WO2021213636A1 - Récipient d'échantillon et procédé permettant d'analyser un échantillon - Google Patents

Récipient d'échantillon et procédé permettant d'analyser un échantillon Download PDF

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Publication number
WO2021213636A1
WO2021213636A1 PCT/EP2020/061078 EP2020061078W WO2021213636A1 WO 2021213636 A1 WO2021213636 A1 WO 2021213636A1 EP 2020061078 W EP2020061078 W EP 2020061078W WO 2021213636 A1 WO2021213636 A1 WO 2021213636A1
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WO
WIPO (PCT)
Prior art keywords
sample
section
closure element
closure
housing
Prior art date
Application number
PCT/EP2020/061078
Other languages
German (de)
English (en)
Inventor
Harald Quintel
Original Assignee
Hombrechtikon Systems Engineering 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 Hombrechtikon Systems Engineering Ag filed Critical Hombrechtikon Systems Engineering Ag
Priority to PCT/EP2020/061078 priority Critical patent/WO2021213636A1/fr
Publication of WO2021213636A1 publication Critical patent/WO2021213636A1/fr

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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
    • B01L3/5082—Test tubes per se
    • B01L3/50825—Closing or opening means, corks, bungs
    • 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
    • G01N21/0303—Optical path conditioning in cuvettes, e.g. windows; adapted optical elements or systems; path modifying or adjustment
    • 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
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0689—Sealing
    • 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
    • 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
    • B01L9/06—Test-tube stands; Test-tube holders
    • 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
    • G01N21/0303—Optical path conditioning in cuvettes, e.g. windows; adapted optical elements or systems; path modifying or adjustment
    • G01N2021/0307—Insert part in cell
    • 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
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/645—Specially adapted constructive features of fluorimeters
    • G01N2021/6482—Sample cells, cuvettes

Definitions

  • the invention relates to a method for analyzing a sample in a container device, as well as a sample container for receiving a sample according to the preambles of the independent claims.
  • sample containers are used in particular in the context of biotechnological methods in order to process a biological sample or a biological material such as, for example, samples containing nucleic acids. They are used, for example, to reproduce nucleic acids in vitro within the scope of amplification reactions such as a polymerase chain reaction (PCR).
  • PCR polymerase chain reaction
  • the sample containers serve to hold the sample comprising the nucleic acid.
  • sample containers are known from the prior art, which are regularly used as single-use products in the context of appropriate biotechnological processes such as PCR.
  • the sample containers are first filled with the sample, then sealed airtight and finally fed to the PCR process.
  • High demands are made on the sealing of the sample containers.
  • the sample containers must be reliably and tightly closed so that the result of the PCR process is not impaired by the inadvertent entry or exit of sample material.
  • a large number of sample containers are regularly used as part of a PCR process, which must be filled and sealed for this purpose. This should therefore be done as automatically as possible.
  • the sample containers must be inexpensive to manufacture especially because they are needed in large numbers and are used as single-use products.
  • a generic sample container in which one end of a cylindrical housing which forms a sample space is provided with a circular opening which extends into the sample space in the form of a channel.
  • the opening channel tapers shortly before the transition into the sample space and thereby forms a sealing seat for a spherical closure element. After the closure element has been placed on the seal seat, it is fixed by means of a closure plug.
  • the sample container known from EP 0449425 A2 is not only relatively complex and therefore expensive, but can also only be closed automatically with relatively great effort.
  • a generic sample container is also known from EP 2 683 485 A1, in which a housing of the sample container forms a sample space for receiving a sample and has at least one opening. The opening is closed by means of a spherical closure element.
  • the object of the invention is therefore to provide a method for analyzing a sample and a sample container which avoid the disadvantageous effects known from the prior art.
  • the object is achieved by a method for analyzing a sample and a sample container for carrying out a method according to the invention with the features of the independent claims.
