CN1933092A - Apparatus and method for ion production enhancement - Google Patents
Apparatus and method for ion production enhancement Download PDFInfo
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- CN1933092A CN1933092A CN 200610001970 CN200610001970A CN1933092A CN 1933092 A CN1933092 A CN 1933092A CN 200610001970 CN200610001970 CN 200610001970 CN 200610001970 A CN200610001970 A CN 200610001970A CN 1933092 A CN1933092 A CN 1933092A
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Abstract
The invention described herein provides a matrix-based ion source including a gas heating device for providing heated gas at a defined temperature to the ionization region of the ion source. The ion source may also include a temperature sensor. The heating device and temperature sensor may be operably connected to work as a closed feedback loop to provide gas at a constant, pre-determined, temperature to the ionization region. Also disclosed is a mass spectrometer system having the matrix-based ion source. A method of producing ions employing gas that is heated to a pre-determined temperature is also provided.
Description
Technical field
The present invention relates to be used for equipment and the method that mass spectrometer uses.
Background technology
The biochemical target of most of complexity need be used the interference with compensation target and matrix of additional multidimensional analysis tool and method.Correct analysis is very important with separating for obtaining reliable qualitative and quantitative information about target.In this respect, mass spectrometer has been widely used as the detector that is used for various separation methods.But, provide relic pattern too complicated for analyzing fast and effectively up to the method for recent most of spectrum.The introducing of atmospheric pressure ionization (API) and substance assistant laser desorpted ionized (MALDI) has improved the result substantially.For example, these methods provide the relic pattern and the high sensitivity that greatly reduce to the analysis of various volatility and non-volatile compounds.This technology is also achieved success on chemical compound lot, and these compounds comprise peptide, protein, carbohydrate, compound sugar, natural prodcuts, cationic drug, organoarsenium compound, ring glucan, taxol, paclitaxel derivatives, metalloporphyrin, porphyrin, kerabitumen, cyclosiloxane, aromatic polyester dendritic, oligodeoxynucleotide, aromatic heterocycle hydrocarbon, polymer and lipid.
According to the ionization method of MALDI, analyte and matrix are painted on metal probe or the target substrate.Along with solvent evaporation, analyte and matrix from solution co-precipitation to form the solid solution of analyte in matrix in target substrate.Use this co-precipitation thing of short laser pulse radiation then, cause that with electron excitation by substrate molecule or molecular vibration lot of energy assembles in the co-precipitation thing.Matrix is brought analyte into gas phase by the desorb dissipation energy.In desorption process, shift to form ion by the electric charge between photoexcitation matrix and the analyte.
Traditionally, utilize Time-of flight analyzer to finish the ionization technique of MALDI, but also can use such as ion trap, ion involution resonant mass spectrometer and other mass analyzer of four utmost point flight time.But these analyzers must be operated under condition of high vacuum degree, and this reduces resolution, capture efficiency with the output of other conditions possibility limited targets, and make to the detection of target difficult and expensive more.
In order to overcome the above-mentioned shortcoming among the MALDI, developed the technology of a kind of AP-MALDI of being referred to as.This technology is used the ionization technique of MALDI, but is under atmospheric pressure.MALDI and AP-MALDI ionization technique have much in common.For example, two kinds of technology are all based on the pulse laser beam desorb/ionization process of the solid target material that causes producing the gas-phase analyte molecules ion.But the pressure reduction that the AP-MALDI ionization technique does not rely between ionization chamber and the mass spectrometer guides ion to flow into the mass spectrometric hole that enters.
AP-MALDI can provide to the detection of 106Da (dalton) molecular mass from the target size in Ah's mole (attamole) scope.In addition, because handle and analyze a lot of histone matter, peptide or other compound, so that level of sensitivity becomes is more and more important by these instruments.In the effort that improves sensitivity, the MALDI mass spectrometer has been carried out the change of various structures and instrument.But, the additional cost that improves instrument of part and assembly.In addition, attempted improving sensitivity by changing the analyte matrix that mixes with target.But these additives and variation provide limited improvement in sensitivity, and have increased cost.
Therefore, in order to increase and effectively ion enhancing (enhancement), need to improve the sensitivity and the effect of AP-MALDI mass spectrometer.
Summary of the invention
The present invention relates to be used for equipment and the method that mass spectrometer uses.The invention provides and be used to provide heated air stream to strengthen the ion enhancement system of the analyte ions that produces and detect by detector by ion source based on matrix.The ion detector of the analyte ions that mass spectrometer of the present invention provides the ion source based on matrix that is used to produce analyte ions, strengthen in the detection based on the ion source downstream of matrix, place the ion enhancement system that is used to strengthen analyte ions between ion source and the ion detector and contiguous ion enhancement system or with the ion enhancement system one be used for the analyte ions that strengthens from the ion enhancement system transmission ion transfer system to detector.
In addition, the present invention also provides the ion source based on matrix, and it comprises and is used to provide the gas-heating apparatus of the heated air of assigned temperature to the ion source ionized space.This ion source can also comprise temperature sensor.Heater and temperature sensor can be coupling in the closed feedback loop to provide the gas of being scheduled to constant temperature to ionized space.The invention also discloses a kind of ionogenic spectrometer system that comprises based on matrix.The present invention also provides the method that produces ion in comprising the ion source that is heated to predetermined temperature gas.
Method of the present invention comprises from producing analyte ions based on the ion source of matrix, strengthening analyte ions and detect the analyte ions that strengthens with detector with ion enhancement system.
