EP1547691A1 - Mikrotiterplatte, System und Verfahren zur Probenhandlung - Google Patents

Mikrotiterplatte, System und Verfahren zur Probenhandlung Download PDF

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Publication number
EP1547691A1
EP1547691A1 EP04077952A EP04077952A EP1547691A1 EP 1547691 A1 EP1547691 A1 EP 1547691A1 EP 04077952 A EP04077952 A EP 04077952A EP 04077952 A EP04077952 A EP 04077952A EP 1547691 A1 EP1547691 A1 EP 1547691A1
Authority
EP
European Patent Office
Prior art keywords
microtiter plate
liquid
chamber
passage
component
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Withdrawn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
EP04077952A
Other languages
English (en)
French (fr)
Inventor
Peter Berndt
Gregor Dernick
Christof Fattinger
Remo Anton Hochstrasser
Dieter Voegelin
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.)
F Hoffmann La Roche AG
Original Assignee
F Hoffmann La Roche 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
Priority claimed from EP03079157A external-priority patent/EP1547686A1/de
Application filed by F Hoffmann La Roche AG filed Critical F Hoffmann La Roche AG
Priority to EP04077952A priority Critical patent/EP1547691A1/de
Publication of EP1547691A1 publication Critical patent/EP1547691A1/de
Withdrawn legal-status Critical Current

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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
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0681—Filter
    • 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
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0409—Moving fluids with specific forces or mechanical means specific forces centrifugal forces

