EP1405056A1 - Corps destine a des cuvettes de circulation et utilisation de celles-ci - Google Patents

Corps destine a des cuvettes de circulation et utilisation de celles-ci

Info

Publication number
EP1405056A1
EP1405056A1 EP02732307A EP02732307A EP1405056A1 EP 1405056 A1 EP1405056 A1 EP 1405056A1 EP 02732307 A EP02732307 A EP 02732307A EP 02732307 A EP02732307 A EP 02732307A EP 1405056 A1 EP1405056 A1 EP 1405056A1
Authority
EP
European Patent Office
Prior art keywords
flow
arrangement
carrier
base plate
cells
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Withdrawn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
EP02732307A
Other languages
German (de)
English (en)
Inventor
Martin A. Bopp
Heinrich Büttgen
Tilo Callenbach
Werner Schoch
Yves Marmier
André Marcel WICKY
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.)
Bayer AG
Original Assignee
Zeptosens 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 Zeptosens AG filed Critical Zeptosens AG
Priority to EP09015283A priority Critical patent/EP2169383A1/fr
Publication of EP1405056A1 publication Critical patent/EP1405056A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03—Cuvette constructions
    • G01N21/05—Flow-through cuvettes
    • 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
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5025—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures for parallel transport of multiple samples
    • 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
    • B01L3/50855—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 using modular assemblies of strips or of individual wells
    • 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
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • 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
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0877—Flow chambers
    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03—Cuvette constructions
    • G01N2021/0346—Capillary cells; Microcells
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/14—Heterocyclic carbon compound [i.e., O, S, N, Se, Te, as only ring hetero atom]
    • Y10T436/142222—Hetero-O [e.g., ascorbic acid, etc.]
    • Y10T436/143333—Saccharide [e.g., DNA, etc.]

