CN106338546A - High-spatial-resolution imaging mass spectrometry device - Google Patents

High-spatial-resolution imaging mass spectrometry device Download PDF

Info

Publication number
CN106338546A
CN106338546A CN201610687230.9A CN201610687230A CN106338546A CN 106338546 A CN106338546 A CN 106338546A CN 201610687230 A CN201610687230 A CN 201610687230A CN 106338546 A CN106338546 A CN 106338546A
Authority
CN
China
Prior art keywords
sample
precision
probe
scanning
mass spectrum
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201610687230.9A
Other languages
Chinese (zh)
Inventor
顾忠泽
赵祥伟
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Southeast University
Original Assignee
Southeast University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Southeast University filed Critical Southeast University
Priority to CN201610687230.9A priority Critical patent/CN106338546A/en
Publication of CN106338546A publication Critical patent/CN106338546A/en
Pending legal-status Critical Current

Links

Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/62Investigating 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
    • G01N27/64Investigating 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 using wave or particle radiation to ionise a gas, e.g. in an ionisation chamber
    • HELECTRICITY
    • H01ELECTRIC ELEMENTS
    • H01JELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00Particle spectrometers or separator tubes
    • H01J49/02Details
    • H01J49/10Ion sources; Ion guns
    • H01J49/16Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission
    • H01J49/161Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission using photoionisation, e.g. by laser
    • H01J49/164Laser desorption/ionisation, e.g. matrix-assisted laser desorption/ionisation [MALDI]

Abstract

The invention discloses a high-spatial-resolution imaging mass spectrometry device. A first high-precision three-dimensional probe scanning platform (2) and a second high-precision three-dimensional probe scanning platform (3) are arranged on a high-precision three-dimensional electric sample platform (1). A sample (9) is positioned between the first high-precision three-dimensional probe scanning platform (2) and the second high-precision three-dimensional probe scanning platform (3). A forward object lens (5) is positioned above the sample (9). An inverted object lens (4) is positioned below the sample (9). A scanning probe (6) is positioned at one side of the sample (9) and is connected to a light source (8) through an optical fiber (7). A capillary syringe (10) is positioned at the other side of the sample (9) and is connected to a mass spectrum (11). By the device of the invention, high-spatial-resolution multi-modal imaging can be conveniently realized. The device is expected to be widely used for high-resolution imaging analysis of single cells and tissues, etc.