Description of drawings
To be described in detail with reference to the attached drawings the present invention:
Fig. 1 illustrates mass spectrometric overall construction drawing.
Fig. 2 illustrates the first embodiment of the present invention.
Fig. 3 illustrates the second embodiment of the present invention.
Fig. 4 illustrates the stereogram of first embodiment of the invention.
Fig. 5 illustrates the decomposition view of first embodiment of the invention.
Fig. 6 illustrates the cutaway view of first embodiment of the invention.
Fig. 7 illustrates the cutaway view of device.
Fig. 8 illustrates the cutaway view of first embodiment of the invention, and illustrates method of the present invention and how to operate.
Fig. 9 is illustrated in the result of femto mole peptide mixture under the situation of not supplying heat according to the present invention.
Figure 10 is illustrated in the result of femto mole peptide mixture under the situation that has increased the heat that is supplied to analyte ions (being produced by the contiguous ion source of gathering in the ionized space capillaceous) according to the present invention.
Figure 11 illustrates embodiments of the invention.
Figure 12 A-12D schematically illustrates the ionogenic various embodiment of air inclusion heater.
Figure 13 schematically illustrates the ion source that comprises the closed feedback loop that is used to control the heated air temperature.
Embodiment
Before describing the present invention in detail, must be noted that: as employed in specification and claims, singulative " " and " being somebody's turn to do " comprise plural object, unless context is clearly indicated.Therefore, for example, for " conduit ", comprise more than one " conduit ".For " matrix ", comprise mixture more than a kind of " matrix " or " multiple matrix ".Term below will using according to following definition of stating is being described and claimed when of the present invention.
Term " vicinity " depends on closely, near or link to each other.Some contiguous things can also contacts with other parts, around other parts, and other parts separate or comprise the part of other parts.For example, the capillary of adjacent pipes can the compartment of terrain near conduit, can contact with conduit, can surround conduit or surrounded by conduit, can holding conduit or held by conduit, can link to each other with conduit or near conduit.
Term " conduit " or " conduit of heating " refer to sleeve pipe, transmitting device, distributor, nozzle, flexible pipe, pipeline, plate, pipette, port, connector, pipe, coupler, container, housing, structure or the equipment in the zone (for example ionized space) of any gas that can be used to guide heating or air-flow appointment in the space.Especially, " conduit " can be designed to surround capillary or the capillaceous part of reception from ionogenic analyte ions.But should explain term widely, thus also comprise can be towards ionized space location and can provide heated air stream towards or enter any device or the equipment of the ion in gas phase and/or the ionized space.For example, term can also comprise and has the recessed or raised plate of steering current towards the slit of ionized space.
Term " enhancing " refers to any external physical excitation, and such as heat, energy, light or variations in temperature etc., it makes easier sign of material or identification.For example, the gas of heating can be used for " enhancing " ion.Ion increases their kinetic energy, potential energy or motion, and is separated bunch or evaporation.Easier of in this state mass analyzer detection ion.It should be noted that when ion is " enhanced ", because by gathering taken a sample more substantial analyte ions and be transported to mass analyzer or detector of capillary, so detected amount of ions increases.
Term " ion source " or " source " refer to produce any source of analyte ions.Ion source can comprise other source except that the AP-MALDI ion source, the ion source such as electron bombardment (below be called EI), chemi-ionization (CI) and other ion source known in the art.Term " ion source " refers to laser, target substrate and the target that will be ionized on target substrate.Target substrate among the AP-MALDI can comprise the grid that is used for the target deposition.Interval between the target on such grid is about 1-10mm.About 0.5 to 2 microlitre is deposited on each position of grid.
Term " ionized space " refers to ion source and gathers intercapillary zone.Especially, this term refers to not be directed to the analyte ions of gathering in the capillary in that zone by being present in of ion source generation.This term should be interpreted as being included in the object support part widely, on the object support part, near the object support part or the ion around the object support part, and the object support part with gather on the capillary or the ion in the gas phase of heating on every side.Ionized space among the AP-MALDI is approximately 1-5mm (or capacity of 1-5mm) from ion source (target substrate) to gathering distance capillaceous.Distance from target substrate to conduit flows to target and target substrate is very important to allowing enough gas from conduit.For example, if arc discharge too near target or target substrate, takes place in conduit so when applying voltage.If distance is excessive, then can not gather ion effectively.
Term " ion enhancement system " refers to be used to strengthen any device, equipment or the parts of analyte ions.This term does not comprise that direct heated capillary is to provide conduction heat to ion flow.For example, " ion enhancement system " comprises conduit and source of the gas.Ion enhancement system can also comprise other device well known in the art, and for example laser, infrared facility, ultraviolet source maybe can apply heat or the energy device to other similar type that is released to the ion in the ionized space or in the gas phase.
Term " ion transfer system " refers to should be in the transmission of analyte ions from a position to another position, motion or any device, equipment, machine, parts, the capillary that help out distributing.This term comprises ion optics, knockout, capillary, transport element and conduit widely.
