EP3334537A1 - Sprühvorrichtung und verfahren zum beschichten von proben - Google Patents
Sprühvorrichtung und verfahren zum beschichten von probenInfo
- Publication number
- EP3334537A1 EP3334537A1 EP16717136.2A EP16717136A EP3334537A1 EP 3334537 A1 EP3334537 A1 EP 3334537A1 EP 16717136 A EP16717136 A EP 16717136A EP 3334537 A1 EP3334537 A1 EP 3334537A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- gas
- layer
- housing
- capillary
- solution
- 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.)
- Granted
Links
- 238000005507 spraying Methods 0.000 title claims abstract description 19
- 238000000576 coating method Methods 0.000 title claims abstract description 10
- 239000011248 coating agent Substances 0.000 title claims abstract description 9
- 238000000034 method Methods 0.000 title claims description 24
- 239000007788 liquid Substances 0.000 claims abstract description 35
- 239000007921 spray Substances 0.000 claims abstract description 32
- 238000006073 displacement reaction Methods 0.000 claims 1
- 239000011159 matrix material Substances 0.000 abstract description 21
- 239000013078 crystal Substances 0.000 abstract description 16
- 230000015572 biosynthetic process Effects 0.000 abstract description 7
- 238000001035 drying Methods 0.000 abstract description 6
- 239000007789 gas Substances 0.000 description 31
- 239000010453 quartz Substances 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 238000000605 extraction Methods 0.000 description 7
- 238000000816 matrix-assisted laser desorption--ionisation Methods 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 239000004696 Poly ether ether ketone Substances 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 229920002530 polyetherether ketone Polymers 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000000859 sublimation Methods 0.000 description 3
- 230000008022 sublimation Effects 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000008021 deposition Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000005684 electric field Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000001871 ion mobility spectroscopy Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 238000011170 pharmaceutical development Methods 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- NQLVQOSNDJXLKG-UHFFFAOYSA-N prosulfocarb Chemical compound CCCN(CCC)C(=O)SCC1=CC=CC=C1 NQLVQOSNDJXLKG-UHFFFAOYSA-N 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 150000003384 small molecules Chemical group 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 239000012808 vapor phase Substances 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
- B05B7/00—Spraying apparatus for discharge of liquids or other fluent materials from two or more sources, e.g. of liquid and air, of powder and gas
- B05B7/02—Spray pistols; Apparatus for discharge
- B05B7/06—Spray pistols; Apparatus for discharge with at least one outlet orifice surrounding another approximately in the same plane
- B05B7/062—Spray pistols; Apparatus for discharge with at least one outlet orifice surrounding another approximately in the same plane with only one liquid outlet and at least one gas outlet
- B05B7/066—Spray pistols; Apparatus for discharge with at least one outlet orifice surrounding another approximately in the same plane with only one liquid outlet and at least one gas outlet with an inner liquid outlet surrounded by at least one annular gas outlet
-
- 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
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
- B05B5/00—Electrostatic spraying apparatus; Spraying apparatus with means for charging the spray electrically; Apparatus for spraying liquids or other fluent materials by other electric means
- B05B5/025—Discharge apparatus, e.g. electrostatic spray guns
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
- B05B7/00—Spraying apparatus for discharge of liquids or other fluent materials from two or more sources, e.g. of liquid and air, of powder and gas
- B05B7/16—Spraying apparatus for discharge of liquids or other fluent materials from two or more sources, e.g. of liquid and air, of powder and gas incorporating means for heating or cooling the material to be sprayed
- B05B7/1606—Spraying apparatus for discharge of liquids or other fluent materials from two or more sources, e.g. of liquid and air, of powder and gas incorporating means for heating or cooling the material to be sprayed the spraying of the material involving the use of an atomising fluid, e.g. air
- B05B7/1613—Spraying apparatus for discharge of liquids or other fluent materials from two or more sources, e.g. of liquid and air, of powder and gas incorporating means for heating or cooling the material to be sprayed the spraying of the material involving the use of an atomising fluid, e.g. air comprising means for heating the atomising fluid before mixing with the material to be sprayed
Definitions
- the present invention relates to a spray device for spraying samples with a solution, wherein a liquid supply for the metered feeding of the solution and a gas supply are provided, which are connected via supply lines to a nozzle head having a gas and a liquid outlet, to spray the solution.
