WO1995015001A2 - Sm par tdv a desorption laser assistee par matrice a resolution amelioree - Google Patents

Sm par tdv a desorption laser assistee par matrice a resolution amelioree Download PDF

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Publication number
WO1995015001A2
WO1995015001A2 PCT/US1994/012963 US9412963W WO9515001A2 WO 1995015001 A2 WO1995015001 A2 WO 1995015001A2 US 9412963 W US9412963 W US 9412963W WO 9515001 A2 WO9515001 A2 WO 9515001A2
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WO
WIPO (PCT)
Prior art keywords
matrix
soud
thin layer
substrate
sample
Prior art date
Application number
PCT/US1994/012963
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English (en)
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WO1995015001A3 (fr
Inventor
Joseph A. Jarrell
Michael J. Tomany
Craig A. Dorschel
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Waters Corporation
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 Waters Corporation filed Critical Waters Corporation
Priority to EP95902508A priority Critical patent/EP0764264A2/fr
Priority to CA002205040A priority patent/CA2205040C/fr
Publication of WO1995015001A2 publication Critical patent/WO1995015001A2/fr
Publication of WO1995015001A3 publication Critical patent/WO1995015001A3/fr

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Classifications

    • 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
    • H01J49/0409—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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/2813—Producing thin layers of samples on a substrate, e.g. smearing, spinning-on

