EP2486387A1 - Appareil d'analyse et procédé - Google Patents

Appareil d'analyse et procédé

Info

Publication number
EP2486387A1
EP2486387A1 EP10770505A EP10770505A EP2486387A1 EP 2486387 A1 EP2486387 A1 EP 2486387A1 EP 10770505 A EP10770505 A EP 10770505A EP 10770505 A EP10770505 A EP 10770505A EP 2486387 A1 EP2486387 A1 EP 2486387A1
Authority
EP
European Patent Office
Prior art keywords
sample
sample container
liquid
unit
particles
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Withdrawn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
EP10770505A
Other languages
German (de)
English (en)
Inventor
Bruno Balluch
Walter Smetana
Ibrahim Atassi
Gottfried KÖHLER
Michael Edetsberger
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.)
Onkotec GmbH
Original Assignee
Onkotec 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 Onkotec GmbH filed Critical Onkotec GmbH
Publication of EP2486387A1 publication Critical patent/EP2486387A1/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Withdrawn legal-status Critical Current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
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/14—Optical investigation techniques, e.g. flow cytometry
    • G01N15/1456—Optical investigation techniques, e.g. flow cytometry without spatial resolution of the texture or inner structure of the particle, e.g. processing of pulse signals
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F35/71—Feed mechanisms
    • B01F35/713—Feed mechanisms comprising breaking packages or parts thereof, e.g. piercing or opening sealing elements between compartments or cartridges
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F35/71—Feed mechanisms
    • B01F35/713—Feed mechanisms comprising breaking packages or parts thereof, e.g. piercing or opening sealing elements between compartments or cartridges
    • B01F35/7137—Piercing, perforating or melting membranes or closures which seal the compartments
    • 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
    • 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
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502715—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/14—Optical investigation techniques, e.g. flow cytometry
    • G01N15/1468—Optical investigation techniques, e.g. flow cytometry with spatial resolution of the texture or inner structure of the particle
    • 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
    • B01L2200/027—Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
    • 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
    • B01L2300/04—Closures and closing means
    • B01L2300/041—Connecting closures to device or container
    • B01L2300/042—Caps; Plugs
    • 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
    • B01L2300/04—Closures and closing means
    • B01L2300/041—Connecting closures to device or container
    • B01L2300/045—Connecting closures to device or container whereby the whole cover is slidable
    • 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
    • B01L2300/04—Closures and closing means
    • B01L2300/046—Function or devices integrated in the closure
    • B01L2300/047—Additional chamber, reservoir
    • 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
    • B01L2300/04—Closures and closing means
    • B01L2300/046—Function or devices integrated in the closure
    • B01L2300/048—Function or devices integrated in the closure enabling gas exchange, e.g. vents
    • 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
    • B01L2300/04—Closures and closing means
    • B01L2300/046—Function or devices integrated in the closure
    • B01L2300/049—Valves integrated in closure
    • 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
    • B01L2300/0672—Integrated piercing tool
    • 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
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • 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
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0478—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure pistons
    • 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
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0677—Valves, specific forms thereof phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers
    • B01L2400/0683—Valves, specific forms thereof phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers mechanically breaking a wall or membrane within a channel or chamber
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/06—Investigating concentration of particle suspensions
    • G01N15/075—Investigating concentration of particle suspensions by optical means
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/14—Optical investigation techniques, e.g. flow cytometry
    • G01N15/1429—Signal processing
    • G01N15/1433—Signal processing using image recognition
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/14—Optical investigation techniques, e.g. flow cytometry
    • G01N15/1468—Optical investigation techniques, e.g. flow cytometry with spatial resolution of the texture or inner structure of the particle
    • G01N2015/1472—Optical investigation techniques, e.g. flow cytometry with spatial resolution of the texture or inner structure of the particle with colour
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N2035/00465—Separating and mixing arrangements
    • G01N2035/00564—Handling or washing solid phase elements, e.g. beads
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N2035/00465—Separating and mixing arrangements
    • G01N2035/00564—Handling or washing solid phase elements, e.g. beads
    • G01N2035/00574—Means for distributing beads
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/0098—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation

