CN106384705B - A kind of high-throughput Nanoliter electrospray analysis system and its application based on miniature array - Google Patents
A kind of high-throughput Nanoliter electrospray analysis system and its application based on miniature array Download PDFInfo
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- CN106384705B CN106384705B CN201610753809.0A CN201610753809A CN106384705B CN 106384705 B CN106384705 B CN 106384705B CN 201610753809 A CN201610753809 A CN 201610753809A CN 106384705 B CN106384705 B CN 106384705B
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- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
- H01J49/00—Particle spectrometers or separator tubes
- H01J49/02—Details
- H01J49/04—Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
- H01J49/0404—Capillaries used for transferring samples or ions
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- G—PHYSICS
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- G01N27/62—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating the ionisation of gases, e.g. aerosols; by investigating electric discharges, e.g. emission of cathode
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- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
- H01J49/00—Particle spectrometers or separator tubes
- H01J49/02—Details
- H01J49/10—Ion sources; Ion guns
- H01J49/16—Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission
- H01J49/165—Electrospray ionisation
- H01J49/167—Capillaries and nozzles specially adapted therefor
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Abstract
The present invention relates to a kind of, and the high-throughput nano based on miniature funnel-form sample holder array upgrades Electrospray Ionization Mass Spectrometry device and its application.It include: electrospray device, mass spectrograph, funnel-form minute sample carrier, bracket, it is characterized in that, funnel-form minute sample carrier is provided between the capillary tip and mass spectrograph injection port of the electron spray, the funnel-form minute sample carrier is located on the bracket；Present apparatus sample is high in loader surface concentration, not only increase the sensitivity of system, and there is preferable practicability, complicated parameter optimisation procedure and sample transfer process are avoided, the array preparation method of invention is passed through, the quick Fabrication of micro- funnel array may be implemented, it is at low cost, it is easy to operate, it is suitable for polypeptides/proteins molecule, the Nanoliter electrospray mass spectral analysis of pesticide molecule, polymer and carbohydrate and antibiotic molecule.
Description
Technical field
The invention belongs to mass spectral analysis field, in particular to a kind of high-throughput Nanoliter electrospray analysis based on miniature array
System and its application.
Background technique
The analysis method of traditional chromatograph-mass spectrometer coupling is by complicated Sample Pretreatment Technique, by object from sample
It is extracted in product matrix, after extract is then passed through purification, then carries out instrument analysis.Common extracting process includes solid phase
Extraction, liquid-liquid extraction, solid phase microextraction, the technologies such as magnetism extraction, in the sample handling processes based on such technology, due to past
It can cause environmental pollution toward to pass through multi step strategy using a large amount of organic reagent；In addition, for small samples, it is complicated
Treatment process the problems such as often will cause the loss or cross contamination etc. of object in sample or sample, for analyzing result
Accuracy have a large effect, and test, waste of manpower and material resources longer with the time.
The method directly analyzed based on mass spectrum is relatively easy, can effectively improve analysis efficiency, such as desorption electrospray skill
Art and extraction electron spray etc..But traditional reflective desorption electrospray technical pattern parameter is complicated, and different types of sample
Product require structural parameters different；Transmission-type desorption electrospray uses network structure load sample, although operation is relatively easy,
But the disadvantages of there are sample surfaces concentration is low and jitter, it is necessary to develop new technology and go to improve the sample point on surface
The concentration of son.Although the relatively traditional electrospray techniques of the direct analytical technology of Nanoliter electrospray are few for sample size demand,
Sample transfer and complex disposal process, loss of the meeting with sample and possible cross contamination, and high-throughput point relatively difficult to achieve
Analysis.Therefore, it is badly in need of establishing a kind of ion source device of direct mass spectral analysis of suitable small samples, realizes quickly analysis.
Summary of the invention
The purpose of the present invention is to solve the above-mentioned problems, provides a kind of based on miniature funnel array nanoliter level electron spray
Mass spectrometric analysis method.The present invention makes funnel device in film surface by micropin and carries out Fuel spray, using it to polypeptide, albumen
Matter and enzymolysis sample are analyzed.
