GB2429776A - Apparatus for producing a tissue array - Google Patents

Apparatus for producing a tissue array Download PDF

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Publication number
GB2429776A
GB2429776A GB0614845A GB0614845A GB2429776A GB 2429776 A GB2429776 A GB 2429776A GB 0614845 A GB0614845 A GB 0614845A GB 0614845 A GB0614845 A GB 0614845A GB 2429776 A GB2429776 A GB 2429776A
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GB
United Kingdom
Prior art keywords
tissue
needle
block
holder
sighting device
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
Application number
GB0614845A
Other versions
GB2429776B (en
GB0614845D0 (en
Inventor
Rolf Metzner
Roland Walter
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.)
Leica Microsystems CMS GmbH
Leica Biosystems Nussloch GmbH
Original Assignee
Leica Microsystems Nussloch GmbH
Leica Microsystems CMS GmbH
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 Leica Microsystems Nussloch GmbH, Leica Microsystems CMS GmbH filed Critical Leica Microsystems Nussloch GmbH
Publication of GB0614845D0 publication Critical patent/GB0614845D0/en
Publication of GB2429776A publication Critical patent/GB2429776A/en
Application granted granted Critical
Publication of GB2429776B publication Critical patent/GB2429776B/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

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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
    • G01N1/36—Embedding or analogous mounting of samples
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00—Apparatus for enzymology or microbiology
    • C12M1/16—Apparatus for enzymology or microbiology containing, or adapted to contain, solid media
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/02—Devices for withdrawing samples
    • G01N1/04—Devices for withdrawing samples in the solid state, e.g. by cutting
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/02—Devices for withdrawing samples
    • G01N1/04—Devices for withdrawing samples in the solid state, e.g. by cutting
    • G01N1/06—Devices for withdrawing samples in the solid state, e.g. by cutting providing a thin slice, e.g. microtome
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/02—Devices for withdrawing samples
    • G01N1/04—Devices for withdrawing samples in the solid state, e.g. by cutting
    • G01N1/08—Devices for withdrawing samples in the solid state, e.g. by cutting involving an extracting tool, e.g. core bit
    • 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
    • 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
    • G01N2001/282—Producing thin layers of samples on a substrate, e.g. smearing, spinning-on with mapping; Identification of areas; Spatial correlated pattern
    • 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
    • G01N1/286—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q involving mechanical work, e.g. chopping, disintegrating, compacting, homogenising
    • G01N2001/2873—Cutting or cleaving
    • 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
    • G01N1/36—Embedding or analogous mounting of samples
    • G01N2001/368—Mounting multiple samples in one block, e.g. TMA [Tissue Microarrays]

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biotechnology (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Microbiology (AREA)
  • Sustainable Development (AREA)
  • General Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

An apparatus for producing a tissue array, having at least one donor block (2) that comprises tissue (3) to be investigated, is described. A marked tissue section of the tissue (3) to be investigated is arranged on a specimen slide (22), a hollow needle (5) for removing a sample from the tissue (3) being present. A sighting device (12) is provided for positioning the hollow needle (5) above the donor block (2). The sighting device may be connected with a pantograph.