Description

A kind of high-space resolution mass spectrum imaging device
Technical field
The present invention relates to super diffraction limit focusing, mass spectrum imaging and multi-modality imaging field, specifically a kind of utilization are scanned Probe and opposed objective system build mass ion source, by scanning probe, exciting light is focused on sub-wavelength scope and sample is entered Row excites, and realizes the mass spectrum imaging of high-space resolution by the high accuracy scanning of example platform.
Background technology
Earliest mass spectrum imaging technology occurs in 1997, using substance assistant laser desorpted ionized (maldi, matrix Assisted laser desorption ionization) realize mass spectroscopy molecular imaging.This technology pass through by maldi mass spectrum from Sub- scanning technique is combined with professional image software, Direct Analysis biological tissue section, produces and is arbitrarily designated mass-to-charge ratio (m/z) The two-dimensional density map of compound, carries out high flux, complete to the composition of compound, relative abundance and distribution situation in tissue Face, quickly analyze, drug candidate in the spatial distribution of potential biomarker that obtained and destination organization can be passed through Distributed intelligence, to carry out the discovery of biomarker and the monitoring of compound.Later, SIMS (sims, Secondary ion mass spectrometry) imaging method appearance, complete scan, three-dimensional imaging can be carried out to sample. Although sims can reach several nanometers of resolution ratio, sims needs high vacuum condition, and the sample composition to analysis There is certain restriction.The development of micro & nano technology, using substrate surface assisted laser desorption attached/ionization (surface- Assisted laser desorption/ionization, saldi) research get more and more, for example scripps research institute carries Nanostructure-initiator mass spectrometry (nims) going out, the vertes of George Washington University carry Laser-induced silicon microcolumn arrays (lisma) mass spectrum going out, silicon nanopost Array (napa) auxiliary desorption/ionization massspectrum etc..These methods mainly make use of the phase interaction of light and silicon nanostructure substrate With ablation (ablation) being carried out with the sample of local area especially by the regulation and control of light energy distribution, and passing through nanometer Electro transfer between structural substrates and sample to be realized with ionizing.But the spot size of laser is micro- used by these methods Rice magnitude, spatial resolution typically in 5 microns, is only used for imaging of tissue in biomedicine, individual cells etc. is needed The sample of high spatial resolution is still helpless (except big egg cell such as Ostrich egg, egg etc.).Therefore mass spectrum imaging divides The raising of resolution is a difficult point and question of common concern, and the mass spectrum imaging that submicron order is differentiated will make single celled non-marked Imaging analysis are realized breaking through, and open more wide space for the development of mass spectrum imaging and single cell analysis.
Content of the invention
Technical problem: in order to improve sample mass spectrum imaging spatial resolution, obtain more rich sample Information in Mass Spectra, this Bright provide a kind of equipment realizing high-space resolution mass spectrum imaging, need high vacuum to solve existing mass spectrum imaging method, point Resolution is low, the problems such as need matrix and image mode single.
Technical scheme: a kind of high-space resolution mass spectrum imaging device of the present invention mainly includes the electronic sample of high-precision three-dimensional Platform, the first high-precision three-dimensional probe scanning platform and the second high-precision three-dimensional probe scanning platform, are inverted object lens, positive glove Mirror, scans probe, optical fiber, light source, capillary syring and mass spectrum;Wherein, the electronic example platform of high-precision three-dimensional is provided with first High-precision three-dimensional probe scanning platform and the second high-precision three-dimensional probe scanning platform, sample is located at the first high-precision three-dimensional probe Between scanning platform and the second high-precision three-dimensional probe scanning platform, positive glove mirror is located at the top of sample, is inverted object lens and is located at The bottom of sample, scanning probe is located at the side of sample, is connected to light source by optical fiber;Capillary syring is located at the opposite side of sample, It is connected with mass spectrum.
Described mass spectrum, its ion gun ionizes (maldi) ion gun for matrix assisted laser desorption ionization or surface is auxiliary Help laser desorption ionisation (saldi) ion gun, exciting light excites sample by scanning probe, and what scanning probe sent excites Light focuses in the range of sub-wavelength through near field optic structure or super surface, excites sample.