Its basic principle is as follows: the fluid sample of small size is applied directly to the miniature funnel (micro- funnel) of sample holder
In, by the way that load high voltage (- 4.5kV) is arranged in mass spectrum injection port, generate it is primary spraying, and in sample holder funnel by
It gradually accumulates, forms high charge liquid film, the analysans of liquid film continued dissolution and extraction funnel surface deposition, in the influence of electric field
Under, it is mobile to mass spectrum injection port direction, formed in aperture secondary spraying, charged ion enters mass spectrum, and acquisition obtains spectrogram (as schemed
Shown in 1).Present apparatus sample is high in loader surface concentration, not only increases the sensitivity of system, and has preferable practical
Property, avoiding complicated parameter optimisation procedure and sample transfer process may be implemented micro- leakage by the array preparation method of invention
The quick Fabrication of bucket array, it is at low cost, it is easy to operate, it is suitable for polypeptides/proteins molecule, pesticide molecule, polymer and sugar
The Nanoliter electrospray mass spectral analysis of class and antibiotic molecule.
To achieve the goals above, the present invention adopts the following technical scheme:
A kind of high-throughput nano upgrading Electrospray Ionization Mass Spectrometry device based on miniature funnel-form sample holder array, packet
It includes: electrospray device, mass spectrograph, funnel-form minute sample carrier/funnel-form minute sample carrier array, bracket；Institute
It states and is provided with funnel-form minute sample carrier/miniature sample of funnel-form between the capillary tip of electron spray and mass spectrograph injection port
Product carrier array, the funnel-form minute sample carrier/funnel-form minute sample carrier array are located on the bracket；
Wherein, the funnel-form minute sample carrier array in a manner of annular array by being evenly spaced in same plane
On the miniature funnel-form sample holder composition.
Preferably, funnel-form minute sample carrier (micro- funnel) central point and mass spectrum injection port distance S1, institute
State funnel-form minute sample carrier central point and the nozzle needle (capillary tip) distance S2, wherein S1/S2=3~3.2:
5~5.1.
In an above-mentioned spray process, need to load solvent in capillary, but it is molten to extract 1mL in funnel for sample
Agent (methanol/water=1:1 mode) also can according to need the type of adjustment solvent.
Preferably, the diameter in the funnel-form minute sample carrier aperture is less than < 200 μm.
Heretofore described " diameter in funnel-form minute sample carrier aperture " refers to: " micro- relatively fine portion of funnel bottle neck
The port diameter of part ".
Preferably, the center line of the axial line of the funnel-form minute sample carrier and mass spectrograph injection port is located at same
On straight line.
Preferably, the aperture highlight of the funnel-form minute sample carrier is located at mass spectrograph injection port side；
Preferably, the sample volume of the funnel-form minute sample carrier is 50~60nL.
The present invention also provides a kind of miniature funnel-form sample carryings for high-throughput nano upgrading Electrospray Ionization Mass Spectrometry
Device, the funnel-form minute sample carrier are funnel-form, are set to high-throughput nano by bracket and upgrade Electrospray Ionization Mass Spectrometry
Between the capillary tip and mass spectrograph injection port of the electron spray of device.
Preferably, the diameter in the funnel-form minute sample carrier aperture is less than < 200 μm；
Preferably, the funnel-form minute sample carrier central point and mass spectrum injection port distance S1, the funnel-form
Minute sample carrier central point and the nozzle needle (capillary tip) distance S2, wherein S1/S2=3~3.2:5~5.1.
The present invention also provides a kind of miniature funnel-form sample carryings for high-throughput nano upgrading Electrospray Ionization Mass Spectrometry
The preparing instrument of device, comprising: horizontally movable platform I, membrane support, vertically moving platform II, punching needle, stepper motor with
And controller, which is characterized in that the membrane support is mounted on the platform I, and the top of the platform I is provided with the platform
II, the punching needle is provided on the platform II, the punching needle axial line intersects with the platform I and perpendicular to described flat
Platform I；When work, horizontal and vertical movement is carried out by the stepper motor and controller control platform I and platform II respectively.
Preferably, the bottom of the membrane support is additionally provided with hollow metal tube.
The present invention also provides the preparation methods of above-mentioned miniature funnel-form sample holder, comprising:
1) film substrate is fixed on membrane support, is mounted directly on platform I；Punching needle is mounted on platform II；
2) punching press of the movement for passing through controller control platform I, platform II, the separation and punching needle of realizing micro- funnel is deep
Degree regulation；
3) hollow metal tube is set in the bottom of film substrate, generates funnel-form sample holder to dock.
