EP3834938A1 - Einsatz für eine anordnung von bohrlöchern, anwendungsverfahren und verwendung - Google Patents

Einsatz für eine anordnung von bohrlöchern, anwendungsverfahren und verwendung Download PDF

Info

Publication number
EP3834938A1
EP3834938A1 EP19215013.4A EP19215013A EP3834938A1 EP 3834938 A1 EP3834938 A1 EP 3834938A1 EP 19215013 A EP19215013 A EP 19215013A EP 3834938 A1 EP3834938 A1 EP 3834938A1
Authority
EP
European Patent Office
Prior art keywords
insert
wells
array
supports
area
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Withdrawn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
EP19215013.4A
Other languages
English (en)
French (fr)
Inventor
Marianne ANGST-HELBLING
Roger MARTY
Adrian Sager
Manfred Lansing
Gerald HABENBACHER
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.)
Tecan Trading AG
Original Assignee
Tecan Trading AG
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 Tecan Trading AG filed Critical Tecan Trading AG
Priority to EP19215013.4A priority Critical patent/EP3834938A1/de
Publication of EP3834938A1 publication Critical patent/EP3834938A1/de
Withdrawn legal-status Critical Current

Links

Images

Classifications

    • 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
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/025—Align devices or objects to ensure defined positions relative to each other
    • 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
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0609—Holders integrated in container to position an object
    • 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
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/069—Absorbents; Gels to retain a fluid
    • 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
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0829—Multi-well plates; Microtitration plates
    • 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
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0848—Specific forms of parts of containers
    • B01L2300/0858—Side walls
    • 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
    • B01L2300/16—Surface properties and coatings
    • B01L2300/161—Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
    • B01L2300/163—Biocompatibility