Definitions

  • the invention concerns a microtiter plate for processing samples having a liquid component or a liquid and a solid component or a liquid and a gel component.
  • the invention further concerns a system for processing samples having a liquid component or a liquid and a solid component or a liquid and a gel component.
  • the invention further concerns a method for processing samples having a liquid component or a liquid and a solid component or a liquid and a gel component.
  • Microtiter plates are multi-well plates that are adapted for receiving samples to be processed at a plurality of wells. Each well defines a reaction site where a sample is usually mixed with one or more reagents in order to form a sample-reagent mixture which is the subject to analysis e.g. by means of a photometer or a fluorometer.
  • the aim of the invention is to provide a microtiter plate that is configured and dimensioned for performing the above-mentioned separations for a large number of samples rapidly and at low cost.
  • a microtiter plate of the above mentioned kind comprising a single piece body which is made by injection molding, said body having an array of cavities and each of said cavities having an open upper end and a closed bottom end, each of said cavities having a bottom inner surface and comprising a first chamber for receiving a sample to be processed, a second chamber and a passage which fluidically connects said first and second chambers with each other, said passage having a top opening, said first chamber, said second chamber and said passage having each a bottom inner surface which is portion of the bottom inner surface of said cavity, a region in the lower part of said passage being adjacent to the bottom end of the cavity, said region being so configured and dimensioned that it allows passage of liquid from one of said chambers to the other only when a centrifugal force is applied to the microtiter plate, but does not allow passage of any solid or gel component the size of which is larger than the width of said region (21).
  • the above aim of the invention is attained with a system for processing samples having a liquid component or a liquid and a solid component or a liquid and a gel component, said system comprising a microtiter plate according to the invention.
  • the above aim of the invention is attained with a method for processing samples having a liquid component or a liquid and a solid component or a liquid and a gel component, said method comprising
  • the above aim of the invention is attained with a method for processing samples having a liquid component or a liquid and a solid component or a liquid and a gel component, said method comprising
  • Fig.1 shows a microtiter plate 11 according to the invention for processing samples having a liquid component or a liquid and a solid component or a liquid and a gel component.
  • Microtiter plate 11 comprises a single piece body 12 made by injection molding of a suitable plastic material, e.g. Polypropylene (PP), Cyclic Olefin Copolymer (COC), Acrylonitrile/Butadien/Styrene (ABS) or Polycarbonate (CC).
  • a suitable plastic material e.g. Polypropylene (PP), Cyclic Olefin Copolymer (COC), Acrylonitrile/Butadien/Styrene (ABS) or Polycarbonate (CC).
  • Body 12 has an array of cavities 13 and side edges 35, 36.
  • the grid spacing is of e.g. 4.5 millimeter measured along each of edges 35, 36, i.e.in both X-direction and Y-direction shown by arrows in Figures 1 and 9.
  • each of cavities 13 has a length axis which forms an angle A of about 45 degrees with a side edge 35, 36 of the microtiter plate 11.
  • This spatial arrangement of cavities makes possible to form a relatively large number of such cavities in a microtiter plate of standard size.
  • This plate has e.g. a length of 127.76 ⁇ 0.25 millimeter and a width of 85.48 ⁇ 0.25 millimeter.
  • single piece body 12 has standard outer dimensions of a microtiter plate and comprises 384 cavities 13. In another preferred embodiment, single piece body 12 has standard outer dimensions of a microtiter plate and comprises 1536 cavities 13.
  • each of cavities 13 has an inner surface the cross-section of which is a closed curve and the inner surface has no corner or sharp edge.
  • the closed curve has approximately the shape of two circular line portions 27, 28 connected with each other by curved line portions 31, 32.
  • each of cavities 13 has an open upper end 14 and a closed bottom end 15 and each of cavities 13 has a bottom inner surface and comprises a first chamber 16 for receiving a sample to be processed, a second chamber 17 and a passage 18 which fluidically connects chambers 16 and 17 with each other.
  • Passage 18 has a top opening 19.
  • the total volume of a cavity 13 is e.g. about 30 microliter.
  • the bottom 23 of chamber 16, the bottom 22 of chamber 17 and the bottom of passage 18 have each an inner surface which is a portion of the inner surface of the bottom 15 of cavity 13.
  • Chambers 16, 17 and passage 18 have side walls with an inclination angle of about 4 degrees.
  • chamber 16 is adapted for receiving a sample having a liquid component or a liquid and a solid component or a liquid and a gel component
  • chamber 17 is adapted for receiving a pipetting tip 33 shown by Fig. 4.
  • microtiter plate 11 further comprises sealing means 34, shown in Figure 4, which seal the contact surface of tip 33 with the microtiter plate 11 and second sealing means (not shown) which seal the top opening of passage 18.
  • passage 18 has a variable width in a direction extending from chamber 16 to chamber 17 and that width has a minimum at a zone 26 located between chambers 16 and 17.
  • a region 21 in the lower part of passage 18 is adjacent to the bottom end 15 of the cavity 13.
  • Region 21 is so configured and dimensioned that it allows passage of liquid from one of chambers to the other only when a centrifugal force is applied to the microtiter plate, but does not allow passage of any solid or gel component the size of which is larger than the width of region 21.
  • region 21 of passage 18 is configured and dimensioned as a capillary passage adapted for supporting or facilitating flow of liquid from one of chambers 16, 17 to the other. This is for instance the case when the entire length of region 21 is a capillary adapted for receiving liquid and is thereby able to provide a fluidic connection between the bottom of chamber 16 and the bottom of chamber 17.