The present invention also provides a kind of, and the high-throughput nano based on miniature funnel-form sample holder array upgrades electron spray matter
Spectrum analysis device detection method, comprising:
1) before acquiring mass spectrum, after sample is diluted or handled, sample is placed in funnel-form minute sample using sample introduction needle
It is to be analyzed in carrier；
2) funnel-form minute sample carrier is docked with mass spectrograph；
3) the sample acquisition and analysis carried out using mass spectrograph.
Preferably, the sample volume of the sample is 50~60nL.
Beneficial effects of the present invention
(1) present invention is using micro- funnel array as the carrier of nano-upgrading sample.Solves small size complex matrices sample
The problem of trace object quickly analyzed in product.Compare traditional nanoliter level spraying device, have it is easy to operate, it is low in cost
The features such as, traditional desorption electrospray technology is compared, there is signal stabilization, the duration is long, high sensitivity, and it is excellent that expanding type is strong etc.
Point is suitable for polypeptides/proteins molecule, pesticide molecule, the mass spectral analysis of polymer and carbohydrate molecule.
(3) apparatus of the present invention structure is simple and convenient to operate, detection efficiency is high, practical, easy to spread.
Detailed description of the invention
The direct electrospray device system schematic of the miniature funnel of Fig. 1；
Wherein, the spraying micro- funnel of 3. peristaltic pump of solvent, 4. capillary nozzle needle, 5. main jet mist, 6. sample bearing plate 7. of 1. ground connection 2.
8. time grade is sprayed 9. mass spectrum injection ports；
The miniature funnel array of Fig. 2；
The miniature funnel array producing device of Fig. 3；
Wherein, a. camera b. stepper motor c. punching needle d. array bracket e. thimble f. stepper motor；
The application of Fig. 4 micro-solid phase extraction array Nanoliter electrospray analysis method: (a) mass spectrogram of 500fmol lysozyme；
(b) mass spectrogram of 1pmol carbonic anhydrase；(c) mass spectrogram of 500fmol bovine serum albumin(BSA)；
The application of Fig. 5 micro-solid phase extraction array Nanoliter electrospray analysis method: (a) mass spectrogram of bovine insulin B chain；
(b) mass spectrogram of cytochrome c；
The application of Fig. 6 micro-solid phase extraction array Nanoliter electrospray analysis method: (a) mass spectrogram of Clenbuterol；(b) horse
Draw the mass spectrogram of sulphur phosphorus, (c) mass spectrogram of maltotriose, (d) mass spectrogram of polyethylene glycol-1000.
The Ofloxacin mass spectrogram of Fig. 7 miniature array Nanoliter electrospray analysis method acquisition.
Fig. 8 miniature array Nanoliter electrospray is compared with polypeptide (SubP) signal of traditional desorption electrospray.
Specific embodiment
Feature of present invention and other correlated characteristics are described in further detail by the following examples, in order to the same industry
The understanding of technical staff:
Embodiment 1
One kind being based on the direct Electrospray Ionization Mass Spectrometry method of miniature funnel.Described device is by a platform, membrane support d, the Chinese
Needle c, stepper motor b, f and controller and mass spectrum composition.The design procedure of device is as follows:
(1) the spraying analysis source preparation method based on film funnel type sample holder is as follows: flexible tacky film is fixed
In on plastic stent d, being mounted directly in a two-dimensional mobile automatic platform, it is provided simultaneously with a level adjustment system.
Punching press Chinese needle c is mounted on the platform vertically moved, and motor platform realizes its micro- leakage by a homemade software program control
The separation of bucket and the press depth for controlling punching needle c.Flexible tacky film may be deformed in the production process, lead to micro- leakage
There are difference for bucket.In order to guarantee punching needle c preparation opening uniformity, hollow metal tube/thimble e be placed in bottom be used to pair
Connect flexible membrane funnel.
(2) the spraying analysis source based on film funnel type sample holder-mass spectrum docking: device is by a platform, sample branch
Frame and spraying system are constituted.After completing sample transfer, miniature film load Solid Phase Extraction cell system is placed on trestle table.Using
Manually linear movement platform and two axis electric platforms are used to adjust and calibrate distance and the position of abstraction pool opening and mass spectrum injection port 9
It sets.Spraying system nozzle needle 4 is made of (interior through 50 μm, 150 μm of outer diameter) quartz capillary.Three-dimensional moving is connected to put down
Platform adjusts its position.Peristaltic pump 3 is connected to quartz capillary and is used to generate by spraying.Nozzle needle 4 locates external camera by spraying and is used to supervise
Depending on the spray condition of ion source, and ensure once spraying stability and duration.