Definitions

  • the invention relates to a body for forming an arrangement of flow-through cells according to the preamble of claim 1 or 3.
  • the invention further relates to a carrier according to the preamble of claim 9 and the arrangement of flow-through cells.
  • Figures 24-28 show embodiments described in International Patent Application PCT / EP 00/12668.
  • Figure 24 is with Figure 1 of PCT / EP patent application
  • 00/12668 identical and shows a partial cross-sectional view of a first flow cuvette arrangement. This figure shows the inlet 1 and the outlet 2 of an individual flow cell as well as parts of the neighboring flow cells.
  • the 24 comprises a base plate 4 and a body 6 brought together with it.
  • the body 6 has a recess 3 which, after the body 6 has been joined to the base plate 4, forms a spatial recess for producing a flow-through cell with inlet 1 and outlet 2.
  • the recess 3 can have any base; for example, it can be rectangular. Corners are preferably rounded in each case.
  • the outlet 2 or the inlet 1 of the flow cells adjacent in the cross-sectional direction are also shown.
  • the inlet and outlet of a flow-through cell are preferably each arranged at opposite end points of the base areas of the recess, in the case of an essentially rectangular base area, for example at the end points of the diagonals.
  • FIG. 25 is identical to FIG. 2 of patent application PCT / EP 00/12668 and shows a partial cross-sectional view of another embodiment of the flow-through cuvette arrangement according to FIG. 24.
  • the reservoir 5 is a depression in the outer wall of the body 6 brought together with the base plate 4. This embodiment makes it possible for liquid emerging from the flow-through cell to enter the reservoir 5 but not be able to feed it back into the flow-through cell as long as the reservoir does not reach the upper edge of the edge on the
  • Liquid outlet side is filled up.
  • FIG. 26 is identical to FIG. 3 of patent application PCT / EP 00/12668 and shows a partial cross-sectional view of a further embodiment of the
  • the body 6 can consist of one part or also of several parts, which are preferably irreversibly combined into one unit.
  • FIG. 27 is identical to FIG. 4 of patent application PCT / EP 00/12668 and shows a partial cross-sectional view essentially restricted to the base plate for an embodiment with an optical layer waveguide as base plate.
  • the base plate is designed as an optical layer waveguide with biological or biochemical or synthetic recognition elements immobilized thereon. 27, this layer waveguide comprises layers a, b and b '.
  • the reference symbols g in FIG. 27 denote the limits of a flow-through cell, which is produced by bringing the base plate together with a body 6. The reference symbol g therefore corresponds to the reference symbol 6 in FIGS. 24 to 26.
  • a thin intermediate layer b 1 and then a layer a, whose refractive index is greater than the refractive indices of layers b and b ', are first applied to a layer b which is transparent in at least part of the visible or near infrared spectrum.
  • Layers a and b ' are also optically transparent in at least part of the visible or near infrared spectrum.
  • Lattice structures c and c ' are formed in the layer b as a relief lattice, which are transferred into the layers above when they are applied.
  • An adhesion-promoting layer (f) is then applied to layer a, which can improve the adhesion to immobilizing biological or biochemical or synthetic recognition elements.
  • these detection elements are immobilized in spatially separated measuring areas d, which are located in this Embodiment are arranged both on and between the lattice structures c and C.
  • the base plate is finally brought together with the body g, which corresponds to the body 6 in FIGS. 24 to 26.
  • FIG. 28 is identical to FIG. 5 of patent application PCT / EP 00/12668 and shows an arrangement of flow-through cuvette arrangements in which column-shaped arrangements of base plates 4 and the bodies 6 respectively brought together form insert blocks 7, which in corresponding receiving openings of a common carrier 8 (Meta carrier) are used. In this way, an arrangement of a total of 6 columns of 6 flow cells each is generated.
  • the carrier has the basic dimensions of a standard microtiter plate.
  • the inlet openings 9 to the inlets 1 are positioned such that they are compatible with the grid of a standard 96-well microtiter plate, i.e. they are in
  • Intervals of an integer multiple of 9 mm positioned (for example: distance of the inlets within a column: 9 mm; distance of the inlets between adjacent columns: 18 mm).
  • the reservoirs 5 are compatible with the grid of a standard 96-well microtiter plate.
  • the carrier 8 is designed in such a way that it can accommodate up to 6 insert blocks. However, spaces for insert blocks can also remain unoccupied.
  • Flow cuvette assembly in a carrier is essential to reliability and accuracy of the measurements carried out, for example optical, electro-optical or electrical measurements.
  • the invention is therefore based on the object of providing a flow-through cuvette arrangement of the type mentioned above, which is designed in such a way that it can be positioned with increased precision in a carrier which is input into an analysis device and in turn can be positioned there with high precision and is automatically processed the processing comprises carrying out measurements, for example optical, electro-optical or electrical measurements, on a relatively large number of very small measurement areas which are close to one another.
  • the invention is also based on the object of providing a body for forming an arrangement of flow-through cells, which - the use of customary, commercially available
  • Pipette tips for supplying the samples or reagents to the cuvettes are possible and - require smaller volumes of the samples or reagents.
  • the first-mentioned object is achieved with a body according to claim 1.
  • the first-mentioned object is achieved with a flow-through cuvette arrangement according to claim 6.
