WO2003054915A1 - Target plate for mass spectometers and use thereof - Google Patents
Target plate for mass spectometers and use thereof Download PDFInfo
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- WO2003054915A1 WO2003054915A1 PCT/SE2002/002284 SE0202284W WO03054915A1 WO 2003054915 A1 WO2003054915 A1 WO 2003054915A1 SE 0202284 W SE0202284 W SE 0202284W WO 03054915 A1 WO03054915 A1 WO 03054915A1
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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
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
- B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
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- G—PHYSICS
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/416—Systems
- G01N27/447—Systems using electrophoresis
- G01N27/44756—Apparatus specially adapted therefor
- G01N27/44769—Continuous electrophoresis, i.e. the sample being continuously introduced, e.g. free flow electrophoresis [FFE]
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- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
- G01N35/028—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations having reaction cells in the form of microtitration plates
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- H—ELECTRICITY
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- 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
- H01J49/0409—Sample holders or containers
- H01J49/0418—Sample holders or containers for laser desorption, e.g. matrix-assisted laser desorption/ionisation [MALDI] plates or surface enhanced laser desorption/ionisation [SELDI] plates
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- B01L3/02—Burettes; Pipettes
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- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/24—Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry
Definitions
- the present invention relates to methods and devices for chemical analysis. More specifically it relates to methods and devices for preparation of small amounts of sample molecules, facilitating a subsequent analysis using e.g. matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS).
- MALDI-TOF MS matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry
- Mass spectrometry involving ionisation by matrix-assisted laser desorption (MALDI) has established itself as a standard procedure for the analysis of biosubstances with large molecules.
- time-of-flight mass spectrometers TOF-MS
- FT-ICR Fourier transform ion cyclotron resonance spectrometers
- quadrupole ion trap mass spectrometers in short: ion traps
- analyte molecules are present either in very diluted form in aqueous solutions, pure or mixed with organic solvents.
- these analytical solutions are very complex and contaminated with respect to the requirements of the analytical procedures, e.g., in the case of body fluids.
- Biopolymers comprise oligonucleotides (i.e. fragments of genetic material in various forms such as DNA or RNA), polysaccharides and proteins (the essential building blocks of the living world) as well as their special analogues and conjugates such as glycoproteins or lipoproteins, and peptides arising from the action of digestive enzymes.
- matrix substance for MALDI depends on the type of analyte molecule; more than a hundred different matrix substances are now known.
- One of the tasks of the matrix substances include to isolate the analyte molecules from each other wherever possible and bind them to the sample carrier plate, to transfer the molecules into the vapour phase by forming a vapour cloud during the laser bombardment, and ultimately to ionise the biomolecules by protonation or deprotonation, i.e., to add or remove one or more protons.
- protonation or deprotonation i.e., to add or remove one or more protons.
- a sample spot consisting of small matrix crystals and having the same size as that of the originally wetted surface area forms.
- the matrix crystals are usually not uniformly distributed throughout the formerly wetted area.
- crystals of the matrix start growing at the inner margin of the wetting surface on the metal plate. They then grow towards the interior of the wetting surface. They often form thin needle crystals, as is the case for example for the frequently used matrices 5- dihydroxybenzoic acid (DHB) or 3-hydroxypicolinic acid (HP A), which often stand out from the carrier plate at the interior of the spot.
- the centre of the spot is frequently empty or covered with fine crystals, although they often cannot be used for MALDI ionisation because of their high concentration of alkaline salts.
- the loading of the crystals with biomolecules is also very uneven. This type of loading therefore requires viewing the sample carrier surface during MALDI ionisation by a video microscope, which can be found in any commercially available mass spectrometer used for this type of analysis. Ion yield and mass resolution vary in the sample spot from place to place. It is often an arduous process to find a suitable position on the sample spot with a satisfactory analyte ion yield and mass resolution, and only experience, trial and error allow for improvements.
- the matrix substance is already present on the carrier plate before application of the solvent droplets, which now only contain analyte molecules. If the surface of the sample carrier plate is not hydrophilic, but hydrophobic, smaller crystal conglomerates are formed, and the droplets tend to wander in an uncontrollable manner during drying. Hence the localisation of the crystal conglomerates cannot be predicted and must be sought during the MALDI process. Furthermore, there is a considerable risk that droplets will conglomerate and thus render a separate analysis of samples impossible.
- the detection limit for analyte molecules improves with reduction of the surface area of the wetting surface.