Definitions

  • the invention relates to an analysis device for the quantitative and / or qualitative analysis of particles in a substantially liquid sample and a method for carrying out the analysis using the aforementioned device.
  • particles such as cells
  • the term particles comprises biological cells of various origins or optionally solids or molecules.
  • liquid samples with a dye, e.g. with individual proteomic markers, which attach to the particles in the sample.
  • a dye e.g. with individual proteomic markers
  • these methods to detect and quantify tumor cells in various body fluids, e.g. in urine.
  • the known methods have the disadvantages that they take more than 50 minutes to prepare a prepared sample preparation and many individual steps are required, which can be performed only by qualified personnel.
  • the use of a wide variety of devices is required, the operation of which also requires specially trained personnel.
  • the invention aims to provide an analysis device and a method which make it possible to shorten the analysis time for the quantitative and qualitative detection of predetermined particles in a liquid in comparison to known methods and thus to make them more economical. Another goal is to make the analysis easy and reliable and to make the result visually tangible.
  • an inventive analyzer with a sample container unit from a sample container for receiving a liquid sample and marking the particles contained in the sample, with a lid for liquid-tight sealing of the sample container; a measuring cell unit, wel che is in fluid communication with the sample container via a drain, which measuring cell unit has a liquid-conducting channel, wherein at least one channel wall is at least partially formed as a transparent window; a carrier unit which has means for contactless transport and / or concentration of labeled particles contained in the sample liquid; and with an optical unit for spectroscopic and / or microscopic detection of the labeled particles, with at least one light source for exciting the marked particles in the sample.
  • the method according to the invention for analyzing a substantially liquid sample with freely mobile particles contained therein comprises the steps of a) marking the particles with a dye and / or magnetic agents, b) spatially bundling the marked particles, optionally magnetically creating a magnetic field for spatial concentration sensitive particles and / or sedimentation, and c) performing a spectroscopic and / or microscopic analysis of the particles contained in the sample.
  • the present invention provides high accuracy for a short incubation period of 5 to 10 minutes, i. a sensitivity and selectivity> 95%, especially for early disease.
  • the analyzer according to the invention has a compact design with short fluid channels, so that only small volumes of
  • Agents and sample liquids are needed, whereby u.a. the analysis costs can be lowered.
  • the analyzer according to the invention and the method carried out with this analyzer allow, in particular, rapid and objectified computer-assisted detection of pathologically altered particles, in particular in body fluids such as urine or sputum, but also of particles in blood and in cell suspensions of tissues.
  • the analysis according to the invention The device as well as the method according to the invention can be advantageously used for the cytological detection of cancers, in doping controls or for the counting of particles and bacteria.
  • a preferred embodiment is characterized in that the lid of the sample container is formed from a screw-on outer cover part and a middle cover part connected thereto via a predetermined breaking point, wherein the outer diameter of the middle lid part approximately corresponds to the inner diameter of the sample container, so that the middle lid part form fit can be lowered into the sample container.
  • a further preferred embodiment is characterized in that the middle lid part comprises an inner lid part which can be moved into the middle lid part and, between the underside of the inner lid part and a foil extending between the lower edge of the middle lid part, a cavity for receiving the agents for Marking of the particles is formed in the sample.
  • a further preferred embodiment is characterized in that additionally prestressed elements are provided in the cavity, which in the triggered state preferably dip into the sample.
  • valves are arranged at the inlet and at the outlet of the liquid-conducting channel.
  • a further preferred embodiment is characterized in that a mixing chamber is arranged between the inlet of the liquid-conducting channel and the spectroscopic and / or microscopic observation chamber.
  • a further preferred embodiment is characterized in that a filter is arranged downstream of the spectroscopic and / or microscopic observation chamber in the liquid-conducting channel.
  • a further preferred embodiment is characterized in that the sample container unit and the carrier unit are releasably connected to one another.
  • sample container unit can be connected to the carrier unit in an alignment-selective manner by means of shaped elements, the carrier unit having counterpart means.
  • a further preferred embodiment is characterized in that the shaped elements are formed as a set of at least two holes with different inner diameters.
