FLOW CELL FOR OPTICAL MEASUREMENTS, OPTICAL MODULE AND SPECTROMETER

DE502023003063D1Active Publication Date: 2026-03-12IRUBIS GMBH
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Patent Information

Authority / Receiving Office
DE · DE
Patent Type
Patents
Current Assignee / Owner
Filing Date
2023-08-09
Publication Date
2026-03-12

AI Technical Summary

Technical Problem

Existing flow cells for optical measurements are prone to contamination from microorganisms and deposits, leading to reactor contamination and degraded optical measurements due to microorganisms entering the flow cell measuring chamber and adhering to the ATR crystal.

Method used

A flow cell design with a base body and aperture made of materials with different thermal expansion coefficients, allowing for differential expansion compensation through specific fixing points, combined with a sealing element and filter system to prevent contamination and maintain chamber integrity during temperature changes.

Benefits of technology

The design effectively prevents contamination and maintains chamber tightness during temperature fluctuations, ensuring accurate optical measurements by preventing external contaminants from entering and adhering to the ATR crystal.

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Description

[0001] The present invention relates to a flow cell for optical measurements. The flow cell comprises a base body with at least one inlet and at least one outlet for substances to be measured and an aperture arranged on a first outer surface of the base body, wherein a recess is provided on the first outer surface of the base body, which contains a flow cell measuring chamber connected to the at least one inlet and the at least one outlet. The flow cell comprises an arrangement clamped between the aperture and at least a first wall region of the recess, comprising an ATR crystal and at least one first sealing element for sealing the flow cell measuring chamber, wherein the at least one first sealing element is arranged on a side of the ATR crystal facing away from the aperture. The present invention further relates to an optical module comprising the flow cell according to the invention and to a spectrometer comprising the optical module.

[0002] In recent decades, the growing interest in integrating continuous bioprocesses has led to the development and implementation of process analytical technologies (PATs) capable of monitoring key process parameters in real time. Adapting these technologies to continuous processing aims to achieve a better understanding of the process. This results in shorter production cycles and ultimately increased yield and productivity.

[0003] Protein concentration is a fundamental parameter that must be monitored in downstream processes. Therefore, there is a growing need to shift protein concentration measurement from offline to inline analysis. For this purpose, spectroscopic techniques have proven to be powerful analytical tools that enable continuous and simultaneous monitoring of critical quality characteristics, particularly the concentrations of metabolites, nutrients, and excipients.

[0004] For optical or spectroscopic measurement inline analysis, a flow cell can be used as part of an optical module of a spectrometer. A portion of the reaction mixture can be drawn from the reactor during the process, then passed through the flow cell, and subsequently returned to the reactor. As the reaction mixture passes through the flow cell, it is optically or spectroscopically measured within a measuring chamber to determine, for example, the concentrations of metabolites, nutrients, and additives in the reaction mixture.

[0005] From Christian Busch et al., "A mobile setup for simultaneous and in situ neutron reflectivity, infrared spectroscopy, and ellipsometry studies," REVIEW OF SCIENTIFIC INSTRUMENTS, AMERICAN INSTITUTE OF PHYSICS, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747, Vol. 93, No. 11, November 10, 2022, a flow cell for optical measurements is known, comprising a PEEK base body with an inlet and an outlet, wherein a recess is provided in a first outer surface of the base body, containing a flow cell measuring chamber connected to the inlet and the outlet and an O-ring. The flow cell also contains an ATR crystal in the form of a silicon prism. The base body and the prism are clamped between two clamping plates by means of screw connections.

[0006] JP H06 331541 A discloses a flow cell with a PTFE base body having an inlet and an outlet, wherein a recess is provided on a first outer surface of the base body, which contains a flow cell measuring chamber connected to the inlet and the outlet. The flow cell also includes an ATR crystal. A sealing element is clamped between the base body and the ATR crystal, wherein the base body, the ATR crystal and the sealing element are located in a stainless steel frame and are pressed together by means of a clamping plate and screws. The stainless steel frame has openings for the measuring light path.

[0007] Bravo-Suarez JJ et al., "Design characteristics of in situ and operando ultraviolet-visible and vibrational spectroscopic reaction cells for heterogeneous catalysis," CATALYSIS REVIEWS: SCIENCE AND ENGINEERING, MARCEL DEKKER INC. NEW YORK, US, Vol. 59, No. 4, October 2, 2017 (2017-10-02), pages 295-445, describe a flow cell with a first stainless steel base body having an inlet and an outlet. A groove for an O-ring, which delimits a flow cell measuring chamber, is provided on a first outer surface of the base body. The chamber comprises a second base body and an ATR crystal. The ATR crystal is arranged in a groove in the second base body. The first base body is fixed to the second base body by screws.

[0008] Problems with such measurements can arise primarily from contamination with microorganisms, such as bacteria, viruses, or fungal spores, or from deposits of microorganisms, biomolecules, or cell debris in the flow cell measuring chamber. For example, microorganisms entering the flow cell measuring chamber from the outside can be carried into the reactor along with the measured reaction mixture, leading to contamination of the reactor and the reaction product produced within it. Furthermore, deposits of microorganisms, biomolecules, or cell debris in the flow cell measuring chamber can degrade the optical measurements.

[0009] Based on this, the object of the present invention was to provide a flow cell for optical measurements with which contamination of the flow cell measuring chamber and / or the substances measured therein can be better avoided.

[0010] This problem is solved with respect to a flow cell with the features of claim 1, with respect to an optical module with the features of claim 12, and with respect to a spectrometer with the features of claim 15. The respective dependent claims represent advantageous embodiments.

[0011] According to the invention, a flow cell for optical measurements (or for use in optical measurements) is provided, comprising a base body with at least one inlet (for substances to be measured) and at least one outlet (for substances measured), as well as an aperture arranged on a first outer surface of the base body, wherein a recess is provided on the first outer surface of the base body, which contains a flow cell measuring chamber connected (fluidically) to the at least one inlet and the at least one outlet, wherein the base body can be made of at least one material having a first coefficient of thermal expansion, and the aperture can be made of at least one material having a second coefficient of thermal expansion that differs from the first coefficient of thermal expansion.

[0012] The first coefficient of thermal expansion and the second coefficient of thermal expansion can be determined, for example, by dilatometry, e.g. according to ISO 11359-2:2021-11.

[0013] Preferably, the second coefficient of thermal expansion differs from the first coefficient of thermal expansion by at least 10 · 10 -6 < K -1 < , preferably by at least 20 · 10 -6 < K -1 < , particularly preferably by at least 50 · 10 -6 < K -1 < , most preferably by at least 80 · 10 -6 < K -1 < , e.g. by 80 · 10 -6 < K -1 < to 200 · 10 -6 < K -1 < .

[0014] Furthermore, the flow cell comprises an arrangement clamped between the aperture and at least one (aperture-facing) first wall region of the recess, comprising an ATR crystal and at least one first sealing element for sealing the flow cell measuring chamber, wherein the at least one first sealing element is arranged on a side of the ATR crystal facing away from the aperture.

[0015] An ATR crystal is understood to be an element that can be used as an ATR crystal or ATR element in ATR infrared spectroscopy (ATR = "attenuated total reflection").

[0016] The aperture can be fixed or fixed at at least one first fixing point on the base body by means of at least one first fixing means such that the base body and the aperture are essentially not movable relative to each other at the at least one first fixing point in an x-direction parallel to the first outer surface of the base body, in a y-direction parallel to the first outer surface of the base body (and perpendicular to the x-direction), and in a z-direction perpendicular to the first outer surface of the base body. "Essentially not movable relative to each other" can be understood to mean that the base body and the aperture are movable relative to each other by less than 10 µm, preferably by at most 9 µm, particularly preferably by at most 5 µm, and most preferably by at most 1 µm, at the at least one first fixing point in the x-direction, in the y-direction, and in the z-direction.Particularly preferred are the base body and the aperture at the at least one first fixing point in the x-direction, in the y-direction and in the z-direction not being movable relative to each other at all.

[0017] Furthermore, the aperture can be fixed or fixed at at least a second fixing point on the base body via at least a second fixing means in such a way that the base body and the aperture are essentially not movable relative to each other in the z-direction at the at least one second fixing point and are movable relative to each other in the x-direction and in the y-direction only to such an extent that different expansions and / or contractions of the components of the flow cell (in particular the base body and the aperture) resulting from temperature changes (preferably up to 80 K, particularly preferably up to 120 K, e.g. from 10 K to 130 K) can be compensated (or can be compensated in such a way that the temperature changes do not cause any bending or a bending of a maximum of 0.1 mm of the components of the flow cell - in particular the base body and the aperture).The term "essentially not movable relative to each other" can be understood to mean that the base body and the aperture are movable relative to each other in the z-direction by less than 10 µm, preferably by at most 9 µm, particularly preferably by at most 5 µm, and most preferably by at most 1 µm, at the at least one second fixing point. Particularly preferably, the base body and the aperture are not movable relative to each other at all in the z-direction.