- smaller quantities of analytes and more diluted solutions can be worked with during sample preparation; such an advantage is expressed in better running biochemical preparatory procedures and reductions in chemical material costs.
- the analytical sensitivity over the surface of the sample is highly uniform.
- the ionisation process can be freed from the need to perform visual or automated searches for favourable sites; instead a "blind" bombardment of the crystal conglomerates with desorbing laser light can be used. This preparation method for prelocated spots of equal sensitivity accelerates the analytical process.
- the crystal conglomerates forming on the hydrophilic anchor surfaces reveal a microcrystalline structure suitable for the MALDI-process. As the speed of the drying process is increased, the crystalline structure becomes finer.
- hydrophobic surface is understood as a water repellant surface, i.e. one resistant to wetting by aqueous solutions.
- a hydrophilic surface is understood as one that can be easily wetted by water.
- Oleophobic and oleophilic also referred to sometimes as “lipophobic” and “lipophilic” refer to surfaces which repel or which can be wetted by oil, respectively.
- Organic solvents that are not miscible with water usually have an oily nature in this meaning of wettability, i.e. they can wet oleophilic faces. They are as a rule miscible with oil.
- Organic solvents that are miscible with water e.g. methanol, acetone or acetonitrile, can wet both oleophilic and hydrophilic surfaces in a pure state. However, the wettability of oleophilic surfaces reduces as the water content increases.
- hydrophobic surfaces are always also oleophilic, and that oleophobic surfaces are always hydrophilic.
- surfaces exist which are both hydrophobic and oleophobic include smooth surfaces of perfluorinated hydrocarbons such as polytetrafluoroethylene (PTFE). Such surfaces are designated here as "lyophobic", a term which has been adopted from colloidal science.
- a surface is particularly designated as "hydrophobic" when a drop retracts on a surface during drying or aspiration with a pipette, reducing the wetted surface reduces in size and leaving behind a dry surface (so called “dynamic hydrophobia”).
- biomolecules are best dissolved in water, sometimes with the addition of organic, water-soluble solvents such as alcohol, acetone or acetonitrile.
- the analytical solutions of biomolecules sometimes also contain other substances such as glycols, glue-like buffering agents, salts, acids or bases depending on their preparation.
- the MALDI process is disrupted considerably by the presence of these impurities, sometimes through prevention of protonation, and sometimes through the formation of adducts.
- alkali ions often form adducts with analyte molecules of varying size and prevent any precise mass determination.
- concentration of alkali ions in the sample preparation, as well as the concentration of other impurity substances must be kept extremely low by careful purification procedures.
- affinity adsorption media similar to those used in affinity chromatography. While in affinity chromatography one uses highly bioselective affinity adsorbents, for the purification of initially unknown mixtures of biopolymers without losses of special types of biomolecules, one needs non-specific adsorbents that can bind all biomolecular constituents of the mixture to as near a similar degree as possible.
- sponge-like microspheres of adsorbent material such as POROS, a registered trademark of Applied Biosystems, Inc.
- pipette tips filled with sponge-like adsorbent such as ZIPTIPs, a registered trademark of Millipore Corporation
- C18 coated magnetised spheres such as GenoPure, a product of Bruker Daltonics, Inc.
- biomolecules can be eluted using aqueous methanol or acetonitrile solutions, and elution can often be assisted by altering the pH-value.
- purification with these materials is labour-intensive since it requires additional materials and additional procedural steps.
- Affinity capture methods have become known also for biospecific selection of certain biomolecules in connection with mass spectrometric analysis, see e.g., U.S. Pat. Nos. 6,020,208, 6,027,942, or 5,894,063 (T. W. Hutchens and T. -T. Yip). Such biospecific affinity adsorption processes can be likewise used for purification.
- US application 20020045270A1 is disclosed a sample support plate with hydrophilic anchors in a strongly hydrophobic environment suitable for MALDI analysis.
- the plate provide areas with affinity adsorbents adjacent to the hydrophilic anchors for purifying biosubstances and, optionally, for performing an affinity selection of biosubstances, whereby the finally prepared matrix sample crystals with the biosubstances for the MALDI analysis are adequately localised on the hydrophilic anchors.
- Ekstr ⁇ m et al. Integrated micro-analytical technology enabling rapid and automated protein identification (Anal. Chem.
- an object of the present invention is to provide a target plate having spots for use in an array format and being provided with pre-positioned functions. Said plate also being devised to support a two-dimensional read-out algorithm by protein sequencing and/or peptide mass fingerprinting.
