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Types of Analyzers:

Sector or double focusing: magnetic and electricTime-of-flight (TOF)Quadrupole (mass filter)Linear ion trap Quadrupole Ion Trap (3D trap)FTICR – fourier transform ion cyclotron resonance (magnet)Orbitrap

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• Mass filter – separation accomplished using combination of DC and RF electric fields.

• Ions oscillate through filter towards detector.

• Only ions with stable trajectory transmitted.

• Scan DC/RF m/z.

DC = Direct current (constant)RF=AC= alternating current

Quadrupole: “mass filter”-part1

http://www.files.chem.vt.edu/chem-ed/ms/quadrupo.html

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An ion that is the right size drifts slightly in the DC of the field, but is always dragged back by the AC. The AC, however, is not quite strong enough to make it spiral out of control into an electrode. Thus an ion just the right size is stable in this quadrupole field and reaches the end, where it can be measured.

A very large ion will not be affected much by the AC, but will gradually drift in the DC part. The AC is not strong enough to drag it back as it wanders, so it also collides with an electrode, and is lost.

A small ion will be dragged a large distance by the AC, and will find itself in stronger and stronger regions of field. It will quickly collide with an electrode and disappear.

The AC field makes the ions go off into spirals as they pass down the quadrupole. The DC drags them in one constant direction, towards one pair of electrodes.

http://www.jic.ac.uk/services/metabolomics/topics/lcms/single1.htm

The stability of an ion depends on the sizes of the AC and DC ratio.

Quadrupole: “mass filter”-part2

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Quadrupole: “mass filter”-part3

Equations of ion motionMathieu functions

DC = Direct current (constant) = U RF=AC= alternating current = V

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Scan: changes of DC and ACat DC/AC constant ratio

Scan-line passes through the stable region

ion will pass through the quadrupole to the detector

Quadrupole: “mass filter”-part3 –scan

http://www.jic.ac.uk/services/metabolomics/topics/lcms/single2.htm

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Quadrupole: “mass filter”-part4 –resolving power

Unit resolution instruments : R= 20 at m/z 20; R= 200 at m/z 200

Mass range m/z aprox 3000

Easy to connect with Chromatography Techniques

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Quadrupole: AC only (RF-only)= ION GUIDE

Also HEXAPOLES , OCTOPOLES = more ”poles” leads to better ion guiding and wider m/z range

Use to adapt Atmospheric Pressure ion sources to mass analyzers acting as pipes and fully permeable to neutrals.

However, the presence of residual gas reduce the ion kinetic energy

Favoring also the ion motion towards the central axis of the quadrupole = Collision Cooling

Ion storage device

Ion Trap

Linear ion trap

iON TRAPPING.exe

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Linear Ion trap : quadrupole+ trapping potential well

Progressively ejected ions by increasing RF voltage (AC)

LIT are used to collect ions before injecting them in bunches into other analyzer (TOF or FTIR) parent ion isolation.exe

Axial or Radial

ejection of the ions

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Benefits. Good reproducibility. Relatively small and low-cost systems. Low-energy collision-induced dissociation (CID) MS/MS spectra

Limitations. Limited resolution. Peak heights variable as a function of mass (mass discrimination). Peak height vs. massresponse must be 'tuned'.

. Not well suited for pulsed ionization methods

. Low-energy collision-induced dissociation (CID) MS/MS depends strongly on energy, collision gas, pressure, and other factors.

Applications. Majority of benchtop GC/MS and LC/MS systems. Triple quadrupole MS/MS systems. Hybrid MS/MS systems

Example : Target analysis in drug detection

Linear Ion trap and Quadrupole:

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iON TRAPPING.exe

parent ion isolation.exeparent ion isolation.exe

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3D Ion trap :

Ion motion

Mathieu Stability diagram

http://www.currentseparations.com/issues/16-3/cs16-3c.pdf

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RF set so that all ions above specific m/z follow stable trajectory , All other ions escape.

Fragmentation by collision induce dissociation (CID) :Ion activated by collision and allowed to dissociate

3D Ion trap : MSn = SEVERAL fragmentation (CID)

parent ion isolation.exe

CID = ion accelerated by electric potential and allowed to collide with neutral molecules = kinetic energy is transformed into internal energy = breakage

CID depends strongly on energy, collision gas, pressure, and other factors = no libraries

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http://www.currentseparations.com/issues/16-3/cs16-3c.pdf

3D Ion trap : Example

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3D Ion trap :

Fast scanning at unit resolution High resolution over smaller m/z rangesMSn exsperiments