[0018] The value for the bending of the components (e.g., the base body and / or the aperture) can be determined as the distance between a point of the component in the undistorted state in the middle (of a direct connecting line) between the first fixing point and the second fixing point and the same point of the component in the bent state.

[0019] The base body and the aperture can be made of different materials; that is, the aperture can be made of a different material than the base body, so that the aperture material has a different coefficient of thermal expansion than the base body material. By constructing the flow cell with a base body and an aperture made of different materials, the various areas of the flow cell can be better adapted to their specific requirements compared to flow cells where the base body and aperture are realized in a single element made of one material.

[0020] The base body can contain a flow structure, e.g., a channel structure, through which the substances to be measured or measured are guided through the flow cell (i.e., from the inlet to the flow cell measuring chamber and from the flow cell measuring chamber to the outlet). The base body is preferably made of a polymer, e.g., a thermoplastic material, which can be manufactured, for example, by 3D printing. This allows for the simple and cost-effective realization of a base body with a suitable—possibly complex—channel structure.

[0021] The aperture can serve as a connecting element between the flow cell and the main body of an optical module. The aperture can be made of a harder material (preferably an alloy, e.g., stainless steel) than the main body, thus ensuring a very strong connection between the flow cell and the main body and allowing a sealing element used to seal the connection between the flow cell and the main body to provide a good seal.

[0022] The aperture is located on the first outer surface of the main body, where the recess containing the flow cell measuring chamber is also located. Thus, the recess containing the flow cell measuring chamber adjoins the aperture. The aperture diaphragm can be positioned in this area of ​​the aperture so that it abuts the recess.

[0023] The arrangement comprising the ATR crystal and the at least one first sealing element for sealing the flow cell measuring chamber is clamped between the aperture and the at least one first wall region of the recess (facing the aperture), with the at least one first sealing element being located on a side of the ATR crystal facing away from the aperture. Consequently, the flow cell chamber can now be configured such that it is bounded by the ATR crystal, the at least one first sealing element, and wall regions of the recess. By fixing the aperture to the base body, the arrangement comprising the ATR crystal and the at least one first sealing element for sealing the flow cell measuring chamber can be clamped between the aperture and the at least one first wall region of the recess (facing the aperture), thus achieving a seal for the flow cell chamber.

[0024] If the base body and the aperture (as well as, where applicable, the ATR crystal and / or the at least one first sealing element) are made of materials with different coefficients of thermal expansion, significant temperature changes (e.g., during sterilization or autoclaving of the flow cell) can lead to differential expansion of the components (i.e., the base body and the aperture, as well as, where applicable, the ATR crystal and / or the at least one first sealing element). If the aperture were fixed to the base body in such a way that the base body and the aperture expand at all fixing points in all three spatial directions (i.e.,Since the components (in the x-direction, y-direction, and z-direction) are essentially not movable relative to each other, the different expansion of the components leads to stresses that can cause the components to bend, which can lead to a loosening of the clamped arrangement comprising the ATR crystal and the at least one first sealing element, ultimately creating leaks in the arrangement where the flow cell measuring chamber is no longer adequately sealed, so that on the one hand the reaction mixture can escape to the outside through the leaks and on the other hand impurities or microorganisms from the outside can enter the flow cell chamber through the leaks.

[0025] This can be prevented by a special attachment of the aperture to the base body. Here, the aperture can be fixed to the base body at least once at a first fixing point via at least one first fixing means, such that the base body and the aperture at at least one first fixing point can be moved in all three spatial directions (i.e.,in the x-direction, in the y-direction, and in the z-direction) are essentially not movable relative to each other, whereas the aperture can be fixed at the base body via the at least one second fixing means in such a way that the base body and the aperture are only essentially not movable relative to each other in the z-direction at the at least one second fixing point, and are only movable relative to each other in the x-direction and in the y-direction to such an extent that different expansions and / or contractions of the components of the flow cell resulting from temperature changes can be compensated for. Thus, the at least one second fixing means guarantees a certain degree of mobility of the base body and the aperture relative to each other in the x- and y-directions, by which different expansions and / or contractions of the components can be compensated for.Consequently, although significant temperature changes (e.g., during sterilization or autoclaving of the flow cell) still cause the components to expand differently, this expansion (due to their inherent flexibility in the x and y directions) no longer leads to bending of the components. Therefore, the clamped assembly comprising the ATR crystal and at least one initial sealing element does not loosen. This prevents the formation of leaks in the assembly where the flow cell measuring chamber is no longer adequately sealed. As a result, the flow cell maintains a high degree of tightness even during significant temperature changes (e.g., during sterilization or autoclaving), preventing contaminants from entering the flow cell chamber through external leaks.Consequently, contamination of the flow cell chamber and the substances measured within it by externally penetrating contaminants or microorganisms can be better avoided.

[0026] Advantageously, the flow cell according to the invention can be used as a replaceable and / or disposable product. Preferably, the flow cell according to the invention is a replaceable and / or disposable product. A replaceable flow cell makes it possible to sterilize and replace it, since the surface of ATR crystals quickly becomes contaminated in bioprocesses.

[0027] A preferred embodiment of the flow cell according to the invention is characterized in that the aperture can be fixed at the base body via the at least one second fixing means in such a way that the base body and the aperture are essentially not movable relative to each other in the z-direction and are movable relative to each other by at least 0.01 mm, preferably at least 0.05 mm, particularly preferably at least 0.1 mm, and / or by at most 1 mm, preferably at most 0.8 mm, particularly preferably at most 0.5 mm, in the x-direction and in the y-direction.The term "essentially not movable relative to each other" can be understood to mean that the base body and the aperture are movable relative to each other in the z-direction by less than 10 µm, preferably by at most 9 µm, particularly preferably by at most 5 µm, and most preferably by at most 1 µm, at the at least one second fixing point. Particularly preferably, the base body and the aperture are not movable relative to each other at all in the z-direction.

[0028] Another preferred embodiment of the flow cell according to the invention is characterized in that the at least one first fixing means is selected from the group consisting of countersunk screws, and combinations thereof, wherein the at least one first fixing means is preferably at least one countersunk screw, and / or the at least one second fixing means is selected from the group consisting of pan head screws, rivets, cylinder head screws, and combinations thereof, wherein the at least one first fixing means is preferably at least one pan head screw

[0029] With these special fixing devices, the desired immobility in all three spatial directions can be easily achieved at the at least one first fixing point and in the z-direction at the at least one second fixing point, as well as the desired limited mobility in the x- and y-directions at the at least one second fixing point.

[0030] Another preferred embodiment of the flow cell according to the invention is characterized in that the at least one material of which the base body is made is at least one polymer, particularly preferably at least one thermoplastic polymer. Most preferably, the material of which the base body is made is at least one polymer selected from the group consisting of polyetheretherketones, polytetrafluoroethylene, polypropylene, polysulfones, polyethersulfones, polycarbonates, polyvinyl chlorides, polylactides, polyamides, thermoplastic polyurethanes, acrylonitrile butadiene styrene, UV-curing (autoclavable) resins, and mixtures thereof. In this case, the base body can be produced simply and cost-effectively by means of 3D printing. A flow or channel structure can be easily implemented in this way.For example, the base body can contain or consist of at least one material: bisphenol-A dimethacrylate, 2-hydroxyethyl methacrylate, and urethane dimethacrylate. For instance, the product "BioMed Clear" from the manufacturer Formlabs can be used as the base body material.

[0031] According to a further preferred embodiment of the flow cell according to the invention, the at least one material of which the aperture is made is selected from the group consisting of metals, e.g., iron; alloys, preferably iron-containing alloys, e.g., stainless steel; polymers, e.g., polyetheretherketones; and mixtures and combinations thereof, wherein the aperture preferably contains or consists of stainless steel. In this way, a very tight connection of the flow cell with a module main body of an optical module can be achieved, so that a sealing element used to seal the connection between the flow cell and the module main body can provide a good seal.

[0032] Another preferred embodiment of the flow cell according to the invention is characterized in that the ATR crystal The ATR crystals contain or consist of at least one material which is at least partially transparent to light with a wavelength in the range of 2 µm to 20 µm, preferably from 4 µm to 12 µm, wherein the ATR crystals preferably contain or consist of at least one material selected from the group consisting of silicon, diamond, germanium, zinc selenide, zinc sulfide, and mixtures and combinations thereof, wherein the ATR crystals particularly preferably contain or consist of silicon, and / or comprise several microprisms, and / or have a structuring on one side facing the aperture, preferably a structuring with grooves or slots, particularly preferably a structuring with V-shaped grooves or V-shaped slots.

