CA3032234C - Electron microscopy - Google Patents
Electron microscopy Download PDFInfo
- Publication number
- CA3032234C CA3032234C CA3032234A CA3032234A CA3032234C CA 3032234 C CA3032234 C CA 3032234C CA 3032234 A CA3032234 A CA 3032234A CA 3032234 A CA3032234 A CA 3032234A CA 3032234 C CA3032234 C CA 3032234C
- Authority
- CA
- Canada
- Prior art keywords
- sample
- fluid
- sample support
- gas
- electron microscopy
- 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.)
- Active
Links
- 238000001493 electron microscopy Methods 0.000 title claims abstract description 123
- 239000012530 fluid Substances 0.000 claims abstract description 288
- 238000000034 method Methods 0.000 claims abstract description 98
- 238000002360 preparation method Methods 0.000 claims abstract description 54
- 239000007789 gas Substances 0.000 claims description 277
- 238000001816 cooling Methods 0.000 claims description 35
- 230000008020 evaporation Effects 0.000 claims description 29
- 238000001704 evaporation Methods 0.000 claims description 29
- 230000000717 retained effect Effects 0.000 claims description 23
- 238000000151 deposition Methods 0.000 claims description 19
- 239000007788 liquid Substances 0.000 claims description 19
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 claims description 14
- 238000012545 processing Methods 0.000 claims description 11
- 230000009471 action Effects 0.000 claims description 10
- 239000000112 cooling gas Substances 0.000 claims description 9
- 230000004913 activation Effects 0.000 claims description 7
- 230000003213 activating effect Effects 0.000 claims 1
- 238000003384 imaging method Methods 0.000 abstract description 31
- 238000000386 microscopy Methods 0.000 abstract description 16
- 238000004017 vitrification Methods 0.000 description 11
- 229920002521 macromolecule Polymers 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- 229910052799 carbon Inorganic materials 0.000 description 7
- 239000011148 porous material Substances 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 230000008021 deposition Effects 0.000 description 5
- 230000003993 interaction Effects 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 230000001627 detrimental effect Effects 0.000 description 3
- 229910001873 dinitrogen Inorganic materials 0.000 description 3
- 230000000704 physical effect Effects 0.000 description 3
- 238000010586 diagram Methods 0.000 description 2
- 238000010894 electron beam technology Methods 0.000 description 2
- 238000007710 freezing Methods 0.000 description 2
- 239000011261 inert gas Substances 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 230000033001 locomotion Effects 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 238000005192 partition Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000004904 shortening Methods 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 238000007792 addition Methods 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000005464 sample preparation method Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000004627 transmission electron microscopy Methods 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- G01N1/312—Apparatus therefor for samples mounted on planar substrates
-
- 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
-
- 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
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L7/00—Heating or cooling apparatus; Heat insulating devices
- B01L7/50—Cryostats
-
- 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
- B01L9/523—Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips for multisample carriers, e.g. used for microtitration plates
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
- G01N30/12—Preparation by evaporation
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
- H01J37/00—Discharge tubes with provision for introducing objects or material to be exposed to the discharge, e.g. for the purpose of examination or processing thereof
- H01J37/02—Details
- H01J37/023—Means for mechanically adjusting components not otherwise provided for
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
- H01J37/00—Discharge tubes with provision for introducing objects or material to be exposed to the discharge, e.g. for the purpose of examination or processing thereof
- H01J37/02—Details
- H01J37/20—Means for supporting or positioning the object or the material; Means for adjusting diaphragms or lenses associated with the support
-
- 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
- B01L2300/1894—Cooling means; Cryo cooling
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
- H01J2237/00—Discharge tubes exposing object to beam, e.g. for analysis treatment, etching, imaging
- H01J2237/002—Cooling arrangements
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Analytical Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Clinical Laboratory Science (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Sampling And Sample Adjustment (AREA)
- Analysing Materials By The Use Of Radiation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1613173.2A GB201613173D0 (en) | 2016-07-29 | 2016-07-29 | Electron microscopy |
| GB1613173.2 | 2016-07-29 | ||
| PCT/EP2017/069240 WO2018020036A1 (en) | 2016-07-29 | 2017-07-28 | Electron microscopy |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA3032234A1 CA3032234A1 (en) | 2018-02-01 |
| CA3032234C true CA3032234C (en) | 2024-02-13 |
Family
ID=56936668
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3032234A Active CA3032234C (en) | 2016-07-29 | 2017-07-28 | Electron microscopy |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US11067486B2 (enExample) |
| EP (1) | EP3491360B1 (enExample) |
| JP (1) | JP6997757B2 (enExample) |
