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Mass spectrometry is an analytical technique that identifies the chemical composition of a compound or sample based on the mass-to-charge ratio of charged particles. Wikipedia

What is Mass Spectrometry?

Mass spectrometry is the art of measuring atoms and molecules to determine their molecular weight. Such mass or weight information is sometimes sufficient, frequently necessary, and always useful in determining the identity of a species. To practice this art one puts charge on the molecules of interest, i.e., the analyte, then measures how the trajectories of the resulting ions respond in vacuum to various combinations of electric and magnetic fields.

John B. Fenn, Nobel Laureate in Chemistry 2002.

Nobel Prize winners for their advancement of Mass Spectrometry

J.J. Thomson 1906 Physics Francis W. Aston1922 Chemistry

Wolfgang Paul & Hans G. Dehmelt1989 Physics

John B. Fenn & Koichi Tanaka* 2002 Chemistry

*As of 2008, he is the only person without a post-bachelor's degree to have won a Nobel Prize in a scientific field.

Ion source

electrospray ionization (ESI) , nanoelectrospray ionization (nanoESI), matrix-assisted laser desorption/ionization (MALDI) ,atmospheric pressure chemical ionization (APCI), corona discharge , desorption/ionization on silicon (DIOS), fast atom/ion bombardment (FAB/SIMS), electron ionization (EI), chemical ionization (CI).

V too lowV too high

http://www.eng.qmul.ac.uk/subsites/electrospray/videos.php

Mass analyzer

Quadrupole mass filter (QMS) , quadrupole ion trap (QIT, 3-D ion trap or Paul trap; 2-D or linear ion trap) , Time-of-Flight (TOF), Magnetic sector, Fourier Transform Ion Cyclotron Resonance (FTMS, Penning trap), orbitrap,

and various tandem combinations: Quad-TOF (Q-TOF), TOF-TOF, Double-focusing EB (normal geometry tandem sector instrument), BE (reversed-geometry tandem sector instrument).

Quadrupole mass filter (QMS)

Paul Trap Penning (ion) traps are used in the physical realization of quantum computation and quantum information processing

QIT, 3-D ion trap or Paul trap

http://www.kore.co.uk/1095.htmTOF-MS

Double focusing sector mass spectrometer

FTMS, Penning trap

Thermo-FisherLTQ-FTLTQ-Orbitrap

VarianBruker Daltonics

Detectors

Faraday CupSecondary Electron Multipliers (SEM) Channel Electron Multiplier (CEM)Multichannel Array Detector

Detector

Electron multiplier, photomultiplier conversion dynodeContinuous dynode electron multiplierVenetian blind/discrete dynode electron multiplier

Organization for Economic Co-operation and Development (OECD) classification of industries - 1973

Industry nameHigh-TechnologyPharmaceuticalsAircraft & spacecraftMedical, precision & optimal instrumentsRadio, television & communication equipmentOffice, accounting & computing machineryMedium-High-TechnologyElectrical machinery & apparatusMotor vehicles, trailers & semi-trailersRailroad & transport equipmentChemical & chemical productsMachinery & equipment

High tech --- Wikipedia

High tech is technology that is at the cutting edge the most advanced technology currently available.

There is no specific class of technology that is high techthe definition shifts over time .

As of 2006, any technology from the year 2000 onward may be considered high tech. Aerospace technology extraterrestrial material meteorites, interplanetary dust Biotechnology Information technology Nanotechnology Robotics

Applications of MS in semiconductor industryProcess gas analysis eg. Contamination and compositionAdsorbed surface layer analysis

Secondary Ion Mass Spectrometry (SIMS)Thin film/layer deposition QC Lateral 2-D pattern (static SIMS) and 3-D depth profiling (dynamic SIMS)Device failure diagnosisReverse engineering ()Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry

Surface analysis using secondary-ion mass spectrometry (SIMS). David G. Castner, Nature 422, 129-130 (2003)

http://images.google.com.tw/imgres?imgurl=http://www.condensed-matter.uni-tuebingen.de/resources/pictures/simsschema.jpg&imgrefurl=http://www.condensed-matter.uni-tuebingen.de/cms/parser/parser.php%3Ffile%3D/en/facilities/sims.htm&us

Ion imaging Ion-images of the surface was recorded with a lateral resolution of up to 5m. The primary ion beam is scanned over the surface and for every point the intensity of the chosen mass is recorded.

