CH 908: Mass Spectrometry
Lecture 6
Mass Analyzers
Prof. Peter B. O’Connor
Objectives
• Types of mass spectrometers and how
they operate
– Time-of-flight
– Quadrupoles
– Ion traps
• Mathieu stability diagram analyss
– FTICR
– Orbitrap
Electron Multiplier
Notes:
channeltron
microchannel plates
chevron
Mass Spectrometers
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.
• Time of Flight
• Magnetic Sector
• Quadrupole
• Triple Quadrupole
• Quadrupole Ion Trap
• FTICRMS
•Orbitrap
Ions in a DC Electric Field
F = qE = m d2x/dt2
+
10 KV
Time of Flight Mass
Spectrometry
The most simple of all mass spectrometers,
at least conceptually.
Linear versus reflectron
• MALDI-TOF
Delayed extraction (time lag focusing)
• EI-TOF
Detection electronics
• ESI-TOF
PSD scan
Orthogonal injection
Basic TOF mass spectrometer
Laser
Source
Oscilloscope
S
+
+
V
+
+
D (field free drift region)
Figure 3. The principle of MALDI time-of-flight mass spectrometry.
1. TOF requires a pulsed ion source
2. TOF requires a small kinetic energy distribution in the ions
3. Radial dispersion causes signal loss
4. TOF requires a detector/oscilloscope/digitizer that’s MUCH
faster than the ion flight time.
TOF fundamental limitations
Resolution limited by:
length of TOF flight tube
kinetic energy distribution
- delayed extraction
- reflectron
- orthogonal injection
propagation delay in detector
Laser
Source
S
D1 (first field free drift region)
First
Detector
+
+
Vs
Vr ≈ Vs
deflector
Oscilloscope
D2 (second field free drift region)
Second
Detector
Figure 4. Combined Linear/Reflectron MALDI time-of-flight mass spectrometer.
Oscilloscope
Delay Generator
Laser
Source
S
Pusher (Vp)
+
+
+
Q0
(RF-only)
Focusing
+
Q1
(mass filter)
+
Q2
(RF-only)
Collision Cell
D (field free drift region)
V
+
Vr ≈ Vp
Figure 14. Quadrupole Time-of-Flight Hybrid
Laser
Source
deflector
Collision Cell (Vc)
+
+
Vs
first field free drift region
Delay Generator
second field free drift region
Detector
Oscilloscope
Figure 6. MALDI tandem time-of-flight mass spectrometer.
Vr ≈ Vs
TOF Parameters
Simple, cheap (in theory), robust, sensitive.
A good modern TOF should give:
 >10k Resolving power
 ~1-10 fmol sensitivity (single scan)
 ~10 ppm mass accuracy internally calibrated (5 ppm if the peak is
particularly large or clean).
 >1000 scans/second
Unlimited mass range
TOFMS Calibration
Equation
m = At2+B
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
Ions in a Magnetic Field
+
F=qv x B
F
V
B
Magnetic Sector Mass
Spectrometry
Large, expensive, obsolete.
• MALDI
Swept beam instrument
• EI
The first “High Resolution” mass
spectrometer (> 10k RP)
• ESI
Lousy sensitivity (~1 nmol)
High energy collisional fragmentation
Extremely linear detector response
(isotope ratio mass spectrometry)
Jeol and Thermo-Finnigan MAT
Sector
Calibration
Equation
m = AB02r2/V
Ions in a magnetic field
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
Quadrupoles
Small, cheap, ubiquitous.
• MALDI
Swept beam instrument
• EI
Resolution typically 1000, mass accuracy
typically 0.1%
• ESI
Sensitivity depends on the source.
Typically in the 100 fmol range.
Wolfgang Paul
(quadrupole ion traps)
Hans Dehmelt
(Penning ion traps)
1989 Nobel Prize in Physics for development of ion
trapping techniques
Quadrupole mass spectrometer
Wiring of a quadrupole
The potential energy diagram of a quadrupole showing the
saddlepoint in the electric field (generated using Simion 7.0)
3D - Quadrupole ion traps
•linear ion traps
•3D ion traps
•They follow exactly the same rules as
quadrupoles
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.