Definitions

  • the present invention relates to an insert for an array of wells and to an application method of the insert in analysis techniques and to a use of the insert.
  • samples from plants or tissue samples from animals or samples of body fluids are collected for analysis in laboratories. Such samples can be collected in small containers or on absorbent filter paper.
  • Absorbent filter paper is suitable if soft samples can be squashed or pressed out on it, so that squeezed juice is soaked into the paper. Or if the sample is a liquid such as blood or another body fluid, it may be dropped onto absorbent filter paper.
  • Absorbent filter paper is also used in the field of clinical diagnostics (e.g. immune assays) or in the field of environmental monitoring.
  • FTA® Fluorescence Activated Cell Sorting
  • a drop of blood is added to the FTA® paper and the bloodstain is allowed to dry.
  • the cells are lysed upon contact with the paper and the DNA or other molecules of interest are bound in a stable form in the matrix of the paper.
  • a small paper disc is punched out from the FTA® paper card bloodstain for processing and analysis in the laboratory.
  • the usual procedure is to place the paper disc into a small tube or in a well of a multi-well microplate, for washing the paper disc with a wash fluid to wash away impurities and non-DNA material from the sample, the DNA being retained on the paper.
  • the clean paper disc with the still bound DNA can then be used for amplification of a DNA segment by PCR (polymerase chain reaction).
  • the amplified DNA is then used for DNA sequencing respectively for DNA profiling.
  • DNA testing different samples on a plurality of individual paper discs are processed, preferably with robotized lab stations.
  • the DNA can either remain attached to the washed paper discs, or it can be removed at first from the washed paper discs by elution respectively extraction.
  • untreated absorbent filter paper is used.
  • Cells are lysed just after elution of the sample from the absorbent filter paper.
  • the lysate may be analysed by immune assay methods or by instrumental analysis (e.g. mass spectroscopy).
  • the authors of this article developed therefore a microplate device and method which allows an automated and failure-free extraction of DNA from solid supports, wherein the DNA solutions are removed by centrifugation.
  • the pertaining device consists of a 96 deep well plate, a 96 spin basket with corresponding matrix which fits as an insert into the wells of the deep well plate, and a U-shaped collar for in between to raise the insert with the baskets after the lysis step into a spin position for centrifugation.
  • First FTA® blood punches or cotton buccal swabs are placed in the individual baskets of the insert.
  • Each individual basket of the insert has seven small holes in the bottom, so that during incubation with the lysis buffer and afterwards during centrifugation, the liquid solution from each basket can pass through the basket holes into the corresponding well of the deep well plate below.
  • the extracted and collected fractions with DNA in the 96 deep well plate can then be further processed and analysed.
  • the present invention also relates to an application method of such an insert in analysis techniques, and to a use of the insert.
  • an insert for an array of wells comprises an insert plate with an array of recesses, wherein each of the recesses includes a cone-shaped hollow recess part devoid of a bottom which comprises at least two leg supports with lateral gaps in between, the leg supports beginning at the edge of the respective recess and having lower ends, wherein the leg supports lie on the surface of a mathematical cone of revolution.
  • the recess parts of the insert of the present invention do not possess a bottom.
  • leg supports extend to the cone end, there lower ends end in a common point.
  • the cone of the cone-shaped hollow recess parts is a truncated cone with truncation of the cone end.
  • the leg supports might be separate legs with interspace between their lower ends.
  • leg supports being connected with each other at their lower ends.
  • connection at the lower ends of the leg supports is not a continuous area, neither a plate nor a disc nor a slice.
  • the connection may for example be bridges between nearby lower ends of the leg supports.
  • leg supports being connected at their lower ends by a ring at the truncation.
  • a ring being defined as a torus with a central opening.
  • the ring at the truncation has offsets at its lower side.
  • each recess part comprises three or four leg supports.
  • the insert plate is provided with flanks for robotic handling.
  • the insert is of a one-piece design.
  • the insert is preferably manufactured by injection moulding or 3D printing from a thermoplastic resin.
  • Suitable thermoplastic resins can for example be selected from the group comprising polypropylene, polycarbonate, polyethylene terephthalate, cycloolefin copolymer, polystyrene, polyamides and polymethyl methacrylate.
  • the insert is not of a one-piece design.
  • the recess parts are designed as spring clips and are clicked into place at the edge of the recesses in the insert plate by spring clip leg supports.
  • This embodiment requires the leg supports being connected with each other at their lower ends of the respective recess parts to be individual spring clips at first.
  • the array of recesses may be one-dimensional or two-dimensional. One-dimensional would mean arranged in one row. Two-dimensional would mean arranged within an area.
  • the array of recesses of the insert according to the invention may be smaller than or equal the array of wells. "Smaller than” would mean, that the insert would only cover a portion of the array of wells and not all the wells.
  • a two-dimensional array of recesses conforms to the inter-well spacing of a standard microplate, and the array of wells being a microplate.
  • the area-measured sample supports are preferably punched out or cut out or cut off paper or fabric snippets or shreds or discs or area-measured pieces or cuts of electrophoresis gels.
  • 2D gel electrophoresis is a method of separating molecules such as for example proteins.
  • a spot of an electrophoresis gel can contain one or more proteins of note. By gel picking, said spots are removed from the gel, and the corresponding pieces or cuts of the electrophoresis gel are transferred into wells and eluted respectively extracted there.
  • the biological samples are body fluids, in particular dried blood spots, or samples containing proteins or other molecules of interest.
  • the dispensed liquid is preferably a washing fluid or a buffer solution or a lysis buffer or an extraction liquid.
  • the invention relates also to a use of an insert in accordance with the features of claim 1 as a retainer or downholder for area-measured sample supports, preferably paper discs, in an array of wells, preferably in the wells of a microplate.
  • the paper discs are absorbent filter paper discs containing DNA or protein samples or other molecules of interest. Proteins also include antibodies. Other molecules of interest comprise for example RNA (ribonucleic acid) or metabolites.
  • an insert according to the invention for processing FTA® paper discs containing DNA samples with pipettes. But also untreated absorbent filter paper may be used as for whole blood collection for newborn screening, e.g. Whatman® 903 and Whatman® 226 filter paper.