Compact = IDEAL FOR FIELD APPLICATIONS

Aqueous Monitoring/sampling

Mass spectrometry detection (MS/MS), EI, Ion Trap

MIMS – Membrane introduction mass spectrometry

Method for airborne and aqueous organics analysis

Morten Martinsen, Rudolf SchmidInstitutt for Kjemi, NTNU, Norway

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Benefits. High sensitivity. Multi-stage mass spectrometry (analogous to FTICR experiments). Compact mass analyzer (Field detector). MSn

Limitations. Very poor dynamic range (can sometimes be compensated for by using auto-ranging). Subject to space charge effects and ion molecule reactions. Collision energy not well-defined MS/MS depends strongly on energy,

collision gas, pressure, and other factors

Applications. Benchtop GC/MS, LC/MS and MS/MS systems. Target compound screening

3D Ion trap :

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Ion in a magnetic field experience Lorentz force and bend them in a circular path

In ICR it is detected the frequency that the ions go around

Mass-selective excitation achieve by a transverse electric field alternating

FT-ICR : Fourier transform ion cyclotron resonance

http://www.youtube.com/watch?v=7EHngA4S3Ws&feature=player_detailpage

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FT-ICR : High resolving power and mass accuracy

High resolving power:

Broad band detection for all frequencies in parallel – FT (FID)

m/z 50-500 frequency bandwidth 3MHz-300KHz

For a R: 100000 in m/z 500 frequency detection = (300KHz/100000)= 3Hz

High mass accuracy :

Elongated recorder FID – allows for extremely precise determination of all cyclotron frequencies

http://www.sciencedirect.com/science/article/pii/S0021967304014396

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FT-ICR :

BenefitsHighest recorded mass resolution of all mass spectrometers and High accuracy ( <1ppm)Wide mass range without lost of sensitivity Non-destructive ion detection= ion re-measurementStable mass calibration

Limitations:Needs Low Background pressure to avoid ion molecule reactions and ion –neutral collisions Need high magnetic field Large and really expensive

Applications :Complex mixture , e.g. crude oil (http://www.magnet.fsu.edu/usershub/scientificdivisions/icr/index.html)MacromoleculesMetabolomicsProteomics ( after protein digestion - fragments determination)

….etc..

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Orbitrap: Ions are trapped in Axial oscillation in a homogenous electrostatic field

Helps to capture andcooling the ions

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1. Ions are stored in the Linear Trap

2. …. are axially ejected

3. …. and trapped in the C-trap

4. …. they are squeezed into a small cloud and injected into the Orbitrap

5. …. where they are electrostatically trapped, while rotating around the central electrodeand performing axial oscillation

The oscillating ions induce an image current into the two outer halves of the orbitrap, which can be detected using a differential amplifier

Ions of only one mass generate a sine wave signal

LTQ-Orbitrap

http://www.youtube.com/watch?v=KjUQYuy3msA

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CID – Collision-Induced DissociationPQD – Pulsed-Q Dissociation

HCD - Higher Energy Collisional Dissociation

LTQ-Orbitrap

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BenefitsParallel acquisition mode available : highly resolved and accurate analysisMS3 fragmentationPolarity switch in the same run (+ to -)Slower Drop in resolution with increasing mass/z

Limitations :Requires Ultra high vacuumMass resolution and accuracy are linearly proportional to signal acquisition time

Applications: http://planetorbitrap.com/data/uploads/1298587945720_69749_XX30168_E02_10C.pdf

LTQ-Orbitrap

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Why need MS/MS?

-The detection of a specific compound in a mixture-Quantitation of a specific compound in a mixture-Structural determination of a compound

Most of the instruments available in the market are hybrid intruments

LTQ-OrbitrapFT-ICR QTOF

Triple quadrouple instruments

Q-TOF-ion mobility

Hybrid and tandem analysers : MS/MS

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PRECURSOR IONSELECTION

PRODUCT IONDETECTION

“Precursor” Ions are selected and isolatedCollision-Induced-Dissociation Results in fragmentation

“Product” Ions are characterized with the second mass analyzer

Tripel-QUAD: Mode 1: Product ion scan

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Precursor ion scan Q3 is held to measure the occurrence of a particular fragment ion, Q1 is scanned. This results is a spectrum of precursor ions that result in that particular product ionNeutral loss scan

Q1 is scanned as above, Q3 is also scanned at a mass off-set to produce a spectrum of

precursor ions that undergo a particular neutral loss.

Mode 2

Mode 3

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Selected reaction monitoring (SRM or also called MRM)Q1 and Q3 are static; user-selected specific ions are transmitted through the first analyser and user-selected specific fragments arising from these ions are measured by the second analyser. The compound must be known and characterised in advance.

BEST FOR QUATIFICATION METHODS

Mode 4

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Comparison of Mass analysers

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Courtesy of EPSRC National Mass Spectrometry Service Center