- the target plate is preferably ready-made prior to sample deposition. This means that all necessary reagents and chemicals such as internal standards and crystallisation agents will be targeted on the plate prior to use.
- the two dimensional approach on the target plate will be made in a way that e. g. 5 different crystallisation agents will be used for the same sample. This will result in that different sequences of the proteins will be detected by the 5 various crystallisation agents, thereby increasing the total sequence coverage of the proteins present in the samples.
- embodiments of the invention can comprise an additive dimension were e. g. 5 different enzymes will be deposited.
- the different enzymes will have varying substrate selectivity. This will ultimately result in a differing cleavage specificity whereby the resulting enzymatic product, the peptide composition will differ.
- Adding a second dimension of diversity in the array target plate performance these differing peptides from the enzymatic first dimension of analysis will then be analysed by the array of crystallisation agents. This will ultimately increase the versatility of protein sequences and sequence coverage of the proteins analysed.
- the present invention satisfies the initially mentioned needs.
- a target plate and a method for use thereof and also a device for depositing an amount of sample on said plate is provided. The method together with subsequent MALDI-TOF analysis and data base search is devised to give fast and accurate analysis results.
- a target plate having a target-plate surface is arranged to receive small, discrete and repeatable amounts of fluid dispensed from a micro dispensing device.
- Said target-plate surface is provided with a two- dimensional array of target spots.
- Each spot is provided with a spot agent, such that an amount of fluid received at a spot can interact with said agent.
- the agent can comprise a matrix solution or alternatively a matrix solution together with one or more digestive enzymes provided to enzymatically cleave analytes.
- a dispensing control unit is arranged to control the dispenser to shoot at the right spot at a controlled pace and dispensing an appropriate amount of fluid for each spot.
- a temperature control unit is connected to a target plate heater, said heater being provided for giving the target plate an appropriate temperature.
- a sample is divided into a number of portions. Each portion is dispensed/shot to a separate spot. Each of the separate spots is provided with a different agent, e.g. different digestive enzymes or different types of matrix.
- spots are arranged to receive different portions of the same sample.
- the spots are provided with different matrix solutions having different ionisation energy, such that (slightly) different spectrograms is obtained for the same analyte, i.e., different portions of the same sample, which enables increased specificity for the analysis.
- the agents on the spots can be different digestive enzymes.
- a computer for matching the output from the mass spectrometer is provided with a database for identifying analysts in the sample.
- Said database is provided with spectrograms for a large number of known substances/parts of substances that has been subjected to different agents prior to mass spectrometry.
- Said computer is also arranged to present the most plausible match, or matches (if any) to a person having interest in the result of the analysis.
- Embodiments of the present invention can easy provide disposable target plates because they are expected to be cheap due to low costs of manufacturing by polymer materials.
- a further advantage of using disposable plates is that both the so-called carry over (contamination stemming from earlier use, not totally removed during wash/clean) and the so-called memory effect is eliminated.
- Fig. la,b,c and d shows a target plate with details of a nanovial including cross sections.
- Fig. 2 shows a flowchart of a method for analysis using a target plate.
- Fig. 3 shows a schematically a part of a MALDI-target plate with deposited matrices and enzymes in a specific pattern.
- the term "annotate” is intended to mean the act of deciding that a spectrum of a MALDI spot corresponds to a certain biopolymer
- biopolymers is intended to designate a group of substances comprising, but not limited to, proteins, nucleic acids, and polysaccharides.
- sample crystal is intended to mean the dry result of chemical and physical reactions concerning matrix and sample on the MALDI-Spot.
- MALDI Spot is intended to mean an area at the MALDI target plate for receiving and holding samples/sample crystals.
- matrix is intended to mean a substance applied on the MALDI- spots prior to or at the same time or after the samples are applied and which substance facilitates different aspects of the analysis of the sample molecules, e.g., adherence to plate, distribution in space, absorption of laser energy.
- spectral data is intended to mean data for a sample crystal comprising the relative intensity and the mass/charge quotient for the ions measured with a MALDI instrument during laser desorption/ionisation of said spot.
- Spectral data for a protein comprises the corresponding data resulting from an identical MALDI analysis of a spot containing only that protein in pure form.
- the present invention is directed towards a target plate for preparing analyte samples for matrix- assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS).
- spectrum fingerprint.
- nanoovial is intended to mean small vials, in this context preferably on a MALDI-plate, and preferably comprising a MALDI-spot.
- a preferred embodiment of the invention is shown in figure 1.
