CH 908: Mass Spectrometry Lecture 6 Mass Analyzers

1
CH 908 Mass SpectrometryLecture 6 Mass
Analyzers

• Prof. Peter B. OConnor

2
Objectives

• Types of mass spectrometers and how they operate
• Time-of-flight
• Quadrupoles
• Ion traps
• Mathieu stability diagram analyss
• FTICR
• Orbitrap

3
Electron Multiplier
4
Notes channeltron microchannel plates chevron
5
Mass Spectrometers

• Time of Flight
• Magnetic Sector
• Quadrupole
• Triple Quadrupole
• Quadrupole Ion Trap
• FTICRMS
• Orbitrap

Mass Spectrometers DO NOT measure mass. They
measure mass/charge ratio. Understanding how
mass spectrometers work is understanding how ions
move in electric and magnetic fields.
6
Ions in a DC Electric Field
F qE m d2x/dt2

10 KV
7
Time of Flight Mass Spectrometry
The most simple of all mass spectrometers, at
least conceptually. Linear versus
reflectron Delayed extraction (time lag
focusing) Detection electronics PSD
scan Orthogonal injection

• MALDI-TOF
• EI-TOF
• ESI-TOF

8
Basic TOF mass spectrometer
9
Laser
Source
S



D (field free drift region)
V
Figure 3. The principle of MALDI time-of-flight
mass spectrometry.

• TOF requires a pulsed ion source
• TOF requires a small kinetic energy distribution
  in the ions
• Radial dispersion causes signal loss
• TOF requires a detector/oscilloscope/digitizer
  thats MUCH faster than the ion flight time.

10
TOF fundamental limitations
Resolution limited by length of TOF flight
tube kinetic energy distribution - delayed
extraction - reflectron - orthogonal
injection propagation delay in detector
11
Laser
Source
S
Vr Vs
D1 (first field free drift region)
First Detector


deflector
Vs
Oscilloscope
D2 (second field free drift region)
Second Detector
Figure 4. Combined Linear/Reflectron MALDI
time-of-flight mass spectrometer.
12
Oscilloscope
Delay Generator
Laser
Source
S
Pusher (Vp)






Q0
Q2
Q1
V
(RF-only)
(mass filter)
(RF-only)
Focusing
Collision Cell
D (field free drift region)

Vr Vp
Figure 14. Quadrupole Time-of-Flight Hybrid
13
Laser
Source
deflector
Collision Cell (Vc)
Vr Vs


first field free drift region
Vs
second field free drift region
Detector
Oscilloscope
Figure 6. MALDI tandem time-of-flight mass
spectrometer.
14
TOF Parameters

• Simple, cheap (in theory), robust, sensitive.
• A good modern TOF should give
• gt10k Resolving power
• 1-10 fmol sensitivity (single scan)
• 10 ppm mass accuracy internally calibrated (5
  ppm if the peak is particularly large or clean).
  
• gt1000 scans/second
• Unlimited mass range

TOFMS Calibration Equation m At2B
15
TOF fundamental limitations
Resolution limited by length of TOF flight
tube kinetic energy distribution propagation
delay in detector Sensitivity limited by ion
stability ion transfer efficiency MS/MS is
difficult
16
Ions in a Magnetic Field
Fqv x B
17
Magnetic Sector Mass Spectrometry

• MALDI
• EI
• ESI

Large, expensive, obsolete. Swept beam
instrument The first High Resolution mass
spectrometer (gt 10k RP) Lousy sensitivity (1
nmol) High energy collisional fragmentation Extrem
ely linear detector response (isotope ratio mass
spectrometry)
Sector Calibration Equation m AB02r2/V
Jeol and Thermo-Finnigan MAT
18
Ions in a magnetic field
19
Sector Fundamental Limitations
Resolution/sensitivity tradeoff by using a mass
filtering slit Resolution limited by
magnetic/electric field homogeneities slit
width Sensitivity limited by ion transfer
efficiency slit width metastable decay Scan
speed / scan stability tradeoff
20
Quadrupoles

• MALDI
• EI
• ESI

Small, cheap, ubiquitous. Swept beam
instrument Resolution typically 1000, mass
accuracy typically 0.1 Sensitivity depends on
the source. Typically in the 100 fmol range.
21
Wolfgang Paul (quadrupole ion traps)
Hans Dehmelt (Penning ion traps)
1989 Nobel Prize in Physics for development of
ion trapping techniques
22
Quadrupole mass spectrometer
23
Wiring of a quadrupole
24
The potential energy diagram of a quadrupole
showing the saddlepoint in the electric field
(generated using Simion 7.0)
25
3D - Quadrupole ion traps

• linear ion traps
• 3D ion traps
• They follow exactly the same rules as quadrupoles

26
z
r
A. a cross-section of a hyperbolic quadrupole
ion trap
B. a potential energy diagram of the QIT showing
the saddlepoint in the electric field (generated
using Simion 7.0)
Figure 11. The shape of Paul ion trap mass
spectrometers.
27
Quadrupole Ion Traps
Skimmer Lenses
Octopole Ion Guide
Entrance Endcap
Capillary
Ring Electrode
Exit Endcap
Lenses
28
Quadrupoles
Matthieu eqn
A U Vsin(?t)

