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WO2018228574A1 - Lame de microscope avec cibles noire et blanche intégrées - Google Patents

Lame de microscope avec cibles noire et blanche intégrées Download PDF

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Publication number
WO2018228574A1
WO2018228574A1 PCT/CN2018/091685 CN2018091685W WO2018228574A1 WO 2018228574 A1 WO2018228574 A1 WO 2018228574A1 CN 2018091685 W CN2018091685 W CN 2018091685W WO 2018228574 A1 WO2018228574 A1 WO 2018228574A1
Authority
WO
WIPO (PCT)
Prior art keywords
microscope slide
reference target
black
white
white reference
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.)
Ceased
Application number
PCT/CN2018/091685
Other languages
English (en)
Inventor
Frederick Knute Husher
Jee Jong Shum
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.)
Sunstone Scientific Ltd
Original Assignee
Sunstone Scientific Ltd
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 Sunstone Scientific Ltd filed Critical Sunstone Scientific Ltd
Priority to EP18817809.9A priority Critical patent/EP3638995A4/fr
Priority to JP2020519172A priority patent/JP7369120B2/ja
Priority to CN201880039127.0A priority patent/CN110770553A/zh
Priority to KR1020207001292A priority patent/KR20200040746A/ko
Publication of WO2018228574A1 publication Critical patent/WO2018228574A1/fr
Anticipated expiration legal-status Critical
Priority to US16/715,715 priority patent/US11662564B2/en
Priority to US18/302,495 priority patent/US12313834B2/en
Ceased legal-status Critical Current

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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
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/06—Means for illuminating specimens
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/34—Microscope slides, e.g. mounting specimens on microscope slides
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/36—Microscopes arranged for photographic purposes or projection purposes or digital imaging or video purposes including associated control and data processing arrangements
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/36—Microscopes arranged for photographic purposes or projection purposes or digital imaging or video purposes including associated control and data processing arrangements
    • G02B21/364—Projection microscopes
    • 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
    • G01N2001/2893—Preparing calibration standards