  • the radius R1 is preferably comprised e.g. in a range between 0.1 to 0.5 millimeter.
  • region 21 of passage 18 is configured and dimensioned as a capillary passage adapted for blocking through passage 18. This is the case when the narrowest point 26 of region 21 is so narrow that it prevents liquid flow through passage 18.
  • the bottom 22 of chamber 17 lies at a lower level than the bottom 23 of first chamber 16 when the microtiter plate 11 is in horizontal position and the upper ends 14 of chambers are on the top side 24 of the microtiter plate 11.
  • the bottom of chamber 16 has an inclination of about 20 degrees with respect to the top side 24 of plate 11.
  • the inner surface of the bottom 29 of passage 18 which fluidically connects chambers 16 and 17 with each other has a shape that contributes to maximize the centrifugal force exerted on a sample contained in first chamber 16 when microtiter plate 11 is centrifuged by means of a centrifugation apparatus.
  • Figure 6 shows such a shape of the bottom 29 of passage 18.
  • microtiter plate 11 At least a portion of the inner surface of the bottom of each of said cavities 13 is a hydrophilic or hydrophobic surface, or is a surface having a hydrophilic or hydrophobic coating.
  • the purpose of these surface properties is to create flow conditions that are suitable for the intended use of the microtiter plate, e.g. when a preferred sense of flow is suitable for the desired liquid handling process.
  • At least a portion of or the entire inner surface of the bottom 29 of passage 18 is a hydrophilic surface or is a surface having a hydrophilic coating 25 shown by Fig. 6. This feature facilitates the flow of liquid through passage 18 and thereby ensures that the entire volume of liquid in chamber 16 is transferable to chamber 17 by centrifugation of microtiter plate 11.
  • At least a portion of or the entire inner surface of the bottom 23 of chamber 16 is a hydrophilic surface or is a surface having a hydrophilic coating (not shown). This feature facilitates the flow of liquid from chamber 16 to passage 18 and thereby ensures that the entire volume of liquid in chamber 16 is transferable to chamber 17 by centrifugation of microtiter plate 11.
  • At least a portion of or the entire inner surface of the bottom 22 of chamber 17 is a hydrophobic surface or is a surface having a hydrophobic coating (not shown). This feature facilitates the flow of liquid from chamber 16 to passage 18 and thereby ensures that the entire volume of liquid in chamber 16 is transferable to chamber 17 by centrifugation of microtiter plate 11.
  • each of cavities 13 tapers towards its bottom end 15, i.e. the cross-section of each cavity 13 diminishes towards the bottom thereof.
  • a solid element 37 which is liquid permeable, is arranged in region 21 of passage 18.
  • Solid element 37 is e.g. a filter element having a porous structure that allows passage of particles having a size that is smaller than a predetermined size.
  • a filter element is made e.g. of glass or of a plastic material.
  • solid element 37 is a membrane that allows passage of particles having a size that is smaller than a predetermined size.
  • Such membrane is made e.g. of a plastic material, paper, a gel or a microfiber.
  • solid element 37 is a test element, e.g. a chromatographic test element.
  • Test element 37 is e.g. a membrane or a strip similar to a chromatographic strip which in a first step is able to retain a sample material of a certain kind as a sample flows from chamber 16 to chamber 17 through passage 18 and in a subsequent step is able to release that sample material when said test element is brought in contact with a suitable reagent, the released sample and reagent mixture being then transferable to chamber 17 e.g. by centrifugation of plate 11.
  • solid test element 37 or at least a portion thereof is a coating having hydrophilic properties or hydrophobic properties.
  • a first system for processing samples having a liquid component or a liquid and a solid component or a liquid and a gel component comprises a microtiter plate 11 of the kind described above with reference to Figures 1-9.
  • this first system further comprises a centrifugation apparatus (not shown in the drawings) for centrifugating the microtiter plate 11.
  • a second system for processing samples having a liquid component or a liquid and a solid component or a liquid and a gel component comprises a microtiter plate 11 of the kind described above with reference to Figures 1-8.
  • this second system further comprises a pipetting tip 33 (shown in Fig. 4) which is insertable into chamber 17 and which is connectable to a pipetting apparatus including overpressure or underpressure generating means
  • a first method for processing samples having a liquid component or a liquid and a solid component or a liquid and a gel component comprises
  • the above-mentioned transfer of liquid is effected exclusively by means of centrifugal force generated by centrifugation of the microtiter plate 11.
  • the sample volume transferred from chamber 16 to chamber 17 by centrifugation is in the range of e.g. 0.05 to 2 microliter.
  • a second method for processing samples having a liquid component or a liquid and a solid component or a liquid and a gel component comprises
  • a third method for processing samples having a liquid component or a liquid and a solid component or a liquid and a gel component comprises
  • the gel component of the sample contains biomolecules to be analyzed.
  • the volume of sample introduced into chamber 16 is smaller than a predetermined maximum value.
  • this condition is fulfilled only the liquid component of the sample passes through region 21 of passage when transferred from chamber 16 to chamber 17 and any solid or gel component of the sample remains in chamber 16. If the above mentioned condition is not fulfilled, some of the solid and/or gel components of the sample can pass from chamber 16 to chamber 17 through the upper part of passage 18 and the desired separation of the liquid from the solid and/or gel components of the sample is not or not completely achieved.