  • Fig. 1 shows an insert 1 according to a preferred embodiment of the invention in a perspective view from oblique above.
  • the shown insert 1 is designed to fit in a 96 well microplate.
  • the insert 1 comprises an insert plate 3 with an array of 96 recesses 4, wherein each of the recesses 4 includes a cone-shaped hollow recess part 5 which comprises in the shown version three leg supports 6 with lateral gaps 7 in between.
  • the leg supports 6 being connected with each other at their lower end by a ring 11 at the truncation 10 of the cone-shaped hollow recess part 5.
  • the shown insert 1 possesses flanks 13 at the insert plate 3 in order to facilitate robotic handling with a gripper.
  • Fig. 2 shows the same perspective view of the insert 1 of Fig. 1 , the insert 1 being here in a position above a microplate 2 with 96 wells 17. As shown in Fig. 2 , the insert 1 is designed to fit with its array of recesses to the geometric pattern of the microplate 2.
  • Microplates usually have round circular wells 17, as shown in Fig. 2 . In rare cases, microplates can have square-based wells. In the latter case it would be preferred for an insert according to the invention that each recess part 5 comprises four leg supports 6 oriented to the corners of the square-based wells. Moreover an embodiment without a ring or with straight connections at the lower ends of the leg supports would fit well in this case.
  • Fig. 4A shows a perspective detail view of a single recess part 5 in a recess 4 of the insert plate 3 of the insert 1 of Fig. 1 .
  • the insert 1 is of a one-piece design.
  • the insert plate 3 and the recess parts 5 are integrally manufactured respectively integrally moulded of one material.
  • the three leg supports 6 begin at the edge 8 of the recess 4 as a continuation of the same material.
  • the leg supports 6 are connected by a ring 11 having a central opening.
  • Fig. 4B shows a perspective detail view of another single recess part 5 in an insert plate 3, without a ring at the lower ends 9 of the leg supports 6.
  • the cone-shaped hollow recess part 5 is a truncated cone, but the leg supports 6 are separate legs with interspace between their lower ends 9 not being connected with each other.
  • FIGS. 5 to 8 illustrate schematically a representative process sequence in an application method for an insert 1 in accordance with the invention.
  • Fig. 5 shows a single well 17 of a microplate 2 in a vertical cross-section, the well 17 being still empty.
  • a paper disc 16 (as an example for an area-measured sample support in a schematic representation) is then placed on the bottom of the well 17. Afterwards a liquid can be dispensed into the well 17 so that the paper disc 16 is submerged and soaked.
  • Fig. 7 shows in further sequence of Fig. 6 a snap-shot with a single recess part of an insert according to the invention inserted into the well of microplate 2 onto the paper disc 16.
  • the paper disc 16 is retained under the recess part of the insert, so that the paper disc 16 does not float to the top.
  • the length of the recess part has just to be designed sufficient in relation to the depth of the well, so that the paper disc 16 is held down near the bottom of the well and cannot be aspirated into the inside of the recess 4 during the subsequent aspiration of the dispensed liquid.
  • the flow of a liquid from the outside to the inside of recess 4 is enabled by the lateral gaps between the leg supports 6 and preferably in addition by offsets 12 at the lower side of ring 11.
  • Fig. 8 shows in addition to Fig. 7 a pipette tip 18 which was subsequently lowered into the recess part of the insert for aspiration.
  • Fig. 8 shows the pipette tip 18 at the so-called z-max position, the maximum possible lowering position in the insert. At this lowest point near the paper disc 16 but in a small distance of it, most of the supernatant solution can be aspirated.
  • the supernatant solution consists of the previously dispensed liquid with eluted sample components from the paper disc 16.
  • the insert according to the invention prevents clogging of the pipette tip 18 during aspiration and enables a safe pipetting off of eluates out of the well.
  • FIGS. 9A and 9B show two variants of a special embodiment of an insert in accordance with the invention, wherein the insert is not of a one-piece design.
  • this embodiment comprises separate recess parts being of a spring clip design which are clicked into place in the recess openings of an insert plate.
  • the spring clip design requires that the leg supports of a recess part being connected with each other at their lower end in order to constitute a part with spring arms.
  • Fig. 9A shows a first possible variant of a recess part being a spring clips 14 clicked into place with the spring clip leg supports 15 in a recess opening of an insert plate 3.
  • the spring clip leg supports 15 have a geometry at their upper beginning which allows to engage at the edge of the recess opening as a form lock fixing.
  • Fig. 9B shows a second possible variant with a spring clips recess part 14.
  • the spring clip leg supports 15 are clicked into place with sideward spikes at their upper beginning which can engage into a groove at the inner side of the recess opening of an insert plate 3.
  • Fig. 10 shows a perspective view from oblique below of a section of an insert according to the invention.
  • an insert plate 3 At the underside of an insert plate 3, there are arranged recess parts 5 with leg supports 6 and lateral gaps 7 between the leg supports 6.
  • the leg supports 6 being connected with each other at their lower end 9 by a ring 11 at the cone truncation, wherein there are offsets 12 at the lower side of the ring 11.
  • Fig. 11 shows a perspective view from oblique below similar as in Fig. 10 , but here of an entire insert 1 according to a preferred embodiment of the invention. Additional flanks 13 are arranged in this example at two corners of the insert plate 3 for precise positioning of the insert 1 in automatic handling.
  • the great advantage of the present invention is that the insert can be used with known pipetting robots, whereby aspiration instead of centrifugation can be applied, which allows an automated and high-throughput processing.
  • Pipetting with the insert according to the invention as a downholder for paper discs in the wells of a microplate is fast and reliable, because the downholder insert prevents filter paper discs from floating and from clogging pipette tips during aspiration of supernatant solutions with extracts. And besides the downholder prevents that filter paper discs are sucked and would hang at the pipette tips and might then fall into another well of the microplate or into another receptacle on the laboratory bench, which would cause a cross-contamination. Finally it should be mentioned that the downholders are transportable with a robotic gripper and are stackable (with or without spacers) due to the cone-shaped hollow recess parts. The stackability is space-saving in the working area of a pipetting robot.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
EP19215013.4A 2019-12-10 2019-12-10 Einsatz für eine anordnung von bohrlöchern, anwendungsverfahren und verwendung Withdrawn EP3834938A1 (de)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP19215013.4A EP3834938A1 (de) 2019-12-10 2019-12-10 Einsatz für eine anordnung von bohrlöchern, anwendungsverfahren und verwendung