| CN (1) | CN109891208A (enExample) |
| AU (1) | AU2017302126B2 (enExample) |
| CA (1) | CA3032234C (enExample) |
| DK (1) | DK3491360T3 (enExample) |
| ES (1) | ES3026360T3 (enExample) |
| GB (1) | GB201613173D0 (enExample) |
| WO (1) | WO2018020036A1 (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3647763B1 (en) | 2018-10-29 | 2021-07-14 | FEI Company | A method of preparing a biological sample for study in an analysis device |
| CN111389478B (zh) * | 2020-03-23 | 2023-07-25 | 西安医学院 | 一种组织切片的实验处理装置及其使用方法 |
| GB2593491A (en) * | 2020-03-24 | 2021-09-29 | Res & Innovation Uk | Electron microscopy support |
| EP4109069A1 (en) | 2021-06-25 | 2022-12-28 | FEI Company | Blotting material with profiled region, method of manufacturing same, and uses thereof |
| NL2033291B1 (en) | 2022-10-12 | 2024-04-26 | Academisch Ziekenhuis Leiden | Device and Method for Cryogenic Electron Microscopy Sample Preparation |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59109840A (ja) | 1982-12-16 | 1984-06-25 | Hitachi Koki Co Ltd | 走査形電子顕微鏡用生物試料の前処理方法 |
| US7112790B1 (en) * | 2003-08-13 | 2006-09-26 | Cypress Semiconductor Corp. | Method to prepare TEM samples |
| JP2007163447A (ja) * | 2005-12-09 | 2007-06-28 | Lee Bing Huan | 電子顕微鏡用の超薄液体制御板 |
| JP4891830B2 (ja) * | 2007-04-18 | 2012-03-07 | 日本電子株式会社 | 電子顕微鏡用試料ホルダおよび観察方法 |
| WO2009065585A2 (en) * | 2007-11-20 | 2009-05-28 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Ultra-rapid freezing device and method |
| GB0724736D0 (en) * | 2007-12-19 | 2008-01-30 | Oxford Nanolabs Ltd | Formation of layers of amphiphilic molecules |
| GB2461708A (en) * | 2008-07-08 | 2010-01-13 | Silson Ltd | Sample holder |
| JP2010054272A (ja) | 2008-08-27 | 2010-03-11 | National Institute Of Advanced Industrial Science & Technology | スピン偏極走査電子顕微鏡 |
| AT507079B1 (de) * | 2009-01-22 | 2010-02-15 | Leica Mikrosysteme Gmbh | Vorrichtung und verfahren zum präparieren von proben |
| JP5550262B2 (ja) * | 2009-05-29 | 2014-07-16 | キヤノン株式会社 | 試料観察システム及び試料観察方法 |
| US9312095B2 (en) * | 2010-03-24 | 2016-04-12 | Brown University | Method and system for automating sample preparation for microfluidic cryo TEM |
| GB201118282D0 (en) | 2011-10-21 | 2011-12-07 | Cancer Rec Tech Ltd | Sample slide preparation method and device |
| JP5930922B2 (ja) * | 2012-09-14 | 2016-06-08 | 株式会社日立ハイテクノロジーズ | 荷電粒子線装置及び試料観察方法 |
| JP6239246B2 (ja) * | 2013-03-13 | 2017-11-29 | 株式会社日立ハイテクノロジーズ | 荷電粒子線装置、試料観察方法、試料台、観察システム、および発光部材 |
| CA2919961C (en) * | 2013-08-13 | 2023-10-10 | Medical Research Council | Electron microscopy sample support comprising porous metal foil |
| GB201318463D0 (en) * | 2013-08-13 | 2013-12-04 | Medical Res Council | Graphene Modification |
| EP2853847B1 (en) * | 2013-09-30 | 2016-02-03 | Fei Company | Preparation of cryogenic sample for charged-particle microscopy |
| CA2932803C (en) | 2013-12-13 | 2020-09-08 | Ventana Medical Systems, Inc. | Thermal management in the context of automated histological processing of biological specimens and associated technology |
| GB2537579A (en) | 2014-11-07 | 2016-10-26 | Linkam Scient Instr Ltd | Microscopic sample preparation |
| EP4215898A1 (en) * | 2015-04-20 | 2023-07-26 | Ventana Medical Systems, Inc. | Inkjet deposition of reagents for histological samples |
| DK3260839T3 (da) * | 2016-06-22 | 2021-04-19 | Univ Maastricht | Fremgangsmåde til forberedelse af prøver til billeddannelses- eller diffraktionseksperimenter under kyrogene betingelser |
| EP3647763B1 (en) * | 2018-10-29 | 2021-07-14 | FEI Company | A method of preparing a biological sample for study in an analysis device |
-
2016
- 2016-07-29 GB GBGB1613173.2A patent/GB201613173D0/en not_active Ceased
-
2017
- 2017-07-28 AU AU2017302126A patent/AU2017302126B2/en active Active
- 2017-07-28 ES ES17745722T patent/ES3026360T3/es active Active
- 2017-07-28 CA CA3032234A patent/CA3032234C/en active Active
- 2017-07-28 JP JP2019503570A patent/JP6997757B2/ja active Active
- 2017-07-28 EP EP17745722.3A patent/EP3491360B1/en active Active
- 2017-07-28 WO PCT/EP2017/069240 patent/WO2018020036A1/en not_active Ceased
- 2017-07-28 DK DK17745722.3T patent/DK3491360T3/da active
- 2017-07-28 CN CN201780047251.7A patent/CN109891208A/zh active Pending
- 2017-07-28 US US16/320,961 patent/US11067486B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| AU2017302126A1 (en) | 2019-02-07 |
| US11067486B2 (en) | 2021-07-20 |
| EP3491360B1 (en) | 2025-03-19 |
| GB201613173D0 (en) | 2016-09-14 |
| ES3026360T3 (en) | 2025-06-11 |
| EP3491360A1 (en) | 2019-06-05 |
| AU2017302126B2 (en) | 2022-07-07 |
| CN109891208A (zh) | 2019-06-14 |
| WO2018020036A1 (en) | 2018-02-01 |
| JP2019528435A (ja) | 2019-10-10 |
| JP6997757B2 (ja) | 2022-02-04 |
| CA3032234A1 (en) | 2018-02-01 |
| DK3491360T3 (da) | 2025-06-10 |
| US20190170618A1 (en) | 2019-06-06 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20220520 |
|
| EEER | Examination request |
Effective date: 20220520 |
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| EEER | Examination request |
Effective date: 20220520 |
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| EEER | Examination request |
Effective date: 20220520 |
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| EEER | Examination request |
Effective date: 20220520 |
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| EEER | Examination request |
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| EEER | Examination request |
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| EEER | Examination request |
Effective date: 20220520 |
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| EEER | Examination request |
Effective date: 20220520 |
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| EEER | Examination request |
Effective date: 20220520 |