldi.
Figure 7. Panel members at the roundtable discu
Contact:Francois HuberSwiss Nanoscience InstituteUniversity of Basel, SwitzerlandTel.: +41 61 267 37 69E-mail: [email protected]
References[1] F. Huber, H.P. Lang, N. Backmann, D.
Rimoldi, C. Gerber, Nature Nanotechnol.
8 (2013) 125.
[2] G.S. Shekhawat, V.P. Dravid, Nature
Nanotechnol. 8 (2013) 77.
Maintenance is key forDO sensors
There is a need for improved main-tenance of dissolved oxygen (DO)sensors to increase the accuracy ofDO measurements that are criticalin the water industry.
A roundtable discussion, hostedby electrochemical-sensor manu-facturer Analytical Technology(ATI), involved leading water-industry and regulatory experts inthe UK. The panel was chaired byMichael Strahand, General Managerof ATI Europe and included AlanHenson from Yorkshire Water, AndyMorse, Richard Bragg and KhaledGajam from United Utilities, JorgenJonsson from The Water ResearchCentre and Robin Lennox fromSouth West Water (Fig. 7).
ssion.
Optical DO sensors developed inthe past few years use a techniquethat essentially measures the rate atwhich oxygen absorbs an opticalsignal generated within a mem-brane impregnated with a fluor-escent dye. Galvanic oxygensensors measure the current pro-duced in an electrochemical reac-tion cell. A membrane serves as abarrier to allow molecular oxygento diffuse into the reaction cellwhere it is reduced at the workingelectrode. This reaction produces asmall current, which is proportionalto oxygen concentration.
There are some fundamentaldifferences between the technolo-gies. Galvanic DO sensors areinherently more precise whenmeasuring low levels of DO. At zerooxygen concentration, there is nocurrent. At low concentrations,there is little quenching of thefluorescence, and the processor hasto measure reliably the smalldifference between two large num-bers. Galvanic sensors consumeoxygen and need a flowing ormoving sample. Optical sensorswork in stagnant water. Oneimportant thing that both types ofsensor have in common is that bothhave a membrane. The membraneon a galvanic sensor controls therate of diffusion into the electro-chemical reaction cell; on an optical
http://www.elsevier.com/locate/trac xi
In the news Trends in Analytical Chemistry, Vol. 45, 2013
sensor, the primary role of themembrane is to prevent ambientlight affecting the measurement.The cleanliness of the membrane isvital to both types of sensor.
Although most water companiesuse optical sensors due to the gui-dance of their frameworks, there isconcern within the water industryas to which type of sensor, if any, ismore accurate and efficient.
Historic lack of confidenceThe panel started discussing whymany water-treatment plants arerunning their treatment plants atDO levels higher than strictly ne-cessary to optimize the process (thatis, with over-aeration). The mainfactors that emerged were a historiclack of confidence in the ability ofmonitors to measure low DO levelsreliably and the need to complywith regulations mapped out by theEnvironment Agency. This over-aeration was blamed in the discus-sion as a reason for high energycosts in running water-treatment
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plants. Producing high DO con-centrations requires large amountsof energy, which are a waste ofenergy if DO levels become too high.However, the roundtable heard thatwater companies prefer to remainon the safe side by over-aeratingsewage in order to over-treat it andthus incur large electricity bills,rather than incur penalties forbreaching consents with theEnvironmental Agency.
There was a consensus amongthe panel that the most pressingproblem with DO sensors is thedifficulty cleaning both optical andgalvanic sensors, resulting in thebuild up of sludge, which affectstheir accuracy. Problems withcleaning DO sensors also unearthedan issue of damaged trust betweenmanufacturers of sensors and watercompanies, as some manufacturershad sold sensors as ‘‘maintenancefree’’. Those present at the meetingclaimed large amounts of time andresources were spent each year oncleaning sensors. Panel members
asked suppliers of DO sensorspresent for more information andguidance on the cleaning theseinstruments.
The overarching conclusion ofthe discussion was that instrumentmaintenance is more important tousers than the technology. Theinstrument must be properly main-tained and regularly cleaned inorder to measure DO accurately. Itwas accepted that electrochemicaland optical sensors are both capableof delivering the accuracy and thereliability required by water com-panies if they are kept clean and arewell maintained. It was suggestedthat manufacturers include amaintenance warranty and a tech-nological demand was raised for theauto-cleaning functions of a DOsensor to include another sensor todetect when the DO sensor needscleaning and to sound an alarm.
Contact:Website: www.atiuk.com