- a target plate 100 is provided with a number of nanovials 110, 111, 112 etc regularly arranged at said plate.
- Each vial 110, 11 letc is provided with walls 140, and a bottom surface, or spot 150.
- Alternative embodiments include vials 160 of other shapes e.g. round, rounded, with slanting or elliptically shaped walls, and having a depth of no more than 100 micrometers, preferably not more than 50 micrometers thereby matching the properties of MALDI laser beams in use today. Deeper vials could affect MALDI-TOF mass resolution negatively.
- said walls are arranged to have a width of 300 micrometer and a height of less than or equal to 50 micrometer, providing the vial with a maximum depth of 50 micrometer and giving the spot 150 an area of approximately 300 times 300 micrometer.
- This area is arranged to match with the effective cross-section area of laser beams of commercially available MALDI lasers, such that the area of the spot is approximately within the range of 25 to 400 percent of laser beam cross-section area.
- the spots are preferably arranged as a two-dimensional array with a distance between spots centre to centre so adapted as to coincide with corresponding measures of commercially available high-density plates used in MALDI spectrometry.
- These centre to centre distances is also preferably such that centre to centre distances of dispenser nozzles of an array dispenser or a dispenser array are made to correspond.
- An alternative preferred embodiment comprises a substantially plane plate having no vials or recesses of any kind, instead the plate is provided with reference points which can comprise the corners and/or edges to facilitate proper application, processing and measurements of the molecules in correct areas of the plate. Analytes and/or other substances/fluids are kept in the right spot by means of surface tension and/or surface modified surfaces such that two nearby amounts of fluid on two nearby spots do not mix even if the distance is 800 micrometers centre to centre.
- a micro dispenser is used to dispense, i.e. shoot small droplets of agent towards the target plate, thereby providing it with the desired agent or pattern of agents
- an embodiment of a method of using the target plate 100 for analysis of samples comprises the following steps: - Loading 210 the target plate spots 150 with one or preferably with a pattern of different MALDI-matrix solutions, i.e. depositing a thin layer of matrix on each spot.
- the MALDI-matrix solution is arranged to i) absorb energy and protect the analyte from excessive energy during laser bombardment, i.e. to prevent analyte decomposition.
- the steps of dispensing 220, facilitating 230 and allowing to dry/solution to evaporate 240 is devised such that a first volume of a protein containing substrate/solution, giving rise to a first concentration of proteins and, by the presence of enzymes, a concentration of peptides, gives rise, because of the evaporation of solution/fluid, to a second concentration of proteins more favourable for enzymatic cleavage than the first, cf. Michaelis-Menten equation of enzyme kinetics.
- the dispensing 220 is preferably performed using a micro dispenser having one or preferably a multitude of dispenser nozzles, making it possible to dispense amounts of the same or different samples at the same time, i.e., in parallel.
- the action of the dispenser is controlled by a control unit that synchronises the action with the flow of analyte.
- the stepwise movement of the target plate for a next row of spots to be placed in front of (under) the dispenser nozzles is also synchronised with the actions of the dispenser.
- the dispensing of droplets is conducted in symphony with the evaporation of the eluant so that the amount of analyte e.g. proteins, deposited on the spot can be increased over time by dispensing more droplets on the same spot.
- the evaporation is devised to take place in a temperature and in a so small volume that it becomes rapid, i.e. the most of the deposited solution is evaporated within a few seconds.
- spots are provided with enzymes that, due to the small dimensions, the controlled temperature and the high concentration of proteins, digest said proteins and form a high concentration of peptides.
- a high concentration of peptide is favourable when performing a further chemical analysis by means of e.g. mass spectrometry.
- the vials/spots are modified using one or more methods coming from the group comprising hydrophilic chemical modification, hydrophobic chemical modification, metalaffinity coated chemical modification, antibody biochemical modification, antigen biochemical modification, peptide biochemical modification, capturing biomacromolecule modification.
- the device is preferably manufactured in silicon, glass or in a polymer material. Silicon is essentially inert when dealing with protein mixtures at room or near room temperature. The material is also very suitable for micro-machining techniques, e.g. for etching away parts of the material with established etching techniques.
- the device can optionally be coated with gold or another high conductivity material in order to lead away charges.
- one or more conductive polymers can be used.
- the spots with enriched analyte molecules arranged in an array format on the target plate will be analysed in the MALDI mass spectrometer using a single dimensional run (simple array format) which means that an array of chemical agents (matrices, enzymes) are screened.
- the sample positioning in the MALDI instrument will run from position A01, A02 and so on.