(3) Mass Spectrometry Conditions: Fourier's series ion cyclotron resonance mass spectrometer is used.Using electron spray, flow rate set is
30uL/hr's, both positive and negative mode is respectively adopted and is ionized, capillary voltage is set as 3kV, and the temperature of transfer capillary is
220℃.Parent ion selection is carried out using front end quadrupole rod, quality width is set as 5m/z, and ion assemble index is set as 1-2s.It adopts
Data acquisition is carried out with broadband mode, mass range is set as 50-1000.
1, instrument and reagent
All reagents are purchase, and processing is further processed before use.Experiment protein/polypeptide (including
Angiotensin II,Insulin chain B oxidized,Ubiquitin,Cytochrome c,Lysozyme,
Carbonic anhydrase, Bovine serum albumin (BSA)) and trypsase purchase in Sigma Aldrich
(St.Louis, MO, USA) acetic acid and ammonium hydrogen carbonate purchase are in Riedel-de Han (Seelze, Germany) .HPLC rank
Methanol by Labscan (Bangkok, Thailand) provide .Parafilm " M " film (Pechiney Plastic
Packaging, Chicago, IL, USA) it is used as the making material .FTICR-MS (4.7Tesla in miniature film load Solid Phase Extraction pond
APEX III and 9.4Tesla Solarix, Bruker Instrument Inc., Billerica, MA) carry out sample acquisition
And analysis, sample carry out transfer processing using (Model 7000.5KH SYR, Hamilton Company, Switzerland).
2, preparation of samples
Sample storing liquid is configured by water or methanol-water (1:1 volume ratio), before experiment, is diluted to as needed corresponding
Concentration.Enzymatic hydrolysis experiment is by solubilising protein/polypeptide in the ammonium bicarbonate soln of 100mM.Trypsase is dissolved in 50mM's
In acetic acid.Two kinds of solution are mixed according to 1:50 ratio, are stayed overnight as 37 DEG C of constant temperature.Enzymolysis process is molten by the acetic acid of addition 10%
Liquid terminates.The mixed liquor ultimate density of protein/polypeptide is 100 μM.It is further again before experiment to be diluted.The sample of 50nL is logical
Cross sample introduction needle be placed in it is to be analyzed in array micro funnel 7；After other samples are diluted to required concentration, be loaded directly into array into
Row mass spectral analysis.
3, spraying analysis source-mass spectrum based on film funnel type sample holder is to interview Summary.
4, mass spectrometer system
Using FTICR-MS (4.7Tesla APEX III and 9.4Tesla Solarix, Bruker Instrument
Inc., Billerica, MA) carry out sample acquisition and analysis.It is typically configured to N2(250 DEG C of at~150to) is used to add
Thermo-capillary and auxiliary go spray droplet solvation.The ion of generation enters mass analyzer after accumulating 1-2s in sextupole bar.
Data acquisition is total with 5-20 signal.
5, it applies
Using 9.4T FTICR-MS combination micro-solid phase extraction array-direct ion mass spectrometric analysis method in biology point
Son analysis application aspect is studied.Such as the mass spectrogram of Fig. 4 (a) 500fmol lysozyme；(b) mass spectrum of 1pmol carbonic anhydrase
Figure；(c) mass spectrogram of 500fmol bovine serum albumin(BSA)；Fig. 5 micro-solid phase extraction array Nanoliter electrospray analysis method is answered
With: (a) mass spectrogram of bovine insulin B chain；(b) mass spectrogram of cytochrome c；Fig. 6 micro-solid phase extraction array Nanoliter electrospray
The application of analysis method: (a) mass spectrogram of Clenbuterol；(b) mass spectrogram of malathion, (c) mass spectrogram of maltotriose,
(d) mass spectrogram of polyethylene glycol-1000.It can be seen that the present apparatus can be applied to pesticide molecule, polymer molecule and polypeptide/albumen
The mass spectral analysis of the biomolecule such as matter.
Embodiment 2
A kind of high-throughput nano upgrading Electrospray Ionization Mass Spectrometry device based on miniature funnel-form sample holder array, packet
It includes: electrospray device, mass spectrograph, funnel-form minute sample carrier (micro- funnel) 7, bracket (sample bearing plate) 6；In the electricity
Spraying capillary (capillary nozzle needle) is provided with funnel-form minute sample carrier 7 between 4 tips and mass spectrograph injection port 9,
The funnel-form minute sample carrier 7 is located on the bracket 6.