Definitions

  • the present invention relates to a microscope slide with integrated targets.
  • the present invention particularly relates to the microscope slide with integrated black and white targets.
  • the microscope slide as disclosed in the present invention with integrated black and white target enables the digital imaging on different systems to be able to set the illumination level do that the process control target arrays and co-resident tissue can be used together and yield similar results.
  • the accepted baseline white reference is a freshly pressed barium sulfate tablet, as established for use with the MacBeth PCM II.
  • Black is generally provided by a void that prevents reflected light from returning to the imaging device.
  • the white target will be some sort of metal oxide which will stain with exposure to eosin unless the oxide surface is protected. While a black target could be printed containing a carbon compound it will have some amount of 1st surface reflection and thus not be a perfect black. However, it will be black enough relative to any staining that could occur with the biomaterials.
  • the object of the present invention to integrate the black and white reference targets on the slide itself.
  • the imaging reference is a part of the slide and can ensure close results between different imaging systems.
  • a microscope slide with integrated black and white targets ensures that digital imaging on different systems will be able to set the illumination level so that the process control target arrays and co-resident tissue section can be used together and yield similar results.
  • the present invention discloses that the white targets will not be perfect it will represent the whitest object on the slide.
  • the present invention discloses the black targets sets the dynamic range for the camera.
  • the present invention discloses that the co-resident targets are included among the microscope slide to provide objective values by which the stain specific targets and the tissue section itself can be evaluated against.
  • Figure 1 illustrates a slide for H&E usage that contains black and white imaging targets on the same line as the chemical targets reactive to Hematoxylin and Eosin Y stains.
  • the black target is at the right and the white target is on the right.
  • Three images are shown for the same slide: left is the slide before the application of tissue sections, the center has three tissue sections applied, and the right is the slide after being stained.
  • the grayed out zones represent a paraffin shield over the targets or captured formaldehyde fixed tissue sections.
  • the results of reference control slides are entirely subjective because there is no inclusion of black and white reference targets the target (s) are inconsistent in density, and unique in reactivity to a single stain reagent.
  • the reference control slide at best has a sausage that contains portions containing known antigen sites. The antigen concentration is unknown so all that can come from the stained slide is that the reagents all appear to be working at enough of a level to signal the antigen presence.
  • no objective measure can be performed as because the result is the cumulative product of the antigen retrieval, primary stain reagents, and secondary stain reagents. Therefore, the reference control slide at best simply provides some comfort to the user that all appears to be working.
  • Digital imaging of microscope slides containing stained biomaterials is evolving to perform prescreening and potentially full diagnostic determination on the stained materials.
  • the imaging system must adjust the illumination light level so that the digital image is not in compression at either the white or black boundaries.
  • the conventional solution is to have black and white targets located where the label is expected to be positioned. The underlying assumption is that the white and black targets represent the extremes that the slide can present. However, in doing so there is compression in the digital scale as the black is much blacker and the white much whiter than can realized by the staining of a tissue section.
  • a microscope slide is disclosed that incorporates control and reference target standards which are co-resident with a tissue section or loose cell deposit.
  • the reference targets and tissue section record the processing experience between tissue capture and cover slipping of the stained slide.
  • the microscope slide target arrays are co-resident black and white reference targets.
  • the black and white reference targets have experienced that same exposure to reagents and processing as the other targets and tissue section.
  • the black and white reference targets enable the imaging system to shift the illumination level so that the working range is expanded. Depending upon the biomaterial type the processing experience can change considerably.
  • the different processing paths can be grouped as but not limited to ImmunoHistoChemical (IHC) , Hematoxylin and Eosin (H&E) plus special stains, Urine smear H&E plus special stains, and Papanicolaou stain (PAP) smear which is composed of five dyes in three solutions.
  • IHC ImmunoHistoChemical
  • H&E Hematoxylin and Eosin
  • PAP Papanicolaou stain
  • a pure black deposit target in general is difficult to produce because, by definition, it must absorb all light.
  • the classic solution is to simply provide a void that folds the light path in such a manner that a reflection cannot be returned.
  • a black target will be somewhat reflective, but it is usually good enough as nothing else on the slide will be nearly so black.