Described first high-precision three-dimensional probe scanning platform and the second high-precision three-dimensional probe scanning platform are located at high accuracy On three-D electric example platform, it is in relative position;During mass spectrum imaging, will be swept by high-precision three-dimensional probe scanning platform Retouch probe and navigate to sample surfaces, capillary syring is pin-pointed to scan probe by the second high-precision three-dimensional probe scanning platform The sample that tip location absorption excites, carries out point by point scanning by the electronic example platform of high-precision three-dimensional to sample, and exciting light swashs The sample sending enters mass spectrum by capillary syring.
The electronic example platform of described high-precision three-dimensional carries transparent sample pond, by inversion object lens, sample can be seen Examine, view mode is fluorescence, details in a play not acted out on stage, but told through dialogues, difference, dic, total internal reflection fluorescent, super-resolution fluorescence or light field.
Described positive glove mirror be located at sample top, by positive glove mirror, sample is observed, view mode be fluorescence, Details in a play not acted out on stage, but told through dialogues, dic, difference or light field;By positive glove mirror to scanning probe observe, the positioning of sub-scanning probe and Scanning to sample.
Described light source is nanosecond, psec or femtosecond pulse light source, wave-length coverage ultraviolet to near-infrared 150nm~ 3000nm, exciting light enters scanning probe by fibre-optic waveguide and excites to sample, or by positive glove mirror or inversion Object lens far field projects and on scanning probe, sample is excited.
Described scanning probe carries out afm or scanning near-field imaging by tuning fork feedback to sample topography, scans probe Or complete scan-type electrochemical imaging by being coupled electrochemical workstation.
The described spectral signal being inverted in object lens and positive glove mirror pair connection spectrometer collection sample photoexcitation process, or synchronous Realize spectroscopy imaging.
The ion gun of described mass spectrum imaging is atmospheric pressure ionizationion, or vacuum ionic source, high accuracy during vacuum ionic source Three-D electric example platform, the first high-precision three-dimensional probe scanning platform, the second high-precision three-dimensional probe scanning platform, scanning are visited Pin is located in vacuum chamber;Auxiliary electric field or heating are applied on capillary syring with the transport of assisting ion;Excitation goes out Sample is directly entered mass spectrum by capillary syring, or enters secondary ion before mass spectrum, and the mode of secondary ion can be Electron spray or laser ionization.
Scanning probe has super surface or near field optic structure, and light can be carried out with sub-wavelength focusing, sample excitation institute Focused in the range of sub-wavelength by scanning probe with LASER Light Source, realize the high-space resolution of sample is excited.Meanwhile, scan Probe can also carry out afm imaging or electrochemistry imaging to the pattern of sample surfaces.Capillary syring is visited by high-precision three-dimensional What pin scanning platform was pin-pointed to probe tips excites site, and the sample exciting suction mass spectrum is carried out further ion Change or mass-to-charge ratio analysis.It is inverted object lens and positive glove mirror constitutes doublet module, the convenient upper and lower surface from sample Observe sample and the positioning of scanning probe, simultaneously can also be during doublet excites sample or collects sample excitation Spectral signal.
Beneficial effect: compared with existing mass spectrum imaging device, apparatus of the present invention can utilize near field optical scanning probe Or the scanning probe with super surface texture is realized the sub-wavelength laser desorption of sample and is echoed ionization;This device high accuracy three Tie up electronic example platform and high-precision three-dimensional probe scanning platform can control respectively and be accurately positioned, can be to sample from individual Carry out accurate three-dimensional scanning, greatly reduce the operation during mass spectrum imaging and control complexity;The doublet system of device Not only ensure that flexible and changeable excitation mode, such as far field excitation and near field excite with optical scanning probe can use, In addition also ensure that sample and probe, the monitoring convenience during capillary syring adjustment, also assures that acquisition optics letter simultaneously The multichannel of breath and multi-pass, that is, acquisition of information convenience.This device can very easily with light spectrum image-forming and electrochemistry Imaging system be coupled, such that it is able to realize the multi-modality imaging to sample on a device it is ensured that acquisition of information comprehensive Property.Because this device has double scanning probe platforms and doublet system, therefore the opening of system very strong in that context it may be convenient to root Instrument is set according to application demand, using flexible.