[0033] The transparency of the at least one material that the ATR crystal contains or consists of can be determined, for example, by means of DIN 4522-4:1993-04.

[0034] Preferably, the at least one material, at least partially, that the ATR crystal contains or consists of has a transmittance for light with a wavelength in the range of 2 µm to 20 µm, preferably from 4 µm to 12 µm, of more than 10%. The transmittance can be determined, for example, according to DIN 4522-4:1993-04.

[0035] The microprisms allow for high light throughput but also lower positioning accuracy. Structuring with grooves or slots facilitates light coupling and reduces positioning accuracy.

[0036] Another preferred embodiment of the flow cell according to the invention is characterized in that the at least one first sealing element contains or consists of at least one polymer selected from the group consisting of ethylene propylene diene monomer rubbers, silicones, and mixtures thereof, and / or is formed in the form of a circular ring, and / or is in sealing contact with the ATR crystal and / or the at least one first wall region of the recess, and / or the flow cell comprises at least one second sealing element arranged around the recess, wherein the at least one second sealing element preferably contains or consists of at least one polymer selected from the group consisting of ethylene propylene diene monomer rubbers, silicones, and mixtures thereof, and / or is formed in the form of a circular ring, and / or is arranged at least partially in a further recess provided on the first outer surface of the base body and arranged around the recess.and / or is in sealing contact with the base body and / or the aperture.

[0037] Because the at least one first sealing element contains or consists of at least one polymer selected from the group consisting of ethylene propylene diene monomer rubbers, silicones, and mixtures thereof, and / or is formed in the form of a circular ring, and / or is in sealing contact with the ATR crystal and / or the at least one first wall region of the recess, a good seal of the flow cell measuring chamber can be easily achieved by the at least one first sealing element. It should be noted that it is also possible, in principle, for the at least one first sealing element not to be in contact with the ATR crystal and / or the at least one first wall region of the recess, for example,then, if a further element is arranged between the at least one first sealing element and the ATR crystal or between the at least one first sealing element and the at least one first wall area of ​​the recess.

[0038] The use of at least one second sealing element ensures that no gases from the environment can enter areas (e.g., a cavity) between the ATR crystal and the aperture.

[0039] Another preferred embodiment of the flow cell according to the invention is characterized in that the flow cell comprises at least one filter element which is arranged in the recess between the ATR crystal and at least one opening connected to the at least one inlet (and / or between the ATR crystal and at least one opening connected to the at least one outlet), wherein preferably the at least one filter element is selected from the group consisting of cellulose filter elements, paper filter elements, glass fiber filter elements, and combinations thereof, and / or has a thickness in the range of 0.001 mm to 5 mm, preferably from 0.01 mm to 1 mm, particularly preferably from 0.02 mm to 0.2 mm.

[0040] The substances being measured, which are passed through the flow cell, may contain larger molecules (e.g., proteins), cell debris, and microorganisms. These can deposit on the ATR crystal, leading to biofouling. This deposition, or biofouling, subsequently degrades the measurement because the deposited components result in a disproportionately large signal in the measurement or the measured spectrum, thus affecting the measurement quality. Furthermore, deposits on the ATR crystal can contaminate the substance being measured in a subsequent measurement. The filter element can then remove larger molecules contained in the substances being measured (e.g., proteins, proteins, and microorganisms).Proteins, cell debris, and microorganisms are kept away from the ATR crystal by the filter element, while the liquid containing the smaller molecules relevant for optical measurement passes through. Consequently, the filter element effectively prevents contamination of the flow cell chamber and the substances to be measured (in the future). Furthermore, the filter element also prevents gas bubbles present in the substances being measured, which would otherwise interfere with the measurement and the measured spectrum.

[0041] Another preferred embodiment of the flow cell according to the invention is characterized in that the flow cell additionally comprises at least one filter holder for holding the at least one filter element, which is arranged between the ATR crystal and the at least one filter element, wherein the at least one filter holder preferably has a grid structure and a frame extending around the grid structure. It is particularly preferred that the frame is in contact with the ATR crystal and the grid structure is not in contact with the ATR crystal, wherein the grid structure is preferably arranged at a distance of 0.001 mm to 5 mm, preferably 0.005 mm to 2 mm, particularly preferably 0.008 mm to 1 mm, most preferably 0.01 mm to 0.1 mm, from the ATR crystal, and / or the at least one filter element is clamped between the frame and at least one second wall area of ​​the recess facing the aperture, and / or a central wall area of ​​the recess facing the aperture has at least one retaining element, preferably at least two retaining elements, wherein the at least one filter element is clamped between the grid structure and the at least one retaining element.

[0042] The filter holders allow the filter element to be positioned at an advantageous distance from the ATR crystal, preventing the filter from coming into contact with it and thus interfering with the optical measurement. The grid structure effectively prevents a central area of ​​the filter, saturated with the substance being measured, from sagging and contacting the ATR crystal. At least one retaining element on the central wall of the recess further secures the filter, preventing it from slipping.

[0043] Another preferred embodiment of the flow cell according to the invention is characterized in that the at least one filter element is arranged in direct contact with at least one photoresist coating applied to the ATR crystal, preferably the at least one photoresist coating has a thickness in the range of 0.1 µm to 100 µm, preferably from 1 µm to 50 µm, particularly preferably from 5 µm to 20 µm, and / or the at least one photoresist coating is applied to the ATR crystal in the form of a grid or stripe, wherein the arrangement of the photoresist coating on the ATR crystal is preferably adapted to a structuring of the ATR crystal that the ATR crystal has on a side facing the aperture, and / or the at least one filter element is attached to the at least one first sealing element, preferably in a materially bonded manner with the at least one first sealing element.

[0044] A conventional photoresist can be used for the photoresist coating. This allows for very precise and thin coating. Consequently, the photoresist coating enables the filter element to be positioned at a very small distance from the ATR crystal, thus preventing the filter from coming into contact with the ATR crystal and interfering with the optical measurement. Furthermore, only very small amounts of liquid remain between the ATR crystal and the filter element, resulting in a very short diffusion time and thus significantly increasing the measurement speed. By applying at least one photoresist coating to the ATR crystal in the form of a grid or strips, interference with the optical measurement caused by the photoresist coating can be prevented or at least minimized.Particularly advantageous is the arrangement of the photoresist coating on the ATR crystal, adapted to a structure of the ATR crystal that the crystal has on one side facing the aperture, so that the photoresist coating is only applied to those areas that are not reached by the optical rays (e.g., infrared rays) during an optical measurement. For example, if the ATR crystal has a structure with grooves or slots on one side facing the aperture, the photoresist coating can be applied, for example, only to those strip-shaped areas that run along these grooves or slots (on the opposite side of the ATR crystal).

[0045] Furthermore, it is also possible in principle for the at least one filter element to be arranged in direct contact with the at least one ATR crystal, i.e., without a gap between the filter element and the ATR crystal. In this case, neither a filter holder nor a photoresist coating is required.

[0046] Another preferred embodiment of the flow cell according to the invention is characterized in that the recess between the at least one first fixing point and the at least one second fixing point, wherein the at least one first fixing point and the at least one second fixing point preferably have the same distance to the recess, and / or has a structure, preferably a serrated structure, on a central wall area of ​​the recess facing the aperture, and / or has at least one opening connected to the at least one inlet on a central wall area of ​​the recess facing the aperture, and / or has at least one opening connected to the at least one outlet on a central wall area of ​​the recess facing the aperture.

[0047] The (jagged) structuring helps to better prevent biofouling on the filter element.

[0048] By arranging the recess between the at least one first fixing point and the at least one second fixing point, or by arranging the fixing points (with the fixing elements) such that the recess (and thus also the flow cell measuring chamber) lies between the two fixing points, particularly exactly in the middle between the two fixing points, a particularly good fixing with a particularly high tightness of the flow cell measuring chamber can be achieved. Preferably, the distance between the at least one first fixing point and the at least one second fixing point is 5 mm to 100 mm, more preferably 15 mm to 50 mm, and most preferably 20 mm to 40 mm.Preferably, the distance between the at least one first fixing point and the recess and / or the distance between the at least one second fixing point and the recess is 2 mm to 50 mm, preferably 7 mm to 25 mm, particularly preferably 10 mm to 20 mm.