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP19215013.4A EP3834938A1 (de) 2019-12-10 2019-12-10 Einsatz für eine anordnung von bohrlöchern, anwendungsverfahren und verwendung

Publications (1)

Publication Number Publication Date
EP3834938A1 true EP3834938A1 (de) 2021-06-16

Family

ID=68848153

Family Applications (1)

Application Number Title Priority Date Filing Date
EP19215013.4A Withdrawn EP3834938A1 (de) 2019-12-10 2019-12-10 Einsatz für eine anordnung von bohrlöchern, anwendungsverfahren und verwendung

Country Status (1)

Country Link
EP (1) EP3834938A1 (de)

Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5474742A (en) * 1992-06-10 1995-12-12 Labsystems Oy Apparatus for removing solid bodies from an array of reaction vessels
US20040091397A1 (en) 2002-11-07 2004-05-13 Corning Incorporated Multiwell insert device that enables label free detection of cells and other objects
US6943009B2 (en) 2002-05-15 2005-09-13 Corning Incorporated Multi-well assembly for growing cultures in-vitro
DE202006017853U1 (de) 2006-11-23 2007-01-18 Forschungszentrum Karlsruhe Gmbh Einsatz für eine Mikrotiterplatte
US20070237683A1 (en) 2006-03-30 2007-10-11 Maxwell Sensors, Inc. Microwell assembly having replaceable well inserts with reduced optical cross-talk
US20100190197A1 (en) * 2009-01-27 2010-07-29 Martin Gregory R Nested permeable support device and method for using the nested permeable support device
WO2011127945A1 (en) 2010-04-15 2011-10-20 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Cell culture system
US20130260410A1 (en) * 2010-12-08 2013-10-03 Novozymes A/S Microplate sampling adapter
WO2014018751A1 (en) * 2012-07-27 2014-01-30 Emory University Cell filtration device
US20170225162A1 (en) * 2007-06-27 2017-08-10 Applied Biosystems, Llc Multi-Material Microplate And Method
WO2019089757A1 (en) * 2017-11-03 2019-05-09 Illumina, Inc. Multi-well plate adaptors