Brief description
Fig. 1 is the general structure schematic diagram of apparatus of the present invention.
Specific embodiment
Below in conjunction with the accompanying drawings, the present invention is elaborated:
As shown in figure 1, being the general structure schematic diagram of apparatus of the present invention, described device includes the electronic sample of high-precision three-dimensional Platform 1, the first high-precision three-dimensional probe scanning platform 2 and the second high-precision three-dimensional probe scanning platform 3, are inverted object lens 4, just put Object lens 5, scan probe 6, optical fiber 7, light source 8, capillary syring 10 and mass spectrum 11.It is inverted object lens 4 to be located on an inverted microscope, Positive glove mirror 5 is just being put on microscope positioned at one, is just putting microscope and is passing through shelf frame directly over inverted microscope, two object lens In adjusting by light path, share same optical axis.The electronic example platform of high-precision three-dimensional 1 is arranged on inverted microscope, scans model Enclose for 80 μm of 80 μm of x, then the first high-precision three-dimensional probe scanning platform 2 and the second high-precision three-dimensional probe are installed on commenting Scanning platform 3, and make both relatively, the first high-precision three-dimensional probe scanning platform 2 and the second high-precision three-dimensional probe scanning are put down Tuning fork ultramagnifier is respectively fixed with platform 3 and is connected with scanning probe 6 and capillary syring 10;First high-precision three-dimensional probe is swept Retouch platform 2 and the second high-precision three-dimensional probe scanning platform 3 sweep limits is all 30 μm of 30 μm of x.355nm pulsed laser light source Pulsewidth 5ns, single pulse energy 100mj passes through Single-Mode Fiber Coupling near field optical scanning probe 6, the tip of probe have containing 100nm micropore buphthalmos lens arrangement, exciting light is focused on sample 9 by buphthalmos lens arrangement, excites the size of focus to exist 100nm about.
When carrying out mass spectrum imaging, the section of cell is placed on the electronic example platform of high-precision three-dimensional 1, passes through The position of 60 times of inversion object lens 4 observation of cell, observes position and the capillary syring 10 of scanning probe 6 by 50 times of positive glove mirrors 5 Position, adjust controller, the top of motion scan probe 6 to sample, open afm pattern, surface topography is carried out to sample and sweeps Retouch, and position scanning probe 6 to a starting point on cell section surface.Under the observation of positive glove mirror 5, mobile most advanced and sophisticated 10 μm Internal diameter capillary syring 10 is to the vicinity scanning probe 6, and makes capillary syring 10 close to 2 μm of probe 6 probe distance of scanning.Open Open LASER Light Source 8 pulse, sample is excited, simultaneously synchronous mass spectrographic analysis, obtains the mass spectrogram of this point.Control high Precision three-D electric example platform 1 moves 200nm, and synchronous laser pulse and mass spectrometry detection, obtains the mass spectrogram of second point. Finally by the mass spectrogram scanning some sites, by data processing software, reconstruct mass spectrum imaging figure.
When carrying out Raman spectrum with the imaging of mass spectrum bimodal, the section of cell is placed on high-precision three-dimensional electronic On example platform 1, by the position of 60 times of inversion object lens 4 observation of cell, observe scanning probe 6 by 50 times of positive glove mirrors 5 Position and the position of capillary syring 10, adjust controller, the top of motion scan probe 6 to sample, open afm pattern, to sample Product carry out surface topography scanning, and position scanning probe 6 to a starting point on cell section surface.Sight in positive glove mirror 5 Examine down, the vicinity of mobile most advanced and sophisticated 10 μm of internal diameter capillary syrings 10 to scanning probe 6, and make capillary syring 10 close to scanning probe At 62 μm of probe distances.Raman Laser Scanning Confocal Microscope is connected with positive glove mirror 5.First pass through positive glove mirror and excite scanning probe 6 The Raman spectrum of tip location sample, then, opens LASER Light Source 8 pulse, sample is excited, simultaneously synchronous mass spectrum Signals collecting, obtains the mass spectrogram of this point.Control the electronic example platform of high-precision three-dimensional 1 to move 200nm, gather Raman spectrum Afterwards, synchronous laser pulse and mass spectrometry detection, obtains Raman spectrum and the mass signal of second point.The like, complete to whole The scanning of individual sample, finally, by data processing software, reconstructs Raman spectral image and the mass spectrum imaging figure of sample.