Definitions

  • This invention relates generally to mass spectrometry, and in particular to f 5 matrix assisted laser desorption and ionization time-of-flight mass spectrometry. Specifically, this invention relates to a method and apparatus for improved sample desorption by laser excitation that results in greatly enhanced mass resolution and sensitivity for a time-of-flight system.
  • Matrix-assisted laser ionization .and desorption time-of-flight mass spectrometry is a recently developed technique which is particularly useful for the sensitive analysis of large biomolecules.
  • the matrix is a material that assists in the transfer of energy to the .analyte molecule, allowing it to be ionized without significant
  • a few microliters of a solution containing sample molecules at concentrations of about 1 ⁇ g/ ⁇ L are mixed with 10-20 ⁇ L of a solution containing matrix molecules at concentrations of about 10 ⁇ g/ ⁇ L. A few microliters of this mixture are then deposited on a suitable substrate and dried in air.
  • these ions are of a type known as (M+H)+ ions, that is, the neutral sample molecule (M) is ionized by the attachment of a proton.
  • negatively charged ions may be produced, for example by the removal of a proton.
  • This ionization process has some similarity to the process called "chemical ionization” used conventionally in gas chromatography/mass spectrometry.
  • chemical ionization used conventionally in gas chromatography/mass spectrometry.
  • Most frequently these ions are analyzed in so-called linear time-of-flight (TOF) mass spectrometers.
  • TOF time-of-flight
  • the ions, once formed, are accelerated by an electric field and then allowed to travel in straight lines until they are detected. The transit time between ion formation and detection can be used to determine the mass of the species from which the ions are generated.
  • Typical linear TOF systems are described in U.S. Pat. No. 5,045,694 ( Beavis and Chait).
  • Such linear devices provide only modest mass resolving power, e.g. 50-800, because they are unable to compensate for various known aberrations.
  • a dominant aberration in such linear systems stems from the fact that the ions are formed with a wide distribution of initial velocities. This means that for an ion of a given mass there will be a distribution of arrival times at the detector that will limit the mass resolving power of such a device, since ions with more initial velocity in the forward direction will arrive sooner than ions with less initial velocity.
  • GB 2236185A discloses a two-dimensional layer comprising a matrix ("absorbing component") underlying the substrate. The appUcation is aimed at macromolecular blotting.
  • GB 2236186A discloses desorption of biomolecules using 337 nm or higher laser radiation on a similar surface. Sinapinic acid is shown 15as the matrix.
  • Cottrell PCT/GB90/00973 discloses a method for preparing a sample for analysis by LDMS that includes electrospraying the matrix (Nicotinic acid) onto a target surface, then sample in TFA is applied and dried down. Finally, the sample is introduced into the mass spectrometer and a laser is directed onto the sample, desorbing the sample.
  • matrix Nicotinic acid
  • Cottrell PCT/GB90/00974, discloses a method for preparing a sample for analysis by LDMS that includes electrospraying a substrate (Nitrocellulose) onto a target, depositing a sample dissolved in aqueous 0.1 % trifluoroacetic acid (TFA), and then drying it down.
  • Matrix material (Nicotinic acid, 30 mM in acetone) is then applied in droplet form to cover the dried-down sample and dissolve the substrate Nitrocellulose. Sample, substrate and matrix dry down together in an intermixed form. If the sample is a protein, the protein adsorbs to the Nitrocellulose by hydrophobic interactions. Loss of mass resolution is caused when excess matrix is evaporated from the surface of the target, causing the plasma effect described supra.
  • Cottrell, PCT/GB90/00975 additionally discloses the use of various matrix materials such as Cinnamic acid, Benzoic acid, or Coumarin in the methods disclosed above.
  • Hutchens Proceedings of the 41st American Society of Mass Spectrometry Conference on Mass Spectrometry and Allied Topics, May 31- June 4, 1993, pp.
  • Figs, la and lb are mass spectra obtained from an insulin sample deposited on a thin film of cellulose acetate and matrix on a glass disc substrate;
  • Fig. lc is a photomicrograph of the same insulin sample on this thin film on this disc.
  • Figs. 2a, 2b, 2c and 2d are scanning electron micrographs of cross- sections of preprepared matrix- cellulose acetate films.
  • Figs. 3a and 3b are mass spectra obtained from an insulin sample prepared by conventional means, deposited and dried on a glass disc; Fig. 3c is a photomicrograph of the same insulin sample on this disc.
  • Figs. 4a and 4b are mass spectra obtained from an insulin sample deposited on a thin film on a glass disc substrate (an alternative embodiment); Fig. 4c is a photomicrograph of the same insulin sample on this disc.
  • Fig. 5 is a high-resolution mass spectrum of a sample of maltoheptaose deposited on a preprepared substrate similar to that one used to generate Figs, la and lb.
  • Fig. 6 is a mass spectrum obtained with insulin on a thin precast film of cellulose nitrate and matrix on a glass disc substrate.
