U.S. patent application number 17/692370 was filed with the patent office on 2022-06-23 for liquid sample introduction method and liquid sample introduction device.
The applicant listed for this patent is SHIMADZU CORPORATION. Invention is credited to Shingo FUJIOKA, Kazuma MAEDA, Daisuke OKUMURA.
Application Number | 20220199385 17/692370 |
Document ID | / |
Family ID | |
Filed Date | 2022-06-23 |
United States Patent
Application |
20220199385 |
Kind Code |
A1 |
OKUMURA; Daisuke ; et
al. |
June 23, 2022 |
LIQUID SAMPLE INTRODUCTION METHOD AND LIQUID SAMPLE INTRODUCTION
DEVICE
Abstract
The other end of an individual sample supply channel one end of
which is connected to a gas buffer container the inside of which is
empty is connected to one sub-port of a valve that selects one of
standard samples to be supplied to an ESI probe. During analysis,
the standard sample stored in one of liquid sample containers is
selected by switching a connection state of the valve. The standard
sample supplied by being pushed by a gas sent to the liquid sample
containers through liquid supply gas branch channels is sent to the
ESI probe through a sample supply main channel. At the time of
finishing analysis, when the valve is switched such that the
sub-port and a main port are communicatively connected, a nitrogen
gas is sent to the sample supply main channel, and the remaining
liquid is discharged.
Inventors: |
OKUMURA; Daisuke;
(Kyoto-shi, JP) ; FUJIOKA; Shingo; (Kyoto-shi,
JP) ; MAEDA; Kazuma; (Kyoto-shi, JP) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
SHIMADZU CORPORATION |
Kyoto-shi |
|
JP |
|
|
Appl. No.: |
17/692370 |
Filed: |
March 11, 2022 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
16613160 |
Nov 13, 2019 |
11309173 |
|
|
PCT/JP2017/029051 |
Aug 10, 2017 |
|
|
|
17692370 |
|
|
|
|
International
Class: |
H01J 49/04 20060101
H01J049/04; G01N 27/623 20060101 G01N027/623; G01N 1/00 20060101
G01N001/00 |
Claims
1. A liquid sample introduction method using a liquid sample
introduction device configured to send a liquid sample and a
nebulizing gas to an ionization probe of an ion source in an ion
analysis device and to nebulize the liquid sample from a tip of the
ionization probe with the help of the nebulizing gas, the liquid
sample introduction device including a plurality of liquid sample
containers which is closed containers in which liquid samples are
stored, a liquid supply gas path connected at one end to a middle
of a channel for supplying the nebulizing gas to the ionization
probe and branched into a plurality of sub-paths connected
respectively to the plurality of liquid sample containers above
liquid levels of the liquid samples, a channel switching unit
configured to selectively connect one outlet port and one of a
plurality of inlet ports to each other, a common sample supply
channel one end of which is connected to the ionization probe and
another end is connected to the outlet port of the channel
switching unit, and a plurality of individual sample supply
channels one ends of which are connected to the plurality of liquid
sample containers below the liquid levels of the liquid samples and
other ends are connected to the plurality of inlet ports of the
channel switching unit, the method comprising: a process of setting
one of the plurality of liquid sample containers as a low-viscosity
liquid sample container in which a liquid having a viscosity lower
than viscosities of the liquid sample stored in the other liquid
sample containers is stored, and switching connection of the
channel switching unit such that the outlet port and the inlet port
connected to the low-viscosity liquid sample container are
connected to each other through one of the plurality of individual
sample supply channels at a time of finishing analysis in the ion
analysis device.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a Divisional of U.S. patent application
Ser. No. 16/613,160, filed Nov. 13, 2019, which is a National Stage
of International Application No. PCT/JP2017/029051 filed Aug. 10,
2017, the contents of all of which are incorporated herein by
reference in their entirety.
TECHNICAL FIELD
[0002] The present invention relates to a method of introducing a
liquid sample into an atmospheric pressure ion source that ionizes
components in a sample in an ion analysis device such as a mass
spectrometer or an ion mobility analysis device, and a liquid
sample introduction device used therefor.
BACKGROUND ART
[0003] In a liquid chromatograph mass spectrometer (LC-MS), a
liquid sample containing components temporally separated by a
column of a liquid chromatograph (LC) is introduced into the mass
spectrometer. The mass spectrometer includes an ion source that
performs ionization by, for example, an electrospray ionization
(ESI) method or an atmospheric pressure chemical ionization (APCI)
method in order to ionize the components (compounds) in the liquid
sample. For example, in an ESI ion source, the liquid sample is
guided to a tip of a thin tube and exposed to a large electric
field, and is nebulized in a substantially atmospheric pressure
with the help of a nebulizing gas. Fine charged droplets having
charges biased by an action of an electric field are formed, the
charged droplets become finer by colliding with the atmosphere, and
components in the droplets become gas ions while the solvent in the
droplets is evaporated.
[0004] In the LC-MS, in order to perform mass calibration and
adjust device parameters, it is necessary to perform an analysis by
introducing a standard sample, instead of the liquid sample
supplied from an LC, into the ion source. For example, a device
described in Patent Literature 1 has a configuration in which the
liquid sample supplied from the LC and the standard sample
pressurized by an air pressure are selectively supplied to the
ionization probe by switching the flow paths using a switching
valve. In the device described in Patent Literature 1, it is
necessary to prepare different gas systems: one for sending the
standard sample and the other for nebulizing the liquid sample to
the ionization probe. Thus, it is problematic in terms of cost.
[0005] In contrast, in the liquid sample introduction device
proposed by the applicant of the present invention in Patent
Literature 2, the gas branched from one gas source is supplied to
both the ionization probe and a liquid sample container in which
the standard sample is stored, and thus, the aforementioned problem
in the device described in Patent Literature 1 is solved.