Quadrupole Ion Traps
Skimmer Lenses
Octopole Ion Guide
Entrance Endcap
Capillary
Ring
Electrode
Lenses
Exit Endcap
Quadrupoles
“Matthieu eqn”
az
-0.4
Operating
z stability Line
-0.2
b=1.0
qz=.908
0.0
Stable
z&r
-0.2
+
-0.4
+
-0.6
+
A± = U ± Vsin(ωt)
r stability
0.5
1.0
1.5
8eU
an 
2 2
m r
qz
4eV
qz 
2 2
m r
• qz a V/m
• qz a fion
• az a U/m
Quadrupole Ion Traps
“Matthieu eqn”
az
-0.4
Operating
z stability Line
-0.2
b=1.0
qz=.908
0.0
Stable
z&r
-0.2
+
-0.4
+
-0.6
+
A± = U ± Vsin(ωt)
r stability
0.5
1.0
1.5
qz
16eU
az 
m 2 (r 2  2 z 2 )
8eV
qz 
m 2 (r 2  2 z 2 )
• qz a V/m
• qz a fion
• az a U/m
qz = 0.908
az
A
B
0.2
z stable
B
A
0.0
r and z
stable
D
-0.2
az = 0.02, qz = 0.7 az = 0.05, qz = 0.1
C
C
D
r stable
-0.4
-0.6
0.0
0.5
1.0
qz
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.
QITMS: Mass-Instability Ion Ejection
az
Operating
Line
-0.4
•
Low
m/z
-0.2
b=1.0
qz=.908
0.0
+-0.2
qz 
High
m/z
qz •
•
•
+-0.4
+-0.6
•
0.5
1.0
1.5
8eV
m 2 (r 2  2 z 2 )
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
az
QITMS: Resonant Ejection
•
Operating
Line
-0.4
Low
m/z
-0.2
Res. Ejection
at bz=2/3
High
m/z
qz
•
•
-0.4
+
-0.6
+
•
b=1.0
qz=.908
0.0
-0.2
+
•
0.5
1.0
1.5
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
QITMS Parameters
Small, cheap, ubiquitous.
Ion trap instrument
• MALDI
Resolution typically 1000, mass accuracy
typically 0.1%
• EI
Sensitivity depends on the source.
Typically in the 100 fmol range.
• ESI
MSn compatible
Operates in 10-4 mbar Helium.
Ion Molecule Reactions (e.g. gas phase H/D
Exchange) Why is this problematic?
QITMS Calibration
Equation
m = AV/r2f2
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
Octopole ion
guide/trap
Octopole ion guide/trap
Hexapole ion trap
Fourier Transform Mass
Spectrometer
Big, expensive, but superior performance.
Ion trap instrument
Resolution typically >50000 broadband, >1,000,000
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
How Does FTMS Work?
Cylindrical
Penning Trap
Actively Shielded 7T
Superconducting
Electromagnet
RF-only
Quadrupole
Ion Guide
Electrospray
Ion Source
Turbo
pump
Turbo
pump
Turbo
pump
Electrospray FTMS
ESI qQq-FTMS Diagram
Gate Valve
(ground)
RF-Only Hexapole
Shutter
Vqtrap
Vftrap
Vinner-rings
GR
IQ3
IQ2
Q2
Q1
ST IQ1
Q0 RNG
OR
SK
How Does FTMS Work?
The Penning Trap
The ions’ view of the cell
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.
How Does FTMS Work?
10 MHz
10 kHz
RF Sweep
High Resolution
(~50,000 FWHM)
Transient Image
current detection
High mass
accuracy (~1 ppm)
FFT
Calibrate
RP≅f•t/2
Sensitivity f•t
Mass Spectrum
600
800
High sensitivity
(femtomoles)
1000 m/z 1200
1400
1600
Good FTICR review article
Effect of transient duration
Beta Casein Tryptic digest,
2 pmol/ul
MS
T15
700
800
900
1000
1100
1200
1300
1500
1400
Isolation
X
1080
1090
1100
X
700
800
900
1000
1100
1200
1300
1400
1500
[M+2H]2+
MS/MS
y10
y7*
y8
b7
700
Y132+
800
b8
y9 b9
b10
*** X
*
900
1000
1100
1200
y11
X
b
b11 Xy12 ?1+ 12
1300
1400
y13
1500
y14
1600
FTMS Calibration Equation
Theory:
Practice:
ω± = ωc/2 ± (ωc2/4 – 2eVα/ma2)1/2
m = A/f + B/f2 + C
m = A/(f-B-CV-DI)
ωc = 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.
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
A new instrument – the orbitrap
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?
CH908: Mass spectrometry
Lecture 6 – Mass Analyzers
Fini…