  • both the targets i.e. the black and white targets are printed paint or ink deposits which are non-reactive to any of the reagents used to process a slide.
  • the white target in an ideal situation would be a perfect white. However, there is very little stained biomaterial usefulness that gets more than halfway from black to white. Thus, the white can be 5-10%away from perfect white and still be of useful value.
  • the main requirement is that the white be of a metal oxide or sulfate composition that is stable with the passage of time when not left exposed to sunlight. Aluminum and Titanium oxides more than meet the requirements.
  • the preferred solution to the above mentioned problem is disclosed.
  • the black and white targets are both based on an anhydride based epoxy paint base that is catalyzed by direct UV light exposure at nominally 365nm.
  • the anhydride catalyzer is composed of methyl tetrahydrophthalic anhydride and diphenyliodonium hexafluroroarsenate.
  • Other than UV initiated, anhydrides require the addition of heat to function in catalyzing the epoxy to cross-link.
  • the preferred UV initiated anhydride and its companion are listed, but there are other solutions possible that can be found when performing a search of anhydride producing companies. While such a paint/ink can be constructed as needed, it is usually a purchased component that has been optimized for the printing method being used.
  • Fabrication of the paint/ink must address the difficulty in achieving good wetting between the pigment particles and the epoxy binder.
  • Anhydride based paints also called an ink when having low viscosity
  • anhydride mixed in with the epoxy often have the anhydride mixed in with the epoxy as the pot life can be many months in duration.
  • To lower the viscosity would be known knowledge of those involved in the printing industry and the formulation varies depending on the surface the epoxy mixture is to applied onto and the printing method used.
  • heat triggered anhydride-epoxy paint/inks are commonly used, the heat necessary to initiate the reaction can potentially damage biomaterials (proteins, peptide, and chemical targets) that may be co-resident with the paint/ink.
  • the anhydride catalyzer eliminates the unreacted amines found with an amino-silane based catalyzer that would otherwise support non-specific staining.
  • Free amine end groups can and will capture both biomaterials and some of the special stains. Specifically, this addresses the issue of undesired staining of the white target by the slide processing reagents, in particular the staining reagents.
  • As a free amine end group on the surface of the paint/ink it can capture both the primary antibody and secondary stain reagents and become stained. Thus, defeating the value of having an integrated white target on the slide.
  • the black pigment uses a carbon dust of less than 2 microns diameter while the white uses aluminum or titanium oxide beads. Titanium oxide is the preferred metal oxide for this application.
  • the printing of the targets can be done by pad stamp or syringe with the syringe the preferred method as it supports better feature size control of the target deposition.
  • the aforementioned white targets are composed of metal oxide pigments within an anhydride catalyzed epoxy.
  • the aforementioned black targets are composed of carbon pigments within a UV initiated anhydride catalyzed epoxy.
  • the anhydride catalyzer is UV initiated by direct UV light exposure. The primary advantage of using the UV initiated anhydride catalyzer is that the heat needed to initiate anhydride-epoxy reaction exceeds what the biomaterials (proteins, peptide, and chemical targets) can tolerate without damage. More importantly is the elimination of any free amines that could react with the stain reagents.
  • the integrated black and white targets are co-resident with a tissue section or loose cells on a microscope slide.
  • the integrated black and white targets are non-reactive to biomaterial stains.
  • the integrated black and white targets are stable through exposure to antigen retrieval activities: buffers, heat, duration and other environmental factors.
  • the integrated black and white targets are non-reactive to hydroxyl, amine, amide, hydrazide, and aromatic benzene compounds.
  • Figure 1 illustrates an H&E usage slide that contains one line of targets, bounded on the ends by black and white pigment targets.
  • the pigment targets are printed separately from the special stains targets.
  • the black/white targets are printed using a modified dispensing pump.
  • the dispensing pump applies a spit and suck cycle to the epoxy mixture fed down a hollow tube that is held to the slide surface. When the print head lifts following the spit and suck cycle the deposit remains as a dot.
  • the balance of the chemical targets are printed at another station and the slide passed through a UV exposed tunnel, initiating the anhydride catalyzer to cure the epoxy.
  • the epoxy plus anhydride is purchased pre-mixed. To ensure homogeneity the epoxy mixture is stirred and then degassed.
  • the paint/ink is purchased with the pigment already blended in. Such a paint/ink is available from a number of vendors, but in all cases the formulation is proprietary to the vendor and will likely be different from each vendor. Viscosity is adjusted as needed using the recommended thinner the vendor supplies.
  • the white pigment is barium sulfate which avoids most chemical interactions with the special stains. This is contrast to titanium dioxide or aluminum oxide, which may react with the Eosin Y.