CITATION LIST
Patent Literature
[0006] Patent Literature 1: U.S. Pat. No. 5,703,360 A
[0007] Patent Literature 2: WO 2017/056173 A
SUMMARY OF INVENTION
Technical Problem
[0008] In the liquid sample introduction device described in Patent
Literature 2, the gas from one gas source is branched and supplied
to a plurality of liquid sample containers. One among different
kinds of liquid samples stored in the plurality of liquid sample
containers is selected by one channel switching valve (N-position
(N+1)-port valve), and the selected liquid sample is supplied to
the ionization probe through one liquid supply channel.
Accordingly, any one of a plurality of different types of liquid
samples can be selectively introduced into the ion source by using
one channel switching valve.
[0009] In the liquid sample introduction device described in Patent
Literature 2, when the supply of the nebulizing gas from the gas
source to the ionization probe is stopped at the time of finishing
the analysis, the liquid sample (or the moving phase supplied from
the liquid chromatograph) remains in the liquid supply channel
between the channel switching valve and the ionization probe. Thus,
even when the supply of the gas to the liquid sample container is
started at the time of executing the next analysis and the liquid
sample in the liquid sample container is accordingly started to be
sent, the liquid sample or the moving phase remaining in the liquid
supply channel from the previous analysis are introduced into the
ion source for a while. Since the analysis cannot be properly
performed during that time, an analysis dead time is caused. Such
dead time leads to a decrease in analysis efficiency.
[0010] The present invention has been made to solve the problems,
and an object of the present invention is to provide a liquid
sample introduction method and a liquid sample introduction device
capable of improving analysis efficiency by shortening a waiting
time (that is, dead time) until a liquid sample to be analyzed is
introduced into an atmospheric pressure ion source at the time of
starting analysis.
Solution to Problem
[0011] According to a first aspect of a liquid sample introduction
method according to the present invention made in order to solve
the aforementioned problems, there is provided a liquid sample
introduction method using a liquid sample introduction device
configured to send a liquid sample and a nebulizing gas to an
ionization probe of an ion source in an ion analysis device and to
nebulize the liquid sample from a tip of the ionization probe with
the help of the nebulizing gas. The liquid sample introduction
device includes a plurality of liquid sample containers each of
which is a closed container and in which a liquid sample is stored,
a liquid supply gas path connected at one end to a middle of a
channel for supplying the nebulizing gas to the ionization probe
and branched into a plurality of sub-paths each end of which is
connected to each of the plurality of liquid sample containers
above liquid level of the liquid sample, a channel switching unit
configured to selectively connect one outlet port and one of a
plurality of inlet ports to each other, a common sample supply
channel one end of which is connected to the ionization probe and
the other end is connected to the outlet port of the channel
switching unit, and a plurality of individual sample supply
channels one ends of which are connected to the plurality of liquid
sample containers below the liquid levels of the liquid samples and
the other ends are connected to the plurality of inlet ports of the
channel switching unit.
[0012] The method includes a process of setting one of the
plurality of liquid sample containers to be in an empty state, and
switching connection of the channel switching unit such that the
outlet port and the inlet port connected to the liquid sample
container which is in the empty state are connected to each other
through one of the plurality of individual sample supply channels
at a time of finishing analysis in the ion analysis device.
[0013] As in the first aspect, according to a second aspect of a
liquid sample introduction method according to the present
invention made in order to solve the aforementioned problems, there
is provided a liquid sample introduction method using a liquid
sample introduction device configured to send a liquid sample and a
nebulizing gas to an ionization probe of an ion source in an ion
analysis device and to nebulize the liquid sample from a tip of the
ionization probe with the help of the nebulizing gas. The liquid
sample introduction device includes a plurality of liquid sample
containers each of which is a closed container and a liquid sample
is stored, a liquid supply gas path connected at one end to a
middle of a channel for supplying the nebulizing gas to the
ionization probe and branched into a plurality of sub-paths
connected respectively to the plurality of liquid sample containers
above liquid levels of the liquid samples, a channel switching unit
configured to selectively connect one outlet port and one of a
plurality of inlet ports to each other, a common sample supply
channel one end of which is connected to the ionization probe and
the other end is connected to the outlet port of the channel
switching unit, and a plurality of individual sample supply
channels one ends of which are connected to the plurality of liquid
sample containers below the liquid levels of the liquid samples and
the other ends are connected to the plurality of inlet ports of the
channel switching unit.
[0014] The method includes a process of setting one of the
plurality of liquid sample containers as a low-viscosity liquid
sample container in which a liquid having a viscosity lower than
viscosities of the liquid sample stored in the other liquid sample
containers is stored, and switching connection of the channel
switching unit such that the outlet port and the inlet port
connected to the low-viscosity liquid sample container are
connected to each other through one of the plurality of individual
sample supply channels at a time of finishing analysis in the ion
analysis device.
[0015] In the liquid sample introduction method and the liquid
sample introduction device according to the present invention, the
"ion analysis device" is typically a mass spectrometer, an ion
mobility analysis device, or an ion mobility-mass spectrometer
obtained by combining the mass spectrometer and the ion mobility
analysis device. The "ion source" in these devices is an ion source
based on an atmospheric pressure ionization method including an
atmospheric pressure photoionization (APPI) method in addition to
the ESI method and the APCI method described above.