Embodiment 3
A kind of high-throughput nano upgrading Electrospray Ionization Mass Spectrometry device based on miniature funnel-form sample holder array, packet
It includes: electrospray device, mass spectrograph, funnel-form minute sample carrier (micro- funnel) 7, bracket (sample bearing plate) 6；In the electricity
Spraying capillary (capillary nozzle needle) is provided with funnel-form minute sample carrier 7 between 4 tips and mass spectrograph injection port 9,
The funnel-form minute sample carrier 7 is located on the bracket 6.
7 central point of funnel-form minute sample carrier and 9 distance S of mass spectrum injection port1, the miniature sample of funnel-form
7 central point of product carrier and 4 distance S of the nozzle needle (capillary tip)2, wherein S1/S2=3~3.2:5~5.1.
Embodiment 4
A kind of high-throughput nano upgrading Electrospray Ionization Mass Spectrometry device based on miniature funnel-form sample holder array, packet
It includes: electrospray device, mass spectrograph, funnel-form minute sample carrier (micro- funnel) 7, bracket (sample bearing plate) 6；In the electricity
Spraying capillary (capillary nozzle needle) is provided with funnel-form minute sample carrier 7 between 4 tips and mass spectrograph injection port 9,
The funnel-form minute sample carrier 7 is located on the bracket 6.
The diameter in 7 aperture of funnel-form minute sample carrier is less than < 200 μm.
Embodiment 5
A kind of high-throughput nano upgrading Electrospray Ionization Mass Spectrometry device based on miniature funnel-form sample holder array, packet
It includes: electrospray device, mass spectrograph, funnel-form minute sample carrier (micro- funnel) 7, bracket (sample bearing plate) 6；In the electricity
Spraying capillary (capillary nozzle needle) is provided with funnel-form minute sample carrier 7 between 4 tips and mass spectrograph injection port 9,
The funnel-form minute sample carrier 7 is located on the bracket 6.
The axial line of the funnel-form minute sample carrier 7 and the center line of mass spectrograph injection port 9 are located at same straight line
On.
Embodiment 6
A kind of high-throughput nano upgrading Electrospray Ionization Mass Spectrometry device based on miniature funnel-form sample holder array, packet
It includes: electrospray device, mass spectrograph, funnel-form minute sample carrier (micro- funnel) 7, bracket (sample bearing plate) 6；In the electricity
Spraying capillary (capillary nozzle needle) is provided with funnel-form minute sample carrier 7 between 4 tips and mass spectrograph injection port 9,
The funnel-form minute sample carrier 7 is located on the bracket 6.
The aperture highlight of the funnel-form minute sample carrier 7 is located at 9 side of mass spectrograph injection port.
Embodiment 7
A kind of high-throughput nano upgrading Electrospray Ionization Mass Spectrometry device based on miniature funnel-form sample holder array, packet
It includes: electrospray device, mass spectrograph, funnel-form minute sample carrier (micro- funnel) 7, bracket (sample bearing plate) 6；In the electricity
Spraying capillary (capillary nozzle needle) is provided with funnel-form minute sample carrier 7 between 4 tips and mass spectrograph injection port 9,
The funnel-form minute sample carrier 7 is located on the bracket 6.
The sample volume of the funnel-form minute sample carrier 7 is 50~60nL.
Embodiment 8
A kind of high-throughput nano upgrading Electrospray Ionization Mass Spectrometry device based on miniature funnel-form sample holder array, packet
It includes: electrospray device, mass spectrograph, funnel-form minute sample carrier array, bracket (sample bearing plate) 6；In the electron spray
Capillary (capillary nozzle needle) funnel-form minute sample carrier array, institute are provided between 4 tips and mass spectrograph injection port 9
Funnel-form minute sample carrier array is stated to be located on the bracket 6；
Wherein, the funnel-form minute sample carrier array in a manner of annular array by being evenly spaced in same plane
On the miniature funnel-form sample holder 7 form.