Term " based on matrix " or " based on the ion source of matrix " refer to not need to use dry gas, the ion source or the mass spectrometer of cover gas (curtain gas) or desolventizing step.For example, some systems need use such gas to remove solvent or the cosolvent mixed with analyte.These systems use volatile liquid to help to form less dripping usually.Above term application is to sample dissolution to wherein non-volatile liquid and solid material.This term comprises the use of cosolvent.Cosolvent can be a volatility or nonvolatile, but final host material can be evaporated in a vacuum.Such material can comprise and be not limited to m-nitrobenzyl alcohol (NBA), glycerine, triethanolamine (TEA), 2,4-diamyl phenol, 1,5-dithiothreitol (DTT)/antierythrite (magic bullet (magicbullet)), 2-nitrobenzene octyl ether (NPOE), thioglycerin, niacin, cinnamic acid, 2,5-dihydroxy-benzoic acid (DHB), 3,5-dimethyl-4-hydroxycinnamic acid (sinapic acid (sinpinicacid)), alpha-cyano-4-hydroxycinnamic acid (CCA), 3-methoxyl group-4-hydroxycinnamic acid (forulic acid), single thioglycerol, polyethylene glycol, 2-(4-hydroxyphenyl azo) benzoic acid (HABA), 3,4-dihydroxycinnamic acid (caffeic acid), 2-amino-4-methyl-5-nitro pyridine and their cosolvent and derivative.Especially, this term refers to MALDI, AP-MALDI, fast atom/ion bombardment (FAB) and other do not need volatile solvent and can be higher than, be equal to or less than the similar system of operating under the atmospheric pressure.
Term " air-flow ", " gas " or " gas that is directed " refer in mass spectrometer any gas that the direction with appointment is directed.This term should be interpreted as to comprise monatomic, diatomic, three atoms and the polyatomic molecule that can pass or flow through pipeline widely.This term also should be interpreted as to comprise mixture, impure mixture or impurity widely.This term comprises inertia and non-inert substance.Gas commonly used used in this invention includes but not limited to ammonia, carbon dioxide, helium, fluorine, argon, xenon, nitrogen, air etc.
Term " source of the gas " refers to produce the gas of needs or any equipment, machine, conduit or the device of air-flow.Source of the gas produces the air-flow of adjusting usually, but this is not essential.
Term " capillary " or " collection capillary " should synonyms, and consistent with the common definition of this area.This term should be interpreted as to comprise any device, equipment, pipe, flexible pipe or the conduit that can receive ion widely.
Term " detector " refers to detect any device, equipment, machine, parts or the system of ion.Detector can comprise or can not comprise hardware and software.In mass spectrometer, detector commonly used comprises also/or be coupled to mass analyzer.
A plurality ofly be meant at least two, for example two, three, four, six, eight, ten, 12 or more than 12.Phrase " a plurality of " and " some " can replace use mutually.A plurality of conduits or air-flow comprise at least the first conduit or air-flow and second conduit or air-flow respectively.
Ion source as described herein can have and is lower than 100mTorr or the ambient pressure of 100mTorr (just ion source housing in temperature) at least.In certain embodiments, for example, it is ambient pressure or the high vacuum pressure of atmospheric pressure (approximately 760mTorr) that ion source can have.
" closed feedback loop " is the system that the feedback of the temperature sensor of the wherein regional temperature origin leisure in the ion source in should the zone is controlled.Closed feedback loop comprises the gas-heating apparatus and the temperature sensor of coupling usually at least.Thermostatic control system comprises an example of closed feedback loop.
" thermostat " be detected temperatures and from dynamic response to change the device of temperature by opening and closing gas-heating apparatus.
" gas-heating apparatus " comprises the device of any type that is used for heated air.Gas-heating apparatus for example can be by convection current, conduction or radiation heating gas.Gas-heating apparatus for example can be the part of source of the gas (for example cylinder), other transmitting catheter or ion source housing or related with them.Can be when gas enters into ion source, afterwards or before by the gas-heating apparatus heated air.
The present invention will describe with reference to the accompanying drawings.Accompanying drawing and not to scale, and especially, some sizes can be by exaggerative with the clarification explanation.
Fig. 1 illustrates mass spectrometric overall construction drawing.This structure chart not to scale (NTS) is also drawn with general format, because the present invention can be used for various dissimilar mass spectrometers.Mass spectrometer 1 of the present invention comprises ion source 3, ion enhancement system 2, ion transfer system 6 and detector 11.Ion enhancement system 2 can place between ion source 3 and the ion detector 11, maybe can comprise the part of ion source 3 and/or the part of ion transfer system 6.
Execution mode.
Contiguous ion enhancement system 2 of ion transfer system 6 and can comprising are gathered capillary 7 or any ion optics, conduit or device known in this field and can transimiison analysis thing ion.
Fig. 2 illustrates the cutaway view of first embodiment of the invention.This illustrates the present invention who is applied to the AP-MADLI spectrometer system.In order to simplify, this illustrates the present invention who has pressure vessel body 14.The use that is used to surround the pressure vessel body 14 of ion source and system is optional.Some parts, parts and system can be under vacuum, or can be not under vacuum.These technology and structure are well known in the art.
Ionized space 15 is between ion source 3 and collection capillary 5.Ionized space 15 comprises at ion source 3 and gathers space and the zone in the zone between the capillary 5.This zone comprises the quilt gasification that produces by ionized sample and is the ion of gas phase.Can how to arrange with respect to collection capillary 5 according to ion source 3 and adjust this regional size and dimension.Most important ground, what be arranged in this zone is the analyte ions that produces by ionization target 13.
Gather capillary 5 and be positioned at the downstream of ion source 3, and can comprise multiple material well known in the art and design.Gather capillary 5 and be designed to receive and assemble the analyte ions that is produced by ion source 3, the analyte ions that is produced by ion source 3 is discharged from as ion flow and enters ionized space 15.Gathering capillary 5 has receiving and analyzing thing ion and they is transferred to the slit or the elongated hole 12 of another capillary or position.In Fig. 2, to gather capillary 5 and be connected to main capillary 18, main capillary 18 is under vacuum and at downstream part more.Gathering capillary 5 can be supported in place by optional insulator 17.Other structure well known in the art or device can be used for supporting collection capillary 5.