[0016] In the liquid sample introduction device used in the liquid
sample introduction method according to the present invention, when
a liquid sample stored in a liquid sample container is analyzed,
the connection of the channel switching unit is switched such that
the inlet port connected to the individual sample supply channel
one end of which is connected to the liquid sample container and
the outlet port are connected to each other. The gas is sent to a
space within the liquid sample container through the liquid supply
gas path, and the pressure in the space is higher than that outside
the container. Thus, the liquid sample in the container pushed by
the pressure passes through the individual sample supply channel,
and is introduced into the ionization probe through the internal
channel of the channel switching unit and the common sample supply
channel. The liquid sample is nebulized from the ionization probe
with the help of the nebulizing gas, and the components in the
liquid sample are ionized by a mechanism according to the
ionization method.
[0017] When the supply of the nebulizing gas is stopped at the time
of finishing the analysis, the supply of the liquid sample is also
stopped, and the liquid sample remains in the common sample supply
channel. Meanwhile, in the first aspect of the liquid sample
analysis method according to the present invention, at the time of
finishing the analysis, the connection of the channel switching
unit is switched such that the outlet port and the inlet port
connected to the individual sample supply channel connected to the
liquid sample container which is in the empty state. Since the
internal pressure of the liquid sample container which is in the
empty state is high, when the connection of the channel switching
unit is switched as described above, the gas (air) flows to the
common sample supply channel through the internal channel of the
channel switching unit, and pushes out the liquid remaining in the
channel. Accordingly, the common sample supply channel is filled
with the gas.
[0018] The viscosity of gas (air) is much smaller than the
viscosity of liquid. If the common sample supply channel is filled
with liquid having a viscosity higher than the viscosity of gas, it
takes time to discharge the liquid and replace the liquid with a
new liquid sample. In contrast, when the common sample supply
channel is filled with gas, when the liquid sample is supplied into
the common sample supply channel, the gas in the channel is quickly
discharged, and the liquid sample enters. That is, in a shorter
time, a new liquid sample fills the common sample supply channel
and is introduced into the ionization probe. Accordingly, a time
required from when the analysis starts to when a target liquid
sample starts to be nebulized from the ionization probe, that is, a
dead time can be shortened.
[0019] Meanwhile, in the second aspect of the liquid sample
analysis method according to the present invention, the connection
of the channel switching unit is switched as described above at the
time of finishing the analysis, and thus, the liquid in the common
sample supply channel is replaced with the liquid having a
viscosity lower than the liquid sample or the moving phase. In
general, a solvent of the liquid sample used in the liquid
chromatograph and the mass spectrometer is an organic solvent or a
mixture of an organic solvent and water. Therefore, the liquid
having a viscosity lower than the viscosity of the liquid sample or
the moving phase is typically water. Since the liquid in the common
sample supply channel is the low-viscosity liquid, the replacement
of the liquid can be completed in a shorter time when the liquid
sample for the next analysis is supplied to the common sample
supply channel compared to a case where the liquid sample or the
moving phase having a higher viscosity remains in the common sample
supply channel. Accordingly, a time required from when the analysis
starts to when a target liquid sample starts to be nebulized from
the ionization probe, that is, a dead time can be shortened.
[0020] In both the first and second aspects of the liquid sample
introduction method according to the present invention, the
switching of the connection of the channel in the channel switching
unit may be automatically performed, or may be manually operated by
an operator.
[0021] According to a first aspect of a liquid sample introduction
device according to the present invention made in order to solve
the aforementioned problems, there is provided a liquid sample
introduction device configured to send a liquid sample and a
nebulizing gas to an ionization probe of an ion source in an ion
analysis device and to nebulize the liquid sample from a tip of the
ionization probe with the help of the nebulizing gas.
[0022] The device includes
[0023] a) a liquid sample container which is a closed container in
which a liquid sample is stored,
[0024] b) a gas buffer container which is in a closed state,
[0025] c) a gas supply auxiliary path connected at one end to a
middle of a path for supplying the nebulizing gas to the ionization
probe and branched into sub-paths one of which is connected to the
liquid sample container above a liquid level and another to the gas
buffer container,
[0026] d) a channel switching unit configured to selectively
connect one outlet port and one of a plurality of inlet ports to
each other,
[0027] e) a common sample supply channel one end of which is
connected to the ionization probe and the other end is connected to
the outlet port of the channel switching unit,
[0028] f) an individual sample supply channel one end of which is
connected to the liquid sample container so as to be positioned
below the liquid level of the liquid sample and another end is
connected to one of the plurality of inlet ports of the channel
switching unit,
[0029] g) a replacement gas path one end of which is connected to
the gas buffer container and the other end is connected to one of
the plurality of inlet ports of the channel switching unit, and
[0030] h) a control unit configured to switch connection of the
channel switching unit such that the outlet port and the inlet port
connected to the replacement gas path are connected to each other
at a time of finishing analysis in the ion analysis device.
[0031] According to a second aspect of a liquid sample introduction
device according to the present invention made in order to solve
the aforementioned problems, there is provided a liquid sample
introduction device configured to send a liquid sample and a
nebulizing gas to an ionization probe of an ion source in an ion
analysis device and to nebulize the liquid sample from a tip of the
ionization probe with the help of the nebulizing gas.
[0032] The device includes
[0033] a) a liquid sample container which is a closed container in
which a liquid sample is stored,
[0034] b) a gas supply auxiliary path connected at one end to a
middle of a path of the nebulizing gas to the ion source and
branched into sub-paths which are connected to the liquid sample
container above a liquid level and one of a plurality of inlet
ports of a channel switching unit,
[0035] c) the channel switching unit configured to selectively
connect one outlet port and one of the plurality of inlet ports to
each other,
[0036] d) a common sample supply channel one end of which is
connected to the ionization probe and the other end is connected to
the outlet port of the channel switching unit,
[0037] e) an individual sample supply channel one end of which is
connected to the liquid sample container so as to be positioned
below a liquid level of the liquid sample and the other end is
connected to one of the plurality of inlet ports of the channel
switching unit, and
[0038] f) a control unit configured to switch connection of the
channel switching unit such that the outlet port and the inlet port
connected to the gas supply auxiliary path are connected to each
other at a time of finishing analysis in the ion analysis
device.