  • the present invention overcomes the disadvantages and limitations of the prior art by providing a surprising enhancement in mass resolution comprising a thin-layer for sample analysis by laser desorption mass spectrometry wherein the band-broadening contribution due to the matrix substrate sample composition is minimized
  • mass resolution and sensitivity are increased by the use of a thin layer comprising a matrix material in a supported dispersion wherein the support is a solid or is formed from a solid.
  • the solid support is preferably a solid that limits matrix crystal growth, most preferably a polymer. Thicknesses not greater th-an 1 ⁇ m are most preferred.
  • the preferred embodiment of the invention is a thin layer for sample analysis by matrix assisted laser desorption mass spectrometry, comprising a matrix-polymer composition disposed upon a substrate.
  • a matrix-polymer composition disposed upon a substrate.
  • Any matrix material may be used, but Sinapinic acid or ⁇ -cyano-4 hydroxycinnamic acid is preferred.
  • the matrix-polymer composition may include a polymer selected from the group consisting of cellulose acetate, cellulose nitrate, and polycarbonate. However, other polymers are also possible.
  • the matrix-polymer composition may preferably range from about 70% polymer to about 30% polymer. Preferably, it is 50%.
  • the mass resolution of the sample is significantly enhanced using this invention, and unexpected mass resolutions of over 8000 have been demonstrated in a linear 150-cm flight tube machine.
  • the invention is also directed to a device for performing matrix- assisted laser desorption mass spectrometry of sample molecules, comprising a substrate capable of receiving on its surface a thin layer as previously described.
  • the device is combined with a solution of sample molecules wherein the sample and matrix are substantially coplanar, .and then subjected to mass analysis.
  • the substrate underlying the device is selected from the group consisting of glass, ceramic, plastic, metal, or similar materials.
  • the thin layer of the device is resistant to decreased mass resolution and sensitivity over time, i.e., it has a substantial shelf life.
  • the invention is also directed to a method for making a thin layer for sample analysis by matrix- assisted laser desorption mass spectrometry, the thin layer comprising a matrix material in a supported dispersion wherein the support is a solid, comprising the steps of: depositing a solution containing matrix, support and solvent upon a substrate; and then evaporating the solvent, thereby interspersing the matrix and support on the substrate in a thin layer.
  • the preferred method is spin casting, however other methods are also possible.
  • the product made by this process is also a part of this invention. The invention will be described in part by referring to the attached figures.
  • the invention is directed to a thin layer for sample analysis by matrix-assisted laser desorption mass spectrometry, comprising a matrix material in a supported dispersion wherein the support is a solid or is formed from a solid.
  • supported dispersion refers to a solid support for maintaining the matrix in a dispersed state in which large crystal formation is inhibited.
  • a preferred embodiment is a thin film of matrix comprising ⁇ -cyano-4-hydroxycinnamic acid and polymer comprising cellulose acetate, having a thickness of not greater than 1 ⁇ m.
  • Other matrices and solids, including polymers, may be used.
  • these may include, but are not limited to, thymine, pyrazinecarboxylic acid, thiourea, nicotinic acid, vanillic acid, ferulic acid, caffeic acid, sinapinic sacid, dihydrobenzoic acid, .and other derivatives of these acids. See GB 2236185 A (Hillenkamp et al.) for other matrices.
  • Polymers that may come within the scope of this invention broadly include all those that may be used in the process of making the matrix-polymer thin film, as described below. These polymers may include cellulose acetate, cellulose nitrate, polycarbonate, nylon, PVDF .and any that may conveniently be prepared as solutions. The specific combination of matrix and polymer does not appear to be critical. Sinapinic acid and ⁇ -cyano-4-hydroxycinnamic acid are preferred matrices, while polycarbonate, cellulose acetate, and cellulose nitrate are preferred polymers. One function of the polymer appears to be to inhibit formation of large, thick crystals of matrix.
  • the solvent used to deposit both matrix and solid must be able to solubilize both.
  • acetone is preferred.
  • cellulose nitrate 75% ether/25% ethanol is preferred.
  • polycarbonate tetrahydrofuran is preferred.
  • One of ordinary skill will be able to determine a suitable solvent for solubilizing both matrix and polymer.
  • Stainless steel, glass and quartz discs are preferred embodiments. Ceramic, plastic and other compositions, porous and non-porous surfaces, are likely to work. Further, it may be useful to impregnate matrix into a thin surface layer, either as a dissolved species or into small voids, into or onto a thick material such as a polymer sheet that can readily be punched into conveniently shaped substrates.
  • a substrate that would control the thickness of the matrix-sample mixtures in these systems would be beneficial.
  • This could be a porous polymer substrate, or any substrate that would absorb and retain the matrix- sample mixture in a thin layer.
  • Microreticulated surfaces are specifically contemplated.