[0049] Another preferred embodiment of the flow cell according to the invention is characterized in that the flow cell comprises at least one third fixing means, preferably a single third fixing means, for attaching the flow cell to a module main body of an optical module, wherein the at least one third fixing means has a principal extension direction, wherein an angle between this principal extension direction and the first outer surface of the base body lies in a range of 20° to 85°, preferably 30° to 70°, particularly preferably 40° to 65°, and / or the at least one third fixing means is selected from the group consisting of socket head screws, pan head screws, and combinations thereof, wherein the at least one third fixing means is preferably at least one socket head screw, particularly preferably a single socket head screw, and / or the aperture has a projecting area that projects beyond a second outer surface of the base body (adjacent to the first outer surface of the base body), wherein the recess is preferably arranged between the second outer surface of the base body and the at least one third fixing means.and / or the flow cell additionally comprises at least one third sealing element arranged around the at least one third fixing means and sealed to the at least one third fixing means.

[0050] The third fixing element allows the flow cell to be easily and firmly connected to the main body of an optical module.

[0051] It is preferred that at least one third sealing element contains or consists of at least one polymer selected from the group consisting of ethylene propylene diene monomer rubbers, silicones, and mixtures thereof, and / or is formed in the form of a circular ring.

[0052] The present invention further relates to an optical module comprising a module main body and a flow cell according to the invention, which is attached to the module main body.

[0053] A preferred embodiment of the optical module according to the invention is characterized in that the flow cell is attached to the module body by means of at least one third fixing means, preferably a single third fixing means, and a stop element arranged on an outer surface of the module body facing the flow cell, wherein the stop element has a stop surface against which the flow cell is pressed by the at least one third fixing means, and wherein preferably an angle between the stop surface and the first outer surface of the base body lies in a range of 20° to 85°, preferably 30° to 65°, particularly preferably 40° to 50°, and / or the at least one third fixing means has a principal extension direction, wherein an angle between this principal extension direction and the first outer surface of the base body lies in a range of 20° to 85°, preferably 30° to 70°, particularly preferably 40° to 65°, and / or the at least one third fixing means is selected from the group consisting of socket head cap screws, pan head screws, and combinations thereof, wherein the at least one third fixing means is preferably at least one socket head cap screw, particularly preferably a single socket head cap screw, and / or the aperture has a projecting area that projects beyond a second outer surface of the base body (adjacent to the first outer surface of the base body).wherein the protruding area is pressed against the stop surface, and wherein the recess is preferably arranged between the second outer surface of the base body and the at least one third fixing means, and / or the flow cell additionally comprises at least one third sealing element which is arranged around the at least one third fixing means and is sealingly connected to the at least one third fixing means.

[0054] The third fixing element and the stop allow the flow cell to be easily and securely connected to the module body. The third fixing element can be positioned at a specific angle to the first outer surface of the base body, so that the flow cell is pressed at a specific angle against both the module body and the stop surface of the stop element. This means that a first force component acts towards the module body, and a second force component acts towards the stop surface. The stop surface can then be positioned at a suitable angle to the first outer surface of the base body to effectively absorb the force component exerted by the fixing element on the stop surface and redirect it to the module body. In this way, a very secure fixation can be achieved.

[0055] A preferred embodiment of the optical module according to the invention is characterized in that the module main body a (single) lens for coupling in a light beam incident on the ATR crystal and for coupling out a light beam reflected from the ATR crystal, wherein the lens preferably contains or consists of zinc selenide, and / or comprises an optical window arranged between the ATR crystal and the lens, wherein the optical window preferably contains or consists of zinc sulfide, and / or comprises at least one fourth sealing element arranged on an outer surface of the module main body facing the flow cell, which is in sealing contact with a side of the flow cell facing the module main body, wherein the at least one fourth sealing element is designed in the form of a circular ring, and / or comprises a polarizer for polarizing a light beam reflected from the ATR crystal and subsequently coupled out.

[0056] The use of a single lens for coupling the light in and out has the advantage that it requires virtually no adjustment, as this design is self-correcting to a certain extent (cat's eye effect). This is advantageous for compensating for inaccuracies in the ATR crystal and the flow cell. The at least one fourth sealing element, located on an outer surface of the module body facing the flow cell, ensures that no gases or liquids penetrate the light path. This improves long-term stability, as water vapor, in particular, is IR-active. It is preferred that the at least one fourth sealing element contains or consists of at least one polymer selected from the group consisting of ethylene propylene diene monomer rubbers, silicones, and mixtures thereof.

[0057] Furthermore, the present invention relates to a spectrometer comprising at least one light source, at least one light detector, and an optical module according to the invention. Preferably, the spectrometer is an FTIR spectrometer and / or a QCL-based infrared spectrometer. Figs. 1a-c show a first exemplary embodiment of a flow cell according to the invention in several views. Fig. 1d shows an enlarged section of Fig. 1a Figs. 2a-c show a second exemplary embodiment of a flow cell according to the invention in several views. Fig. 2d shows an enlarged section of Fig. 2a Figs. 3a-c show a third exemplary embodiment of a flow cell according to the invention in several views. Fig. 3d shows an enlarged section of Fig. 3aFig. 4 shows a sectional view of an exemplary embodiment of a spectrometer according to the invention. Fig. 5 shows a sectional view of an exemplary embodiment of a spectrometer according to the invention. Example of implementation 1

[0058] In the Figs. 1a to 1c Figure 1 shows a first exemplary embodiment of a flow cell according to the invention in several views. Fig. 1a shows a top view of flow cell 100. In Fig. 1b A lateral sectional view of flow cell 100 is shown, with the section along the in Fig. 1a The depicted line AA has been completed. Furthermore, it shows Fig. 1c An exploded view of the flow cell.

[0059] The flow cell 100 comprises a polymer base body 1 (e.g., from the product "BioMed Clear" by the manufacturer Formlabs) with an inlet 2 for substances to be measured and an outlet 3 for measured substances, as well as an aperture 4 arranged on a first outer surface of the base body 1, which consists of an alloy, e.g., stainless steel. The base body 1 and the aperture 4 are thus made of different materials that have different coefficients of thermal expansion.

[0060] A recess 5 is provided on the first outer surface of the base body 1, containing a flow cell measuring chamber fluidically connected to the inlet 2 and the outlet 3. The aperture 4 is located on the first outer surface of the base body 1, where the recess 5 containing the flow cell measuring chamber is also provided. Thus, the recess 5 with the flow cell measuring chamber adjoins the aperture 4. The aperture diaphragm 6 is also located in this area of ​​the aperture 4, so that the aperture diaphragm 6 adjoins the recess 5.

[0061] In Fig. 1d an enlarged section from Fig. 1aFigure 1 shows an enlarged side view of the recess 5 and the elements arranged therein. The flow cell 100 further comprises an arrangement of an ATR crystal 7 and a first sealing element 8 for sealing the flow cell measuring chamber, which is clamped between the aperture 4 and a first wall region of the recess 5 facing the aperture 4. The first sealing element 8 is arranged on a side of the ATR crystal 7 facing away from the aperture 4 and is in sealing contact with the ATR crystal 7 and the first wall region of the recess 5. A central wall region of the recess facing the aperture 4 has an opening connected to one inlet 2 and an opening connected to the outlet 3.

[0062] The ATR crystal 7, which consists, for example, of silicon, comprises several microprisms and has a structure 7a with V-shaped grooves or slots on one side facing the aperture. The first sealing element 8 consists of a polymeric material (e.g., ethylene propylene diene monomer rubber or silicone) and is designed in the form of a circular ring (O-ring).

[0063] The flow cell chamber is now designed such that it is bounded by the ATR crystal 7, the sealing element 8, and wall sections of the recess 5. By fixing the aperture 4 to the base body 1, the assembly comprising the ATR crystal 7 and the sealing element 8 can be clamped between the aperture 4 and the first wall section of the recess 5, thereby sealing the flow cell chamber.

[0064] Here, the aperture 4 can be fixed to the base body 1 at a first fixing point via a first fixing element 9 and at a second fixing point via a second fixing element 10. The recess 5 is arranged between the first fixing point (or the first fixing element 9) and the second fixing point (or the second fixing element 10), with the first fixing point (or the first fixing element 9) and the second fixing point (or the second fixing element 10) being equidistant from the recess 5. The first fixing element 9 is a countersunk screw and the second fixing element 10 is a pan head screw.The countersunk screw allows the aperture 4 to be fixed at the first fixing point on the base body 1 in such a way that the base body 1 and the aperture 4 at the first fixing point are essentially not movable relative to each other in an x-direction parallel to the first outer surface of the base body 1, in a y-direction parallel to the first outer surface of the base body 1 and in a z-direction perpendicular to the first outer surface of the base body 1.The lens-head screw allows the aperture 4 to be fixed at the second fixing point on the base body 1 in such a way that the base body 1 and the aperture 4 are essentially not movable relative to each other in the z-direction at the second fixing point, and are only movable relative to each other to a limited extent in the x-direction and the y-direction, so that different expansions and contractions of the components of the flow cell that occur during temperature changes can be compensated for.