[0039] According to a third aspect of a liquid sample introduction
device according to the present invention made in order to solve
the aforementioned problems, there is provided a liquid sample
introduction device configured to send a liquid sample and a
nebulizing gas to an ionization probe of an ion source in an ion
analysis device and to nebulize the liquid sample from a tip of the
ionization probe with the help of the nebulizing gas.
[0040] The device includes
[0041] a) a liquid sample container which is a closed container in
which a liquid sample is stored,
[0042] b) a gas supply auxiliary path one end of which is connected
in a middle of a channel for supplying the nebulizing gas to the
ionization probe and the other end is connected to the liquid
sample container above a liquid level of the liquid sample,
[0043] c) a channel switching unit configured to selectively
connect one outlet port and one of a plurality of inlet ports to
each other,
[0044] d) a common sample supply channel one end of which is
connected to the ionization probe and the other end is connected to
the outlet port of the channel switching unit,
[0045] e) an individual sample supply channel one end of which is
connected to the liquid sample container so as to be positioned
below the liquid level of the liquid sample and the other end is
connected to one of the plurality of inlet ports of the channel
switching unit,
[0046] f) a replacement gas introduction path one end of which is
connected to one of the plurality of inlet ports and the other end
is open to an atmosphere, and
[0047] g) a control unit configured to switch connection of the
channel switching unit such that the outlet port and the inlet port
connected to the replacement gas introduction path are connected to
each other in a state in which the nebulizing gas is supplied to
the ionization probe at a time of finishing analysis in the ion
analysis device.
[0048] The first aspect of the liquid sample introduction device
according to the present invention automatically switches the
connection of the channel switching unit, that is, according to a
predetermined sequence or program by the control unit by using the
gas buffer container as the liquid sample container which is in the
empty state in the liquid sample introduction method according to
the first aspect at the time of finishing the analysis.
Accordingly, when the next analysis for the liquid sample is
performed, the common sample supply channel is filled with the gas
(air). Thus, when the liquid sample to be analyzed is supplied to
the common sample supply channel, a new liquid sample fills the
common sample supply channel in a shorter time, and is introduced
into the ionization probe. As a result, the time required from when
the analysis starts to when the target liquid sample starts to be
nebulized from the ionization probe, that is, a dead time can be
shortened.
[0049] In the second aspect of the liquid sample introduction
device according to the present invention, when the control unit
switches the connection of the channel switching unit at the time
of finishing the analysis, the gas is directly supplied to the
common sample supply channel through the gas supply auxiliary path,
and the liquid in the common sample supply channel is replaced with
the gas. Accordingly, as in the liquid sample introduction device
of the first aspect, when the next liquid sample to be analyzed is
supplied to the common sample supply channel, a new liquid sample
fills the common sample supply channel in a shorter time, and is
introduced into the ionization probe. As a result, the time
required from when the analysis starts to when the target liquid
sample starts to be nebulized from the ionization probe, that is, a
dead time can be shortened.
[0050] In the third aspect of the liquid sample introduction device
according to the present invention, when the control unit switches
the connection of the flow channel switching unit at the time of
finishing the analysis, the other end of the common sample supply
channel one end of which is connected to the ionization probe is
open to the atmosphere through the internal channel of the channel
switching unit and the replacement gas introduction path. Since the
nebulizing gas is supplied to the ionization probe, the end of the
common sample supply channel on the ionization probe side becomes
negative pressure due to the flow. Thus, due to the pressure
difference between the two ends of the common sample supply
channel, the air flows from the atmosphere at the open end into the
common sample supply channel, and the liquid in the common sample
supply channel is replaced with the air. Accordingly, as in the
liquid sample introduction device of the first and second aspects,
when the next liquid sample to be analyzed is supplied to the
common sample supply channel, a new liquid sample fills the common
sample supply channel in a shorter time, and is introduced into the
ionization probe. As a result, the time required from when the
analysis starts to when the target liquid sample starts to be
nebulized from the ionization probe, that is, a dead time can be
shortened.
Advantageous Effects of Invention
[0051] According to the liquid sample introduction method and the
liquid sample introduction device according to the present
invention, it is possible to reduce the time required from when the
analysis starts to when the target liquid sample starts to be
nebulized from the ionization probe, that is, the analysis dead
time. Accordingly, it is possible to improve analysis efficiency.
Whenever the analysis is performed, the liquid remaining in the
common sample supply channel is replaced with the gas (air) or the
liquid (for example, water) having a lower viscosity than the
remaining liquid, and thus, there is also an advantage that it is
possible to reduce undesirable contamination due to mixing of
components.
BRIEF DESCRIPTION OF DRAWINGS
[0052] FIG. 1 is a configuration diagram of a main part of an
example of a mass spectrometer using a liquid sample introduction
device according to the present invention.
[0053] FIG. 2 is a channel configuration diagram illustrating an
embodiment (first embodiment) of a liquid sample introduction unit
in the mass spectrometer illustrated in FIG. 1.
[0054] FIG. 3 is a diagram illustrating a state when a residual
solution is discharged in the liquid sample introduction unit
illustrated in FIG. 2.
[0055] FIG. 4 is a channel configuration diagram illustrating
another embodiment (second embodiment) of the liquid sample
introduction unit.
[0056] FIG. 5 is a channel configuration diagram illustrating
another embodiment (third embodiment) of the liquid sample
introduction unit.