- a real time data base search is performed simultaneously with the ongoing analysis, where the identity of the protein is queried for by comparing the resulting spectrum, said spectrum comprises the relative intensity and the mass/charge for the incorporated peptides.
- Automatic retrieval of the peptide sequences comprising the proteins is accomplished by searching a database, also called map, that has been compiled in advance.
- Real-time identifications are also performed from position A01 where the spot is analysed for possible multi proteins present in the MALDI spot. Such real- time identifications are made by subtracting the peptide masses/spectral data that belongs to the protein that was identified as a significant hit, and perform a second pass search where ongoing ionisation in real-time is made by laser pulsing onto position A01 where additional peptides are ionised from the sample crystal spot. If a second protein identity is confirmed a third pass search is made by the instrument on the very same spot position, A01 subtracting the peptide masses/spectra corresponding to both the first and second protein. After querying the third pass in real-time, additional data base searches are not performed by the instrument on the given target plate in the automated run in this so-called real-time MALDI-target protein screening cascade. - Moving from sample 1 to sample 2 on the target plate;
- the annotation of that protein sample is confirmed in real-time and the instrument switches over to analyse position (spot) A02 on the MALDI sample plate.
- the array dispenser will be operated in a number of functions together with the target plate; o Static mode Sample array mapping o Separation mode of array mapping
- Dispensing sample droplets can be accomplished with a dispenser array or with an array of dispensers such that simultaneous array deposition provides reduced experimental variation in-between sample spots.
Abstract
Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2002359113A AU2002359113A1 (en) | 2001-12-11 | 2002-12-11 | Target plate for mass spectometers and use thereof |
JP2003555544A JP2005513490A (en) | 2001-12-11 | 2002-12-11 | Target plate for mass spectrometer and use of the target plate |
EP02793621A EP1461822A1 (en) | 2001-12-11 | 2002-12-11 | Target plate for mass spectometers and use thereof |
CA002469841A CA2469841A1 (en) | 2001-12-11 | 2002-12-11 | Target plate for mass spectometers and use thereof |
US10/498,043 US20050031496A1 (en) | 2001-12-11 | 2002-12-11 | Target plate for mass spectometers and use thereof |
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
SE0104125-0 | 2001-12-11 | ||
SE0104125A SE0104125D0 (en) | 2001-12-11 | 2001-12-11 | High sensitivity protein workstation and techniques |
SE0202223A SE0202223D0 (en) | 2001-12-11 | 2002-07-15 | Target plate and use thereof for improved analysis |
SE0202223-4 | 2002-07-15 | ||
SE0202398-4 | 2002-08-13 | ||
SE0202398A SE0202398D0 (en) | 2001-12-11 | 2002-08-13 | Target plate and use thereof for improved analysis |
Publications (1)
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WO2003054915A1 true WO2003054915A1 (en) | 2003-07-03 |
Family
ID=27354777
Family Applications (1)
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PCT/SE2002/002284 WO2003054915A1 (en) | 2001-12-11 | 2002-12-11 | Target plate for mass spectometers and use thereof |
Country Status (7)
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---|---|
US (1) | US20050031496A1 (en) |
EP (1) | EP1461822A1 (en) |
JP (1) | JP2005513490A (en) |
AU (1) | AU2002359113A1 (en) |
CA (1) | CA2469841A1 (en) |
SE (1) | SE0202398D0 (en) |
WO (1) | WO2003054915A1 (en) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005083418A1 (en) | 2004-02-26 | 2005-09-09 | Japan Science And Technology Agency | Sample target having surface-treated plane for holding sample and method for manufacture thereof, and mass spectrometer using the sample target |
JPWO2006046697A1 (en) * | 2004-10-29 | 2008-08-07 | 独立行政法人科学技術振興機構 | Substrate for MALDI-TOFMS and mass spectrometric method using the same |
DE102008035079B4 (en) * | 2007-08-27 | 2018-06-21 | Jeol Ltd. | Mass spectrometer with MALDI ion source |
CN108709927A (en) * | 2018-05-24 | 2018-10-26 | 华东理工大学 | It can disposal type mass spectrum target plate and its preparation method and application |