Source of the gas 7 provides the gas of heating to conduit 9.Source of the gas 7 can comprise that the device of any amount is to provide the gas of heating.Source of the gas is well known in the art and describes elsewhere.Source of the gas 7 can be the separated components shown in Fig. 2-3, or can with coupler 34 (shown in Fig. 4) one, coupler 23 is operably connected and gathers capillary 5, conduit 9 and main capillary 18.Source of the gas 7 can provide a large amount of gases to conduit 9.For example, the gas such as nitrogen, argon gas, xenon, carbon dioxide, air, helium etc. can be used for the present invention.Gas needs not to be inertia, and should carry the energy or the heat of capacity.Other gas well known in the art that comprises these characteristic properties also can be used for the present invention.
Fig. 3 illustrates the cutaway view of second embodiment of the invention.Conduit 9 can be positioned at many positions with guiding gas towards ionized space 15.Fig. 3 be specifically shown in gather the pattern that capillary 5 separates in conduit 9.Importantly conduit 9 can guide enough heated air stream to provide enhancing to the analyte ions that is arranged in ionized space 15 for purposes of the invention.Conduit 9 can be positioned to distance objective 13 or object support part 10 about 1-5mm.The heated air that is applied to target 13 and object support part 10 should be in 60-150 degree centigrade scope.Specific gas flow rate should be about 2-15 liter/minute.
Molecule is gathered inlet capillaceous to move to ion by the identical direction of ion collection capillary from the object support part with their transmission usually.Thus, for purpose of the present disclosure, ion source of the present invention can comprise by ion gathers the ion motion axle that the longitudinal axis capillaceous limits, and just, ion is gathered capillary and comprised that ion is along its longitudinal axis that moves.In addition, for purpose of the present disclosure, the axle of heating air flow is limited by the longitudinal axis (just Jia Re gas is along its molecular axis that moves) of the conduit that heated air is provided.
In certain embodiments, and shown in Fig. 2 and 3, with respect to the ion motion axle of gathering the capillary inlet from target substrate to ion, the axle of air-flow can be arbitrarily angled from 0 degree to 360 degree, comprises 0 degree and 360 angles of spending.For example, the axle of air-flow can be opposite with the axle of ion flow or antiparallel (just about 180 degree), parallel (just about 0 degree) or vertical, or arbitrarily angled between them.
In certain embodiments, the relative axle of ion flow, the direction that heated air flows can be arbitrarily angled in the following ranges: 0-30 degree, 30-60 degree, 60-90 degree, 90-120 degree, 120-150 degree, 150-180 degree, 180-210 degree, 210-240 degree, 240-270 degree, 270-300 degree, 300-330 degree, 330-360 degree.In certain embodiments, the axle of heated air is positioned to perpendicular to the ion motion axle.
Above listed angle can be arbitrarily angled in two dimension or the three dimensions.In other words, this angle can be on the x/y plane (plane just same as shown in Figure 3), or in z-plane (just the axle of heated air can be more than the x/y plane of Fig. 3 or be following) or its combination.In other words, from the side (as shown in Figure 3) or from " above " when (for example gathering inlet capillaceous from ion) observed, the axle of heated air can be at the arbitrarily angled place with respect to the ion transfer axle.
The Fig. 2 and the 4-7 diagram first embodiment of the present invention.Conduit 9 is designed to surround collection capillary 5.Conduit 9 can surround gathers all or part of of capillary 5.But importantly conduit 9 vicinities are gathered capillary pipe ends 20 and are made that entering or gathered the gas that heats before capillary 5 gatherings at analyte ions can be sent to the analyte ions that is arranged in ionized space 15.Fig. 1-6 and 8 only illustrates minority embodiment of the present invention and only is used to illustrational purpose.They should not be interpreted as dwindling broad range of the present invention.Conduit 9 can be the part that separated components maybe can comprise coupler 23.Fig. 4-6 illustrates the conduit 9 as separating component.
Fig. 4-6 illustrates and is used to connect the coupler 23 and the design thereof of gathering capillary 5, main capillary 18 and conduit 9.Coupler 23 is designed to be attached to fixing strutting piece 31 (shown in Fig. 7 and 8).Coupler 23 comprises that pad 33, housing 35, capillary cover 34 (see figure 5)s.Capillary lid 34 and pad 33 are designed to be installed in the housing 35.Pad 33 is designed to apply pressure to capillary lid 34 and makes that maintenance seals closely between capillary lid 34 and main capillary 18.Capillary lid 34 is designed to hold main capillary 18.Between pad 33 and capillary lid 34, limit little gap 36 (see figure 6)s.Little gap 36 allows gas to flow to from source of the gas 7 and gathers capillary 5, and this is opposite with the outflow housing of being realized by one type of prior art syringe 35.
With reference now to Fig. 1-8,, detector 11 is positioned at the downstream of ion source 3 and conduit 9.Detector 11 can be mass analyzer or other similar device well known in the art, and it is used to detect by gathering capillary 5 gathers and be transferred to the analyte ions of the enhancing of main capillary 18.Detector 11 can also comprise known in this field and can help to detect any hardware and software of the analyte ions of enhancing.