[0057] FIG. 6 is a channel configuration diagram illustrating
another embodiment (fourth embodiment) of the liquid sample
introduction unit.
[0058] FIGS. 7A-7B are diagrams illustrating a chromatogram
obtained by actual measurement for describing a difference in
effect between the liquid sample introduction device according to
the present invention and a device of the related art.
DESCRIPTION OF EMBODIMENTS
[0059] Hereinafter, embodiments of a liquid sample introduction
device according to the present invention will be described with
reference to the accompanying drawings.
[0060] For example, the liquid sample introduction device according
to the present invention is used for introducing a standard sample
for mass calibration into an ion source simultaneously with, or
immediately before or after mass analysis for various components
included in a liquid sample eluted from a column of a liquid
chromatograph (LC) (not illustrated) in a quadrupole-time-of-flight
mass spectrometer (so-called "Q-TOFMS") illustrated in FIG. 1. Of
course, the present invention is not limited to the Q-TOFMS, and it
is apparent that a liquid sample introduction device according to
the following various embodiments and a liquid sample introduction
device having the same configuration as that in these embodiments
can also be used in a mass spectrometer having another
configuration and an ion mobility analysis device as long as an
atmospheric ion source is provided.
[Entire Configuration of Mass Spectrometer]
[0061] In FIG. 1, a measurement unit 1 includes a mass spectrometry
unit 2, an LC unit 3, and a liquid sample introduction unit 4. The
mass spectrometry unit 2 includes an ionization room 201 which is
under a substantially atmospheric pressure atmosphere and a main
analysis room 205 which is evacuated by a vacuum pump (not
illustrated) and is maintained under a high vacuum atmosphere
within a chamber 200. A first intermediate vacuum room 202, a
second intermediate vacuum room 203, and a pre-stage analysis room
204 whose a degree of vacuum is step-wisely increased are arranged
between the ionization room and the main analysis room. The
ionization room 201 and the first intermediate vacuum room 202 are
communicatively connected to each other via a small-diameter
desolvation tube 208, and the first intermediate vacuum room 202
and the second intermediate vacuum room 203 are communicatively
connected to each other via a small-diameter orifice formed at a
top of a conical skimmer 210.
[0062] A first ESI probe 206 connected to the LC unit 3 and a
second ESI probe 207 connected to the liquid sample introduction
unit 4 are arranged in the ionization room 201. In the first
intermediate vacuum room 202, an ion guide 209 including a
plurality of electrode plates are arranged so as to surround an ion
optical axis C. In the second intermediate vacuum room 203, an ion
guide 211 including a plurality of rod electrodes arranged so as to
surround the ion optical axis C is disposed. A quadrupole mass
filter 212 and a collision cell 213 in which ion guides 214 are
arranged are arranged within the pre-stage analysis room 204, and
an ion transport optical system 215 including a plurality of
ring-shaped electrodes is disposed over the pre-stage analysis room
204 and the main analysis room 205. An orthogonal acceleration unit
216, a flight space 217 including a reflector 218, and an ion
detector 219 are arranged within the main analysis room 205.
[0063] A control unit 5 includes a storage unit 51, an analysis
condition setting unit 52, and an analysis control unit 53, and
controls operations of the units included in the measurement unit
1. An input unit 6 and a display unit 7 are connected to the
control unit 5, as user interfaces. Although not illustrated
herein, a data processing unit that processes detection data
obtained by the ion detector 219 is provided. Usually, the control
unit 5 and the data processing unit (not illustrated) are personal
computers. A required software installed on the computer operates
on the computer, and thus, functions of the control unit 5 and the
data processing unit are exhibited.
[Description of Analysis Operation of Mass Spectrometer]
[0064] An example of an analysis operation in this mass
spectrometer will be schematically described.
[0065] A plurality of method files storing analysis conditions is
stored in the storage unit 51 in advance. The analysis condition
setting unit 52 reads out an appropriate method file from the
storage unit 51 according to an instruction through the input unit
6, and the analysis control unit 53 controls the units of the
measurement unit 1 according to the readout method file. Under this
control, a liquid sample containing various components temporally
separated by the column of the LC unit 3 is continuously supplied
to the first ESI probe 206. The first ESI probe 206 nebulizes, as
fine charged droplets, the liquid sample into the ionization room
201. As will be described below, the standard sample for mass
calibration sent from the liquid sample introduction unit 4 is
similarly nebulized, as fine charged droplets, from the second ESI
probe 207 into the ionization room 201.
[0066] These charged droplets collide with the atmosphere in the
ionization room 201, and thus, finer charged droplets are obtained.
Components in the droplets are ionized when a solvent is vaporized.
The generated ions are drawn into the desolvation tube 208 by a
differential pressure between the ionization room 201 and the first
intermediate vacuum room 202, pass through the two intermediate
vacuum rooms 202 and 203 while being converged by the ion guides
209 and 211, and are introduced into the quadrupole mass filter 212
in the pre-stage analysis room 204.
[0067] A voltage obtained by combining a high-frequency voltage and
a DC voltage is applied to each rod electrode constituting the
quadrupole mass filter 212. Ions (usually, called precursor ions)
having a specific mass-to-charge ratio m/z corresponding to this
voltage selectively pass through the mass filter 212, and are
introduced into the collision cell 213. A collision gas such as Ar
is introduced into the collision cell 213. The precursor ions come
into contact with the collision gas, and dissociate to generate
various product ions. The generated product ions are introduced
into the orthogonal acceleration unit 216 within the main analysis
room 205 while being converged by the ion transport optical system
215.