The picture on the left shows an image of a metal surface. In the right corner of the window there was a SED - image of the sample. The width of this image is about 300m. The right picture shows the titanium impurities of a natural SnO2 single crystal surface (110). The width of this picture is about 700m

http://images.google.com.tw/imgres?imgurl=http://www.condensed-matter.uni-tuebingen.de/resources/pictures/simsschema.jpg&imgrefurl=http://www.condensed-matter.uni-tuebingen.de/cms/parser/parser.php%3Ffile%3D/en/facilities/sims.htm&us

Inductively Coupled Plasma Time-of-Flight (TOF) Mass Spectrometer

Staticic SIMS

Depth profiling Dynamic SIMS http://images.google.com.tw/imgres?imgurl=http://www.condensed-matter.uni-tuebingen.de/resources/pictures/simsschema.jpg&imgrefurl=http://www.condensed-matter.uni-tuebingen.de/cms/parser/parser.php%3Ffile%3D/en/facilities/sims.htm&usDepth profile of a sample, the beam is scanned in a spiral and the counters are only open, when the beam reaches a central region of the sputter-crater. With this method it is possible to avoid edge effects and to get only a signal of a defined sputter-depth.Both profiles have been taken on the same sample (tinoxide coated silicium wafer), detecting positive (left) and negative (right) ions with a total depth of about 350nm

MS Applications in Biotechnology: Genomics Proteomics Metabolomics Glycomics Lipidomics Interactomics

Protein Biomarker identification

The official NIH (USA) definition of a biomarker is:

"a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention."

Advantages of protein MarkersProteins are the direct machinery executing biological functions much more direct indication than DNAs or RNAs of pathologic status.Proteins with the correct amino acid sequence as mandated by a normal DNA can still be the cause of a disease state, as amino modifications, such as phosphorylation, glycosylation, alkylation, etc. can all affect a proteins 3-D structures and thus functions. (Post-translational modification)Secretory proteins can be sampled remote from the nidus, well before metastasis occurs.

General Proteomic workflowApplication of Proteomics in Cancer Research

MudPIT (Multidimensional Protein Identification Technology)

MudPIT is a technique for the separation and identification of complex protein and peptide mixtures. Rather than use traditional 2D gel electrophoresis, MudPIT separates peptides in 2D liquid chromatography. In this way, the separation can be interfaced directly with the ion source of a mass spectrometer.

Crude Separation Proteins from Small MoleculesSmall molecules, e.g., peptides, amino acids, and metabolites, adversely influence MudPIT performance and mass spectrometric analysis.

Many methods for removal of interfering small molecules had been evaluated. Among these attempts, dialysis, various protein precipitation protocols with the addition of organic acids and/or organic additives, and molecular weight cut-off ultrafiltration, were either too laborious or too lossy.

Soluble proteins with MW > 4 kD is separated from small molecules by size exclusion (gel filtration) chromatography for further MudPIT-MS analyses.

Major Approaches for Protein IdentificationScience 2006, 314, 65 66.

Potential problems with bottom-up approachA mixture of n-proteins is converted into a (10~50)xn-peptide mixture. Increase in complexity is more than compensated by gain in MS detection sensitivity.

The exact intactness of the proteins in the starting sample is not assured.

Quantitation of each parent protein content is almost impossible.