Description

1 2429776
APPARATUS FOR PRODUCING TISSUE ARRAYS
The invention concerns an apparatus for producing tissue arrays, according to the preamble of Claim 1.
Tissue arrays, also called tissue microarrays (TMAs), contain a plurality of different tissue samples in a singte receiver block or paraffin block. The receiver block is sectioned in the usual manner with a microtome, and the section is applied onto a specimen slide. The specimen slide then contains a plurality of different tissue samples. Because of the large number of tissue samples on a single specimen slide, it is possible to stain or process all the samples under the same conditions. As a result, even very complex and expensive staining methods, for example those derived from immunohistochemistry (IHC) or in-site hybridization (ISH) for revealing DNA or RNA, can be applied effectively.
The production of tissue arrays is very time-consuming, however, since a plurality of different samples (up to 1,000) are arranged next to one another in one receiver block. From the various tissue or sample blocks, a tissue core is punched out with a hollow needle and transferred into a correspondingly prepared receiver block.
Before a tissue core is removed from a sample block, the corresponding site on the sample block must be located and marked. It has proven useful for this purpose, in practice, first to produce usual microtome sections from a sample block, apply them onto specimen slides, stain them using a standard method, and have them inspected by a pathologist. The pathologist then selects the sites of interest cii the specimen slide, and marks that site directly on the specimen slide.
The laboratory worker producing the tissue arrays then has the task of locating, on the tissue block, the sites marked on the specimen slide, and removing a tissue core at the corresponding sites.
Punched-out portions or paraffin cores are also removed, using a hollow needle, from the receiver block, which as a rule is made of paraffin. The tissue cores are then introduced into the cavity thus created. As mentioned, as many as 1,000 tissue cores -- depending on the application - can be arranged to form an array on one paraffin block. From these dimensions alone, it is apparent that the diameter of the tissue cores is less than 1 mm, and reliable and simple transfer of the tissue cores into the punched hole in the paraffin block is therefore possible only with special equipment.
An apparatus for producing a tissue array is known from US 6,103,518. This apparatus is characterized in that the receiver block is arranged in stationary fashion, and possesses a pivotably mounted needle holder for two hollow needles. The needle holder is aligned onto the receiver block by way of an X-Y micrometer displacement device. The two needles -- one for punching out the receiver block, the other for removing the tissue core -- can be brought alternately into the working position.
For removal of the tissue core from the tissue block, the latter is placed manually, together with a U-shaped frame, above the paraffin block and aligned onto the hollow needle.
With this apparatus, it has proven difficult to locate, on the tissue block, the site marked on the specimen slide, and furthermore to ensure reliable introduction of the tissue core into the paraffin block.
An automated device for producing tissue arrays is known from US 6,383, 801 Bi. Here both multiple paraffin blocks and multiple tissue blocks are arranged on an X-V scanning stage.
AJso provided here are two hollow needles operating independently of one another, of which one makes the punched holes in the paraffin block and the other is responsible for tissue core removal.
This device is very complex and moreover does not solve the problem of easily locating a marked site on the tissue block.
It is the object of the present invention to improve a manually operating apparatus for producing tissue arrays in such a way that simple location of a specific site on the tissue block, and targeted removal of a tissue core, becomes possible.
This object is achieved, according to the present invention, by the features described in the characterizing portion of Claim 1. Further advantageous developments of the invention are the subject matter of the dependent claims.
The invention is characterized in that a sighting device is provided for positioning the hollow needle above the donor block, and the marked site is determined via the sighting device.
In a development of the invention, the sighting device is joined to a movably arranged arm, and is thus embodied to be arbitrarily movable above the marked site on the specimen slide.
In a further embodiment of the invention, the arm is embodied as a pantograph, the pantograph comprising two scissor arms joined to one another.
In a development of the invention, the scissor arms are embodied in rotatably mounted fashion.
In a further embodiment of the invention, the second scissor arm is joined to a sight holder for the sighting device, so that the sighting device is configured to be freely movable above the donor block by way of the pantograph. A movement of the second scissor arm also results in a synchronous movement of the first scissor arm, so that a position sighted onto on the donor block is transferred directly to the end of the second scissor arm.
In a development of the invention, the sighting device has associated with it a specimen slide holder for receiving the marked specimen slide.
In a further embodiment of the invention, the donor block is arranged on a turntable and can be placed either in a defined position below the first scissor arm or in a defined position below the second scissor arm.
In a development of the invention, the specimen slide holder is arranged in freely positionable fashion above the donor block, thus ensuring congruent alignment of the tissue section on the specimen slide with respect to the donor block and thereby making possible unimpeded sighting onto the marked tissue site.
In a further embodiment of the invention, the hollow needle is arranged on a needle holder and the needle holder is embodied movably, the first scissor arm comprising a receptacle for a punching lever for actuating the hollow needle. As a result of the arrangement of the sighting device on the second scissor arm, the movement is transferred directly to the needle holder and the hollow needle on the first scissor arm, and the tissue site to be removed on the donor block is thus defined.
In a development of the invention, multiple hollow needles, having different diameters, are arranged circularly next to one another on the needle holder, so that differently dimensioned tissue cores can be removed.
The invention will be explained in more detail with reference to an exemplifying embodiment, with the aid of the schematic drawings in which: FIG. 1 is a view of the apparatus having the pantograph; FIG. 2 is a detail view of the apparatus having a needle holder.
FIG. 1 is a view of the apparatus for producing a tissue array, having a receiver block or paraffin block I and a donor block or tissue block 2 that contains tissue 3 to be investigated.
Donor block 2 and receiver block 1 are arranged on a turntable 13. Also provided is a pivotably embodied needle holder 14 that carries a first hollow needle 4 and a second hollow needle 5. First hollow needle 4 serves to create a punched hole in receiver block 1, and second hollow needle 5 is provided in order to remove a tissue core from tissue 3.
The apparatus comprises a pantograph 6, mounted via a rotary shaft 16, having two scissor arms 7 and 8 joined to one another, the end of first scissor arm 7 carrying a receptacle 9 for a punching lever 15 for selectable actuation of first and second hollow needles 4; 5. The end of second scissor arm 8 is equipped with a positioning knob 10 for manual movement of pantograph 6.
The position of positioning knob 10 is transferred via the rotatably mounted pantograph 6 to receptacle 9 for punching lever 15. Needle holder 14 is joined in positively engaged fashion (FIG. 2) to first scissor arm 7, and thereby follows the movement of punching lever 15.
Selection of the corresponding hollow needle is accomplished by a pivoting motion of needle holder 14 about rotary shaft 16. For punching, receiver block 1 is positioned via turntable 13 below the corresponding first hollow needle 4; first hollow needle 4 is then driven by punching lever 15 into receiver block 1 and makes a punched hole therein.
Also provided is a fixedly arranged slider receptacle 19 for a specimen slide holder 11.
Specimen slide holder Ills arranged movably via a slider 20 in slider receptacle 19, and carries a marked specimen slide 22. Present on specimen slide 22 is a microtome section of donor block 2 having tissue 3.
Donor block 2 is arranged below specimen slide holder 22. By way of the movably mounted specimen slide holder 11, congruency is created between the microtome section and tissue 3 in donor block 2.
A sighting device 12 is arranged on second scissor arm 8 via a sight holder 21. Sighting device 12 is aligned onto the marked site on specimen slide 22 via positionin9 knob 10. This movement is transferred via pantograph 6 to punching lever 15 and needle holder 14.
Removal of a tissue core from donor block 2 is then performed by the fact that donor block 2 is rotated via turntable 13 out of its position beneath sighting device 12 into a position beneath needle holder 14. and second hollow needle 5 is moved via punching lever 15 into tissue 3 in order to remove a tissue core. Pantograph 6 and sighting device 12 ensure that tissue 3 is removed from the site being sighted onto.
It is of course within the scope of the invention to immobilize the respective positions of the turntable by way of additional detents in order to ensure simple and rapid operation.
FIG. 2 is a detail view of needle holder 14, which is mounted rotatably and displaceably about rotary shaft 16. Needle holder 14 comprises a groove 18 into which a cam 17 positively engages. Cam 17 is joined to first scissor arm 7. A movement of scissor arm 7 is transferred via cam 17 and groove 18 to needle holder 14.
Precise removal of a paraffin core from the receiver block is depicted and described in the parallel Application submitted simultaneously.