[0068] In FIG. 1, the ions (product ions) introduced into the
orthogonal acceleration unit 216 in an X-axis direction are
accelerated in a pulse shape in a Y-axis direction at a
predetermined timing. The accelerated ions enter the flight space
217 and fly. The ions are turned back by a reflected electric field
formed by the reflector 218, and finally reach the ion detector
219. Among the ions which are almost simultaneously ejected from
the orthogonal acceleration unit 216, ions having a smaller
mass-to-charge ratio fly faster, and reach the ion detector 219
with a time difference corresponding to the mass-to-charge ratio.
The ion detector 219 outputs, as a detection signal, a current
corresponding to the amount of reached ions. It is possible to
create a time-of-flight spectrum by plotting a time (that is,
flight time) when the ions arrive by using a point of time when the
ions are ejected from the orthogonal acceleration unit 216 as a
starting point, and it is possible to obtain a mass spectrum by
converting the flight time into the mass-to-charge ratio.
[Configuration and Operation of Liquid Sample Introduction
Unit]
[0069] Next, the detailed configuration and operation of the liquid
sample introduction unit 4 according to the first embodiment which
supplies a liquid to the second ESI probe 207 for generating ions
derived from the standard sample mass calibration will be mainly
described. FIG. 2 is a configuration diagram of the liquid sample
introduction unit 4 in the mass spectrometer, and FIG. 3 is a
diagram illustrating a state of the liquid sample introduction unit
4 when the residual solution is discharged.
[0070] One end of a nebulizing gas path 401 connected to a nitrogen
gas cylinder (atomization gas source) 400 is connected to a
nebulizing gas conduit (not illustrated) of the second ESI probe
207 disposed in the ionization room 201. A valve 402 and a branch
part 403 are provided at the nebulizing gas path 401 in order from
a side closer to the nitrogen gas cylinder 400, and one end of a
liquid supply gas main channel 404 is connected to the branch part
403. A regulator 405 and a branch part 406 are provided at the
liquid supply gas main channel 404, and a relief channel 408
connected to a relief valve 407 is connected to the branch part
406. The other end of the liquid supply gas main channel 404 is
branched into six liquid supply gas branch channels 410a to 410f
Ends of the five liquid supply gas branch channels 410a to 410e are
connected to spaces above liquid levels of solutions in containers
(liquid sample containers) 420a to 420e in which standard sample
solutions are stored. An end of one liquid supply gas branch
channel 410f is connected to a gas buffer container 421 which is a
substantially closed empty bottle. An atmosphere release channel
412 connected to an atmosphere release valve 411 is provided in
parallel with the liquid supply gas branch channels 410a to 410f
All of the liquid sample containers 420a to 420e are substantially
closed.
[0071] In the second ESI probe 207, one end of a common sample
supply channel 60 is connected to a capillary (not illustrated)
through which a liquid sample flows, and the other end is connected
to a main port (outlet port) g of a 6-position 7-port valve 415.
One ends of individual sample supply channels 414a to 414e are
connected to sub-ports (inlet ports) a to e of the 6-position
7-port valve 415, and the other ends of these channels 414a to 414e
are connected below the liquid levels of the solutions (that is, in
the solutions) within the liquid sample containers 420a to 420e.
One end of a replacement gas path 413 is connected to the sub-port
f of the 6-position 7-port valve 415, and the other end thereof is
connected within the gas buffer container 421. The standard samples
stored in the five liquid sample containers 420a to 420e are
solutions in which components for generating a plurality of ions
having different known mass-to-charge ratios are dissolved. The
replacement gas path 413 and the individual sample supply channels
414a to 414e are substantially the same, and when gas replacement
at the time of finishing the analysis to be described below is not
performed, it is also possible to provide a liquid sample container
containing another standard sample instead of the gas buffer
container 421.
[0072] The operation of the liquid sample introduction unit 4 of
this embodiment during the above-described mass spectrometry will
be described.
[0073] When mass analysis for the ions derived from the components
in the liquid sample introduced from the LC unit 3 to the first ESI
probe 206 is performed as described above, the analysis control
unit 53 controls the connection of the valve 415 such that any one
of the sub-ports (inlet ports) a to e of the 6-position 7-port
valve 415 is communicatively connected to the main port g within a
predetermined measurement time range according to the analysis
method which is created in advance and is stored in the storage
unit 51.
[0074] During the analysis, a nitrogen gas is supplied from the
nitrogen gas cylinder 400 to the nebulizing gas path 401 at a
predetermined flow rate and a predetermined pressure. A part of the
nitrogen gas flows into the liquid supply gas main channel 404
through the branch part 403, is reduced to a predetermined pressure
by the regulator 405, and is sent to the liquid sample containers
420a to 420e and the gas buffer container 421 through the liquid
supply gas branch channels 410a to 410f. Accordingly, the insides
of the liquid sample containers 420a to 420e and the gas buffer
container 421 are simultaneously pressurized, and the standard
samples stored in the liquid sample containers 420a to 420e are
sent to the individual sample supply channels 414a to 414e,
respectively. When an abnormality occurs in the regulator 405 and a
gas pressure in the liquid supply gas main channel 404 is equal to
or greater than a predetermined value, the relief valve 407 is
opened and the nitrogen gas is released to the outside.
[0075] A flow rate and a pressure of the nebulizing gas supplied
from the nitrogen gas cylinder 400 may be determined according to
the specifications of the ionization probe (second ESI probe 207 in
this embodiment) to be used, and a pressure of the liquid supply
gas flowing to the liquid supply gas main channel 404 may be
determined according to a target delivery amount of the standard
sample. However, it is natural that both the pressures of the
nebulizing gas and the liquid supply gas are higher than the
pressure within the ionization room 201.