In some embodiments of the invention, can comprise based on the ion source of matrix and be used to guide a plurality of heated air streams (for example, at least the first and second heated air stream) device towards ionogenic ionized space.In these embodiments, this device can comprise and be used to guide a plurality of (for example at least the first and second) hole (for example nozzle) of heated air stream towards ionized space, and those holes can be arranged in around the ionized space.In certain embodiments, these holes can be equidistant from ionized space.
Therefore in certain embodiments, the ion source based on matrix of the present invention can comprise target substrate, ion is gathered capillary, placed Target Board and ion to gather intercapillary ionized space, is used to guide first heated air to flow to first conduit of ionized space and is used to guide second heated air to flow to second conduit of ionized space.Can also comprise by ion based on the ion source of matrix and to gather ion motion axle that the longitudinal axis capillaceous limits and the first and second air-flow axles that limit by first and second conduits.As mentioned above, the first and second air-flow axles can become arbitrarily angled with respect to the ion motion axle.
This device can provide a plurality of heated air streams (for example at least the first and second heated air stream), and they are with respect to gathering ion flow direction capillaceous (as mentioned above, it is identical with the collection longitudinal axis capillaceous) from Target Board to ion with positioned at arbitrary angles.In a certain embodiments, heated air stream is positioned to perpendicular to ion flow direction (surface that for example is parallel to target substrate), and heated air stream enters ionized space from the side.In other words, if target substrate is represented three-dimensional x and y axle, then heated air stream can become arbitrarily angled with respect to the z axle of same space.
As mentioned above, this device can comprise and be used to guide a plurality of holes of a plurality of heated air streams towards ionized space.In certain embodiments, this device can comprise a plurality of conduits that are positioned to towards ionized space, and each conduit ends in the hole.But in other embodiments, this device can comprise single gas transfer element, and this single gas transfer element comprises a plurality of holes that are positioned to around ionized space.In this embodiment, the gas transfer element can form around ionized space or the split ring on ionized space or the ring of remaining silent, and the hole of gas transfer element can be positioned to guide a plurality of air-flows towards ionized space.
Therefore in certain embodiments, be used to provide a plurality of heating air flow (for example can comprise a plurality of conduits towards the device of ionogenic ionized space, at least two, three, four or five or more conduits), each has the longitudinal axis towards the ionized space location.In certain embodiments, the longitudinal axis of conduit can be positioned to the direction (surface that for example is parallel to the object support part) perpendicular to ion flow.In optional embodiment, device can comprise open loop shape or loop-like gas transfer element, and the gas transfer element is included in a plurality of holes (for example at least two, three, four or five or more porous) of guiding gas on the direction of ionized space.The gas transfer element can be positioned at the ionized space top or center on ionized space.
An embodiment who illustrates this respect of the present invention is shown schematically among Figure 11.In this embodiment, ion source 1 comprises target substrate 10, ion is gathered capillary 5, placed Target Board and ion to gather intercapillary ionized space 15, is used to guide first heated air to flow to first conduit 9 of ionized space and is used to guide second heated air to flow to the second conduit 9a of ionized space.First and second conduits can be operatively attached to source of the gas 7 and 7a.Source of the gas 7 can be identical or different sources of the gas with 7a.
This device provides from a plurality of air-flows in any direction contact ionization zone, just from respect to any direction of ionized space (comprise from respect to the side (vertically just) of ion flow direction or the angle that tilts arbitrarily) towards the ionized space airflow flowing.Described the present invention and parts in detail, will describe the present invention according to order and how to operate.
Fig. 7 illustrates the cutaway view of device.Gather capillary 5 and be connected to main capillary 18 by capillary lid 34.The capillary lid is designed to admit main capillary 18 and is arranged in the housing 35.Housing 35 is connected directly to securing supports 31.Notice that source of the gas 7 provides gas by the passage 38 that is limited between housing 35 and the capillary lid 34.Gas passes through passage 24 from source of the gas 7 flow channels 38, and enters ionization chamber 30 afterwards.Gas is released in the ionization chamber 30 and do not play a role this moment.
Fig. 8 illustrates the cutaway view of first embodiment of the invention, and it has the conduit 9 that is arranged between ion source 3 and the source of the gas 7.Conduit 9 work are to carry heated air to gathering capillary pipe end 20 from source of the gas 7.Method of the present invention produces the analyte ions that is easy to the enhancing of detection in mass spectrometer 1.This method comprises that the gas heated with guiding is arranged in the analyte ions that is adjacent to the ionized space 15 of gathering capillary 5, so that they are detected easilier by detector 11.Gas is produced by source of the gas 7, is guided through passage 38 and little gap 36.Gas is transported in the annular space 42 that is limited between conduit 9 and the collection capillary 5 therefrom.The gas of heating contacts the device 40 (not shown among Fig. 8) in optional the putting then.The device of putting 40 is arranged in to be gathered between capillary 5 and the conduit 9, and is shaped in the mode that adjustment flows to the gas flow of ionized space 15.Gas flows out conduit 9 and enters the contiguous ionized space 15 of gathering capillary pipe end 20.Analyte ions in the ionized space 15 is by being incorporated into this regional gas heated.The analyte ions that is enhanced is then assembled by gathering capillary 5, is transported to main capillary 18 and is sent to detector 11.It should be noted that after heat was added to the analyte ions of adjacent source, detectable limit and signal quality improved significantly.This result does not reckon with fully.For example because there is not solvent to be used for AP-MALDI and MALDI ion source and mass spectrometer, so do not expect desolventizing and/or gas be applied in enhancing based in the ion source of matrix and the ion detection in the mass spectrometer effectively.But what make us believing is that the present invention is decomposed by big ion cluster and turns round to produce this fact of exposed analyte ions, easier being detected of ion that these are exposed.In addition, Re application has also helped the evaporation of sample.