Embodiment 9
A kind of high-throughput nano upgrading Electrospray Ionization Mass Spectrometry device based on miniature funnel-form sample holder array, packet
It includes: electrospray device, mass spectrograph, funnel-form minute sample carrier array, bracket (sample bearing plate) 6；In the electron spray
Capillary (capillary nozzle needle) funnel-form minute sample carrier array, institute are provided between 4 tips and mass spectrograph injection port 9
Funnel-form minute sample carrier array is stated to be located on the bracket 6；
Funnel-form minute sample carrier array center point and 9 distance S of mass spectrum injection port1, the funnel-form it is micro-
Type sample holder array center point and 4 distance S of the nozzle needle (capillary tip)2, wherein S1/S2=3~3.2:5~
5.1。
Embodiment 10
A kind of high-throughput nano upgrading Electrospray Ionization Mass Spectrometry device based on miniature funnel-form sample holder array, packet
It includes: electrospray device, mass spectrograph, funnel-form minute sample carrier array, bracket (sample bearing plate) 6；In the electron spray
Capillary (capillary nozzle needle) funnel-form minute sample carrier array, institute are provided between 4 tips and mass spectrograph injection port 9
Funnel-form minute sample carrier array is stated to be located on the bracket 6；
The diameter in each aperture is smaller than < 200 μm in the funnel-form minute sample carrier array.
Embodiment 11
A kind of high-throughput nano upgrading Electrospray Ionization Mass Spectrometry device based on miniature funnel-form sample holder array, packet
It includes: electrospray device, mass spectrograph, funnel-form minute sample carrier array, bracket (sample bearing plate) 6；In the electron spray
Capillary (capillary nozzle needle) funnel-form minute sample carrier array, institute are provided between 4 tips and mass spectrograph injection port 9
Funnel-form minute sample carrier array is stated to be located on the bracket 6；
The axial line of the funnel-form minute sample carrier array and the center line of mass spectrograph injection port 9 are located at always
On line.
Embodiment 12
A kind of high-throughput nano upgrading Electrospray Ionization Mass Spectrometry device based on miniature funnel-form sample holder array, packet
It includes: electrospray device, mass spectrograph, funnel-form minute sample carrier array, bracket (sample bearing plate) 6；In the electron spray
Capillary (capillary nozzle needle) funnel-form minute sample carrier array, institute are provided between 4 tips and mass spectrograph injection port 9
Funnel-form minute sample carrier array is stated to be located on the bracket 6；
Each aperture highlight of the funnel-form minute sample carrier array is all located at 9 side of mass spectrograph injection port.
Embodiment 13
A kind of high-throughput nano upgrading Electrospray Ionization Mass Spectrometry device based on miniature funnel-form sample holder array, packet
It includes: electrospray device, mass spectrograph, funnel-form minute sample carrier array, bracket (sample bearing plate) 6；In the electron spray
Capillary (capillary nozzle needle) funnel-form minute sample carrier array, institute are provided between 4 tips and mass spectrograph injection port 9
Funnel-form minute sample carrier array is stated to be located on the bracket 6；
The sample volume of each micro- funnel 7 is all 50~60nL in the funnel-form minute sample carrier array.
Embodiment 14
A kind of miniature funnel-form sample holder for high-throughput nano upgrading Electrospray Ionization Mass Spectrometry, the funnel-form are micro-
Type sample holder 7 is funnel-form, is set to high-throughput nano by bracket (sample bearing plate) 6 and upgrades Electrospray Ionization Mass Spectrometry dress
The capillary (capillary nozzle needle) for the electron spray set is between 4 tips and mass spectrograph injection port 9.
Embodiment 15
A kind of miniature funnel-form sample holder for high-throughput nano upgrading Electrospray Ionization Mass Spectrometry, the funnel-form are micro-
Type sample holder 7 is funnel-form, is set to high-throughput nano by bracket (sample bearing plate) 6 and upgrades Electrospray Ionization Mass Spectrometry dress
The capillary (capillary nozzle needle) for the electron spray set is between 4 tips and mass spectrograph injection port 9.
The diameter in 7 aperture of funnel-form minute sample carrier is less than < 200 μm；
Embodiment 16
A kind of miniature funnel-form sample holder for high-throughput nano upgrading Electrospray Ionization Mass Spectrometry, the funnel-form are micro-
Type sample holder 7 is funnel-form, is set to high-throughput nano by bracket (sample bearing plate) 6 and upgrades Electrospray Ionization Mass Spectrometry dress
The capillary (capillary nozzle needle) for the electron spray set is between 4 tips and mass spectrograph injection port 9.
7 central point of funnel-form minute sample carrier and 9 distance S of mass spectrum injection port1, the miniature sample of funnel-form
7 central point of product carrier and 4 distance S of the nozzle needle (capillary tip)2, wherein S1/S2=3~3.2:5~5.1.