Claims (9)

1. a kind of high-space resolution mass spectrum imaging device it is characterised in that: this device mainly includes the electronic sample of high-precision three-dimensional Platform (1), the first high-precision three-dimensional probe scanning platform (2) and the second high-precision three-dimensional probe scanning platform (3), are inverted object lens (4), positive glove mirror (5), scanning probe (6), optical fiber (7), light source (8), capillary syring (10) and mass spectrum (11);Wherein, in height Precision three-D electric example platform (1) is provided with the first high-precision three-dimensional probe scanning platform (2) and the second high-precision three-dimensional is visited Pin scanning platform (3), sample (9) is swept with the second high-precision three-dimensional probe positioned at the first high-precision three-dimensional probe scanning platform (2) Retouch between platform (3), positive glove mirror (5) is located at the top of sample (9), be inverted the bottom that object lens (4) are located at sample (9), scanning Probe (6) is located at the side of sample (9), is connected to light source (8) by optical fiber (7);Capillary syring (10) is located at the another of sample (9) Side, is connected with mass spectrum (11).
2. a kind of high-space resolution mass spectrum imaging device according to claim 1 it is characterised in that: described mass spectrum (11), its ion gun is mald ion gun or saldi ion gun, and exciting light passes through scanning probe (6) and excites sample (9), sweeps Retouch the exciting light that probe (6) sends to focus in the range of sub-wavelength through near field optic structure or super surface, excite sample (9).
3. a kind of high-space resolution mass spectrum imaging device according to claim 1 it is characterised in that described first high accuracy Three-dimensional probe scanning platform (2) is located at the electronic example platform of high-precision three-dimensional with the second high-precision three-dimensional probe scanning platform (3) (1), on, it is in relative position;During mass spectrum imaging, probe (6) will be scanned by high-precision three-dimensional probe scanning platform (2) Navigate to sample surfaces, capillary syring (10) is pin-pointed to scanning by the second high-precision three-dimensional probe scanning platform (3) and visits The sample that the absorption of pin (6) tip location excites, carries out pointwise by the electronic example platform of high-precision three-dimensional (1) to sample (9) and sweeps Retouch, the sample that excitation goes out enters mass spectrum (11) by capillary syring (10).
4. a kind of high-space resolution mass spectrum imaging device according to claim 1 it is characterised in that: described high-precision three-dimensional Electronic example platform (1) carries transparent sample pond, by being inverted object lens (4), sample (9) can be observed, view mode is Fluorescence, details in a play not acted out on stage, but told through dialogues, difference, dic, total internal reflection fluorescent, super-resolution fluorescence or light field.
5. a kind of high-space resolution mass spectrum imaging device according to claim 1 it is characterised in that: described positive glove mirror (5) be located at sample (9) top, by positive glove mirror (5), sample (9) is observed, view mode be fluorescence, details in a play not acted out on stage, but told through dialogues, Dic, difference or light field;By positive glove mirror (5), scanning probe (6) is observed, the positioning of sub-scanning probe (6) And the scanning to sample (9).
6. a kind of high-space resolution mass spectrum imaging device according to claim 1 it is characterised in that: described light source (8) is Nanosecond, psec or femtosecond pulse light source, wave-length coverage is passed through in ultraviolet to near-infrared 150nm~3000nm, exciting light Optical fiber (7) waveguide enters scanning probe (6) and excites to sample (9), or by positive glove mirror (5) or is inverted object lens (4) far field projects and in scanning probe (6), sample (9) is excited.
7. a kind of high-space resolution mass spectrum imaging device according to claim 1 it is characterised in that: described scanning probe (6) afm or scanning near-field imaging are carried out by tuning fork feedback to sample (9) pattern, scan probe (6) or by being coupled electricity Chem workstation completes scan-type electrochemical imaging.
8. a kind of high-space resolution mass spectrum imaging device according to claim 1 it is characterised in that: described inversion object lens (4) spectral signal and in positive glove mirror (5) coupling spectrometer collection sample (9) photoexcitation process, or synchronously realize spectroscopy Imaging.
9. a kind of high-space resolution mass spectrum imaging device according to claim 2 it is characterised in that: described mass spectrum imaging Ion gun is atmospheric pressure ionizationion, or vacuum ionic source, the electronic example platform of high-precision three-dimensional (1) during vacuum ionic source, the One high-precision three-dimensional probe scanning platform (2), the second high-precision three-dimensional probe scanning platform (3), scanning probe (6) are located at vacuum In chamber;Capillary syring (10) is upper to apply auxiliary electric field or heating with the transport of assisting ion;The sample that excitation goes out leads to Cross capillary syring (10) and be directly entered mass spectrum (11), or enter secondary ion before mass spectrum, the mode of secondary ion is permissible It is electron spray or laser ionization.
CN201610687230.9A 2016-08-18 2016-08-18 High-spatial-resolution imaging mass spectrometry device Pending CN106338546A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201610687230.9A CN106338546A (en) 2016-08-18 2016-08-18 High-spatial-resolution imaging mass spectrometry device