In another embodiment, the invention provides the ion source based on matrix, according to the above, wherein gas is supplied to ionized space under predetermined temperature.In this embodiment, except the above element that proposes, can comprise gas-heating apparatus based on the ion source of matrix.Ion source based on matrix can also comprise temperature sensor.The gas-heating apparatus that combines with temperature sensor can be supplied to the heated air temperature of ionized space with the feedback loop running of closure with control and maintenance.In certain embodiments, the temperature of heated air can be controlled by ionogenic manual operation, and the operator can change the temperature of heated air as required.Figure 12 A-12D and 13 illustrates examples of the present invention and it be not desired to limit the invention to a certain embodiments.For example and as mentioned above, heated air can provide to ionized space via many different modes, for example utilize and gather the coaxial conduit of capillary, utilization and ion with ion and gather the conduit that capillary separates or utilize a plurality of conduits.Heated air can be directed toward ionized space, perhaps in certain embodiments, can fill with the gas of heating and just fill with ion source.The General Principle that is shown in Figure 12 A-12D and 13 can be applied in the above-mentioned any embodiment.
With reference to figure 12A, the invention provides the ion source 50 based on matrix, ion source 50 comprises and has ion that ion enters hole 54 and gather capillary 52, enter Target Board 56 that hole 54 is close to ion, place the ionized space that enters between hole 54 and the sample panel 56, be connected to source of the gas 62 and be used for supply gas to the conduit 60 of ionized space 58 and be used for the gas-heating apparatus 64 of heated air to assigned temperature.Gas-heating apparatus 64 is typically connected to the temperature controller 66 that is arranged in the ion source outside.By received signal (its can manually or automatically), temperature controller 66 can increase or the less power that is supplied to gas-heating apparatus 64, increases or reduce the temperature of gas.By increasing or reduce the temperature of gas-heating apparatus, temperature that can adjustments of gas.Gas-heating apparatus 64 can be arranged in any suitable location in the ion source housing 67.Gas-heating apparatus can also be related with the outer gas conduit of ion source (for example within it, around or as its part).For example and shown in the element among Figure 12 B 70, gas-heating apparatus can be related with the gas conduit in the ion source housing.Shown in the element 71 of Figure 12 C, replacedly, gas-heating apparatus can link to each other with the gas conduit outside the ion source housing.In one embodiment, and shown in Figure 12 D, gas-heating apparatus can be positioned between the outlet (for example optional position in the gas feedthroughs that connects source of the gas and housing) and ionized space of gas conduit.In other words, in certain embodiments, the gas heated element can be related with gas conduit, makes that it is heated when gas passes conduit.In other embodiments, gas-heating apparatus is not related with gas conduit, and is positioned at ionogenic housing and makes and be heated after conduit comes out at gas." comprise " the whole embodiment shown in the ion source composition diagram 12A-12D of gas-heating apparatus, and other is to the very tangible embodiment of those skilled in the art.
As shown in figure 13, within ionogenic housing, ion source can also comprise the temperature sensor 80 that is used to monitor the heated air temperature.Be similar to the gas heated element, temperature sensor 80 can be positioned at any correct position of ion source.But in certain embodiments, temperature sensor 80 is oriented to monitor the gas temperature in the ionized space.Thus, as shown in figure 13, temperature sensor 80 can be positioned at and make the probe of transducer be close to ionized space in the ion source.Temperature sensor can be the temperature sensor of any type, for example includes but not limited to occasionally resistance temperature detector (RTD) temperature sensor of thermistor, thermoelectricity, or other any other temperature sensor known in the art.
In addition as shown in figure 13, temperature sensor 80 and gas-heating apparatus 82 (only in this diagram, being associated for illustrative purposes) and temperature controller 83 with gas conduit 84 can be used as closed reponse system running with the temperature that keeps heated air at predetermined temperature.In fact, temperature sensor 80 detects the temperature of heated air, and, if the temperature of heated air below predetermined temperature, is then signaled to the temperature of temperature controller 83 with the increase gas-heating apparatus.On the contrary, if the temperature of heated air more than predetermined temperature, then signal to temperature controller 83 to reduce the temperature of gas-heating apparatus.For example, temperature that can optimized choice is used for the ion cooling and conciliates bunch.As shown in figure 13, temperature sensor 80, gas-heating apparatus 82 and temperature controller 83 can be operatively attached to the user interface 86 that shows the heated air temperature.This user interface allows ionogenic operator to observe the temperature of heated air in ionization process, monitors the temperature of heated air in ionogenic use, and controls the temperature of heated air as required.For example, for the temperature (for example in order to detect different ions) that increases or reduce heated air, the operator can import the temperature that needs via user interface 86 as required, and user interface guides temperature controller 83 to increase or reduce the temperature of gas-heating apparatus 84.Under the situation that does not have further to change the operator, heated air will reach the temperature that needs, and will remain on the temperature that needs via the feedback loop of closure.
In general term, closed feedback loop system allows the operator to set the temperature of the temperature of heated air to appointment.In certain embodiments, the temperature of appointment about 50 ℃ to about 300 ℃ scope, for example about 60 ℃ to about 250 ℃ scope, but also can use predetermined temperature outside these scopes easily.