  • a method for analyzing a sample in a container device comprises the provision of the container device, which container device comprises a closure element and a sample container.
  • a sample space for receiving the sample is formed in a housing of the sample container and the housing has at least one opening.
  • the housing also comprises a sample section and a closure section arranged between the opening and the sample section.
  • the sample space is arranged in the sample section.
  • the sample arranged in the sample space is irradiated by means of primary radiation from a radiation source.
  • a secondary radiation originating from the sample is detected by means of a detector.
  • the method according to the invention is characterized in that the closure element is arranged on, in particular in, the closure section and is optically transparent in such a way that the primary radiation and / or the secondary radiation can be emitted through the closure element.
  • the radiation source is arranged in relation to the closure element in such a way that the primary radiation is radiated from the radiation source through the closure element onto the sample and / or the detector is arranged in relation to the closure element in such a way that the secondary radiation from the sample through the closure element is blasted / reaches the detector.
  • sample can be understood in particular as a fluid sample which comprises a liquid with substances such as biomolecules (including DNA, RNA, nucleic acids, proteins, cells and cell components, monomers) or other chemical substances.
  • biomolecules including DNA, RNA, nucleic acids, proteins, cells and cell components, monomers
  • a liquid can be a suitable solvent in the context of the invention.
  • the method according to the invention can in particular be a PCR method (polymerase chain reaction) in which DNA is replicated (in vitro) in the sample space according to the invention. Enzymes (DNA polymerase) can be used for this.
  • optically transparent means that the closure element is permeable to electromagnetic waves / radiation, in particular to electromagnetic waves / radiation in the UV / Vis range and / or NIR range (i.e. in particular translucent), particularly preferably for primary radiation and / or secondary radiation.
  • the closure element according to the invention is thus permeable to the primary radiation and / or secondary radiation in such a way that an analysis of the sample can be carried out (particularly preferably translucent for primary radiation and / or secondary radiation).
  • the closure element can be optically transparent (translucent) in such a way that the closure element is permeable to electromagnetic radiation in the UV / Vis range, in particular in the range of 180-1000 nm, in particular in the range of 365-720 nm.
  • the closure element consists particularly preferably of an optical glass, in particular borosilicate glass or of a polymer, in particular an amorphous polymer, in particular a plastic such as polycarbonate, polymethyl methacrylate or cyclo-olefin (co) polymer, or of a crystalline material, in particular such as calcium fluoride or sapphire .
  • an optical glass in particular borosilicate glass or of a polymer, in particular an amorphous polymer, in particular a plastic such as polycarbonate, polymethyl methacrylate or cyclo-olefin (co) polymer, or of a crystalline material, in particular such as calcium fluoride or sapphire .
  • the housing is designed to be optically transparent at least in a section of the closure section and / or the sample section so that it can penetrate (largely) undisturbed Housing is made possible.
  • the closure element according to the invention has in particular no or only minor inhomogeneities, low absorption of the primary radiation and / or secondary radiation and low interactions with the primary radiation and / or secondary radiation.
  • closure elements of the prior art are mostly optically anisotropic and, due to mechanical stresses and inhomogeneities in the material of the closure element, there is a dispersion of the primary radiation and / or Secondary radiation too great to carry out an optical analysis of the sample through the closure element.
  • the method according to the invention can also include steps in which the sample is introduced into the sample space and, after the sample has been introduced into the sample space, the closure element is arranged on the closure section in such a way that the sample space is closed by the closure element, preferably tightly closed (e.g. for biotechnological processes).
  • a calibration measurement can be carried out before the sample is introduced into the sample space.
  • the radiation source can be arranged in relation to / on the sample section in such a way that the primary radiation is radiated from the radiation source through the closure element onto the sample (in this case the detector is preferably arranged on the closure element).
  • the detector can be, for example, a diode, in particular a silicon photodiode, an APD (Avelanche photodiode), or a photoelectron multiplier.