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US7405083B2 (en) * | 2003-05-13 | 2008-07-29 | Becton, Dickinson And Company | Method and apparatus for purifying and desalting biological samples |
US20090215192A1 (en) * | 2004-05-27 | 2009-08-27 | Stratos Biosystems, Llc | Solid-phase affinity-based method for preparing and manipulating an analyte-containing solution |
US20060266941A1 (en) * | 2005-05-26 | 2006-11-30 | Vestal Marvin L | Method and apparatus for interfacing separations techniques to MALDI-TOF mass spectrometry |
WO2007133714A2 (en) * | 2006-05-12 | 2007-11-22 | Stratos Biosystems, Llc | Analyte focusing biochips for affinity mass spectrometry |
US7667195B2 (en) * | 2007-05-01 | 2010-02-23 | Virgin Instruments Corporation | High performance low cost MALDI MS-MS |
US7589319B2 (en) | 2007-05-01 | 2009-09-15 | Virgin Instruments Corporation | Reflector TOF with high resolution and mass accuracy for peptides and small molecules |
US7564026B2 (en) * | 2007-05-01 | 2009-07-21 | Virgin Instruments Corporation | Linear TOF geometry for high sensitivity at high mass |
US7663100B2 (en) * | 2007-05-01 | 2010-02-16 | Virgin Instruments Corporation | Reversed geometry MALDI TOF |
US7564028B2 (en) * | 2007-05-01 | 2009-07-21 | Virgin Instruments Corporation | Vacuum housing system for MALDI-TOF mass spectrometry |
US7838824B2 (en) * | 2007-05-01 | 2010-11-23 | Virgin Instruments Corporation | TOF-TOF with high resolution precursor selection and multiplexed MS-MS |
JP2009288160A (en) * | 2008-05-30 | 2009-12-10 | Hitachi High-Technologies Corp | Biosample analysis system, biosample analysis method, biosample pretreatment device, and biosample pretreatment method |
US20110290008A1 (en) * | 2010-05-28 | 2011-12-01 | Ebstein Steven M | Novel technique for uniformly applying analyte to a structured surface |
JP7354832B2 (en) | 2019-03-20 | 2023-10-03 | 株式会社リコー | MALDI mass spectrometry measurement sample preparation method, MALDI mass spectrometry measurement sample preparation device, and MALDI mass spectrometry measurement sample preparation program |
CN110887892B (en) * | 2019-12-23 | 2022-08-19 | 复旦大学 | Mass spectrum detection method for small amount of samples |
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NZ516848A (en) * | 1997-06-20 | 2004-03-26 | Ciphergen Biosystems Inc | Retentate chromatography apparatus with applications in biology and medicine |
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- 2002-12-11 JP JP2003555544A patent/JP2005513490A/en active Pending
- 2002-12-11 US US10/498,043 patent/US20050031496A1/en not_active Abandoned
- 2002-12-11 CA CA002469841A patent/CA2469841A1/en not_active Abandoned
- 2002-12-11 AU AU2002359113A patent/AU2002359113A1/en not_active Abandoned
- 2002-12-11 EP EP02793621A patent/EP1461822A1/en not_active Withdrawn
- 2002-12-11 WO PCT/SE2002/002284 patent/WO2003054915A1/en not_active Application Discontinuation
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Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005083418A1 (en) | 2004-02-26 | 2005-09-09 | Japan Science And Technology Agency | Sample target having surface-treated plane for holding sample and method for manufacture thereof, and mass spectrometer using the sample target |
JPWO2005083418A1 (en) * | 2004-02-26 | 2007-08-09 | 独立行政法人科学技術振興機構 | Sample target having surface-treated sample holding surface, manufacturing method thereof, and mass spectrometer using the sample target |
JPWO2006046697A1 (en) * | 2004-10-29 | 2008-08-07 | 独立行政法人科学技術振興機構 | Substrate for MALDI-TOFMS and mass spectrometric method using the same |
JP4649416B2 (en) * | 2004-10-29 | 2011-03-09 | 独立行政法人科学技術振興機構 | MALDI-TOFMS substrate and mass spectrometry method using the same |
DE102008035079B4 (en) * | 2007-08-27 | 2018-06-21 | Jeol Ltd. | Mass spectrometer with MALDI ion source |
CN108709927A (en) * | 2018-05-24 | 2018-10-26 | 华东理工大学 | It can disposal type mass spectrum target plate and its preparation method and application |
Also Published As
Publication number | Publication date |
---|---|
CA2469841A1 (en) | 2003-07-03 |
EP1461822A1 (en) | 2004-09-29 |
US20050031496A1 (en) | 2005-02-10 |
SE0202398D0 (en) | 2002-08-13 |
AU2002359113A1 (en) | 2003-07-09 |
JP2005513490A (en) | 2005-05-12 |
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