EP3866977A1 - Appareil de préparation d'échantillon - Google Patents

Appareil de préparation d'échantillon

Info

Publication number
EP3866977A1
EP3866977A1 EP19783539.0A EP19783539A EP3866977A1 EP 3866977 A1 EP3866977 A1 EP 3866977A1 EP 19783539 A EP19783539 A EP 19783539A EP 3866977 A1 EP3866977 A1 EP 3866977A1
Authority
EP
European Patent Office
Prior art keywords
heat conducting
conducting body
receiving section
contact surface
cartridge
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.)
Withdrawn
Application number
EP19783539.0A
Other languages
German (de)
English (en)
Inventor
Ronald Martinus Alexander Heeren
Alain Vincent Jacques CREISSEN
Paul Frans Jozef Laeven
Lars Catharina Pascal SMEETS
Pascal Paul Marie Huysmans
Lennart Randolf Sibren HUIZING
Shane Raymond ELLIS
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.)
Universiteit Maastricht
Academisch Ziekenhuis Maastricht
Original Assignee
Universiteit Maastricht
Academisch Ziekenhuis Maastricht
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 Universiteit Maastricht, Academisch Ziekenhuis Maastricht filed Critical Universiteit Maastricht
Publication of EP3866977A1 publication Critical patent/EP3866977A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L9/00—Supporting devices; Holding devices
    • B01L9/52—Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
    • 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
    • G01N1/30—Staining; Impregnating ; Fixation; Dehydration; Multistep processes for preparing samples of tissue, cell or nucleic acid material and the like for analysis
    • G01N1/31—Apparatus therefor
    • 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
    • G01N1/44—Sample treatment involving radiation, e.g. heat
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0678—Facilitating or initiating evaporation
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • B01L2300/1827—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using resistive heater
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • B01L2400/049—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics vacuum
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D—PROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D1/00—Processes for applying liquids or other fluent materials
    • B05D1/60—Deposition of organic layers from vapour phase
    • 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

Definitions

  • the invention relates to a sample preparation apparatus comprising a vacuum chamber, at least one sample holding unit for holding a sample in the vacuum chamber, and at least one sublimation device arranged in the vacuum chamber at a distance from the at least one sample holding unit, wherein the sublimation device comprises a heat conducting body having at least one receiving section configured to receive a substance to be sublimated and at least one temperature conditioner for cooling/heating the receiving section of the heat conducting body to carry out a sublimation and deposition process on the sample in the vacuum chamber.
  • the sample preparation apparatus comprises:
  • the heat conducting body has an optimized thermal geometry to provide a sample preparation apparatus configured for processing the substance to be sublimated in a more efficient manner.
  • the optimized thermal geometry of the heat conducting body is achieved by varying the thickness of the heat conducting body below the receiving section.
  • the optimized thermal geometry of the heat conducting body further permits to use a relatively low number of temperature conditioners, as the amount of material of the heat conducting body to be cooled/heated by each temperature conditioner can be reduced significantly.
  • the or each temperature conditioner is capable of cooling/heating the heat conducting body in a more efficient manner than a heat conducting body without varying thickness below the receiving section.
  • the thermal geometry of the heat conducting body is configured to provide a uniform temperature distribution in the surface of the receiving section contacting directly or indirectly the substrate to be sublimated.
  • the relatively low amount of material of the heat conducting body also provides an improved temperature controllability for the substance to be sublimated, because the heat conducting body is able to react in a faster manner for adapting the temperature conditions for the substance.
  • the vacuum chamber 15 has connectors 5, 6 to be connected to an auxiliary liquid or gas reservoir, i.e. a first connector 5 allows the introduction of water or solvent vapor for further enhancement of the surface chemistry, including rehydration of the component layer atop the sample to enhance the co-crystallization of the components with the biological samples and a second connector 6 allowing the introduction of for example nitrogen.
  • the apparatus 100 may comprise automated valves (not shown) in the connections 5, 6 between the vacuum chamber 15 and the liquid or gas reservoir to allow automated introduction of water or solvent vapor at a specific time point and under specific pressure condition.
  • the round shape seen in a cross section view in the longitudinal direction follows substantially a circle having a radius of curvature of at least two times the longitudinal dimension I of the I contact surface 144.
  • This slightly curved contact surface 144 reduces or even eliminates gap(s) between the heat conducting body 132 and the cartridge 150. These gaps, in particular during vacuum conditions, have the result that the contact surface of the cartridge is not heated in an efficient manner at all.
  • the sublimation device 4; 104 further comprises a temperature sensor 70 (figure c) connected by a cable 71 to a connector 73 to be connected to a temperature controller (not shown) controlling the temperature conditioners 36; 136, wherein the temperature sensor 70 is positioned closer to the recess 38; 138 than to the at least one temperature conditioner 36; 136. More specific, the temperature sensor 70 is arranged in the heat conducting body 32; 132 adjacent to the recess 36; 136 of the heat conducting body 32; 132. By positioning the temperature sensor 70 in such a position it is possible to obtain a temperature by a single sensor 70 which provides a good representation of the temperature in the contact surface 44; 144.
  • the controller By using in the controller the measured temperature and the characteristics of the thermal conductivity of the heat conducting body 32; 132 heated or cooled by the temperature conditioners 36; 136, the controller is able to achieve or maintain the desired temperature of the contact surface 44; 144.
  • the figures 3 and 4a-c further show that the heaters 36 are connected by cables 76 to connectors 78.
  • the heat conducting body 32 is further provided with seals 81 to maintain a vacuum in the chamber 15 and an insulator 83 near the rear side wall 45 to maintain the heat inside the heat conducting body 32; 132.
  • the rear side wall 45 of the vacuum chamber 15 comprises the vacuum connection 1 , a support for supporting the sample holding unit 8 in the vacuum chamber 15 and a support for supporting the sublimation device 4 in the vacuum chamber 15, and the first and second connectors 5, 6 as discussed above.
  • all electrical connections are moved to the outside of the chamber 15, creating a safer, more robust and easier to clean chamber 15 of the apparatus 100.
  • this configuration provides an apparatus comprising more serviceability, because it makes the clam shell design having two pivotally portions possible which provide great access to the interior of the chamber 15 for cleaning, inspection and maintenance.
  • the arrangement of the various functions in the rear wall 45 also reduced the time to create a vacuum atmosphere inside the apparatus 100.
  • the sample holding unit 8 is arranged between the vacuum connection 1 and the sublimation device 4 in the chamber 15.
  • the sublimation device 4 is arranged in the vacuum chamber 15 between the first and second connectors 5, 6 and the sample holding unit 8. Hence, seen in vertical direction the sample holding unit 8 and the sublimation device 4 are arranged between the vacuum connection 1 and the first and second connections 5, 6.
  • This configuration of the apparatus 100 provides an excellent sublimation process and an excellent deposition process on the sample. Further, it is possible to provide on a single outer side of the apparatus, i.e. the rear side wall 45, all the connections for temperature control and vacuum control.
  • the temperature conditioners 36; 136 outside (not shown) the heat conducting body 32; 132 in contact with an outer surface of the heat conducting body.
  • the substance to be sublimated is pre-prepared as follows: a matrix powder is added to a solvent, for instance acetone, to obtain a mixture of the matrix powder and the solvent. The mixture is applied into the matrix tray, for example pipetted in the basin. The matrix tray is (pre-)heated and the solvent evaporates. During this process the matrix substance will stick to the surface of the matrix tray in an uniform manner, such that an optimal heat transfer can be obtained in the sublimation device for the sublimation process of the matrix substance for preparing a sample.
  • a solvent for instance acetone