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201610687230.9A CN106338546A (en) 2016-08-18 2016-08-18 High-spatial-resolution imaging mass spectrometry device

Publications (1)

Publication Number Publication Date
CN106338546A true CN106338546A (en) 2017-01-18

Family

ID=57825690

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201610687230.9A Pending CN106338546A (en) 2016-08-18 2016-08-18 High-spatial-resolution imaging mass spectrometry device

Country Status (1)

Country Link
CN (1) CN106338546A (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108133879A (en) * 2017-12-21 2018-06-08 厦门大学 The near field ion source obtained in situ simultaneously for micro/nano-scale pattern and chemical information
CN109374928A (en) * 2018-09-12 2019-02-22 东南大学 It is a kind of based on equal near-field scanning probe from focusing
CN113768472A (en) * 2021-11-10 2021-12-10 华中科技大学 Three-dimensional image acquisition device with fluorescent marker and method

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004264043A (en) * 2003-01-31 2004-09-24 National Institute Of Advanced Industrial & Technology Ionizing device, and micro-area analyzer
CN1685195A (en) * 2002-07-24 2005-10-19 Jpk仪器股份公司 Method for locally highly resolved, mass-spectroscopic characterization of surfaces using scanning probe technology
CN101949848A (en) * 2010-09-08 2011-01-19 华中科技大学 Photoactivation positioning microscopic imaging system based on micronano optical fiber evanescent field illuminator
CN102339721A (en) * 2011-09-28 2012-02-01 厦门大学 Near-field needle-point reinforced photoionization ion source
US20130026359A1 (en) * 2010-04-15 2013-01-31 Shimadzu Research Laboratory (Shanghai) Co., Ltd. Method and apparatus for generating and analyzing ions
CN102914531A (en) * 2012-10-22 2013-02-06 上海大学 System for detecting internal components and environment of cell by using SERS (Surface Enhanced Raman Scattering) nano optical fiber probe
CN103413748A (en) * 2013-08-13 2013-11-27 中国科学院化学研究所 Multi-channel optical imaging laser ionization source
CN104749160A (en) * 2015-03-06 2015-07-01 华南师范大学 Parallel double-tip enhanced Raman spectrum scanning imaging method

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1685195A (en) * 2002-07-24 2005-10-19 Jpk仪器股份公司 Method for locally highly resolved, mass-spectroscopic characterization of surfaces using scanning probe technology
JP2004264043A (en) * 2003-01-31 2004-09-24 National Institute Of Advanced Industrial & Technology Ionizing device, and micro-area analyzer
US20130026359A1 (en) * 2010-04-15 2013-01-31 Shimadzu Research Laboratory (Shanghai) Co., Ltd. Method and apparatus for generating and analyzing ions
CN101949848A (en) * 2010-09-08 2011-01-19 华中科技大学 Photoactivation positioning microscopic imaging system based on micronano optical fiber evanescent field illuminator
CN102339721A (en) * 2011-09-28 2012-02-01 厦门大学 Near-field needle-point reinforced photoionization ion source
CN102914531A (en) * 2012-10-22 2013-02-06 上海大学 System for detecting internal components and environment of cell by using SERS (Surface Enhanced Raman Scattering) nano optical fiber probe
CN103413748A (en) * 2013-08-13 2013-11-27 中国科学院化学研究所 Multi-channel optical imaging laser ionization source
CN104749160A (en) * 2015-03-06 2015-07-01 华南师范大学 Parallel double-tip enhanced Raman spectrum scanning imaging method