- MALDI Imaging Matrix Assisted Laser Desorption Ionization
- MALDI Imaging Applied to tissue samples, this technique is referred to as "MALDI Imaging.” It has pioneered imaging mass spectrometry, which has been established in cancer research, pharmaceutical development, and protein research for about 10 years MALDI technique is that the tissue samples can be prepared without great effort for the ban ⁇ chung, whereby not only fresh frozen but fixed by formalin and embedded in silicone and thus virtually unlimited shelf life, samples for this new and highly sensitive method of analysis to ⁇ are accessible, as well as, for example, very old Pro ⁇ benmaterial that may be over 100 years old.
- the basis of the MALDI technique is that the tissue sections are placed on steel plates designated as target or on microscope slides on which they adhere permanently after drying and fix themselves. Subsequently, the sections are coated with a mostly polar organic compound called matrix, which has the property of irradiation with laser beams absorb the light in the UV range and then evaporate due to the high energy input.
- matrix a mostly polar organic compound called matrix
- those substances of the tissue sample to be drawn back into the vapor phase which are not vaporized Eigent ⁇ Lich and would burn at normal warming. Due to the extremely rapid evaporation, it is possible to evaporate such samples.
- these molecules are ionized and absorbed by ei ⁇ nem mass spectrometer. In these mass spectrometers, they are then separated according to their charge and size, whereby software decodes and identifies the composition from these two parameters.
- the modified airbrush method is produced annul ⁇ , wherein an optimized spray head with an exact amount of liquid per unit of time is fed.
- the airbrush technique in which the air flow entrains the liquid according to the ej ector principle and finely distributed.
- Such a method is very well suited for extraction, the achievable crystal sizes after the drying of the matrix are in the order of 30 to 100 ym.
- the resolution in MALDI imaging is determined by the crystal size of the matrix and the laser diameter. The smaller the resolution of these two parameters, the more detailed information is obtained through the tissue, such as the tissue. As liver, kidney, skin and brain and all other internal organs, or their fine structure. This provides a wealth of new information, for example about the development of a cancer or the new compounds that are newly created by the cancer, which in turn allows early detection of the disease.
- very detailed Informa ⁇ functions on the distribution of a drug in a living body and their metabolites as well as the elimination from the body is obtained.
- the object of the present invention is to improve a spray device of the type mentioned in that formation of smaller crystals of Maxtrix in the coating after drying is made possible.
- the coating should also be formed as homogeneously as possible in order to enable the detection of the molecules not only qualitatively but also semi-quantitatively or quantitatively.
- the object of the present invention is achieved by a spray device of the type mentioned at the outset, in which the liquid outlet is provided at the end of a capillary line. is seen, for example, protrudes centrally through the gas outlet ⁇ out.
- gases or nitrogen are suitable as gases, depending on the type of matrix solution to be sprayed and the sample to be investigated.
- the end of the capillary is tapered at its outer periphery, preferably tapered conically. It has been shown that a particularly fine droplet formation is made possible by this measure, because by the taper, preferably in a conical shape, the swirling
- Gas flow is particularly effectively deflected in the direction of sosstechniksaus ⁇ let.
- the gas outlet is formed by an annular gap between the outer wall of the capillary and a guide tube or tube.
- the guide tube or the guide tube serves at the same time to stabilize the sensitive capillary, which is usually designed as a quartz capillary.
- the guide tube or the guide tube which may for example consist of PEEK (polyether ether ketone), may in turn be stabilized by a larger diameter, wherein in the end the guide tube and / or the capillary are preferably kept gas-tight in a housing.
- the Ge ⁇ housing has on the one hand the task of defining the position of the nozzle head exactly on the other hand, the housing preference ⁇ as a gas connection for the gas supply, in which Ge ⁇ housing a gas passage in an annular gap between the Füh ⁇ extension tube or the Guide tube and the capillary is provided. In this way, the housing comes to the functi ⁇ on to direct the gas flow from the gas supply into the annular gap between the guide tube or the guide tube and the capillary.
- the capillary line of the housing extends through and is connected at its other end with an already mentioned feed pump for the liquid supply, wherein instead of a pump and a dispenser with a suitable high resolution, for example 24,000 steps per Spritzen spal ⁇ ment can be used.
- a pump and a dispenser with a suitable high resolution for example 24,000 steps per Spritzen spal ⁇ ment can be used.
- the housing has front ⁇ preferably via a shoulder, which is arranged at a defined distance from the liquid outlet.
- The gives the position of the SI ⁇ senkopfes with its exact position.
- the nozzle head is held on a traversing device, which allows a method of the position of the nozzle head in the X, Y and / or Z direction.