  • a further preferred embodiment is characterized in that the light source is formed by at least one monochromatic LED and that the light is conducted to the spectroscopic and / or microscopic observation chamber by means of an optical waveguide integrated in the carrier unit.
  • a further preferred embodiment is characterized in that the carrier unit has at least one coil system for generating magnetic fields, by means of which magnetically sensitive particles in the sample can be spatially bundled or distributed.
  • a further preferred embodiment is characterized in that the carrier unit further comprises at least one temperature sensor and at least one heating element for heating the sample before and / or after the analysis location.
  • a further preferred embodiment is characterized in that the carrier unit has a liquid-conducting channel.
  • a further preferred embodiment is characterized in that the carrier unit has sensors for determining further sample parameters.
  • a preferred embodiment of the method is characterized in that after the analysis of the sample it comprises the step of: backwashing the particulate fraction as well as the sample liquid followed by a cleaning solution in the sample container and / or disinfecting the carrier unit.
  • FIG. 1a to 1f show a longitudinal section through a sample container unit from a sample container with a lid and a measuring cell unit at different stages of the analysis method
  • FIG. 2 shows a schematic cross-sectional view of a measuring cell unit
  • FIG. 3 shows a schematic view of a combination of a carrier unit and an optical unit
  • Fig. 4a to 4e is a schematic representation of a connector
  • Fig. 5 is a schematic representation of the analyzer.
  • a first functional part of the analyzer is the sample container unit 1 shown in FIG. 1a, which essentially consists of three functional groups: a sample container 2, a lid 3 and the container bottom, e.g. By plugging connectable, separately shown measuring cell unit 4 consists.
  • the function of the sample container 2 is the recording of the substantially liquid sample to be examined, in particular during the marking of the particles contained therein.
  • the sample container has in its bottom an outflow 43, through which the sample passes from the sample container 2 into the measuring cell unit 4 for analysis.
  • the agents required for the analysis such as a dye, and / or magnetic beads, protected against environmental influences and aging, may be incorporated in the lid 3 of the sample container 2, optionally in chambers separated from one another by chambers, if desired , Into the sample container insert elements (not shown) which serve, for example, pre-filtering to prevent clogging of the outflow 43 to the measuring cell unit 4 by coarse impurities (kidney stone fragments, tissue obfuscations of OPs) or or as a depot for additional agents.
  • coarse impurities kidney stone fragments, tissue obfuscations of OPs
  • plug-in elements (not shown) of the same functionality can be connected in a form-fitting, non-detachable and liquid-tight manner externally to the container bottom via the connecting pins 6.
  • These plug-in elements have on their underside connection possibilities for the measuring cell unit 4.
  • As a translation pieces (adapter) these plug-in elements allow a connection between modified types of the measuring cell unit 4 with the sample container.
  • the measuring cell unit 4 shown in FIG. 2 is connected via connecting pins 6 to the sample container bottom via two-latching holes 53, whereby a fluid connection is established between the outflow 43 and a liquid-conducting channel 49 provided in the measuring cell unit, and contains functional according to the analytical task Cell analysis components arranged along the liquid-conducting channel 49. These components are i.a. a mixing chamber 7, a spectroscopic and / or microscopic observation chamber 8, which optionally serves for sedimentation, and a filter 9 for filtering particles.
  • the measuring cell unit 4 also has valves 42 and 44 to control the flow of the sample during the analysis.
  • At the bottom of the observation chamber 8 there is a transparent window 45 in order to be able to examine the sample spectroscopically and / or microscopically, preferably by fluorescence spectroscopy and / or fluorescence microscopy.
  • the sample container unit 1 is preferably designed as a plastic disposable part. Each sample in this case requires its own sample container unit. Fulfill your subcomponents Microfluidic functions for separating the particles present in the liquid, but preferably contain no sensors. The particulate portion of the sample remains before, during and also after the analysis always within the measuring cell unit 4 of the sample container unit 1 and can be disposed of properly with this after the successful analysis.
  • the carrier unit 10 shown in FIGS. 3 and 5, on which the sample container unit 1 is placed serves primarily as a carrier of components which, in cooperation with the measuring cell unit 4, support a fluorescence spectroscopic and / or fluorescence microscopic analysis of the particulate portion of the sample by controlling the transport, the concentration and the environmental conditions of the particles to be determined.