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Engineering & Computer Science (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Sampling And Sample Adjustment (AREA)

Abstract

L'invention concerne un appareil de préparation d'échantillon comprenant une chambre à vide, au moins une unité de maintien d'échantillon destinée à maintenir un échantillon dans la chambre à vide, et au moins un dispositif de sublimation agencé dans la chambre à vide à une certaine distance de l'au moins une unité de maintien d'échantillon, le dispositif de sublimation comprenant un corps thermoconducteur comprenant au moins une section de réception configurée pour recevoir une substance à sublimer et au moins un conditionneur de température pour chauffer/refroidir la section de réception du corps conducteur de chaleur afin de réaliser un processus de sublimation et de dépôt sur l'échantillon dans la chambre à vide.
EP19783539.0A 2018-10-15 2019-10-10 Appareil de préparation d'échantillon Withdrawn EP3866977A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP18200471 2018-10-15
PCT/EP2019/077514 WO2020078830A1 (fr) 2018-10-15 2019-10-10 Appareil de préparation d'échantillon

Publications (1)

Publication Number Publication Date
EP3866977A1 true EP3866977A1 (fr) 2021-08-25

Family

ID=63862040

Family Applications (1)

Application Number Title Priority Date Filing Date
EP19783539.0A Withdrawn EP3866977A1 (fr) 2018-10-15 2019-10-10 Appareil de préparation d'échantillon

Country Status (2)

Country Link
EP (1) EP3866977A1 (fr)
WO (1) WO2020078830A1 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP4341849A1 (fr) 2021-05-19 2024-03-27 Universiteit Maastricht Pathologie numérique du cancer du sein basée sur une base de données d'imagerie par spectrométrie de masse sur une seule cellule
CN114384146B (zh) * 2021-12-24 2024-06-14 天津国科医疗科技发展有限公司 一种样品进出装置以及质谱仪

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH1025563A (ja) * 1996-07-08 1998-01-27 Shinko Seiki Co Ltd 真空蒸着装置及び真空蒸着方法
JP3508484B2 (ja) * 1997-07-14 2004-03-22 松下電器産業株式会社 機能性薄膜の形成方法及び形成装置
JP2011256427A (ja) * 2010-06-09 2011-12-22 Hitachi Zosen Corp 真空蒸着装置における蒸着材料の蒸発、昇華方法および真空蒸着用るつぼ装置
WO2014162557A1 (fr) 2013-04-04 2014-10-09 株式会社島津製作所 Procédé de préparation d'un échantillon pour maldi et dispositif associé

Also Published As

Publication number Publication date
WO2020078830A1 (fr) 2020-04-23

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