  • a laser, a deuterium lamp, a tungsten lamp, a halogen lamp, a mercury vapor lamp and / or an LED can be used as the radiation source.
  • the primary radiation can be coupled into the closure element via a glass fiber. It is preferred here that the radiation source generates primary radiation in the UV / Vis range, in particular in the range from 180-1000 nm, in particular in the range from 365-720 nm.
  • luminescence spectroscopy is an important analysis method in which the emission light (secondary radiation), which is generated on the basis of photon absorption by the biomolecules, is evaluated.
  • fluorescent chemical groups can also be attached to large biomolecules by means of fluorescent marking, which then serve as markers for this biomolecule.
  • Fluorescence is to be understood as the short-term, spontaneous emission of light, which occurs when an electronic The excited system returns to a state of lower energy. Fluorescence is a form of luminescence in which the excitation occurs through the absorption of photons (photoluminescence). In formal terms, fluorescence represents the reversal of the adsorption of light, in which excited electronic states are deactivated by re-emission of the excitation energy as radiation. The change in wavelength caused by the loss of energy is called the Stokes shift.
  • the concentration of the fluid samples plays a role in further processing, which can be easily determined in particular by fluorescence analysis (in particular fluorescence spectroscopy).
  • fluorescence analysis in particular fluorescence spectroscopy.
  • a fluorescence analysis of the sample is therefore carried out (e.g. fluorescence analysis in a PCR method).
  • the detector and the radiation source can be integrated into a detection device.
  • the detection device can also comprise a multiplicity of detectors and / or radiation sources.
  • the radiation sources can emit different wavelengths or wavelength ranges as primary radiation. Particularly preferred is the use of two radiation sources, which are designed as a first radiation source (preferably first LED) with a first wavelength (e.g. 450-490nm) and a second radiation source (preferably second LED) with a second wavelength (e.g. 600-630nm) are.
  • the detection device can be a spectrometer, in particular a photometer, in particular a fluorometer / fluorescence photometer.
  • the fluorometer measures the parameters of the fluorescence of the sample: intensity and wavelength distribution of the emission spectrum (of the secondary radiation) after excitation by the primary radiation.
  • Fluorescence spectroscopy is particularly preferably used as the measuring principle in the context of the invention, with the radiation source Primary radiation generated in the UV / Vis range and / or NIR range and the fluorescence emission (secondary radiation) of the fluid sample is detected by means of the detector.
  • the analysis of the sample / the method according to the invention can also be carried out in a laboratory machine.
  • the closure element can be a spherical closure element.
  • the closure element can be designed as an optical lens, in particular a spherical lens.
  • the optical lens has a low dispersion and little or no inhomogeneity in the refractive index.
  • the lens as the closure element enables the primary radiation to be focused on the sample and / or the secondary radiation to be focused on the detector. In this way, in particular, an optical structure during the analysis of the sample can also be simplified.
  • the closure element is an optical lens
  • the closure element is arranged on the closure area and in particular the detector and / or the radiation source is arranged in relation to the closure element in such a way that a primary focus of the primary radiation is in the sample and / or a secondary focus of the secondary radiation is in the detector .
  • the focusing of divergent light is also made possible with the spherical lens as the shutter element.
  • the focal length of the ball lens is determined by the refractive index and the diameter and is therefore easy to determine.
  • the focal point of the ball lens (when it is embedded in air) is very close to the interface.
  • the ball lens is particularly suitable for biotechnological / biochemical processes in which small amounts of sample are analyzed in small containers, whereby the focal point near the interface of the ball lens is very advantageous.
  • Ball lenses with a diameter of 2-10mm, particularly preferably 4-5mm can be used.
  • the container device can be designed so that a first expansion of the closure element exceeds a second expansion in at least a part of the closure section only to such an extent that the closure element is in contact with the housing in such a way that the closure element has a circumference of the first expansion the closure section can be fixed in a force-locking manner. It is of course advantageous here if a shape of the opening (and also that of the closure section) corresponds to a shape of the closure element. The closure element is therefore in contact with the housing.