  • the first-mentioned object is achieved with a carrier according to claim 9.
  • the first-mentioned object is achieved with a flow-through cuvette arrangement according to claim 11.
  • the first-mentioned object is achieved with a flow-through cuvette arrangement according to claim 12.
  • the second object is achieved by a body according to claim 3.
  • the embodiment or arrangement according to the invention enables high-precision positioning of an arrangement of flow-through cells of the type mentioned at the beginning with the aid of mechanical positioning aids, the achievable accuracy of the positioning being of the order of 50 micrometers and, surprisingly, no adjustments need to be made.
  • the preferred area of use of the flow cuvette arrangement according to the invention is the simultaneous (parallel) determination of a large number of analytes in one or more samples. This can happen in that the sample containers with the base plate in one embodiment as a sensor platform, so-called “microarrays" are housed.
  • the flow cuvette arrangement according to the invention can be used in all analytical measuring methods which are described or mentioned in the above-mentioned patent application PCT / EP 00/12668.
  • Figures 1 to 7 show different views of an embodiment of a body according to the invention for forming a straight line - that is, a one-dimensional arrangement - of flow-through cells.
  • Fig. 1 shows a perspective view of the body from above
  • F Fiigg .. 2 2 shows the front view of Fig. 1
  • Fig. 3 shows the view from behind according to FIG. 1,
  • Fig. 4 shows the view from the left side according to FIG. 1,
  • Fig. 5 shows the view from the right side according to FIG. 1,
  • Fig. 6 shows the view from above according to FIG. 1
  • F Fiigg. 7 7 shows the view from below according to FIG. 1.
  • FIGS. 8 to 15 show different views of an embodiment of a flow cuvette arrangement according to the invention, which is formed by joining a body according to FIGS. 1 to 7 and a base plate.
  • FIG. 10 shows the front view according to FIG. 8,
  • FIG. 11 shows the view from the rear according to FIG. 8
  • FIG. 12 shows the view from the left side according to FIG. 8,
  • FIG. 13 shows the view from the right side according to FIG. 8,
  • FIG. 14 a shows a partial cross section through the plane I-I in FIG. 14
  • FIG. 14 b shows an enlargement of the part encircled in FIG. 14
  • FIG. 15 shows the bottom view according to FIG. 8.
  • FIGS. 16 to 23 show different views of an embodiment of a carrier according to the invention for receiving a flow-through cuvette arrangement or a plurality of flow-through cuvette arrangements according to FIGS. 8-15.
  • FIG. 18 shows the front view according to FIG. 16
  • FIG. 19 shows the view from the rear according to FIG. 16
  • FIG. 20 shows the view from the left side according to FIG.
  • FIG. 21 shows the view from the right side according to FIG. 16
  • FIG. 22 shows the view from above according to FIG. 16
  • FIG. 23 shows the bottom view according to FIG. 16.
  • Figures 24-28 show embodiments described in International Patent Application PCT / EP 00/12668 and contained therein as Figures 1-5.
  • a one-dimensional or two-dimensional arrangement of flow-through cells serves as a component of an array of sample containers, the arrangement being formed from a base plate and a top body brought together with it, which has an arrangement of spatial recesses that corresponds to the arrangement of the sample containers, where at least one inlet and outlet is available for each sample container, and wherein the base plate, for example can be a glass plate, waveguide plate or a sensor platform.
  • the one- or two-dimensional arrangement of flow-through cells enables even very small amounts of samples or reagents to be fed to and / or removed from the sample containers, which can be arranged in large numbers on a small base area, for each sample container at least one reservoir for receiving liquid to be removed from the sample container and one peripheral system of liquid inlets and outlets is integrated into the arrangement.
  • FIGS. 1-7 A body according to the invention for forming a rectilinear row - that is to say a one-dimensional arrangement - of flow-through cells is shown in FIGS. 1-7.
  • Such an arrangement of flow-through cells (shown in FIGS. 8-15) is formed by joining the body 11 to a base plate 31 (not shown in FIGS. 1-7), which e.g. biological or biochemical or synthetic recognition elements. These detection elements are used for binding and detection of the analytes to be determined in supplied samples.
  • the body 11 has an outer shape which fits into a receiving opening 42 of a carrier 41 (shown in Figures 16-23), i.e. the body has an external shape which enables it to be inserted into a receiving opening in the wearer.
  • the body 11 has the following elements, which serve for the exact positioning of the body in the receiving opening of the wearer:
  • the Z direction is perpendicular to the plane spanned by two axes, namely an axis in the X direction and an axis in the Y direction.
  • the spring 51 lies approximately opposite the stop 52.
  • the spring 53 (or 55) is located approximately opposite the stop 54 (or 56), but slightly offset such that the outer edge of the stop lies in the plane of symmetry of the spring 53 (or 55) parallel to the ZY plane.
  • the above-mentioned positioning elements of the body 11 enable the body 11 and thus the arrangement of flow cells formed therewith without any adjustment with an accuracy of +/- 50 micrometers in each of the three mutually perpendicular directions X, Y and Z in a receiving opening of a carrier 41 to position according to Figures 16-23.
  • the snap hooks 61, 62 allow the arrangement to be inserted into the carrier by a slight pressure in the Z direction and secure the arrangement against falling out of the carrier.
  • the arrangement of the arrangement is designed in such a way that incorrect insertion is mechanically impossible.