  • the thickness of these films is believed to be an important aspect of the invention. Increased mass resolution is shown in those films which comprise a thin layer, i.e. having thicknesses under 2 ⁇ m.
  • the range of thicknesses over which this invention is operable is from 5 to .005 ⁇ m.
  • a preferred range is from 2 to 0.1 ⁇ m, and the most preferred range is from 1 to 0.05 ⁇ m.
  • FIG. 2b shows scanning electron micrographs of films of the matrix ⁇ -cyano-4-hydroxycinnamic acid and cellulose acetate. These pictures were obtained by taking glass discs onto which had been deposited thin films, and fracturing them so that the films could be observed in cross-section.
  • Fig. 2a shows a cross section of a film such as those used to obtain the spectra displayed in Figs, la, lb, and 5. Its thickness can be measured as approximately 0.37 ⁇ m.
  • Fig. 2b shows a film in cross-section which was prepared in a similar fashion except that the substrate was spun at roughly 30,000 rpm instead of 5000 rpm resulting in a thinner film Its thickness can be measured as approximately 0.09 ⁇ m.
  • Fig. 2c shows a thick film approximately 2.2 ⁇ m thick which provides lower resolution and lower sensitivity spectra.
  • Fig. 2d is a picture at greater magnification of the same film shown in Fig. 2b. The exact reason for this increased performance is not completely evident at this point, but it is likely that several different factors are relevant. Although the invention is not limited to any particular theory, the following may explain the observed results.
  • One model for the matrix assisted desorption and ionization process proposes that it is necessary for the solid matrix to be converted to a gaseous plume by absorbing incident laser radiation which then serves to expel the sample molecule or ion into the vacuum (A.
  • the same model proposes that as sample ions are formed and accelerated in the acceleration region of the mass spectrometer, they undergo coUisions with neutral and charged matrix molecules and ions and that these coUisions contribute to an energy "spread" of the ion population. It is therefore possible that ions formed from sample molecules in or contiguous to a thin film of matrix wiU undergo fewer coUisions and thus suffer less energy spread. It may weU be that the importance of the relatively inert polymer in this film is to provide mechanical integrity, but also to prevent the aggregation of the matrix into large structures when the sample molecule solvent is appUed and thus to maintain the sample molecules and the matrix molecules in a physicaUy constrained and hence thin environment. This explanation is consistent with the improved resolution demonstrated in Figs, la and lb relative to Figs. 3 a and 3b.
  • the invention also includes a method of making a thin layer for sample analysis by matrix assisted laser desorption mass spectrometry, the layer comprising a matrix material in a supported dispersion wherein the support is a soUd, comprising the steps of depositing a solution containing matrix, soUd and solvent upon a substrate, and then evaporating the solvent, thereby interspersing the matrix and support on the substrate in a thin layer.
  • the method is accompUshed by depositing roughly 10 ⁇ L of a solution of 30 mg/ml of a polymer, most preferably ceUulose acetate, and 30 mg/ml of a matrix, most preferably o.-cyano-4-hydroxycinnamic acid, onto a substrate, preferably a glass or metal disc roughly 0.5" in diameter, spinning at roughly 5000 rpm.
  • a substrate preferably a glass or metal disc roughly 0.5" in diameter, spinning at roughly 5000 rpm.
  • the resulting film dries rapidly (typicaUy less than a few seconds) and is usuaUy less than 1 ⁇ m thick. These discs may be stored .and used at a later time.
  • Thickness of the film is controUed by the concentration of the ⁇ cyano-4-hydroxycinnamic acid and ceUulose acetate in solution; the rate of spinning; .and the rate of solvent evaporation.
  • Spin casting is only one method of making the thin film; others such as electrospray deposition (See WO 91/02961) and chemical vapor deposition are within the knowledge of one of ordinary skiU in the art.
  • a sample molecule such as Bovine Insulin was apphed by dispensing a smaU volume, 0.5 ⁇ L is typical, of an Insulin solution onto the substrate and then aUowing it to dry in air.
  • FIG. 2c A sphotomicrograph of such a film, after a sample of 0.5 ⁇ L of a solution of 0.001 ⁇ g/ ⁇ L of Insulin in water and 0.1% trifluoroacetic acid has been deposited on it and aUowed to dry, is shown in Fig. 2c. This dried sample may then be introduced into a laser desorption time-of-flight mass spectrometer.
  • Example 1 Mass spectra obtained from such a sample are shown in Example 1 (Fig. la and lb).
  • the spectrum shown in Fig. la was acquired with two laser shots from a Nitrogen laser emitting at 337 nm (see Materials under Examples). Other lasers emitting at different frequencies are also possible, and weU known to those of ordinary skiU.
  • the spectrum shown in Fig. lb was acquired by scanning the laser beam across the sample and averaging together only those spectra which had an insulin peak above a certain threshold intensity. Spectra obtained from such samples show much better mass resolution and reproducibility than spectra obtained from samples prepared by the most common prior art technique, which does not show a thin layer of polymer-matrix.