  • a one-piece closure can be formed through the direct contact of the closure element with the housing.
  • a diameter of the ball lens can only exceed a diameter in at least part of the closure section to such an extent that the ball lens is in contact with the housing in such a way that the largest circumference of the ball lens can be positively fixed in the closure section .
  • the opening is a circular opening and, in particular, the closure area is cylindrical.
  • a projection can be formed between the closure section and the sample section which reduces an opening cross section of the sample section compared to an opening cross section in the closure section.
  • a further projection can be formed between the closure section and the opening which reduces an opening cross section of the opening (in particular an opening area with an inlet chamfer) compared to the opening cross section of the closure section.
  • the opening cross-section in the area of the further projection can be larger than the opening cross-section in the area of the lead.
  • a fixation of the closure element can in particular be achieved in that the closure element is clamped in the closure area of the housing of the sample container according to the invention in such a way that not only a good sealing effect but also a process-reliable fixation can be achieved. An additional sealing plug for fixation is not necessary.
  • the (second or further) projection is formed between the closure section and the opening.
  • a projection which can be formed for example (closed) ring-shaped or also by one or more, preferably ring-shaped, individual projections arranged next to one another, can in particular serve as a safety stop to prevent the closure element from being accidentally released from the closure section, for example as a result of an unexpectedly high increase in pressure in the sample space, which can be caused, for example, by heating during the PCR process.
  • the closure element can - if necessary after a slight displacement within the closure section - be supported on the projection, whereby a secure and especially tight Closing the sample container can be achieved. Since the (second or further) projection has to be passed by the closure element when the sample container is closed, it can be provided that it is dimensioned so that the closure element is introduced into the closure section while exerting a defined press-in force that is not so high should that this leads to damage to the closure element or the housing of the sample container as a result of excessive deformation, but greater than the maximum force to be expected, based on an increase in pressure in the sample space.
  • the opening cross section in the area of the (second) projection is larger than in the area of the first projection. It can thereby be achieved that the force which is applied to press the closure element into the closure section is sufficiently high that the closure element passes the second projection, but is not so high that it can also pass the first projection.
  • the housing can be tubular and the opening can be arranged at one (longitudinally axial) end of the housing.
  • the housing can be designed to taper to a point at a second end.
  • the housing can be designed with a smaller wall thickness in the area of the tapering end than in at least a second area of the sample space.
  • the tapering end can be designed to be optically transparent, since this is preferably used to receive the sample.
  • the thinnest possible wall thickness of the housing in particular in the sample area, can simplify the examination of the sample by means of optical methods, while a thicker wall thickness, in particular in a dead space of the sample space that is not filled with the sample, allows evaporation through the can avoid or reduce housing preferably made of plastic.
  • the housing can comprise a shoulder on a housing side facing away from the sample space in such a way that a support surface is formed for the sample container.
  • the forces that are applied to press in the closure element can be supported on a holder carrying the sample container via this support surface.
  • the support surface can be formed at a point on the housing that is in the vicinity of the closure section. In this way it can be avoided that the forces are transmitted via other sections of the housing, which may be designed with smaller wall thicknesses and thus more sensitive (in particular the wall of the housing surrounding the sample space).
  • the housing can be provided with a predetermined breaking point in order to enable the sample container to be opened easily after use.
  • the housing can be divided at the predetermined breaking point by a defined force.
  • Such a type of opening is particularly suitable for sample containers that are only intended to be used once (disposable sample container).
  • An advantage of this embodiment of the sample container according to the invention can in particular be that the process of opening can be less complex than removing the closure element fixed in the closure section, which, however, is also possible.
  • a predetermined breaking point there is also the possibility of designing the housing in two parts, with the two parts being connectable to one another, for example, via a plug-in or snap-in connection. To open the closed sample container, the housing can then be opened again at this connection point.