  • a slight counter pressure in the Z direction is sufficient, by means of which the snap hooks 61, 62 are pressed slightly inwards become.
  • the snap hooks can also be released by pressure from below using an appropriately designed tool.
  • Asymmetrical mechanical positioning aids in the form of recesses and tabs of the body 11 and the carrier 41 and additional circular recesses on one half of the tabs of the body 11 and the carrier 41 serve as an optical positioning aid and enable a unique positioning of each flow cuvette arrangement in the carrier. An incorrect positioning of the arrangements in the carrier is therefore excluded.
  • the grid of the reservoirs 15 visible from the outside with the associated inlet openings 14 is offset from the grid of the flow-through cells 18 such that the inlet openings 14 to the flow-through cells are each located in one of their outer corners.
  • the outer surface of the body 11 for each flow cell can have a wholly or partially circumferential groove 21 with a cross section with the typical dimensions between 50 x 50 microns and 500 x 500 microns.
  • the inlet opening 14 and the outlet opening 17 for each flow cell 18 are located in two diagonally opposite corner points of this groove 21.
  • This groove 21 enables the flow cell to be filled without bubbles. If the formation of air bubbles during the filling process or during the methods for the detection of analytes to be carried out in the flow-through cells cannot be avoided in principle, a groove 21 can prove to be advantageous in that Air bubbles formed escape from the interior 13 of the flow-through cell and collect in the groove 21. In a preferred embodiment, this property is additionally ensured by chemical surface treatment of the inner surface of the groove 21 or of the entire inner surface of the flow-through cell, including said groove. This treatment serves to create a hydrophilic, i.e. more wettable surface.
  • the body 11 preferably has stops 22, 23, 24 which are used for the exact positioning of the base plate 31 (see FIGS. 8-15) in relation to the body 11 prior to its assembly, e.g. by gluing. There is no mechanical coupling between the stops 22, 23, 24 and the abovementioned stops, which serve for the exact positioning of the body 11 or the arrangement of flow-through cells formed therewith in a receiving opening 42 of the carrier 41.
  • the body 11 preferably has protective angles 25, 26, 27 which protect the base plate 31 against tearing off or damage which might otherwise occur in the carrier 41 in particular when the flow-through cuvette arrangement is inserted.
  • a circumferential web 29 is provided on the top of each of the flow-through cells, on which a film can be welded.
  • this film prevents "cross-contamination" between the cuvettes; on the other hand, it prevents fluid losses that might otherwise occur, in particular in nucleic acid hybridization assays with process steps at elevated temperatures up to, for example, approximately 80 ° C.
  • the following materials are suitable for the production of the body 11:
  • thermoplastics plastics
  • metals plastics
  • silicates such as glass, quartz or ceramics.
  • Examples of the materials for producing the body 11 are in particular:
  • PC polycarbonate
  • PBT Polybutylene terephthalate
  • ABS acrylonitrile / butadiene / styrene graft copolymer
  • the body 11 of the flow-through cuvette arrangement is colored black, unless a light guided in the base plate 31 (if embodied as a waveguide) is to be passed under the walls of the body 11 which directly touch the base plate.
  • This exemplary embodiment is a body according to the invention for forming a two-dimensional, matrix-like arrangement of flow-through cells, which comprises a multiplicity of cell rows with the structure of the body 11 described above and contains all the elements or elements described above with an equivalent function.
  • the characteristics of such Body can therefore be seen essentially from Figures 1-7.
  • a body according to this second embodiment is also suitable, by joining it to a base plate, e.g. biological or biochemical or synthetic recognition elements carries to form a flow cuvette arrangement.
  • a base plate e.g. biological or biochemical or synthetic recognition elements carries to form a flow cuvette arrangement.
  • this body itself can already have the external dimensions and external features of a standard microtiter plate according to the SBS standard.
  • This body can also have such an outer shape that fits into a receiving opening of a correspondingly designed carrier (e.g. with external dimensions according to the SBS standard).
  • the body can have the following elements, which are used for precise positioning of the body in the receiving opening of the wearer:
  • FIGS. 8-15 Flow-through cells, which comprise a rectilinear row - ie a one-dimensional arrangement - of flow-through cells are shown in FIGS. 8-15.
  • Such an arrangement of flow-through cells is formed by assembling the body 11 described above with reference to FIGS. 1-7 with a base plate 31, which e.g. biological recognition elements.
  • the base plate 31 and the body 11 are joined together, for example, by gluing or clipping.
  • the base plate 31 is suitable for serving as a waveguide.
  • the flow-through cells can be filled more easily and with pipette tips of larger diameter than in the earlier version according to FIG. 25 (version according to FIG. 2 of PCT / EP 00/12668).
  • pipette tips of larger diameter than in the earlier version according to FIG. 25 (version according to FIG. 2 of PCT / EP 00/12668).
  • regular, commercially available tips according to industry standards can be used.
  • the body has a delimitation wall 16 which serves to delimit the
  • Reservoirs 15 of the inlet opening 14 serves each cuvette and is arranged around this inlet opening.
  • the materials for the base plate, the body brought together with it and any additional cover plate that may be used must meet the requirements for the planned use of the arrangement. Depending on the specific application, these requirements relate to chemical and physical resistance, for example against acidic or basic