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  • Physics & Mathematics (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Optics & Photonics (AREA)
  • Engineering & Computer Science (AREA)
  • Multimedia (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Microscoopes, Condenser (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

L'invention concerne une lame de microscope avec des cibles intégrées, qui comprend une cible de référence noire et une cible de référence blanche co-résidentes sur la lame de microscope. La lame de microscope avec cibles noire et blanche intégrées permet à l'imagerie numérique sur différents systèmes de pouvoir régler le niveau d'éclairage de sorte que les réseaux cibles de commande de processus et le tissu co-résidents peuvent être utilisés ensemble et produire des résultats similaires.
PCT/CN2018/091685 2017-06-15 2018-06-15 Lame de microscope avec cibles noire et blanche intégrées Ceased WO2018228574A1 (fr)

Priority Applications (6)

Application Number Priority Date Filing Date Title
EP18817809.9A EP3638995A4 (fr) 2017-06-15 2018-06-15 Lame de microscope avec cibles noire et blanche intégrées
JP2020519172A JP7369120B2 (ja) 2017-06-15 2018-06-15 一体化した黒色標的及び白色標的を備えた顕微鏡スライド
CN201880039127.0A CN110770553A (zh) 2017-06-15 2018-06-15 集成黑白目标的显微镜载片
KR1020207001292A KR20200040746A (ko) 2017-06-15 2018-06-15 통합된 흑백 타깃이 있는 현미경 슬라이드
US16/715,715 US11662564B2 (en) 2017-06-15 2019-12-16 Paraffin shield coating for microscope slide
US18/302,495 US12313834B2 (en) 2017-06-15 2023-04-18 Paraffin shield coating for microscope slide

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201762520178P 2017-06-15 2017-06-15
US62/520,178 2017-06-15

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2018/091686 Continuation WO2018228575A1 (fr) 2017-06-15 2018-06-15 Lame d'enregistrement de processus destinée à une coloration immunohistochimique

Related Child Applications (3)

Application Number Title Priority Date Filing Date
PCT/CN2018/091383 Continuation WO2018228508A1 (fr) 2017-06-15 2018-06-15 Revêtement de protection en paraffine de lame de microscope
US16/715,715 Continuation US11662564B2 (en) 2017-06-15 2019-12-16 Paraffin shield coating for microscope slide
US18/302,495 Continuation US12313834B2 (en) 2017-06-15 2023-04-18 Paraffin shield coating for microscope slide

Publications (1)

Publication Number Publication Date
WO2018228574A1 true WO2018228574A1 (fr) 2018-12-20

Family

ID=64659981

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2018/091685 Ceased WO2018228574A1 (fr) 2017-06-15 2018-06-15 Lame de microscope avec cibles noire et blanche intégrées

Country Status (5)

Country Link
EP (1) EP3638995A4 (fr)
JP (1) JP7369120B2 (fr)
KR (1) KR20200040746A (fr)
CN (1) CN110770553A (fr)
WO (1) WO2018228574A1 (fr)

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4190314A (en) * 1973-07-13 1980-02-26 Stephen Goldsmith Microscope and microscope slide for cytological analysis
CN1288158A (zh) * 1999-09-09 2001-03-21 申洪 免疫组织化学显微比色器及其制作方法
US20050142654A1 (en) * 2002-10-18 2005-06-30 Kazuji Matsumoto Slide glass, cover glass and pathologic diagnosis system
CN101529247A (zh) * 2006-08-25 2009-09-09 利·H·安格罗斯 具有可标记部分的分析片和使用方法
CN102812392A (zh) * 2010-01-15 2012-12-05 Qbc诊断股份有限公司 荧光显微镜载玻片
US20140022631A1 (en) * 2012-07-21 2014-01-23 General Data Company, Inc. Microscope slide for specimen tracking and verification, and method of making same

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8976239B2 (en) 2012-08-24 2015-03-10 Datacolor Holding Ag System and apparatus for color correction in transmission-microscope slides

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4190314A (en) * 1973-07-13 1980-02-26 Stephen Goldsmith Microscope and microscope slide for cytological analysis
CN1288158A (zh) * 1999-09-09 2001-03-21 申洪 免疫组织化学显微比色器及其制作方法
US20050142654A1 (en) * 2002-10-18 2005-06-30 Kazuji Matsumoto Slide glass, cover glass and pathologic diagnosis system
CN101529247A (zh) * 2006-08-25 2009-09-09 利·H·安格罗斯 具有可标记部分的分析片和使用方法
CN102812392A (zh) * 2010-01-15 2012-12-05 Qbc诊断股份有限公司 荧光显微镜载玻片
US20140022631A1 (en) * 2012-07-21 2014-01-23 General Data Company, Inc. Microscope slide for specimen tracking and verification, and method of making same

Also Published As

Publication number Publication date
EP3638995A1 (fr) 2020-04-22
EP3638995A4 (fr) 2021-03-31
JP2020523646A (ja) 2020-08-06
JP7369120B2 (ja) 2023-10-25
KR20200040746A (ko) 2020-04-20
CN110770553A (zh) 2020-02-07

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