[0065] Consequently, although the base body 1 and the aperture 4 expand differently during significant temperature changes (e.g., during sterilization or autoclaving of the flow cell) due to their different coefficients of thermal expansion, this does not lead to bending of the components (due to their inherent flexibility in the x and y directions). Therefore, the clamped assembly comprising the ATR crystal 7 and the first sealing element 8 does not loosen. This prevents the formation of leaks in the assembly where the flow cell measuring chamber is no longer adequately sealed. Consequently, the flow cell maintains a high degree of tightness even during significant temperature changes (e.g., during sterilization or autoclaving), preventing contaminants from entering the flow cell chamber through external leaks.Consequently, contamination of the flow cell chamber and the substances measured within it by externally penetrating contaminants or microorganisms can be better avoided.

[0066] The flow cell 100 additionally includes a second sealing element 11, which is arranged around the recess 5, wherein the second sealing element consists of a polymeric material (e.g. ethylene propylene diene rubber or silicone) and is designed in the form of a circular ring (O-ring).

[0067] Furthermore, the flow cell 100 comprises a single third fixing element 12 for attaching the flow cell to a module main body of an optical module. The third fixing element 12 is a socket head cap screw. This screw is arranged such that the angle between the main extension direction of the socket head cap screw (or the third fixing element 12) and the first outer surface of the base body 1 lies within a range of 40° to 65°. The aperture 4 also has a projecting area 13 that extends beyond a second outer surface of the base body 1 adjacent to the first outer surface. The recess 5 is located between the second outer surface of the base body 1 and the third fixing element 12. The aperture also additionally includes a third sealing element 14, which is arranged around the at least one third fixing element and is sealingly connected to the third fixing element 12. Example 2

[0068] In the Figs. 2a to 2c A second exemplary embodiment of a flow cell according to the invention is shown in several views. Fig. 2a shows a top view of flow cell 100. In Fig. 2b A lateral sectional view of flow cell 100 is shown, with the section along the in Fig. 2a The depicted line AA has been completed. Furthermore, it shows Fig. 2c An exploded view of the flow cell.

[0069] The flow cell 100 comprises a polymer base body 1 (e.g., from the product "BioMed Clear" by the manufacturer Formlabs) with an inlet 2 for substances to be measured and an outlet 3 for measured substances, as well as an aperture 4 arranged on a first outer surface of the base body 1, which consists of an alloy, e.g., stainless steel. The base body 1 and the aperture 4 are thus made of different materials that have different coefficients of thermal expansion.

[0070] A recess 5 is provided on the first outer surface of the base body 1, containing a flow cell measuring chamber fluidically connected to the inlet 2 and the outlet 3. The aperture 4 is located on the first outer surface of the base body 1, where the recess 5 containing the flow cell measuring chamber is also provided. Thus, the recess 5 with the flow cell measuring chamber adjoins the aperture 4. The aperture diaphragm 6 is also located in this area of ​​the aperture 4, so that the aperture diaphragm 6 adjoins the recess 5.

[0071] In Fig. 2d an enlarged section from Fig. 2aFigure 1 shows an enlarged side view of the recess 5 and the elements arranged therein. The flow cell 100 further comprises an arrangement of an ATR crystal 7 and a first sealing element 8 for sealing the flow cell measuring chamber, which is clamped between the aperture 4 and a first wall region of the recess 5 facing the aperture 4. The first sealing element 8 is arranged on a side of the ATR crystal 7 facing away from the aperture 4 and is in sealing contact with the ATR crystal 7 and the first wall region of the recess 5. A central wall region of the recess facing the aperture 4 has an opening connected to one inlet 2 and an opening connected to the outlet 3.

[0072] The ATR crystal 7, which consists, for example, of silicon, comprises several microprisms and has a structure 7a with V-shaped grooves or slots on one side facing the aperture. The first sealing element 8 consists of a polymeric material (e.g., ethylene propylene diene monomer rubber or silicone) and is designed in the form of a circular ring (O-ring).

[0073] The flow cell chamber is now designed such that it is bounded by the ATR crystal 7, the sealing element 8, and wall sections of the recess 5. By fixing the aperture 4 to the base body 1, the assembly comprising the ATR crystal 7 and the sealing element 8 can be clamped between the aperture 4 and the first wall section of the recess 5, thereby sealing the flow cell chamber.

[0074] Here, the aperture 4 can be fixed to the base body 1 at a first fixing point via a first fixing element 9 and at a second fixing point via a second fixing element 10. The recess 5 is arranged between the first fixing point (or the first fixing element 9) and the second fixing point (or the second fixing element 10), with the first fixing point (or the first fixing element 9) and the second fixing point (or the second fixing element 10) being equidistant from the recess 5. The first fixing element 9 is a countersunk screw and the second fixing element 10 is a pan head screw.The countersunk screw allows the aperture 4 to be fixed at the first fixing point on the base body 1 in such a way that the base body 1 and the aperture 4 at the first fixing point are essentially not movable relative to each other in an x-direction parallel to the first outer surface of the base body 1, in a y-direction parallel to the first outer surface of the base body 1 and in a z-direction perpendicular to the first outer surface of the base body 1.The lens-head screw allows the aperture 4 to be fixed at the second fixing point on the base body 1 in such a way that the base body 1 and the aperture 4 are essentially not movable relative to each other in the z-direction at the second fixing point, and are only movable relative to each other to a limited extent in the x-direction and the y-direction, so that different expansions and contractions of the components of the flow cell that occur during temperature changes can be compensated for.

[0075] Consequently, although the base body 1 and the aperture 4 expand differently during significant temperature changes (e.g., during sterilization or autoclaving of the flow cell) due to their different coefficients of thermal expansion, this does not lead to bending of the components (due to their inherent flexibility in the x and y directions). Therefore, the clamped assembly comprising the ATR crystal 7 and the first sealing element 8 does not loosen. This prevents the formation of leaks in the assembly where the flow cell measuring chamber is no longer adequately sealed. Consequently, the flow cell maintains a high degree of tightness even during significant temperature changes (e.g., during sterilization or autoclaving), preventing contaminants from entering the flow cell chamber through external leaks.Consequently, contamination of the flow cell chamber and the substances measured within it by externally penetrating contaminants or microorganisms can be better avoided.

[0076] The flow cell 100 additionally includes a second sealing element 11, which is arranged around the recess 5, wherein the second sealing element consists of a polymeric material (e.g. ethylene propylene diene rubber or silicone) and is designed in the form of a circular ring (O-ring).

[0077] Furthermore, the flow cell 100 comprises a single third fixing element 12 for attaching the flow cell to a module main body of an optical module. The third fixing element 12 is a socket head cap screw. This screw is arranged such that the angle between the main extension direction of the socket head cap screw (or the third fixing element 12) and the first outer surface of the base body 1 lies within a range of 40° to 65°. The aperture 4 also has a projecting area 13 that extends beyond a second outer surface of the base body 1 adjacent to the first outer surface. The recess 5 is located between the second outer surface of the base body 1 and the third fixing element 12. The aperture also additionally includes a third sealing element 14, which is arranged around the at least one third fixing element and is sealingly connected to the third fixing element 12.

[0078] Furthermore, the flow cell 100 additionally includes a filter element 15, which is arranged in the recess 5 between the ATR crystal 7 and the opening connected to the inlet 2, as well as between the ATR crystal 7 and the opening connected to the outlet 3. The filter element 15 can, for example, be a cellulose filter element with a thickness in the range of 0.02 mm to 0.2 mm.

[0079] The substances being measured, which are passed through the flow cell, may contain larger molecules (e.g., proteins), cell debris, and microorganisms. These can deposit on the ATR crystal, leading to biofouling. This deposition, or biofouling, subsequently degrades the measurement because the deposited components result in a disproportionately large signal in the measurement or the measured spectrum, thus affecting the measurement quality. Furthermore, deposits on the ATR crystal can contaminate the substance being measured in a subsequent measurement.