Information on the x-yth dimensional section

Top-Down Bottom-UpD-x (LC retention time)D-y (Mass)D-x (LC retention time)D-y (Mass)

Introductory Mass Spectrometry Website by Dr. Lhost G.J.J. http://www.specmetcrime.com/mass__spectrometry.htmIonization methods in MSAPCI and ESIFAST ATOM AND ION BOMBARDMENTPHOTOIONIZATIONCHEMICAL IONIZATION ELECTRON IONIZATION (EI) AnalyzersMAGNETIC AND ELECTROMAGNETICTIME- OF- FLIGHTQuadrupole Mass FilterTandem MS with triple quadrupole mass spectrometersQuadrupole Ion Trap (QUIT/Paul trap) Fourier Transform Ion Cyclotron Spectroscopy (FTICR/Penning Trap)Detectors Faraday CupSecondary Electron Multipliers (SEM) Channel Electron Multiplier (CEM)Multipoint Array Detector

The basics of mass spectrometry in the twenty-first centuryGary L. Glish & Richard W. VachetNature Reviews Drug Discovery 2, 140-150 (February 2003)a | Mass analysis in time-of-flight (TOF) spectrometry is achieved because ions of different mass-to-charge (m/z) values have different velocities and therefore reach the detector at different times. b | A double-focusing analyser provides direction focusing through both the electric and magnetic sectors. Ions with the same kinetic energy-to-charge ratio follow a common path through an electric sector, and ions can then be dispersed according to their momentum-to-charge ratio in a magnetic sector. Overall analysis according to m/z is achieved. c | In a quadrupole mass analyser (top rod not shown), the correct magnitude of the radio frequency and direct current voltages applied to the rods allows ions of a single m/z to maintain stable trajectories from the ion source to the detector, whereas ions with different m/z values are unable to maintain stable trajectories.

2009

Secondary Ions Mass Spectrometry (SIMS) is one of the analytical techniques adopted by the semiconductor industry that provides an advantage for process development, transfer to multiple fabrication plants and that enables companies to meet the time-to-market deadlines for product release. SIMS is used extensively for the dopant depth profiling on implanter matching in front-end semiconductor processing and depth profiling of high-k dielectrics used as gate materials. In the back-end processing SIMS analytical applications include depth profiling of different metals and dielectric films. Other SIMS applications include metallic contamination analysis, interface composition analysis and imaging of any materialthat can be retained in solid steady state after introduction in UHV chambers of the instruments.

time-of-flight secondary ion mass spectrometry (SIMS) emission microscope

SIMS is a widespread technique in which a stream of energetic, primary ions bombards the surface of a material under investigation. Upon impact, these ions generate positively and negatively charged secondary ions, which are gathered by electrically charged lenses, imaged, and identified. (Neutral atoms and molecules are also given off but are not detected.) "The higher the charge, the greater the 'pop,' the more ions that come off." More ions mean more--and faster--information about the composition of the surface layer, including any contaminants.

during the first few femtoseconds (quadrillionths of a second) of impact, the highly charged ions deposit a huge amount of potential energy into a surface area several nanometers (billionths of a meter) square. In contrast, single-charged ions deposit large amounts of kinetic, not potential, energy. This kinetic energy transfer is not localized at the surface but is distributed more deeply into the sample. https://www.llnl.gov/str/Hamza.html

If the primary beam is composed of positively charged ions, the resultant ionization favors production of negative ions; primary beams of negative ions favor generation of positive ions

For SIMS the sample surface must be highly polished (~1 micrometer) and coated with a conducting, pure metal (particularly for non-conducting specimens) to avoid charge buildup on the surface

SIMS is a surface sensitive technique to characterize the elemental and chemical composition of the upper first monolayers

analytical tool for common materials research, process development, failure analysis, and production quality control application

Fundamentals and Applications of SIMS Secondary Ion Mass Spectrometry

TOF-SIMS Surface Metals

Bulk Techniques Glow Discharge Mass Spectrometry Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry Inductively Coupled Plasma-Optical Emission Spectrometry/Mass Spectrometry Instrumental Gass Analysis

Mainstream types of high-performance mass spectrometers

Double focusing sector mass spectrometer Tandem magnetic and electrostatic sectors forward geometry(E-B), reverse geometry (B-E)QuadrupoleIon trapToFFT: ICR & Orbitrap