  • the material of the body brought together with the base plate is selected from the group consisting of moldable, sprayable or millable plastics, thermoplastics, metals, silicates, such as glass, quartz or ceramics.
  • the material of the additional continuous cover plate can be selected from the group consisting of moldable, sprayable or millable plastics, metals, silicates, such as glass, quartz or ceramics.
  • the material of the base plate comprises materials from the group consisting of moldable, sprayable or millable plastics, thermoplastic plastics, metals, silicates, such as glass, quartz or ceramics.
  • the components mentioned can each consist of a uniform material or also comprise a mixture or layer-by-layer or lateral joining of different materials, the materials being able to replace one another.
  • the surfaces of the body 11, which form the "cover” and the side walls of the sample containers, should be as little reflective as possible in order to keep the disturbing influence of the excitation light reflected there as small as possible.
  • the excitation light is generally always radiated through the base plate and the measuring light (at excitation wavelength and / or at
  • the material of the base plate is preferably selected so that it is used at least in the one or more Excitation wavelengths and optionally also at corresponding luminescence wavelengths is transparent.
  • the base plate should also be as free as possible from self-luminescence.
  • the base plate can consist of a uniform material (e.g. as a plate made of glass or correspondingly transparent plastic) and can be illuminated with excitation light in a classic incident light arrangement, for example. It can also be a multi-layer system (for
  • Example formed as a thin film waveguide The light irradiation can then also take place in the classic arrangement just described. It is preferred that the base plate is a (thin) layer waveguide with the properties and embodiments described in PCT / EP 00/12668.
  • the following materials are suitable, for example, for the production of the base plate 31: moldable, sprayable or millable plastics, thermoplastic plastics (preferred
  • the material of the base plate is selected such that the base plate is largely transparent, at least at the wavelength of this excitation light.
  • the base plate 31 serves as an optical layer waveguide
  • the base plate has, for example, the structure according to FIG. 27, which essentially restricted one to the base plate Cross-sectional partial view shows.
  • the base plate is designed as an optical layer waveguide with biological or biochemical or synthetic recognition elements immobilized thereon. 27 includes this
  • the reference symbol (g) in FIG. 27 denotes the limits of a flow-through cell, which is produced by bringing the base plate together with a body.
  • the reference symbol (g) therefore corresponds to the reference symbol 11 in FIGS. 1 to 15.
  • a layer (b) which is transparent in at least part of the visible or near infrared spectrum there is first a thin intermediate layer (b 1 ) and then one
  • Layer (a) applied the refractive index of which is greater than the refractive indices of layers (b) and (b 1 ).
  • Layers (a) and (b ') are also optically transparent in at least part of the visible or near infrared spectrum.
  • Lattice structures (c) and (c ') are formed in the layer (b) as a relief lattice, which are transferred into the layers above when they are applied.
  • An adhesion-promoting layer (f) is then applied to layer (a), which can improve the adhesion to immobilizing biological or biochemical or synthetic recognition elements.
  • these recognition elements are immobilized in spatially separated measuring areas (d), which in this embodiment are arranged both on and between the grating structures (c) and (C).
  • the base plate is finally brought together with the body (g), which corresponds to the body 11 in FIGS. 1 to 15.
  • Layer (a) of the base plate is, for example, a high-index metal oxide layer on layer (b).
  • Examples of materials for the second optically transparent layer b are:
  • - silicates e.g. B. glass or quartz, or
  • thermoplastic or sprayable plastic preferably from the group formed by polycarbonate, polyimide, polymethyl methacrylate or polystyrene.
  • This second arrangement of flow-through cells according to the invention is formed by combining a body which, in accordance with the second exemplary embodiment described above under 2) according to one of the two embodiments of such a body described there, is suitable for forming a matrix-like arrangement of flow-through cells, and a base plate which, for example, biological recognition elements.
  • the base plate and the body are joined together, for example, by gluing or clipping.
  • the flow cuvette arrangement thus formed can be used in an analysis system either as an independent unit, i.e. can be used without using a carrier, or with a carrier that has at least one recess for receiving the flow-through cuvette arrangement.
  • the base plate 31 is preferably suitable for serving as a waveguide.
  • Flow cuvette arrangements can be used the same materials that are given above under 3).
  • a carrier 41 according to the invention for a body 11 for forming a straight line - that is to say a one-dimensional arrangement - of flow-through cells is shown in FIGS. 16-23.
  • the carrier 41 has a multiplicity of recesses 42, the shape and dimensions of which are adapted to the outer shape of the body 11 in such a way that an exact positioning of the body 11 in the recess 42 is made possible.
  • the outside dimensions of the carrier preferably correspond to the SBS standard.
  • the carrier therefore has the dimensions of a standard microtiter plate, i.e. approx. 85 mm x 128 mm.
  • the carrier can be designed for single use or as a reusable component, from which the flow cuvette arrangements used therein can be released by pressing together the snap hooks S.
  • the snap hooks can also be released by pressure from below using an appropriately designed tool.