In certain embodiments, the invention provides the method that is used to utilize based on the ion source generation analyte ions of matrix.To ionogenic ionized space, ionized sample is to produce analyte ions to the present invention includes a plurality of heated air streams of guiding (for example first and second heated air stream); And with the analyte ions output ion source that produces.
This method provides: the gas of guiding assigned temperature is towards the ionogenic ionized space based on matrix, and ionized sample to be producing ion, and with described ion output ion source.This method can also comprise the temperature of monitoring gas, and changes the temperature of gas in certain embodiments.
Be described in conjunction with its specific embodiment although should be understood that the present invention, aforementioned description and following example intended as illustrative illustrate rather than limit the scope of the invention.Others, advantage and modification in the scope of the invention are conspicuous for the those skilled in the art in the technical field of the invention.
More than reach all patents, patent application and open its integral body by reference of the following stated and be contained in this.
Present patent application is that the sequence number of submitting on January 21st, 2005 is 11/041,118 part continuity, sequence number is 11/041,118 application is that the sequence number of submission on October 15th, 2004 is 10/966,278 part continuity, and sequence number is 10/966,278 application is that the sequence number of submitting on February 22nd, 2002 is 10/080,879 and be authorized to be 6,825,462 continuity now.Specially it is whole and be included in here by reference for the content of these patent applications.
Example 1
Bruker Esquire-LC ion trap mass spectrometer is used for AP-MALDI research.The mass spectrometer ion optics is made amendment by (knockout, have two ends of the earth guide of subregion), and the ion of this instrument sampling inlet is made up of ion sampling capillary extending, and has the conduit concentric with capillary extending.Ion sampling inlet receive the 4-10 liter/minute flow of warm nitrogen gas.(337.1nm 10Hz) is passed on the target by single condenser lens by 400 micron optical fibers laser beam.Laser power estimates to be about 50 to 70 little joules.By the maximum capture time that is provided for the mass spectrometer scanning optical spectrum is that 300ms (three Laser emission) uses ion charging to control to obtain data.Each spectrum is the mean value of 400 to 2200AMU eight micro scannings.Employed matrix is that 8mM is dissolved in the alpha-cyano-4-hydroxyl-cinnamic acid in the acetate of 25% methyl alcohol, 12%TPA, 67% water and 1%.The matrix target is pre-mixed, and matrix/target mixture of 0.5ul is coated onto on the gold-plated stainless steel target.Used target comprises the trypsin hydrolysis liquid of bovine serum albumin(BSA) and comprises the standard peptide mixture of angiotensin I and IT, bradykinin and fibrinopeptide A.The gas phase temperature of target proximity (ionized space) is 25 degrees centigrade.Fig. 9 illustrates the effect that does not have heated air to add to target or ionized space.This figure is not illustrated in higher mass-to-charge ratio place and has summit (ion enhancing).
Example 2
Except heated air acts on the target (ionized space) with about 100 degrees centigrade, as above-mentioned preparation and use same target.Figure 10 illustrates heated air is applied to the effect on the target in the ionized space.This illustrates and has summit (ion enhancing) at higher mass-to-charge ratio place.
Claims (26)
1. ion source based on matrix comprises:
Have the ion that ion enters the hole and gather capillary;
Be adjacent to described ion and enter the Target Board in hole;
Place the described ionized space that enters between hole and the described Target Board;
Be used for the conduit of supply gas to described ionized space;
Be used to heat the gas-heating apparatus of described gas to assigned temperature; And
Be arranged in the temperature sensor that is used to monitor described gas temperature in the described ion source.
2. the ion source based on matrix as claimed in claim 1, wherein said temperature sensor is a thermostat.
3. the ion source based on matrix as claimed in claim 1, wherein said temperature sensor comprise occasionally resistance temperature detector transducer of thermistor, thermoelectricity.
4. the ion source based on matrix as claimed in claim 3, wherein said temperature sensor and described gas-heating apparatus are operably connected, and turn round to keep described gas in stationary temperature in the feedback loop of closure.
5. the ion source based on matrix as claimed in claim 4, wherein said temperature sensor and described gas-heating apparatus may be operably coupled to the user interface of the described temperature that shows described heated air.
6. the ion source based on matrix as claimed in claim 5, wherein said user interface allow the operator to change the described temperature of described heated air.
7. the ion source based on matrix as claimed in claim 1, the temperature of wherein said appointment about 50 ℃ to about 250 ℃ scope.
8. the ion source based on matrix as claimed in claim 1, wherein said assigned temperature about 60 ℃ to about 200 ℃ scope.
9. the ion source based on matrix as claimed in claim 1, wherein said gas-heating apparatus is arranged in the described ion source.
10. the ion source based on matrix as claimed in claim 1, wherein said ion source based on matrix may be operably coupled to source of the gas.
11. it is outside and related with described conduit that the ion source based on matrix as claimed in claim 10, wherein said gas-heating apparatus are arranged in described ion source.
12. the ion source based on matrix as claimed in claim 1, wherein said ion source turns round more than 100mTorr.
13. the ion source based on matrix as claimed in claim 1, wherein said ion source under atmospheric pressure turns round.
14. the ion source based on matrix comprises:
Have the ion that ion enters the hole and gather capillary;
Be adjacent to described ion and enter the Target Board in hole;
Place the ionized space between described ion collection capillary and the described Target Board;
Be used for the conduit of supply gas to described ionized space;
Be used to heat the gas-heating apparatus of described gas to assigned temperature; And
Be used to detect the transducer of heated air temperature described in the described ion source;
Wherein said transducer and described gas-heating apparatus are operably connected, and turn round in the feedback loop of closure to keep described heated air in predetermined temperature.