  • the sample container can also be opened by pushing the closure element into the sample space.
  • the sample space should have a larger cross-sectional area than the closure element, at least in one section, in order to be able to empty the sample space.
  • the choice of materials and the dimensions of the closure element and the housing in the area of the closure section can be made in a targeted manner with regard to the desired deformation behavior.
  • a closure element that is soft compared to the housing (which thus deforms significantly more than the housing) can have advantages in terms of the sealing effect. However, this advantage may have disadvantages if the closure element is designed as a lens, since the deformation affects the focusing and focal point.
  • a closure element that is hard compared to the housing on the other hand, can be handled well during insertion and does not show any change in focus due to deformation, but it can entail the risk of overstretching the housing (right into the plastic area).
  • the sample container comprises a housing in which a sample space for receiving the sample is formed and which has at least one opening, the housing comprising a sample section and a closure section arranged between the opening and the sample section, the sample space being arranged in the sample section and a closure element can be arranged on, in particular in, the closure section in such a way that the sample space can be closed by the closure element.
  • the sample container is characterized in that the closure element is an optically transparent closure element.
  • the container device comprises the sample container and the closure element, the closure element being arranged in particular on the closure section.
  • FIG. 1 shows a container device according to the invention
  • FIG. 2 shows a detail of the container device from FIG. 1 in a sectional side view
  • FIG. 3 shows the introduction of the closure element into the sample container according to FIGS. 1 and 2 by means of a plunger
  • FIG. 11 shows a device for closing the container device.
  • 1 shows a container device 100 according to the invention with a sample container 1 and a closure element 8 in a first embodiment.
  • the sample container 1 comprises a housing 2 in which a sample space 5 is formed.
  • the sample 7 is arranged in the sample space 5.
  • the housing 2 also has an opening 10.
  • the housing 2 includes a
  • the sample space 5 is arranged in the sample section 4 and the closure element 8 is arranged on / in the closure section 3 in such a way that the sample space 5 is closed by the closure element 3.
  • the closure element 8 is an optically transparent closure element 8, so that the closure element is permeable to electromagnetic waves / radiation, in particular to electromagnetic waves / radiation in the UV / Vis range.
  • the sample 7 is particularly preferably a fluid sample 7 which comprises biomolecules (including DNA) and a suitable solvent.
  • the sample section 4 of the housing 2 comprises a largely cylindrical jacket surface 41, which jacket surface only includes a slight conical taper 42 at the lower end of the housing 2. The housing 2 is therefore tapered and is thus designed to taper to a point in the broader sense.
  • the sample section 4 can be at least partially made of an (optically) transparent material so that a method according to the invention can be carried out in the sample container 1 with irradiation through the housing (in particular as part of a biotechnological method, such as a PCR process) .
  • the housing 2 On the outside between the closure section 3 and the sample section 4, the housing 2 forms a shoulder 6 which serves as a support surface via which the housing 2 can be supported on a sample container carrier 27 (as shown in FIG. 2).
  • the closure element 8 according to FIG. 2 is designed as an optically transparent, spherical closure element.
  • a closure effect ie both the sealing and the fixing of the closure element 8 in the closure section 3, is achieved in that the largest outside diameter of the closure element 8 is slightly larger than the diameter of the closure section 3 (at least one diameter in a part of the closure section 3), so that the closure element 8 is fixed in a clamping manner in the closure section 3.
  • the housing is initially provided with an inlet bevel 9 (opening area) which has a relatively large opening cross-section (relative to the outer diameter of the closure element 8) (largest diameter: e.g. 4, 5 mm).
  • the inlet bevel 9 facilitates the central attachment of the closure element 8 (largest diameter: for example 4.1 mm to 4.2 mm).
  • the inlet bevel 9 merges into a first annular projection 13 which has the opening cross section (diameter: for example 3.7 mm) in relation to the opening cross section in the
  • the rest of the closure section (diameter: for example approx. 4.0 mm) is reduced in size.