[0076] The standard samples sent to the individual sample supply
channels 414a to 414e reach the five sub-ports a to e of the
6-position 7-port valve 415. As described above, during the
analysis, only one of the sub-ports a to e of the 6-position 7-port
valve 415 is connected to the main port g. This connection is
switched as an analysis time elapses. However, the standard sample
(the standard sample stored in any one of the liquid sample
containers 420a to 420e) sent to any one of the sub-ports a to e
communicatively connected to the main port g flows to the sample
supply main channel 416 through the main port g, and is introduced
into the second ESI probe 207. Therefore, as the connection is
switched in the 6-position 7-port valve 415, the kind of the
standard sample introduced into the second ESI probe 207 via the
sample supply main channel 416 also changes.
[0077] When a series of analyses are finished, the analysis control
unit 53 controls the valve 415 such that the sub-port f and the
main port g are connected in the 6-position 7-port valve 415 (see
FIG. 3). The liquid such as the standard sample is not stored in
the gas buffer container 421 communicatively connected to the
sub-port f via the replacement gas path 413, and the pressurized
nitrogen gas is supplied to the sub-port f Therefore, when the
sub-port f and the main port g are communicatively connected to
each other as described above, the nitrogen gas flows into the
sample supply main channel 416 through the main port g, pushes out
the standard sample remaining in the sample supply main channel
416, and is discharged from the second ESI probe 207. Accordingly,
the standard sample in the sample supply main channel 416 is
replaced with nitrogen gas. After a predetermined time elapses, the
pressurization in the liquid sample containers 420a to 420e and the
gas buffer container 421 is released by closing the valve 402 of
the nebulizing gas path 401 and then opening the atmosphere release
valve 411.
[0078] Not only at the time of finishing the analysis but also when
the analysis is interrupted in the middle by, for example, an
instruction of a user, a process of flowing the nitrogen gas into
the sample supply main channel 416 may be similarly performed.
[0079] As described above, in the liquid sample introduction unit 4
of the present embodiment, the liquid sample remaining in the
sample supply main channel 416 and an internal channel that
connects the main port and the sub-ports of the 6-position 7-port
valve 415 to each other is replaced with the nitrogen gas at the
time of finishing the analysis. Thus, at the time of the next
analysis or at the time of resuming the interrupted analysis, when
the standard sample is sent from any one of the sub-ports a to e of
the 6-position 7-port valve 415 to the sample supply main channel
416 via the main port g, the standard sample quickly reaches the
second ESI probe 207, and the charged droplets are nebulized from
the second ESI probe 207.
[0080] FIGS. 7A-7B are chromatograms obtained by measuring changes
in signal strength over time for the components in the standard
sample in a case (a) where the liquid starts to be sent by
switching the 6-position 7-port valve 415 from a state in which
there is an air in the sample supply main channel 416 and a case
(b) where the liquid starts to be sent by switching the 6-position
7-port channel 415 from a state in which the sample supply main
channel 416 is filled with a solvent. In FIGS. 7A-7B, times to and
tb from when the liquid starts to be sent to when the signal
strength rises are delay times at the time of starting to send the
liquid, and these delay times are desirably short. As can be seen
from FIGS. 7A-7B, the rise in (a) is about 10 seconds faster than
the rise in (b). This is because, since an air has a remarkably
lower viscosity than a liquid (here, a solvent), a channel
resistance within the sample supply main channel 416 after the
liquid starts to be sent is small, and a liquid supply speed is
high. From this measurement result, it is possible to confirm that
the liquid sample can be quickly nebulized from the second ESI
probe 207 at the time of the next analysis or at the time of
resuming the interrupted analysis in the liquid sample introduction
unit 4 of the aforementioned embodiment.
[Configuration and Operation of Liquid Sample Introduction Unit
According to Another Embodiment]
[0081] FIGS. 4 to 6 are channel configuration diagrams of the
liquid sample introduction unit according to second to fourth
embodiments, respectively.
[0082] In the liquid sample introduction unit illustrated in FIG.
4, the replacement gas path 413 and the liquid supply gas branch
channel 410f connected to the sub-port f of the 6-position 7-port
valve 415 are directly connected by using a joint 430 instead of
providing the gas buffer container in the first embodiment.
Accordingly, at the time of finishing the series of analyses, the
branched nitrogen gas is sent into the sample supply main channel
416 through the replacement gas path 413 and the internal channel
of the 6-position 7-port valve 415, and thus, the standard sample
and the solvent remaining in the sample supply main channel 416 can
be quickly removed.
[0083] In the liquid sample introduction unit illustrated in FIG.
5, the other end of the replacement gas path 441 one end of which
is connected to the sub-port f of the 6-position 7-port valve 415
is connected to a drain 442. The end of the replacement gas path
441 connected to the drain 442 is substantially open to the
atmosphere, and a gas pressure at this end is substantially an
atmospheric pressure. At the time of finishing the series of
analyses, when the main port g and the sub-port f are connected in
the 6-position 7-port valve 415, the replacement gas path 441 and
the sample supply main channel 416 are communicatively connected to
each other through the internal channel of the valve 415. At this
time, the nitrogen gas is continuously supplied from the nitrogen
gas cylinder 400 to the nebulizing gas path 401, and the gas is
ejected, as the nebulizing gas, from the second ESI probe 207 into
the ionization room 201.
[0084] Due to this gas flow, the end of the sample supply main
channel 416 connected to the second ESI probe 207 has a negative
pressure (a pressure lower than the atmospheric pressure).
Therefore, a pressure difference occurs between both the ends of
the sample supply main channel 416 and the replacement gas path 441
via the internal channel of the valve 415, and thus, the air sucked
into the replacement gas path 441 from the end on the drain 442
side flows to the sample supply main channel 416. Thus, the
standard sample and the solvent remaining in the sample supply main
channel 416 are pushed out and are removed. The supply of the
nitrogen gas from the nitrogen gas cylinder 400 to the nebulizing
gas path 401 may be executed for a predetermined time.