  • components such as temperature sensors 11, flow sensors 12 for detecting flow rates, piezoactuators 13 for an autofocus function of an optical part or else for generating an ultrasound field, coil systems 14 for generating magnetic fields, electromechanical or pneumatic systems can be used in this carrier unit.
  • matic encoder for valves of the measuring cell unit 4, elements for cooling or temperature control of the measuring cell unit 4 and the coil system 14 are integrated.
  • the carrier unit preferably has controllable magnetic coil systems 14. These coil systems 14, arranged in an array, can be switched on and off as desired, thereby generating alternating magnetic fields for controlled mixing, but also fields for immobilizing magnetic beads with afflicted particles.
  • controllable magnetic coil systems 14 are arranged both above and below the measuring cell unit 4 of the sample container unit 1.
  • a recess 41 is provided between the sample container unit 1 with attached measuring cell unit 4, which receives a web 18 of the carrier unit 10, in which coil systems 14 are provided.
  • This web 18 of the carrier unit 10 can optionally be integrated into the analyzer as a module to support the sedimentation of the cells or particles.
  • the carrier unit 10 is preferably designed for continuous operation.
  • preference is given to using ceramic multilayer circuit technology which is known to the person skilled in the art.
  • the coil systems 14 shown in FIGS. 3 and 5 can be produced integrally, which are flowed through with currents of up to 10 amperes, whereby stronger magnetic forces of the order of nano-Newton are available for controlling the magnetically marked particles .
  • ferritic films with a relative magnetic permeability of 100 to 400 in the linear range can be used, with which the magnetic field can be focused specifically in the sample medium.
  • the ceramic allows by suitable arrangement of the components and a dissipation of the resulting heat.
  • a temperature control system in the form of heating elements 15 with temperature sensors can also be integrated into the carrier unit 10, since this maintains the activity of the particles or cells and the sensitivity of the entire analysis system can be increased.
  • Heating elements 15 may also be provided in areas of liquid-conducting channels 54 provided in the carrier unit 10 for the purpose of forwarding or discharging the sample liquids in order to permit thermal sterilization of these channels.
  • sensors 17 for determining additional parameters such as the liquid portions of the sample for determining their pH, ammonia content and / or protein content can be variably integrated into the carrier unit in an optional analysis section.
  • optical unit 20 serves for the detection of the marked target cells in the measuring cell unit 4 as well as optionally for the excitation of the marked target cells.
  • the optical unit 20 in a conventional construction of an LED 21 as an excitation source, a collimator 22 to the parallel direction of the radiation, a diaphragm 23, an excitation filter 24, a dichroic beam splitter 25 which reflects waves of the excitation frequency and waves of emission frequency in the direction of a camera 26, a microscope objective 27, an emission filter 28, a plano-convex converging lens 29 and finally a suitable camera 26.
  • This optical function group can be composed of standard components.
  • the further evaluation can be computer-assisted, for which purpose a corresponding electronic device 55 is provided.
  • the excitation can also be effected by a preferably narrow-band emitting, preferably monochromatic LED 19 via an optical waveguide 30 via the carrier unit 10 by means of a specific refractive index controlled light guide, as likewise shown in FIG.
  • a specific refractive index controlled light guide as likewise shown in FIG.
  • the measuring method using the analyzer according to the invention will also be explained in more detail with reference to the drawings.
  • FIG. 1b there is a sample container unit 1 provided with the sample with the lid 3 closed, with the measuring cell unit 4 plugged on. A seal 57 is still closed, and the measuring cell unit by spring tongues 33 spaced from the container bottom.
  • an inner cover part 36 is screwed into a middle cover part 47, whereby a film 35 opens, the agents 5 fall into the sample and incubate it.
  • the sample container unit 1 is pushed in counterparts or alignment-selective position according to FIGS. 4 a to 4 e and 5 onto counterparts 31, for example in the form of load-bearing guide pins of the carrier unit 10.
  • the counterparts 31 are shown in cross-section, which engage in opposite mold elements 52 in the form of holes in the sample container 2 during the pushing-on.
  • this pushing buckles predetermined bending zones 32 of those spring tongues 33 which, as spacers, prevent inadvertent fluid connection of the measuring cell unit 4 placed on the container bottom with the sample container 2.
  • the sample container 2 can not be pulled off until the end of the measuring process according to FIGS.
  • the counter-piece means 31 with wedge-shaped recess 34 prevent, in unit with the bent spring tongues 33 on the container bottom, a release of the sample container 2, for example by means of barbs.
  • the counterpart means 31 are designed rotatable according to FIG. 4e about their longitudinal axis.