- the Verfahr fürkeit in X- and Y-direction is important, since, if necessary, that is a fixed distance from the liquid outlet to the sample surface gearbei ⁇ tet can also be at a fixed position.
- the nozzle head is brought, for example with the aid of the paragraph described above on the housing in a defi ⁇ ned position with respect to the tissue surface.
- the subject of the present invention is also a method for coating samples by spraying with a solution using the spraying device described above. This is used in such a way that the sample is sprayed successively several times, wherein a subsequent spraying is carried out only when the previously applied layer is dried.
- a preferred embodiment of the method provides that the first applied layer is sprayed with a smaller amount of solution per area, the amount in the subsequent layers is increased until a certain amount of matrix per area is reached, and this amount of solution is repeatedly applied several times per area for the last layers.
- a typical number of Schich ⁇ th is in the range between 5 to 10, for example, 8 layers, so that the overall result is an appropriate thickness of the matrix, which then evaporates upon irradiation with the laser locally on a reduced down to the nearest crystal size surface.
- the first 1-3 layers, which are sprayed with the smaller amount of solution per area, thereby dry very quickly, so that no changes in position of small molecules are to be feared.
- the spray head then moves back into the initial position and repeats the on ⁇ supporting line by line for the next layer.
- FIG. 1 shows a section of an overall view of a spray head of a spray device.
- Fig. 2 is a detailed view of the exit areas of the spray head ⁇ ;
- Fig. 3 is a schematic view of a sprayer with adjustable spray head.
- a nozzle head 10 is shown, which can also be referred to as a spray ⁇ head.
- the nozzle head 10 is connected via a rear end 12 of a quartz capillary 14 as Kapillarlei ⁇ tion with a liquid supply, which is not shown in detail.
- This fluid delivery can be achieved by a constant-delivery syringe pump or a dispenser with a very high resolution of 24,000 steps per
- Syringe filling are adopted to promote the most accurate amounts of liquid through the capillary of the quartz capillary 14 to a liquid outlet 16 (see also Fig. 2).
- the Quarzkapillar effet 14 is guided through a housing 18 which is closed at its rear end by means of a union nut 20, the union nut 20 engages in a thread 22 in the housing 18 and the housing 18 against the outer circumference of the quartz capillary 14 seals off ⁇ ,
- the housing itself is stepped with a shoulder 24, whose function will be discussed in more detail later.
- the housing is internally provided with a central bore 26 which communicates with a radial port 28 in gas connection, which is connected to a gas supply (not shown) to ver ⁇ bind.
- the gas supply provides by suitable pumping means for the supply of air or other suitable gas such. As nitrogen, under a pressure of usually 2 to 3 bar, which is kept constant during operation, although other pressure values can be realized.
- a first guide tube 32 which may also be formed as a guide tube, within which a further guide tube 34 is inserted pressure-tight.
- the second guide ⁇ hose 34 surrounds the quartz capillary 14 on its outer ⁇ circumference with an annular gap, ie between the second guide tube 34 and the quartz capillary is a gas passage between the bore 26 of the housing 10 and a gas outlet 36 (see FIG. 2) at the end of the second guide Sly ⁇ ches 34, the quartz capillary 14 protrudes in the middle of a ⁇ be-determined span over the end of the second guide Sly ⁇ ches 34th As can be clearly seen from Fig.
- the annular gap 38 is provided to blow out the gas supplied through the gas port 28 at the end of the second guide tube 34, which is indicated by the arrows.
- the liquid outlet 16, he ⁇ thereby follows with a distance from the gas outlet 36 and is illustrated by the outlined drops. Due to the distance between the gas outlet 36 and the liquid outlet 16, the gas flow can easily swirl, with the end of the glass capillary 14 is provided with a conical taper 40, which promotes the fluidized gas flow in the direction of dosed promoted, exiting from the liquid outlet 16 liquid stream.
- this conical taper which may also be formed spherical, there is a particularly fine droplet formation, wherein the gas stream further promotes the fine liquid droplets in the direction of a arranged below the liquid outlet 16 sample.
- the nozzle head shown in Fig. 1 and 2 is mounted in a spray device 100, wherein the shoulder 24 rests in a defined position of a receptacle, so that the liquid ⁇ outlet 16 is at a defined distance to arranged on a table metallic targets 110, on which is applied to prepare for further investigation to be sprayed tissue 112.