[0085] In the aforementioned embodiments, the liquid in the sample
supply main channel 416 is removed by the nitrogen gas or the air.
However, in the liquid sample introduction unit illustrated in FIG.
6, a low-viscosity liquid sample container 420f in which a
low-viscosity liquid is stored is disposed instead of the gas
buffer container 421 in the liquid sample introduction unit 4
illustrated in FIG. 2. The low-viscosity liquid mentioned herein is
a liquid having viscosity lower than the viscosity of the liquid
likely to remain in the sample supply main channel 416, such as the
standard sample, the liquid eluted from the LC unit 3, and the
moving phase used in the LC unit 3. In general, the solvent of the
standard sample and the moving phase used in the LC unit 3 are
organic solvents or a mixture of water and organic solvents. Since
the organic solvent has viscosity higher than water, water has
viscosity lower than the organic solvent alone or a mixture of
water and an organic solvent. Therefore, water may be generally
used as the low viscosity liquid.
[0086] At the time of finishing the series of analyses, when the
main port g and the sub-port f are connected in the 6-position
7-port valve 415, the low-viscosity liquid flows to the sample
supply main channel 416 through the internal channel of the valve
415, and a remaining higher-viscosity liquid is pushed out and is
removed. Therefore, at the time of the next analysis or at the time
of resuming the temporarily interrupted analysis, the sample supply
main channel 416 is filled with the low-viscosity liquid, and is
more quickly discharged than a general standard sample which is not
as much as the air or the nitrogen gas. Accordingly, it is possible
to quickly introduce the liquid sample to the second ESI probe 207
at the time of the next analysis or at the time of resuming the
interrupted analysis, and it is possible to achieve an effect close
to the effect of the above embodiments.
[0087] Although it has been described in the mass spectrometer of
the aforementioned embodiment that a plurality of kinds of standard
samples are selectively introduced to the second ESI probe 207, the
liquid sample sent to the second ESI probe 207 is not limited to
only the standard sample for mass calibration. For example, a
liquid sample to be analyzed can be introduced. A cleaning solution
for cleaning the sample supply main channel 416 and the individual
sample supply channels 414a to 414f can be sent. The eluted liquid
or the standard sample is selectively ionized by switching the
connection of the valve 415 by supplying the liquid eluted from the
LC unit 3 to one of the sub-ports of the 6-position 7-port valve
415 in the liquid sample introduction unit 4. In this case, the
first ESI probe 206 is not required unless it is necessary to
simultaneously ionize the eluted liquid sent from the LC unit 3 and
the standard sample.
[0088] Although it has been described in the mass spectrometer of
the aforementioned embodiments that the ESI is used as the
ionization method, the present invention can be applied to ACPI and
APPI as long as an ionization probe appropriate for the ionization
method is used.
[0089] The aforementioned embodiments are merely examples of the
present invention, and it is apparent that points other than the
above description are included in the scope of the present
application even though appropriate changes, corrections, and
additions are made within the scope of the gist of the present
invention.
REFERENCE SIGNS LIST
[0090] 1 . . . Measurement Unit [0091] 2 . . . Mass Spectrometry
Unit [0092] 200 . . . Chamber [0093] 201 . . . Ionization Room
[0094] 202 . . . First Intermediate Vacuum Room [0095] 203 . . .
Second Intermediate Vacuum Room [0096] 204 . . . Pre-Stage Analysis
Room [0097] 205 . . . Main Analysis Room [0098] 206 . . . First ESI
Probe [0099] 207 . . . Second ESI Probe [0100] 208 . . .
Desolvation Tube [0101] 209, 211, 214 . . . Ion Guide [0102] 210 .
. . Skimmer [0103] 212 . . . Quadrupole Mass Filter [0104] 213 . .
. Collision Cell [0105] 215 . . . Ion Transport Optical System
[0106] 216 . . . Orthogonal Acceleration Unit [0107] 217 . . .
Flight Space [0108] 218 . . . Reflector [0109] 219 . . . Ion
Detector [0110] 3 . . . LC Unit [0111] 4 . . . Liquid Sample
Introduction Unit [0112] 400 . . . Nitrogen Gas Cylinder [0113] 401
. . . Nebulizing Gas Path [0114] 402 . . . Valve [0115] 403, 406 .
. . Branch Part [0116] 404 . . . Liquid Supply Gas Main Channel
[0117] 405 . . . Regulator [0118] 407 . . . Relief Valve [0119] 408
. . . Relief Channel [0120] 410a to 410f . . . Liquid Supply Gas
Branch Channel [0121] 411 . . . Atmosphere Release Valve [0122] 412
. . . Atmosphere Release Channel [0123] 413, 441 . . . Replacement
Gas Path [0124] 414a to 414e . . . Individual Sample Supply Channel
[0125] 415 . . . 6-Position 7-Port Valve [0126] A to F . . .
Sub-Port [0127] G . . . Main Port [0128] 416 . . . Sample Supply
Main Channel [0129] 420a to 420e . . . Liquid Sample Container
[0130] 420f . . . Low-Viscosity Liquid Sample Container [0131] 421
. . . Gas Buffer Container [0132] 430 . . . Joint [0133] 442 . . .
Drain [0134] 5 . . . Control Unit [0135] 51 . . . Storage Unit
[0136] 52 . . . Analysis Condition Setting Unit [0137] 53 . . .
Analysis Control Unit [0138] 6 . . . Input Unit [0139] 60 . . .
Common Sample Supply Channel [0140] 7 . . . Display Unit [0141] C .
. . Ion Optical Axis
* * * * *