[0080] The filter element 15 prevents larger molecules (e.g., proteins), cell debris, and microorganisms contained in the substances being measured from reaching the ATR crystal 8. These components are retained by the filter element 15, while the liquid containing the smaller molecules relevant for optical measurement passes through it. Consequently, deposits or biofouling on the ATR crystal 7 are better prevented. Therefore, the filter element 15 also helps to prevent contamination of the flow cell chamber and the substances to be measured therein. Furthermore, the filter element 15 also prevents gas bubbles present in the substances being measured from reaching the ATR crystal 7. If these bubbles were to adhere to the ATR crystal 7, they would also undesirably affect the measurement or the measured spectrum.

[0081] Furthermore, the flow cell 100 additionally comprises a filter holder 16 for holding the filter element 15, which is arranged between the ATR crystal 7 and the filter element 15. The filter holder 16 has a grid structure and a frame extending around the grid structure. Preferably, the frame can be in contact with the ATR crystal 7, and the grid structure can be in contact with the ATR crystal 7. For example, the grid structure can be arranged at a distance of 0.01 mm to 1 mm from the ATR crystal 7. The filter element 15 can preferably be clamped between the frame and a second wall region of the recess 5 facing the aperture 4. Preferably, the central wall region of the recess 5 facing the aperture 4 can have three retaining elements, wherein the filter element 15 can be clamped between the grid structure and the retaining elements.Furthermore, the central wall area of ​​the recess 5 can have a jagged structure, which can reduce the risk of biofouling occurring on the filter element 15. Example 3

[0082] In the Figs. 3a to 3c A third exemplary embodiment of a flow cell according to the invention is shown in several views. Fig. 3a shows a top view of flow cell 100. In Fig. 3b A lateral sectional view of flow cell 100 is shown, with the section along the in Fig. 3a The depicted line AA has been completed. Furthermore, it shows Fig. 3c An exploded view of the flow cell.

[0083] The flow cell 100 comprises a polymer base body 1 (e.g., from the product "BioMed Clear" by the manufacturer Formlabs) with an inlet 2 for substances to be measured and an outlet 3 for measured substances, as well as an aperture 4 arranged on a first outer surface of the base body 1, which consists of an alloy, e.g., stainless steel. The base body 1 and the aperture 4 are thus made of different materials that have different coefficients of thermal expansion.

[0084] A recess 5 is provided on the first outer surface of the base body 1, containing a flow cell measuring chamber fluidically connected to the inlet 2 and the outlet 3. The aperture 4 is located on the first outer surface of the base body 1, where the recess 5 containing the flow cell measuring chamber is also provided. Thus, the recess 5 with the flow cell measuring chamber adjoins the aperture 4. The aperture diaphragm 6 is also located in this area of ​​the aperture 4, so that the aperture diaphragm 6 adjoins the recess 5.

[0085] In Fig. 3d an enlarged section from Fig. 3aFigure 1 shows an enlarged side view of the recess 5 and the elements arranged therein. The flow cell 100 further comprises an arrangement of an ATR crystal 7 and a first sealing element 8 for sealing the flow cell measuring chamber, which is clamped between the aperture 4 and a first wall region of the recess 5 facing the aperture 4. The first sealing element 8 is arranged on a side of the ATR crystal 7 facing away from the aperture 4 and is in sealing contact with the ATR crystal 7 and the first wall region of the recess 5. A central wall region of the recess facing the aperture 4 has an opening connected to one inlet 2 and an opening connected to the outlet 3.

[0086] The ATR crystal 7, which consists, for example, of silicon, comprises several microprisms and has a structure 7a with V-shaped grooves or slots on one side facing the aperture. The first sealing element 8 consists of a polymeric material (e.g., ethylene propylene diene monomer rubber or silicone) and is designed in the form of a circular ring (O-ring).

[0087] The flow cell chamber is now designed such that it is bounded by the ATR crystal 7, the sealing element 8, and wall sections of the recess 5. By fixing the aperture 4 to the base body 1, the assembly comprising the ATR crystal 7 and the sealing element 8 can be clamped between the aperture 4 and the first wall section of the recess 5, thereby sealing the flow cell chamber.

[0088] Here, the aperture 4 can be fixed to the base body 1 at a first fixing point via a first fixing element 9 and at a second fixing point via a second fixing element 10. The recess 5 is arranged between the first fixing point (or the first fixing element 9) and the second fixing point (or the second fixing element 10), with the first fixing point (or the first fixing element 9) and the second fixing point (or the second fixing element 10) being equidistant from the recess 5. The first fixing element 9 is a countersunk screw and the second fixing element 10 is a pan head screw.The countersunk screw allows the aperture 4 to be fixed at the first fixing point on the base body 1 in such a way that the base body 1 and the aperture 4 at the first fixing point are essentially not movable relative to each other in an x-direction parallel to the first outer surface of the base body 1, in a y-direction parallel to the first outer surface of the base body 1 and in a z-direction perpendicular to the first outer surface of the base body 1.The lens-head screw allows the aperture 4 to be fixed at the second fixing point on the base body 1 in such a way that the base body 1 and the aperture 4 are essentially not movable relative to each other in the z-direction at the second fixing point, and are only movable relative to each other to a limited extent in the x-direction and the y-direction, so that different expansions and contractions of the components of the flow cell that occur during temperature changes can be compensated for.

[0089] Consequently, although the base body 1 and the aperture 4 expand differently during significant temperature changes (e.g., during sterilization or autoclaving of the flow cell) due to their different coefficients of thermal expansion, this does not lead to bending of the components (due to their inherent flexibility in the x and y directions). Therefore, the clamped assembly comprising the ATR crystal 7 and the first sealing element 8 does not loosen. This prevents the formation of leaks in the assembly where the flow cell measuring chamber is no longer adequately sealed. Consequently, the flow cell maintains a high degree of tightness even during significant temperature changes (e.g., during sterilization or autoclaving), preventing contaminants from entering the flow cell chamber through external leaks.Consequently, contamination of the flow cell chamber and the substances measured within it by externally penetrating contaminants or microorganisms can be better avoided.

[0090] The flow cell 100 additionally includes a second sealing element 11, which is arranged around the recess 5, wherein the second sealing element consists of a polymeric material (e.g. ethylene propylene diene rubber or silicone) and is designed in the form of a circular ring (O-ring).

[0091] Furthermore, the flow cell 100 comprises a single third fixing element 12 for attaching the flow cell to a module main body of an optical module. The third fixing element 12 is a socket head cap screw. This screw is arranged such that the angle between the main extension direction of the socket head cap screw (or the third fixing element 12) and the first outer surface of the base body 1 lies within a range of 40° to 65°. The aperture 4 also has a projecting area 13 that extends beyond a second outer surface of the base body 1 adjacent to the first outer surface. The recess 5 is located between the second outer surface of the base body 1 and the third fixing element 12. The aperture also additionally includes a third sealing element 14, which is arranged around the at least one third fixing element and is sealingly connected to the third fixing element 12.

[0092] Furthermore, the flow cell 100 additionally includes a filter element 15, which is arranged in the recess 5 between the ATR crystal 7 and the opening connected to the inlet 2, as well as between the ATR crystal 7 and the opening connected to the outlet 3. The filter element 15 is attached to the first sealing element 8. It is bonded to the inner edge of the annular first sealing element 8, so that the entire area between the inner edge of the annular first sealing element 8 is sealed by the filter element 15. The first sealing element 8 is thus arranged around the filter element 15 or runs along its edge. The first sealing element 8 and the filter element 15 can also be considered a single sealing filter element. The filter element 15 can, for example, be a cellulose filter element with a thickness in the range of 0.02 mm to 0.2 mm.

[0093] The filter element 15 is arranged in direct contact with at least one photoresist coating 16 applied to the ATR crystal. The photoresist coating 16 is applied to the ATR crystal in a strip-like pattern, the arrangement of the photoresist coating on the ATR crystal being adapted to the structure 7a of the ATR crystal, which the ATR crystal has on the side facing the aperture. The photoresist coating can, for example, have a thickness in the range of 0.1 µm to 100 µm.

[0094] The substances being measured, which are passed through the flow cell, may contain larger molecules (e.g., proteins), cell debris, and microorganisms. These can deposit on the ATR crystal, leading to biofouling. This deposition, or biofouling, subsequently degrades the measurement because the deposited components result in a disproportionately large signal in the measurement or the measured spectrum, thus affecting the measurement quality. Furthermore, deposits on the ATR crystal can contaminate the substance being measured in a subsequent measurement.