  • Mass resolution is defined as the mass (parent ion mass divided) by the mass represented by the width of the peak at half of its height. This may be seen by comparing Figs la and lb to Figs. 3a and 3b respectively. The former and the latter spectra were obtained in the same instrument and with the same initial instrument parameters. It should be noted that 10 times as much insulin was deposited on the disc used to obtain the prior art Figs. 3a, 3b and 3c as was deposited on the disc used to obtain Figs, la, lb and lc, highlighting the fact that surprizingly increased sensitivity is also a hallmark of this invention. A further embodiment is shown by Figs. 4a, 4b and 4c.
  • a sim ar linear time-of-flight mass spectrometer was used on a sample of the oUgosaccharide Maltoheptaose, except that in this case the flight tube length was approximately 1.5 m and the ion detector used was a dual chevron channel plate assembly such as the #F TO-2003 time-of-flight detector sold by GaUleo Electrooptics.
  • the essential characteristic of this detector is that it has a very fast response time and a 50 ⁇ output impedance.
  • a higher speed digitizer such as LeCroy #9360 sampling at 5 GHz with an analog bandwidth of 300 MHz was used.
  • a micro-reticulated surface such as can routinely be generated on glass or siUcon (or by molding plastics or epoxies from masters) when coated with a thin film of matrix, may prove to be an effective substrate, the micro-reticulation serving to prevent the aggregation of matrix and/or sample when the sample is deposited.
  • laminated structures consisting of thin, and if necessary porous, layers of matrix and an inert substance may be effective.
  • pre-prepared substrates by coating or polymerizing the inert material around smaU preformed matrix crystals or particles. It may also be appropriate and convenient to polymerize matrix monomers (or more generaUy energy absorbing monomers) around predeposited sample molecules. It will also be evident that these thin films need not be continuous, e.g. thin patches of such films may work too. Having now generaUy described this invention, the same wiU become better understood by reference to certain specific examples which are included herein for purposes of iUustration only and are not intended to be limiting unless otherwise specified. AU U.S. patents cited herein are fuUy incorporated by reference in their entirety.
  • AU spectra displayed in Figs la, lb, 3a, 3b, 4a and 4b were obtained by introducing the respective samples into a linear time-of-flight mass spectrometer with a flight tube length of approximately 55 cm and a fast response time response discrete dynode electron multipUer, such as Model # AF820H manufactured by ETP PTY Ltd., with the last few dynodes buffered by extra capacitance.
  • Pulses of laser radiation at 337 nm from a nitrogen laser such as is Model #VSL337ND manufactured by L.S.I, were used for the matrix- assisted desorption and ionization.
  • the output of the electron multipUer was sampled at 100 Msamples/sec by a nominal 8 bit digitizer with an analog bandwidth of 300 MHz such as is offered by several manufacturers such as LeCroy Inc.
  • Bovine Insulin was obtained from Sigma (St. Louis, MO).
  • Sinapinic acid and ⁇ -cyano-4 hydroxycinnamic acid were obtained from Aldrich Chemical Co. (MUwaukee, Wisconsin).
  • Example 1 Construction of a Thin Films of ⁇ -cyano-4-hydroxvcinnamic acid and CeUulose Acetate
  • a thin film of ⁇ -cyano-4-hydroxycinnamic acid and ceUulose acetate was prepared by dropping roughly 10 ⁇ L of a solution of 30 mg/ml of ceUulose acetate and 30 mg/ml of ⁇ -cyano-4hydroxycinnamic acid onto a glass disc spinning at roughly 5000 rpm. The glass disc was spun by mounting it onto a Dremel (Racine, WI) Moto-tool Model 395 type 3. The resulting film dried rapidly (typicaUy less than a few seconds) and is typicaUy less than 1 ⁇ m thick.
  • a sample such as insulin may be appUed by dispensing a smaU volume, 0.5 ⁇ L is typical, of an insulin solution onto the substrate and then aUowing it to dry in air.
  • a photomicrograph of such a film after a sample of 0.5 ⁇ L of a solution of 0.001 ⁇ g/ ⁇ L of insulin in water and 0.1% trifluoroacetic acid has been deposited on it and aUowed to dry, is shown in Fig. lc. This dried sample was then introduced into a laser desorption time-of-flight mass spectrometer. Mass spectra obtained from such a sample are shown in Fig. la and lb.
  • Fig. la The spectrum shown in Fig. la was acquired with two laser shots.
  • the spectrum shown in Fig. lb was acquired by scanning the laser beam across the sample and averaging together only those spectra which had an insulin peak above a certain threshold intensity. Spectra obtained from such samples show surprizingly better mass resolution and better reproducibiUty than spectra obtained from samples prepared by the most common prior art technique.
  • Example 2 Construction of Thin Films of ⁇ -cyano-4-hydroxycinnamic acid and CeUulose Nitrate These thin films were prepared according to the procedure of Example 1 except that the solution of ceUulose nitrate and ⁇ -cyano-4-hydroxycinnamic acid was prepared in a mixture of 75% anhydrous ether and 25% ethanol by volume. A spectrum from insulin deposited on such a thin film is shown in Fig. 6.
  • Example 3 Construction of Thin Films using Polycarbonate and -cyano-4-hydroxycinnamic acid
  • These thin films are prepared according to the procedure of Example 1 except that the solution of polycarbonate ⁇ -cyano-4-hydroxycinnamic acid was prepared in tetrahydrofuran.