  • the carrier can e.g. hold up to 5 flow cuvette arrangements, e.g. 6 flow cells included.
  • elevations 43 in the outer corners, 44, 45 and another elevation 46 different therefrom correspond to corresponding recesses 63, 64, 65, 66 in the underside of the carrier 41 (see FIG. 17).
  • elevations and recesses make it possible to stack a plurality of carriers one above the other and at the same time to keep the undersides of the base plates 31 to be glued into the body 11 (glass plates, waveguide plates or sensor platforms) contact-free so that contamination of the undersides of the base plates is avoided.
  • a receiving web with elevations complementary to the two recesses moves under the carrier in order to then raise it slightly.
  • Two light barriers run parallel to the long sides of the carrier. If the carrier is inserted into the input device with an incorrect orientation, its side with the smaller lateral recess is raised too much. This is confirmed by a corresponding
  • Photoelectric sensor detects, which results in the refusal to accept the carrier in the automatic analysis system.
  • thermoplastic plastics plastics (preferred production by means of "Injection Molding"), metals, silicates, such as glass, quartz or ceramics,
  • Examples of the materials for producing the carrier 41 are in particular:
  • PC polycarbonate
  • PBT Polybutylene terephthalate
  • PPS polyphenyl sulfide
  • ABS acrylonitrile / butadiene / styrene graft copolymer
  • the support is colored black.
  • This second embodiment of a carrier is used to hold at least one body according to 2) above, i.e. a body for the formation of a two-dimensional, matrix-like arrangement of flow-through cells.
  • This second exemplary embodiment of a carrier has at least one recess, the shape and dimensions of which are matched to the outer shape of the body to be accommodated in such a way that it enables the body to be precisely positioned in the recess.
  • This exemplary embodiment of a flow-through cuvette arrangement contains one or more flow-through cuvette arrangements, each inserted in a receiving opening 42 of a carrier 41 according to FIGS. 16-23, like the one described above under 3) with reference to FIGS. 8-15.
  • the base plate 31 and the body 11 are joined together, for example, by gluing.
  • the base plate 31 is clamped between the body 11 and the carrier 41, and is joined to the body exclusively by means of a force which is generated by the composition of the body 11 and the carrier 41.
  • the base plate is held as follows:
  • the carrier 41 On the underside of the carrier 41 there are thin (e.g. 0.3 mm thick) supporting webs all around the receiving openings, so that the base plates 31 (on their top side) provided with the biological or biochemical or synthetic recognition elements (e.g.
  • Glass plates, waveguide plates, sensor platforms can first be inserted into the carrier 41. Only then are the bodies 11, with integrated sealing lips or 0-rings (e.g. made of elastic plastic), which can contain the grooves 21 shown in FIG. 7, inserted into the carrier 41 with, for example, barb-like holders such that between the Bodies 11 and the base plate 31 a pressure of a defined thickness is generated so that a mutual fluidic sealing of the flow cell produced together with the base plate 31 is effected.
  • the bodies 11, with integrated sealing lips or 0-rings e.g. made of elastic plastic
  • Bodies 11 suitable for this variant consisting of rigid and elastic plastic parts, are preferably produced in a two-component injection molding process.
  • this variant can comprise a suitably designed rigid plastic body and sealing rings to be inserted into corresponding recesses in the body.
  • Such an embodiment also makes it possible, in particular, that the immobilization of the biological or biochemical or synthetic recognition elements (for example by "spotting") on the base plates 31 is only carried out on site by the customer.
  • thermoelastic plastics e.g.
  • SEBS Styrene ethylene butadiene styrene
  • silicone / silicone silicone / silicone
  • elastomers rubber
  • This exemplary embodiment of a flow-through cuvette arrangement contains at least one inserted in a receiving opening of a carrier according to 6) above
  • the flow cuvette assembly can be shaped to form a self-contained unit that does not require a carrier to be used in an analysis system.
  • Such a flow cuvette arrangement can e.g. 96 flow cells or more, e.g. 384 or 1536 flow-through cells arranged on the same footprint, or arrays of any size.
  • the base plate and the body are joined together, for example, by gluing or clipping.
  • the base plate is clamped between the body according to a variant according to exemplary embodiment 7 and the carrier, and is joined to the body exclusively by means of a force which is generated by the composition of the body and the carrier.
  • the base plate comprising an optical waveguide which is continuous or divided into individual areas, excitation light is guided via an optical coupling element in said optical waveguide and measurement light is detected by the measurement areas with one or more detectors, which interact in an optical manner with said optical waveguide.
  • ⁇ said optical waveguide is formed as an optical film waveguide with a first optically transparent layer (a) on a second optically transparent layer (b) with lower refractive index than layer (a), wherein furthermore excitation light using one or several lattice structures, which in the optically transparent
  • Layer (a) are pronounced, coupled into the optically transparent layer (a) and to those located thereon Measuring ranges (d) is guided as a guided wave, and the luminescence of luminescent molecules generated in the evanescent field of said guided wave is also detected with one or more detectors and the concentration of one or more analytes is determined from the intensity of these luminescence signals.
  • Body fluids such as blood, serum, plasma, lymph or urine or tissue fluids or egg yolk.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Optical Measuring Cells (AREA)