  • To introduce the closure element 8 into the closure section it is loaded with a force which is coaxial or parallel to the longitudinal axis of the housing 2, specifically in the direction of the sample section 4 of the housing 2.
  • the force is so high that there is a deformation of both the housing 2 in the area of the closure section 3 and the closure element 8 itself, which enables the closure element 8 to pass the first projection 13 and be pushed from the opening into the closure section 3 will.
  • the closure element 8 is fixed in a force-locking manner, ie clamped, due to its larger (maximum) diameter compared to the diameter of the closure section 3.
  • the forces are achieved by a (largely elastic) deformation of the housing 2 in the area of the closure section 3 and of the closure element 8.
  • the first projection 13, which has to be passed by the closure element 8 when it is introduced into the closure section 3, serves on the one hand as an end stop which prevents the closure element 8 from developing in the event of excess pressure within the closed sample space 5, for example due to heating in the frame a biotechnological process, such as a PCR process, is pushed out of the closure section 3 and the sample container 1 opens unintentionally. Furthermore, this projection 13 is used to generate a characteristic force curve when inserting the closure element 8, by means of which an actual insertion of the closure element 8 into the closure section 3 can be detected (in the manner of a latching).
  • the transition from the closure section 3 to the sample section 4 of the housing 2 is designed as an annular shoulder. This shoulder represents a second projection 12 which serves as an end stop for the closure element 8 and thus delimits the closure section 3 on the side of the sample space 5.
  • FIG. 3 shows the use of a plunger 23 (in two embodiments) in order to push the closure element 8 into the closure section 3.
  • the illustrated closure element 8 is a spherical closure element 8.
  • closure element 8 by means of the plunger 23, also works in an equivalent manner with an optically transparent closure element of a different shape, which is configured, for example, in the shape of a lens or cuboid.
  • a shape of the opening and also the closure section
  • a shape of the closure element preferably corresponds to a shape of the closure element in order to achieve a sealing effect when the corresponding closure element is introduced.
  • a first expansion of the closure element should in particular be selected so that it exceeds a second expansion of the closure section in at least a part of the closure section, but only to an extent that allows the closure element to be introduced into the closure section so far that the force-fit fixation is achieved by a contact of the largest circumference of the closure element comprising area with the closure section.
  • FIGS. 4 and 5 show a sample container 1 in a further embodiment, in which it is provided to open it again in that the closure element 8 is pressed completely into the sample space 5 up to the closed end by means of a plunger 23.
  • the fluid sample 7 displaced in the process can flow off via a bypass channel 14 introduced into the wall of the housing 2 on one side and can thus be removed from the sample container 1.
  • 6 shows a sample container 1 in which the housing 2 is provided with a varying wall thickness in a partial area of the sample section. In the area of the sample space that receives the sample, the housing 2 has the smallest possible wall thickness of, for example, 0.2 to 0.3 mm. A small wall thickness simplifies the examination of the sample by means of the method according to the invention for optical analysis of the sample.
  • the wall thickness is made thicker (e.g. twice as thick, e.g. 0.4 to 0.6 mm), which not only increases the mechanical stability of the housing 2 can be increased, but in particular evaporation of the sample through the housing 2 can also be reduced.
  • FIGS. 7 to 10 show a container device 100 according to the invention, in which the method according to the invention is carried out.
  • the sample 7 arranged in the sample space 5 is irradiated by means of a primary radiation 21 from a radiation source 20 and a secondary radiation 31 originating from the sample 7 is detected by means of a detector 30.
  • the secondary radiation 31 is an electromagnetic secondary radiation 31 emitted by the sample, which secondary radiation 31 is induced by an interaction of the primary radiation 21 with the sample.