[0095] The filter element 15 prevents larger molecules (e.g., proteins), cell debris, and microorganisms contained in the substances being measured from reaching the ATR crystal 8. These components are retained by the filter element 15, while the liquid containing the smaller molecules relevant for optical measurement passes through it. Consequently, deposits or biofouling on the ATR crystal 7 are better prevented. Therefore, the filter element 15 also helps to prevent contamination of the flow cell chamber and the substances to be measured therein. Furthermore, the filter element 15 also prevents gas bubbles present in the substances being measured from reaching the ATR crystal 7. If these bubbles were to adhere to the ATR crystal 7, they would also undesirably affect the measurement or the measured spectrum. Example 4

[0096] In Fig. 4Figure 1 shows a sectional view of an exemplary embodiment of a spectrometer according to the invention. This comprises an exemplary embodiment of an optical module 1000 according to the invention (characterized by the dashed frame in Figure 2). Fig. 4 ), which comprises a module main body 200 and an exemplary embodiment of a flow cell 100 according to the invention, which is attached to the module main body 200.

[0097] The module body 200 comprises a lens 17 for coupling in a light beam incident on the ATR crystal 7 and for coupling out a light beam reflected from the ATR crystal 7, wherein the lens 17 is made, for example, of zinc selenide. Furthermore, the module body 200 comprises an optical window 18, which is arranged between the ATR crystal 7 and the lens 17, wherein the optical window 18 is made, for example, of zinc sulfide. The module body 200 also comprises a fourth sealing element 19 arranged on an outer surface of the module body 200 facing the flow cell 100, which is in sealing contact with a side of the flow cell 100 facing the module body 200, wherein the fourth sealing element 19 is designed in the form of a circular ring (O-ring).In addition, the main module body 200 includes a polarizer 20 for polarizing a light beam reflected from the ATR crystal 7 and then coupled out, a motor 21 for rotating the polarizer 20 and two mirrors 22d, 22e.

[0098] The flow cell 100 is attached to the module main body 200 by a single third fixing element 12 and a stop element 23 arranged on an outer surface of the module main body 200 facing the flow cell 100. The stop element 23 has a stop surface against which the flow cell 100 is pressed by the third fixing element 12. The third fixing element 12 is a socket head cap screw. This screw is arranged such that the angle between the main direction of extension of the socket head cap screw (or of the third fixing element 12) and the first outer surface of the main body 1 is in the range of 40° to 65°. The angle between the stop surface and the first outer surface of the main body 1 is also in the range of 40° to 50°.Furthermore, the aperture 4 has a projecting area 13 that extends beyond a second outer surface of the base body 1 adjacent to the first outer surface of the base body 1, the projecting area 13 being pressed against the stop surface of the stop element 23. The recess 5 is arranged between the second outer surface of the base body 1 and the third fixing element 12.

[0099] The third fixing element 12 and the stop element 23 enable the flow cell 100 to be easily and securely connected to the module main body 200. The third fixing element 12 is positioned at a specific angle to the first outer surface of the base body 1, such that the flow cell 100 is pressed at a specific angle against both the module main body 200 and the stop surface of the stop element 23. This means that a first force component acts towards the module main body 200, and a second force component acts towards the stop surface. The stop surface can be positioned at a suitable angle to the first outer surface of the base body 1 to effectively absorb the force component exerted on it by the third fixing element 12 and redirect it onto the module main body 200. In this way, a very secure fixation can be achieved.

[0100] The spectrometer also includes a light source 24, a light detector 25, a beam splitter 26, three mirrors 22a, 22b, 22c and two parabolic mirrors 27a, 27b. Example 5

[0101] In Fig. 5 Figure 1 shows a sectional view of an exemplary embodiment of a spectrometer according to the invention. This comprises an exemplary embodiment of an optical module 1000 according to the invention (characterized by the dashed frame in Figure 2). Fig. 5 ), which comprises a module main body 200 and an exemplary embodiment of a flow cell 100 according to the invention, which is attached to the module main body 200.

[0102] The module body 200 comprises a lens 17 for coupling in a light beam incident on the ATR crystal 7 and for coupling out a light beam reflected from the ATR crystal 7, wherein the lens 17 is made, for example, of zinc selenide. Furthermore, the module body 200 comprises an optical window 18, which is arranged between the ATR crystal 7 and the lens 17, wherein the optical window 18 is made, for example, of zinc sulfide. The module body 200 also comprises a fourth sealing element 19 arranged on an outer surface of the module body 200 facing the flow cell 100, which is in sealing contact with a side of the flow cell 100 facing the module body 200, wherein the fourth sealing element 19 is designed in the form of a circular ring (O-ring). In addition, the module body 200 comprises two mirrors 22d, 22e.

[0103] The flow cell 100 is attached to the module main body 200 by a single third fixing element 12 and a stop element 23 arranged on an outer surface of the module main body 200 facing the flow cell 100. The stop element 23 has a stop surface against which the flow cell 100 is pressed by the third fixing element 12. The third fixing element 12 is a socket head cap screw. This screw is arranged such that the angle between the main direction of extension of the socket head cap screw (or of the third fixing element 12) and the first outer surface of the main body 1 is in the range of 40° to 65°. The angle between the stop surface and the first outer surface of the main body 1 is also in the range of 40° to 50°.Furthermore, the aperture 4 has a projecting area 13 that extends beyond a second outer surface of the base body 1 adjacent to the first outer surface of the base body 1, the projecting area 13 being pressed against the stop surface of the stop element 23. The recess 5 is arranged between the second outer surface of the base body 1 and the third fixing element 12.

[0104] The third fixing element 12 and the stop element 23 enable the flow cell 100 to be easily and securely connected to the module main body 200. The third fixing element 12 is positioned at a specific angle to the first outer surface of the base body 1, such that the flow cell 100 is pressed at a specific angle against both the module main body 200 and the stop surface of the stop element 23. This means that a first force component acts towards the module main body 200, and a second force component acts towards the stop surface. The stop surface can be positioned at a suitable angle to the first outer surface of the base body 1 to effectively absorb the force component exerted on it by the third fixing element 12 and redirect it onto the module main body 200. In this way, a very secure fixation can be achieved.

[0105] The spectrometer further comprises a light source 24, two light detectors 25a, 25b, a spectrometer-internal polarizer 28, a beam splitter 26, four mirrors 22a, 22b, 22c, 22f and three parabolic mirrors 27a, 27b, 27c.

Claims

1. Flow cell (100) for optical measurements, comprising a base body (1) with at least one inlet (2) and at least one outlet (3) as well as an aperture (4) arranged at a first outer side of the base body (1), a recess (5) being provided at the first outer side of the base body (1); this recess containing a flow cell measuring chamber connected to the at least one inlet (2) and the at least one outlet (3), the base body (1) consisting of at least one material that has a first thermal expansion coefficient, and the aperture (4) consisting of at least one material that has a second thermal expansion coefficient that differs from the first thermal expansion coefficient, the flow cell (100) further comprising an arrangement comprising an ATR crystal (7) and at least one first sealing element (8) for sealing the flow cell measuring chamber, clamped between the aperture (4) and at least one first wall region of the recess (5), the at least one first sealing element (8) being arranged on a side of the ATR crystal (7) facing away from the aperture (4), the aperture (4) being fixable via at least one first fixing agent (9) to at least one first fixing location at the base body (1) such that the base body (1) and the aperture (4) are essentially immovable relative to each other at the at least one first fixing point in an x-direction running parallel to the first outer side of the base body (1), in a y-direction running parallel to the first outer side of the base body (1) and in a z-direction running perpendicular to the first outer side of the base body (1), and the aperture being fixable via at least one second fixing agent (10) to at least one second fixing location at the base body (1) such that the base body (1) and the aperture (4) are essentially immovable relative to each other at the at least one second fixing location in the z-direction and are movable relative to each other at the at least one second fixing location in the x-direction and in the y-direction, in each case only to the extent that different expansions and / or contractions of the components of the flow cell (100) occurring during temperature changes can be compensated for.

2. Flow cell (100) according to the preceding claim, characterised in that the aperture (4) is fixable to the at least one second fixing location at the base body (1) via the at least one second fixing agent (10) such that the base body (1) and the aperture (4) are essentially immovable relative to each other at the at least one second fixing point in the z-direction and are movable relative to each other at the at least one second fixing point in the x-direction and in the y-direction by at least 0.01 mm, preferably at least 0.05 mm, particularly preferably at least 0.1 mm, and / or by a maximum of 1 mm, preferably a maximum of 0.8 mm, particularly preferably a maximum of 0.5 mm.

3. Flow cell (100) according to any one of the preceding claims, characterised in that - the at least one first fixing agent (9) is selected from the group consisting of countersunk screws and combinations of these, the at least one first fixing agent (9) being preferably at least one countersunk screw, and / or - the at least one second fixing agent (10) is selected from the group consisting of pan head screws, rivets, cylinder head screws and combinations of these, the at least one first fixing agent (10) being preferably at least one pan head screw.