• qz a V/m
• qz a fion
• az a U/m

29
Quadrupole Ion Traps
Matthieu eqn
A U Vsin(?t)

• qz a V/m
• qz a fion
• az a U/m

30
qz 0.908
z stable
B
A
r and z stable
D
az 0.02, qz 0.7
az 0.05, qz 0.1
C
r stable
az -0.2, qz 0.2
az -0.04, qz 0.2
Figure 12. Mathieu stability diagram with four
stability points marked. Typical corresponding
ion trajectories are shown on the right.
31
QITMS Mass-Instability Ion Ejection

• Mass Analysis Ramp RF Volt. on ring electrode
• Ions increase in qz value
• Ions become axially unstable at qz 0.908
• Ions are ejected from ion trap
• Low m/z ions are detected first

32
QITMS Resonant Ejection

• Mass Analysis Ramp RF Volt. on ring electrode
• As RF increases ions increase in qz
• Apply dipolar AC signal to endcap electrodes for
  resonant ejection
• Ions are ejected radially from trap
• Low m/z ions are detected first

33
(No Transcript)
34
QITMS Parameters
Small, cheap, ubiquitous. Ion trap
instrument Resolution typically 1000, mass
accuracy typically 0.1 Sensitivity depends on
the source. Typically in the 100 fmol range. MSn
compatible Operates in 10-4 mbar Helium. Ion
Molecule Reactions (e.g. gas phase H/D Exchange)
Why is this problematic?

• MALDI
• EI
• ESI

QITMS Calibration Equation m AV/r2f2
35
Quadrupole MS Fundamental Limitations
Resolution homogeneity of the electric field
(charging of the electrodes, or inaccurate
machining distorts this) scan speed Sensitivity
scan speed ion transfer efficiency Mass
range limited on high end by size of trap and
potentials available limited on low end by
stability diagram
36
Octopole ion guide/trap
37
Octopole ion guide/trap
38
Hexapole ion trap
39
Fourier Transform Mass Spectrometer
Big, expensive, but superior performance. Ion
trap instrument Resolution typically gt50000
broadband, gt1,000,000 narrowband Mass accuracy
typically 1 ppm internally calibrated 5-10 ppm
externally calibrated Sensitivity depends on the
source. Typically in the 100 fmol range. MSn
compatible Ion Molecule Reactions (e.g. gas phase
H/D Exchange)

• MALDI
• EI
• ESI

40
How Does FTMS Work?
RF-only Quadrupole Ion Guide
Cylindrical Penning Trap
Electrospray Ion Source
Actively Shielded 7T Superconducting Electromagnet
Turbo pump
Turbo pump
Turbo pump
Electrospray FTMS
41
ESI qQq-FTMS Diagram
42
How Does FTMS Work?
The Penning Trap
The ions view of the cell
43
How Does FTMS Work?
-

Ions are trapped and oscillate with low,
incoherent, thermal amplitude
Excitation sweeps resonant ions into a large,
coherent cyclotron orbit
Preamplifier and digitizer pick up the induced
potentials on the cell.
44
How Does FTMS Work?
10 MHz
10 kHz
High Resolution (50,000 FWHM) High mass accuracy
(1 ppm) High sensitivity (femtomoles)
Transient Image current detection
FFT
Calibrate
RP?ft/2 Sensitivity? ft
Mass Spectrum
600
800
1000
1200
1400
1600
m/z
45
Good FTICR review article
46
Effect of transient duration
47
Beta Casein Tryptic digest, 2 pmol/ul
MS
T15
Isolation
X
X
M2H2
MS/MS
y10
Y132

y11
y7
y9
b9
y8
b10
b12
b8
y12
y13
y14
b7
b11

?1
X
X



X
48
FTMS Calibration Equation
Theory ? ?c/2 (?c2/4 2eVa/ma2)1/2
Practice m A/f B/f2 C m
A/(f-B-CV-DI)
?c qB0/m
1. Zhang, L. K. Rempel, D. Pramanik, B. N.
Gross, M. L. Accurate mass measurements by
fourier transform mass spectrometry Mass Spectrom
Rev 2005, 24, 286-309.
49
FTMS Fundamental Limiting Factors

• Resolution
• Pressure
• Magnetic field (strength and homogeneity)
• Electric field (homogeneity)
• Space charge
• Sensitivity
• Preamplifier Noise
• Magnetic field strength
• Space charge
• Mass range
• Magnetic field
• Frequency performance of electronics

50
A new instrument the orbitrap
51
Self Assessment

• In TOF-MS, which ions arrive at the detector
  first? Why?
• In a QIT, what q-value corresponds to the low m/z
  cutoff in RF-only mode?
• What part of the Mathieu stability diagram is
  used in mass filtering mode in a quadrupole or
  QIT?
• In FTICR, doubling the detection time will result
  in what change to the resolving power? Doubling
  the magnetic field will result in what change?

52
CH908 Mass spectrometry Lecture 6 Mass
Analyzers
Fini