15. the ion source based on matrix as claimed in claim 14, wherein said gas-heating apparatus and described sensors coupled are to the user interface of described ion source outside.
16. the ion source based on matrix as claimed in claim 14, wherein said user interface allow the operator to change the described temperature of described heated air.
17. a spectrometer system comprises:
A) based on the ion source of matrix, comprising:
Have the ion that ion enters the hole and gather capillary;
Be adjacent to described ion and enter the Target Board in hole;
Place the ionized space between described ion collection capillary and the described Target Board;
Be used to supply the conduit of heated air to described ionized space; With
Be used to heat the gas-heating apparatus of described gas to assigned temperature; And
B) be positioned at the ion transfer system in described ion source downstream based on matrix; And
C) be positioned at the ion detector of described ion transfer system downstream.
18. spectrometer system as claimed in claim 17 also is included in the temperature sensor that is used to monitor described heated air temperature in the described ion source based on matrix.
19. spectrometer system as claimed in claim 18, wherein said temperature sensor and described gas-heating apparatus turn round in the feedback loop of closure to keep described heated air in stationary temperature.
20. spectrometer system as claimed in claim 17, wherein said temperature sensor and described gas-heating apparatus may be operably coupled to the user interface that shows described heated air temperature.
21. spectrometer system as claimed in claim 20, wherein said user interface allow the operator to change the temperature of described heated air.
22. spectrometer system as claimed in claim 17, wherein said ion source under atmospheric pressure turns round.
23. spectrometer system as claimed in claim 17, wherein said ion source turns round more than 100mTorr.
24. a method that produces ion in based on the ion source of matrix comprises:
The gas of guiding assigned temperature is towards the ionogenic ionized space based on matrix;
Ionized sample is to produce ion;
Described ion is exported described ion source.
25. method as claimed in claim 24 also comprises the temperature of monitoring described gas.
26. method as claimed in claim 24 also comprises the temperature that changes described gas.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11/041,118 US7135689B2 (en) | 2002-02-22 | 2005-01-21 | Apparatus and method for ion production enhancement |
| US11/041,118 | 2005-01-21 | ||
| US11/155,070 | 2005-06-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1933092A true CN1933092A (en) | 2007-03-21 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200610001970 Pending CN1933092A (en) | 2005-01-21 | 2006-01-23 | Apparatus and method for ion production enhancement |
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| CN (1) | CN1933092A (en) |
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| CN101871914A (en) * | 2009-04-24 | 2010-10-27 | 岛津分析技术研发（上海）有限公司 | Method and device thereof for desorption ionization |
| CN102414779A (en) * | 2009-05-01 | 2012-04-11 | 萨莫芬尼根有限责任公司 | Ion transfer tube and mass spectrometer system |
| US20120085903A1 (en) * | 2009-06-03 | 2012-04-12 | Wayne State University | Mass spectometry using laserspray ionization |
| CN102903596A (en) * | 2012-09-18 | 2013-01-30 | 清华大学 | Ion source temperature control heating device |
| CN101308125B (en) * | 2007-05-18 | 2013-03-13 | 华瑞科学仪器(上海)有限公司 | Photoionization detector, gas-chromatography detection system and chromatographic detector method |
| CN103298232A (en) * | 2012-03-02 | 2013-09-11 | 株式会社东芝 | Ion source |
| CN105122422A (en) * | 2013-04-19 | 2015-12-02 | 株式会社岛津制作所 | Mass spectroscopy device |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101308125B (en) * | 2007-05-18 | 2013-03-13 | 华瑞科学仪器(上海)有限公司 | Photoionization detector, gas-chromatography detection system and chromatographic detector method |
| CN101871914A (en) * | 2009-04-24 | 2010-10-27 | 岛津分析技术研发（上海）有限公司 | Method and device thereof for desorption ionization |
| CN102414779A (en) * | 2009-05-01 | 2012-04-11 | 萨莫芬尼根有限责任公司 | Ion transfer tube and mass spectrometer system |
| CN102414779B (en) * | 2009-05-01 | 2015-07-08 | 萨莫芬尼根有限责任公司 | Ion transfer tube and mass spectrometer system |
| US9202680B2 (en) | 2009-06-03 | 2015-12-01 | Wayne State University | Mass spectometry using laserspray ionization |
| CN102741965A (en) * | 2009-06-03 | 2012-10-17 | 韦恩州立大学 | Mass spectrometry using laser spray ionization |
| US20120085903A1 (en) * | 2009-06-03 | 2012-04-12 | Wayne State University | Mass spectometry using laserspray ionization |
| US20180012745A1 (en) * | 2009-06-03 | 2018-01-11 | Wayne State University | Mass spectrometry using laserspray ionization |
| CN103298232A (en) * | 2012-03-02 | 2013-09-11 | 株式会社东芝 | Ion source |
| CN103298232B (en) * | 2012-03-02 | 2017-04-12 | 株式会社东芝 | Ion source |
| US9859086B2 (en) | 2012-03-02 | 2018-01-02 | Kabushiki Kaisha Toshiba | Ion source |
| CN102903596A (en) * | 2012-09-18 | 2013-01-30 | 清华大学 | Ion source temperature control heating device |
| CN102903596B (en) * | 2012-09-18 | 2015-08-12 | 清华大学 | A kind of ion source temperature control heating device |
| CN105122422A (en) * | 2013-04-19 | 2015-12-02 | 株式会社岛津制作所 | Mass spectroscopy device |
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