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)
EP04077952A 2003-12-22 2004-10-26 Mikrotiterplatte, System und Verfahren zur Probenhandlung Withdrawn EP1547691A1 (de)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP04077952A EP1547691A1 (de) 2003-12-22 2004-10-26 Mikrotiterplatte, System und Verfahren zur Probenhandlung

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP03079157 2003-12-22
EP03079157A EP1547686A1 (de) 2003-12-22 2003-12-22 Mikrotiterplatte, System und Verfahren zur Probenhandlung
EP04077952A EP1547691A1 (de) 2003-12-22 2004-10-26 Mikrotiterplatte, System und Verfahren zur Probenhandlung

Publications (1)

Publication Number Publication Date
EP1547691A1 true EP1547691A1 (de) 2005-06-29

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EP04077952A Withdrawn EP1547691A1 (de) 2003-12-22 2004-10-26 Mikrotiterplatte, System und Verfahren zur Probenhandlung

Country Status (1)

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EP (1) EP1547691A1 (de)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2186564A1 (de) * 2008-11-12 2010-05-19 F. Hoffmann-Roche AG MWP-Klappentrennung
GB2472321A (en) * 2009-07-31 2011-02-02 Simon Stafford A microplate and microplate holder
WO2011120819A1 (de) * 2010-03-31 2011-10-06 Roche Diagnostics Gmbh Mikrofluidisches element mit multifunktionaler messkammer
WO2021224408A3 (en) * 2020-05-08 2021-12-16 Scienion Ag Assay plate with nano-vessels and sample recovery assembly

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4980293A (en) * 1988-09-02 1990-12-25 Multi-Technology Inc. Dispensing reagents in a specimen well
EP0569115A2 (de) * 1992-05-05 1993-11-10 General Atomics Hoch Durchsatz DNS-Darstellungssystem
WO1995026798A1 (en) * 1994-03-30 1995-10-12 Sorenson Bioscience, Inc. Temporary liquid storage cavities in a centrifuge tube
EP0791394A2 (de) * 1996-02-26 1997-08-27 Grupo Grifols, S.A. Vorrichtung zur Durchführung von Reaktionen mit Erythrocyten

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4980293A (en) * 1988-09-02 1990-12-25 Multi-Technology Inc. Dispensing reagents in a specimen well
EP0569115A2 (de) * 1992-05-05 1993-11-10 General Atomics Hoch Durchsatz DNS-Darstellungssystem
WO1995026798A1 (en) * 1994-03-30 1995-10-12 Sorenson Bioscience, Inc. Temporary liquid storage cavities in a centrifuge tube
EP0791394A2 (de) * 1996-02-26 1997-08-27 Grupo Grifols, S.A. Vorrichtung zur Durchführung von Reaktionen mit Erythrocyten

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2186564A1 (de) * 2008-11-12 2010-05-19 F. Hoffmann-Roche AG MWP-Klappentrennung
EP2189218A1 (de) * 2008-11-12 2010-05-26 F. Hoffmann-Roche AG Trennung in einer Mikrowell platte unter Zuhilfenahme des Deckels
US9316656B2 (en) 2008-11-12 2016-04-19 Roche Molecular Systems, Inc. Lid separation device and methods
GB2472321A (en) * 2009-07-31 2011-02-02 Simon Stafford A microplate and microplate holder
GB2472321B (en) * 2009-07-31 2014-03-05 Oxley Hughes Ltd Means for improved liquid handling in a microplate
WO2011120819A1 (de) * 2010-03-31 2011-10-06 Roche Diagnostics Gmbh Mikrofluidisches element mit multifunktionaler messkammer
US8759081B2 (en) 2010-03-31 2014-06-24 Roche Diagnostics Operations, Inc. Microfluidic element with multi-functional measuring chamber for the analysis of a fluid sample
WO2021224408A3 (en) * 2020-05-08 2021-12-16 Scienion Ag Assay plate with nano-vessels and sample recovery assembly

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