  • the counterparts 31, on which the sample container 1 is locked are lowered together with the upper part of the carrier unit 10 according to FIGS. 4c and 4d.
  • the measuring cell unit 4 which as a first part of the sample container unit 1 is fixed on the carrier unit 10, subsequently pressed against the upper carrier unit 10 and the container bottom 1, so that according to FIG. 4d, the transition piece 56 of the measuring cell unit 4 pierces the seal 57 of the container bottom (see also FIG. Ld).
  • the connection between sample container 2 and measuring cell unit 4 produced by the connecting pins 6 snaps in indissolubly.
  • the sample container 2 assumes the function of a perfusion cartridge during the measuring process.
  • the cover 3 acts as shown in FIG. Ld as a stamp. It is constructed for this purpose from an outer cover part 46 and a central cover part 48, which are connected to one another according to Fig. La to lc via a predetermined breaking point 47.
  • an inner cover part 36 is screwed in as far as the stop via the perfusor spindle drive, which opens the sealing film 35.
  • the sample liquid is incubated with the dye 5 and, if necessary, with magnetic beads. About barbs are from this phase middle cover part 48 and inner cover part 36 liquid-tightness secured against re-screwing. Further screwing can break the predetermined breaking point 47 and now lowers the inner cover part 36 and the middle cover - part 48 together as a stamp from FIG. Ld.
  • the agents 5 are contained, for example, in solid form in the lid 3, optionally applied flat on the film 35, or are present as a coating of mixed beads.
  • biased elements 37 hidden inside the lid, biased elements 37, for example made of plastic, unfold spontaneously and when breaking the film support the mixing of the agents 5 with the sample liquid.
  • a special geometry of the inside of the cover in the form of paddles or spoilers can additionally promote the mixing during the further, rotating retraction of the cover 3 as a stamp.
  • Any residual air present in the container 2 can escape through a venting valve 38 in the lid 3, which, however, does not allow any escape of liquid.
  • An optional backwashing of the sample in the sample container 2 after the analysis is carried out by tensile load on the lid 3, as shown in Fig le.
  • the vent valve 38 locks, for example, by engaging a valve plunger or float.
  • the incubated sample liquid passes into the mixing chamber 7 of the measuring cell unit 4.
  • additional agents can be supplied as required via an optionally second switchable inlet 51 in the measuring cell unit 4, as shown in FIG.
  • the feed is in turn controlled by a valve 50.
  • the subsequent mixing is carried out by a combined method, on the one hand fluidically through integrated in the mixing chamber 7 and / or the observation chamber 8 barriers or diaphragms (not shown) in a coordinated control of the flow rate, or field-induced by controllable coil systems 14, the are located in the below or above the measuring cell unit positioned carrier unit 10.
  • the thus marked and mixed sample flows to the observation chamber 8, where the color-coded and optionally also magnetically marked particles sediment or by a strong inhomogeneous magnetic field, caused by example Neodymium magnets (not shown) or by the coil systems 14, are collected. After switching off the magnetic field, the particles can also sediment freely. Alternatively, the particles may be concentrated in an upright field by slow mechanical / pneumatic induced lowering of an observation chamber cap 39 of soft and dark-colored plastic which suppresses background spurious reflections.
  • the measuring cell unit 4 contains a filter 9 for the separation of further particles. Premature closing of the filter membrane of the filter 9 by obstruction or occlusion can be detected by a pressure increase in the measuring cell unit and suppressed by backwash pulses on the one hand orthogonal through the filter membrane and the prefilter side tangentially along the filter membrane by means of an additional, not shown channel unit with valve , Likewise, after flowing through the entire sample volume, those particles which sediment in the region of the filter chamber can be flushed back in the direction of the observation chamber by means of such a countercurrent flow. If desired, the sample liquid can be subjected to further analyzes in an analysis section 16 and is finally collected in a waste unit 40 for disposal.
  • the sample liquid can be rinsed back into the sample container 2 in the course of device disinfection.
  • the particulate portion of the sample and also the sample liquid followed by a cleaning solution are rinsed back into the sample container and the carrier unit 10 disinfected, after which the closed sample container 2 can be safely disposed of professionally.
  • this can be done, for example, according to Fig. 4e by rotating the guide pins formed as a counterpart means 31 and therefore canceling the lock, and the sample container 1 can be removed.
  • the method and the components of the measuring cell unit 4, the carrier unit 10 and the optical unit 20 are preferably controlled via an electronic device 55, such as a computer.
  • the qualitative and / or quantitative analysis of the labeled particles or cells preferably also takes place computer-assisted.
  • dichroic beam splitter 54 liquid-conducting channel 26 camera 55 electronic device