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
JESSICA A. STOLEE ET AL.: "Observation of Subcellular Metabolite Gradients in Single Cells by Laser Ablation Electrospray Ionization Mass Spectrometry", 《ANGEWANDTE CHEMIE》 *
RAOUL STOCKLE ET AL.: "Nanoscale Atmospheric Pressure Laser Ablation-Mass Spectrometry", 《ANALYTICAL CHEMISTRY》 *
龚晓云等: "单细胞质谱分析方法研究进展", 《中国科学:化学》 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108133879A (en) * 2017-12-21 2018-06-08 厦门大学 The near field ion source obtained in situ simultaneously for micro/nano-scale pattern and chemical information
CN108133879B (en) * 2017-12-21 2020-04-03 厦门大学 Near-field ion source for simultaneous in-situ acquisition of micro-nano scale morphology and chemical information
CN109374928A (en) * 2018-09-12 2019-02-22 东南大学 It is a kind of based on equal near-field scanning probe from focusing
CN113768472A (en) * 2021-11-10 2021-12-10 华中科技大学 Three-dimensional image acquisition device with fluorescent marker and method

Similar Documents

Publication Publication Date Title
US20220065772A1 (en) Method and apparatus for enhanced photo-thermal imaging and spectroscopy
US10942116B2 (en) Method and apparatus for enhanced photo-thermal imaging and spectroscopy
US7735146B2 (en) Protein microscope
CN103743718B (en) The burnt microscopic Raman of copolymerization and Laser-induced Breakdown Spectroscopy coupling laser spectral analysis instrument
CN203606288U (en) Confocal micro-raman and laser-induced breakdown spectroscopy combined laser spectrum analysis meter
CN105136750A (en) Laser differential confocal LIBS, Raman spectrum-mass spectrum imaging method and Raman spectrum-mass spectrum imaging device
CN105241849A (en) Spectral pupil laser differential confocal LIBS, Raman spectrum-mass spectrum microscopic imaging method and Raman spectrum-mass spectrum microscopic imaging device
JP2823970B2 (en) Near-field scanning optical microscope
CN104697982B (en) High-space resolution laser differential confocal mass spectrum micro imaging method and device
CN106338546A (en) High-spatial-resolution imaging mass spectrometry device
CN105241850A (en) Biaxial laser differential confocal LIBS, Raman spectrum-mass spectrum microscopic imaging method and Raman spectrum-mass spectrum microscopic imaging device
CN101539457A (en) Miniature spectrometer based on MEMS micro lens array
CN104390943A (en) Microscopic imaging system capable of simultaneously obtaining appearance image and element distribution image
CN111044481A (en) Near-field microscope system and construction method thereof
CN105067570A (en) Dual-axis laser differential confocal LIBS (laser-induced breakdown spectroscopy), RS (Raman spectroscopy) and MS (mass spectrometry) imaging method and device
CN104697967A (en) High-spatial-resolution laser double-axis confocal spectrum-mass spectrum microimaging method and device
CN204269547U (en) A kind of micro imaging system simultaneously obtaining appearance images and Elemental redistribution image
US20230236112A1 (en) Method and apparatus for enhanced photo-thermal imaging and spectroscopy
Hong et al. Scanning near-field infrared microscope with a free electron laser illumination source
CN109187723A (en) Postposition is divided pupil differential confocal Raman spectra-mass spectrum micro imaging method and device
CN113533294B (en) Time domain, space domain and spectrum domain single molecule characterization device based on nanometer gap electrode pair
CN115406871A (en) System and method for imaging and ablating a sample
CN115421288A (en) Three-dimensional isotropic single-objective super-resolution imaging method and device based on high-order nonlinear fluorescence
CN109187501A (en) Postposition is divided pupil laser differential confocal LIBS spectrum micro imaging method and device
CN104698066A (en) High-spatial resolution laser splitting-pupil differential confocal spectrum-mass spectrometry microimaging method and device

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
RJ01 Rejection of invention patent application after publication
RJ01 Rejection of invention patent application after publication

Application publication date: 20170118