TY - JOUR
T1 - Enhanced detection of high-mass proteins by using an active pixel detector
AU - Ellis, S.R.
AU - Jungmann, JH
AU - Smith, D.F.
AU - Soltwisch, J.
AU - Heeren, R.M.A.
PY - 2013
Y1 - 2013
N2 - Since their emergence in the 1980s, matrix-assisted laser
desorption/ionization (MALDI)[1] and electrospray ionization
(ESI)[2] have been widely applied to the analysis of proteins
and have been key drivers in the growth of the proteomics
field.[3] A significant difference between the two ionization
techniques is that MALDI, unlike ESI, typically produces
singly or doubly charged ions for large molecules and
therefore requires mass analyzers and ion detection
approaches suitable for these species with higher m/z ratios.
MALDI is often coupled with time-of-flight (TOF) mass
analysers because of their theoretically unlimited mass range.
However, in practice, such systems are ultimately limited by
the ability to efficiently detect singly charged ions with high
m/z ratios. Ion detection in TOF-mass spectrometry (TOFMS)
is traditionally accomplished by using the ion-to-electron
conversion abilities of microchannel plates (MCPs). However,
the ion-to-electron conversion efficiency of an MCP is
well known to decrease with decreasing ion momentum (i.e.,
at higher mass).[4] Thus, although many high-mass ions can be
generated, they may not be efficiently detected and their
observed ion abundance may appear artificially low or
possibly not be detected at all. To overcome this limitation,
a variety of alternative non-MCP-based ion detection systems
have been developed and have been demonstrated for m/z
values up to 1 MDa.[4b, 5] Herein we describe the first reported
application of the Timepix active pixel detector[6] to a commercial
MALDI linear TOF instrument that provides ion
acceleration voltages up to 25 kV. This combination of high
ion acceleration voltages and a highly sensitive pixelated
detector are shown to allow detection of ions up 400 kDa with
high m/z ratios by using MCP-based detection with significant
enhancements in signal-to-noise ratios compared with conventional
detection approaches.
AB - Since their emergence in the 1980s, matrix-assisted laser
desorption/ionization (MALDI)[1] and electrospray ionization
(ESI)[2] have been widely applied to the analysis of proteins
and have been key drivers in the growth of the proteomics
field.[3] A significant difference between the two ionization
techniques is that MALDI, unlike ESI, typically produces
singly or doubly charged ions for large molecules and
therefore requires mass analyzers and ion detection
approaches suitable for these species with higher m/z ratios.
MALDI is often coupled with time-of-flight (TOF) mass
analysers because of their theoretically unlimited mass range.
However, in practice, such systems are ultimately limited by
the ability to efficiently detect singly charged ions with high
m/z ratios. Ion detection in TOF-mass spectrometry (TOFMS)
is traditionally accomplished by using the ion-to-electron
conversion abilities of microchannel plates (MCPs). However,
the ion-to-electron conversion efficiency of an MCP is
well known to decrease with decreasing ion momentum (i.e.,
at higher mass).[4] Thus, although many high-mass ions can be
generated, they may not be efficiently detected and their
observed ion abundance may appear artificially low or
possibly not be detected at all. To overcome this limitation,
a variety of alternative non-MCP-based ion detection systems
have been developed and have been demonstrated for m/z
values up to 1 MDa.[4b, 5] Herein we describe the first reported
application of the Timepix active pixel detector[6] to a commercial
MALDI linear TOF instrument that provides ion
acceleration voltages up to 25 kV. This combination of high
ion acceleration voltages and a highly sensitive pixelated
detector are shown to allow detection of ions up 400 kDa with
high m/z ratios by using MCP-based detection with significant
enhancements in signal-to-noise ratios compared with conventional
detection approaches.
U2 - 10.1002/anie.201305501
DO - 10.1002/anie.201305501
M3 - Article
SN - 1433-7851
VL - 52
SP - 11261
EP - 11264
JO - Angewandte Chemie-International Edition
JF - Angewandte Chemie-International Edition
IS - 43
ER -