- the receptacle 102 of the nozzle head 10 is laterally arranged in a Y-direction movable on a support 104, which in turn is movably mounted on a rail 106 in an X-direction, so that the nozzle ⁇ head by moving the receptacle 102 on the carrier 104 and Method of the carrier 104 on the rail 106 in the X and Y direction is adjustable.
- the receptacle 102 may be adjustable in the Z direction in order to set the liquid outlet 16 in its distance from the targets 110 or prepared Glasträ ⁇ like. In general, but during the actual spraying an adjustment of the distance between the spray head 10 and the targets 110 not erforder ⁇ lich.
- the spraying of the tissue 112 in such a manner takes place, that the nozzle head 10 which leaves zei ⁇ lenweise surface to be sprayed, as is usually the detected through the spray area is smaller than the area of spraying ⁇ the tissue.
- the sprayed solution Matrixlö ⁇ detects a strip-shaped area of a width of about 2 mm at a line-wise manner.
- the outer diameter of the selected quartz capillary was 280 ym, wherein between the second guide tube 34 and 14, an annular gap with a Hö ⁇ he was provided of 60 ym to the outer diameter of the quartz capillary, that is, the inner diameter of the fabricated from PEEK second guide tube was 400 ym.
- the quartz capillary 14 had an inner channel 42 with a diameter of 75 ym.
- the latter was run line by line until a desired area had been completely sprayed with the matrix solution. It is at the selected nozzle geometry and the selected 2 mm directly sprayed, wherein the line spacing is selected so that an overlap neigh ⁇ barter sprayed lines only minimally exists to avoid deviating layer thicknesses in the overlap region.
- a second layer was applied by spraying, which has been carried out in otherwise moving ⁇ chen process parameters under a doubling of the liquid supply 20 ⁇ per minute.
- Egg ⁇ ne third layer was washed with 30 ⁇ per minute, a fourth with 40 ⁇ per minute is applied, wherein a total of 8 layers have been applied, all under ei ⁇ ner hydration of 40 ⁇ from the fourth layer have been applied per minute.
- Differ quartz capillary and the guide hose significantly, but also the amount of liquid may differ significantly from the values depending on the type to versprü ⁇ Henden matrix solution. Deviations from the selected pressure are also possible with the gas supply in order to be able to apply correspondingly different layers depending on the desired examination.
Landscapes
- Physics & Mathematics (AREA)
- Optics & Photonics (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Sampling And Sample Adjustment (AREA)
Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE102015113170.6A DE102015113170A1 (de) | 2015-08-10 | 2015-08-10 | Sprühvorrichtung und Verfahren zum Beschichten von Proben |
PCT/EP2016/058451 WO2017025205A1 (de) | 2015-08-10 | 2016-04-15 | Sprühvorrichtung und verfahren zum beschichten von proben |
Publications (2)
Publication Number | Publication Date |
---|---|
EP3334537A1 true EP3334537A1 (de) | 2018-06-20 |
EP3334537B1 EP3334537B1 (de) | 2020-10-07 |
Family
ID=55759592
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP16717136.2A Active EP3334537B1 (de) | 2015-08-10 | 2016-04-15 | Verfahren zum beschichten von proben |
Country Status (4)
Country | Link |
---|---|
US (1) | US20180236470A1 (de) |
EP (1) | EP3334537B1 (de) |
DE (1) | DE102015113170A1 (de) |
WO (1) | WO2017025205A1 (de) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2024047722A1 (ja) * | 2022-08-30 | 2024-03-07 | 株式会社日立ハイテク | 液体霧化装置及びそれを用いた分析装置 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5772964A (en) * | 1996-02-08 | 1998-06-30 | Lab Connections, Inc. | Nozzle arrangement for collecting components from a fluid for analysis |
DE20210784U1 (de) * | 2001-11-14 | 2003-11-27 | CARBOTEC Gesellschaft für instrumentelle Analytik mbH | Fokussierte Elektrosprayvorrichtung |
-
2015
- 2015-08-10 DE DE102015113170.6A patent/DE102015113170A1/de active Pending
-
2016
- 2016-04-15 US US15/751,865 patent/US20180236470A1/en not_active Abandoned
- 2016-04-15 EP EP16717136.2A patent/EP3334537B1/de active Active
- 2016-04-15 WO PCT/EP2016/058451 patent/WO2017025205A1/de active Application Filing
Also Published As
Publication number | Publication date |
---|---|
WO2017025205A1 (de) | 2017-02-16 |
EP3334537B1 (de) | 2020-10-07 |
DE102015113170A1 (de) | 2017-02-16 |
US20180236470A1 (en) | 2018-08-23 |
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