  • the primary radiation and secondary radiation are electromagnetic waves / radiation in the UV / Vis range and / or NIR range (in particular in the range from 180-1000 nm, in particular in the range from 365-720 nm).
  • the closure element 8 is arranged on the sample container 1 and is optically transparent in such a way that the primary radiation 21 and / or the secondary radiation 31 can be emitted through the closure element 8.
  • the primary radiation 21 is radiated onto the sample 7 through the closure element 8.
  • the secondary radiation 31 is detected by means of the detector 30, which is arranged on the sample region 4 to record the secondary radiation 31.
  • the closure element 8 is designed as a cuboid which is largely transparent to the primary radiation 21 (i.e. optically transparent) so that the primary radiation can reach the sample 7 through the closure element 8 without hindrance.
  • the closure element 8 is designed as a spherical lens which is not only largely transparent to the primary radiation 21, but also focuses the primary radiation 21 onto the sample 7.
  • the radiation source 20 is arranged on the sample section 5 in such a way that the primary radiation 21 is radiated from the radiation source 20 through the housing 2 onto the sample 7.
  • the detector 30 is arranged in relation to the closure element 8 in such a way that the secondary radiation 31 from the sample
  • the closure element 8 is designed as a spherical lens so that the secondary radiation 31 is focused on the detector 30.
  • the primary radiation 21 is radiated through the closure element 8 onto the sample 7.
  • the detector 30 is such with respect to the closure element
  • the closure element 8 is designed as a spherical lens, so that the primary radiation 21 is focused in the sample 7 and the secondary radiation 31 is focused on the detector 30.
  • detector 30 and radiation source 20 are integrated into a detection device which is arranged “above” the closure element 8.
  • a fluorescence analysis is carried out on sample 7.
  • the spherical lens not only provides a particularly suitable closure for sealing biotechnological processes such as PCR, but the optical properties of the spherical lens can simplify the optical structure and the arrangement during the analysis of the sample. Particularly in the case of container arrays, it is very complex to measure each sample individually, since the containers have to be separated before irradiation and analysis in order to enable a suitable measurement setup. Due to the optically transparent closure element, the detector and the radiation source can be arranged much more flexibly. In particular in the embodiment according to FIG. 10, since both irradiation and detection take place from above (from one direction).
  • FIG. 11 shows a device for closing a sample container 1 according to the invention with a closing element 8, as is already known from the prior art WO2012 / 123376 A1.
  • the movements of the two tappets 23, 23a are coupled to one another.
  • a bolt 40 which is resiliently mounted in a section of the tappet 13, engages in a corresponding opening in the tappet 23a.
  • the movement of the ram 23 is thus transmitted to the ram 23a.
  • the plunger 23 itself is constructed in several parts and comprises a plunger element 41, which is mounted axially displaceably in the lower end of a base body 32 of the plunger 23.
  • the plunger element 41 is connected to a threaded pin 33, which is part of a force-limiting unit, via a central bore with an internal thread.
  • the force limiting unit also includes a spring 34 (cylindrical helical spring) which is pretensioned by two contact plates 35.
  • the pretensioning forces are supported via a contact between the upper contact plate 35 and an annular projection of the plunger element 41 on corresponding contact surfaces of the base body 32.
  • the preload of the helical spring can be changed via the screw-in depth of the threaded bolt 33 into the plunger element 41, and thus a limit value for the force exerted by the plunger element 41 on the closure element 8 can be set.
  • the tappet stroke is (partially) compensated by the tappet element 23 retreating.