Abstract

L'invention concerne un dispositif de cuvettes de circulation formé par assemblage d'un corps (11) avec une plaque de base. Le corps (11) présente les éléments suivants destinés à positionner précisément le corps dans l'orifice de réception d'un support dans trois directions (directions x, y, z) : (a) un premier élément ressort et une première butée disposés dans des zones terminales opposées du corps (11) ; (b) au moins un deuxième élément ressort et une deuxième butée correspondante, disposés sur des côtés opposés du corps (11) ; et, (c) au moins un élément support et au moins un élément de fixation.
EP02732307A 2001-06-15 2002-06-10 Corps destine a des cuvettes de circulation et utilisation de celles-ci Withdrawn EP1405056A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP09015283A EP2169383A1 (fr) 2001-06-15 2002-06-10 Organe pour l'écoulement à travers des cuvettes et son utilisation

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CH10892001 2001-06-15
CH108901 2001-06-15
PCT/CH2002/000309 WO2002103331A1 (fr) 2001-06-15 2002-06-10 Corps destine a des cuvettes de circulation et utilisation de celles-ci

Publications (1)

Publication Number Publication Date
EP1405056A1 true EP1405056A1 (fr) 2004-04-07

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EP02732307A Withdrawn EP1405056A1 (fr) 2001-06-15 2002-06-10 Corps destine a des cuvettes de circulation et utilisation de celles-ci
EP09015283A Withdrawn EP2169383A1 (fr) 2001-06-15 2002-06-10 Organe pour l'écoulement à travers des cuvettes et son utilisation

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EP09015283A Withdrawn EP2169383A1 (fr) 2001-06-15 2002-06-10 Organe pour l'écoulement à travers des cuvettes et son utilisation

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EP (2) EP1405056A1 (fr)
WO (1) WO2002103331A1 (fr)

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Also Published As

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WO2002103331A1 (fr) 2002-12-27
US20040185576A1 (en) 2004-09-23
US20080274451A1 (en) 2008-11-06
US7399628B2 (en) 2008-07-15
EP2169383A1 (fr) 2010-03-31

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