Embodiment 17
A kind of preparing instrument of the miniature funnel-form sample holder for high-throughput nano upgrading Electrospray Ionization Mass Spectrometry, packet
It includes: horizontally movable platform I, membrane support (array bracket) d, vertically moving platform II, punching needle c, stepper motor b, f
And controller, the membrane support d are mounted on the platform I, the top of the platform I is provided with the platform II, described
The punching needle c is provided on platform II, the punching needle c-axis heart line intersects with the platform I and perpendicular to the platform I；
When work, horizontal and vertical movement is carried out by described stepper motor b, f and controller control platform I and platform II respectively.
Embodiment 18
A kind of preparing instrument of the miniature funnel-form sample holder for high-throughput nano upgrading Electrospray Ionization Mass Spectrometry, packet
It includes: horizontally movable platform I, membrane support (array bracket) d, vertically moving platform II, punching needle c, stepper motor b, f
And controller, the membrane support d are mounted on the platform I, the top of the platform I is provided with the platform II, described
The punching needle c is provided on platform II, the punching needle c-axis heart line intersects with the platform I and perpendicular to the platform I；
When work, horizontal and vertical movement is carried out by described stepper motor b, f and controller control platform I and platform II respectively.
The bottom of the membrane support d is additionally provided with hollow metal tube (thimble) e.
Embodiment 19
A kind of preparation method of miniature funnel-form sample holder, comprising:
1) film substrate is fixed on membrane support d, is mounted directly on platform I；Punching needle c is mounted on platform II；
2) movement for passing through controller control platform I, platform II, realizes the separation of micro- funnel and the punching press of punching needle c
Depth regulation；
3) hollow metal tube (thimble) e is set in the bottom of film substrate, generates funnel-form sample holder to dock.
Embodiment 20
A kind of high-throughput nano upgrading Electrospray Ionization Mass Spectrometry device detection based on miniature funnel-form sample holder array
Method, comprising:
1) before acquiring mass spectrum, after sample is diluted or handled, sample is placed in funnel-form minute sample using sample introduction needle
It is to be analyzed in carrier；
2) funnel-form minute sample carrier is docked with mass spectrograph；
3) the sample acquisition and analysis carried out using mass spectrograph.
Embodiment 21
A kind of high-throughput nano upgrading Electrospray Ionization Mass Spectrometry device detection based on miniature funnel-form sample holder array
Method, comprising:
1) before acquiring mass spectrum, after sample is diluted or handled, sample is placed in funnel-form minute sample using sample introduction needle
It is to be analyzed in carrier；
2) funnel-form minute sample carrier is docked with mass spectrograph；
3) the sample acquisition and analysis carried out using mass spectrograph.
Wherein, the sample volume of the sample is 50~60nL.
Finally it should be noted that the foregoing is only a preferred embodiment of the present invention, it is not limited to this hair
It is bright, although the present invention is described in detail referring to the foregoing embodiments, for those skilled in the art, still
It can modify to technical solution documented by previous embodiment, or part is equivalently replaced.It is all in this hair
Within bright spirit and principle, any modification, equivalent replacement, improvement and so on should be included in protection scope of the present invention
Within.Above-mentioned, although the foregoing specific embodiments of the present invention is described with reference to the accompanying drawings, not to the scope of the present invention
Limitation, those skilled in the art should understand that, based on the technical solutions of the present invention, those skilled in the art are not required to
Make the creative labor the various modifications or changes that can be made still within protection scope of the present invention.
Claims (10)
1. a kind of high-throughput nano based on miniature funnel-form sample holder array upgrades Electrospray Ionization Mass Spectrometry device, comprising:
Electrospray device, mass spectrograph, miniature funnel-form sample holder array, bracket, which is characterized in that in the electrospray device
Miniature funnel-form sample holder array, the miniature funnel-form sample are provided between capillary tip and mass spectrograph injection port
Carrier array is located on the bracket；
Wherein, the miniature funnel-form sample holder array in a manner of annular array by being evenly spaced on same plane
Miniature funnel-form sample holder composition；
The miniature funnel-form sample holder is the flexible tacky film for being provided with single micropore；
The miniature funnel-form sample holder array is the flexible tacky film for being provided with multiple micropores；
The micropore is microcosmic funnel-shaped；
Solvent is loaded in the capillary, the sample load is in the micropore of flexible tacky film.
2. device as described in claim 1, which is characterized in that the miniature funnel-form sample holder central point and mass spectrograph
The distance S of injection port1, the miniature funnel-form sample holder central point and the capillary tip distance S2, wherein S1/
S2=3~3.2:5~5.1.