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

Abstract

L'invention se rapporte à un procédé permettant d'analyser un échantillon (7) dans un dispositif de récipient (100), comprenant les étapes suivantes consistant : à fournir le dispositif de récipient (100) comportant un élément de fermeture (8) et un récipient d'échantillon (1), une chambre d'échantillon (5) pour recevoir un échantillon (7) étant formée dans un boîtier (2) du récipient d'échantillon (1) et le boîtier (2) présentant au moins une ouverture (10), le boîtier (2) présentant une section d'échantillon (4) et une section de fermeture (3) disposée entre l'ouverture (2) et la section d'échantillon (4), et la chambre d'échantillon (5) étant agencée dans la section d'échantillon (4) ; à irradier l'échantillon (7) disposé dans la chambre d'échantillon (5) au moyen d'un rayonnement primaire (21) provenant d'une source de rayonnement (20) ; et à détecter un rayonnement secondaire (31) provenant de l'échantillon (7) au moyen d'un détecteur (3) ; caractérisé en ce que l'élément de fermeture (8) est agencé sur le récipient d'échantillon (1) et est optiquement transparent de telle sorte que le rayonnement primaire (21) et/ou le rayonnement secondaire (31) puissent être irradiés à travers l'élément de fermeture (8) la source de rayonnement (20) étant agencée par rapport à l'élément de fermeture (8) de telle sorte que le rayonnement primaire (21) soit irradié à partir de la source de rayonnement (20), à travers l'élément de fermeture (8) et sur l'échantillon (7) et/ou que le détecteur (30) soit agencé par rapport à l'élément de fermeture (8) de telle manière que le rayonnement secondaire (31) soit irradié depuis l'échantillon (7), à travers l'élément de fermeture (7) vers le détecteur (30).
PCT/EP2020/061078 2020-04-21 2020-04-21 Récipient d'échantillon et procédé permettant d'analyser un échantillon WO2021213636A1 (fr)

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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0449425A2 (fr) 1990-03-30 1991-10-02 Beckman Instruments, Inc. Tube centrifuge à joint d'étanchéité automatique
EP0706649A1 (fr) * 1994-04-29 1996-04-17 Perkin-Elmer Corporation Systeme de detection en temps reel de produits d'amplification d'acides nucleiques
EP0717779A1 (fr) * 1992-04-06 1996-06-26 Abbott Laboratories Procede et dispositif de detection d'acide nucleique ou d'analyte au moyen d'une technique de reflexion interne totale
US20040224317A1 (en) * 2003-05-08 2004-11-11 Mj Research Systems and methods for fluorescence detection with a movable detection module
WO2012123376A1 (fr) 2011-03-11 2012-09-20 Qiagen Instruments Ag Dispositif servant à obturer un récipient à échantillons avec un élément d'obturation sphérique
WO2012123375A1 (fr) * 2011-03-11 2012-09-20 Qiagen Gmbh Récipient à échantillon
US20190137397A1 (en) * 2011-05-16 2019-05-09 Universal Bio Research Co., Ltd. Optical measurement device for reaction vessel and method therefor

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0449425A2 (fr) 1990-03-30 1991-10-02 Beckman Instruments, Inc. Tube centrifuge à joint d'étanchéité automatique
EP0717779A1 (fr) * 1992-04-06 1996-06-26 Abbott Laboratories Procede et dispositif de detection d'acide nucleique ou d'analyte au moyen d'une technique de reflexion interne totale
EP0706649A1 (fr) * 1994-04-29 1996-04-17 Perkin-Elmer Corporation Systeme de detection en temps reel de produits d'amplification d'acides nucleiques
US20040224317A1 (en) * 2003-05-08 2004-11-11 Mj Research Systems and methods for fluorescence detection with a movable detection module
WO2012123376A1 (fr) 2011-03-11 2012-09-20 Qiagen Instruments Ag Dispositif servant à obturer un récipient à échantillons avec un élément d'obturation sphérique
WO2012123375A1 (fr) * 2011-03-11 2012-09-20 Qiagen Gmbh Récipient à échantillon
EP2683485A1 (fr) 2011-03-11 2014-01-15 Qiagen GmbH Récipient à échantillon
US20190137397A1 (en) * 2011-05-16 2019-05-09 Universal Bio Research Co., Ltd. Optical measurement device for reaction vessel and method therefor

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