Claims (12)

1. An apparatus for producing a tissue array, comprising at least one donor block which comprises tissue to be investigated, a specimen slide with a marked tissue section of the tissue to be investigated, a hollow needle for removing a sample from the tissue, and a sighting device for positioning the needle above the donor block.
2. Apparatus according to claim 1, wherein the sighting device is connected with a movable arm.
3. Apparatus according to claim 2, wherein the arm has the form of a pantograph.
4. Apparatus according to claim 3, wherein the pantograph comprises two interconnected scissor arms.
5. Apparatus according to claim 4, wherein the scissor arms are rotatable.
6. Apparatus according to claim 5, wherein the second scissor ami comprises a sight holder for the sighting device.
7. Apparatus according to any one of the preceding claims, wherein the sighting device is associated with a specimen slide holder.
8. Apparatus according to any one of the preceding claims, wherein the donor block is arranged on a turntable.
9. Apparatus according to claim 7, wherein the specimen slide holder is arranged above the donor block to be freely positionable.
10. Apparatus according to any one of claims 4 to 6, wherein the needle is arranged on a movable needle holder, the first scissor arm having a receptacle for a punching lever for actuating the needle.
11. Apparatus according to claim 10, comprising multiple hollow needles having different diameters arranged circularly adjacent to one another on the needle holder.
12. A method of producing a tissue array by apparatus as claimed in any one of the preceding claims, comprising the steps of positioning the needle above the donor block and removing a sample from the tissue of the block by the needle.
GB0614845A 2005-09-01 2006-07-26 Apparatus for producing tissue arrays Expired - Fee Related GB2429776B (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE102005041780A DE102005041780A1 (en) 2005-09-01 2005-09-01 Device for the production of tissue arrays

Publications (3)

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GB0614845D0 GB0614845D0 (en) 2006-09-06
GB2429776A true GB2429776A (en) 2007-03-07
GB2429776B GB2429776B (en) 2007-10-24

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JP (1) JP2007064983A (en)
CN (1) CN1924542A (en)
DE (1) DE102005041780A1 (en)
GB (1) GB2429776B (en)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000052132A1 (en) * 1999-03-05 2000-09-08 Beecher Instruments Instrument for constructing tissue arrays
US20030186358A1 (en) * 1997-09-17 2003-10-02 Genentech, Inc. Secreted and transmembrane polypeptides and nucleic acids encoding the same
US6699710B1 (en) * 1998-02-25 2004-03-02 The United States Of America As Represented By The Department Of Health And Human Services Tumor tissue microarrays for rapid molecular profiling

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030186358A1 (en) * 1997-09-17 2003-10-02 Genentech, Inc. Secreted and transmembrane polypeptides and nucleic acids encoding the same
US6699710B1 (en) * 1998-02-25 2004-03-02 The United States Of America As Represented By The Department Of Health And Human Services Tumor tissue microarrays for rapid molecular profiling
WO2000052132A1 (en) * 1999-03-05 2000-09-08 Beecher Instruments Instrument for constructing tissue arrays

Also Published As

Publication number Publication date
DE102005041780A1 (en) 2007-03-08
GB2429776B (en) 2007-10-24
CN1924542A (en) 2007-03-07
GB0614845D0 (en) 2006-09-06
JP2007064983A (en) 2007-03-15

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PCNP Patent ceased through non-payment of renewal fee

Effective date: 20160726