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Abstract

L'invention porte sur une couche mince servant à l'analyse par spectrométrie de masse à désorption laser assistée par matrice, dans laquelle la matrice est une dispersion sur support solide ou formé à partir d'un solide. L'invention porte également sur un procédé d'élaboration d'une couche mince pour l'analyse d'échantillons par spectrométrie de masse à désorption laser assistée par matrice où ladite couche comprend une composition matrice/solide déposée sur substrat obtenue par dépôt de la matrice, du solide et du solvant sur un substrat rotatif, à une vitesse de dépôt suffisante pour permettre l'évaporation du solvant de façon à imbriquer la matrice et le support sur le substrat en une couche mince. On obtient ainsi une résolution en masse améliorée.
PCT/US1994/012963 1993-11-12 1994-11-09 Sm par tdv a desorption laser assistee par matrice a resolution amelioree WO1995015001A2 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP95902508A EP0764264A2 (fr) 1993-11-12 1994-11-09 Sm par tdv a desorption laser assistee par matrice a resolution amelioree
CA002205040A CA2205040C (fr) 1993-11-12 1994-11-09 Sm par tdv a desorption laser assistee par matrice a resolution amelioree

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US15149093A 1993-11-12 1993-11-12
US08/151,490 1993-11-12

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WO1995015001A2 true WO1995015001A2 (fr) 1995-06-01
WO1995015001A3 WO1995015001A3 (fr) 1995-09-21