3. device as described in claim 1, which is characterized in that diameter < 200 in the miniature funnel-form sample holder aperture
μm。
4. device as described in claim 1, which is characterized in that the axial line and mass spectrum of the miniature funnel-form sample holder
The center line of instrument injection port is located along the same line.
5. device as described in claim 1, which is characterized in that the aperture highlight position of the miniature funnel-form sample holder
In mass spectrograph injection port side；
The sample volume of the miniature funnel-form sample holder is 50~60nL.
6. a kind of miniature funnel-form sample holder for high-throughput nano upgrading Electrospray Ionization Mass Spectrometry, which is characterized in that institute
Stating funnel-form minute sample carrier is funnel-form, is set to high-throughput nano by bracket and upgrades Electrospray Ionization Mass Spectrometry device
Between the capillary tip and mass spectrograph injection port of electron spray；
The miniature funnel-form sample holder is the flexible tacky film for being provided with single micropore；
The micropore is microcosmic funnel-shaped；
Solvent is loaded in the capillary, the sample load is in the micropore of flexible tacky film.
7. carrier as claimed in claim 6, which is characterized in that the diameter in the miniature funnel-form sample holder aperture <
200μm；
The miniature funnel-form sample holder central point and mass spectrum injection port distance S1, the miniature funnel-form sample carrying
Device central point and the capillary tip distance S2, wherein S1/S2=3~3.2:5~5.1.
8. the preparing instrument of miniature funnel-form sample holder described in claim 6 or 7 characterized by comprising horizontal can move
Dynamic platform I, membrane support, vertically moving platform II, punching needle, stepper motor and controller, which is characterized in that described
Membrane support is mounted on the platform I, and the top of the platform I is provided with the platform II, is arranged on the platform II
Punching needle is stated, the punching needle axial line intersects with the platform I and perpendicular to the platform I；When work, pass through the stepping
Motor and controller control platform I and platform II carry out horizontal and vertical movement respectively.
9. the method for preparing miniature funnel-form sample holder using preparing instrument described in claim 8 characterized by comprising
1) film substrate is fixed on membrane support, is mounted directly on platform I；Punching needle is mounted on platform II；
2) movement for passing through controller control platform I, platform II, realizes the separation of miniature funnel and the press depth of punching needle
Regulation；
3) hollow metal tube is set in the bottom of film substrate, generates miniature funnel-form sample holder to dock.
10. a kind of high-throughput nano upgrading based on the described in any item miniature funnel-form sample holder arrays of claim 1-5
The detection method of Electrospray Ionization Mass Spectrometry device characterized by comprising
1) before acquiring mass spectrum, after sample is diluted or handled, sample is placed in miniature funnel-form sample using sample introduction needle and is carried
It is to be analyzed in device；
2) miniature funnel-form sample holder is docked with mass spectrograph；
3) the sample acquisition and analysis carried out using mass spectrograph.
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| CN109541093B (en) * | 2018-10-29 | 2019-08-27 | 山东省分析测试中心 | A kind of pretreatment of nanoliter level mass spectrum sample and sample introduction combined apparatus and its method |
| CN110021516A (en) * | 2019-04-09 | 2019-07-16 | 武汉大学 | A kind of mass spectrometer for high-throughput online photochemical reaction research |
| CN110988102B (en) * | 2019-12-10 | 2022-09-30 | 北京工业大学 | Visual sheath-flow-free single-cell mass spectrometry system |
| CN111413172A (en) * | 2020-04-17 | 2020-07-14 | 山东省分析测试中心 | In-situ enzymolysis-direct mass spectrometry analysis system and analysis method |
| CN114361005A (en) * | 2020-10-13 | 2022-04-15 | 中国科学院大连化学物理研究所 | Mass spectrometer interface device for nanoliter electrospray ionization |
| CN112630289B (en) * | 2020-12-08 | 2021-11-30 | 广东省科学院测试分析研究所(中国广州分析测试中心) | Nanoliter spray-FTICR-MS analysis method and device for dissolved organic matters in environmental solid sample |
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| CN105474352A (en) * | 2013-09-05 | 2016-04-06 | 株式会社日立高新技术 | Hybrid ion source and mass spectrometric device |
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| CN105474352A (en) * | 2013-09-05 | 2016-04-06 | 株式会社日立高新技术 | Hybrid ion source and mass spectrometric device |
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