4. Flow cell (100) according to any one of the preceding claims, characterised in that - the at least one material of which the base body (1) consists of is at least one polymer, which is preferably selected from the group consisting of polyether ether ketones, polytetrafluoroethylene, polypropylene, polysulfones, polyether sulfones, polycarbonates, polyvinyl chlorides, polylactides, polyamides, thermoplastic polyurethanes, acrylonitrile-butadiene-styrene, UV-curing synthetic resins, as well as mixtures of these, and / or - the at least one material of which the aperture (4) consists of is selected from the group consisting of metals, e.g. iron; alloys, preferably iron-containing alloys, e.g. stainless steel; polymers, e.g. polyether ether ketones; and mixtures and combinations of these, wherein the aperture (4) preferably contains or consists of stainless steel.

5. Flow cell (100) according to any one of the preceding claims, characterised in that the ATR crystal (7) - contains or consists of at least one material that is at least partially transparent to light with a wavelength in the range from 2 µm to 20 µm, preferably from 4 µm to 12 µm, the ATR crystal (7) preferably containing or consisting of at least one material selected from the group consisting of silicon, diamond, germanium, zinc selenide, zinc sulphide, and mixtures and combinations thereof, the ATR crystal particularly preferably containing or consisting of silicon, and / or - comprises multiple microprisms, and / or - has a structure (7a) on a side facing the aperture, preferably a structure (7a) with grooves or slots.

6. Flow cell (100) according to any one of the preceding claims, characterised in that - the at least first sealing element (8) • contains or consists of at least one polymer selected from the group consisting of ethylene-propylene-diene rubbers, silicones, and mixtures thereof, and / or • is configured in the shape of an annular ring, and / or • is engaged in sealing contact with the ATR crystal (7) and / or the at least one first wall region of the recess (5) and / or - the flow cell (100) comprises at least one second sealing element (11) which is arranged around the recess (5), the at least one second sealing element (11) preferably • containing or consisting of at least one polymer selected from the group consisting of ethylene-propylene-diene rubbers, silicones, and mixtures thereof, and / or • is configured in the shape of an annular ring, and / or • is at least partially arranged in a further recess provided at the first outer side of the base body (1) and arranged around the recess (5), and / or • is engaged in sealing contact with the base body (1) and / or the aperture (4).

7. Flow cell (100) according to any one of the preceding claims, characterised in that the flow cell (100) comprises at least one filter element (15) which is arranged in the recess (5) between the ATR crystal (7) and at least one opening connected to the at least one inlet (2) and / or between the ATR crystal (7) and at least one opening connected to the at least one outlet (3), wherein preferably - the at least one filter element (15) is selected from the group consisting of cellulose filter elements, paper filter elements, glass fibre filter elements, and combinations of these, and / or - has a thickness in the range of 0.001 mm to 5 mm, preferably 0.01 mm to 1 mm, particularly preferably 0.02 mm to 0.2 mm.

8. Flow cell (100) according to claim 7, characterised in that the flow cell (100) additionally comprises at least one filter holder (16) to hold the at least one filter element (15), which is arranged between the ATR crystal (7) and the at least one filter element (15), the at least one filter holder (16) preferably having a grid structure and a frame that goes around the grid structure, - the frame being in contact with the ATR crystal (7) and the grid structure being not in contact with the ATR crystal (7), the grid structure preferably being arranged from the ATR crystal (7) at a distance of 0.001 mm to 5 mm, preferably 0.005 mm to 2 mm, particularly preferably 0.008 mm to 1 mm, more particularly preferably from 0.01 mm to 0.1 mm, and / or - the at least one filter element (15) being clamped between the frame and at least one second wall region of the recess (5) facing the aperture (4), and / or - a central wall region of the recess (5) facing the aperture (4) having at least one retaining element, preferably at least two retaining elements, the at least one filter element (15) being clamped between the grid structure and the at least one retaining element.

9. Flow cell (100) according to claim 7, characterised in that the at least one filter element (15) is arranged in direct contact with at least one photoresist coating (16) applied to the ATR crystal (7), wherein preferably - the at least one photoresist coating (16) has a thickness in the range from 0.1 µm to 100 µm, preferably from 1 µm to 50 µm, particularly preferably from 5 µm to 20 µm, and / or - the at least one photoresist coating (16)is applied to the ATR crystal (7) in the form of a grid or stripes, the arrangement of the photoresist coating (16) on the ATR crystal (7) being preferably adjusted to a structure of the ATR crystal (7) which the ATR crystal (7) has on a side facing the aperture (4), and / or - the at least one filter element (15) is attached to the at least one first sealing element (8), preferably integrally connected to the at least one first sealing element (8).

10. Flow cell (100) according to any one of the preceding claims, characterised in that the recess (5) - is arranged between the at least one first fixing location and the at least one second fixing location, the at least one first fixing location and the at least one second fixing location preferably having an equal distance from the recess (5), and / or - having a structure, preferably a jagged structure, on a central wall region of the recess (5) facing the aperture (4), and / or - having at least one opening connected to the at least one inlet (2) on a central wall region of the recess (5) facing the aperture (4), and / or - having at least one opening connected to the at least one outlet (3) on a central wall region of the recess (5) facing the aperture (4).

11. Flow cell (100) according to any one of the preceding claims, characterised in that the flow cell (100) comprises at least one third fixing agent (12), preferably a single third fixing agent (12), to attach the flow cell (100) to a module main body of an optical module, - the at least one third fixing agent (12) having a main direction of extension, an angle between this main direction of extension and the first outer side of the base body (1) lying in a range from 20° to 85°, preferably from 30° to 70°, particularly preferably from 40° to 65°, and / or - the at least one third fixing agent (12) being selected from the group consisting of cylinder head screws, pan head screws, and combinations of these, the at least one third fixing agent (12) being preferably at least one cylinder head screw, more preferably a single cylinder head screw, and / or - the aperture (4) having a protruding region (13) which protrudes beyond a second outer side of the base body (1), the recess (5) being preferably arranged between the second outer side of the base body (1) and the at least one third fixing agent (12), and / or - the flow cell (100) additionally having at least one third sealing element (14) which is arranged around the at least one third fixing agent (12) and is engaged in sealing contact with the at least one third fixing agent (12).

12. Optical module (1000) comprising a module main body (200) and a flow cell (100), which is attached to the module main body, according to any one of the preceding claims.

13. Optical module (1000) according to claim 12, characterised in that the flow cell (100) is attached to the module main body (200) via at least one third fixing agent (12), preferably a single third fixing agent (12), and a stop element (23) arranged on an outer side of the module main body (200) facing the flow cell (100), the stop element (23) having a stop surface against which the flow cell (100) is pressed by the at least one third fixing agent (12), and preferably - an angle between the stop surface and the first outer side of the base body (1) lying in a range from 20° to 85°, preferably from 30° to 65°, particularly preferably from 40° to 50°, and / or - the at least one third fixing agent (12) having a main direction of extension, an angle between this main direction of extension and the first outer side of the base body (1) lying in a range from 20° to 85°, preferably from 30° to 70°, particularly preferably from 40° to 65°, and / or - the at least one third fixing agent (12) being selected from the group consisting of cylinder head screws, pan head screws, and combinations of these, the at least one third fixing agent (12) being preferably at least one cylinder head screw, more preferably a single cylinder head screw, and / or - the aperture (4) having a protruding region (13) which protrudes beyond a second outer side of the base body (1), the protruding region (13) being pressed against the stop surface, and the recess (5) preferably being arranged between the second outer side of the base body (1) and the at least one third fixing agent (12), and / or - the flow cell (100) additionally having at least one third sealing element (14) which is arranged around the at least one third fixing agent (12).

14. Optical module (1000) according to claim 12 or 13, characterised in that the module main body (200) - contains a lens (17) for coupling a light beam incident on the ATR crystal (7) and for decoupling a light beam reflected by the ATR crystal (7), the lens (17) preferably containing or consisting of zinc selenide, and / or - comprises an optical window (18) arranged between the ATR crystal (7) and the lens (17), the optical window (18) preferably containing or consisting of zinc sulfide, and / or - comprises at least one fourth sealing element (19) arranged at an outer side of the module main body (200) facing the flow cell (100), which is in sealing contact with one side of the flow cell (100) facing the module main body (200), the at least one fourth sealing element (19) preferably being configured in the form of an annular ring, and / or - comprises a polariser (20) for polarising a light beam reflected by the ATR crystal (7) and thereafter decoupled.

15. Spectrometer comprising at least one light source, at least one light detector, as well as an optical module (1000) according to any one of claims 12 to 14, the spectrometer preferably being an FTIR spectrometer or a QCL-based infrared spectrometer.