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Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2299445A (en) * 1995-03-28 1996-10-02 Bruker Franzen Analytik Gmbh Ionization of analyte molecules
GB2312550A (en) * 1996-04-27 1997-10-29 Bruker Franzen Analytik Gmbh Matrix-assisted laser desorption and ionization
GB2312782A (en) * 1996-05-04 1997-11-05 Bruker Franzen Analytik Gmbh Prefabricated MALDI layers suitable for storage
WO1999057318A2 (fr) * 1998-05-07 1999-11-11 Sequenom, Inc. Analyse de molecules par spectrometrie de masse a desorption/ionisation par laser, assistee par matrice absorbant l'infrarouge
WO2000054309A1 (fr) 1999-03-09 2000-09-14 The Scripps Research Institute Desorption/ionisation ameliorees de substances a analyser a partir d'un semi-conducteur poreux absorbeur de lumiere
US6436640B1 (en) 1999-03-18 2002-08-20 Exiqon A/S Use of LNA in mass spectrometry
EP1481244A2 (fr) * 2002-01-25 2004-12-01 Ciphergen Biosystems, Inc. Monomeres et polymeres a groupes fonctionnels d'absorption d'energie utiles dans la desorption/ionisation d'analytes
WO2005022583A2 (fr) * 2003-08-21 2005-03-10 Applera Corporation Reduction d'une interaction due a la matrice pour analyse par spectrometrie de masse maldi
WO2006124003A1 (fr) * 2005-05-20 2006-11-23 Agency For Science, Technology And Research Matériau composite à matrice maldi et ses procédés d’utilisation et ensembles préfabriqués correspondants pour maldi
EP1802961A2 (fr) * 2004-09-29 2007-07-04 Ciphergen Biosystems, Inc. Complexe d'absorption d'energie hote-invite
KR101231157B1 (ko) 2011-07-07 2013-02-08 한국과학기술연구원 매트릭스 레이져 탈착/이온화 질량분석법을 이용한 종이 내 혈액 시료로부터 생체화합물의 직접 분석 방법

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WO1991003068A1 (fr) * 1989-08-23 1991-03-07 Finnigan Mat Ltd. Procede de preparation d'un echantillon pour analyse
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GB2236185A (en) * 1989-08-22 1991-03-27 Finnigan Mat Gmbh Laser desorbtion of analyte bound on a surface
GB2257295A (en) * 1991-06-21 1993-01-06 Finnigan Mat Ltd Sample holder for use in a mass spectrometer.

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0333912A2 (fr) * 1988-03-22 1989-09-27 Bruker Franzen Analytik GmbH Méthode d'évaporation d'un échantillon
GB2236185A (en) * 1989-08-22 1991-03-27 Finnigan Mat Gmbh Laser desorbtion of analyte bound on a surface
WO1991003068A1 (fr) * 1989-08-23 1991-03-07 Finnigan Mat Ltd. Procede de preparation d'un echantillon pour analyse
WO1991002961A1 (fr) * 1989-08-23 1991-03-07 Finnigan Mat Ltd. Procede de preparation d'un echantillon pour analyse
GB2257295A (en) * 1991-06-21 1993-01-06 Finnigan Mat Ltd Sample holder for use in a mass spectrometer.

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AIP CONFERENCE PROCEEDINGS, no. 288, April 1993 KNOXVILLE USA, pages 447-458, KARAS ET AL. 'maldi mass spectrometry, fundamentals and applications' *
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY, vol. 4, no. 12, December 1993 pages 955-963, CURRIE 'analysis of oligo-deoxy-nucleotides by negative-ion maldi-ms' *
RAPID COMMUNICATIONS IN MASS SPECTROMETRY, vol. 5, 1991 pages 145-148, S.J.DOKTYCZ 'matrix-sample interactions in uv-desorption of proteins' *

Cited By (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2299445A (en) * 1995-03-28 1996-10-02 Bruker Franzen Analytik Gmbh Ionization of analyte molecules
GB2299445B (en) * 1995-03-28 1998-12-09 Bruker Franzen Analytik Gmbh Method for the ionization of heavy molecules at atmospheric pressure
GB2312550A (en) * 1996-04-27 1997-10-29 Bruker Franzen Analytik Gmbh Matrix-assisted laser desorption and ionization
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GB2312782A (en) * 1996-05-04 1997-11-05 Bruker Franzen Analytik Gmbh Prefabricated MALDI layers suitable for storage
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