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Dispersion Chemistry (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Engineering & Computer Science (AREA)
  • Signal Processing (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Optical Measuring Cells (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

La présente invention concerne un appareil d'analyse comprenant une unité récipient à échantillon (1), une unité cellule de mesure (4), une unité support (10), et une unité optique (20). L'unité récipient à échantillon (1) comporte un récipient à échantillon, qui sert à recevoir un échantillon essentiellement liquide et à marquer les particules contenues dans l'échantillon, et qui comporte un couvercle assurant la fermeture étanche au liquide du récipient. L'unité cellule de mesure (4), qui est reliée fluidiquement au récipient à échantillon par l'intermédiaire d'un conduit d'écoulement, comporte un canal conduisant les liquides, l'une au moins de parois du canal étant au moins partiellement réalisée de façon à être transparente. L'unité support (10) comporte un organe permettant, sans contact, de transporter et/ou de concentrer de particules marquées contenues dans le liquide d'échantillon. Enfin, l'unité optique (20) qui sert à la détection spectroscopique et/ou microscopique des particules marquées, comporte au moins une source de lumière (19, 21) servant à exciter les particules marquées contenues dans l'échantillon.
EP10770505A 2009-10-07 2010-10-07 Appareil d'analyse et procédé Withdrawn EP2486387A1 (fr)

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ATA1582/2009A AT508806B1 (de) 2009-10-07 2009-10-07 Analysegerät und verfahren
PCT/AT2010/000374 WO2011041814A1 (fr) 2009-10-07 2010-10-07 Appareil d'analyse et procédé

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EP2486387A1 true EP2486387A1 (fr) 2012-08-15

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EP (1) EP2486387A1 (fr)
AT (1) AT508806B1 (fr)
WO (1) WO2011041814A1 (fr)

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EP2563901A4 (fr) * 2010-04-28 2018-03-21 Siemens Healthcare Diagnostics Inc. Système d'analyse d'échantillons et procédé d'utilisation
DE102012102296A1 (de) * 2012-03-19 2013-09-19 Endress + Hauser Conducta Gesellschaft für Mess- und Regeltechnik mbH + Co. KG Messanordnung umfassend mindestens ein erstes Analysegerät zur automatisierten Bestimmung einer Messgröße einer Flüssigkeit und eine Probenvorbereitungseinrichtung
WO2015088942A1 (fr) * 2013-12-12 2015-06-18 3M Innovative Properties Company Appareil et procédé de préparation d'échantillon biologique pour analyse
US20160090617A1 (en) * 2014-09-25 2016-03-31 U.S. Environmental Protection Agency Concentration device for microorganisms in large volumes of turbid water and method therefor
DE102014115594A1 (de) * 2014-10-27 2016-04-28 Endress + Hauser Conducta Gesellschaft für Mess- und Regeltechnik mbH + Co. KG Probennahmevorrichtung
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CN117706102B (zh) * 2024-02-05 2024-04-12 遂宁市中心医院 一种肿瘤康复用光学检测装置及检测方法

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AT508806A2 (de) 2011-04-15
AT508806B1 (de) 2013-06-15
AT508806A3 (de) 2013-03-15
WO2011041814A1 (fr) 2011-04-14

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