Patent Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5474742A (en) * 1992-06-10 1995-12-12 Labsystems Oy Apparatus for removing solid bodies from an array of reaction vessels
US6943009B2 (en) 2002-05-15 2005-09-13 Corning Incorporated Multi-well assembly for growing cultures in-vitro
US20040091397A1 (en) 2002-11-07 2004-05-13 Corning Incorporated Multiwell insert device that enables label free detection of cells and other objects
US20070237683A1 (en) 2006-03-30 2007-10-11 Maxwell Sensors, Inc. Microwell assembly having replaceable well inserts with reduced optical cross-talk
DE202006017853U1 (de) 2006-11-23 2007-01-18 Forschungszentrum Karlsruhe Gmbh Einsatz für eine Mikrotiterplatte
US20170225162A1 (en) * 2007-06-27 2017-08-10 Applied Biosystems, Llc Multi-Material Microplate And Method
US20100190197A1 (en) * 2009-01-27 2010-07-29 Martin Gregory R Nested permeable support device and method for using the nested permeable support device
US8163537B2 (en) 2009-01-27 2012-04-24 Corning Incorporated Nested permeable support device and method for using the nested permeable support device
WO2011127945A1 (en) 2010-04-15 2011-10-20 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Cell culture system
US20130260410A1 (en) * 2010-12-08 2013-10-03 Novozymes A/S Microplate sampling adapter
WO2014018751A1 (en) * 2012-07-27 2014-01-30 Emory University Cell filtration device
WO2019089757A1 (en) * 2017-11-03 2019-05-09 Illumina, Inc. Multi-well plate adaptors

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
A. TEREBAJ. KRUEGERR. OLSONP. MANDREKARB. MCLAREN: "High-Throughput Processing of Samples on Solid Supports Using the SlicprepTM 96 Device", September 2005, PROMEGA CORPORATION

Similar Documents

Publication Publication Date Title
JP5133411B2 (ja) 法医学試料における生体物質用収集／抽出容器
AU2022202342B2 (en) Systems, methods, and apparatuses for performing automated reagent-based assays
US6054325A (en) Method and apparatus for transferring and combining distinct chemical compositions with reagents
US6083761A (en) Method and apparatus for transferring and combining reagents
EP2027925A2 (de) Verteileranordnung
US11268885B2 (en) Sample collection device
JP2007171169A (ja) 核酸サンプルを保管し、提供するためのサンプル管およびシステム
JP2005515773A (ja) ハイブリダイゼーションの装置および方法
CN109562374B (zh) 样品制备架和其使用方法
US9656264B2 (en) Biological sample holder and method of assembling same
WO2013072698A2 (en) Cartridge
EP1265710B1 (de) Verfahren und gerät zur verarbeitung von substanzen in einem einzigen behälter
EP3834938A1 (de) Einsatz für eine anordnung von bohrlöchern, anwendungsverfahren und verwendung
CN214716756U (zh) 一种毛细管移液装置及其模具
EP1491258B1 (de) Multifunktionale Absaugvorrichtung
EP2423688B1 (de) Suspensionsbehälter für Bindepartikel zur Isolierung von biologischem Material
WO2009074177A1 (en) Forensic sample processor
US20130288343A1 (en) Biological sample holder and method of assembling a storage device
WO2023007224A1 (en) Biological material pooling device for biological or biomolecule purification
WO2000066267A1 (en) Preventing cross-contamination in a multi-well plate
EP2719457A1 (de) Multiwellplatte und Verwendungsverfahren dafür

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION HAS BEEN PUBLISHED

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20211217